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NMR studies of carbohydrates in the solid state Lim, Tang Kuan 1985

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NMR STUDIES OF CARBOHYDRATES IN THE SOLID STATE by TANG KUAN LIM B.Sc. (Hons.), U n i v e r s i t y of Mal a y a , M a l a y s i a , 1977 A THESIS SUBMITTED IN PARTIAL FULFILMENT OF THE REQUIREMENTS FOR THE DEGREE OF DOCTOR OF PHILOSOPHY i n THE FACULTY OF GRADUATE STUDIES (Department of C h e m i s t r y ) We a c c e p t t h i s t h e s i s as c o n f o r m i n g t o the rec^u-irr^ed s t a n d a r d THE UNIVERSITY OF BRITISH COLUMBIA November 1985 Tang Kuan Lim CP In presenting this thesis in partial fulfilment of the requirements for an advanced degree at the University of British Columbia, I agree that the Library shall make it freely available for reference and study. I further agree that permission for extensive copying of this thesis for scholarly purposes may be granted by the head of my department or by his or her representatives. It is understood that copying or publication of this thesis for financial gain shall not be allowed without my written permission. Department of Cl*2MiS7fc. v/ The University of British Columbia 1956 Main Mall Vancouver, Canada V6T 1Y3 DE-6(3/81) i i ABSTRACT The work d e s c r i b e d h e r e i n e n t a i l s the a p p l i c a t i o n of s o l i d - s t a t e n.m.r. methods t o both mono- and p o l y -s a c c h a r i d e c a r b o h y d r a t e s . Two major n.m.r. methods have been e v a l u a t e d f o r s t u d y i n g t h e s e s u b s t a n c e s , namely, the carbon-13 c r o s s - p o l a r i z a t i o n - m a g i c a n g l e s p i n n i n g method and the d e u t e r i u m q u a d r u p o l e echo method. H e p t a k i s - ( 2 , 6 - d i - 0 - m e t h y l ) - / 3 - c y c l o d e x t r i n and 0-c y c l o d e x t r i n p e r a c e t a t e were p r e p a r e d and, t o g e t h e r w i t h a-and 0 - c y c l o d e x t r i n s as h o s t s , were used t o encage a v a r i e t y of o r g a n i c guest m o l e c u l e s . A number of me t a l sugar c o n j u g a t e s were p r e p a r e d a c c o r d i n g t o the p r o c e d u r e s documented i n t h i s l a b o r a t o r y . F i r s t l y , c h e l a t e c o o r d i n a t i o n complexes were s y n t h e s i z e d by fo r m i n g s a l i c y l a l d i m i n e l i g a n d s d e r i v e d from c o m b i n a t i o n s of amino sugars (methyl 3 , 4 , 6 - t r i - 0 - a c e t y l - 2 - a m i n o - 2 -deoxy-/3-D-glucopyranoside or 1 , 3 , 4 , 6 ~ t e t r a - 0 - a c e t y l - 2 -amino-2-deoxy-0-D-glucopyranose) and s a l i c y l a l d e h y d e , w i t h subsequent c o m p l e x a t i o n of the s e t o c o p p e r ( I I ) , z i n c ( l l ) , and c o b a l t ( I l ) i o n s . S i m i l a r l y , c h i t o s a n S c h i f f ' s bases were p r e p a r e d and complexed t o c o p p e r ( I I ) i o n . A p p l i c a t i o n of the 1 3 C - c r o s s - p o l a r i z a t i o n - m a g i c a n g l e s p i n n i n g method i n the s p e c t r a l assignment of c y c l o d e x t r i n i n c l u s i o n complexes and me t a l sugar c o n j u g a t e s i n the s o l i d s t a t e has been demonstrated. In a l l c a s e s , r e c o u r s e t o s o l u t i o n s p e c t r a was n e c e s s a r y f o r c o r r e c t assignments of i n d i v i d u a l carbon r e s o n a n c e s . The sugar resonances of c y c l o d e x t r i n s a r e r e l a t i v e l y broad and are c o m p l i c a t e d by the s u b s t a n t i a l s p l i t t i n g s . The r a t i o n a l e s f o r such o b s e r v a t i o n s were drawn from c o m p a r a t i v e s t u d i e s , based on c l o s e l y r e l a t e d guest m o l e c u l e s . The s m a l l e r guest m o l e c u l e s were l e a s t a f f e c t e d by the c a v i t y s i z e of the host m o l e c u l e h e p t a k i s - ( 2 , 6-di-O-methyl) - / 3 - c y c l o d e x t r i n and the i s o t r o p i c c h e m i c a l s h i f t v a l u e s were s i m i l a r t o those measured f o r s o l u t i o n s . These v a l u e s suggest t h a t the guest m o l e c u l e s undergo a n i s o t r o p i c m o t i o n , which can be d e t e c t e d by the use of the d i p o l a r d e p h a s i n g t e c h n i q u e . S t u d i e s of metal sugar c o n j u g a t e s by 1 3 C n.m.r. r e v e a l e d t h a t paramagnetic i o n s have p r o f o u n d e f f e c t s on the r e s o l u t i o n o b t a i n e d . The h i g h c o n c e n t r a t i o n s of these i o n s r e s u l t i n broad f e a t u r e l e s s s p e c t r a . On the o t h e r hand, the d i a m a g n e t i c i o n s proved t o have l i t t l e e f f e c t on the i s o t r o p i c c h e m i c a l s h i f t s of the sugar c h e l a t e s . The d e u t e r i u m q u a d r u p o l e echo method has been used s p e c i f i c a l l y t o study the m o b i l i t y of the guest m o l e c u l e s encaged i n c y c l o d e x t r i n s . The "powder-type" s p e c t r a o b t a i n e d were then compared w i t h r e s u l t s r e p o r t e d i n the l i t e r a t u r e i n o r d e r t o d e f i n e the types of m o l e c u l a r m o t i o n . i v TABLE OF CONTENTS INTRODUCTION CHAPTER I - GENERAL BACKGROUND 10 S o l i d - S t a t e N.M.R. Methods 11 1.1. - H i g h - R e s o l u t i o n 1 3C N.M.R 11 1.1.1. - I n t r o d u c t i o n 11 1.1.2. - L i n e - B r o a d e n i n g Mechanisms 13 1.1.2.1. - P r o t o n D i p o l a r B r o a d e n i n g 13 1.1.2.. 2. - Chemical S h i f t A n i s o t r o p y 18 1.1.3. - S e n s i t i v i t y Enhancement 23 1.1.3.1. - S p i n Temperature 25 1.1.3.2. - C r o s s - P o l a r i z a t i o n 27 1.1.4. - The 1 3C-C.P.-M.A.S. Experiment 29 1.1.4.1. - P o l a r i z a t i o n of 1H 31 1.1.4.2. - S p i n L o c k i n g 31 1.1.4.3. - 1 3 C - 1 H Thermal C o n t a c t 32 1.1.4.4. - O b s e r v a t i o n of 1 3 C F r e e I n d u c t i o n Decay. 32 1.1.4.5. - O p t i m i z a t i o n of the C r o s s - P o l a r i z a t i o n Experiment 33 1.1.4.6. - E x p e r i m e n t a l A s p e c t s of Magic Angle S p i n n i n g 34 1.1.4.7. - S p e c t r a l R e s o l u t i o n . 3-7 1.1.5. - U s e f u l P u l s e Sequences and R e l a t e d Techniques 37 1.2. - 2H N.M.R 44 1.2.1. - I n t r o d u c t i o n 44 V 1.2.2. - N.M.R. of Quadrupolar N u c l e i i n the S o l i d S t a t e . 45 1.2.3. - E l e c t r i c F i e l d G r a d i e n t E f f e c t s 49 1.2.4. - Deuterium N.M.R. of L i q u i d C r y s t a l s 50 1.2.5. - Deuterium N.M.R. of P o l y c r y s t a l l i n e Samples 52 1.2.5.1. - S t a t i c O r i e n t a t i o n of a C-D bond 52 1.2.5.2. - R e o r i e n t a t i o n a l M o t i o n s f o r a C-D bond.. 56 1.2.6. - S p i n Echoes i n S o l i d s 59 1.2.7. - Deuterium N.M.R. Expe r i m e n t s 62 CHAPTER I I - CYCLODEXTRINS AND THEIR INCLUSION COMPLEXES 70 Ch e m i s t r y of C y c l o d e x t r i n s 71 I I . 1. - I n t r o d u c t i o n 71 I I . 1.1. - The S t r u c t u r e of C y c l o d e x t r i n s 74 I I . 1.2. - The D r i v i n g F o r c e f o r C o m p l e x a t i o n 76 I I . 1.3. - C y c l o d e x t r i n I n c l u s i o n Complexes 78 I I . 1.4. - C y c l o d e x t r i n s as Enzyme Models 82 11.1.5. - C y c l o d e x t r i n s as Models f o r S t a r c h 85 11.1.6. - Chem i c a l M o d i f i c a t i o n of C y c l o d e x t r i n s . . 86 I I . 1.7. - C y c l o d e x t r i n Polymers 87 N.M.R. S t u d i e s of I n c l u s i o n Complexes 88 11.2. - I n t r o d u c t i o n 88 11.2.1. - S o l u t i o n - S t a t e N.M.R. S t u d i e s 89 11.2.2. - S o l i d - S t a t e N.M.R. S t u d i e s 91 11.3. - S y n t h e s i s 92 v i 11.3.1. - P r e v i o u s Work 92 11.3.2. - S y n t h e s i s of C y c l o d e x t r i n I n c l u s i o n Complexes 96 11.4. - 13C-N.M.R. S t u d i e s - Some S p e c i f i c Examples 99 11.5. - X-ray S t u d i e s 106 11.6. - R e s u l t s and D i s c u s s i o n 110 11.6.1. - 13C-N.M.R. E x p e r i m e n t a l Methods 110 11.6.2. - 13C-N.M.R. S t u d i e s of C y c l o d e x t r i n I n c l u s i o n Complexes w i t h L i q u i d Guest M o l e c u l e s 113 11.6.3. - 13C-N.M.R. S t u d i e s of C y c l o d e x t r i n I n c l u s i o n Complexes w i t h S o l i d Guest M o l e c u l e s 135 11.6.4. - 2H-N.M.R. S t u d i e s of C y c l o d e x t r i n I n c l u s i o n Complexes 145 D i a n i n ' s I n c l u s i o n Complexes 164 11.7. - I n t r o d u c t i o n 164 11.8. - S y n t h e s i s 166 11.9. - R e s u l t s and D i s c u s s i o n 167 11.10. - Summary and C o n c l u s i o n s 177 CHAPTER I I I - METAL-CHELATES OF SUGARS 188 111.1. - I n t r o d u c t i o n 189 111.2. - Par a m a g n e t i c s i n S o l u t i o n 191 111.2.1 . - R e l a x a t i o n P r o c e s s e s 191 I I I . 2 . 2 . - E l e c t r o n - S p i n R e l a x a t i o n 195 v i i I I I . 2 . 3 . - I s o t r o p i c S h i f t s 196 I I I . 3 . - Pa r a m a g n e t i c s i n the S o l i d S t a t e 201 111.3.1. - C h a r a c t e r i s t i c s of Paramagnetic S p e c t r a . 201 111.3.2. - S p e c t r a l Assignments 203 I I I .4. - S y n t h e s i s 204 111.4.1. - S c h i f f ' s Base F o r m a t i o n 204 111.4.2. - S c h i f f ' s Base M e t a l Complexes 205 111.5. - R e s u l t s and D i s c u s s i o n 209 111.6. - Summary and C o n c l u s i o n s 226 CHAPTER IV - EXPERIMENTAL 231 IV. 1 . - N u c l e a r Magnetic Resonance 232 IV.1.1. - Measurements i n the S o l u t i o n S t a t e 232 IV. 1.2. - Measurements i n the S o l i d S t a t e 232 IV.2. - G e n e r a l S y n t h e t i c P r o c e d u r e s 236 IV.3. - Chapter I I 237 IV.3.1. - Sources of M a t e r i a l s 237 IV.3.2. - S y n t h e s i s 238 IV.4. - Chapter I I I 244 IV.4.1. - Sources of M a t e r i a l s 244 IV.4.2. - P r e v i o u s Work 244 LIST OF TABLES Ta b l e CHAPTER I I 11 — 1. Complex f o r m i n g a b i l i t y of host m o l e c u l e s [3] and [4] w i t h v a r i o u s guest m o l e c u l e s I I - 2 . 1 3 C Chemical s h i f t v a l u e s of a r o m a t i c m o l e c u l e s as neat l i q u i d s and as encaged a r o m a t i c " s o l i d s " CHAPTER I I I 111 — 1 . Ground s t a t e s of t r a n s i t i o n m e tal i o n s as a f u n c t i o n of d c o n f i g u r a t i o n , geometry, and s p i n s t a t e (from Ref. [ 6 ] ) i x LIST OF FIGURES F i g u r e CHAPTER I 1-1. I n t e r a c t i o n between two i s o l a t e d magnetic p o i n t d i p o l e s a t a d i s t a n c e r 1 ) 2 14 1-2. A x i s system and p o l a r c o o r d i n a t e s f o r I-S d i p o l a r c o u p l i n g 15 1-3. R a p i d r o t a t i o n of p r o t o n s p i n 2, e f f e c t e d by h i g h power d e c o u p l i n g 18 1-4. Chemical s h i e l d i n g powder p a t t e r n : (A) a r b i t r a r y second rank t e n s o r ( ff^", ± <r2 * 0^ 3 ) ; (B) a x i a l l y symmetric second rank t e n s o r ( 071 = #2 2 * tfaa) (from Ref. [ 9 ] ) 20 1-5. Magic a n g l e s p i n n i n g of a specimen: (A) by r o t a t i n g i n a f i e l d of a s o l e n o i d under the magic a n g l e of 54°44'; (B) the tim e - a v e r a g e d v a l u e of a l l the b i n d i n g v e c t o r s becomes 54°44', i . e . <# 1 ) 2> = <^ 3,«> = 54°44' i n s p i t e of 0 , , 2 * $3,*  2 1 1-6. 1 3C-N.m.r. s p e c t r a of p o l y ( m e t h y l m e t h a c r y l a t e ) as a f u n c t i o n of s p i n n i n g f r e q u e n c y (from Ref. [18]) 23 1-7. ^C-^H C r o s s - p o l a r i z a t i o n experiment ( s p i n temperature c o n c e p t ) 24 1-8. R e p r e s e n t a t i o n of energy l e v e l s : (A) i n the l a b o r a t o r y frame; (B) i n the r o t a t i n g frame X (from Ref. [ 6 ] ) 26 1-9. T i m i n g sequence f o r c r o s s - p o l a r i z a t i o n e x p e r i m e n t : (A) p o l a r i z a t i o n of the 1H s p i n system; (B) s p i n l o c k i n g i n the r o t a t i n g frame; (C) t h e r m a l c o n t a c t between the 'H and the 1 3 C s p i n systems; (D) o b s e r v a t i o n of the 1 3 C f r e e i n d u c t i o n decay (from Ref. [ 6 ] ) 30 1-10. Schematic r e p r e s e n t a t i o n of high- s p e e d sample s p i n n e r s : (A) Andrew-Beams; (B) b u l l e t (from Ref. [10]) 35 1-11. A s p i n n e r system s u i t a b l e f o r v a r i a b l e t e m p e r a t u r e magic a n g l e s p i n n i n g s t u d i e s (from Ref. [27]) 36 1-12. P u l s e sequence used t o suppress the D e l r i n s i g n a l , and s i g n a l s from p r o t o n a t e d - c a r b o n atoms i n s o l i d s 39 1-13. C r o s s - p o l a r i z a t i o n w i t h f l i p - b a c k of 'H-spin m a g n e t i z a t i o n : (A) p u l s e t i m i n g f o r the c r o s s -p o l a r i z a t i o n ; (B) p h a s e - a l t e r n a t e d v e r s i o n of the f l i p - b a c k experiment (from Ref. [10]) 41 1-14. 1 3C-N.m.r. s p e c t r a of 2 - m e t h y l - 4 - n i t r o a n i l i n e : (A) normal c.p.-m.a.s.; (B) t h e o r e t i c a l spectrum, c a l c u l a t e d as d e s c r i b e d i n Ref. [40] 43 1-15. Energy l e v e l diagram f o r s p i n , 1 = 1 , showing the e f f e c t of a weak e l e c t r i c q u a d r u p o l e i n t e r a c t i o n , Q, on the Zeeman l e v e l s 48 x i 1-16. C a l c u l a t e d powder p a t t e r n f o r s p i n , I = 1, i n the f o l l o w i n g e l e c t r i c f i e l d g r a d i e n t s : (A) | = 0 . 0 ; (B) ^  = 0.67; (C) ^  = 1.0 (from Ref. [50]) 51 1-17. Schematic r e p r e s e n t a t i o n of a l i p i d b i l a y e r . [ n i s the normal t o the b i l a y e r . i l i s the ang l e between the magnetic f i e l d B 0 and r , ® i s the a n g l e between the C-D v e c t o r and B 0, and ® n i s the a n g l e between the C-D v e c t o r and r>.] 53 1-18. A n n u l a r r i n g between 6 and 6\6 w i t h a r e a 27rr2sin0d0 54 1-19. T h e o r e t i c a l powder p a t t e r n f o r a de u t e r o n i n a symmetric e l e c t r i c f i e l d g r a d i e n t ( = 0 ) . The dashed l i n e s i n d i c a t e the i n d i v i d u a l components of t h e m = -1 <--> m = 0 (£+) and m = 0 <—> m = +1 (£.) t r a n s i t i o n s , w h i l e the s o l i d l i n e r e p r e s e n t s the sum of the two components (from Ref. [51]) 57 1-20. I l l u s t r a t i o n of r e o r i e n t a t i o n a l motions f o r a C-D bond i n c l i n e d a t /3 degrees w i t h r e s p e c t t o an a x i s of m o t i o n a l a v e r a g i n g , z', which i n t u r n i s i n c l i n e d a t 7 degrees w i t h r e s p e c t t o anot h e r a x i s of m o t i o n a l a v e r a g i n g , z'' 58 1-21. R o t a t i n g frame r e p r e s e n t a t i o n of the s p i n i s o c h r o m a t s i n a Hahn echo sequence 60 x i i CHAPTER I I 11 — 1 . C y c l o d e x t r i n s : (A) dime n s i o n s of a-, 0-, and 7 - c y c l o d e x t r i n s ; (B) s t r u c t u r e of 0 - c y c l o d e x t r i n (from Ref. [ 8 ] ) 72 I I - 2 . C h a r a c t e r i s t i c s t r u c t u r a l f e a t u r e s of c y c l o -d e x t r i n s (from Ref. [8]) 74 11-3. Schematic r e p r e s e n t a t i o n of the f o r m a t i o n of c y c l o d e x t r i n i n c l u s i o n complexes 81 11-4. Schematic r e p r e s e n t a t i o n of the c a t a l y t i c h y d r o l y s i s of p h e n y l a c e t a t e by c y c l o d e x t r i n (from Ref. [ 6 ] ) 84 I I - 5 . T u r b i d i t y c u r v e s f o r 3 %, aqueous 0-cyclo-d e x t r i n s o l u t i o n s + 5 % of the c o r r e s p o n d i n g s o l v e n t (from Ref. [ 8 ] ) 93 I I - 6 . 1 3C-N.m.r. s p e c t r a of [A] [1] and (B) [2] i n D 20, (C) [3] i n C D C I 3 , and (D) [4] i n (CD 3) 2CO a t ambient temperature 101 I I - 7 . 1 3C-C.p.-m.a.s. s p e c t r a of an epoxy r e s i n , d i g l y c i d y l e t h e r of b i s p h e n o l A (DGEBA) r e c o r d e d over a 200°C temperature range (from Ref. [59]) 105 I I - 8 . Schematic diagrams of the a - c y c l o d e x t r i n (A) and 2,3,6-tri-O-Me-a-CD (B) complexes. Water m o l e c u l e s a re i n d i c a t e d by W (from Ref. [ 6 2 ] ) . 108 I I - 9 . S t r u c t u r e and numbering scheme of 2, 3, 6 - t r i-O-Me-a-CD (from Ref. [62]) 109 11-10. 1 3C-N.m.r. s p e c t r a of 1,2:3,4-di-O-x i i i i s o p r o p y l i d e n e - 6 - O - p - t o l y l s u l f o n y l - a - D -g a l a c t o p y r a n o s e . [ ( A ) N o r m a l 1 3 C - c . p . - m . a . s . s p e c t r u m , 5 - m s c o n t a c t t i m e , a n d 3 , 3 5 0 s c a n s . ( B ) D e l r i n - s i g n a l s u p p r e s s i o n , o b t a i n e d b y s e t t i n g a d e l a y t i m e o f 5 0 0 ms b e t w e e n t h e 1 8 0 ° a n d 9 0 ° p u l s e s o f 1 H . ( C ) N o n p r o t o n a t e d -c a r b o n s p e c t r u m , o b t a i n e d b y s e t t i n g a 40-/(S p e r i o d w i t h o u t p r o t o n d e c o u p l i n g , p r i o r t o 1 3 C d a t a - a c q u i s i t i o n . D e u t e r a t i o n a t C - 6 o f t h e c o m p o u n d i s r e c o r d e d i n ( B ) a n d ( C ) . D e l r i n s i g n a l s a n d s p i n n i n g s i d e - b a n d s a r e i n d i c a t e d a s X a n d S S B , r e s p e c t i v e l y . ] 111 1 1 - 1 1 . T h e d i m e n s i o n s o f t h e b e n z e n e r i n g , t a k i n g i n t o c o n s i d e r a t i o n t h e v a n d e r W a a l s r a d i i o f t h e a r o m a t i c h y d r o g e n s ( A ) a n d t h e m o l e c u l a r o r i e n t a t i o n s o f a m o n o s u b s t i t u t e d b e n z e n e r i n g i n c y c l o d e x t r i n ( B ) 114 1 1 - 1 2 . D i p o l a r - d e c o u p l e d c . p . 1 3 C - n . m . r . s p e c t r a o f [ 3 ] , w i t h a n d w i t h o u t m a g i c a n g l e s p i n n i n g . T h e s e a r e c o m p a r e d t o t h e s o l u t i o n - s t a t e s p e c t r u m o f t h e s a m e c o m p o u n d ( i n C D C I 3 ) 1 1 6 11 - 1 3 . 1 3 C - N . m . r . s p e c t r a o f t h e a m o r p h o u s s a m p l e s [ 4 ] : ( A ) p r e c i p i t a t e d s a m p l e ; ( B ) r e c r y s t a l l i z e d s a m p l e [ 2 4 ] , w i t h t h e g u e s t ( s o l v e n t ) m o l e c u l e s r e m o v e d , , b y h e a t i n g 1 1 8 11 - 1 4 . 1 3 C - N . m . r . s p e c t r a o f 2 , 6 - d i - 0 - M e - / 3 - C D i n c l u s i o n c o m p l e x e s : ( A ) [ 5 ] ; ( B ) [ 6 ] ; x i v (C) [ 7 ] ; (D) [ 8 ] ; (E) [ 9 ] ; (F) [ 1 0 ] ; (G) [11].; (H) [12] 119 11-15. 1 3C-N.m.r. s p e c t r a of 2,3,6-tri-O-Ac-0-CD i n c l u s i o n complexes: (A) [ 2 3 ] ; (B) [ 2 4 ] ; (C) [25] 124 11-16. D i p o l a r - d e p h a s i n g 1 3C-n.m.r. s p e c t r a : (A) [ 5 ] ; (B) [ 7 ] ; (C) [ 8 ] ; (D) [ 2 3 ] ; (E) [ 2 4 ] ; (F) [25] 128 11-17. 1 3C-N.m.r. s p e c t r a of [ 5 ] , p r e h e a t e d a t the te m p e r a t u r e s i n d i c a t e d 131 11-18. 1 3C-N.m.r. s p e c t r a of [ 6 ] , p r e h e a t e d a t the tem p e r a t u r e s i n d i c a t e d 133 11-19. 1 3C-N.m.r. s p e c t r a of 2 r6-di-0-Me-/3-CD-d-limonene complex: (A) normal c.p.-m.a.s.; (B) w i t h d i p o l a r d ephasing 134 11-20. Schematic drawings of the i n c l u s i o n p o s s i b i l i t i e s f o r l a r g e r guest m o l e c u l e s (from Ref. [61]) 136 11-21. 1 3C-N.m.r. s p e c t r a of (A) b i p h e n y l and (B) 2, 6-di-0-Me-/3-CD-biphenyl i n c l u s i o n complex, [13] 138 11-22. 1 3C-N.m.r. s p e c t r a of (A) 4 , 4 ' - d i m e t h y l -b i p h e n y l and (B) 2 ,6-di-0-Me-/3-CD-4 , 4 ' - d i m e t h y l b i p h e n y l i n c l u s i o n complex, [ 1 4 ] . 140 11-23. 1 3C-N.m.r. s p e c t r a of (A) p - d i - t e r t . -b u t y l b e n z e n e and (B) 2,6-di-O-Me-0-CD-p-di-t e r t , - b u t y l b e n z e n e i n c l u s i o n complex, [ 1 5 ] . . . . 142 XV 11-24. 1 3C-N.m.r. s p e c t r a of [ 1 5 ] : (A) normal c.p.-m.a.s. (sample i n a d e u t e r a t e d , p l e x i g l a s s p i n n e r ) ; (B) D e l r i n - s i g n a l s u p p r e s s i o n ; (C) d i p o l a r d e p h a s i n g spectrum ( o b t a i n e d by s e t t i n g a 40-/ts p e r i o d w i t h o u t p r o t o n d e c o u p l i n g , p r i o r t o 1 3 C d a t a - a c q u i s i t i o n ) ; (D) same as ( C ) , but w i t h a l o n g e r w a i t i n g p e r i o d of 100 jus; (E) D e l r i n - s i g n a l s u p p r e s s i o n and d i p o l a r dephasing 143 11-25. I l l u s t r a t i o n of an i s o l a t e d m e t h y l - d 3 group o r i e n t e d w i t h i t s C 3 a x i s i n c l i n e d a t the p o l a r c o o r d i n a t e s (6,^) w i t h r e s p e c t t o the l a b o r a t o r y frame 147 11-26. 2H-N.m.r. s p e c t r a of (A) (CD 3) 2SO i n [ 2 6 ] ; (B) (CD 3) 2CO i n [ 2 7 ] ; (C) (CD 3) 2SO i n [ 2 8 ] ; (D) (CD 3) 2CO i n [ 2 9 ] ; (measured a t 20°C) 148 11-27. 2H-N.m.r. s p e c t r a of (CD 3) 2SO i n (A) [26] and (B) [28] r e c o r d e d a t the te m p e r a t u r e s i n d i c a t e d 149 11-28. 2H-N.m.r. s p e c t r a of (A) f r o z e n C 6D 6; (B) C 6D 6 i n [ 5 ] ; (C) C 6D 6 i n [ 2 3 ] ; {(A) and ( B ) , measured a t 20°C] 1 56 11-29. V a r i a t i o n of w i t h temperature f o r C 6D 6 i n [5] and [ 2 3 ] , and C 6H 5CH 2D i n [6] 157 11-30. 2H-N.m.r. s p e c t r a of C 6D 6 i n [ 5 ] : (A) i n un s e a l e d and (B) i n s e a l e d t u b e s , r e c o r d e d a t the t e m p e r a t u r e s i n d i c a t e d 159 x v i 1 1 - 3 1 . 2H-N.m.r. s p e c t r a of (A) C 6H 5CH 2D i n [ 6 ] ; (B) C 6H 5CH 2D i n [ 2 4 ] ; (C) C 6H 5CH 2CH 2D i n [ 7 ] ; (measured a t 20°C) 161 11-32. M o l e c u l a r r e o r i e n t a t i o n of t o l u e n e a l o n g the z' - a x i s 1 62 11 - 3 3 . 2H-N.m.r. s p e c t r a of (A) C 6H 5CH 2D i n [6] and (B) C 6H 5CH 2CH 2D i n [7] r e c o r d e d a t the • tem p e r a t u r e s i n d i c a t e d 163 11-34. The s t r u c t u r e s of D i a n i n ' s compound (A and B) and m o d i f i e d D i a n i n ' s compound which l a c k s the 2-methyl groups t r a n s t o the p-hydr o x y p h e n y l s u b s t i t u e n t (C) (from Ref. [93]) 165 11 - 3 5 . 1 3C-N.m.r. s p e c t r a of D i a n i n ' s compound and i t s i n c l u s i o n complexes, w i t h o u t and w i t h d i p o l a r dephasing ( t o p and bottom s p e c t r a , r e s p e c t i v e l y ) : (A) [ 3 0 ] ; (B) [ 3 1 ] ; (C) [ 3 2 ] ; (D) [33] 168 11-36 . S t r u c t u r e of D i a n i n ' s compound d e p i c t i n g the o r i e n t a t i o n of the a r o m a t i c guest m o l e c u l e . . . . 174 11-37. T h e o r e t i c a l 2H-n.m.r. s p e c t r a of p o l y c r y s t a l l i n e p h e n y l a l a n i n e - d 5 where e 2qQ/h = 180 kHz and \ = 0.05. ( B ) , powder p a t t e r n averaged by f a s t 180° f l i p s about the C / 3 - C Y a x i s . ( C ) , powder p a t t e r n averaged by f a s t r o t a t i o n about the C^ s - C R a x i s (from Ref. [101]) 1 75 11-3 8 . 2H-N.m.r. s p e c t r a of (A) C 6 D 6 i n [ 3 1 ] ; (B) x v i i C 6H 5CH 2D i n [ 3 2 ] ; (measured a t 20°C) 176 CHAPTER I I I 111 — 1. Energy l e v e l s f o r a p r o t o n w i t h weak h y p e r f i n e c o u p l i n g t o an e l e c t r o n . V e r t i c a l arrows r e p r e s e n t a l l o w e d n u c l e a r t r a n s i t i o n s (from Ref. [6]) 192 I I I - 2 . 1 3C-C.p.-m.a.s. s p e c t r a of m e t h y l - 3 , 4 , 6 - t r i - 0 -a c e t y l - 2 - d e o x y - 2 - s a l i c y l ideneamino-/3-D-g l u c o p y r a n o s i d e and i t s complex: (A) f r e e l i g a n d [ 5 ] ; (B) d i a m a g n e t i c z i n c ( I I ) complex [ 1 3 ] . (C) D i p o l a r d ephasing spectrum of the z i n c ( I I ) complex 210 111-3. 1 3C-N.m.r. s p e c t r a of paramagnetic c o p p e r ( I I ) complexes: (A) [ 1 5 ] ; (B) and (C) [ 1 2 ] , w i t h c o n t a c t t i m e s of 0.1 and 1 ms, r e s p e c t i v e l y . . . 213 I I I - 4 . High-power, gated d e c o u p l i n g spectrum of copper (I I ) complex [12] 217 I I I - 5 . R e p r e s e n t a t i o n of p o l y m e r i c s t r u c t u r e s : (A) a l g i n a t e ; (B) c h i t o s a n 219 I I I - 6 . 1 3C-N.m.r. s p e c t r a of c h i t o s a n and i t s S c h i f f ' s base d e r i v a t i v e s : (A) c h i t o s a n [ 1 8 ] ; (B) s a l i c y l i d e n e c h i t o s a n [ 1 9 ] ; (C) 4 - n i t r o -b e n z y l i d e n e c h i t o s a n [21] 221 I I I - 7 . 1 3C-N.m.r. s p e c t r a of mixed S c h i f f ' s bases of b e n z y l i d e n e c h i t o s a n and s a l i c y l i d e n e c h i t o s a n [20] w i t h and w i t h o u t c o p p e r ( I I ) i o n s : (A) f r e e l i g a n d ; (B) and (C) copper complexed, x v i i i w i t h c o n t a c t times s e t a t 0.5 and 3 ms, r e s p e c t i v e l y 223 111-8. 1 3C-N.m.r. s p e c t r a of [ 2 1 ] , "doped" w i t h c o p p e r ( I I ) i o n s . C o n d i t i o n s were: (A) 3 ms and (B) 0.1 ms c o n t a c t t i m e s 225 x i x ACKNOWLEDGEMENT I e x p r e s s my g r a t i t u d e t o Dr. L. D. H a l l f o r h i s guidance and c o n s t a n t encouragement throughout the c o u r s e of t h i s work. Wh i l e i t i s i m p o s s i b l e t o thank a l l thos e who c o n t r i b u t e d t o the c o m p l e t i o n of t h i s t h e s i s , I am t r u l y i n d e b t e d t o Dr. A. N a i t o f o r many h e l p f u l d i s c u s s i o n s . I t i s a l s o a p l e a s u r e t o thank M e s s r s . L. T a l a g a l a , V. Rajanayagam, K. Holme and S. Luck f o r p r o o f - r e a d i n g the m a n u s c r i p t . F i n a l l y , s p e c i a l thanks a r e due t o Mr. K. S u k u l and o t h e r s i n the e l e c t r i c a l shop of t h i s department f o r t h e i r e x p e r t t e c h n i c a l back-up. Dedi cat i on my I at e Fat he 1 INTRODUCTION 2 C a r b o h y d r a t e s a r e amongst the most abundant t y p e s of mo l e c u l e i n n a t u r e , and they p l a y a v i t a l r o l e i n every form of l i f e . In r e c e n t y e a r s , many new examples of t h e i r i m p o r t a n t b i o m e d i c a l and i n d u s t r i a l a p p l i c a t i o n s have been u n r a v e l l e d ; these i n c l u d e the development of new p h a r m a c e u t i c a l s 1 and chromatography m a t e r i a l s , 2 and t h e i r use i n o i l r e c o v e r y . 3 These and o t h e r a r e a s (not mentioned here) would b e n e f i t from the development of g e n e r a l m e t h o d o l o g i e s i n which c a r b o h y d r a t e s can be c h e m i c a l l y m o d i f i e d . In t u r n , t h i s r e q u i r e s the development of new s p e c t r o s c o p i c t o o l s f o r e v a l u a t i n g the p h y s i c a l and c h e m i c a l p r o p e r t i e s of what a r e f r e q u e n t l y i n t r a c t a b l e m a t e r i a l s . In t h i s t h e s i s , emphasis was p l a c e d on the l a t t e r a r e a , and n.m.r. s p e c t r o s c o p y has been used e x t e n s i v e l y throughout the co u r s e of the work. P r o t o n and carbon-13 n u c l e a r magnetic resonance ( 1H-n.m.r. and 1 3C-n.m.r.) s p e c t r o s c o p y have p r e v i o u s l y been shown t o be u s e f u l f o r the c h a r a c t e r i z a t i o n of c a r b o h y d r a t e s " i n s o l u t i o n . Both mono- and p o l y - s a c c h a r i d e c h e m i s t r y have b e n e f i t e d from both t h e s e methods f o r s t u d y i n g the s t r u c t u r e and f u n c t i o n of the " n a t u r a l " and " m o d i f i e d " forms of t h e s e m a t e r i a l s . U n f o r t u n a t e l y , 1H-n.m.r. s p e c t r o s c o p y as a method f o r s t u d y i n g p o l y s a c c h a r i d e s s u f f e r s because the resonances a r e e x c e s s i v e l y b r o a d . 5 F o r t u n a t e l y , t h i s problem i s somewhat l e s s s e v e r e f o r 1 3 C n.m.r., and the wide range of c h e m i c a l s h i f t s (>200 p a r t s per m i l l i o n ) f o r the carbon resonances 3 g e n e r a l l y a l l o w s assignments t o be made f o r the r e s o l v a b l e , i n d i v i d u a l peaks i n most s p e c t r a . 6 A minor s h o r t c o m i n g of t h i s method i s t h a t the 1 3C-n.m.r. spectrum of a s a c c h a r i d e cannot be d i r e c t l y i n t e r p r e t e d w i t h o u t comparison w i t h s p e c t r a of known compounds. T h i s i s compensated by the w e a l t h of i n f o r m a t i o n p r o v i d e d f o r m o l e c u l a r s t r u c t u r e , e s p e c i a l l y on the n a t u r e of the anomeric l i n k a g e s f o r the s p e c i f i c t y p e s of r e s i d u e s . U n f o r t u n a t e l y , t h e r e are many i n s t a n c e s where the s t r u c t u r a l c h a r a c t e r i z a t i o n of c a r b o h y d r a t e s cannot be a i d e d by the normal h i g h - r e s o l u t i o n F o u r i e r t r a n s f o r m ( F . t . ) 1 H - and 1 3C-n.m.r. approaches. T h i s i s the s i t u a t i o n f o r samples which cannot be d i s s o l v e d under c o n d i t i o n s t h a t would r e t a i n t h e i r s t r u c t u r a l i n t e g r i t y , or where t h e r e i s the p o s s i b i l i t y t h a t s o l v e n t - s o l u t e i n t e r a c t i o n s c o u l d c o m p l e t e l y change the m o l e c u l a r s t r u c t u r e or c o n f o r m a t i o n . F i n a l l y , h i g h - r e s o l u t i o n n.m.r. methods are i l l - s u i t e d f o r s t u d i e s of p o l y s a c c h a r i d e s t h a t are of low s o l u b i l i t y or t h a t are i n s o l u b l e . In the l a t t e r s i t u a t i o n , no resonance s i g n a l i s observed by normal F . t . n.m.r. t e c h n i q u e s f o r the f o l l o w i n g p r a c t i c a l r e a s o n s : " l i n e - b r o a d e n i n g " , caused by a n i s o t r o p i c d i p o l e - d i p o l e i n t e r a c t i o n s and c h e m i c a l s h i f t a n i s o t r o p y , and " l o w - s e n s i t i v i t y " a s s o c i a t e d w i t h the e x t r e m e l y l o n g 1 3C s p i n l a t t i c e r e l a x a t i o n t i m e s . I t i s now w e l l known t h a t such problems can be l a r g e l y overcome by the combined use of h i g h power d e c o u p l i n g 7 ( t o remove 1 3 C - 1 H d i p o l a r c o u p l i n g ) , magic a n g l e s p i n n i n g 8 ( t o 4 remove c h e m i c a l s h i f t a n i s o t r o p y ) , and c r o s s - p o l a r i z a t i o n 9 ( t o overcome 1 3 C s e n s i t i v i t y p r o b l e m s ) . As a r e s u l t , 1 3C n.m.r. measured i n the s o l i d s t a t e can prove u s e f u l f o r c h e m i c a l and s t r u c t u r a l i n v e s t i g a t i o n s of o r g a n i c m o l e c u l e s i n the s o l i d s t a t e . Many m o d i f i c a t i o n s 1 0 of the b a s i c methods have been r e p o r t e d , which f u r t h e r f a c i l i t a t e s o l i d -s t a t e s t u d i e s . The methodology of s o l i d - s t a t e n.m.r. s p e c t r o s c o p y complements s i n g l e - c r y s t a l s t r u c t u r a l a n a l y s i s i n t h a t i t i s c a p a b l e of c o n f i r m i n g the c o r r e c t n e s s of e x i s t i n g X-ray s t r u c t u r e s . The growing p o p u l a r i t y of t h i s method i s dominated by the ease of sample h a n d l i n g , and the reduced time needed t o a c q u i r e a spectrum. The main theme of t h i s T h e s i s c o n s i s t s of the a p p l i c a t i o n of s o l i d - s t a t e n.m.r. methods t o both mono- and p o l y - s a c c h a r i d e c a r b o h y d r a t e s . Two major n.m.r. methods have been e v a l u a t e d f o r s t u d y i n g t h e s e s u b s t a n c e s ; these are the carbon-13 c r o s s - p o l a r i z a t i o n - m a g i c a n g l e s p i n n i n g ( 1 3C-c.p.-m.a.s.) m e t h o d 1 1 r e f e r r e d t o above, and the d e u t e r i u m ( 2H) qu a d r u p o l e echo m e t h o d . 1 2 The l a t t e r method i s used s p e c i f i c a l l y t o study the a n i s o t r o p i c motion of m o l e c u l e s . The r e s o l u t i o n , s e n s i t i v i t y , as w e l l as the t h e o r y of the c.p. and c.p.-m.a.s. methods, w i l l be d i s c u s s e d i n some d e t a i l i n the f i r s t p a r t of Chapter I ; the second p a r t d e s c r i b e s b r i e f l y the t h e o r y of s o l i d - s t a t e 2H n.m.r. p e r t i n e n t t o randomly o r i e n t e d samples. Our i n i t i a l m o t i v a t i o n was t o study the m o l e c u l a r m o b i l i t i e s of some s a c c h a r i d e systems which might have 5 p o t e n t i a l p r a c t i c a l use as p h a r m a c e u t i c a l s . C y c l o d e x t r i n s were the o b v i o u s i n i t i a l c h o i c e because of t h e i r known a b i l i t y t o form i n c l u s i o n c o m p l e x e s , 1 3 and t h e i r s e l e c t i v e c a t a l y t i c a c t i v i t y . 1 " These s u b s t a n c e s are m a c r o c y c l i c g l u c o s e polymers produced by the a c t i o n 1 5 of B a c i l l u s  macerans amylase on s t a r c h . I n t e r e s t i n g l y , complexes of drugs and i n s e c t i c i d e s w i t h c y c l o d e x t r i n s o f t e n e x h i b i t p h y s i c o c h e m i c a l and b i o c h e m i c a l p r o p e r t i e s , which are not shown i n the absence of the c y c l o d e x t r i n . For t h a t r e a s o n , e x t e n s i v e s t u d i e s by s o l u t i o n - s t a t e n.m.r. s p e c t r o s c o p y of both " i n c l u s i o n " and " c a t a l y s i s " of c y c l o d e x t r i n s have been d e s c r i b e d 1 6 i n the l a s t decade. However, no such s t u d i e s had been made i n the s o l i d s t a t e and i t was d e c i d e d t o f o c u s our a t t e n t i o n on the m o l e c u l a r r e o r i e n t a t i o n of the i n c l u s i o n complexes of a- and 0 - c y c l o d e x t r i n s i n the s o l i d s t a t e . C o n s i d e r a b l e advances i n the f o r m u l a t i o n of t h e o r i e s on the e f f e c t of v a r i o u s dynamic modes on 2H-n.m.r. l i n e s h a p e s had a l r e a d y been made, and more were a n t i c i p a t e d , which would enable us t o a n a l y z e our r e s u l t s q u a l i t a t i v e l y . As w i l l be seen, the p r e p a r a t i o n of s u i t a b l e complexes has i n v o l v e d a number of d e u t e r a t e d guest m o l e c u l e s , a r o m a t i c or o t h e r w i s e , w i t h c y c l o d e x t r i n s and some of t h e i r d e r i v a t i v e s . O v e r a l l , the s e r i e s of compounds p r e p a r e d has been used t o e s t a b l i s h a r e l a t i o n s h i p between m o t i o n , s t r u c t u r e , and s t a b i l i t y . We were e n t i c e d i n t o making f u r t h e r e x p l o r a t i o n s w i t h s o l i d - s t a t e n.m.r. by the slow growth i n e a r l y 1981 of the 6 a p p l i c a t i o n of c.p.-m.a.s. methods t o c h e m i c a l problems. At t h a t t i m e , most of the l i t e r a t u r e r e p o r t s were c e n t e r e d on the t e c h n i q u e s t h e m s e l v e s , or on i n v e s t i g a t i o n s of a more p h y s i c a l n a t u r e . In c o n t r a s t , i t was d e c i d e d t h a t t h i s t h e s i s s h o u l d encompass a broad d i s c u s s i o n , from an o r g a n i c c h e m i s t ' s v i e w p o i n t , of the t y p e s of c h e m i c a l i n f o r m a t i o n t h a t may be d e r i v e d from the 1 3 C s p e c t r a of c a r b o h y d r a t e s . E l u c i d a t i o n of the s t r u c t u r e s and motion of c y c l o d e x t r i n i n c l u s i o n complexes would, b e s i d e s c o n s t i t u t i n g an i m p o r t a n t and i n t e r e s t i n g c h e m i c a l problem i n i t s own r i g h t , h e l p i l l u s t r a t e broader o p p o r t u n i t i e s . Chapter I I of t h i s T h e s i s i s devoted m a i n l y t o s o l i d - s t a t e n.m.r. s t u d i e s of c y c l o d e x t r i n s and t h e i r i n c l u s i o n complexes. I t was f e l t t h a t i t was d e s i r a b l e t o make c o m p a r a t i v e s t u d i e s w i t h another c l a s s of i n c l u s i o n complexes and D i a n i n ' s compound was chosen because complexes analogous t o those of c y c l o d e x t r i n s c o u l d be r e a d i l y s y n t h e s i z e d . 1 7 T h i s w i l l be d i s c u s s e d as a s u b - s e c t i o n of Chapter I I . Chapter I I I , summarizes the a p p l i c a t i o n of s o l i d - s t a t e n.m.r. methods t o another a r e a which has p r e v i o u s l y been of i n t e r e s t a t U.B.C., namely, m e t a l - s u g a r c o n j u g a t e s . The i n t e r a c t i o n of v a r i o u s m e t a l s and sugars has p r e v i o u s l y been s t u d i e d i n s o l u t i o n by n.m.r., and by e l e c t r o n s p i n resonance ( e . s . r . ) i n both s o l u t i o n and s o l i d s t a t e . The work d e s c r i b e d i n t h i s T h e s i s r e p r e s e n t s an i n i t i a l e f f o r t t o adapt some of the e x p e r i e n c e p r e v i o u s l y g a i n e d d u r i n g the work of Chapter I I t o the use of metal i o n s f o r p a r t i a l 7 assignment of 1 3C-c.p.-m.a.s. s p e c t r a . S c h i f f ' s bases formed from amino d e r i v a t i v e s of mono- and p o l y - s a c c h a r i d e s were the main f o c u s of those s t u d i e s s i n c e an e x t e n s i v e knowledge of t h e i r c h e l a t i n g p r o p e r t i e s had been p r e v i o u s l y e s t a b l i s h e d . 1 8 S i n c e c o p p e r ( I I ) complexes were used, t h i s work l e d t o the e v a l u a t i o n of the paramagnetic e f f e c t s of c o p p e r ( I I ) i o n on the sugars i n the s o l i d s t a t e . The s y n t h e s e s of the s p e c i f i c m e t a l - s u g a r compounds i n v o l v e d e x t e n s i o n s of p r o c e d u r e s p r e v i o u s l y documented i n t h i s l a b o r a t o r y . 8 R e f e r e n c e s 1. H. H. Baer, J . L. S t r o m i n g e r , The Amino Sugars, The  C h e m i s t r y and B i o l o g y of Compounds C o n t a i n i n g Amino  Sugars, Academic P r e s s , New York, IA, 1969; R. L. Whis11er, I n d u s t r i a l Gums, P o l y s a c c h a r i d e s and T h e i r  D e r i v a t i v e s , Academic P r e s s , New York, 1973. 2. H. F. H i x s o n , E. P. G o l d b e r g , Polymer G r a f t s i n  B i o c h e m i s t r y , Dekker, New York, 1976. 3. R. L. W h i s t l e r , I n d u s t r i a l Gums, Academic P r e s s , New York, 1973; C. T. G i t h e n s , J . W. Burnham, S o c i e t y of P e t r o l e u m E n g i n e e r s J o u r n a l , J_7, 5( 1977); R. T i n e r , Southwestern P e t r o l e u m S h o r t Course P r o c e e d i n g s , 23, 1976; B. S a n d i f o r d , Energy Communications, 4, 53(1978); H. E. G i l l i l a n d , i b i d . , 4, 83(1978). 4. A. S. P e r l i n , G. K. Hamer, ACS Symp. S e r . No. 103, 1979, 123. 5. A. S. P e r l i n , B. Casu, G. R. Sanderson, L. F. Johnson, Can. J . Chem., 48, 2260(1968). 6. A. Darke, E. G. F i n e r , R. Moorhouse, D. A. Rees, J . Mol. B i o l . , 99, 477(1975). 7. F. B l o c h , Phys. Rev., 111, 841(1958); L. R. S a r l e s , R. M. C o t t s , i b i d . , _m, 853(1958). 8. E. R. Andrew, P r o g . N u c l . Magn. Reson. S p e c t r o s c , 8, 1(1971). 9. S. R. Hartmann, E. L. Hahn, Phys. Rev., 128, 2042(1962). 10. D. A. T o r c h i a , J . Magn. Reson., 3_0, 613(1978); J . 9 T e g e n f e l d t , U. H a e b e r l e n , i b i d . , 36, 453(1979); S. J . O p e l l a , M. H. F r e y , J . Am. Chem. S o c , J_01_, 5854(1979). 11. J . S c h a e f e r , E. 0. S t e j s k a l , i b i d . , 98, 1031(1976). 12. J . D a v i s , K. J e f f r e y , M. Bloom, M. V a l i c , T. H i g g s , Chem. Phys. L e t t . , 42, 390(1976). 13. F. Cramer, Chem. Ber., 86, 1576(1953). 14. F. Cramer, W. Saenger, H.-Ch. S p a t z , J . Am. Chem. Soc., 89, 14(1967). 15. D.. F r e n c h , Adv. Carbohydr. Chem., j_2, 189(1957); F. S c h a r d i n g e r , Z e n t r a l b l . B a k t e r i o l . P a r a s i t e n k d . I n f e k t i o n s k r . Hyg. I I , 29, 188(1911). 16. J . P. Behr, J . M. Lehn, J . Am. Chem. S o c , 98, 1743(1976); M. Komiyama, M. L. Bender, P r o c . Nat. Acad. S c i . U.S.A., 73, 2969(1976). 17. D. D. M a c N i c o l , J . J . Mc K e n d r i c k , D. R. W i l s o n , Chem. S o c Rev., 7, 65(1978). 18. R. A. A. M u z z a r e l l i , C h i t i n , Pergamon, O x f o r d , 1977; M. J . Adam, L. D. H a l l , J . Chem. Soc. Chem. Comm., 1979, 234; L. D. H a l l , M. Y a l p a n i , Carbohydr. Res., 8^ 3, C5(1980). 10 CHAPTER I GENERAL BACKGROUND 11 S o l i d - S t a t e N.M.R. Methods  1.1. H i g h - R e s o l u t i o n 1 3 C N.M.R.  1.1.1. I n t r o d u c t i o n The development of h i g h - r e s o l u t i o n , p u l s e F o u r i e r t r a n s f o r m 1 3 C n.m.r. as a r o u t i n e t o o l d u r i n g the e a r l y 1970's c o n s t i t u t e d a major advance i n the a n a l y s i s of o r g a n i c l i q u i d s . More r e c e n t l y , t h e r e has been an i n c r e a s i n g i n t e r e s t i n the a p p l i c a t i o n of n.m.r. t e c h n i q u e s t o problems i n v o l v i n g o r g a n i c s o l i d s . In s o l i d s , the l a c k of m o l e c u l a r motion a l l o w s the d i p o l a r - and a n i s o t r o p i c -magnet i n t e r a c t i o n s between s p i n s t o dominate the a b s o r p t i o n spectrum which i s , t h e r e f o r e , v e r y much broader than t h a t of l i q u i d . I f thos e i n t e r a c t i o n s c o u l d be e f f e c t i v e l y removed, the r e s u l t a n t h i g h - r e s o l u t i o n n.m.r. spectrum would be of g r e a t v a l u e i n the s t r u c t u r a l and dy n a m i c a l a n a l y s i s of m o l e c u l e s , s i n c e the s o l i d - s t a t e 1 3 C -n.m.r. s p e c t r o s c o p y would then p r o v i d e a d i r e c t l i n k between n.m.r. s t u d i e s i n s o l u t i o n and X-ray d a t a from the s o l i d s t a t e . The two t e c h n i q u e s n e c e s s a r y f o r o b t a i n i n g the r e q u i r e d h i g h - r e s o l u t i o n n.m.r. s p e c t r a from s o l i d s a r e now w e l l e s t a b l i s h e d ; they a r e g e n e r a l l y r e f e r r e d t o as " c r o s s -p o l a r i z a t i o n " (c.p.) and " m a g i c - a n g l e - s p i n n i n g " (m.a.s.). The s e n s i t i v i t y - e n h a n c e d , c r o s s - p o l a r i z a t i o n n.m.r. experiment was f i r s t i n t r o d u c e d by Hartmann and Hahn 1 i n 1962, but was not a p p l i e d t o n a t u r a l - a b u n d a n c e 1 3 C s t u d i e s of o r g a n i c s o l i d s by P i n e s e t a l . 2 u n t i l some t e n y e a r s l a t e r . I n d e p e n d e n t l y of t h a t a pproach, i n the l a t e f i f t i e s , 1 2 Andrew 3 and Lowe," each i n t r o d u c e d a d i f f e r e n t d e s i g n f o r magic a n g l e s p i n n i n g , each w i t h i t s own unique advantages. However, i t was o n l y by combining these two t e c h n i q u e s , t h a t S c h a e f e r and S t e j s k a l 5 became the f i r s t workers i n 1975, t o r e p o r t h i g h - r e s o l u t i o n 1 3C-n.m.r. s p e c t r a of polymers i n the g l a s s y s t a t e . The c o m b i n a t i o n d e v e l o p e d by them has g a i n e d widespread p o p u l a r i t y because of i t s s i m p l i c i t y , the ease of i n t e r p r e t a t i o n of the s p e c t r a , and the f a c t t h a t the observed l i n e w i d t h s can be l e s s than 0.1 p a r t s per m i l l i o n (p.p.m.) i n e x c e p t i o n a l c a s e s . The 1 3C~c.p.-m.a.s. method has a l r e a d y been s u c c e s s f u l l y a p p l i e d t o a wide d i v e r s i t y of m a t e r i a l s , r a n g i n g from c r y s t a l s of s i m p l e o r g a n i c m o l e c u l e s , t o o i l s h a l e s and c o a l s . 6 A l t h o u g h the method has been a v a i l a b l e f o r almost a decade, i t s a p p l i c a t i o n t o the c a r b o h y d r a t e f i e l d i s s t i l l f a i r l y new, and d u r i n g the c o u r s e of the p r e s e n t work, o n l y a few 1 3C~c.p.-m.a.s. s p e c t r a have been r e p o r t e d f o r h i g h - m o l e c u l a r - w e i g h t p o l y s a c c h a r i d e s 7 of l i m i t e d s o l u b i l i t y and h i g h s o l u t i o n - v i s c o s i t y . T h i s L a b o r a t o r y has a l s o demonstrated the use of t h i s method f o r s t u d y i n g the p r i m a r y s t r u c t u r e of p o l y s a c c h a r i d e s . 8 In o r d e r t o u n d e r s t a n d the 1 3C-c.p.-m.a.s. method, i t i s n e c e s s a r y t o d i s c u s s the d u a l problems of r e s o l u t i o n and s e n s i t i v i t y , and the p r i n c i p l e s which have l e d t o t h e i r s o l u t i o n , i n some d e t a i l . 1 3 1.1.2. L i n e - B r o a d e n i n g Mechanisms  1.1.2.1. P r o t o n D i p o l a r B r o a dening C l a s s i c a l l y , the energy of i n t e r a c t i o n between two i s o l a t e d magnetic p o i n t d i p o l e s /U, and /*2 i s g i v e n by ( F i g . I - 1 ) 9 E m = j Ai, .M». - 3 ( M, . r ) (Mt.r) l M° ( 1 ) ) F 3 - F 5 j 4TT where the v e c t o r r i s the d i s t a n c e between /<, and / ( z , and A " i s the p e r m e a b i l i t y c o n s t a n t (47r x 10" 7 kg m s ~ 2 A ~ 2 ) . The a p p r o p r i a t e H a m i l t o n i a n f o r the d i p o l a r i n t e r a c t i o n of a s u b s t a n c e c o n t a i n i n g two d i f f e r e n t magnetic s p e c i e s , I and S, of m a g n e t o g y r i c r a t i o y and y , i s H j = H „ + H s s + H I S (2) In the d i s c u s s i o n t h a t f o l l o w s o n l y the l a s t term of Eq. (2) i s i n v o l v e d ; by s u b s t i t u t i n g ju = 7T1I i n t o Eq. ( 1 ) , H j S may be w r i t t e n as H i s = 1r%^2 \ I» ^ s " 3 (Ix «r) (Is . r ) I Mo (3) j r 3 P \ in When the s c a l a r p r o d u c t s a r e expanded and the e q u a t i o n i s t r a n f o r m e d t o s p h e r i c a l p o l a r c o o r d i n a t e s ( F i g . 1-2), the f o l l o w i n g e x p r e s s i o n i s o b t a i n e d : F i g . 1 - 1 . I n t e r a c t i o n between two i s o l a t e d magnetic p o i n t d i p o l e s a t a d i s t a n c e r 1 ( 2 * The e x p r e s s i o n s f o r the s i x terms, A t o F, can be found i n s t a n d a r d t e x t s 9 - 1 1 and a r e summarized i n Appendix I . Each of them c o n t a i n s a s p i n f a c t o r and a g e o m e t r i c f a c t o r , and t h e i r v a l u e s are a v e r a g e d t o z e r o f o r r a p i d i s o t r o p i c mot i o n . In the absence of i n t e r a c t i o n s i n v o l v i n g s c a l a r c o u p l i n g and c h e m i c a l s h i f t a n i s o t r o p y , the t o t a l s p i n H a m i l t o n i a n f o r the IS ( h e t e r o n u c l e a r ) system i s reduced t o the sum of Zeeman and d i p o l a r terms, t h a t i s , 1 5 h" 'H = -( V x I l x + V sI* S z ) + h" 'Hd where V x and V s are the Larmor f r e q u e n c i e s , and Hd i s g i v e n F i g . 1-2. A x i s system and p o l a r c o o r d i n a t e s f o r I-S d i p o l a r c o u p l i n g . by Eq. ( 4 ) . S i n c e the d i p o l e e n e r g i e s a r e v e r y much s m a l l e r than the Zeeman e n e r g i e s , o n l y the A term commutes w i t h the Zeeman o p e r a t o r and the t r u n c a t e d H a m i l t o n i a n 1 2 becomes h" 1H = -(\>jllz + V sT S z ) + R I i 2 t S z ( l - 3 c o s 2 0 ) (5) where 6 i s the a n g l e between r I S and the a p p l i e d s t a t i c magnetic f i e l d , B 0 , and R = ( ^0/4^) r ~ 3 7 Z -y$ (h/2jr) ( i n fre q u e n c y u n i t s ) i s sometimes r e f e r r e d t o as the d i p o l a r c o u p l i n g c o n s t a n t . The c o r r e s p o n d i n g energy l e v e l s c a l c u l a t e d a r e E m = h " 1 E m = -( Vjm^ + %ms ) + Rm xm s(l - 3 c o s 2 0 ) (6) The u s u a l s e l e c t i o n r u l e s a p p l y (AMx = ±1 ,AMS = 0 and 1 6 AMj = 0,AMs = ±1 f o r a l l o w e d I and S t r a n s i t i o n s , r e s p e c t i v e l y ) so t h a t f o r the case of two i s o l a t e d s p i n - l / 2 n u c l e i , I and S, i n a s i n g l e c r y s t a l w i t h o n l y one o r i e n t a t i o n f o r r I S , t h e r e a re two S t r a n s i t i o n s a t V = V S ± 1/2R( 1 - 3 c o s 2 0 ) (7) and two c o r r e s p o n d i n g I l i n e s . The s p l i t t i n g of the d o u b l e t , Avis , i s g i v e n by R(1 - 3 c o s 2 0 ) , and i t s v a r i a t i o n w i t h o r i e n t a t i o n i n the magnetic f i e l d w i l l y i e l d both R and the r e l a t i o n of 6 t o the c r y s t a l s e t t i n g . For an o r g a n i c s o l i d , the major source of l i n e b r o a d e n i n g i n the 1 3 C spectrum i s the d i p o l a r b r o a d e n i n g from nearby ( e . g . , d i r e c t l y bonded) p r o t o n s . The z-component, B Z H, of the l o c a l f i e l d which 1H e x e r t s on the 1 3 C magnetic moment i s o b t a i n e d from the e x p r e s s i o n d e r i v e d e a r l i e r f o r the s p l i t t i n g ( i n H e r t z ) : 1 3 AU (8) 4TT w i t h B Z H = ± Mt (1 - 3 c o s 2 0 ) r - 7 CH i n which Mi~ 7^/2 i s the magnetic moment. In a powder sample, t h e r e e x i s t many p a i r s of s p i n s w i t h d i f f e r e n t v a l u e s of r 0 H and 8, which r e s u l t s i n a broad resonance l i n e . T y p i c a l 1 3C- 1H d i p o l a r i n t e r a c t i o n s can be ve r y 17 l a r g e ; f o r a C-H bond p a r a l l e l t o B 0, Av C H of 40 k i l o h e r t z (kHz) would be e x p e c t e d . 1 " The e x p r e s s i o n f o r the d i p o l a r s p l i t t i n g s as shown above, i s d e r i v e d from the c o u p l i n g between 1 3 C n u c l e i and " s t a t i c " p r o t o n magnetic moments. I t has been demonstrated t h a t t h e s e s p l i t t i n g s a r e g e n e r a l l y reduced e x p e r i m e n t a l l y by the " f l i p - f l o p " s p i n motion of d i p o l a r - c o u p l e d p r o t o n s which have a n t i p a r a l l e l moments. 1 5 T h i s p r o c e s s , c a l l e d s p i n d i f f u s i o n , i s p a r t i c u l a r l y i m p o r t a n t because i t p r o v i d e s an e f f i c i e n t p a th f o r the s p i n - s p i n r e l a x a t i o n of p r o t o n s . Thus, i t l i m i t s the l i f e t i m e of the s p i n s t a t e , l e a d i n g t o u n c e r t a i n t y i n br o a d e n i n g of the resonance. The 'H-'H d i p o l a r s p l i t t i n g (A\?MH ) i s a p p r o x i m a t e l y e q u a l t o the f l i p - f l o p r a t e , and the s p i n f l u c t u a t i o n s average the 1 3C- 1H i n t e r a c t i o n t o A\>c* ( A V C H / A V H H ) • 16 S i n c e A V > H H > A V C H f o r most o r g a n i c s o l i d s , the 1 3 C d i p o l a r l i n e w i d t h may t h e r e f o r e be s c a l e d by the f a c t o r ( A\)<LH/A\>HH ) . S t i l l , the reduced l i n e w i d t h i s i n the o r d e r of k i l o h e r t z . The d i p o l a r i n t e r a c t i o n i s l a r g e l y removed by c o n t i n u o u s l y i r r a d i a t i n g the 1H s p i n system w i t h a s t r o n g r a d i o f r e q u e n c y ( r . f . ) f i e l d s e t t o the a p p r o p r i a t e Larmor f r e q u e n c y . T h i s means t h a t B Z H i s su p p r e s s e d v i a a r e d u c t i o n of the e f f e c t i v e magnetic moment, /<". The e f f e c t of the r . f . i r r a d i a t i o n i s t o induce r a p i d r o t a t i o n of p r o t o n s p i n s , t h a t e f f e c t i v e l y makes < Mz > - 0 ( F i g . 1-3). N o r m a l l y , s p i n d e c o u p l i n g f i e l d s of 40 kHz or more are needed t o remove the 1 3 C - 1 H d i p o l a r i n t e r a c t i o n s . However 18 s u b s t a n t i a l b r o a d e n i n g s t i l l r e m ains, due t o c h e m i c a l s h i f t a n i s o t r o p y i n t e r a c t i o n s ( c . s . a . ) and 1 3 C - 1 3 C homonuclear i n t e r a c t i o n s , which cannot be removed by h i g h power d e c o u p l i n g . Az,B. F i g . 1-3. R a p i d r o t a t i o n of p r o t o n s p i n 2, e f f e c t e d by h i g h power d e c o u p l i n g . 1.1 .2.2. Chemical S h i f t A n i s o t r o p y W i t h d i p o l a r d e c o u p l i n g , the r e s o l u t i o n of the 1 3 C spectrum i s improved, but the s p e c t r a l l i n e s s t i l l e x h i b i t an a n i s o t r o p i c l i n e s h a p e . The maximum c h e m i c a l s h i f t a n i s o t r o p y f o r carbon resonances ( e . g . , of a r o m a t i c and c a r b o n y l carbons) i n n e u t r a l m o l e c u l e s can c o v e r a s p e c t r a l range of 200 p.p.m., 1 7 or of the or d e r of 10 kHz (at 19 50.3 MHz). T h i s l i n e - b r o a d e n i n g a r i s e s from the non s y m m e t r i c a l e l e c t r o n d e n s i t y around the 1 3 C n u c l e i i n the m o l e c u l e . Thus these c a r b o n s , which e x p e r i e n c e d i f f e r e n t s h i e l d i n g s of the magnetic f i e l d depending upon the o r i e n t a t i o n of m o l e c u l a r - f i x e d axes w i t h r e s p e c t t o the a p p l i e d f i e l d , 1 0 would have d i f f e r e n t c h e m i c a l s h i f t s . For s u f f i c i e n t l y s i m p l e systems i n v o l v i n g o n l y a few c h e m i c a l l y d i f f e r e n t t y p e s of c a r b o n s , r e s o l v e d or p a r t i a l l y r e s o l v e d c h e m i c a l s h i f t a n i s o t r o p i e s a r e a r i c h s ource of new i n f o r m a t i o n about the geometry and e l e c t r o n i c s t r u c t u r e of the s o l i d s . The l i n e s h a p e f o r a carbon resonance ( F i g . 1-4) i s g e n e r a l l y " t e n t - l i k e " , and i t can be d e s c r i b e d by the t h r e e p r i n c i p a l components ( i . e . , a M , a 2 l , and a 3 3 ) c o n t a i n e d i n the c h e m i c a l s h i f t t e n s o r , <r. However, i n most c a s e s , i t i s i m p o s s i b l e t o e x t r a c t the a n i s o t r o p y i n f o r m a t i o n because of the e x t e n s i v e o v e r l a p of the d i f f e r e n t s i g n a l s o r i g i n a t i n g from the many k i n d s of carbon atoms i n the m o l e c u l e . The resonance f r e q u e n c y can be e x p r e s s e d as v 0 = 2TT B 0 ( 1 - o z x ) ( 9) where ozz i s the s h i e l d i n g c o n s t a n t measured a l o n g B 0. azz can be r e l a t e d t o the t h r e e p r i n c i p a l components by the d i r e c t i o n c o s i n e s : 1 1 20 Ozz = L °jj c o s 2 6; (10) J--< where the a n g l e s , 8j , a r e those between the j d i r e c t i o n and B 0. The c o n v e n t i o n an < o2Z S o33 i s u s u a l l y adopted. In °11=° 2 2 ^rO 0 3 3 F i g . 1-4. Chemical s h i e l d i n g powder p a t t e r n : (A) a r b i t r a r y second rank t e n s o r (o", , * <y-22 # 6~33); (B) a x i a l l y symmetric second rank t e n s o r ( 0 T 1 = <r"22 * c"*3 3 ) (from Ref. [9]).. s o l u t i o n , m o l e c u l a r motion averages the a n i s o t r o p i c p a r t of t h i s c h e m i c a l s h i f t t e n s o r , t h a t i s , the s h i e l d i n g c o n s t a n t i s independent of o r i e n t a t i o n i n B 0. Thus, the e f f e c t i v e i s o t r o p i c c h e m i c a l s h i f t (a-) i s g i v e n by 21 o- = l / 3 t r c r = 1/3(a„ + o22. + a J 3 ) (11) where the i s o t r o p i c average of each c o s 2 0 j term i s 1/3. I f a r i g i d specimen i s m e c h a n i c a l l y spun w i t h a n g u l a r v e l o c i t y u>r about an a x i s i n c l i n e d a t a n g l e (3 t o B„, and a t a n g l e s t o the p r i n c i p a l axes of (t as shown i n F i g . 1-5, we have A B © © © © © © © F i g . 1-5. Magic a n g l e s p i n n i n g of a specimen: (A) by r o t a t i n g i n a f i e l d of a s o l e n o i d under the magic a n g l e of 54°44'; (B) the time averaged v a l u e of a l l the b i n d i n g v e c t o r s becomes 54°44', i . e . < 0 , 2> = <# 3,«> = 54°44' i n s p i t e of 0 , 2 * 63 « . (see Appendix I I ) c o s f l j = cos/3cosXj + s i n / J s i n ^ - cos ( w r t + ) (12) 22 where Vj i s the a z i m u t h a l a n g l e of the j t h p r i n c i p a l a x i s of o* a t t = 0. S u b s t i t u t i n g (12) i n t o (10) and t a k i n g the time a v e r a g e , the s h i e l d i n g c o n s t a n t f o r each k i n d of n u c l e u s i s w r i t t e n as Tzt = 3/2 ( s i n 2/3^ ) + 1/2(3C O S 2/3 -1)2, ojj cos2 Xj (13) In g e n e r a l t h i s l a t t e r term produces a powder p a t t e r n when summed over a l l p o s s i b l e n u c l e a r o r i e n t a t i o n s . However, when 0 = 54.7°, then cos 2/3 = 1/3, and sin 2/3 = 2/3 and Eq. (13) reduces t o the e x p r e s s i o n o~zz = o (14) T h i s means t h a t i n a p o l y c r y s t a l l i n e sample o n l y a s i n g l e s h a r p l i n e w i l l be obser v e d f o r each s e t of i n e q u i v a l e n t n u c l e i , p r o v i d e d t h a t the r o t a t i o n a l r a t e i s s u f f i c i e n t l y f a s t . I f the s p i n n i n g r a t e i s l e s s than the c h e m i c a l s h i f t a n i s o t r o p y , the spectrum i s broken up i n t o a complex p r o f i l e of sidebands ( F i g . 1-6), which t r a c e out a t e n t -l i k e p a t t e r n r e l a t e d t o the s p a t i a l a n i s o t r o p y , c e n t e r e d around each i s o t r o p i c s h i f t . 1 8 T h i s c o m p l i c a t e s s t r u c t u r a l a s s i g n m e n t s and a l s o r e s u l t s i n a l o s s of s e n s i t i v i t y . I n c r e a s i n g the magnetic f i e l d , B 0, does not n e c e s s a r i l y i n c r e a s e the r e s o l u t i o n of the spectrum because the c h e m i c a l s h i f t a n i s o t r o p y i s f i e l d dependent, and thus h i g h e r f i e l d s t r e n g t h s r e q u i r e h i g h e r s p i n n i n g r a t e s . 23 F i g . 1-6. 1 3C-N.m.r. s p e c t r a of p o l y ( m e t h y l m e t h a c r y l a t e ) as a f u n c t i o n of s p i n n i n g f r e q u e n c y (from Ref. [ 1 8 ] ) . 1.1.3. S e n s i t i v i t y Enhancement In s o l u t i o n n.m.r. s t u d i e s of " d i l u t e s p i n s " such as 1 3 C and 1 5 N , n u c l e a r Overhauser enhancement ( n . O . e . ) , 1 9 24 F o u r i e r t r a n s f o r m and s i g n a l a v e r a g i n g t e c h n i q u e s can be employed t o improve the s i g n a l - t o - n o i s e r a t i o . In s o l i d s , poor s p e c t r a l r e s o l u t i o n and l o n g s p i n - l a t t i c e r e l a x a t i o n t i m e s may pose s e r i o u s problems f o r s i g n a l d e t e c t i o n , t h e r e b y making c o n v e n t i o n a l s o l u t i o n t e c h n i q u e s d i f f i c u l t t o s t u d y . These problems have been l a r g e l y overcome by the i n g e n i o u s t e c h n i q u e of c r o s s - p o l a r i z a t i o n , d e v e l o p e d by P i n e s et a l . . 2 'H spins T j ^ H ) 13C spins T S ( 1 3 C ) T,s T,H / / / / / / / / / Lattice, // / / //// F i g . 1-7. ^C-'H C r o s s - p o l a r i z a t i o n experiment ( s p i n temperature c o n c e p t ) . As shown i n F i g . 1-7, the 1 3 C - c . p . n.m.r. experiment i n v o l v e s the t r a n f e r of . p o l a r i z a t i o n (hence s i g n a l i n t e n s i t y ) from the "more abundant" 'H s p i n s t o the " d i l u t e " 1 3 C s p i n system. T h i s t e c h n i q u e i s a l s o c a l l e d " p r o t o n enhanced n u c l e a r i n d u c t i o n s p e c t r o s c o p y " ( p . e . n . i . s . ) ; i t p r o v i d e s a new r e l a x a t i o n p a t h f o r 1 3 C 25 s p i n s , so t h a t t h e i r e f f e c t i v e r e l a x a t i o n time i s d r a s t i c a l l y reduced. I t i s a p a r t i c u l a r l y e f f e c t i v e v e r s i o n of double resonance i n the r o t a t i n g frame, 1 based on the dynamics and thermodynamics of n u c l e a r s p i n systems. Thus, the language of s p i n thermodynamics i s w e l l s u i t e d t o the d i s c u s s i o n of these phenomena, and w i l l be used. 1.1.3.1. S p i n Temperature When a s o l i d sample c o n t a i n i n g 1H and 1 3 C n u c l e i i s p l a c e d , i n a magnetic f i e l d B Q, the energy l e v e l s of these n u c l e i a r e s p l i t i n t o two l e v e l s , ±(7/27r)Bo/2, c o r r e s p o n d i n g t o s p i n a l i g n m e n t p a r a l l e l and a n t i p a r a l l e l t o B 0 ( F i g . I-8A). The p o p u l a t i o n r a t i o , n,/n z, of these two l e v e l s 1 and 2 of a s p i n system i s g i v e n by the Boltzmann law: 9 n,/n 2 = exp -AE/RT S (15) where AE i s the energy d i f f e r e n c e between the two l e v e l s , and T s i s the s p i n t e m p e r a t u r e . A s m a l l p o p u l a t i o n d i f f e r e n c e i m p l i e s a h i g h s p i n temperature T s ( i n the l i m i t , n, = n 2 means T =oo); c o n v e r s e l y , a l a r g e p o p u l a t i o n d i f f e r e n c e s i g n i f i e s a low temperature T s. P r o t o n s , which are p a r t of a l a r g e s p i n system, can i n t e r a c t w i t h each o t h e r by the p r o c e s s of s p i n d i f f u s i o n , as mentioned p r e v i o u s l y i n S e c t i o n 1.1.2.1. C o n s i d e r now a s i n g l e p r o t o n which changes Zeeman 26 E A U J H ^ B OC /VWWVVV* Abundant Spins B E A A E / / / / / <*>c = yc Bo Rare Spins A E Z Abundant Spins Rare Spins F i g . 1-8. R e p r e s e n t a t i o n of energy l e v e l s : (A) i n the l a b o r a t o r y frame; (B) i n the r o t a t i n g frame (from Ref. [ 6 ] ) . l e v e l s by exchanging energy w i t h the l a t t i c e . T h i s i n f o r m a t i o n i s conveyed i n a s h o r t time (<100 /*s) t o a l a r g e number of n e i g h b o r i n g p r o t o n s by t h e i r mutual s p i n f l i p s . As a r e s u l t , d u r i n g t h a t time a l l the pr o t o n s a c h i e v e a s t a t e of i n t e r n a l e q u i l i b r i u m , and hence can be c o n s i d e r e d as a s i n g l e thermodynamic r e s e r v o i r , as r e p r e s e n t e d by Eq. ( 1 5 ) . A f t e r a l a p s e e q u i v a l e n t t o s e v e r a l s p i n - l a t t i c e r e l a x a t i o n t i m e s , T , ( 1 H ) , the p r o t o n r e s e r v o i r w i l l come t o e q u i l i b r i u m w i t h the l a t t i c e , and T S ( 1 H ) w i l l be e q u a l t o the l a t t i c e t e m perature T L. The 1H m a g n e t i z a t i o n produced i n the l a b o r a t o r y frame i s then g i v e n by the C u r i e Law as 27 M 0 ( , H ) = C„B 0/T U (16) where C H = l / 4 ( y H 2 h 2 N H ) / k i s the p r o t o n C u r i e c o n s t a n t , i n which N H i s the number of p r o t o n s and k i s the Boltzmann c o n s t a n t . S i m i l a r l y , t he s m a l l 1 3 C m a g n e t i z a t i o n can be r e p r e s e n t e d as 1.1.3.2. C r o s s - P o l a r i z a t i o n With t h o s e c o n c e p t s on hand, the c.p. experiment can be e x p l a i n e d . The f i r s t s t e p i n v o l v e s t r a n s f e r of the 1H m a g n e t i z a t i o n t o the r o t a t i n g frame by s p i n - l o c k i n g a l o n g the d i r e c t i o n of the r . f . f i e l d , B 1 H . I n i t i a l l y , the p r o t o n s a r e p e r t u r b e d ( s i n c e B 1 H « < B 0 ) , but s h o r t l y , they r e g a i n t h e i r i n t e r n a l e q u i l i b r i u m . The p o p u l a t i o n of the s e s t a t e s i s a g a i n governed by the Boltzmann d i s t r i b u t i o n , which i s c h a r a c t e r i z e d by T s i n the r o t a t i n g frame. Thus, the 1H m a g n e t i z a t i o n i s g i v e n by M 0 ( 1 3 C ) = C C B 0 / T L (17) C HB 0/T L = C H B 1 H / T S i . e . T s = ( B 1 H / B 0 ) T L (18) S i n c e B 1 H <<< B 0, the p r o t o n s p i n s a re e f f e c t i v e l y at a v e r y low s p i n t e m p e r a t u r e ; f o r a sample a t room t e m p e r a t u r e , T s i s a p p r o x i m a t e l y 3 K 1 3 and the t o t a l s p i n 28 energy i s - C H B 0 2 / T S . At t h i s j u n c t u r e , the 1H s p i n s a re brought i n t o t h e r m a l c o n t a c t w i t h the 1 3 C s p i n s by i r r a d i a t i n g the carbons on resonance. A l b e i t t h a t the 1 3 C m a g n e t i z a t i o n i s s m a l l a l o n g the B 0 d i r e c t i o n a t the s t a r t of the p u l s e , the carbon n u c l e i w i l l s t i l l p r e c e s s about the r . f . f i e l d , B 1 c , a t the frequ e n c y o J i c = Y c B 1 t . Hence, t h e r e a r e two o s c i l l a t i n g components a l o n g the z d i r e c t i o n i n the r o t a t i n g frame, one f o r the 1H m a g n e t i z a t i o n at fre q u e n c y u>1H = V HB 1 H, and the o t h e r f o r the 1 3C m a g n e t i z a t i o n . I f the a m p l i t u d e of B 1 C i s a d j u s t e d so t h a t the Hartmann-Hahn c o n d i t i o n i s s a t i s f i e d ( F i g . I - 8 B ) , then the f r e q u e n c i e s of the o s c i l l a t o r y components w i l l be i d e n t i c a l , t h a t i s , Y CB 1 C = u) i c = COIH = *HBIH ( 1 9 ) The above c o n d i t i o n i m p l i e s t h a t the e f f e c t i v e e n e r g i e s of p r o t o n s and carbons a r e comparable, and p o l a r i z a t i o n t r a n s f e r now o c c u r s between the p r o t o n and carbon p o o l s v i a p r o t o n - c a r b o n s p i n f l i p s . T h i s i s m a i n t a i n e d f o r a time c o n s t a n t , T Cn ( t y p i c a l l y 0.5-5 ms), d u r i n g which the s p i n energy i s r e d i s t r i b u t e d between the p r o t o n - and the ca r b o n -p o o l s so t h a t a common s p i n t e m p e r a t u r e , T$ , i s a c h i e v e d : C HB 1 H 2 /T s = ( C H B 1 H 2 + C CB,<? )/TZ (20) S i n c e C c << C H ( i . e . , N c ~ 10~ 2N ), t h i s t emperature w i l l 29 be a p p r o x i m a t e l y e q u a l t o t h a t of the s p i n - l o c k e d p r o t o n m a g n e t i z a t i o n . D u r i n g t h i s p r o c e s s the p r o t o n s l o s e o n l y a v e r y s m a l l amount of t h e i r t o t a l m a g n e t i z a t i o n (remember, T i j >> T C H ), and the r e s u l t i n g 1 3 C m a g n e t i z a t i o n i s g i v e n by M ( 1 3 C ) = C CB 1 C/T^ = C C B 1 C / T S (21) S u b s t i t u t i n g Eqs. (18) and (19) i n t o (21) g i v e s the r e l a t i o n s h i p M( 1 3 C ) = ( V V e ) C C B 0 / T L (22) = 4 M 0 ( 1 3 C ) where M 0 ( 1 3 C ) i s the m a g n e t i z a t i o n which would be ge n e r a t e d i n B 0 a f t e r w a i t i n g f o r the e q u i v a l e n t of 3-5 T 1 C p e r i o d . In t h i s way, a f o u r f o l d enhancement 2 i n 1 3 C s i g n a l -i n t e n s i t y can be o b t a i n e d from a s i n g l e c r o s s - p o l a r i z a t i o n p r o c e s s . 1.1.4. The 1 3C-C.P.-M.A.S. Experiment The e x p e r i m e n t a l d e t a i l shown i n F i g . 1-9 r e p r e s e n t s the t i m i n g sequence f o r the c.p. e x p e r i m e n t . E s s e n t i a l l y the p r o c e d u r e can be d i v i d e d i n t o f o u r p a r t s : 1) p o l a r i z a t i o n of the 1H s p i n system, 2) s p i n l o c k i n g i n the r o t a t i n g frame, 3) t h e r m a l c o n t a c t between the 1H and ' 3C 30 90° pulse Z , B 0 Irradiation at 'H frequency X' B IH = V B 0 B Decay of'H in rotating frame Z , B Irradiation at , 3 C frequency Acquire FID oscillating z component Z , B C F i g . 1-9. T i m i n g sequence f o r c r o s s - p o l a r i z a t i o n e x p e r i m e n t : (A) p o l a r i z a t i o n of the 1H s p i n system; (B) s p i n l o c k i n g i n the r o t a t i n g frame; (C) t h e r m a l c o n t a c t between the 1H and the 1 3C s p i n systems; (D) o b s e r v a t i o n of the 1 3 C f r e e i n d u c t i o n decay (from Ref. [ 6 ] ) . 31 s p i n systems, and 4) o b s e r v a t i o n of the 1 3 C f r e e i n d u c t i o n decay ( f . i . d . ) . D u r i n g the whole c.p. e x p e r i m e n t , s p i n n i n g of the sample i s m a i n t a i n e d a t the magic a n g l e . 1.1.4.1. P o l a r i z a t i o n of 1H I n i t i a l l y , the 1H m a g n e t i z a t i o n i s a l l o w e d t o b u i l d up a l o n g B 0 , w i t h the p o p u l a t i o n d i f f e r e n c e governed by AE as shown i n Eq. ( 1 5 ) . T h i s m a g n e t i z a t i o n i s then brought by a 90° p u l s e i n t o the x'y' p l a n e , a l o n g y'. The 'H and 1 3 C s p i n s a r e assumed t o be r o t a t i n g about B 0 a t t h e i r r e s p e c t i v e Larmor f r e q u e n c i e s , t h a t i s , the 1H c o o r d i n a t e system x'y' p r e c e s s e s a t W 0H = *HB 0, and the 1 3 C system x"y" at uioc = Y C B 0 . 1.1.4.2. S p i n L o c k i n g Immediately a f t e r the 90° p u l s e ( i n m i c r o s e c o n d s ) , the phase of the r . f . f i e l d , B 1 H , i s e l e c t r o n i c a l l y s h i f t e d by 90° t o the y' d i r e c t i o n , so t h a t i t i s c o l i n e a r w i t h the *H m a g n e t i z a t i o n . In t h i s way a s t a t e of low s p i n temperature i s p r e p a r e d ; the s t r o n g m a g n e t i z a t i o n produced i n the h i g h B 0 f i e l d i s now p a r a l l e l t o the s m a l l B 1 H f i e l d , which r e s u l t s i n a h i g h l e v e l of p o l a r i z a t i o n i n the r o t a t i n g frame. At t h i s time the 1 3 C m a g n e t i z a t i o n i s z e r o i n the x"y" p l a n e , which c o r r e s p o n d s t o an i n f i n i t e s p i n t e m p e r a t u r e . In the presence of the s t r o n g B 0 f i e l d , t h i s " s p i n -32 l o c k e d " c o n d i t i o n cannot be m a i n t a i n e d i n d e f i n i t e l y . In p r a c t i c e , t h i s m a g n e t i z a t i o n e v e n t u a l l y decays t o z e r o by s p i n - l a t t i c e r e l a x a t i o n i n the r o t a t i n g frame, w i t h . a t i m e -c o n s t a n t denoted by T y ( 1 H ) . 1.1.4.3. 1 3C- 1H Thermal C o n t a c t D u r i n g the s p i n - l o c k c o n d i t i o n , B l c i s a p p l i e d a l o n g the x" d i r e c t i o n . I t i s a d j u s t e d t o t h e Hartmann-Hahn c o n d i t i o n , and m a i n t a i n e d f o r a t i m e , t C p , which i s p r e f e r a b l y e q u a l t o , or s l i g h t l y l o n g e r t h a n , T C H . The t r a n s f e r of m a g n e t i z a t i o n v i a c r o s s - p o l a r i z a t i o n now o c c u r s , r e s u l t i n g i n a r a p i d i n c r e a s e i n the 1 3 C m a g n e t i z a t i o n and a v e r y s m a l l d e c r e a s e i n the 1H m a g n e t i z a t i o n . 1.1.4.4. O b s e r v a t i o n of 1 3 C Free I n d u c t i o n Decay The l a s t s t e p of the c.p. experiment i s t o s w i t c h o f f the 1 3 C r . f . f i e l d and then t o o b s e r v e the "proton enhanced" 1 3 C f . i . d . . D u r i n g t h e 1 3 C o b s e r v a t i o n t i m e , the 1H r . f . f i e l d i s s t i l l m a i n t a i n e d i n o r d e r t o p r o v i d e the high-power d e c o u p l i n g f i e l d . In p r a c t i c e , the e n t i r e sequence has t o be r e p e a t e d u n t i l a s u i t a b l e s i g n a l - t o -n o i s e (S/N) r a t i o i s o b t a i n e d . F i n a l l y , the r e s u l t a n t f . i . d . i s F o u r i e r t r a n s f o r m e d t o g i v e the fr e q u e n c y domain spectrum. 33 1.1.4.5. O p t i m i z a t i o n of the C r o s s - P o l a r i z a t i o n Experiment The s u c c e s s of c.p. depends on s e v e r a l e x p e r i m e n t a l c o n d i t i o n s , which can be met i n most c a s e s . These i n c l u d e the r e q u i r e m e n t t h a t the magnitudes of B 1 C , B 1 H be g r e a t e r than the n a t u r a l l i n e w i d t h s of the 1H and 1 3 C resonances and t h a t T 1 C > T 1 H ^ T 1j>( 1H) > t c p > T C M . I f the above c o n d i t i o n s a r e not f u l f i l l e d , optimum g a i n i n the 1 3 C s i g n a l i n t e n s i t y cannot be a c h i e v e d . The be s t c o m b i n a t i o n of parameters from the p o i n t of view of c.p. e x p e r i m e n t s i s a s h o r t T 1 H a s s o c i a t e d w i t h a v e r y l o n g T 1 j ) ( 1 H ) . These c o n d i t i o n s a r e o f t e n s a t i s f i e d i n m o l e c u l e s w i t h r e o r i e n t i n g methyl g r o u p s . 2 0 The a c t u a l c.p. r a t e , 1/T<-H, r e s u l t s from a summation over a l l p o s s i b l e 1 3 C - 1 H s p i n i n t e r a c t i o n s of the m o l e c u l a r system. A number of parameters a r e i n v o l v e d ; the most i m p o r t a n t one i s the second moment of the 1 3 C - 1 H bond, (T C H " 1 c< M 2 C H ), which i s w r i t t e n a s 1 5 = l7^7 uh/Uo 2 5" (1 ~ 3cos 26Jk V (23) where the sum, I [(1 - 3 c o s 2 8jk ) / r j k 3 ) ] 2 , i n c l u d e s a l l r e l e v a n t p r o t o n n u c l e i , k, i n r e l a t i o n t o the c o n s i d e r e d c a r b o n n u c l e u s j . Based on t h i s e x p r e s s i o n , i t can be seen t h a t the magnitude of a v a i l a b l e c r o s s - p o l a r i z a t i o n i s dependent on the 1 3 C - 1 H d i p o l a r i n t e r a c t i o n s ; t h e s e v a r y as 34 r C H " 3 , where r C H i s the d i s t a n c e s e p a r a t i n g the n u c l e i . In g e n e r a l t h e n , n o n p r o t o n a t e d carbons a r e expected t o become magnetized v i a t h i s mechanism much more s l o w l y than p r o t o n a t e d c a r b o n s , p r o v i d i n g t h a t t h e r e i s no r a p i d m o l e c u l a r motion t h a t can average the s t a t i c i n t r a m o l e c u l a r i n t e r a c t i o n s . A c c o r d i n g l y , the r e l a t i v e c.p. r a t e s of carbons a r e as f o l l o w s : C H 3 ( s t a t i c ) > CH 2 > CH > C H 3 ( r o t a t i n g ) > C ( n o n p r o t o n a t e d ) . 1 3 Q u a n t i t a t i v e l y a c c u r a t e c.p. s p e c t r a , i n which the r e l a t i v e s i g n a l i n t e n s i t i e s agree w i t h the known carbon r a t i o s , have been o b t a i n e d f o r h i g h l y p r o t o n a t e d , o r g a n i c d i a m a g n e t i c s o l i d s . 2 1 For t h i s t o be p o s s i b l e , i t i s mandatory f o r the c h e m i c a l system t o be homogeneous, so t h a t a l l the s p i n - l o c k e d 'H m a g n e t i z a t i o n can be c h a r a c t e r i z e d by the same r a t e of decay, T 1 j , ( 1 H ) . A l s o , the T,j>( 1H) s h o u l d be much l o n g e r than T C H t o ensure complete p o l a r i z a t i o n of a l l c a r b o n s , p a r t i c u l a r l y the n o n p r o t o n a t e d ones, b e f o r e r e l a x a t i o n i n the r o t a t i n g r e f e r e n c e frame dominates the 1H m a g n e t i z a t i o n . 1.1.4.6. E x p e r i m e n t a l A s p e c t s of Magic Angle S p i n n i n g Adjustment of t h e magic a n g l e i s c a r r i e d out t o m i n i m i z e the observed l i n e w i d t h s of the sample under s t u d y . Any m i s s e t t i n g of the a n g l e i s r e f l e c t e d i n the shape and w i d t h of t h e r e s u l t i n g l i n e s . S i n c e t h e s h i e l d i n g c o n s t a n t , a}z , c o n t a i n s the r e d u c t i o n f a c t o r | 1 / 2 ( 3 C O S 2 ^ - 1)| ' [Eq. ( 1 3 ) ] , the r e s o l u t i o n of each l i n e s h o u l d be s e n s i t i v e 35 t o s m a l l d e v i a t i o n s i n the a c t u a l a n g l e from the magic angl e v a l u e . In p r a c t i c e , the i n c r e a s e i n l i n e w i d t h i s e q u i v a l e n t t o a p p r o x i m a t e l y 2.5 % of i t s s t a t i c l i n e w i d t h f o r every degree of d e v i a t i o n from the magic a n g l e . 2 2 The s t a t i c l i n e w i d t h r e f e r s t o the w i d t h o b t a i n e d when the i n t e n d e d s p i n n i n g a x i s i s p a r a l l e l t o B 0. I t has been shown e x p e r i m e n t a l l y 2 3 t h a t a h i g h l e v e l of a c c u r a c y i n s e t t i n g the magic a n g l e can be a t t a i n e d i f adequate p r e c a u t i o n s are t a k e n . Many t y p e s of h i g h - s p e e d sample s p i n n e r s have been employed i n s o l i d - s t a t e n.m.r.; they are e s s e n t i a l l y m o d i f i c a t i o n s of e i t h e r the c o n i c a l 2 " ( F i g . I-10A) or the c y l i n d r i c a l 2 5 s p i n n e r . The former i s r e f e r r e d t o as the Andrew-type r o t o r , which has the p r i n c i p l e advantage of s i m p l i c i t y of c o n s t r u c t i o n . However, i t s d i s a d v a n t a g e i s r e l a t e d t o the d i f f i c u l t y of r o u t i n e l y o b t a i n i n g s t a b i l i t y , e s p e c i a l l y w i t h inhomogeneous samples, s p i n n i n g at h i g h r a t e s . The c y l i n d r i c a l r o t o r was f i r s t d e s c r i b e d by Lowe, but i t too has i t s own share of p roblems. B F i g . 1-10. Schematic r e p r e s e n t a t i o n of h i g h - s p e e d sample s p i n n e r s : (A) Andrew-Beams; (B) b u l l e t (from Ref. [ 1 0 ] ) . 36 B a r t u s k a and M a c i e l 2 6 have d e s i g n e d a b u l l e t - s h a p e d r o t o r ( F i g . I-10B), which can f a v o r a b l y w i t h s t a n d s p i n n i n g r a t e s up t o c a . 3.5 kHz. S i n c e i t resembles the Andrew s p i n n e r , t h e i r r e l a t i v e m e r i t s have been d i s c u s s e d . Yannoni et a l . 2 7 have deve l o p e d a v a r i a b l e - t e m p e r a t u r e ( v . t . ) s p i n n i n g a p p a r a t u s t o ad d r e s s a v a r i e t y of i n t e r e s t i n g c h e m i c a l problems ( F i g . 1-11); t h e i r r o t o r can s u s t a i n 3-4 kHz a t l i q u i d n i t r o g e n t e m p e r a t u r e w i t h h e l i u m as the p r o p e l l a n t gas. Rotor J I Holder Stator Cover F i g . 1-11. A s p i n n e r system s u i t a b l e f o r v a r i a b l e temperature magic a n g l e s p i n n i n g s t u d i e s (from Ref. [ 2 7 ] ) . A number of m a t e r i a l s have been used t o c o n s t r u c t the s p i n n e r s . They i n c l u d e K e l - F ( p o l y t r i f l u o r o c h l o r o e t h y l e n e ) , D e l r i n [ p o l y ( o x y m e t h y l e n e ) ] , T e f l o n , P l e x i g l a s [ p o l y ( m e t h y l m e t h a c r y l a t e ) ] , boron n i t r i d e , 2 8 and aluminium o x i d e . D e l r i n and K e l - F r o t o r s a r e commonly used by most r e s e a r c h groups; t h e former i s s t r o n g e r and can a c h i e v e a s p i n n i n g r a t e of about 4.5 kHz. U n f o r t u n a t e l y , D e l r i n i t s e l f has a l a r g e 1 3 C resonance; f o r t u n a t e l y t h i s can be s u p p r e s s e d 2 9 37 from the sp e c t r u m of i n t e r e s t . For r o t a t i o n r a t e s up t o c a . 5 kHz, the t u r b i n e may be d r i v e n w i t h compressed a i r of about 3 atmospheres p r e s s u r e . Compressed he l i u m or hydrogen gas must be used i f h i g h e r r o t a t i o n r a t e s are needed. 1.1.4.7. S p e c t r a l R e s o l u t i o n Even under o p t i m a l c o n d i t i o n s f o r high-power p r o t o n d e c o u p l i n g and magic a n g l e s p i n n i n g , s t a t i c and/or dynamic e f f e c t s can l i m i t the r e s o l u t i o n a t t a i n a b l e from some o r g a n i c s o l i d s . I t has been found f o r amorphous m a t e r i a l s , t h a t the l a c k of a f i x e d , s i n g l e c o n f o r m a t i o n may l e a d t o a d i s t r i b u t i o n of i s o t r o p i c c h e m i c a l s h i f t s f o r i n d i v i d u a l c a r b o n s . 3 0 U s u a l l y t h i s g i v e s r i s e t o s u b s t a n t i a l l i n e -b r o a d e n i n g , of the or d e r of s e v e r a l p.p.m., t h a t may r e s u l t i n a " f e a t u r e l e s s " spectrum. In o t h e r c a s e s , s p l i t t i n g s of resonance l i n e s a r e caused by magnetic i n e q u i v a l e n c e s 1 2 which a r e p r e s e n t i n the s o l i d s t a t e but not i n s o l u t i o n . Other m e c h a n i s m s 2 2 which can a f f e c t the r e s o l u t i o n i n c l u d e m o t i o n a l m o d u l a t i o n of both the 1 3 C - 1 H d i p o l a r d e c o u p l i n g and of the c h e m i c a l s h i f t a n i s o t r o p y . As a r e s u l t , the 1 3 C -n.m.r. l i n e w i d t h s of s o l i d s a r e 10 t o 100 t i m e s broader than those measured i n s o l u t i o n . 1.1.5. U s e f u l P u l s e Sequences and R e l a t e d Techniques To an o r g a n i c c h e m i s t , the i d e a l outcome of a s o l i d -s t a t e n.m.r. measurement i s the complete assignment of a l l 38 the carbon resonances. T h i s g o a l c o n t i n u e s t o p r o v i d e a c o m p e l l i n g reason f o r e x p l o r a t i o n of both the t e c h n i c a l and c h e m i c a l a s p e c t s of t h i s a r e a . I t has a l r e a d y been shown t h a t p u l s e t e c h n i q u e s can be employed t o remove s p i n n e r -s i g n a l s and s p i n n i n g - s i d e b a n d s , 3 1 ' 3 2 t o i n c r e a s e S/N r a t i o , and t o d i s t i n g u i s h d i f f e r e n t c l a s s e s of c a r b o n s . 3 3 A l s o , c h e m i c a l m o d i f i c a t i o n of the samples by i n t r o d u c t i o n of m e t a l i o n s , of d e u t e r o n s , 3 " or of 1 3 C - e n r i c h e d n u c l e i 3 5 can a s s i s t i n s p e c t r a l a s s i g n m e n t s . G e n e r a l i z a t i o n of these p r e l i m i n a r y f i n d i n g s would encourage more r o u t i n e a p p l i c a t i o n of s o l i d - s t a t e 1 3 C n.m.r. t o s t r u c t u r a l a n a l y s i s of i m p o r t a n t o r g a n i c compounds; indeed such s t u d i e s w i l l p r o b a b l y not o c c u r u n t i l such a u x i l i a r y methods are w i d e l y a v a i l a b l e . As mentioned e a r l i e r , D e l r i n i s s t i l l a v e r y c o n v e n i e n t m a t e r i a l f o r the manufacture of high-speed s p i n n e r s , except t h a t i t s 1 3 C s i g n a l , c e n t e r e d a t 89.11 p.p.m. c o n c e a l s a r e g i o n of the spectrum which i s . v i t a l l y i m p o r t a n t , e s p e c i a l l y f o r c a r b o h y d r a t e s . To expose t h i s s p e c t r a l r e g i o n , a method i s used which i s analogous t o , the s o l v e n t s u p p r e s s i o n r o u t i n e s t h a t a r e f a m i l i a r l y a p p l i e d t o s o l u t i o n - s t a t e n.m.r. s p e c t r o s c o p y ; i n the p r e s e n t c o n t e x t , i t i n v o l v e s t h e s u p p r e s s i o n of the resonance s i g n a l from the s a m p l e - s p i n n e r . I t depends on the f a c t t h a t the m a g n e t i z a t i o n of the p r o t o n s of D e l r i n u s u a l l y decays f a r more r a p i d l y than t h a t of the o r g a n i c s u b s t r a t e ; t h i s o c c u r s because the p o l y m e r i c m a t e r i a l i s 39 p r o b a b l y q u i t e m o b i l e i n the s o l i d s t a t e . 3 0 Thus, the i n t r o d u c t i o n of an a p p r o p r i a t e d e l a y i m m e d i a t e l y f o l l o w i n g the 180° p u l s e (at p o s i t i o n 1 i n F i g . 1-12), ensures t h a t the subsequent c r o s s - p o l a r i z a t i o n sequence t r a n s f e r s p r o t o n m a g n e t i z a t i o n o n l y t o the carbons of the o r g a n i c s u b s t r a t e . 180 Delay (wi th or without spin locking) F i g . 1 - 1 2 . P u l s e sequence used t o suppress the D e l r i n s i g n a l , and s i g n a l s from p r o t o n a t e d - c a r b o n atoms i n s o l i d s . C o n s i d e r a t i o n of the time c o u r s e f o r n u c l e a r r e l a x a t i o n has l e d t o another u s e f u l p u l s e sequence which a s s i s t s i n assignment. T h i s was f i r s t t e s t e d by A l i a and L i p p m a a 3 6 and p r o v i d e s , i n p r i n c i p l e a t l e a s t , an u n e q u i v o c a l means f o r d i s c r i m i n a t i n g between the resonances of carbon atoms t h a t bear p r o t o n s from those t h a t bear none. In t h i s c a s e , advantage i s taken of the f a c t t h a t , w i t h o u t s p i n l o c k i n g , the m a g n e t i z a t i o n of the p r o t o n a t e d carbon atoms decays more r a p i d l y than t h a t of those which a r e n o n p r o t o n a t e d . Thus i n s e r t i o n of a s u i t a b l e d e l a y time 40 at p o s i t i o n 2 i n the p u l s e sequence ensures t h a t , even though a l l carbon atoms are magnetized t o the same e x t e n t a t the end of the m i x i n g t i m e , o n l y those h a v i n g r e l a t i v e l y l o n g e r 1 3 C r e l a x a t i o n t i m e s r e t a i n a measurable m a g n e t i z a t i o n a t the s t a r t of the carbon a c q u i s i t i o n - t i m e . The o v e r a l l r e p e t i t i o n time of the c.p. experiment i s e s s e n t i a l l y d e t e r m i n e d by the s h o r t e r T 1 H . I f T , j ( 1 H ) i s l o n g compared w i t h " T C H p l u s the a c q u i s i t i o n time f o r the o b s e r v a t i o n - o f the 1 3 C f . i . d . " ( t y p i c a l l y 50-100 ms), then a s u b s t a n t i a l amount of p r o t o n p o l a r i z a t i o n w i l l s t i l l remain at the end of the f i r s t o b s e r v a t i o n p e r i o d . Thus, i t i s p o s s i b l e t o c a r r y out m u l t i p l e - c o n t a c t c r o s s -p o l a r i z a t i o n b e f o r e the p r o t o n p o l a r i z a t i o n r e q u i r e s r e p l e n i s h m e n t . A l t h o u g h t h i s p r o c e d u r e produces a f u r t h e r g a i n i n s e n s i t i v i t y , g e n e r a l l y i t i s not used i n p r a c t i c e because i t r e q u i r e s the B 1 H f i e l d t o be on f o r a l o n g t i m e , and s u b s t a n t i a l problems of heat d i s s i p a t i o n may r e s u l t . R e c e n t l y , a p u l s e s e q u e n c e 3 7 has been i n t r o d u c e d which s h o r t e n s the o v e r a l l w a i t i n g p e r i o d between s u c c e s s i v e s p i n - l o c k i n g sequences. The r e s u l t a n t p r o c e s s i n v o l v e s f l i p p i n g the p r o t o n m a g n e t i z a t i o n back a l o n g the B 0 d i r e c t i o n ; t h u s , a 90° p u l s e r e v e r s e d i n phase w i t h r e s p e c t t o the i n i t i a l p u l s e , 90° x , i s a p p l i e d a t the end of the s p i n - l o c k i n g p u l s e ( F i g . 1-13). A d e l a y time i s then s e t t o the minimum c o n s i s t e n t w i t h the a v o i d a n c e of heat d i s s i p a t i o n problems. T h i s t e c h n i q u e i s not s u i t a b l e f o r systems h a v i n g v e r y s h o r t T 1»( 1H) and l o n g T 1 H v a l u e s . 41 I m p o r t a n t l y , however, the experiment i s u s e r - f r i e n d l y i n t h a t t h e r e w i l l never be a de c r e a s e i n S/N r a t i o i n comparison w i t h the s t a n d a r d s i n g l e - c o n t a c t e x p e r i m e n t . 90° 90° 90° 90° 1 3 C B 90° 90° •t, 9 90° Time Time 90° Time F i g . 1-13. C r o s s - p o l a r i z a t i o n w i t h f l i p - b a c k of 1 H - s p i n m a g n e t i z a t i o n : (A) p u l s e t i m i n g f o r the c r o s s -p o l a r i z a t i o n ; (B) p h a s e - a l t e r n a t e d v e r s i o n of the f l i p - b a c k experiment (from Ref. [ 1 0 ] ) . I t i s p o s s i b l e f o r the 'H s p i n - l a t t i c e r e l a x a t i o n time t o be v e r y l o n g ( g r e a t e r than 100 s) i n the extreme c o r r e l a t i o n l i m i t s of oo O Hx >> 1 f o r v e r y slow, and u) 0 Ht- << 1 f o r ve r y f a s t m o t i o n , r e s p e c t i v e l y . T h i s i s c h a r a c t e r i s t i c of the c o r r e l a t i o n time f o r t h e p a r t i c u l a r motion i n v o l v e d , and i t i s n e c e s s a r y t o d e v i s e an e f f e c t i v e method f o r r e t r i e v i n g 1 3C-c.p.-m.a.s. s p e c t r a of such specimens. I t i s w e l l known t h a t the i n t r o d u c t i o n of paramagnetic i m p u r i t i e s i n t o a h o s t l a t t i c e can reduce i t s 42 r e l a x a t i o n t i m e s . 3 8 Because t h i s e f f e c t depends on the i n v e r s e s i x t h power of the d i s t a n c e , the T, v a l u e s a re ex p e c t e d t o be reduced most f o r those p r o t o n s and carbons t h a t a re l o c a t e d c l o s e s t t o the paramagnetic c e n t e r s . S i n c e a l l the p r o t o n s are i n v o l v e d i n mutual s p i n f l i p s w i t h t h e i r n e i g h b o r s , the o v e r a l l T, of the e n t i r e p r o t o n p o o l i s reduced. However, such i n t e r a c t i o n s a r e v e r y weak f o r carbons a t n a t u r a l abundance, and hence o n l y those t h a t a r e c l o s e r t o the paramagnetic c e n t e r s a re s i g n i f i c a n t l y a f f e c t e d . Low c o n c e n t r a t i o n s of paramagnetic i m p u r i t y do not a l t e r the space group symmetry or the c r y s t a l s t r u c t u r e of the host m o l e c u l e s , nor produce any o b s e r v a b l e i s o t r o p i c s h i f t or br o a d e n i n g of the 1 3C reso n a n c e s . The e f f e c t s of metal i o n s on the i s o t r o p i c s h i f t s of s t o i c h i o m e t r i c m e tal complexes have been r e p o r t e d r e c e n t l y . 3 9 In the case of paramagnetic complexes, the resonances of the carbons c l o s e s t t o the m e t a l c e n t e r a re broadened or not v i s i b l e a t a l l . By b i n d i n g s u i t a b l e m e tal i o n s t o s e l e c t i v e s i t e s of l a r g e m o l e c u l e s , p a r t i a l a s s i g n m e n t s of the s p e c t r a a r e made p o s s i b l e . Quadrupole n u c l e i , such as n i t r o g e n - 1 4 4 0 and d e u t e r i u m , can a l s o be v e r y u s e f u l i n s p e c t r a l a s s i g n m e n t s . The asymmetric d o u b l e t p a t t e r n and b r o a d e n i n g of the resonances from carbons d i r e c t l y bonded t o n i t r o g e n - 1 4 can be e a s i l y seen i n the spectrum ( F i g . 1-14). T h i s l i n e s h a p e i s caused by the 1 3C- 1 f tN d i p o l a r i n t e r a c t i o n , which i s not averaged by magic a n g l e s p i n n i n g . S e l e c t i v e d e u t e r a t i o n of 43 F i g . 1-14. 1 3C-N.m.r. s p e c t r a of 2 - m e t h y l - 4 - n i t r o a n i l i n e : (A) normal c.p.-m.a.s.; (B) t h e o r e t i c a l spectrum, c a l c u l a t e d as d e s c r i b e d i n Ref. [ 4 0 ] . o r g a n i c m o l e c u l e s has been w i d e l y e x p l o r e d , and i t i s a g r e a t a s s e t t o s o l i d - s t a t e s t u d i e s . A l b e i t t h a t 1 3C e n r i c h e d samples can be used, such s y n t h e s e s may not be t h a t s t r a i g h t f o r w a r d , and t h i s l i m i t s the a p p l i c a b i l i t y of the method. 44 1.2. f H N.M.R.  1.2.1. I n t r o d u c t i o n Deuterium n.m.r. r e p r e s e n t s a p o w e r f u l t o o l f o r p r o b i n g both the s t a t i c and dynamic p r o p e r t i e s of o r g a n i c s o l i d s and s o l i d p o l y m e r s . T h i s i s because the p r o p e r t i e s of the spectrum a r e dominated by the s p i n - e l e c t r i c q u a d r u p o l e i n t e r a c t i o n ; " 1 the i n t e r n u c l e a r magnetic d i p o l a r i n t e r a c t i o n s , which a r e r e l a t i v e l y weak, do not a f f e c t the l i n e s h a p e a n a l y s i s . However, t h r e e o b s t a c l e s , each of which l o w e r s the o v e r a l l s i g n a l - t o - n o i s e , had t o be overcome i n o r d e r t o make 2H n.m.r. an a t t r a c t i v e method: ( l ) the low n a t u r a l abundance (0.0156 %) of 2H, (2) the low magnetogyric r a t i o , which i s s m a l l e r by a f a c t o r of 6.51 by comparison w i t h 1H, and (3) the qu a d r u p o l e s p l i t t i n g which can r e s u l t i n a s p e c t r a l w i d t h >250 kHz f o r r i g i d s o l i d s . Recent developments of e x p e r i m e n t a l s o l i d - s t a t e n.m.r. t e c h n i q u e s , " 2 ' " 3 p l u s the use of 2 H - e n r i c h e d compounds, have paved the way f o r t h i s method. The low n a t u r a l abundance of 2H can be used t o an advantage, s i n c e s e l e c t i v e l a b e l l i n g up t o 100 % i s f a i r l y s i m p l e , and the n e g l i g i b l e l e v e l of background s i g n a l a t n a t u r a l abundance does not c o m p l i c a t e the o v e r a l l spectrum. F u r t h e r m o r e , a n a l y s i s of the e x p e r i m e n t a l l i n e s h a p e s can be performed f o r some m o b i l e systems where f o r m u l a t i o n of t h e o r i e s of the dependence on m o t i o n a l dynamics has been e s t a b l i s h e d . " " D euterium n.m.r. s p e c t r a of r i g i d s o l i d s show the c h a r a c t e r i s t i c " P a k e - d o u b l e t " p a t t e r n . " 5 The magnitude of 4 5 the q u a d r u p o l e c o u p l i n g i s dete r m i n e d by the o r i e n t a t i o n of the m o l e c u l e i n the magnetic f i e l d . Any r e o r i e n t a t i o n a l p r o c e s s e s r e s u l t i n changes of the Pake p a t t e r n , and by measuring the changes i n the shape of the p a t t e r n , i t i s p o s s i b l e t o c h a r a c t e r i z e both the r a t e and the mechanism of the m o l e c u l a r r e o r i e n t a t i o n . 1 . 2 . 2 . N.M.R. of Quadrupolar N u c l e i i n the S o l i d S t a t e In an a p p l i e d magnetic f i e l d B 0, the t o t a l s p i n H a m i l t o n i a n f o r a s p i n I > 1 i s g i v e n by H = H Z + Ha. + He + H C 5 A + H S C ( 2 4 ) where H z, H &, Hp, H C S A , and Hsc a r e the Zeeman, q u a d r u p o l e , d i p o l e , c h e m i c a l s h i f t a n i s o t r o p y , and s c a l a r c o u p l i n g H a m i l t o n i a n s , r e s p e c t i v e l y . For de u t e r o n s which have n u c l e a r s p i n 1 = 1 , H D, H C S A , and H Sc are e s s e n t i a l l y n e g l i g i b l e and hence, the t r u n c a t e d H a m i l t o n i a n may be w r i t t e n as H = H z + H Q_ ( 2 5 ) At c o n v e n t i o n a l n u c l e a r resonance f r e q u e n c i e s ( i . e . , " h i g h f i e l d " c a s e s ) , the qua d r u p o l e i n t e r a c t i o n i n s o l i d s i s much weaker than the Zeeman i n t e r a c t i o n , t h u s , o n l y a f i r s t - o r d e r p e r t u r b a t i o n i s r e q u i r e d f o r d e s c r i p t i o n of the 46 the energy l e v e l s . The Zeeman i n t e r a c t i o n H a m i l t o n i a n i s g i v e n by H z = - W B 0 I Z (26) = - h V 0 I z w i t h B 0 a l o n g the z - a x i s of the l a b o r a t o r y c o o r d i n a t e frame, and the Larmor frequency v 0 = YB 0/27f. The Zeeman l e v e l s w i l l then have e n e r g i e s E m = -mh\)0 (27) where m i s the magnetic quantum number. For a s p i n 1 n u c l e u s , m t a k e s v a l u e s of 1, 0, - 1 . S i n c e the magnetic f i e l d ( r a t h e r than the e l e c t r i c f i e l d ) d e t e r m i n e s the d i r e c t i o n of q u a n t i z a t i o n , the f i r s t -o r d e r t h e o r y w i l l g i v e r i s e t o the energy l e v e l s " 1 E m - Ena h (28) •mV0 + Va» 4 3m 2-I(1+1) 3 c o s 2 0 ~ 1 + 71 s i n 2 g c o s 2 T ' 2 1 2 where 0 and V are the E u l e r a n g l e s d e f i n i n g the o r i e n t a t i o n of the p r i n c i p a l a x i s of the e l e c t r i c f i e l d g r a d i e n t ( e . f . g . ) t e n s o r ( u s u a l l y a l o n g the C-D bond d i r e c t i o n ) w i t h r e s p e c t t o the l a b o r a t o r y c o o r d i n a t e s . Q^. i s the q u a d r u p o l e c o u p l i n g c o n s t a n t , and i s the asymmetry parameter which 47 p r o v i d e s the measure of the d e v i a t i o n of the e . f . g . from a x i a l symmetry. For the case of C-D bonds, ^ i s u s u a l l y l e s s than 0.05 a c c o r d i n g t o the t h e o r e t i c a l c a l c u l a t i o n s and c r y s t a l s t u d i e s . " 6 - * 9 U s i n g the assumption of a x i a l symmetry ( i . e . ^ = 0) t o e l i m i n a t e f dependence, as i s c e r t a i n l y t r u e f o r deuterons i n s p 3 bonds t o c a r b o n , the t h r e e energy l e v e l s f o r a s i n g l e d e u t e r o n ( F i g . 1-15) may be w r i t t e n as E_, = V 0 + Va. 3 c o s 2 9 - 1 4 2 E 0 = - 3 c o s 2 6 - 1 2 2 (29) E, = - v 0 + -0a. 3 c o s 2 B - 1 2 2 The a l l o w e d t r a n s i t i o n s a re governed by the s e l e c t i o n r u l e Am = ±1; the resonance f r e q u e n c y V+ ( f o r Am = -1 t r a n s i t i o n ) i s g i v e n by V+= E_, - E 0 = v'o + 3 vL, 3 c o s 2 & - 1 4 2 (30) \)-= E 0 - E + , = 00 ~ 3 o a 3 c o s 2 $ - 1 4 2 Thus, two resonance l i n e s of e q u a l i n t e n s i t y a r e o b s e r v e d , and t h e i r s e p a r a t i o n r e s u l t s i n the "quadrupole s p l i t t i n g " . 48 A v a = V+ - V- = 3 V a 3cos 2(9 - 1 2 2 (31) = 3 e 2qQ 3 c o s 2 6 - 1 2 h 2 The term e 2qQ/h i s g e n e r a l l y r e f e r r e d t o as the s t a t i c q u a drupole c o u p l i n g c o n s t a n t , where eQ i s the n u c l e a r q u a d r u p o l e moment, eq i s the e . f . g . a t the d e u t e r i u m n u c l e u s , and h i s P l a n c k ' s c o n s t a n t . Q*0 Ve+Q V0 \>o-Q V0 Vo+Q i - i> , Q = 0 i " \ " ~ ~ \ \ I1> v-F i g . 1-15. Energy l e v e l diagram f o r s p i n , I = 1, showing the e f f e c t of a weak e l e c t r i c q u a d r u p o l e i n t e r a c t i o n , Q, on the Zeeman l e v e l s . 49 1.2.3. E l e c t r i c F i e l d G r a d i e n t E f f e c t s The e . f . g . i s c h a r a c t e r i z e d by a symmetric second rank t e n s o r , V, w i t h p r i n c i p a l elements g i v e n by V*x , V y / , and V 2 Z . These t h r e e parameters a r e not independent, t h a t i s , Vxx + Vyy + V Z Z = 0 where V** = -1(1 -V ) V Z 2 2 L (33) Vyy = -H 1 + f ) V ? 2 2 C o n v e n t i o n a l l y , the e . f . g . p r i n c i p a l axes are chosen such t h a t V 2 Z > V™ > Vyy where V z z i s a l o n g the C-D bond, V y y i s p e r p e n d i c u l a r t o the p l a n e of the bond, and V x x i s o r t h o g o n a l t o these two a x e s . T h e r e f o r e , *j = Vxx ~ Vyy (34) which a s s u r e s t h a t i t s v a l u e l i e s between 0 and 1. In g e n e r a l , i t i s u s u a l l y not p o s s i b l e t o g i v e a s i m p l e a n a l y t i c a l e x p r e s s i o n f o r the q u a d r u p o l a r energy t o i n c l u d e the e f f e c t s of f i e l d g r a d i e n t asymmetry. However, the f o l l o w i n g e q u a t i o n s h o l d t r u e f o r the s p i n 1 c a s e : Av, = 3 ^ ( 1 4 -V 50 AV 2 = 3 \U 1 + 1 ) A L (35) 3 - 1A 2 The e f f e c t of ^ on the l i n e s h a p e i s t o s p l i t the s i n g u l a r i t y (which c o r r e s p o n d s t o 6 = 90°) i n t o two p a r t s . 5 0 A s h o u l d e r grows out of the s i n g u l a r i t y and moves away from V 0 w i t h i n c r e a s i n g >^(Fig. 1-16). At the same t i m e , the s i n g u l a r i t y i t s e l f s h i f t s an e q u a l amount away from i t s o r i g i n a l (/j = 0) p o s i t i o n back towards V0. E v i d e n t l y , as ^ approaches z e r o , the y dependence i s e v e n t u a l l y e l i m i n a t e d t o y i e l d Eq. ( 3 1 ) . 1.2.4. Deuterium N.M.R. of L i q u i d C r y s t a l s In the l i q u i d or gaseous s t a t e , where m o l e c u l a r r e o r i e n t a t i o n i s r a p i d r e l a t i v e t o the r e c i p r o c a l of the quadr u p o l e c o u p l i n g c o n s t a n t , the term ( 3 c o s 2 0 - 1) i n Eq. (31) i s averaged t o z e r o . The q u a d r u p o l e s p l i t t i n g c o l l a p s e s t o y i e l d a s i n g l e peak a t V0. Some m a t e r i a l s a r e known t o form l i q u i d c r y s t a l s , i n which c e r t a i n domains e x i s t where t h e r e i s c o n s i d e r a b l e o r d e r i n g of the m o l e c u l e s . In the presence of B 0, some l i q u i d c r y s t a l l i n e phases t e n d t o become a l i g n e d , w i t h the l o n g a x i s of the l i q u i d c r y s t a l - f o r m i n g m o l e c u l e s o r i e n t e d a p p r o x i m a t e l y p a r a l l e l t o the f i e l d . Due t o r a p i d 51 — I 1 1 1 1— 2V_ _^ 0 V* 2V* 0=90° 0° F i g . 1-16. C a l c u l a t e d powder p a t t e r n f o r s p i n , I = 1, i n the f o l l o w i n g e l e c t r i c f i e l d g r a d i e n t s : (A) 1 = 0.0; (B) n = 0.67; (C) 1 = 1.0 (from Ref. [ 5 0 ] ) . r e o r i e n t a t i o n of the m o l e c u l e s (about an a x i s of a t l e a s t C3 symmetry) w i t h i n the l i q u i d c r y s t a l , o n l y a p a r t i a l o r d e r i n g of the m o l e c u l e s e x i s t s , and the tim e - a v e r a g e " o r d e r parameter", S C D , i s r e l a t e d t o the obser v e d q u a d r u p o l e s p l i t t i n g a c c o r d i n g t o the e x p r e s s i o n 5 1 AVa = 3 e 2qQ S c o 2 h (36) s C D = / 3 c o s 2 e - 1 where 0 i s the a n g l e between the C-D v e c t o r and B 0. I f the l o n g a x i s i s not p a r a l l e l t o the f i e l d d i r e c t i o n but makes 52 an a n g l e fl w i t h t h i s a x i s ( F i g . 1-17), the obser v e d d o u b l e t s p a c i n g may be w r i t t e n a s : AV^(0 ,0) = 3 e 2qQ / 3 c o s 2 6 n - A / 3cos 2Q - A 2 h \ 2 / \ 2 J(21) = 3 e 2qQ S C D / 3 c o s 2 a - 1 2 h " \ 2 where 0 n i s the a n g l e between the C-D bond d i r e c t i o n and the normal n. The quadr u p o l e s p l i t t i n g c o l l a p s e s i f the lo n g a x i s i s i n c l i n e d a t the "magic a n g l e " (fl = 54.7°) w i t h r e s p e c t t o B 0. For a l i p i d b i l a y e r c o n s i s t i n g of a l y o t r o p i c l i q u i d c r y s t a l d e r i v e d from a d e u t e r a t e d l o n g - c h a i n h y d r o c a r b o n , S tD n i s a measure of the time-average f l u c t u a t i o n of the C-D bond a x i s w i t h r e s p e c t t o n t o the b i l a y e r s u r f a c e . R o w e l l e t a l . 5 2 have shown t h a t t he d e u t e r i u m n.m.r. s p e c t r a of a r o m a t i c compounds d i s s o l v e d i n a nematic m a t r i x always g i v e r i s e t o a d o u b l e t which i s s p l i t by the quadru p o l e i n t e r a c t i o n . Such m o l e c u l e s p a r t i c i p a t e i n the a n i s o t r o p i c motion of the s o l v e n t , and the a n a l y s i s of t h e i r n.m.r. s p e c t r a i s q u i t e s t r a i g h t f o r w a r d . 1.2.5. Deuterium N.M.R. of P o l y c r y s t a l l i n e Samples  1.2.5.1. S t a t i c O r i e n t a t i o n of a C-D bond For r i g i d p o l y c r y s t a l l i n e (or powder) samples where many s m a l l c r y s t a l s a r e randomly o r i e n t e d w i t h r e s p e c t t o 53 F i g . 1-17. Schematic r e p r e s e n t a t i o n ' o f a l i p i d b i l a y e r . [n i s the normal t o the b i l a y e r . ft i s the a n g l e between the magnetic f i e l d B 0 and n, 0 i s the a n g l e between the C-D v e c t o r and B 0, and ©n i s the a n g l e between the C-D v e c t o r and fi.] B 0, the d e u t e r i u m resonance i s observed as a broad e n v e l o p e . The shape of the "powder-type" spectrum i s then the average over the resonances of a l l v a l u e s of 6 of the n u c l e a r s p i n s . Each of the i n d i v i d u a l o r i e n t a t i o n s i n the p o l y c r y s t a l l i n e sample g i v e s two re s o n a n c e s , and each o r i e n t a t i o n must be g i v e n e q u a l s t a t i s t i c a l w e i g h t . For a u n i f o r m d i s t r i b u t i o n of N n u c l e i over a s u r f a c e of a sphere of r a d i u s r , the number of n u c l e i per u n i t a r e a i s N/47rr 2. The f r a c t i o n dN of n u c l e i o r i e n t e d between 6 and 6 + df? w i t h r e s p e c t t o B c ( F i g . 1-18) i s g i v e n by the a r e a 54 of a zone of the sphere, 27rr 2 s i n 0 d 0 , m u l t i p l i e d by the s p i n s u r f a c e d e n s i t y : 5 1 e / / r F i g . 1-18. A n n u l a r r i n g between 6 and d0 w i t h a r e a 27rr 2 s i n 0 d 0 . dN = (N/47rr 2 ) 2 7 r r 2 s i n 0 d 0 (38) = (N/2)sin0d0 The p r o b a b i l i t y d e n s i t y p(0) i s then g i v e n by p(0) = l / 2 ( s i n 0 ) / p(0)d0 = 1 -'o (39) (40) 5 5 A c c o r d i n g t o E q . ( 3 0 ) , t h e r e s o n a n c e f r e q u e n c y ^ ± i s d e p e n d e n t o n t h e o r i e n t a t i o n a n g l e 6: V ± = \>0 ± 3 Vra 3 c o s 2 0 - 1 2 a 2 F o r c o n v e n i e n c e , a " r e d u c e d " r e s o n a n c e f r e q u e n c y £ ± i s d e f i n e d a s t = Vt - Vo = ± 3 c o s 2 e - 1 ( 4 1 ) w h e r e 1 > £ + > - 1 / 2 a n d - 1 < $_ < + 1 / 2 . T h e p r o b a b i l i t y f u n c t i o n p ( £ ) i s d e f i n e d s u c h t h a t p ( £ ) d £ d e s c r i b e s t h e f r a c t i o n o f s p i n s b e t w e e n % a n d £ + d £ . T h e t w o p r o b a b i l i t y d e n s i t i e s p ( 0 ) a n d p ( £ ) a r e r e l a t e d t o e a c h o t h e r b y pU) = p ( 0 ) d _ 0 = l s i n 0 d _ 0 = - I d c o s f l ( 4 2 ) d £ 2 d £ 2 d $ Now t h e d e u t e r i u m s p e c t r u m c a n b e e x p r e s s e d i n t e r m s o f t h e t w o r e s o n a n c e s £ + a n d s o t h a t p ( £ ) = p U t ) + p(*_) ( 4 3 ) C o m b i n i n g E q s . ( 4 1 ) a n d ( 4 2 ) , t h e p r o b a b i l i t y d e n s i t i e s a r e g i v e n b y t h e f o l l o w i n g r e l a t i o n s h i p . 56 P( £»)<>< 1 (44) /±2« ± + 1 A t y p i c a l powder spectrum ( F i g . 1-19) i s o b t a i n e d by p l o t t i n g the p r o b a b i l i t y d e n s i t i e s p ( i j + ) , p(£_), and p(£) a g a i n s t £. Because p($) d i v e r g e s a t f r e q u e n c i e s £ = ±1/2, a peak s e p a r a t i o n c o r r e s p o n d i n g t o 6 = 90° and a s h o u l d e r s e p a r a t i o n c o r r e s p o n d i n g t o 6 = 0° a r e obse r v e d . For >| = 0, t h e i r r e s p e c t i v e s e p a r a t i o n s a r e g i v e n by Av<^ = 3 e 2qQ 4 h and (45) 2AV^ = 3 e 2qQ 2 h These e x p r e s s i o n s assume t h a t t h e r e a r e no f a s t (>10 5 s " 1 ) , l a r g e - a m p l i t u d e motions of the C-D v e c t o r s i n the s o l i d sample. I t s h o u l d be noted t h a t the e x p e r i m e n t a l spectrum i s s l i g h t l y d i f f e r e n t from i t s t h e o r e t i c a l c o u n t e r p a r t due to the d i p o l a r b r o a d e n i n g , and the measured peak t o peak v a l u e i s l e s s than the a c t u a l s p l i t t i n g . 5 3 As an e m p i r i c a l e x p e r i m e n t a l c o r r e c t i o n , peak p o s i t i o n s a r e u s u a l l y taken s l i g h t l y t o the o u t e r - s i d e of the s p e c t r a l peaks. 1.2.5.2. R e o r i e n t a t i o n a l M o t i o n s f o r a C-D Bond In the case of " f a s t " r e o r i e n t a t i o n a l m o t i o n , w i t h a c o r r e l a t i o n time Zc< 1/AV a, i t i s n e c e s s a r y t o make a time average of the f i e l d g r a d i e n t t e n s o r . 4 " T h i s motion s h o u l d 57 — I 1 1 I i i I i L_L_I i L_ - 1 0 - 0 5 0 0 5 1 0 i F i g . 1-19. T h e o r e t i c a l powder p a t t e r n f o r a d e u t e r o n i n a symmetric e l e c t r i c f i e l d g r a d i e n t ( *J = 0 ) . The dashed l i n e s i n d i c a t e the i n d i v i d u a l components of the m = -1 <--> m = 0 ( S t ) and m = 0 <--> m = +1 ( ) t r a n s i t i o n s , w h i l e the s o l i d l i n e r e p r e s e n t s the sum of the two components (from Ref. [ 5 1 ] ) . be u n i f o r m about an a r b i t r a r y a x i s z' (Brownian m o t i o n , or p l a n a r jumps between e q u i v a l e n t s i t e s of symmetry h i g h e r t h a n , or e q u a l t o , C i v ) i n o r d e r t h a t p a r t i a l a v e r a g i n g of the o r i g i n a l q uadrupole t e n s o r t o an e f f e c t i v e a x i a l l y symmetric t e n s o r , w i t h i t s p r i n c i p a l a x i s a l o n g z', would o c c u r . U s i n g the n o t a t i o n of F i g . 1-20, i t can be shown t h a t the m o t i o n a l l y averaged s p l i t t i n g , AVQ ( , i s M R , = 3 e 2qQ ( 3 c o s 2 0 ' - 1 ) (3cos 2/3 - 1 ) (46) 2 h 2 2 where 0' i s the a n g l e between the a x i s of m o t i o n a l a v e r a g i n g and the magnetic f i e l d d i r e c t i o n , and 0 i s the a n g l e between the p r i n c i p a l a x i s of the e . f . g . t e n s o r and 58 I I F i g . 1 - 2 0 . I l l u s t r a t i o n of r e o r i e n t a t i o n a l motions f o r a C-D bond i n c l i n e d at 0 degrees w i t h r e s p e c t to an a x i s of m o t i o n a l a v e r a g i n g , ' z ' , which i n t u r n i s i n c l i n e d a t 7 degrees w i t h r e s p e c t t o another a x i s of m o t i o n a l a v e r a g i n g , z ' 1 . the a x i s of the m o t i o n a l a v e r a g i n g . From the e x p e r i m e n t a l v a l u e of AVd, , the a n g l e /? can thus be o b t a i n e d . Any o t h e r r a p i d motion o c c u r r i n g about a second d i f f u s i o n a x i s z" would f u r t h e r reduce the quad r u p o l e s p l i t t i n g , by f u r t h e r s h r i n k i n g of the e f f e c t i v e quadrupole t e n s o r . By measuring the c o r r e s p o n d i n g v a l u e s Av Q i and AV)q1, the a n g l e 7 between z' and z" can be d e r i v e d from 59 AVQ2= AVa, (3cos 2Y - 1 ) (47) 2 I t i s p o s s i b l e t o compute the l i n e s h a p e c o r r e s p o n d i n g t o the presence of any o t h e r type of motion by c o n s i d e r i n g the a n g l e s , a m p l i t u d e s , and the r a t e s i n v o l v e d . D i f f e r e n t t y p e s of models f o r m o l e c u l a r r e o r i e n t a t i o n have been i n v e s t i g a t e d , however, t h i s i s u s u a l l y d i f f i c u l t , time consuming, and a r b i t r a r y . 5 * In g e n e r a l , the problem i s s i m p l e r f o r f a s t motion where the a n g l e s i n v o l v e d a r e the o n l y parameters r e q u i r e d f o r the c a l c u l a t i o n s of s p e c t r a f o r w e l l - d e f i n e d m o t i o n a l models. I.2.6. S p i n Echoes i n S o l i d s The f i r s t example, of what i s now a whole f a m i l y of i n g e n i o u s e x p e r i m e n t s which have been d e s i g n e d t o remove the e f f e c t of the a p p l i e d f i e l d inhomogeneity, was f i r s t r e p o r t e d by Hahn i n 1 9 5 0 . 5 5 I n i t i a l l y , a 90° p u l s e i s a p p l i e d a l o n g x' a t time z e r o t o a s p i n system ( F i g . 1-21). The m a g n e t i z a t i o n t h a t has decayed i n the r o t a t i n g x'-y' p l a n e due t o e x t e r n a l f i e l d inhomogeneity can be r e f o c u s s e d i n t o an echo by an a p p r o p r i a t e p u l s e (which can be 90° out of phase, a l t h o u g h t h i s i s not mandatory). An i n v e r t e d s p i n echo i s o b t a i n e d when a 180° p u l s e i s a p p l i e d a l o n g the x' a x i s . A l s o , an echo can be o b s e r v e d f o l l o w i n g a 90° p u l s e (90° out o f p h a s e ) ; t h a t t h i s can o n l y be a d i p o l a r echo demonstrates the e x i s t e n c e of an average s t a t i c i 1 i 60 z F i g . 1-21. R o t a t i n g frame r e p r e s e n t a t i o n of the s p i n i s o c h r o m a t s i n a Hahn echo sequence. i n t e r a c t i o n . The (180°) Hahn echo cannot be formed f o r d i p o l a r c o u p l e d s o l i d s because the l o c a l f i e l d i s not s t a t i c ; now the second p u l s e s i m p l y i n v e r t s a l l s p i n s and, c o n s e q u e n t l y , the l o c a l f i e l d s as w e l l . Quadrupole echoes were f i r s t o b s e r v e d from s o l i d s by S o l o m o n 5 6 f o r the I = 5/2 s p e c i e s 1 2 7 I i n K I . The c a l c u l a t i o n s were c a r r i e d out f o r a 90 - t - / 3 0 , (XX) sequence, where /3 i s the v a r i a b l e w i d t h of the second p u l s e , and the n o t a t i o n |30o i n d i c a t e s a z e r o - d e g r e e p h a s e - s h i f t between the i n i t i a l , 90° p u l s e and the second, /3 p u l s e . The a n a l y s i s was based on the assumption t h a t the d i p o l a r i n t e r a c t i o n s were n e g l i g i b l y s m a l l i n comparison w i t h the 61 q u a d r u p o l a r terms. A c c o r d i n g t o the a u t h o r , no s p i n - e c h o response f o r any r o t a t i o n a n g l e , 0, i n the s o l i d s t a t e f o r s p i n s I = 1 i s a n t i c i p a t e d , u s i n g t h i s p u l s e sequence. Deuterium n.m.r. s p i n echoes were s u b s e q u e n t l y o b s e r v e d by a p p l y i n g the 90-T-/3o° s e q u e n c e 5 7 t o p e r d e u t e r a t e d o r g a n i c s o l i d s , under the c o n d i t i o n s such t h a t (3 * k.90°, and k = 0,1,2,... T h i s e x p e r i m e n t a l o b s e r v a t i o n p roves t h a t d i p o l a r i n t e r a c t i o n s between deu t e r o n s i n these systems cannot be n e g l e c t e d , s i n c e such echoes a r i s e o n l y i n t h e i r p r e s e n c e . T h i s t h e o r y p r e d i c t s t h a t the ec h o - a m p l i t u d e i s dependent on 0 and X, the w i d t h of the second p u l s e and the i n t e r p u l s e s p a c i n g , r e s p e c t i v e l y . The d e u t e r o n s p i n echo response f o r a 90°-T-/3(?oo (XY) sequence i s g i v e n by the e x p r e s s i o n : 5 7 E X Y ( p \ x ) = a ( T ) s i n 2 / 3 + b ( x ) s i n 2 0 c o s 2 / 3 (48) The sin 2/3 component dominates E x y ( 0 , T ) a t s h o r t X, but i t decays much f a s t e r than the sin 2/?cos 2|3 component. Thus, the maximum echo a m p l i t u d e s h i f t s t o /3 < 90° w i t h i n c r e a s i n g X. In the absence of d i p o l a r i n t e r a c t i o n s , the second term v a n i s h e s . T h e o r e t i c a l l y , o n l y t h e f i r s t term of the XY echo i s p r e d i c t e d f o r the i s o l a t e d s p i n I = 1 s u b j e c t e d t o qua d r u p o l e i n t e r a c t i o n s . For the XX sequence, i n t h e presence of d i p o l a r i n t e r a c t i o n s between s p i n s , the dependence i s 62 E X x ( 0 , t ) = -c (T)sin 2/3cos 2/3 ( 4 9 ) T h i s term v a n i s h e s i f t h e r e a re no d i p o l a r i n t e r a c t i o n s . I n thes e e x p r e s s i o n s , a, b, and c are c o n s t a n t s f o r a g i v e n T v a l u e , s i n c e they a r e independent of 0. Ap a r t from a change of s i g n , the t h e o r y a l s o p r e d i c t s t h a t the echo shape i s the same f o r the two p u l s e sequence. 1.2.7. Deuterium N.M.R. Exper i m e n t s The u s u a l e x p e r i m e n t a l p r o c e d u r e f o r a p u l s e F . t . n.m.r. measurement i n v o l v e s the a c c u m u l a t i o n of the f . i . d . f o l l o w i n g a p p l i c a t i o n of a 9 0 ° p u l s e which i s a p p l i e d a t a fr e q u e n c y , V, s e t c l o s e t o the sample's resonant f r e q u e n c y , vo• The f r e q u e n c y spectrum of t h i s sample i s then o b t a i n e d by F o u r i e r t r a n s f o r m a t i o n of the f . i . d . . T h i s same t e c h n i q u e i s a l s o a p p l i c a b l e t o d e u t e r i u m q u a d r u p o l a r systems, i n which the spectrum of a g i v e n d e u t e r o n i s a d o u b l e t w i t h l i n e s a t ^ 0 ± V. However, such powder s p e c t r a a r e o f t e n v e r y broad, which p r e s e n t s some s e r i o u s problems f o r p u l s e d F . t . n.m.r.. For example, i t i s d i f f i c u l t t o e x c i t e the sample u n i f o r m l y a c r o s s the whole s p e c t r a l range u s i n g a r . f . p u l s e of f i n i t e power. F u r t h e r m o r e , the t o t a l decay time of the f . i . d . f o l l o w i n g a s i n g l e e x c i t a t i o n p u l s e i s o n l y a few tens of m i c r o s e c o n d s ; t h i s i s s h o r t e r than the r e c o v e r y time of the probe f o l l o w i n g the p u l s e . S i n c e much of the i n f o r m a t i o n i s c o n t a i n e d i n the v e r y e a r l y p a r t of the f . i . d . , i t i s mandatory t o c i r c u m v e n t the 63 "dead-time" of the r e c e i v e r . 4 2 ' " 3 L a r g e l y because of the l a t t e r problem, the a p p l i c a t i o n of F . t . methods t o d e u t e r i u m n.m.r. i n h i g h f i e l d s e n j o y e d l i t t l e s u c c e s s u n t i l the development i n 1976, of the F . t . s o l i d echo method, which i s now r o u t i n e l y used t o overcome the r e c e i v e r dead t i m e . T h i s i n v o l v e s a t w o - p u l s e , quadrupole echo sequence as shown below: An i n i t i a l p u l s e , 9 0 ° y 9 0 ° x Schematic r e p r e s e n t a t i o n of a 2H s o l i d echo p u l s e sequence. which r o t a t e s the m a g n e t i z a t i o n by 90°, i s f o l l o w e d a t a time T; l a t e r by a second 90° p u l s e which i s . phase s h i f t e d by 90° w i t h r e s p e c t t o the f i r s t . A c h a r a c t e r i s t i c s i g n a l c a l l e d the "quadrupole s o l i d - e c h o " i s obse r v e d a t t = 2T, which has maximum a m p l i t u d e when the f l i p a n g l e of th e s e p u l s e s i s e x a c t l y 90°. I f X i s s e t l a r g e , the probe w i l l have s u f f i c i e n t time f o r f u l l r e c o v e r y from the e f f e c t of 64 the e x c i t a t i o n p u l s e s , and the s i g n a l may be accumulated w i t h z e r o time s e t a t the top of the echo. The r e f o c u s s i n g of the n u c l e a r m a g n e t i z a t i o n i s complete under these c o n d i t i o n s , a s i d e from the e f f e c t s of r e l a x a t i o n and s t a t i c magnetic f i e l d i n h o m o g e n e i t i e s . I t s h o u l d be noted t h a t t h i s echo method does not n e c e s s a r i l y l e a d t o an u n d i s t o r t e d spectrum. In f a c t , the f i n i t e w i d t h of the second p u l s e g r e a t l y reduces the i n t e n s i t y i n the wings of the s p e c t r u m . 5 8 A l s o , the appearance of the spectrum i s a f f e c t e d i f F o u r i e r t r a n s f o r m a t i o n of the s i g n a l does not s t a r t a t the top of the q u a d r u p o l a r e c h o . 5 8 ' 5 9 The bandwidth of the p r o b e , 4 3 r e c e i v e r , 6 0 and t r a n s m i t t e r may a l s o l e a d t o d i s t o r t i o n s of the spectrum. Another k i n d of d i s t o r t i o n o c c u r s when the time s c a l e f o r m o l e c u l a r r e o r i e n t a t i o n i s comparable t o the echo r e f o c u s s i n g t i m e . 6 1 Thus, i t i s e s s e n t i a l t o r e c o g n i z e t h e s e e f f e c t s i n o r d e r t o i n t e r p r e t the s p e c t r a c o r r e c t l y . In an a c t u a l e x p e r i m e n t , the p u l s e l e n g t h s a r e u s u a l l y not e x a c t l y 90°, and the phases do not bear e x a c t l y the c o r r e c t r e l a t i o n t o the r e c e i v e r phase. S i n c e the second p u l s e not o n l y produces an echo, but a l s o a f . i . d . (90° out of phase t o the e c h o ) , i t i s n e c e s s a r y t o e l i m i n a t e the l a t t e r by a l t e r n a t i n g the phase a t the f i r s t p u l s e between 0° and 180° and t h a t of the second p u l s e between 90° and 270° . The use of p u l s e s s h o r t e r than 90° may generate problems when q u a d r a t u r e phase d e t e c t i o n i s used, s i n c e the 65 q u a d r a t u r e component c o n t a i n i n g the f . i . d . f o l l o w i n g the second p u l s e would r e s u l t i n a s e r i o u s d i s t o r t i o n of the spectrum on F o u r i e r t r a n s f o r m a t i o n . In o r d e r t o r e s o l v e t h i s problem, T. i s set as l o n g as 240 f*-s t o ensure t h a t the f . i . d . has decayed at the time the echo maximum o c c u r s . " 3 T h i s a l s o e f f e c t i v e l y e l i m i n a t e s any remnant of the f r e e i n d u c t i o n s i g n a l a r i s i n g from the f i r s t p u l s e , t h a t i s not r e f o c u s s e d by the second p u l s e . For a broad d e u t e r i u m n.m.r. spectrum, the s p e c t r a l wings are p r o g r e s s i v e l y s u p p r e s s e d r e l a t i v e t o the c e n t e r as the p u l s e l e n g t h i s i n c r e a s e d . T h i s o c c u r s as a r e s u l t of the p r e c e s s i o n of the n u c l e a r s p i n s due to the q u a d r u p o l a r i n t e r a c t i o n s , d u r i n g the r . f . p u l s e . T h i s e f f e c t can be reduced by d e c r e a s i n g the p u l s e l e n g t h , but o n l y f o r s p e c t r a w i t h good s i g n a l - t o - n o i s e r a t i o , s i n c e d r a s t i c r e d u c t i o n i n i n t e n s i t y o c c u r s when the f l i p - a n g l e of the p u l s e , 6, i s s i g n i f i c a n t l y s h o r t e r than ir/2. 66 R e f e r e n c e s 1. S. R. Hartmann, E. L. Hahn, Phys. Rev., 128, 2042(1962). 2. A. P i n e s , M. G. Gibby, J . S. Waugh, J . Chem. Phys., 59, 569(1973). 3. E. R. Andrew, A r c h . Sc i . (Geneva) , J_2, 1 03(1959). 4. I . J . Lowe, Phys. Rev. L e t t . , 2, 285(1959). 5. J . S c h a e f e r , E. 0. S t e j s k a l , J . Am. Chem. S o c , 98, 1031(1976). 6. F. P. M i k n i s , Magn. Reson. Rev., 7, 87(1982). 7. H. S a i t o , R. Tabeta, T. Harada, Chem. L e t t . , 1981, 571. 8. L. D. H a l l , M. Y a l p a n i , Carbohydr. Res., 9J_, C1.O980). 9. M. 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H u i s , A. D. H. C l a g u e , B u l l . Magn. Reson., 2, 120(1981). 29. N. Zumbulyadis, J . Magn. Reson., 49, 329(1982). 30. J . S c h a e f e r , E. 0. S t e j s k a l , R. Buchdahl, M a c r o m o l e c u l e s , j_0, 384( 1 977). 68 31. W. T. D i x o n , J . Magn. Reson., 44, 220(1981). 32. M. A. Hemminga, P. A. De J a g e r , K. P. Datema, J . Breg, i b i d . , 50, 508(1982). 33. S. J . O p e l l a , M. H. F r e y , J . Am. Chem. S o c , 101, 5854(1979). 34. L. D. H a l l , T. K. Lim, Carbohydr. Res., V2A, C1(1983). 35. P. E. P f e f f e r , K. B. H i c k s , M. H. F r e y , S. J . O p e l l a , W. L. E a r l , J . Magn. Reson., 55, 344(1983). 36. M. A l i a , E. Lippmaa, Chem. Phys. L e t t . , 37, 260(1976). 37. J . T e g e n f e l d t , U . H a e b e r l e n , J . Magn. Reson., 36, 453(1979). 38. S. Ganapathy, A. N a i t o , C. A. McDowell, J . Am. Chem. Soc., 103, 6011(1981). 39. V. P. Chacko, S. Ganapathy, R. G. B r y a n t , i b i d . , 105, 5491(1983). 40. S. J . 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S i l l e s c u , J . Magn. Reson., 42_, 3 8 1 ( 1 9 8 1 ) . CHAPTER I I CYCLODEXTRINS AND THEIR INCLUSION COMPLEXES 71 C h e m i s t r y of C y c l o d e x t r i n s  11 .1 . I n t r o d u c t i o n C y c l o d e x t r i n s (CDs) were f i r s t i s o l a t e d as d e g r a d a t i o n p r o d u c t s of s t a r c h i n the l a s t c e n t u r y by V i l l i e r s (1891 J , 1 and were s u b s e q u e n t l y c h a r a c t e r i z e d as c y c l i c -o l i g o s a c c h a r i d e s i n 1904 by S c h a r d i n g e r . 2 * 3 In 1938 Freudenberg e t a l . " r e p o r t e d p r o c e d u r e s f o r p r e p a r i n g pure c y c l o d e x t r i n s , and a l s o the e l u c i d a t i o n of t h e i r c h e m i c a l s t r u c t u r e s . By the m i d - f i f t i e s , many of the e a r l i e r c o n f l i c t s on t h e i r p h y s i c a l and c h e m i c a l p r o p e r t i e s had been r e s o l v e d , and r e c e n t l y the c h e m i s t r y of c y c l o d e x t r i n s has been updated i n review a r t i c l e s 5 ' 6 and b o o k s . 7 ' 8 They ar e now c o r r e c t l y d e s c r i b e d as c y c l i c , n o n - r e d u c i n g o l i g o s a c c h a r i d e s c o n t a i n i n g between s i x and t w e l v e a ( l - * 4 ) -l i n k e d g l u c o p y r a n o s e u n i t s . C y c l o d e x t r i n s a re a l s o r e f e r r e d t o as c y c l o a m y l o s e s , c y c l o g l u c a n s , S c h a r d i n g e r d e x t r i n s , and sometimes s i m p l y as d e x t r i n s . The most common ones t h a t can be o b t a i n e d i n l a r g e s c a l e a r e the a-, 0-, and 7-c y c l o d e x t r i n s t h a t c o n s i s t of s i x , seven, and e i g h t g l u c o s e u n i t s , r e s p e c t i v e l y . A l t e r n a t i v e l y , they may be d e s i g n a t e d by the names c y c l o h e x a - , c y c l o h e p t a - , and c y c l o c t a -a myloses, which are more d e s c r i p t i v e of the s t r u c t u r e s . They have t o r u s - l i k e m a c r o r i n g s t h a t a re c a p a b l e of f o r m i n g i n c l u s i o n compounds w i t h s m a l l e r "guest", m o l e c u l e s which f i t i n t o t h e i r 6-10 A c a v i t y ( F i g . I I - 1 ) . However, the r i n g s of the h i g h e r homologues a r e h i g h l y f l e x i b l e ; t h e i r wide c a v i t i e s may not e n c l o s e the guest m o l e c u l e s t i g h t l y 72 F i g . 11 — 1 . C y c l o d e x t r i n s : (A) d i m e n s i o n s of a-, /3-, and y-c y c l o d e x t r i n s ; (B) s t r u c t u r e of 0 - c y c l o d e x t r i n (from Ref. [ 8 ] ) . 7 3 enough t o promote complex f o r m a t i o n . A g r e a t d e a l of a t t e n t i o n has been f o c u s s e d on them as e x c e l l e n t m o d e l s 9 of h y d r o l y t i c enzymes, both i n terms of s u b s t r a t e c o m p l e x a t i o n and r e a c t i v i t y . They a r e most o u t s t a n d i n g i n f a c i l i t a t i n g c h e m i c a l r e a c t i o n s amongst heterogeneous and homogeneous r e a g e n t s . C y c l o d e x t r i n s are a l s o used i n the p r o d u c t i o n of p h a r m a c e u t i c a l s , p e s t i c i d e s , f o o d s t u f f s , and t o i l e t a r t i c l e s ; the s e n s i t i v e s u b stances e n c l o s e d w i t h i n them are p r o t e c t e d from the e f f e c t s of l i g h t and the atmosphere, t h e r e b y e n a b l i n g easy h a n d l i n g and s t o r a g e i n the powder form. By c o m p l e x a t i o n , the i r r i t a n t e f f e c t s of some s u b s t a n c e s can be s u p p r e s s e d (e.g. t r e a t m e n t of i o d i n e p o i s o n i n g w i t h s t a r c h ) , and many un p l e a s a n t t a s t e s or odors may be reduced or even e l i m i n a t e d c o m p l e t e l y . The c y c l o d e x t r i n - i o d i n e c o m p l e x e s 1 0 a l s o s e r v e as models f o r the i n v e s t i g a t i o n of the more c o m p l i c a t e d p o l y m e r i c s t a r c h - i o d i n e r e a c t i o n . C y c l o d e x t r i n s have been employed i n g e l i n c l u s i o n 1 1 and a f f i n i t y c h r o m a t o g r a p h y 1 2 by b i n d i n g c h e m i c a l l y t o a polymer c a r r i e r and as s e l e c t i v e s y n t h e t i c membranes 1 3 by merely i n c o r p o r a t i n g them i n t o the polymer m a t r i x . S e l e c t i v e c h e m i c a l m o d i f i c a t i o n 1 * of c y c l o d e x t r i n s p r o v i d e s o p p o r t u n i t i e s t o i n f l u e n c e t h e i r c omplexing b e h a v i o r by i n t r o d u c i n g v a r i o u s groups or compounds e i t h e r by i o n i c or c o v a l e n t bonding i n t o the m a c r o r i n g . M e t h y l a t e d c y c l o d e x t r i n s have been p r e p a r e d 1 5 and shown t o be v e r s a t i l e c o m p l e x i n g a g e n t s , i n b oth aqueous and o r g a n i c 74 s o l v e n t s . The s t a b i l i t y of t h e i r c r y s t a l l i n e complexes depends on the shape and s i z e of the encaged m o l e c u l e . A c e t y l a t e d c y c l o d e x t r i n s may a l s o s e r v e as hos t f o r s m a l l e r - s i z e o r g a n i c m o l e c u l e s ; t h i s has been demonstrated i n t h i s t h e s i s , u s i n g /3-cyclodextr i n p e r a c e t a t e . 11 . 1 . 1 . The S t r u c t u r e of C y c l o d e x t r i n s I t i s n e c e s s a r y t o have an a c c u r a t e u n d e r s t a n d i n g of the n a t u r e of the c a v i t y of the c y c l o d e x t r i n s i n o r d e r t o e s t a b l i s h the f o r c e s t h a t s t a b i l i z e i n c l u s i o n complexes. The i n t e r m o l e c u l a r i n t e r a c t i o n s r e s p o n s i b l e f o r complex f o r m a t i o n have been d i s c u s s e d f o r known complexes, and some s u g g e s t i o n s on the c a v i t y of the c y c l o d e x t r i n s have been p r o p o s e d . 6 The " l i n i n g " of the c a v i t y , edge of secondary c o n s i s t i n g of -CH groups and 0(2) and 0(3) h y d r o x y l s g l y c o s i d i c l i n k a g e s , edge of p r i m a r y 0(6) h y d r o x y l s F i g . 11-2. C h a r a c t e r i s t i c s t r u c t u r a l f e a t u r e s of c y c l o -d e x t r i n s (from Ref. [ 8 ] ) . The c o n f o r m a t i o n of the c y c l o d e x t r i n s has an im p o r t a n t b e a r i n g on the p h y s i c a l and c h e m i c a l p r o p e r t i e s . From the e v i d e n c e accumulated by X-ray c r y s t a l l o g r a p h i c and n.m.r. 75 s t u d i e s , 1 6 ' 1 7 a more or l e s s u n d i s t o r t e d C l ( D ) - c h a i r c o n f o r m a t i o n of the g l u c o s e u n i t s i s f a v o r e d . The narrower opening of these t o r o i d a l - s h a p e d m o l e c u l e s ( F i g . I I - 2 ) c o n t a i n s the p r i m a r y 0(6) h y d r o x y l groups whereas the w i d e r opening i s o c c u p i e d by the secondary 0(2) and 0(3) h y d r o x y l s . Hence, the o u t s i d e of the c a v i t y i s h y d r o p h i l i c i n c h a r a c t e r , w h i l e , the i n s i d e i s hydrophobic as the l i n i n g c o n s i s t s of -CH groups and g l y c o s i d i c l i n k a g e s . The C ( 6 ) - 0 ( 6 ) bonds a r e p r e f e r e n t i a l l y d i r e c t e d away from the c a v i t y except f o r hydrogen bonding o c c u r r i n g between the h y d r o x y l groups and the i n c l u d e d guest m o l e c u l e s , which a r e m a i n l y h e l d by c l o s e c o n t a c t s t o the -CH hydrogen atoms l i n i n g the c a v i t y . I t was o b s e r v e d t h a t c y c l o d e x t r i n s always adopt a "round" s t r u c t u r e , w i t h i n t r a m o l e c u l a r hydrogen bonds 0(3)-H..O(2) and 0(3)..H-0(2) e x i s t i n g between a d j a c e n t g l u c o p y r a n o s e u n i t s . 6 These i n t e r a c t i o n s s t a b i l i z e the m a c r o c y c l e and a t the same time s i g n i f i c a n t l y i n f l u e n c e i t s s o l u b i l i t y i n water. Deuterium exchange s t u d i e s 1 8 ' 1 9 of the h y d r o x y l groups have been f o l l o w e d by n.m.r. s p e c t r o s c o p y , and the e q u i l i b r i u m c o n s t a n t s a r e 0.75 and 0.65 f o r a- and / 3 - c y c l o d e x t r i n s , r e s p e c t i v e l y ; these v a l u e s a r e s m a l l e r than t h a t f o r amylose ( 0 . 8 5 ) . T h i s i n d i c a t e s t h a t the i n t e r a c t i o n s a r e s t r o n g e s t f o r 0-c y c l o d e x t r i n whose f l e x i b i l i t y i s the weaker of the two c y c l o d e x t r i n s . I t i s t h e r e f o r e r e a s o n a b l e t o assume t h a t the s t r u c t u r a l f e a t u r e s d e r i v e d from the c r y s t a l l i n e s t a t e w i l l be l a r g e l y r e t a i n e d i n s o l u t i o n , because of the 76 c o n f o r m a t i o n a l r e s t r a i n t s imposed on them by t h e i r looped arrangement. 11.1 .2 . The D r i v i n g F o r c e f o r C o m p l e x a t i o n There has been r e l a t i v e l y l i t t l e emphasis p l a c e d on the u n d e r s t a n d i n g of the i n t e r a c t i o n s r e s p o n s i b l e f o r s u b s t r a t e b i n d i n g . A number of s u g g e s t i o n s as t o the o r i g i n s of t h e s e d r i v i n g f o r c e s have been made, and the t h r e e major ones a r e as f o l l o w s : r e l e a s e of c y c l o d e x t r i n s t r a i n energy, r e l e a s e of h i g h - e n e r g y c a v i t y w a t e r , and van der Waals and London d i s p e r s i o n f o r c e s . V e r i f i c a t i o n of t h e s e b i n d i n g f o r c e s would r e q u i r e some knowledge of the complexes i n s o l u t i o n . R e c e n t l y , Bergeron et a l . 2 0 were a o l e t o show t h a t r e l e a s e of s t r a i n energy c o u l d o n l y p l a y a minor r o l e i n c o m p l e x a t i o n . In the "empty" a - c y c l o d e x t r i n - w a t e r complex, Manor and S a e n g e r 2 1 p o i n t e d out t h a t the two water m o l e c u l e s , w i t h a van der Waals r a d i u s of 3.8 A, are l o c a t e d i n a f i x e d p o s i t i o n w i t h i n the 5.0 A wide c a v i t y t h a t i s s l i g h t l y c o l l a p s e d . T h i s can be a c h i e v e d by the r o t a t i o n of one of the s i x g l u c o p y r a n o s e u n i t s , t h e r e b y , r e s u l t i n g i n a snug f i t w i t h the s m a l l m o l e c u l e s . However, t h i s would d i s r u p t the i n t r a m o l e c u l a r hydrogen bonding of the secondary h y d r o x y l groups and a l s o would impose s t e r i c s t r a i n a t the g l y c o s i d i c l i n k a g e s . Upon complex f o r m a t i o n , the s t r a i n i s r e l i e v e d t o g e t h e r w i t h a drop i n p o t e n t i a l e nergy, but t h i s d r i v i n g f o r c e i s of l i t t l e i mportance t o 77 "empty" 0- and 7- c y c l o d e x t r i n s which are not s t r a i n e d . C r y s t a l l o g r a p h i c s t u d i e s 2 2 of c y c l o d e x t r i n s and t h e i r i n c l u s i o n complexes, r e v e a l t h a t water m o l e c u l e s occupy the hydrophobic c a v i t y i n the absence of a guest m o l e c u l e . These water m o l e c u l e s a r e thought t o be u n s t a b l e ( h i g h i n e n t h a l p y ) due t o t h e i r i n a b i l i t y t o form hydrogen bonds w i t h the b u l k water m o l e c u l e s and the groups l i n i n g the c a v i t y . However on c o m p l e x a t i o n , a guest m o l e c u l e would d i s p l a c e the water b e f o r e o c c u p y i n g the c a v i t y and a t the same time s t r i p o f f i t s own h y d r a t i o n sphere. The former would r e s u l t i n a f a v o r a b l e d e c r e a s e i n e n t h a l p y , and t h i s d r i v i n g f o r c e may be c o n s i d e r e d t o be n o n s p e c i f i c . When the r e l e a s e d water m o l e c u l e s a r e taken up by the b u l k water, t h i s i n c r e a s e s the s t a b i l i t y of the complex due t o an i n c r e a s e i n e n t r o p y . For a r e l a t i v e l y a p o l a r guest m o l e c u l e , t h i s p r o c e s s i s e x p e c t e d t o generate a f a v o r a b l e b i n d i n g f o r c e which dominates when e l e c t r o s t a t i c or c o o r d i n a t i o n i n t e r a c t i o n s a r e l e s s i m p o r t a n t . 8 The i n t e r a c t i o n s between the s u b s t r a t e and the s u r r o u n d i n g c y c l o d e x t r i n a r e u s u a l l y weak and are m a i n l y due t o van der Waals and d i s p e r s i o n f o r c e s . 6 Thus, s m a l l m o l e c u l e s a r e u s u a l l y d i s o r i e n t e d w i t h i n the c a v i t y , even i n the p resence of hydrogen bonding w i t h the 0(6) h y d r o x y l groups. More r e c e n t e x p e r i m e n t s and t h e o r e t i c a l c o n s i d e r a t i o n s have i n d i c a t e d t h a t these f o r c e s p r o b a b l y dominate i n c l a t h r a t i o n . The o t h e r f o r c e s d i s c u s s e d above may a l s o be i n v o l v e d t o a c e r t a i n e x t e n t , depending on the 78 n a t u r e of the encaged m o l e c u l e . 11 . 1 . 3 . C y c l o d e x t r i n I n c l u s i o n Complexes I n c l u s i o n complexes are m o l e c u l a r compounds h a v i n g the c h a r a c t e r i s t i c s t r u c t u r e of an a d d u c t , i n which the " h o s t " m o l e c u l e s p a t i a l l y e n c l o s e s the " g u e s t " . The l a t t e r i s s i t u a t e d i n the c a v i t y t h a t o f t e n remains p r a c t i c a l l y u n a l t e r e d , beyond a s l i g h t d e f o r m a t i o n . Research on c a r b o h y d r a t e i n c l u s i o n complexes has been reviewed by s e v e r a l a u t h o r s , 2 2 ' 2 3 and c y c l o d e x t r i n s have drawn the most a t t e n t i o n . The most i n t e r e s t i n g f e a t u r e of t h e s e c y c l o d e x t r i n s i s t h e i r a b i l i t y t o form complexes w i t h a v a r i e t y of guest m o l e c u l e s i n t h e i r c a v i t y . These guest m o l e c u l e s range from p o l a r r e a g e n t s such as a c i d s , amines, s m a l l i o n s such as C10 4", SCN", and halogen a n i o n s , 2 * t o h i g h l y a p o l a r a l i p h a t i c and a r o m a t i c hydrocarbons and, even, r a r e g a s e s . 2 5 The s t a b i l i t y of these complexes v a r i e s w i t h the s i z e of the guest and the h o s t , and the o b v i o u s requirement i s a mutual f i t between them. Large s u b s t r a t e s w i l l not be a b l e t o p e n e t r a t e i n t o the c a v i t y and t h e r e f o r e no b i n d i n g w i l l o c c u r . On the c o n t r a r y , s m a l l s u b t r a t e s w i l l move f r e e l y i n and out of the c a v i t y w i t h l i t t l e or no apparent b i n d i n g . Thus, the "best f i t " phenomenon 2 6 can be used i n s e p a r a t i n g the c y c l o d e x t r i n s from each o t h e r . For example, a-, j3-, and 7 - c y c l o d e x t r i n s are e f f e c t i v e l y p r e c i p i t a t e d from aqueous s o l u t i o n by benzene. However, o n l y 7-79 c y c l o d e x t r i n can form i n s o l u b l e complex w i t h a n t h r a c e n e , w h i l e the o t h e r two remain i n s o l u t i o n because the s u b s t r a t e w i l l not e f f e c t i v e l y p e n e t r a t e t h e i r c a v i t i e s . S i m i l a r l y f o r /3-cyclodextr i n , bromobenzene i s a b e t t e r p r e c i p i t a n t than benzene, whereas the r e v e r s e i s t r u e f o r a - c y c l o d e x t r i n . In some i n s t a n c e s , the e x t e n t of c o m p l e x a t i o n depends on the p o l a r i t y of the guest m o l e c u l e . P a r t i a l p e n e t r a t i o n by c e r t a i n groups or s i d e c h a i n s i n t o the c h a n n e l may a l s o promote complex f o r m a t i o n . A c c o r d i n g t o Cohen and L a c h , 2 7 g e o m e t r i c f a c t o r s a r e d e c i s i v e i n d e t e r m i n i n g the type of s u b s t r a t e s t h a t w i l l form i n c l u s i o n complexes. Cramer and H e n g l e i n 2 8 c a r r i e d out the f i r s t s y s t e m a t i c s tudy of 54 guest components w i t h i n c y c l o d e x t r i n s and r e a l i z e d t h a t the law of c o n s t a n t p r o p o r t i o n s a p p l i e s t o the i n c l u s i o n . Complexes w i t h a c o n s t a n t g u e s t / c y c l o d e x t r i n r a t i o always c r y s t a l l i z e d out r e g a r d l e s s of t h e i r molar r a t i o s i n aqueous s o l u t i o n ; t h i s i s i n d i c a t i v e of a r e a l i n c l u s i o n phenomenon. In the c r y s t a l l i n e s t a t e , Lammars 2 9 showed t h a t the guest m o l e c u l e s can be accomodated not o n l y i n the c a v i t i e s of the h o s t m o l e c u l e s , but a l s o i n t h e i r i n t e r m o l e c u l a r c a v i t i e s formed by the c r y s t a l l a t t i c e . The c r y s t a l l a t t i c e of t h e s e c y c l o d e x t r i n s i s s t a b l e even when the c a v i t i e s of some of the c y c l o d e x t r i n m o l e c u l e s are not o c c u p i e d or c o n t a i n water m o l e c u l e s . T h e r e f o r e , the molar r a t i o s of c r y s t a l l i n e c y c l o d e x t r i n complexes a r e u s u a l l y n o n s t o i c h i o m e t r i c , but i n s o l u t i o n the r a t i o s a r e u s u a l l y 80 1:1. A n o t a b l e e x c e p t i o n 3 0 i s w i t h l o n g - c h a i n a l k a n e s and f a t t y a c i d s ( w i t h n > 4 ) , where the c y c l o d e x t r i n s may form c h a n n e l s t r u c t u r e s i n s o l u t i o n i n o r d e r t o accommodate the cha i n s . The encaged m o l e c u l e s a r e p r e f e r a b l y o r i e n t e d i n a p o s i t i o n such t h a t maximum c o n t a c t between the hydrophobic p a r t of the guest and the c y c l o d e x t r i n c a v i t y i s a c h i e v e d . On the o t h e r hand, the h y d r o p h i l i c p a r t of the guest m o l e c u l e w i l l remain a t the o u t e r f a c e of the complex t o ensure c l o s e p r o x i m i t y w i t h b oth the s o l v e n t and the h y d r o x y l groups of the host ( F i g . I I - 3 ) . In s o l u t i o n , s t e r i c r e q u i r e m e n t s a re l e s s s t r i n g e n t and complexes which ar e not c r y s t a l l i z a b l e may be formed. a - C y c l o d e x t r i n can form a 1:1 complex w i t h b e n z o i c a c i d , however, o n l y the 0-c y c l o d e x t r i n - b e n z o i c a c i d complex can be c r y s t a l l i z e d r e a d i l y . The f a c t t h a t the guest m o l e c u l e was a c t u a l l y c o n t a i n e d i n the c a v i t y was f i r s t shown by X-ray s t u d i e s . 3 1 Depending on the s i z e and i o n i c or m o l e c u l a r c h a r a c t e r of the g u e s t , two d i f f e r e n t forms of i n c l u s i o n complexes, namely, " c h a n n e l " or "cage" s t r u c t u r e s can be formed. Channel s t r u c t u r e s d e v e l o p when c y c l o d e x t r i n m o l e c u l e s a r e " s t a c k e d - l i k e - c o i n s - i n - a - r o l l " t o y i e l d e n d l e s s c h a n n e l s , i n which the guest m o l e c u l e s a re i n c l u d e d . Cage s t r u c t u r e s a r e a r e s u l t of a d i s p l a c e d arrangement of c y c l o d e x t r i n s i n a " h e r r i n g - b o n e " p a t t e r n , i n which the guest m o l e c u l e s a r e l o c a t e d i n d i s c r e t e , s m a l l c a v i t i e s . The c r y s t a l s t r u c t u r e s 81 F i g . I I - 3 . Schematic r e p r e s e n t a t i o n of the f o r m a t i o n of c y c l o d e x t r i n i n c l u s i o n complexes. 82 of a - c y c l o d e x t r i n complexes t h a t have been a n a l y z e d i n c l u d e the f o l l o w i n g g u e s t s : 6 water, methanol, i o d i n e , p o l y i o d i d e , k r y p t o n , 1-propanol, p - i o d o a n i l i n e , d i m e t h y l s u l f o x i d e and methanol, m - n i t r o p h e n o l , methyl orange, and p o t a s s i u m a c e t a t e . In the case of /3-cyclodextr i n , i t s complexes w i t h w ater, 1-propanol, p - i o d o p h e n o l , 2 , 5 - d i i o d o b e n z o i c a c i d , and p - n i t r o a c e t a n i l i d e have been d e t e r m i n e d . R e c e n t l y , two s t r u c t u r e s of 7 - c y c l o d e x t r i n complexes w i t h 1-p r o p a n o l / w a t e r and water have been d e s c r i b e d . 11.1.4. C y c l o d e x t r i n s as Enzyme Models In r e c e n t y e a r s , c y c l o d e x t r i n s have drawn much a t t e n t i o n as models f o r e n z y m e - c a t a l y z e d r e a c t i o n s . 7 The hydrophobic i n t e r a c t i o n between the s u b s t r a t e and the c a v i t y c o n t r i b u t e s s i g n i f i c a n t l y t o the h y d r o p h o b i c r e c o g n i t i o n by c y c l o d e x t r i n s . Here, they p a r t i c i p a t e not o n l y i n c o m p l e x a t i o n ; c o v a l e n t bonds are a c t u a l l y b e i n g broken and formed. C y c l o d e x t r i n s have been suggested as e x c e l l e n t models of h y d r o l y t i c enzymes. The h y d r o l y s e s 3 2 of e s t e r s and amides i n v o l v e the f o l l o w i n g s t a g e s : b i n d i n g , a c y l a t i o n , and d e a c y l a t i o n , which a r e c o n s i s t e n t w i t h those i n v o l v e d by h y d r o l y t i c enzymes. F u r t h e r m o r e , the c y c l o d e x t r i n - a c c e l e r a t e d c l e a v a g e of th e s e s u b s t r a t e s e x h i b i t s many of the k i n e t i c f e a t u r e s shown by enzymatic r e a c t i o n s , i n c l u d i n g s u b s t r a t e - s p e c i f i c i t y and c o m p e t i t i v e -i n h i b i t i o n s . The f i r s t o b s e r v a t i o n 3 3 of an a - c y c l o d e x t r i n -a c c e l e r a t e d r e a c t i o n was the h y d r o l y s i s of e t h y l p-83 c h l o r o m a n d e l a t e . The a d d i t i o n of 1.32 x 10" 3 M a-c y c l o d e x t r i n caused an a c c e l e r a t i o n i n the h y d r o l y s i s of the e s t e r by a f a c t o r of 1.38. The h y d r o l y s i s of p h e n y l e s t e r s i n the presence of c y c l o d e x t r i n s has been e x t e n s i v e l y i n v e s t i g a t e d . Most of the i n f o r m a t i o n o b t a i n e d from t h e s e systems i s a p p l i c a b l e t o o t h e r c o v a l e n t c a t a l y s e s 7 by c y c l o d e x t r i n s ( F i g . 11-4). The geometry of the guest m o l e c u l e w i t h i n the a nnulus does p l a y an i m p o r t a n t r o l e i n the d e a c y l a t i o n of e s t e r s . 3 4 Both a- and / 3 - c y c l o d e x t r i n s a c c e l e r a t e the c l e a v a g e 8 of p-n i t r o p h e n y l a c e t a t e a t pH 7.5; t h e i r a c c e l e r a t i o n f a c t o r s are 2-3- and 5 - f o l d , r e s p e c t i v e l y . Here, the guest m o l e c u l e i s s i t u a t e d i n the c a v i t y of a - c y c l o d e x t r i n , w i t h the m o l e c u l a r axes of the two b e i n g a l i g n e d c o a x i a l l y . In t h i s way, the e s t e r group i s not f a v o r a b l y o r i e n t e d w i t h r e s p e c t t o the secondary h y d r o x y l groups of c y c l o d e x t r i n t h a t i n i t i a t e the a c y l a t i o n p r o c e s s . A l t h o u g h t h i s o r i e n t a t i o n i s p o s s i b l e w i t h i n the c a v i t y of /3-cyclodextr i n , now the h i g h m o b i l i t y of the guest r e s u l t s o n l y i n a moderate a c c e l e r a t i o n . The h y d r o l y s i s of m - n i t r o p h e n y l a c e t a t e shows an a c c e l e r a t i o n of about 70 f o l d by a - c y c l o d e x t r i n . 8 Presumably, the e s t e r - f u n c t i o n i s l o c a t e d v e r y c l o s e t o the secondary h y d r o x y l g roups, t h e r e b y , a c h i e v i n g a c l o s e c o n t a c t . The l a r g e r / 3 - c y c l o d e x t r i n r i n g , which i s unable t o s e c u r e the s u b s t r a t e t i g h t l y , produces o n l y a 2 0 - f o l d a c c e l e r a t i o n . 84 F i g . I I - 4 . Schematic h y d r o l y s i s (f rom Ref. r e p r e s e n t a t i o n of of p h e n y l a c e t a t e [ 6 ] ) . the c a t a l y t i c by c y c l o d e x t r i n 85 11.1 .5. C y c l o d e x t r i n s as Models f o r S t a r c h C o n f o r m a t i o n a l l y , c y c l o d e x t r i n s may be regard e d as a p r o j e c t i o n of p a r t of a s t a r c h h e l i x down the c y l i n d r i c a l a x i s . Both m o l e c u l e s e x h i b i t s i m i l a r C 1-glucopyranose c o n f o r m a t i o n , and t h e r e f o r e the s p a t i a l arrangements of atoms l i n i n g t h e i r c a v i t i e s resemble each o t h e r . I t i s then ob v i o u s t h a t c y c l o d e x t r i n s c o u l d be used as models f o r s t a r c h s i n c e the X-ray d i f f r a c t i o n s t u d i e s on f i b e r s of i o d i n e - s t a r c h complex gave no e x p l i c i t d e s c r i p t i o n of the s t r u c t u r e of the i o d i n e c h a i n i n the complex, or the i o d i n e - s t a r c h i n t e r a c t i o n s . 3 5 Hence, the a - c y c l o d e x t r i n -i o d i n e - i o d i d e system has been the most e x t e n s i v e l y s t u d i e d of the c y c l o d e x t r i n i n c l u s i o n systems, because the " f i n i t e columns" of the s t a c k e d c y c l o d e x t r i n m o l e c u l e s mimic the s t a r c h h e l i x . A cage-type complex of c o m p o s i t i o n a -C D . I 2 . 4 H 3 O c r y s t a l l i z e s as r e d d i s h n e e d l e s from an aqueous s o l u t i o n of a - c y c l o d e x t r i n and m o l e c u l a r i o d i n e . 3 6 In the presence of m e t a l i o d i d e s , almost b l a c k , c h a n n e l - t y p e complexes a r e formed. From a s e r i e s of complexes s t u d i e d , i t was c o n c l u d e d t h a t the deep c o l o r i s a r e s u l t of charge t r a n s f e r w i t h i n the i o d i n e c h a i n s . Thus, the charge t r a n s f e r between i o d i n e and oxygen atoms of the s u r r o u n d i n g a - c y c l o d e x t r i n m o l e c u l e s p r e v i o u s l y p r o p o s e d , 3 7 can be r u l e d o u t . The dominant i n t e r a c t i o n s between them are merely van der Waals c o n t a c t between i o d i n e and the i n w a r d l y d i r e c t e d H atoms a t C(3) and C ( 5 ) . 86 11 . 1 . 6. Chemical Modi f i c a t i o n of C y c l o d e x t r i n s Chemical m o d i f i c a t i o n of the h y d r o x y l groups i n o r d e r t o a f f e c t the c o m p l e x a t i o n p r o p e r t i e s and/or t o a t t a c h r e a c t i v e f u n c t i o n a l groups, e i t h e r by i o n i c or c o v a l e n t bonding i n t o the m a c r o r i n g , i s a major a r e a of i n t e r e s t . The s o l u b i l i t y of i n c l u s i o n complexes formed w i t h a p o l a r guest m o l e c u l e s i s g e n e r a l l y l o w . 8 T h i s i s e s p e c i a l l y u n f a v o r a b l e i n the case of complexes of p h a r m a c e u t i c a l s , s i n c e r e a d i l y w a t e r - s o l u b l e complexes are h i g h l y d e s i r a b l e . P a r t i a l m e t h y l a t i o n of the c y c l o d e x t r i n s i n c r e a s e s t h e i r s o l u b i l i t y , presumably due t o the d i s r u p t i o n of i n t r a m o l e c u l a r hydrogen bonds. The w a t e r - s o l u b i l i t y of p a r t i a l l y m e t h y l a t e d / 3 - c y c l o d e x t r i n c o n t a i n i n g seven methyl groups i s a p p r o x i m a t e l y f o u r f o l d h i g h e r than t h a t of non-s u b s t i t u t e d p a r e n t c y c l o d e x t r i n . 8 A c c o r d i n g t o Casu e t a l . 3 8 the m e t h y l a t e d c y c l o d e x t r i n s i n c r e a s e the s o l u b i l i t y and s t a b i l i t y of the complexes formed w i t h l e s s s u i t a b l e , a p o l a r g u e s t s . C o n c o m i t a n t l y , the methyl groups a r e not e x p e c t e d t o o b s t r u c t the m a c r o r i n g s , and thus would a l l o w a d i r e c t comparison of t h e i r c o m p l e x i n g p r o p e r t i e s w i t h those of the p a r e n t m o l e c u l e s . C y c l o d e x t r i n s may s e r v e as b e t t e r enzyme models i f one s i d e of the c a v i t y , p r e f e r a b l y the p r i m a r y h y d r o x y l s i d e , i s more or l e s s c l o s e d . D e r i v a t i z a t i o n a t t h i s end would a l s o p r o v i d e a more a p o l a r c o n t i n u a t i o n of the c a v i t y . S e l e c t i v e and e f f i c i e n t m o d i f i c a t i o n of c y c l o d e x t r i n s , e s p e c i a l l y p o l y s u b s t i t u t i o n s , poses many s y n t h e t i c and 87 s t r u c t u r a l problems because of the l a r g e number of h y d r o x y l groups. F u r t h e r m o r e , i n the p r o c e s s of s u b s t i t u t i o n , the s t e r i c i n t e r a c t i o n s d e v e l o p e d may o f f s e t the ongoing s e l e c t i v i t y . One p r a c t i c a l way of p r e p a r i n g c y c l o d e x t r i n d e r i v a t i v e s i s t o r e a c t a l l p r i m a r y h y d r o x y l groups w i t h p-t o l u e n e s u l p h o n y l or m e s i t y l e n e s u l p h o n y l , c h l o r i d e . By s u i t a b l e n u c l e o p h i l i c s u b s t i t u t i o n , 3 9 the p r o d u c t s can be f u r t h e r c o n v e r t e d t o 6 - a z i d o - or 6-deoxy-6-h a l o g e n o c y c l o d e x t r i n and o t h e r p r o d u c t s . M e t h y l a t i o n 4 0 of h e p t a k i s ( 6 - b r o m o - 6 - d e o x y ) - | 3 - c y c l o d e x t r i n w i t h d i m e t h y l s u l p h a t e / b a r i u m h y d r o x i d e a f f o r d s the 2-0-methyl d e r i v a t i v e which, a f t e r replacement of the 6-bromo moiety w i t h benzoate and h y d r o l y s i s , can be c o n v e r t e d t o 2-0-methyl-/3-c y c l o d e x t r i n . 11 .1 .7 . C y c l o d e x t r i n Polymers H i g h m o l e c u l a r weight d e r i v a t i v e s of c y c l o d e x t r i n s a r e c a l l e d c y c l o d e x t r i n p o l y m e r s . The s p e c i a l p r o p e r t i e s of c y c l o d e x t r i n s a re l a r g e l y r e t a i n e d when they a r e i n c o r p o r a t e d i n t o the polymer c h a i n as a d e f i n i t e s t r u c t u r a l u n i t . S e v e r a l polymers c o n t a i n i n g c y c l o d e x t r i n s have been s y n t h e s i z e d " 1 t o i n v e s t i g a t e the r o l e p o r t r a y e d by the a t t a c h e d sugar m o i e t i e s i n b i n d i n g and c a t a l y s i s . The p o l y m e r i z a t i o n of 0 - c y c l o d e x t r i n a c r y l a t e y i e l d s a w a t e r - s o l u b l e homopolymer ( m o l e c u l a r weight 10* — 1 0 s ) , which e x h i b i t s almost the same p r o p e r t i e s as the f r e e 88 c y c l o d e x t r i n . C y c l o d e x t r i n copolymers are produced by the r e a c t i o n of c y c l o d e x t r i n s w i t h some d i - or p o l y - f u n c t i o n a l r e a g e n t s . S i n c e the former a r e a l s o p o l y f u n c t i o n a l , b r a n c h i n g s i t e s may be formed i n the p r o c e s s of p o l y m e r i z a t i o n . These polymers a r e o n l y s o l u b l e up t o a c e r t a i n m o l e c u l a r w e i g h t ; c r o s s l i n k i n g and s u f f i c i e n t l y h i g h degree of p o l y m e r i z a t i o n r e s u l t i n i n s o l u b l e g e l s . " 2 The c o m p l e x i n g b e h a v i o r can be d i f f e r e n t f o r monomeric and p o l y m e r - f i x e d c y c l o d e x t r i n s . Both h o s t s show 1:1 s t o i c h i o m e t r y f o r s m a l l s u b s t r a t e s (gas m o l e c u l e s ) , but the l a t t e r a f f o r d a weaker b i n d i n g . For l a r g e r guest m o l e c u l e s t h a t can accommodate two m a c r o r i n g s , the polymer complexes were shown t o be more s t a b l e ; the h i g h l o c a l c o n c e n t r a t i o n of the c y c l o d e x t r i n w i t h i n the polymer a l l o w s such c o o p e r a t i v e b i n d i n g . N.M.R. S t u d i e s of I n c l u s i o n Complexes  11.2. I n t r o d u c t i o n To d a t e , the complex f o r m a t i o n of c y c l o d e x t r i n s has been m o s t l y i n v e s t i g a t e d i n s o l u t i o n . I n c l u s i o n of s u b s t r a t e s i n the c y c l o d e x t r i n c a v i t y can be f o l l o w e d by the f o l l o w i n g s p e c t r o s c o p i c methods; n u c l e a r magnetic resonance, u l t r a v i o l e t a b s o r p t i o n , f l u o r e s c e n c e , and o p t i c a l r o t a t i o n . The n.m.r. methods" 3 p r o v i d e the most d i r e c t e v i d e n c e f o r the . i n c l u s i o n of any k i n d of guest m o l e c u l e s , by m o n i t o r i n g the s h i f t s i n t h e i r r e s o n a n c e s . The o t h e r methods a r e c o n f i n e d t o m o l e c u l e s p o s s e s s i n g 89 c e r t a i n f u n c t i o n a l i t i e s which a r e s e n s i t i v e t o those s p e c i f i c d e t e c t i o n t e c h n i q u e s . The dynamics of i n c l u s i o n complexes i n s o l u t i o n and i n the s o l i d s t a t e can best be d e s c r i b e d by n.m.r. measurements. In s o l u t i o n , m o l e c u l a r motions of the guest m o l e c u l e s have been i n v e s t i g a t e d by 2H and 1 3 C n u c l e a r r e l a x a t i o n s t u d i e s ; " " the analogous s o l i d - s t a t e s t u d i e s of m o l e c u l a r r e o r i e n t a t i o n form p a r t of t h i s t h e s i s . For c r y s t a l l i n e samples, X-ray s t r u c t u r e a n a l y s i s i s the best method f o r d e t e r m i n i n g t h e i r s t o i c h i o m e t r y , and v i s u a l i z i n g the i n c l u d e d guest m o l e c u l e s . However t h i s t e c h n i q u e i s too time-consuming f o r r o u t i n e a n a l y s i s , and the X-ray d a t a o f f e r no i n f o r m a t i o n on the m o b i l i t y , i f any, of the guest m o l e c u l e s . An e v a l u a t i o n of the n.m.r. t e c h n i q u e s on these a s p e c t s i n the s o l i d s t a t e w i l l be d i s c u s s e d i n g r e a t d e t a i l , l a t e r i n t h i s t h e s i s . 11.2.1. S o l u t i o n - S t a t e N.M.R. S t u d i e s The 1H- and 1 3C~n.m.r. methods have been used e x t e n s i v e l y t o study complexes of u n s u b s t i t u t e d c y c l o d e x t r i n s . However, the s p e c t r a o b t a i n e d a re u s u a l l y u n s a t i s f a c t o r y because of the low s o l u b i l i t y of the complexes i n d e u t e r a t e d water. T h e r e f o r e , most of the r e s u l t s o b t a i n e d so f a r i n v o l v e complexes of p o l a r guest m o l e c u l e s t h a t a r e r e l a t i v e l y s o l u b l e i n t h i s s o l v e n t . By o b s e r v i n g the c o m p l e x a t i o n - i n d u c e d s h i f t s i n 1H- and 1 3 C -n.m.r. s p e c t r a of both the guest and the h o s t , i t i s 90 p o s s i b l e t o determine the b i n d i n g and the geometry of the complex. The complex f o r m a t i o n w i t h a r o m a t i c guest m o l e c u l e s i s i n d i c a t e d by the " u p f i e l d s h i f t " of the hydrogen atoms a t C(3) and C(5) due t o the a n i s o t r o p i c s h i e l d i n g e f f e c t of the a r o m a t i c r i n g . On the o t h e r hand, the hydrogens of C ( 1 ) , C ( 2 ) , and C ( 4 ) , s i t u a t e d on the e x t e r i o r of the c a v i t y , w i l l not be a f f e c t e d by the p e n e t r a t i o n of the guest m o l e c u l e s . Sunamoto e t a l . 4 5 have suggested t h a t the observed changes i n the s h i f t s may not be caused by the a n i s o t r o p i c e f f e c t , but r a t h e r by the m i c r o s o l v e n t e f f e c t . T h i s i n v o l v e s the e x p u l s i o n of water m o l e c u l e s , which i n c r e a s e s the hy d r o p h o b i c c h a r a c t e r of the c a v i t y on c o m p l e x a t i o n . Bergeron and C h a n n i n g 1 9 employed 1 3 C n.m.r. as a probe i n the d e t e r m i n a t i o n of c y c l o d e x t r i n s u b s t r a t e c o n f o r m a t i o n s . By measuring the changes i n the c h e m i c a l s h i f t v a l u e s of the guest m o l e c u l e , i t s o r i e n t a t i o n can be de t e r m i n e d ; the carbons most i n t i m a t e l y a s s o c i a t e d w i t h the c a v i t y s h o u l d be s h i f t e d most. They c o n c l u d e d t h a t a t l e a s t f o u r of t h e f o l l o w i n g parameters may account f o r the observ e d 1 3 C s h i f t s of the complexed c y c l o d e x t r i n : removal of water from the c a v i t y , s h i e l d i n g by the 7r-cloud of the a r o m a t i c guest m o l e c u l e , c o n f o r m a t i o n a l changes, and s t e r i c i n t e r a c t i o n s . I n c l u s i o n complexes i n s o l u t i o n a r e not s t a t i c s p e c i e s ; the system i s u s u a l l y i n the f a s t - e x c h a n g e l i m i t from a n.m.r. p o i n t of v i e w . 7 That i s , the s u b s t r a t e 91 resonances appear a t the average of t h e i r f r e e and bound forms, which can have d i f f e r e n t o r i e n t a t i o n s w i t h i n the c a v i t y , w e i g h t e d by the f r a c t i o n a l p o p u l a t i o n of the m o l e c u l e s i n each environment. A c c o r d i n g t o the r e s u l t s o b t a i n e d from 1 3C-n.m.r. r e l a x a t i o n s t u d i e s , M the dynamic c o u p l i n g between the mononuclear a r o m a t i c compounds and a-c y c l o d e x t r i n i s weak and the a r o m a t i c r i n g i s r a p i d l y r o t a t i n g w i t h i n the an n u l u s of the h o s t . I I . 2 . 2 . S o l i d - S t a t e N.M.R. S t u d i e s S o l i d - s t a t e n.m.r. t e c h n i q u e s have r e c e n t l y been used t o study c l a t h r a t e s , weakly hydrogen-bonded complexes, and po l y m o r p h i c f o r m s " 6 of the same m a t e r i a l t h a t a re d i f f i c u l t or i m p o s s i b l e t o r e l a t e i n s o l u t i o n . H i g h - r e s o l u t i o n 1 3 C -n.m.r. s p e c t r o s c o p y d e t e c t s not o n l y c h e m i c a l d i s t i n c t i o n s , but a l s o magnetic i n e q u i v a l e n c e s p r e s e n t i n the s o l i d complexes. The l a t t e r may be c o n f i r m e d by X-ray d a t a based on c r y s t a l l o g r a p h i c i n e q u i v a l e n c e i n the u n i t c e l l . Hence, the s o l i d - s t a t e 1 3C-n.m.r. s p e c t r a can be used t o p r o v i d e an immediate i n d i c a t i o n of the presence of any c o n f i g u r a t i o n a l or c o n f o r m a t i o n a l m u l t i p l i c i t y t h a t may e x i s t , p r i o r t o u n d e r t a k i n g the more time-consuming c r y s t a l s t r u c t u r e a n a l y s i s . On the o t h e r hand, d e u t e r i u m n.m.r. i s a u s e f u l t o o l f o r the study of m o l e c u l a r motion i n s o l i d s . As mentioned e a r l i e r , p r e v i o u s s t u d i e s of i n c l u s i o n complexes of c y c l o d e x t r i n s u s i n g n.m.r. methods have p r o v i d e d v a l u a b l e i n s i g h t , however, those s t u d i e s have been 92 c o n f i n e d t o s o l u b l e complexes. Prompted by the r a p i d l y growing i n t e r e s t i n the use of m o d i f i e d c y c l o d e x t r i n s as model enzymes, and a l s o by commercial use of s o l i d c y c l o d e x t r i n s t o s e q u e s t e r a v a r i e t y of o r g a n i c s u b s t a n c e s , we have e v a l u a t e d two n.m.r. methods f o r s t u d y i n g t h e s e s u b s t a n c e s . As w i l l be seen, the c r o s s - p o l a r i z a t i o n - m a g i c a n g l e s p i n n i n g method a l l o w s i n d i v i d u a l resonances t o be a s s i g n e d t o the s p e c i f i c carbon atoms i n the sample and a l s o p r o v i d e s a d i r e c t measure of the e x t e n t of c o m p l e x a t i o n . F u r t h e r m o r e , the d e u t e r i u m q u a d r u p o l e echo method g i v e s i n s i g h t c o n c e r n i n g the a n i s o t r o p i c motion of the g u e s t - s u b s t r a t e w i t h i n the ann u l u s of the c y c l o d e x t r i n r i n g . 11. 3 . S y n t h e s i s 11. 3.1. P r e v i o u s Work The a b i l i t y of the c y c l o d e x t r i n s t o form i n c l u s i o n complexes r e l i e s upon the s i z e and n a t u r e of the s u b s t r a t e s which must f i t e n t i r e l y , or a t l e a s t p a r t i a l l y , i n t o the c a v i t y . Depending on the p r o p e r t i e s of the guest m o l e c u l e s , the f o l l o w i n g g e n e r a l methods have been adopted by s e v e r a l r e s e a r c h groups i n the s y n t h e s i s of t h e s e c o m p l e x e s : 6 1) At l e a s t an e q u i m o l a r p r o p o r t i o n of a w a t e r - s o l u b l e s u b s t a n c e i s d i s s o l v e d d i r e c t l y i n a c o n c e n t r a t e d , h o t , aqueous s o l u t i o n of the c y c l o d e x t r i n . The i n c l u s i o n complex g e n e r a l l y c r y s t a l l i z e s out on slow c o o l i n g . 2) W a t e r - i n s o l u b l e s u b s t a n c e s a r e d i s s o l v e d i n non-93 c o m p l e x i n g s o l v e n t s such as e t h e r , c h l o r o f o r m , e t c . and the s o l u t i o n s a r e shaken w i t h , or l a y e r e d over or underneath, a c o n c e n t r a t e d c y c l o d e x t r i n s o l u t i o n . For l i q u i d - g u e s t s u b s t a n c e s , s o l v e n t i s not n e c e s s a r y f o r the p r e p a r a t i o n . P r e c i p i t a t e s are u s u a l l y o b t a i n e d ; however, v e r y slow c o o l i n g may a l l o w c r y s t a l s t o form a t the i n t e r f a c e . T 60 50 40 30 F i g . I I - 5 . T u r b i d i t y c u r v e s f o r 3 %, aqueous / 3 - c y c l o d e x t r i n s o l u t i o n s + 5 % of the c o r r e s p o n d i n g s o l v e n t (from Ref. [ 8 ] ) . The c r y s t a l l i z a t i o n of /3-cyclodextr i n and i t s i n c l u s i o n complexes from aqueous s o l u t i o n has been s t u d i e d " 7 by f o l l o w i n g the t u r b i d i t y as a f u n c t i o n of t e mperature ( F i g . I I - 5 ) . C e r t a i n s o l v e n t s such as benzene, t o l u e n e , n-hexane, carbon t e t r a c h l o r i d e , i s o p r o p y l e t h e r , d i c h l o r o e t h a n e , amongst o t h e r s can a f f e c t p r e c i p i t a t i o n of c r y s t a l l i n e complexes at r e l a t i v e l y h i g h t e m p e r a t u r e s . In g e n e r a l , h i g h e r c o n c e n t r a t i o n s of guest would r e s u l t i n the onset of t u r b i d i t y a t h i g h e r t e m p e r a t u r e s . A s e r i e s of complexes formed w i t h w a t e r - i m m i s c i b l e l i q u i d s has been r e p o r t e d by Cramer and H e n g l e i n . 2 8 The 94 l i q u i d component was added t o an aqueous s o l u t i o n of c y c l o d e x t r i n and the m i x t u r e a l l o w e d t o s t a n d f o r 5-8 d, w i t h o c c a s i o n a l s t i r r i n g . The r e s u l t i n g p r e c i p i t a t e was washed w i t h w a t e r , a c e t o n e , and f i n a l l y w i t h e t h e r t o remove any a d h e r i n g m o l e c u l e s . Then, i t was a l l o w e d t o dry o v e r n i g h t i n a d e s i c c a t o r . a - C y c l o d e x t r i n i s known t o form complexes w i t h d i m e t h y l s u l f o x i d e (DMSO) and methanol. C r y s t a l s of a-c y c l o d e x t r i n - m e t h a n o l p e n t a h y d r a t e have been p r e p a r e d " 8 from a m e t h a n o l i c s o l u t i o n . S i m i l a r l y , a -cyclodextrin-DMSO-methanol (1:1:2) d i h y d r a t e can be o b t a i n e d " 9 from a DMSO-methanol s o l u t i o n c o n t a i n i n g a - c y c l o d e x t r i n h e x a h y d r a t e . S e l e c t i v e c h e m i c a l m o d i f i c a t i o n of c y c l o d e x t r i n s i s ne c e s s a r y t o i n c r e a s e the molar r a t i o of g u e s t / c y c l o d e x t r i n . M e t h y l a t i o n and a c e t y l a t i o n of c y c l o d e x t r i n s have been r e p o r t e d ; 1 5 ' 5 0 the s u b s t i t u e n t groups a r e e x p e c t e d t o a f f e c t the c a v i t y s i z e t o a c e r t a i n degree. In p a r t i c u l a r , the s y n t h e s e s of h e p t a k i s - ( 2 , 6 - d i - 0 -methyl)-/3-cyclodextrin (2,6-di-O-Me-0-CD) and 0-c y c l o d e x t r i n p e r a c e t a t e (2,3,6-tri-O-Ac-0-CD) a r e r e l e v a n t t o the work r e p o r t e d i n t h i s t h e s i s . T h e o r e t i c a l l y , t h e r e a r e t h r e e p o s s i b l e i s o m e r i c h e p t a k i s - d i - 0 - m e t h y l - 0 - c y c l o d e x t r i n s . Only the s y n t h e s i s of 2,6-di-O-Me-0-CD has been r e p o r t e d , but the s t r u c t u r e was i n i t i a l l y i d e n t i f i e d as b e i n g t h a t of the 3,6-isomer. U s i n g s p e c t r o s c o p i c methods, Casu e t a l . 1 5 p r o v e d t h a t on m e t h y l a t i o n w i t h d i m e t h y l s u l p h a t e i n the presence of BaO 95 and Ba (OH) 2 . 8H2.O, the 2,6-isomer was the p r o d u c t . However, i t s y i e l d and the d e t a i l s of the p r o c e d u r e were not i n c l u d e d i n the r e p o r t . R e c e n t l y , S z e j t l i et a l . 5 1 r e p e a t e d the same experiment and a t t e m p t s were made t o o p t i m i z e the r e a c t i o n and i s o l a t i o n c o n d i t i o n s . They noted t h a t s u c c e s s f u l s e l e c t i v e r e a c t i o n of the f o u r t e e n 2 , 6 - h y d r o x y l groups depended c r u c i a l l y on the a b i l i t y t o keep the r e a c t i o n below 20°C s i n c e the l a r g e amount of heat which i s e v o l v e d r a t h e r u n p r e d i c t a b l y i n the p r o c e s s of m e t h y l a t i o n can cause 3-O-methylation t o o c c u r . A f t e r s t i r r i n g f o r 4 d a t room t e m p e r a t u r e , a homogeneous s u s p e n s i o n was formed. The e x c e s s reagent was quenched w i t h ammonium h y d r o x i d e , and the m i x t u r e was suspended i n a s m a l l volume of c h l o r o f o r m and f i l t e r e d . P e t r o l e u m e t h e r was added t o induce c r y s t a l l i z a t i o n , and the crude m a t e r i a l was f u r t h e r r e c r y s t a l l i z e d from hot w a t e r . 0 - C y c l o d e x t r i n p e r a c e t a t e can be o b t a i n e d i n h i g h y i e l d by a d a p t i n g the s y n t h e t i c p r o c e d u r e s d e s c r i b e d i n R e f s . 52 and 53. In the f i r s t p r o c e d u r e , p e r a c e t y l a t i o n of t h i s compound was c a r r i e d out a t room temperature i n a c e t i c a n h y d r i d e w i t h d r y p y r i d i n e as the c a t a l y s t . The crude p r o d u c t was p r e c i p i t a t e d by p o u r i n g the s o l u t i o n w i t h s t i r r i n g i n t o i c e and w a t e r . The second method i n v o l v e d the a d d i t i o n of / 3 - c y c l o d e x t r i n t o b o i l i n g a c e t i c a n h y d r i d e c o n t a i n i n g anhydrous sodium a c e t a t e . The m i x t u r e was heated under r e f l u x f o r t h i r t y m i n u t e s , a l l o w e d t o c o o l t o room temp e r a t u r e and poured w i t h s t i r r i n g i n t o i c e and water. 96 The crude p r o d u c t was then c r y s t a l l i z e d from t o l u e n e . 11. 3 . 2 . S y n t h e s i s of C y c l o d e x t r i n I n c l u s i o n Complexes The e x p e r i m e n t a l r e s u l t s above encouraged us t o s y n t h e s i z e a- and / 3 - c y c l o d e x t r i n ( [ 1 ] and [ 2 ] ) complexes w i t h d e u t e r a t e d DMSO-d6 i n aqueous or m e t h a n o l i c s o l u t i o n . T h e r e a f t e r , a t t e m p t s were made t o s y n t h e s i z e some of those known complexes ( u s i n g the method of Cramer and H e n g l e i n 2 8 ) w i t h a p o l a r a r o m a t i c s u b s t r a t e s , but w i t h l i t t l e s u c c e s s . Presumably, the guest components merely aggregated t o the o u t s i d e of the c y c l o d e x t r i n m o l e c u l e i n the p r o c e s s of f a s t p r e c i p i t a t i o n . Thorough washings c o u l d w e l l remove th e s e m o l e c u l e s , and reduce the molar r a t i o of g u e s t / c y c l o d e x t r i n . T h e r e f o r e t h e s e complexes, which a r e seldom of s t o i c h i o m e t r i c c o m p o s i t i o n , a r e not s u i t a b l e f o r s o l i d - s t a t e 1 3C-n.m.r. s t u d i e s . I t was d e c i d e d t o s y n t h e s i z e 2,6-di-G~Me-/3-CD [3] and 2 , 3 , 6 - t r i-0-Ac-/3-CD [4] because of the f o l l o w i n g : 1) They a r e s o l u b l e i n l e s s - p o l a r o r g a n i c s o l v e n t s , even i n water f o r the m e t h y l a t e d d e r i v a t i v e . 2) The i n f l u e n c e of c a v i t y s i z e on c o m p l e x a t i o n w i t h a s e r i e s of guest m o l e c u l e s , and t h e i r molar r a t i o s can be compared. I t i s known 8 t h a t m e t h y l a t i o n or a c e t y l a t i o n of the sugar s h o u l d i n c r e a s e the h y d r o p h o b i c environment around the c a v i t y , and a t the same t i m e , the h y d r o p h o b i c i n t e r a c t i o n w i t h the guest m o l e c u l e s i s e x p e c t e d t o be 97 enhanced. Hence, the t y p e s of s u b s t i t u e n t groups a t t a c h e d t o the s u b s t r a t e s s h o u l d p l a y an i m p o r t a n t r o l e i n complex f o r m a t i o n . The presence of p o l a r m o i e t i e s such as amino, n i t r o , c a r b o n y l , and h y d r o x y l groups on the s u b s t r a t e s h o u l d lower the s t a b i l i t y of the complex. These p o l a r m o l e c u l e s a r e v e r y s o l u b l e i n the c r y s t a l l i z i n g s o l v e n t , m ethanol, and w i l l t h e r e f o r e p r e f e r t o remain i n the b u l k s o l v e n t . A l k y l s u b s t i t u e n t s s h o u l d g r e a t l y i n c r e a s e the h y d r o p h o b i c c h a r a c t e r of the guest m o l e c u l e s ; a methyl or e t h y l s u b s t i t u e n t t h a t i s o r t h o t o a c a r b o n y l group has a s h i e l d i n g e f f e c t on the l a t t e r , t h e r e b y i n c r e a s i n g the h y d r o p h o b i c c h a r a c t e r of the whole m o l e c u l e and i t s s t a b i l i t y . 8 A s i m i l a r group p l a c e d a t the p a r a p o s i t i o n s h o u l d have a r e l a t i v e l y weak e f f e c t on the m o l e c u l e , and the h y d r o p h o b i c e f f e c t s s h o u l d i n c r e a s e i n the o r d e r p a r a < meta < o r t h o . These a n t i c i p a t e d s u b s t i t u e n t e f f e c t s were v e r i f i e d i n our s t u d i e s by the r e s u l t s o b t a i n e d w i t h compound [3] ( T a b l e I I - 1 ) . An e x c e p t i o n i s p-bromotoluene, i n which i t s c o m p l e x - f o r m i n g a b i l i t y i s lower than t h a t of bromobenzene. I t s h o u l d be noted t h a t the c r y s t a l l i z a t i o n of the l a t t e r d e r i v a t i v e w i t h the h o s t m o l e c u l e [3] was done w i t h g r e a t d i f f i c u l t y . Another o b s e r v a t i o n i s t h a t l a r g e r m o l e c u l e s such as durene and n a p h thalene f a i l e d t o form i n c l u s i o n complexes. The i n a b i l i t y of t h e s e m o l e c u l e s t o p e n e t r a t e d e e p l y i n t o the c a v i t y c o u l d have a f f e c t e d the m o l e c u l a r p a c k i n g , caused by the l a r g e p r o t r u d i n g segments. 98 T a b l e 11- 1 Complex no, 5] 6] 7] 8] 9] 10] 11] 12] 13] 14] 15] 16] 17] 18] 19] 20] 21] 22] 23] 24] 25] C r y s t a l l i n e complexes formed by c y c l o d e x t r i n s S u b s t r a t e Host Molar r a t i o * w i t h a p o l a r compounds benzene [3] t o l u e n e [3] e t h y l b e n z e n e [3] p- x y l e n e [3] chlorobenzene.' [3] bromobenzene [3] c y c l o h e x a n e [3] m e t h y l c y c l o h e x a n e [3] b i p h e n y l [3] 4 , 4 ' - d i m e t h y l b i p h e n y l . . . [3] p - d i - t e r t . - b u t y l b e n z e n e . [3] bromotoluene [3] 1:0.2 durene [3] 1:0.1 naphthalene [3] 1:0.2 w i t h p o l a r compounds pyr i d i n e [3] 1:0.2 p - h y d r o x y t o l u e n e [3] 1:0.2 p - t o l u i d i n e [3] 1:0.1 b e n z o i c a c i d [3] 1:0.1 w i t h a p o l a r compounds benzene [4] t o l u e n e [4] 1:1 p-x y l e n e [ 4 ] 1:1 * molar r a t i o of c y c l o d e x t r i n : s u b s t r a t e . 99 I n c l u s i o n complexes of host [ 3 ] were p r e p a r e d by c r y s t a l l i z i n g the sugar from a s o l v e n t t h a t c o u l d a l s o f u n c t i o n as a g u e s t , or from a s o l u t i o n of the guest i n a non-complexing s o l v e n t such as c h l o r o f o r m or methanol. ^-N.m.r. and u.v. methods were then used t o c o n f i r m the i n c l u s i o n of guest m o l e c u l e s , and t o e s t i m a t e the s t o i c h i o m e t r y of the complexes. A l i t e r a t u r e s e a r c h f o r a ' known, c r y s t a l l i n e /3-c y c l o d e x t r i n p e r a c e t a t e d i d not r e v e a l any complex formed between the s o l v e n t and the c y c l o d e x t r i n m o l e c u l e s . To our knowledge, no i n c l u s i o n complexes of t h i s m o l e c u l e w i t h any o r g a n i c s u b s t r a t e s have been r e p o r t e d b e f o r e . I t was d e c i d e d t o i n v e s t i g a t e t h i s compound by 1H-n.m.r. s p e c t r o s c o p y , and produce a l i m i t e d s e r i e s of i n c l u s i o n complexes. The p e r m e t h y l a t e d a - c y c l o d e x t r i n was a l s o p r e p a r e d , but w i t h much d i f f i c u l t y f o l l o w i n g the method of Lehn et a l . . 1 * The crude p r o d u c t showed more than one spot on t h i n -l a y e r chromatography p l a t e s , and p u r i f i c a t i o n on a column d i d not g i v e a c o m p l e t e l y pure compound. S i n c e a l a r g e q u a n t i t y of t h i s r e a s o n a b l y e x p e n s i v e m a t e r i a l was needed f o r the s y n t h e s i s of i t s i n c l u s i o n complexes, i t was d e c i d e d not t o choose t h i s as the p o t e n t i a l h o s t m o l e c u l e . I I . 4 . 13C-N.M.R. S t u d i e s - Some S p e c i f i c Examples Because the a- and / 3 - c y c l o d e x t r i n s can be o b t a i n e d e a s i l y , they a r e best s u i t e d f o r n.m.r. s t u d i e s . A number 100 of m o d i f i e d c y c l o d e x t r i n s have been f u l l y c h a r a c t e r i z e d i n s o l u t i o n by Lehn et a l . . 1 " A c c o r d i n g t o S z e j t l i e t a l . , 5 1 t h e i r 1 3C-n.m.r. s o l u t i o n i n v e s t i g a t i o n s r e v e a l e d t h a t the assignments g i v e n by Lehn f o r the C-3 and C-5 atoms of 2,6-di-0-Me-|3-CD s h o u l d be i n t e r c h a n g e d . There was no a m b i g u i t y f o r the case of 2,3,6-tri-O-Ac-0-CD, which was f i r s t s t u d i e d by Takeo et a l . . 5 0 Owing t o the s i m p l e symmetry of these c y c l o d e x t r i n s and t h e i r d e r i v a t i v e s , a l l the c o n s t i t u e n t g l u c o p y r a n o s e r e s i d u e s i n the d e x t r i n s a r e e x p e c t e d t o be c h e m i c a l l y and p h y s i c a l l y i n d i s t i n g u i s h a b l e , i n the absence of c o n f o r m a t i o n a l i s o m e r i s m . S u p p o r t i n g e v i d e n c e a l s o comes from the work r e p o r t e d i n t h i s t h e s i s on the s o l u t i o n 1 3C-n.m.r. s p e c t r a of compounds [1] t o [ 4 ] , which a r e shown i n F i g . I I - 6 . The complex f o r m a t i o n of many compounds, e s p e c i a l l y a r o m a t i c s , w i t h h o s t s [3] and [4] w i l l be the main f o c a l p o i n t of d i s c u s s i o n i n the l a t t e r p a r t of t h i s c h a p t e r . There i s a common m i s c o n c e p t i o n t h a t c h e m i c a l s h i f t s measured i n h i g h - r e s o l u t i o n e x p e r i m e n t s f o r the s o l i d s t a t e and f o r s o l u t i o n s a r e the same f o r a p a r t i c u l a r compound. Lippmaa et a l . 5 f l c a r r i e d out e x p e r i m e n t s w i t h some r e p r e s e n t a t i v e groups of o r g a n i c compounds t o i l l u s t r a t e the s o l i d - s t a t e e f f e c t s on the c h e m i c a l s h i f t s and s p l i t t i n g s of 1 3 C r e s o n a n c e s . S e v e r a l r a t h e r g e n e r a l c o n c l u s i o n s about the 1 3 C c h e m i c a l s h i f t s can be drawn from the r e s u l t s put f o r w a r d by s e v e r a l o t h e r r e s e a r c h g r o u p s . 4 6 ' 5 4 " 5 8 In the absence of s p e c i f i c s o l i d - s t a t e C-1 C-3,5,2 C-4 C-6 B T — i 1 — i 1 1 1 1 1 — i — | 1 1 1 1 1 1 1 i i r 150 100 50 p p m - 0 F i g . I I - 6 . 1 3C-N.m.r. s p e c t r a of (A) [1] and (B) [2] i n D 20, (C) [3] i n CDC1 3, and (D) [ 4 ] i n (CD 3) 2CO at ambient temperature. 1 02 u in O VO ro i O I I ( J o o II u E a h d. - o o hO o | - l O 4-> c o u I •H 1 03 e f f e c t s , d i f f e r e n c e s between the i s o t r o p i c c h e m i c a l s h i f t v a l u e s measured f o r the s o l u t i o n and p u l v e r i z e d c r y s t a l l i n e samples a r e s m a l l and do not n o r m a l l y exceed the s o l v e n t e f f e c t s . " 6 S i g n i f i c a n t changes may a r i s e from i n t r a m o l e c u l a r ( c o n f o r m a t i o n a l ) and i n t e r m o l e c u l a r ( c r y s t a l l o g r a p h i c ) e f f e c t s , which determine the a c t u a l magnetic environment of n u c l e i i n s o l i d samples. Hence, i t i s of i n t e r e s t t o f i n d examples where the s o l i d - s t a t e c h e m i c a l s h i f t d a t a can be e x p l a i n e d i n terms of those e f f e c t s s e p a r a t e l y . There a r e many ways i n which the m o l e c u l a r s t r u c t u r e i n the s o l i d s t a t e can d i f f e r from t h a t i n s o l u t i o n . These commonly i n c l u d e m o l e c u l a r c o n f o r m a t i o n , h i n d e r e d i n t r a m o l e c u l a r m o t i o n , t a u t o m e r i s m , i n t r a m o l e c u l a r hydrogen bonding, and i n t r a m o l e c u l a r nonbonded i n t e r a c t i o n s . S p e c i f i c examples a r e chosen here t o h i g h l i g h t some of thes e a r e a s t h a t a r e r e l e v a n t t o l a t e r d i s c u s s i o n on c y c l o d e x t r i n i n c l u s i o n complexes. S t u d i e s of c e l l u l o s e p o l y m o r p h s 5 5 ' 5 6 have shown v e r y d e f i n i t e s o l i d - s t a t e n.m.r. s p l i t t i n g s of the s i g n a l s of C-1 and C-4 atoms, which anchor the g l y c o s i d i c l i n k a g e s between t h e g l u c o p y r a n o s e u n i t s . These s p l i t t i n g s p r o v i d e d i r e c t e v i d e n c e f o r the presence of two t y p e s of g l u c o s e monomer. Subsequent s t u d i e s on the c o n f o r m a t i o n s of o l i g o -and p o l y - s a c c h a r i d e s , v i z . c y c l o a m y l o s e s and amylose, have been r e p o r t e d by S a i t o and T a b e t a . 5 7 They have shown t h a t the 1 3 C c h e m i c a l s h i f t s of a - c y c l o d e x t r i n a r e v e r y s i m i l a r 1 04 t o those of h i g h m o l e c u l a r weight c r y s t a l l i n e amylose, by comparing the resonances of carbons a t the g l y c o s i d i c l i n k a g e s which are v e r y s e n s i t i v e t o c o n f o r m a t i o n a l changes. T h e i r s p e c t r a do not r e f l e c t the presence of d i f f e r e n t c o n f o r m a t i o n s , and the l i n e w i d t h s of th e s e s i g n a l s a r e s i g n i f i c a n t l y narrow. In c o n t r a s t , 1 3 C s i g n a l s of 0- and 7 - c y c l o d e x t r i n s a r e s p l i t i n t o a t l e a s t two s e t s of s i g n a l s , s u g g e s t i n g t h a t t h e r e a r e two or more d i f f e r e n t c o nformers p r e s e n t i n the s o l i d s t a t e . 5 7 T h i s c o u l d be e x p l a i n e d by the l e s s s y m m e t r i c a l n a t u r e of "empty" c y c l o d e x t r i n s , h a v i n g d i s t o r t e d g l y c o s i d i c l i n k a g e s . P r o c e s s e s such as i n t e r n a l r o t a t i o n and r i n g i n v e r s i o n a re e x p e c t e d t o occur much more s l o w l y i n the s o l i d s t a t e than i n s o l u t i o n a t the same t e m p e r a t u r e . 5 8 The s o l i d s t a t e may induce magnetic i n e q u i v a l e n c e i n a p a i r or p a i r s of carbon atoms, which a r e e q u i v a l e n t i n s o l u t i o n . T h i s k i n d of r e s t r i c t e d motion i s n o r m a l l y observed f o r i n t e r n a l r o t a t i o n about s i n g l e C-C bonds a t ambient temperature i n the s o l i d . By i n c r e a s i n g the t e m p e r a t u r e , i t i s p o s s i b l e t o render t h e s e atoms e q u i v a l e n t , p r o v i d e d the r o t a t i o n r a t e s a r e g r e a t e r or comparable t o the f r e q u e n c y s e p a r a t i o n of the s i g n a l s . Garroway e t a l . 5 9 have i n v e s t i g a t e d a p i p e r i d i n e - c u r e d epoxy, based on a r e s i n from the d i g l y c i d y l e t h e r of b i s p h e n o l A. The resonances f o r the C-3,C-3' ca r b o n s ( F i g . I I - 7 ) appear as two d i s t i n c t peaks t h a t f i n a l l y c o a l e s c e t o a sharp peak, over the tem p e r a t u r e range of -123 t o 77°C. 105 As mentioned p r e v i o u s l y , the s p l i t t i n g s of 1 3 / C H 3 2 3 79°C -26°C •122°C 200 100 p.p.m. 0 F i g . I I - 7 . 1 3C-C.p.-m.a.s. s p e c t r a of an epoxy r e s i n , d i g l y c i d y l e t h e r of b i s p h e n o l A (DGEBA) r e c o r d e d over a 200°C temperature range (from Ref. [ 5 9 ] ) . resonances can a r i s e from a m i x t u r e of i n t r a m o l e c u l a r and i n t e r m o l e c u l a r e f f e c t s . I f the average s h i f t s a r e c l o s e t o those o b s e r v e d i n s o l u t i o n , then i t i s r e a s o n a b l e t o c o n c l u d e t h a t i n t r a m o l e c u l a r i n t e r a c t i o n s predominate over the o t h e r e f f e c t s . In the case of p-dimethoxybenzene, the 1,4-nonbonded i n t r a m o l e c u l a r i n t e r a c t i o n between the 1 06 s u b s t i t u e n t group and the a r o m a t i c r i n g l e a d s t o a s p l i t t i n g of about 6 p.p.m. f o r the s i g n a l s of the o r t h o c a r b o n s . 5 " T h i s k i n d of magnetic i n e q u i v a l e n c e r e s u l t s from the methyl groups l o c a t e d on the p l a n e of the r i n g , t h e r e b y g e n e r a t i n g a c o n f o r m a t i o n of minimum energy, i n which they a r e c l o s e r t o one of the two o r t h o c a r b o n s . N u c l e i which a r e c r y s t a l l o g r a p h i c a l l y i n e q u i v a l e n t i n the s o l i d may g i v e r i s e t o s e p a r a t e n.m.r. a b s o r p t i o n s . The importance of such i n t e r m o l e c u l a r e f f e c t s has been i l l u s t r a t e d r e c e n t l y 6 0 f o r 2 , 4 - d i n i t r o t o l u e n e , whose spectrum shows a s p l i t t i n g of about 3 p.p.m. f o r the methyl peak. T h i s s u g g e s t s t h a t t h e r e a r e two non-congruent m o l e c u l e s i n the u n i t c e l l , and a subsequent X-ray r e p o r t has c o n f i r m e d the f i n d i n g . However, the a r o m a t i c r e g i o n of the spectrum does not show any s i g n of s p l i t t i n g . T h e r e f o r e the e f f e c t s of l o c a l environment would appear t o be l a r g e s t f o r the methyl groups. E v a l u a t i o n of a number of c l a t h r a t e s and po l y m o r p h i c forms of hydroquinone has a l s o y i e l d e d l i n e s p l i t t i n g s t h a t can be r e l a t e d t o c r y s t a l s t r u c t u r e s . * 6 The au t h o r has shown t h a t the i n t e r m o l e c u l a r i n t e r a c t i o n s may induce i s o t r o p i c c h e m i c a l s h i f t d i f f e r e n c e s as l a r g e as 4 p.p.m., and t h i s magnitude of d i s p e r s i o n c o u l d be i m p o r t a n t i n the st u d y of more complex systems. I I . 5 . X-ray S t u d i e s I t i s p e r t i n e n t t o have some knowledge of the c r y s t a l 107 s t r u c t u r e s of c y c l o d e x t r i n s and t h e i r i n c l u s i o n complexes, b e f o r e t r y i n g t o e x t r a c t any u s e f u l i n f o r m a t i o n from the s o l i d - s t a t e 1 3C-n.m.r. s p e c t r a . The c r y s t a l s t r u c t u r e s of s e v e r a l c y c l o d e x t r i n complexes have been e x t e n s i v e l y i n v e s t i g a t e d by X-ray a n a l y s i s . H a r a t a et a l . 6 1 have shown the s t r u c t u r e s of s e v e r a l c y c l o d e x t r i n complexes w i t h mono-and d i - s u b s t i t u t e d benzenes; the s u b s t r a t e s a r e bound i n s i d e the c a v i t y or s i t u a t e d w i t h i n a column formed by the s t a c k of c y c l o d e x t r i n r i n g s . In the case of m o n o s u b s t i t u t e d benzenes, the p h e n y l group i s l o c a t e d i n s i d e the h o s t c a v i t y , w h i l e the s u b s t i t u e n t group p r o t r u d e s from the s e c o n d a r y - h y d r o x y l s i d e of the c a v i t y . When d i s u b s t i t u t e d benzenes a r e i n c l u d e d , the b u l k i e r group i s t h r u s t i n t o the r i n g i n s t e a d of the s m a l l e r s u b s t i t u e n t , which has t o be l o c a t e d o u t s i d e the c a v i t y . The i n c l u s i o n geometry may be i n t e r p r e t e d m a i n l y i n terms of the s t e r e o s p e c i f i c r e l a t i o n s h i p between the guest and the h o s t . H e x a k i s - ( 2 , 3 , 6 - t r i - O - m e t h y l ) - a - c y c l o d e x t r i n (2,3,6-tri-O-Me - a-CD) a l s o forms i n c l u s i o n complexes, and t h e i r s t r u c t u r e s 6 2 have been compared w i t h t h o s e of a -c y c l o d e x t r i n complexes. As shown i n F i g . I I - 8 , the benzaldehyde and p - n i t r o p h e n o l m o l e c u l e s a r e i n c l u d e d i n r e v e r s e o r i e n t a t i o n when the shape and s i z e of the a -c y c l o d e x t r i n c a v i t y a r e a l t e r e d . The i n t r o d u c t i o n of methyl groups i n t o the c y c l o d e x t r i n r i n g e n l a r g e s the 0 ( 2 ) , 0 ( 3 ) s i d e of the c a v i t y , so t h a t the guest m o l e c u l e appears t o be l o o s e l y bound i n i t . At the same t i m e , the l a r g e 108 A B p-Nitrophenol F i g . I I - 8 . Schematic diagrams of the a - c y c l o d e x t r i n (A) and 2,3,6-tri-O-Me-a-CD (B) complexes. Water m o l e c u l e s a r e i n d i c a t e d by W (from Ref. [ 6 2 ] ) . 1 09 i n c l i n a t i o n of the 2 , 3 , 6 - t r i - O - m e t h y l g l u c o p y r a n o s e r e s i d u e s makes the p r i m a r y - h y d r o x y l s i d e of the c a v i t y so narrow t h a t the n i t r o p h e n y l group cannot be d e e p l y i n s e r t e d . Thus, the c h o i c e of s u b s t i t u e n t group t o be i n c l u d e d i s m a i n l y d e t e r m i n e d by the s t e r i c e f f e c t . The water m o l e c u l e i n t h i s complex may a l s o p l a y a p a r t i n f i x i n g the s u b s t r a t e i n s i d e the c a v i t y by hydrogen bonding. The r a t i o n a l e f o r the s i m i l a r i n c l u s i o n p a t t e r n o b s e r v e d i n the benzaldehyde complex i s t h a t the whole m o l e c u l e may be more a b l e t o f i l l t he c a v i t y . In c o n t r a s t t o tho s e two complexes, the o r i e n t a t i o n of p - i o d o a n i l i n e w i t h i n the c a v i t y i s the same as t h a t i n a - c y c l o d e x t r i n . A l t h o u g h the i n c l u s i o n of e i t h e r the aminophenyl or the i o d o p h e n y l group i s s t e r i c a l l y p o s s i b l e , the l a t t e r i s p r e f e r r e d because of i t s s t r o n g e r van der Waals i n t e r a c t i o n w i t h the hy d r o p h o b i c c a v i t y . F i g . 11 -9. S t r u c t u r e and numbering scheme of 2 , 3 , 6 - t r i - O -Me-a-CD (from Ref. [ 6 2 ] ) . P e r m e t h y l a t i o n of the r i n g not o n l y a f f e c t s the p o s i t i o n and o r i e n t a t i o n of the guest m o l e c u l e s , but a l s o the m a c r o c y c l i c c o n f o r m a t i o n of the h o s t . 6 2 The C ( 6 ) - 0 ( 6 ) 1 10 bonds i n the G4 and G5 r e s i d u e s ( F i g . I I - 9 ) a r e i n a gauche-gauche c o n f o r m a t i o n , w h i l e the o t h e r s have a gauche-t r a n s c o n f o r m a t i o n . The s i x g l y c o s i d i c oxygen atoms form an e l l i p t i c a l l y d i s t o r t e d hexagon, which may change i t s m a c r o c y c l i c c o n f o r m a t i o n s l i g h t l y t o s u i t the shape of the i n c l u d e d group or m o l e c u l e . A l a r g e c o n f o r m a t i o n a l change i s r e s t r i c t e d due t o s t e r i c h i n d r a n c e imposed by the C(8) methyl groups of the p e r m e t h y l a t e d c y c l o d e x t r i n . To our knowledge, the c r y s t a l s t r u c t u r e s of 2,6-di-O-Me-/3~CD and i t s i n c l u s i o n complexes have not been a n a l y z e d . Thus, i n t h i s work we have had t o use the X-ray d a t a of the a - c y c l o d e x t r i n complexes t o en a b l e c o m p a r a t i v e s t u d i e s of the s o l i d - s t a t e 1 3C-n.m.r. r e s u l t s t o be made. I I . 6 . R e s u l t s and D i s c u s s i o n I I . 6 . 1 . 13C-N.M.R. E x p e r i m e n t a l Methods A p p l i c a t i o n of d i p o l a r d ephasing and D e l r i n s u p p r e s s i o n m e t h o d s 6 3 ' 6 " a r e i n c l u d e d i n t h i s t h e s i s as i n t e g r a l p a r t s of the 1 3C-n.m.r. s o l i d - s t a t e s t u d i e s . As s t a t e d i n the i n t r o d u c t i o n , t h e s e methods f a c i l i t a t e the p o t e n t i a l l y complex t a s k of u n r a v e l l i n g and a s s i g n i n g complex s p e c t r a of o r g a n i c m o l e c u l e s . P r i o r t o the d i s c u s s i o n on c y c l o d e x t r i n s and t h e i r i n c l u s i o n complexes, we b r i e f l y i n t r o d u c e the t o s y l a t e d sugar d e r i v a t i v e s here t o i l l u s t r a t e t h i s p o i n t because t h e i r w e l l - d i s p e r s e d 1 3 C s p e c t r a c o u l d be r e a d i l y o b t a i n e d . A l s o , the s y n t h e s e s 6 5 were e a s i l y a c c o m p l i s h e d g i v i n g pure 111 B I — i — i — i — i — i — I — i — i — i — i — i — I — i — i — r 2 0 0 1 5 0 1 0 0 - i — | — i — i — r 5 0 T— r 0 p.p.m. F i g . 11-10. 1 3 , 4 - d i - 0 -'C-N.m.r. s p e c t r a of 1,2:3, i s o p r o p y l i d e n e - 6 - 0 - p - t o l y l s u l f o n y l - a - D -g a l a c t o p y r a n o s e . [(A) Normal 1 3 O c .p. -m.a . s . spectrum, 5-ms c o n t a c t t i m e , and 3,350 sca n s . (B) D e l r i n - s i g n a l s u p p r e s s i o n , o b t a i n e d by s e t t i n g a d e l a y time of 500 ms between the 180° and 90° p u l s e s of 1H. (C) Nonprotonated-carbon spectrum, o b t a i n e d by s e t t i n g a 40-/<s p e r i o d w i t h o u t p r o t o n d e c o u p l i n g , p r i o r t o 1 3 C d a t a -a c q u i s i t i o n . D e u t e r a t i o n a t C-6 of the compound i s r e c o r d e d i n (B) and ( C ) . D e l r i n s i g n a l s and s p i n n i n g side-bands a r e i n d i c a t e d as X and SSB, r e s p e c t i v e l y . ] 1 12 c r y s t a l l i n e compounds i n h i g h y i e l d . F i g . II-10A shows a t y p i c a l example of the 1 3C-c.p.-m.a.s. spectrum of a c r y s t a l l i n e sample, namely, 1 , 2 : 3 , 4 - d i - 0 - i s o p r o p y l i d e n e - 6 -t o s y l - a - D - g a l a c t o p y r a n o s e , i n a D e l r i n r o t o r . The d i p o l a r d e p h a s i n g spectrum, o b t a i n e d by s e t t i n g a 40-^s p e r i o d w i t h o u t p r o t o n d e c o u p l i n g p r i o r t o data a c q u i s i t i o n i s shown i n F i g . I I - 1 0 C . W i t h the conc o m i t a n t s o l u t i o n s p e c t r a , p a r t i a l a ssignments of the 1 3 C resonances a r e made p o s s i b l e . B e s i d e s those of the no n p r o t o n a t e d c a r b o n s , methyl and d e u t e r a t e d - c a r b o n resonances a r e d i s c e r n i b l e ; the r a p i d methyl group r o t a t i o n s and l a r g e 1 3 C - 1 H d i s t a n c e s can reduce the p r o t o n - c a r b o n d i p o l a r c o u p l i n g d r a s t i c a l l y . The immense D e l r i n s i g n a l can be s u p p r e s s e d q u i t e c l e a n l y i f the e x p e r i m e n t a l c o n d i t i o n s a r e f a v o r a b l e . F i g . II-10B i n d i c a t e s an i n c o m p l e t e s u p p r e s s i o n of the s i g n a l when the d e l a y time between the two p u l s e s (180°X and 90°-x) was s e t a t 500 ms; f o r a d u r a t i o n of 600 ms, a " c l e a n e r " spectrum was o b s e r v e d . S t i l l , a r e s i d u a l , D e l r i n s i g n a l i s u s u a l l y o b s e r v e d . T h i s c o u l d be due e i t h e r t o r . f . - p u l s e i m p e r f e c t i o n s or t o p h y s i c a l inhomogeneity of the s p i n n e r m a t e r i a l . As a c a u t i o n a r y n o t e , a t t e n t i o n may be drawn t o the f a c t t h a t the s i g n a l s of the f o u r p r o t o n a t e d carbon atoms of the t o s y l o x y moiety a t 129.9 p.p.m. are so broad t h a t t hey a r e b a r e l y d e t e c t a b l e . T h i s i s c h a r a c t e r i s t i c of o t h e r t o s y l a t e d sugars t h a t we have s t u d i e d , and s e v e r a l a l t e r n a t i v e e x p l a n a t i o n s can be c i t e d . 6 * 1 1 3 I I . 6 . 2 . 13C-N.M.R. S t u d i e s of C y c l o d e x t r i n I n c l u s i o n  Complexes w i t h L i q u i d Guest M o l e c u l e s In t h i s s e c t i o n we r e p o r t s t u d i e s of complexes of c y c l o d e x t r i n s i n the s o l i d s t a t e by ' 3C n.m.r., u s i n g the c.p.-m.a.s. method. I n t e r p r e t a t i o n of t h e s e 1 3C-n.m.r. s p e c t r a i s f a c i l i t a t e d by comparison w i t h the 1H- and 1 3 C -n.m.r. s t u d i e s of t h e s e complexes i n s o l u t i o n , and w i t h the X-ray d a t a o b t a i n e d i n the s o l i d s t a t e . S i n c e the c r y s t a l s t r u c t u r e s of the host m o l e c u l e s [3] and [ 4 ] , and t h e i r i n c l u s i o n complexes have not been c o n f i r m e d by X-ray c r y s t a l l o g r a p h y , s t u d i e s of a r e l a t e d s e r i e s of guest m o l e c u l e s p r o v i d e a b a s i s f o r some i n t e r p r e t a t i o n . Compound [3] was found t o a f f o r d c r y s t a l l i n e complexes of molar r a t i o 1:1 w i t h many guest m o l e c u l e s and, t h e r e f o r e , p r o v i d e d a good s e r i e s of complexes f o r s t u d y i n g t h e i r p r o p e r t i e s i n the s o l i d s t a t e . In c o n t r a s t , compound [4] was shown t o be l e s s s u i t a b l e as a h o s t , p r o b a b l y due t o space r e s t r i c t i o n a t b o t h ends of i t s c a v i t y . R eported X-ray d a t a 6 2 of 2,3,6-tri-O-Me-a-CD show t h a t the s i x 0 ( 2 ) -C(7) bonds a r e d i r e c t e d o u t s i d e the c y c l o d e x t r i n r i n g , w i t h the s i x 0 ( 3 ) - C ( 8 ) bonds t u r n e d i n s i d e the r i n g . N e v e r t h e l e s s , as compared t o / 3 - c y c l o d e x t r i n we would expect a w i d e r opening f o r the 0 ( 2 ) , 0 ( 3 ) s i d e of the c a v i t y of compound [ 3 ] , but p r o b a b l y not i n the case of compound [ 4 ] . A l i s t of guest m o l e c u l e s which were used t o study the c o m p l e x i n g b e h a v i o r of t h e s e h o s t s i s shown i n T a b l e 11 — 1 (see Pg. 9 8 ) . 1 14 F i g . 11-11. The d i m e n s i o n s of the benzene r i n g , t a k i n g i n t o c o n s i d e r a t i o n the van der Waals r a d i i of the a r o m a t i c hydrogens (A) and the m o l e c u l a r o r i e n t a t i o n s of a m o n o s u b s t i t u t e d benzene r i n g i n c y c l o d e x t r i n ( B ) . A c c o r d i n g t o Van Hooidonk and B r e e b a a r t - H a n s e n , 6 7 the d i a m e t e r of the / 3 - c y c l o d e x t r i n c a v i t y i s 7.5 A and the s i z e of the benzene r i n g i s about 6.8 A, t h a t i s the d i s t a n c e measured between H(2) and H(6) ( F i g . 11-11). One would e x p e c t a m o n o s u b s t i t u t e d benzene r i n g t o o r i e n t a l o n g i t s l o n g a x i s i n the c a v i t y , r a t h e r than i n a " c r o s s w i s e " manner. However, the " u p r i g h t " p o s i t i o n a l l o c a t e d t o the benzene r i n g c o u l d be e i t h e r " h e a d - f i r s t " or " h e a d - l a s t " . As mentioned e a r l i e r , 6 1 ' 6 2 the m o l e c u l a r d i s p o s i t i o n s of s u b s t i t u t e d benzenes may d i f f e r from one h o s t t o a n o t h e r , and t h e i r complexes may c r y s t a l l i z e i n "cage"- or " c h a n n e l " - t y p e s t r u c t u r e s , depending on the n a t u r e and s i z e of the guest m o l e c u l e . I t may not be p o s s i b l e t o d i s t i n g u i s h the c o r r e c t o r i e n t a t i o n s o l e l y by the 1 3 C - c . p . -115 m.a.s. method i n t h i s c o m p l i c a t e d system. Such u n c e r t a i n t i e s w i l l not s e r i o u s l y l i m i t our d i s c u s s i o n on o t h e r i n t e r e s t i n g s t a t i c and m o t i o n a l a s p e c t s of the " g u e s t - h o s t " s t r u c t u r e i n the s o l i d s t a t e . The s o l i d - s t a t e 1 3 C s p e c t r a of compound [ 3 ] , w i t h and w i t h o u t magic a n g l e s p i n n i n g , a r e compared t o i t s s o l u t i o n spectrum i n F i g . 11-12. The l i n e w i d t h s of the s p e c t r a of the s p i n n i n g s o l i d s a r e r e l a t i v e l y broad, even a t a s p i n n i n g f r e q u e n c y of about 4.3 kHz. T h i s i s a t t r i b u t e d t o a d i s p e r s i o n of c h e m i c a l s h i f t s , a l o n g w i t h s m a l l e r magnetic s u s c e p t i b i l i t y c o n t r i b u t i o n s which s u r v i v e the sample s p i n n i n g . S u r p r i s i n g l y , the methoxyl groups show a r e a s o n a b l y l a r g e s e p a r a t i o n . S i n c e the n.m.r. i n s t r u m e n t i s o n l y c a p a b l e of p r o d u c i n g l i n e w i d t h s of 0.5 p.p.m. i n f a v o r a b l e c a s e s , the t r u e s p l i t t i n g cannot be a c c u r a t e l y measured. N e v e r t h e l e s s , the s e p a r a t i o n of c a . 2 p.p.m. f a r exceeds the c h e m i c a l d i f f e r e n c e (0.9 p.p.m.) of the C(2) and C(6) m ethoxyl groups measured i n s o l u t i o n . T h i s can be e x p l a i n e d i n terms of a c o e x i s t e n c e of c r y s t a l l i n e and amorphous domains; the l a t t e r b e i n g caused by the p a r t i a l " m e l t i n g " of the c r y s t a l l i n e sample i n the s i n t e r e d g l a s s f u n n e l d u r i n g the p r o c e s s of s u c t i o n f i l t r a t i o n . 5 1 The broad s h o u l d e r a t 68.2 p.p.m. a l s o s u g g e s t s such e x i s t e n c e . S i m i l a r r e s u l t s were a l s o o b t a i n e d when complex [5] was heated t o 170°C f o r 3 h t o r e g e n e r a t e the f r e e h o s t [ 3 ] , R e c r y s t a l l i z a t i o n of compound [3] from c h l o r o f o r m / p e t . e t h e r or methanol d i m i n i s h e d the apparent s p l i t t i n g of the 1 16 X || C 7 3 , 6 , 5 C c.p.-m.a.s.| h i9 h Power I d e c o u p l i n g s o l u t i o n H o w P ° w e r I d e c o u p l i n g 150 100 50 p.p m. i 0 F i g . 11-12, D i p o l a r - d e c o u p l e d c.p. 1 3C-n.m.r. s p e c t r a of [3], w i t h and w i t h o u t magic a n g l e s p i n n i n g . These a r e compared t o the s o l u t i o n - s t a t e spectrum of the same compound ( i n CDC1 3). 1 17 s i g n a l s of the methoxyl m o i e t i e s . I t i s known 5 7 t h a t any s l i g h t i r r e g u l a r i t i e s i n the c r y s t a l p a c k i n g can d i s t o r t the 2 ,6-di-O-methyl-glucopyranose monomer or change the hydrogen bonding i n the s o l i d , and t h e r e b y produce s l i g h t l y d i f f e r e n t s h i f t s f o r d i f f e r e n t monomers. However, t h e r e i s no i n d i c a t i o n of the presence of more than one k i n d of d i f f e r e n t conformer i n the l i n e s h a p e of the C-1 resonance f o r any of t h e s e samples. T h i s c o u l d be f u r t h e r v e r i f i e d i f t h e r e were no o v e r l a p p i n g of s i g n a l s i n the C-4 r e g i o n f o r t h i s m o l e c u l e . A genuine example of an amorphous sample i s i l l u s t r a t e d by a p r e c i p i t a t e d sample [ 4 ] , which r e v e a l s an u n o r i e n t e d powder spectrum as shown i n F i g . 1 1 - 1 3 . H e a t i n g the r e c r y s t a l l i z e d sample [24] t o 130°C f o r 1 d removed i t s guest m o l e c u l e , t o l u e n e , and a t the same time i t d e s t r o y e d the c r y s t a l l i n e s t r u c t u r e . F i g . 11-14 shows the 1 3C-n.m.r. s p e c t r a o b t a i n e d f o r s e v e r a l r e l a t e d i n c l u s i o n complexes of 2,6-di-O-Me-/3-CD. The g r a d u a l change i n the l i n e s h a p e p a t t e r n s of the sugar resonances from complex [5] t o [ 1 0 ] , s u g g e s t s the same " u p r i g h t " o r i e n t a t i o n i n s i d e the host c a v i t y f o r the benzene r i n g as has been found f o r o t h e r a r o m a t i c m o l e c u l e s . 8 Presumably, the l o n g a x i s of the a r o m a t i c m o l e c u l e l i e s a l most p a r a l l e l t o the c h a n n e l ( c a v i t y ) a x i s of the c y c l o d e x t r i n . The s p l i t t i n g s of the 1 3 C resonances of the h o s t may be d i s c u s s e d i n terms of the parameters which a r e known 1 9 1 18 A F i g . 11-13. 1 3C-N.m.r. s p e c t r a of the amorphous samples [ 4 ] : (A) p r e c i p i t a t e d sample; (B) r e c r y s t a l l i z e d sample [ 2 4 ] , w i t h the guest ( s o l v e n t ) m o l e c u l e s removed by h e a t i n g . 1 19 ® SSB C-1 C - 3 , 6 , 5 OCH 3 I C f 4 , 2 SSB B T 1 r —I 1 1 1 1 1 1 1 1 1 J— 150 100 50 n i 1 r p.p.m, F i g . 11-14. 1 3C-N.m.r. s p e c t r a of 2,6-di-0-Me-/3-CD i n c l u s i o n complexes: (A) [ 5 ] ; (B) [ 6 ] ; (C) [ 7 ] ; (D) [ 8 ] ; (E) [ 9 ] ; (F) [ 1 0 ] ; (G) [ 1 1 ] ; (H) [ 1 2 ] . 121 E F i g . 11-14 c o n t ' d 123 t o c o n t r i b u t e t o changes i n the c h e m i c a l s h i f t s on complex-f o r m a t i o n i n s o l u t i o n . I f the n — c l o u d d e s h i e l d i n g e f f e c t was of s i g n i f i c a n c e i n p e r t u r b i n g the carbon r e s o n a n c e s , t h i s p e r t u r b a t i o n s h o u l d be s l i g h t l y d i f f e r e n t f o r a g i v e n s e t of carbons due t o r e s t r i c t e d m o b i l i t y of the guest m o l e c u l e . As i n s o l u t i o n , such an e f f e c t i s u n l i k e l y because s i m i l a r s p l i t t i n g p a t t e r n s were observed f o r the host w i t h s m a l l e r a r o m a t i c and nonaromatic guest m o l e c u l e s . Hence, the major c o n t r i b u t i o n s may w e l l come from the s t e r i c i n t e r a c t i o n s and c o n f o r m a t i o n a l changes of the c a v i t y on s u b s t r a t e c o m p l e x a t i o n . I t i s o b v i o u s from the s e t of s p e c t r a above t h a t the s p l i t t i n g s become more complex w i t h i n c r e a s i n g s i z e of the s u b s t i t u e n t groups i n m o n o s u b s t i t u t e d benzenes, and more so i n the d i s u b s t i t u t e d benzenes. Here, the p a r t i c i p a t i o n of c o n f o r m a t i o n a l change may be c o n s i d e r e d l a r g e s i n c e the m a c r o c y c l i c c o n f o r m a t i o n of the h o s t i s r e l a t i v e l y f r e e of s t e r i c h i n d r a n c e at the C-2,C-3 s i d e of the c a v i t y . T h i s would p r o v i d e a good f i t between the guest and the h o s t . On the o t h e r hand, the b u l k y a c e t y l groups of compound [4] may impose severe r e s t r i c t i o n on bond d i s t o r t i o n s , and a l s o c o n s t r i c t i o n of the opening a t both ends of the t r u n c a t e d cone. F i g . 11-15 r e v e a l s the c o m p l e x i t y of the 1 3 C resonances of the h o s t , even w i t h benzene as the guest m o l e c u l e . A g a i n , a s i m i l a r t r e n d was observed i n t h e i r s p l i t t i n g p a t t e r n s ; the e f f e c t i s most pronounced f o r the complex w i t h the l a r g e s t s u b s t r a t e , p - x y l e n e , t h a t can be accommodated i n s i d e the 124 F i g . 11-15. 1 3C-N.m.r. s p e c t r a of 2,3,6-tri-O-Ac-0-CD i n c l u s i o n complexes: (A) [ 2 3 ] ; (B) [ 2 4 ] ; (C) [ 2 5 ] . 125 c a v i t y . Depending on the e x t e n t of the h o s t - g u e s t i n t e r a c t i o n s , n o t i c e a b l e changes i n the c h e m i c a l s h i f t s of the guest m o l e c u l e s can be a n t i c i p a t e d . T a b l e I I - 2 l i s t s the c h e m i c a l s h i f t v a l u e s of the 1 3 C resonances of the a r o m a t i c m o l e c u l e s as neat l i q u i d s and as encaged a r o m a t i c " s o l i d s " . The i s o t r o p i c c h e m i c a l s h i f t v a l u e s of these m o l e c u l e s remain p r a c t i c a l l y t he same, on g o i n g from the f r e e t o the complexed forms w i t h h o s t m o l e c u l e [ 3 ] . T h i s i n d i c a t e s t h a t the guest m o l e c u l e s have v e r y weak van der Waals c o n t a c t s w i t h the i n t e r i o r s u r f a c e of the c a v i t y , and t h a t they a r e e s s e n t i a l l y " f r e e " . In the case of /3-c y c l o d e x t r i n p e r a c e t a t e complexes, the i s o t r o p i c c h e m i c a l s h i f t d i f f e r e n c e s a r e g r e a t e r than 1.0 p.p.m.; the maximum e x p e r i m e n t a l d r i f t i n c h e m i c a l s h i f t f o r t h i s n.m.r. in s t r u m e n t i s e s t i m a t e d t o be ±0.5 p.p.m.. Hence, the d o w n f i e l d s h i f t of the guest resonances c o u l d be a t t r i b u t e d t o the s m a l l c a v i t y of the h o s t m o l e c u l e , i n which the a c e t y l groups bestow a s t r o n g d e s h i e l d i n g e f f e c t on the guest m o l e c u l e . An i n t e r e s t i n g o b s e r v a t i o n i s the s p l i t t i n g s of the a r o m a t i c carbon resonances of p- x y l e n e i n t o d o u b l e t s i n complex [ 2 5 ] , We suggest t h a t t h i s may be caused by i n c o m p l e t e p e n e t r a t i o n of the r i g i d guest m o l e c u l e i n t o the c a v i t y . In the s o l i d s t a t e , the a r o m a t i c r i n g of the guest m o l e c u l e s i s not f r e e l y r o t a t i n g about i t s t w o - f o l d a x i s w i t h i n t he annulus of the h o s t . However, i t can undergo T a b l e 11-2 . Chemical s h i f t s (p.p.m. ) f o r the 1 i q u i d guest molecu 1es S u b s t r a t e benzene. t o l u e n e . p-xy1ene. ethy1 benzene. c h l o r o b e n z e n e . Host [3] [4] [30]* [3] [4] [30] [3] [4] [30] [3] [3] bromobenzene.. [3] * D i a n i n ' s compound. (unsub) 128 . 5 128 .7 129 . 7 126 . 7 o r t h o meta para CH; CH 3 137 . 7 138 .0 140.5 134 . 1 134 . 5 135 .0 129.2 128.G (128.7) (130.0) (129.2) (129 . 1 ) (128.7 ) ( 137.5, 136.5) ( 130.3, 129. 1 ) 132 . 2 144 . 1 144 . 5 134 . 7 134 . 3 123 .0 122 .0 (128.3) 128.4 127.9 128.8 128.9 128 . 6 131.9 131.5 127 .7 130. 1 130.0 130. 5 130.3 125.6 126 . 2 126.6 (obscured) 125.8 (obscured) 126.8 (obscured) 127 . 3 128.5 29. 1 29.5 20. 8 2 1.6 (obscured) 20. 7 15.7 17.1 127 l i b r a t i o n a l f l i p motion w i t h a v e r y s m a l l a m p l i t u d e . 6 6 Large a n g l e r o t a t i o n by the a r o m a t i c r i n g about i t s l o n g a x i s may be r e s t r i c t e d i n the c a v i t y of compounds [3] and [ 4 ] ; t h i s i s p a r t i c u l a r l y t r u e i n the l a t t e r because of s e v e r e s t e r i c h i n d r a n c e imposed by the a c e t y l groups. The p e r t u r b a t i o n from the r i g i d c r y s t a l l i n e f i e l d may u l t i m a t e l y determine the d i f f e r e n c e s i n the time s c a l e and mode of motion of the a r o m a t i c r i n g s i n s o l u t i o n and i n the s o l i d c o m p l e x e s . 6 6 S u p p o r t i n g e v i d e n c e f o r d i f f e r e n t i a l motion of i n d i v i d u a l segments of the guest stems from the 1 3 C - c . p . -m.a.s. measurements used t o d i f f e r e n t i a t e between the resonances of p r o t o n a t e d and n o n p r o t o n a t e d c a r b o n s . The d i p o l a r d ephasing t e c h n i q u e 6 3 can be used t o e l i m i n a t e s p e c t r a l s i g n a l s from carbons s t r o n g l y c o u p l e d t o p r o t o n s , l e a v i n g s i g n a l s from n o n p r o t o n a t e d carbons and weakly c o u p l e d carbons because of a v e r a g i n g of d i p o l a r i n t e r a c t i o n s by e x t e n s i v e m o l e c u l a r r e o r i e n t a t i o n . In t h i s way, the s i g n a l s from t h e i r pendant s u b s t i t u e n t s such as the methoxyl and a c e t o x y l m o i e t i e s a r e r e t a i n e d . S u b s t a n t i a l s i g n a l s were o b t a i n e d f o r a l l the resonances of the guest m o l e c u l e s w i t h i n the c r y s t a l l i n e m a t r i x of compound [3] as d e p i c t e d i n F i g . 11-16. However, the resonances of the a r o m a t i c carbons of complexes [24] and [25] a r e e s s e n t i a l l y s u p p r e s s e d because r e s i d u a l , or no, motion i s a l l o w e d f o r the r i n g t h a t i s i n t i m a t e l y a s s o c i a t e d w i t h the c a v i t y . Only the methyl groups g i v e F i g . 11-16. D i p o l a r - d e p h a s i n g 1 3C-n.m.r. s p e c t r a : (A) [ 5 ] ; (B) [ 7 ] ; (C) [ 8 ] ; (D) [ 2 3 ] ; (E) [ 2 4 ] ; (F) [ 2 5 ] . 129 130 s u b s t a n t i a l s i g n a l s , t h a t r e f l e c t the v a r i o u s a d d i t i o n a l degrees of freedom a v a i l a b l e t o a l l t h e s e carbon atoms. In p r i n c i p l e , v a r i a b l e - t e m p e r a t u r e ( v . t . ) 1 3 C - c . p . -m.a.s. e x p e r i m e n t s 5 8 s h o u l d p r o v i d e v a l u a b l e i n s i g h t i n t o the dynamics and c o m p o s i t i o n s of i n c l u s i o n complexes i n v o l v i n g l i q u i d s u b s t r a t e s . U n f o r t u n a t e l y , such s t u d i e s were not p o s s i b l e a t U.B.C. because of the u n a v a i l a b i l i t y of a v.t.-m.a.s. probe. N e v e r t h e l e s s , s t u d i e s of t e mperature e f f e c t s on c r y s t a l l i n e complexes a r e p r e s e n t e d by r e c o r d i n g a s e r i e s of s p e c t r a from samples which had been heated p r i o r t o each n.m.r. measurement, over a wide range of t e m p e r a t u r e s . F i g s . 11-17 and 11-18 r e v e a l the t h e r m a l s t a b i l i t y of the complexes w i t h benzene and t o l u e n e , r e s p e c t i v e l y ; t h e s e were g r a d u a l l y " d i s t i l l e d " from the c a v i t y of the h o s t m o l e c u l e [ 3 ] . The s p l i t t i n g s of the h o s t resonances d i m i n i s h g r a d u a l l y , and the peaks a r e p r o g r e s s i v e l y moved towards those of the f r e e host a t h i g h e r t e m p e r a t u r e s . The importance of a r o m a - c y c l o d e x t r i n complexes i n the food i n d u s t r y has been e x t e n s i v e l y i n v e s t i g a t e d by s e v e r a l r e s e a r c h g r o u p s . 6 8 The p r e p a r a t i o n of these complexes i s r e l a t i v e l y s i m p l e , and the 0 - c y c l o d e x t r i n complex of d-limonene has been r e p o r t e d by S u z u k i and I k u r a . 6 9 Compounds [ 2 ] , [ 3 ] , and [4] were used t o encage t h i s s u b s t r a t e , but w i t h l i m i t e d s u c c e s s . Only compound [3] a f f o r d e d a complex w i t h a g u e s t / c y c l o d e x t r i n molar r a t i o of 1:1; the 1 3 C c h e m i c a l s h i f t s of the guest resonances ( F i g . 11-19) ar e 131 F i g . 11-17. 1 3C-N.m.r. s p e c t r a of [ 5 ] , t e m p e r a t u r e s i n d i c a t e d . p r e h e a t e d a t the F i g . 11-17 c o n t ' d 133 F i g . 11-18. 1 3C-N.m.r. s p e c t r a of [ 6 ] , p r e h e a t e d a t the t e m p e r a t u r e s i n d i c a t e d . 134 F i g . 11-19. 1 3C-N.m.r. s p e c t r a of 2,6-di-0-Me-/3-CD-d-limonene complex: (A) normal c.p.-m.a.s.; (B) w i t h d i p o l a r d e p h a s i n g . 135 q u i t e c l o s e t o those o b t a i n e d i n s o l u t i o n , except f o r C-4,C-5, and C-9. The d i f f e r e n c e s i n the i s o t r o p i c c h e m i c a l s h i f t v a l u e s of the s e carbons may be e x p l a i n e d by the r i g i d i t y of the m o l e c u l e w i t h i n the c a v i t y . 11.6.3. 13C-N.M.R. S t u d i e s of C y c l o d e x t r i n I n c l u s i o n  Complexes w i t h S o l i d Guest M o l e c u l e s I t was found t h a t v a r i a t i o n s i n c r y s t a l l i n e f i e l d can a l t e r the c h e m i c a l s h i f t d i s p e r s i o n s of s o l i d s u b s t r a t e s between t h e i r f r e e s t a t e , and complexed s t a t e w i t h the hos t m o l e c u l e [ 3 ] , T h i s o c c u r s when r e l a t i v e l y l a r g e guest m o l e c u l e s a r e i n v o l v e d i n the c o m p l e x a t i o n ; e.g., b i p h e n y l , 4 , 4 ' - d i m e t h y l b i p h e n y l , and p - d i - t e r t . - b u t y l b e n z e n e . One would expect t h e i r c o m b i ning r a t i o s of guest t o host t o be 1:2; t h i s i s o n l y t r u e f o r b i p h e n y l , whereas the o t h e r s y i e l d 1:1 complexes. S i n c e t h e s e guest m o l e c u l e s a r e e l o n g a t e d , t h e i r complexes may w e l l c r y s t a l l i z e i n c h a n n e l -or d i s c o n t i n u o u s " c h a n n e l " - t y p e s t r u c t u r e s . 6 1 In the former, one guest m o l e c u l e i s i n c l u d e d w i t h i n the c y l i n d e r , w h i l e the o t h e r i s l o c a t e d o u t s i d e the c y c l o d e x t r i n r i n g t o a f f o r d a molar r a t i o of 1:1. A l t e r n a t i v e l y , one guest m o l e c u l e i s a s s i g n e d t o a r i n g , t h e r e b y d i s r u p t i n g the c h a n n e l - t y p e s t r u c t u r e of the hos t as i l l u s t r a t e d i n F i g . 11-20. B i p h e n y l c r y s t a l s a r e known 7 0 t o be m o n o c l i n i c , w i t h 2 m o l e c u l e s i n the u n i t c e l l of space group P2,/a. The 136 £ai Ca\ . ta l a l a tei teS tei £21 &i &\ rav TODO F i g . 11-20. Schematic drawings of the i n c l u s i o n p o s s i b i l i t i e s f o r l a r g e r guest m o l e c u l e s (from Ref. [ 6 1 ] ) . 137 s i n g l e , symmetry-independent m o l e c u l e , which i s s i t u a t e d on a c e n t e r of symmetry, has a c o m p l e t e l y p l a n a r s t r u c t u r e f o r the carbon s k e l e t o n . A l b e i t t h a t the hydrogen atoms a r e s i t u a t e d i n the p l a n e d e f i n e d by the carbon atoms of b i p h e n y l , t h e r e a r e s m a l l i n - p l a n e d i s p l a c e m e n t s of the o r t h o hydrogen atoms from i d e a l i z e d p o s i t i o n s , t h a t reduce the s t e r i c s t r a i n . The g a i n i n s t a b i l i z a t i o n energy from a t t a i n m e n t of p l a n a r i t y i s p r o b a b l y of the same or d e r as t h a t r e q u i r e d t o compress the C and H atoms s l i g h t l y ; 7 1 t h u s , i t i s r e a s o n a b l e t o suppose t h a t p l a n a r or n o n - p l a n a r arrangements c o u l d occur i n the c r y s t a l , depending on the p a c k i n g . The b e h a v i o r of the b i p h e n y l m o l e c u l e i n o t h e r s i t u a t i o n s has been d i s c u s s e d i n the l i t e r a t u r e ; 7 2 ' 7 3 the d i h e d r a l a n g l e between the two r i n g s i s 40-50° i n the vapor phase, and 20-25° i n s o l u t i o n . The 1 3C-n.m.r. s p e c t r a of s o l i d b i p h e n y l and i t s complex w i t h compound [3] a r e shown i n F i g . 11-21. The l i n e w i d t h s and c h e m i c a l s h i f t s of the carbon resonances 4 4' 138 A 3 2 2* 3* 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 150 100 50 _ _ _ 0 p.p.m. F i g . 11-21. 1 3C-N.m.r. s p e c t r a of (A) b i p h e n y l and (B) 2,6-di-O-Me-p'-CD-biphenyl i n c l u s i o n complex, [ 1 3 ] . 1 3 9 b e l o n g i n g t o the guest m o l e c u l e a r e a f f e c t e d by the change i n i t s environment. Carbon atoms C-1,C-1' or C-4,C-4' p r o b a b l y have e q u i v a l e n t m o l e c u l a r and c r y s t a l e nvironments s i n c e a s i n g l e 1 3 C resonance was observed i n the s o l i d s t a t e f o r the C-1,C-1' p a i r of c a r b o n s . I t s h o u l d be noted t h a t c r y s t a l symmetry does not r e q u i r e the o r t h o or meta carbon p a i r s t o be e q u i v a l e n t . 7 " In t h i s c a s e , the d i f f e r e n c e i s not s u f f i c i e n t l y l a r g e and, hence, o n l y broad resonances were observed f o r the o r t h o and meta c a r b o n s . The i n - p l a n e d i s p l a c e m e n t s of the hydrogen atoms may not cause any b r o a d e n i n g of the carbon resonances because the o v e r a l l symmetry of the m o l e c u l e i s s t i l l r e t a i n e d . The encaged b i p h e n y l m o l e c u l e would p r o b a b l y adopt a c o p l a n a r s t r u c t u r e w i t h i n the a n n u l u s of the r i n g . T h i s i s e v i d e n t from the narrower and w e l l - r e s o l v e d l i n e w i d t h s , and any s l i g h t magnetic i n e q u i v a l e n c e i n the p a i r s of carbon atoms i s now removed because the m o l e c u l e i s e x p e r i e n c i n g a " s o l u t i o n - l i k e " environment. At the same t i m e , the s t e r i c c o m p r e s s i o n s 7 5 a r e r e l i e v e d as i n d i c a t e d by the d o w n f i e l d s h i f t s of the C-1 and o r t h o c a r b o n s , which a r e c l o s e t o t h o s e v a l u e s measured i n s o l u t i o n . L i b r a t i o n a l motion of the m o l e c u l e , about i t s l o n g a x i s , i s suggested from the d i p o l a r d e p h a s i n g spectrum. Based on the X-ray d a t a r e p o r t e d by Casalone e t a l . , 7 1 the s o l i d - s t a t e spectrum of 4 , 4 ' - d i m e t h y l b i p h e n y l s h o u l d be more c o m p l i c a t e d than t h a t of b i p h e n y l . The c r y s t a l s a re m o n o c l i n i c , w i t h 8 m o l e c u l e s i n the u n i t c e l l of space 140 A F i g . 11-22. 1 3C-N.m.r. s p e c t r a of (A) 4 , 4 ' - d i m e t h y l b i p h e n y l and (B) 2 , 6-di-0-Me-/3-CD-4 , 4' - d i m e t h y l b i p h e n y l i n c l u s i o n complex, [14]. 141 group P 2 1 / c . There a r e 2 m o l e c u l e s i n the asymmetric u n i t , w i t h d i h e d r a l a n g l e s of 36° and 40°, r e s p e c t i v e l y . T h e r e f o r e , each carbon resonance i s e x p e c t e d t o s p l i t a t l e a s t i n t o a d o u b l e t t e d - d o u b l e t ; i n s t e a d , broad s i g n a l s w i t h fewer s p l i t t i n g s were obser v e d ( F i g . 11-22). The i n t r a m o l e c u l a r and i n t e r m o l e c u l a r e f f e c t s may not be l a r g e enough t o g i v e r e s o l v a b l e s p l i t t i n g s due t o the s m a l l d i f f e r e n c e i n the d i h e d r a l a n g l e s , y e t c o n s i d e r a b l e s h i f t s a r e i nduced by the l a t t e r . The s p l i t t i n g s and s h i f t s i n the carbon resonances can be removed by encaging the m o l e c u l e i n s i d e the c a v i t y of compound [ 3 ] . I f t h i s complex c r y s t a l l i z e s i n a c h a n n e l - t y p e s t r u c t u r e , the c h e m i c a l s h i f t s of the guest m o l e c u l e s i t u a t e d i n s i d e and o u t s i d e the l o n g column s h o u l d d i f f e r . But sharp s i g n a l s w i t h i s o t r o p i c c h e m i c a l s h i f t s c l o s e t o those d a t a o b t a i n e d i n s o l u t i o n were o b s e r v e d . T h e r e f o r e the m o l e c u l e i s p r o b a b l y p l a n a r , and u n d e r g o i n g m o l e c u l a r r e o r i e n t a t i o n w i t h i n the d i s c o n t i n u o u s " c h a n n e l " - t y p e s t r u c t u r e of the h o s t . The c r y s t a l s t r u c t u r e of p - d i - t e r t . - b u t y l b e n z e n e has been r e p o r t e d , 7 6 w i t h no i n d i c a t i o n of i n e q u i v a l e n t m o l e c u l e s i n the u n i t c e l l of space group P 2 1 / n . The 1 3 C -n.m.r. spectrum shows two peaks f o r the o r t h o c a r b o n s , which a r e due t o i n e q u i v a l e n t m o l e c u l a r and c r y s t a l e n vironments (as d i s c u s s e d e a r l i e r f o r the b i p h e n y l m o l e c u l e ) , w h i l e the o t h e r carbon s i g n a l s appear as s i n g l e t s . The asymmetric l i n e s h a p e of the C-1 resonance a r i s e s because of the s l i g h t m i s s e t of the magic a n g l e , 1 42 F i g . 11-23. 1 3C-N.m.r. s p e c t r a of (A) p - d i - t e r t . -b u t y l b e n z e n e and (B) 2,6-di-O-Me-0-CD-p-di-t e r t . - b u t y l b e n z e n e i n c l u s i o n complex, [ 1 5 ] . 143 A C H , B C-1 W W 50 150 100 p.p.m. F i g . 11-24 1 3C-N.m.r. s p e c t r a m.a.s. (sample i n of [ 1 5 ] : (A) normal c.p.-a d e u t e r a t e d , p l e x i g l a s s p i n n e r ) ; (B) D e l r i n - s i g n a l s u p p r e s s i o n ; (C) d i p o l a r d e p h a s i n g spectrum ( o b t a i n e d by s e t t i n g a 40-/<s p e r i o d w i t h o u t p r o t o n d e c o u p l i n g , p r i o r t o 1 3 C d a t a - a c q u i s i t i o n ) ; (D) same as ( C ) , but w i t h a l o n g e r w a i t i n g p e r i o d of l O O ^ s ; (E) D e l r i n - s i g n a l s u p p r e s s i o n and d i p o l a r d e p h a s i n g . F i g . 11-24 c o n t ' d 145 r e s u l t i n g i n i n c o m p l e t e a v e r a g i n g of i t s l a r g e c h e m i c a l s h i f t a n i s o t r o p y . S i m i l a r l y , m o l e c u l a r r e o r i e n t a t i o n of the guest m o l e c u l e w i t h i n the c a v i t y of the h o s t a f f o r d s sharp s i g n a l s ( F i g . 11-23); a s i n g l e t f o r the o r t h o carbons and, s u r p r i s i n g l y , a d o u b l e t of e q u a l i n t e n s i t y f o r the methyl c a r b o n s . We c o n c l u d e t h a t the two t e r t . - b u t y l m o i e t i e s p r o b a b l y e x p e r i e n c e d i f f e r e n t l o c a l environments t h a t appear t o be l a r g e s t f o r the methyl groups. The subsequent s p e c t r a ( F i g . 11-24) summarize the r e s u l t s t h a t a r e o b t a i n e d from the d i p o l a r d e p h a s i n g and D e l r i n s u p p r e s s i o n methods. 11.6.4. 2H-N.M.R. S t u d i e s of C y c l o d e x t r i n I n c l u s i o n  Complexes There has been an i m p r e s s i v e number of d e u t e r i u m n.m.r. s p e c t r o s c o p i c s t u d i e s of the dynamics of the "guest" m o l e c u l e s d i s s o l v e d i n l i q u i d c r y s t a l s y s t e m s , 7 7 " 7 9 and r e c e n t l y i n s o l i d c l a t h r a t e s 8 0 " 8 2 as w e l l . Such s p e c t r a a r e p r o f o u n d l y s i m p l i f i e d by the l a r g e and u s u a l l y u n c o m p l i c a t e d q u a d r u p o l e s p l i t t i n g s , and the l i n e s h a p e s o f f e r a c r i t i c a l t e s t f o r models of a n i s o t r o p i c m o l e c u l a r r o t a t i o n . Thus, the s p l i t t i n g s can r e v e a l new and d i r e c t i n f o r m a t i o n on the motion of a guest m o l e c u l e w i t h i n the h o s t m a t e r i a l s . R e c e n t l y , an X-ray s t u d y " 9 of the complex of d i m e t h y l s u l f o x i d e w i t h a - c y c l o d e x t r i n , showed the guest m o l e c u l e t o be l o c a t e d i n the h o s t c a v i t y n e a r e s t t o the secondary 146 h y d r o x y l groups and w i t h two hydrogen bonds t o the a d j a c e n t a - c y c l o d e x t r i n m o l e c u l e s . The complexes of DMSO w i t h both a- and /3-cyc l o d e x t r i n s , were p r e p a r e d from s o l u t i o n s i n DMSO/water or DMSO/methanol/water; however, o n l y approximate s t o i c h i o m e t r y of the s e complexes c o u l d be o b t a i n e d from the m i c r o a n a l y s i s d a t a . F o r t u n a t e l y , t h i s d i d not compromise the p r e s e n t study of the e f f e c t of r i n g - s i z e on the m o b i l i t y of the ( C D j ^ S O m o l e c u l e . As mentioned e a r l i e r (Chapter I , Pg. 5 6 ) , the 2H-n.m.r. spectrum of the p o l y c r y s t a l l i n e powder of s t a t i c C-D b e a r i n g d i m e t h y l s u l f o x i d e m o l e c u l e s w i l l have a peak maxima s e p a r a t i o n of AV^ = 3 e 2 q Q ( c o s 2 0 - 1 ) ( 1 ) 2 h 2 = 3 e 2qQ ; f o r 8 = 90°, 4 h where 8 i s the a n g l e between the magnetic f i e l d , B 0, and the p r i n c i p a l a x i s of the e l e c t r i c f i e l d g r a d i e n t t e n s o r ( u s u a l l y a l o n g the C-D bond d i r e c t i o n ) . The quadr u p o l e c o u p l i n g c o n s t a n t of (C D 3 ) 2 S O , e 2qQ/h, has been de t e r m i n e d e x p e r i m e n t a l l y 8 3 t o be 162 kHz. Due t o the f a s t C 3 r o t a t i o n of the methy l group, i t i s n e c e s s a r y t o ta k e the average over a l l d i r e c t i o n s of the C-D bond a x i s ( F i g . 11-25). In the case of s p 3 bonds, the asymmetry parameter i s assumed t o be z e r o , and the m o t i o n a l l y averaged s p l i t t i n g i s then g i v e n by 147 A V Q , = Z W ^ ^ 3 c o s 2 / 3 - 1 j (2 ) where 0 = 109°28' f o r a t e t r a h e d r a l geometry of the methyl groups. The f u l l r i g i d - l a t t i c e b r e a d t h of the d e u t e r i u m n.m.r. spectrum would be reduced by the f a c t o r , (3cos 2109°28' - 1)/2, t o g i v e a s p l i t t i n g of 40.5 kHz. F i g . 11-25. I l l u s t r a t i o n of an i s o l a t e d m e t h y l - d 3 group o r i e n t e d w i t h i t s C 3 a x i s i n c l i n e d at the p o l a r c o o r d i n a t e s ( 9 , f ) w i t h r e s p e c t t o the l a b o r a t o r y frame. The d e u t e r i u m n.m.r. s p e c t r a (see F i g s . 11-26 and I I -27) of the /3-CD-DMSO-^-H20 complex [26] i n d i c a t e d t h a t the m o l e c u l a r motion i s not s t r i c t l y c o n f i n e d t o the methyl 1 48 A B C D 1 1 1 62.5 0 -62.5 . ii kHz F i g . 11-26. 2H-N.m.r. s p e c t r a of (A) ( C D 3 ) 2 S O i n [ 2 6 ] ; (B) (CD 3) 2CO i n [ 2 7 ] ; (C) ( C D 3 ) 2 S O i n [ 2 8 ] ; (D) (CD 3) 2CO i n [ 2 9 ] ; (measured a t 20°C). 149 F i g . 11-27. 2H-N.m.r. s p e c t r a of (CD 3) 2SO i n (A) [26] and (B) [28] r e c o r d e d a t the te m p e r a t u r e s i n d i c a t e d . 1 50 groups. Thus, t o account f o r the s m a l l s p l i t t i n g s (10 kHz) observ e d above ambient t e m p e r a t u r e , the m o l e c u l e must e x p e r i e n c e a d d i t i o n a l a n i s o t r o p i c motion which i s f a s t on the n.m.r. t i m e s c a l e . A p o s s i b l e r o t a t i o n of the m o l e c u l e about the a x i s t h rough the s u l f u r and oxygen atoms would f u r t h e r reduce the s p l i t t i n g by a f a c t o r of ( 3 C O S 2 1 0 7 ° -1)/2, t o a f f o r d a 13.8 kHz s p l i t t i n g , i n not unr e a s o n a b l e agreement w i t h the e x p e r i m e n t a l v a l u e . M o l e c u l a r r e o r i e n t a t i o n about the second a x i s i s reduced or " f r o z e n " , w i t h d e c r e a s e i n t e m p e r a t u r e s ; t h u s , a 38.8 kHz s p l i t t i n g was obser v e d a t -23°C, c o r r e s p o n d i n g t o a pure C j r o t a t i o n . The s u c c e s s of t h i s s i m p l e model, prompted us t o examine the complex [27] of a c e t o n e - d 6 w i t h j 3 - c y c l o d e x t r i n . The o b s e r v e d s p l i t t i n g a t 20°C i s <5 kHz. A l t h o u g h the acetone m o l e c u l e i s of p l a n a r symmetry, r o t a t i o n about the c a r b o n y l bond would reduce the s p l i t t i n g by (3cos 2123° -l ) / 2 , t o g i v e a s e p a r a t i o n of 4.6 kHz. F a s t r o t a t i o n about an a x i s p e r p e n d i c u l a r t o the p l a n e of the acetone m o l e c u l e seems u n l i k e l y s i n c e i t would l e a d t o a s u b s t a n t i a l l y l a r g e r s p l i t t i n g (20 kHz) than t h a t observed e x p e r i m e n t a l l y . Thus, t h e s e r e s u l t s suggest t h a t b oth guest m o l e c u l e s behave s i m i l a r l y w i t h i n the a n n u l u s of 0-c y c l o d e x t r i n . Comparison w i t h the analogous a - c y c l o d e x t r i n complexes e n a b l e s an e v a l u a t i o n t o be made of the e f f e c t s of r i n g -s i z e . The quadrupole s p l i t t i n g f o r (CD 3) ; lSO i n the a-CD complex [29] a t 20°C i s l a r g e r (40 kHz) than t h a t of the /J-151 CD complex (10 kHz), which s u g g e s t s a s u b s t a n t i a l l y t i g h t e r f i t w i t h i n the s m a l l e r a n n u l a r space of the former. A f u r t h e r i m p o r t a n t d i f f e r e n c e i s the presence of a s m a l l , sharp i s o t r o p i c peak, which i s i n d i c a t i v e of " f r e e " ( 0 0 3 ) ^ 5 0 m o l e c u l e s . H e a t i n g the sample t o h i g h e r t e m p e r a t u r e s , i n c r e a s e d the i n t e n s i t y of the i s o t r o p i c peak and, c o n c o m i t a n t l y , d e c r e a s e d the b r e a d t h of the l a r g e s p l i t t i n g . F u r t h e r m o r e , the former c o u l d not be removed even by c a r e f u l washing of the c r y s t a l s w i t h c o l d methanol. The a - c y c l o d e x t r i n complex of acetone [30] a l s o r e v e a l e d two k i n d s of guest m o l e c u l e s w i t h i n the c r y s t a l l a t t i c e , a l t h o u g h i n t h i s case the i s o t r o p i c peak was more i n t e n s e than t h a t of complex [ 2 9 ] . I t i s of i n t e r e s t t o note t h a t when the s e complexes were c r y s t a l l i z e d from methanol/water s o l u t i o n , no s i g n i f i c a n t changes of t h e i r l i n e s h a p e s were ob s e r v e d . Presumably, the methanol and/or water m o l e c u l e s p r e s e n t i n the c r y s t a l l a t t i c e have no s u b s t a n t i a l i n f l u e n c e on the m o l e c u l a r r e o r i e n t a t i o n of the guest m o l e c u l e s . I t has been shown by p r o t o n n.m.r. 8 f l t h a t benzene m o l e c u l e s undergo t h e r m a l l y a c t i v a t e d r e o r i e n t a t i o n about t h e i r C 6 a x i s i n the s o l i d s t a t e ; however, the d e t a i l e d mechanism of the p r o c e s s i s s t i l l not f u l l y u n d e r s t o o d . The temperature dependence of the quadrupole s p l i t t i n g of p o l y c r y s t a l l i n e benzene has been r e p o r t e d , 7 8 and the v a l u e s of the q u a d r u p o l e c o u p l i n g c o n s t a n t a r e i n the range of 177 t o 193 kHz. The l i n e s h a p e can be c a l c u l a t e d by t r a n s f o r m i n g 1 52 the e . f . g . t e n s o r from the s t a t i c m o l e c u l a r frame p r i n c i p a l a x i s system t o a r e f e r e n c e frame r o t a t i n g about the a p p r o p r i a t e f i x e d a x i s w i t h a u n i t a r y m a t r i x e x p r e s s e d i n terms of the E u l e r a n g l e s . Without g o i n g i n t o the mathematics of t r a n s f o r m a t i o n from one c o o r d i n a t e system t o a n o t h e r , a q u a l i t a t i v e t r e a t m e n t of the e f f e c t of m o l e c u l a r r e o r i e n t a t i o n on the powder spectrum governed by e . f . g . t e n s o r s i s i l l u s t r a t e d . For the p a r t i c u l a r case c o n s i d e r e d h e r e , the p r i n c i p a l elements of the e . f . g . t e n s o r a r e r e l a t e d t o the m o l e c u l a r frame i n which the p r i n c i p a l a x i s VZ3E. , l i e s a p p r o x i m a t e l y a l o n g the C-D bond. Hence, V y y w i l l (a) e i t h e r be a l o n g or p e r p e n d i c u l a r t o C 6 and V z z , which are c o l i n e a r f o r r a p i d r e o r i e n t a t i o n . T h i s can be v e r i f i e d by examining t h e e f f e c t of m o l e c u l a r r o t a t i o n on the spectrum, u s i n g the e x p r e s s i o n s d e r i v e d f o r the c h e m i c a l s h i f t t e n s o r s . 8 5 The averaged e . f . g . t e n s o r w i l l be a x i a l l y symmetric w i t h r e s p e c t t o the C 6 a x i s : c o s 2 a s i n 2 / 3 ) V x x s i n 2 a s i n 2 | 3 ) V y y + 1 /2s i n 2 0VXZ sin 2/3cos 2aV* x + s i n 2 / 3 s i n 2 a V y y + c o s 2 0 V i r (3) where t h e E u l e r a n g l e s (a,0) r e l a t e the e f f e c t i v e a x i a l l y symmetric t e n s o r t o the o r i g i n a l t e n s o r . For V y y l y i n g a l o n g t h e r o t a t i o n a x i s (a = 90° and 0 = 90°), the (A) V„ = V yy = 1/2(1 -+ 1/2(1 -V zz. 153 p r i n c i p a l elements a re r e p r e s e n t e d by 8 e VxxR) = V y} R > = 1/2(VX» + V« ) = "1/2 (Vyy) and (4) V "° = V 1/2(1 + 1 )v zz T h e r e f o r e , the f r e q u e n c i e s f o r s p e c t r a l d i s c o n t i n u i t i e s a r e g i v e n by v, = v 2 = ±v*? = ±VyyR) = ± 3_ e 2qQ ( 1 + »1 ) (5) 16 h l ^ 3 = ±v£ = ± 3 e 2qQ (1 + ») ) 8 h 1 where V Z 2 = 3 e 2qQ 4 h In t h e case of V y y l y i n g p e r p e n d i c u l a r t o the r o t a t i o n a x i s (a = 0° and /3 = 90°), the f r e q u e n c i e s a r e g i v e n by \>, = v 2 = ±vx„ = ±Vy> = ± 3_ e 2qQ ( 1 - rj ) (6) 16 h * ^3 = ±V« = ± 3 e 2qQ (1 - A ) 8 h 1 Hence, by measuring the s p l i t t i n g Av 0 | i n the r o t a t i o n a l l y 1 54 averaged spectrum, the c o r r e c t assignment can be made. The qu a d r u p o l e c o u p l i n g c o n s t a n t s p r e v i o u s l y measured f o r benzene were 190 ± 3 kHz from p o l y c r y s t a l l i n e n.m.r. and 186 ± 1.6 kHz from s i n g l e c r y s t a l n.m.r., 8 7 but the asymmetry parameter was not d e t e r m i n e d i n e i t h e r c a s e . Barnes and B l o o m 8 8 have o b t a i n e d the v a l u e s e 2qQ/h = 180 ± 1.5 kHz and | = 0.041 ± 0.007 at -196°C; the former was found t o be independent of temperature between the range of -123 t o -23°C. T h i s can a l s o be seen from the q u a d r u p o l e s p l i t t i n g s ( r e f e r t o F i g . 11-28) o b t a i n e d i n t h i s s t u d y . By s u b s t i t u t i n g the averaged v a l u e of AVQ, = 70.10 ± 1.0 kHz and ^ = 0.041 ± 0.007 i n t o the Eqs. (5) and ( 6 ) , the r e s p e c t i v e e 2qQ/h v a l u e s a r e 179.6 ± 2.8 and 194.9 ± 2.8 kHz. Thus, the a p p r o p r i a t e assignment s h o u l d p l a c e V yy a l o n g the r o t a t i o n a x i s as shown on Pg. 155. The m o l e c u l a r motion of a p o l a r , a r o m a t i c m o l e c u l e s w i t h i n the i n c l u s i o n c h a n n e l of c y c l o d e x t r i n have been d i s c u s s e d e a r l i e r i n our 1 3C-c.p.-m.a.s. s t u d i e s . R e c e n t l y , Inoue et a l . 8 9 r e p o r t e d s i m i l a r s t u d i e s on complexes of and / ^ - c y c l o d e x t r i n s w i t h p o l a r , a r o m a t i c m o l e c u l e s . C o n t i n u a t i o n of the work u s i n g the d e u t e r i u m n.m.r. method p r o v i d e s a b e t t e r u n d e r s t a n d i n g of the t y p e s of motion e x e c u t e d by the guest m o l e c u l e . F u l l a n a l y s i s of the e x p e r i m e n t a l l i n e s h a p e s u s i n g (a) p l a n a r Brownian d i f f u s i o n 9 0 and (b) d i s c r e t e jumps between t h r e e e q u i v a l e n t s i t e s 9 0 ' 9 1 (symmetric jumps about a d i f f u s i o n a x i s of 155 symmetry C3V ) models has been p r e s e n t e d i n the l i t e r a t u r e . However, i t was d e c i d e d i n t h i s study not t o s i m u l a t e the l i n e s h a p e s based on the above p o s s i b l e models t o i l l u s t r a t e the v a r i o u s dynamic modes e x p e r i e n c e d by the benzene and o t h e r a r o m a t i c m o l e c u l e s . The 2H quadrupole s p l i t t i n g s of benzene-d 6 s e q u e s t e r e d i n the hos t m o l e c u l e s [3] and [ 4 ] , c l e a r l y i l l u s t r a t e the i n f l u e n c e of c a v i t y s i z e on i t s m o b i l i t y . The v a l u e s measured a t 20°C f o r complexes [5] and [23] a r e 48 and 68.5 kHz, r e s p e c t i v e l y ( F i g s . 11-28 and 11-29). For a r i g i d l y bound benzene m o l e c u l e , a s p l i t t i n g of 141 kHz would be e x p e c t e d ; r a p i d r o t a t i o n of the benzene about i t s C 6 a x i s (>10 8 s" 1) w i t h i n the c a v i t y would g i v e an observed s p l i t t i n g of 70 kHz, and about a C 2 a x i s , a 15 kHz 156 F i g . 11-28. 2H-N.m.r. s p e c t r a of (A) f r o z e n C 6D 6; (B) C 6D 6 i n [ 5 ] ; (C) C 6D 6 i n [ 2 3 ] ; {(A) and ( B ) , measured a t 20°C]. 157 F i g . 11-29. V a r i a t i o n of w i t h temperature f o r C 6D 6 i n [5] and [ 2 3 ] , and C 6D 5CH 2D i n [ 6 ] . 158 s p l i t t i n g . From these v a l u e s , i t i s c l e a r t h a t r a p i d r o t a t i o n o c c u r s p r i n c i p a l l y about the C 6 a x i s ; an a d d i t i o n a l a n g u l a r f l u c t u a t i o n of the a x i s would account f o r the s m a l l e r v a l u e o b s e r v e d e x p e r i m e n t a l l y f o r complex [ 5 ] , I n t e r e s t i n g l y , i t i s p o s s i b l e t o f r e e z e out t h i s a n g u l a r f l u c t u a t i o n by d e c r e a s i n g the temperature of sample [ 5 ] , as i n d i c a t e d by the l a r g e r q uadrupole s p l i t t i n g v a l u e s o b t a i n e d a t lower t e m p e r a t u r e s ( F i g . 11-30). F u r t h e r m o r e , the m o l e c u l a r motion can a l s o be p e r t u r b e d f u r t h e r by r a i s i n g the temperature up t o a l i m i t of 90°C. Above t h i s t e m p e r a t u r e , steady " d i s t i l l a t i o n " of benzene from the annu l u s makes i t d i f f i c u l t t o o b t a i n a spectrum. When the experiment i s performed i n a s e a l e d tube, the f r e e benzene appears as a s i n g l e peak c e n t e r e d a t the Larmor f r e q u e n c y , and a t h e r m a l e q u i l i b r i u m e x i s t s between the guest and the h o s t . The a x i a l l y symmetric powder s p e c t r a 8 1 observed s u g g e s t , a t l e a s t f o r h i g h e r t e m p e r a t u r e s , t h a t the benzene m o l e c u l e may a l s o r e o r i e n t about a second d i f f u s i o n a x i s p e r p e n d i c u l a r t o the r a p i d l y r o t a t i n g C 6 a x i s . S i n c e the benzene r i n g assumes an u p r i g h t p o s i t i o n w i t h i n the i n c l u s i o n c h a n n e l , b o t h t h e c h a n n e l and the second d i f f u s i o n axes a re l i k e l y t o be c o l i n e a r . As a consequence of m o t i o n a l a v e r a g i n g a l o n g t h i s a x i s , the qu a d r u p o l e s p l i t t i n g o bserved f o r the pure C 6 r o t a t i o n would be f u r t h e r reduced by a g e o m e t r i c f a c t o r of (3cos 290° - 1)/2, t o a f f o r d a v a l u e of 35.1 kHz. In the case of 0 -159 F i g . 11-30. 2H-N.m.r. s p e c t r a of C 6D 6 i n [ 5 ] : (A) i n un s e a l e d and (B) i n s e a l e d t u b e s , r e c o r d e d a t the t e m p e r a t u r e s i n d i c a t e d . 160 c y c l o d e x t r i n p e r a c e t a t e complex [ 2 3 ] , the m o b i l i t y of the guest m o l e c u l e i s r e s t r i c t e d by the c a v i t y s i z e t o r o t a t i o n about i t s C 6 a x i s , even a t h i g h e r t e m p e r a t u r e s . A s i m i l a r d i f f e r e n t i a l was found f o r o< - d , - t o l u e n e , C 6H 5CH 2D, s e q u e s t e r e d i n the same two host m o l e c u l e s [3] and [ 4 ] . The observed s p l i t t i n g s measured a t 20°C ( F i g . I I -31) a re 29 and 40 kHz, r e s p e c t i v e l y . The l a t t e r v a l u e i s c l o s e t o t h a t (45 kHz) e x p e c t e d 8 8 f o r f a s t r o t a t i o n of a methyl group about i t s C 3 a x i s . A d d i t i o n a l f a s t motion about the l o n g m o l e c u l a r a x i s i n which the a r o m a t i c r i n g undergoes molecular- r e o r i e n t a t i o n , may be the source of the s m a l l a d d i t i o n a l r e d u c t i o n o b s e r v e d . That same motion would a l s o e x p l a i n the r e s u l t s d e s c r i b e d e a r l i e r from the d i p o l a r d ephasing 1 3 C spectrum of [ 6 ] . I t s h o u l d be n o t e d 9 2 t h a t r e o r i e n t a t i o n of t o l u e n e p r e c i s e l y about i t s l o n g a x i s would not f u r t h e r a l t e r the powder p a t t e r n of the methyl group because the r e d u c t i o n f a c t o r c o r r e s p o n d i n g t o (3cos 20° - l ) / 2 i s u n i t y . Presumably, the f a s t motion o c c u r s about an a x i s , z', which i s t i l t e d s l i g h t l y away from the l o n g m o l e c u l a r a x i s ( F i g . 1 1 - 3 2 ) . On h e a t i n g the sample above ambient t e m p e r a t u r e , the t o l u e n e g r a d u a l l y d i s t i l l e d o f f and t h i s was accompanied by a de c r e a s e d q u a d r u p o l e s p l i t t i n g ; a r e d u c t i o n i n s p l i t t i n g was not obv i o u s f o r y 3 - c y c l o d e x t r i n p e r a c e t a t e complex [ 2 4 ] , I n t u i t i v e l y , i t seemed r e a s o n a b l e t o expect an i n c r e a s e i n motion w i t h i n c r e a s e i n d i s t a n c e of the pendant group from t h e a n n u l u s , due t o d e c r e a s e d energy b a r r i e r s t o 161 F i g . 11-31. 2H-N.m.r. s p e c t r a of (A) C 6H 5CH 2D i n [ 6 ] ; (B) C 6H 5CH 2D i n .[24]; (C) C 6H 5CH 2CH 2D i n [ 7 ] ; (measured a t 20°C). 162 F i g . 11-32. M o l e c u l a r r e o r i e n t a t i o n of t o l u e n e a l o n g the z'-ax i s. a l i p h a t i c c o n f o r m a t i o n a l changes. T h i s i s n i c e l y i l l u s t r a t e d by the dec r e a s e i n the magnitude of the quadrupole s p l i t t i n g a t 20°C i n g o i n g from the 2,6-di-O-Me-fi-CD complex of C 6H 5CH 2D (29 kHz), t o t h a t of C 6H 5CH 2CH 2D (<5 kHz) ( F i g . 11-33). For f a s t motion about the l o n g m o l e c u l a r a x i s , t he quadr u p o l e s p l i t t i n g of the methyl group would be reduced by a f u r t h e r f a c t o r of ( 3 C O S 2 1 0 9 . 5 ° - 1)/2, t o g i v e a v a l u e of about 15 kHz. The sh a r p , i s o t r o p i c - l i k e , peak obse r v e d a t ambient temperature f o r complex [7] sug g e s t s t h a t the a r o m a t i c r i n g of 163 (  62.5 F i g . 11-33, 0 kHz — r ~ i — -62.5 62.5 70°C 1 7°C 42°C 80°C 0 kHz "62.5 2H-N.m.r. s p e c t r a of (A) C 6H 5CH 2D i n [6] and (B) C 6H 5CH 2CH 2D i n [7] r e c o r d e d a t the temp e r a t u r e s i n d i c a t e d . 1 64 e t h y l b e n z e n e a l s o r e o r i e n t s about a s i m i l a r a x i s as t o l u e n e . On c o o l i n g the sample t o -90°C, the observed s p l i t t i n g of complex [7] i n c r e a s e d t o 37 kHz. T h i s o b s e r v a t i o n i n d i c a t e s t h a t the m o l e c u l a r motion i s almost c o m p l e t e l y c o n f i n e d t o the meth y l group, w i t h some a d d i t i o n a l motion of the a l i p h a t i c c h a i n b e i n g r e s p o n s i b l e f o r the s l i g h t r e d u c t i o n of the quad r u p o l e s p l i t t i n g from the 44 kHz v a l u e e x p e c t e d f o r a pure methyl r o t a t i o n . 8 8 D i a n i n ' s I n c l u s i o n Complexes  11.7. I n t r o d u c t i o n D i a n i n ' s compound [ 3 0 ] , which i s a nonsugar host m o l e c u l e , was i n c l u d e d i n t h i s c h a p t e r so t h a t some comparison can be made w i t h the c y c l o d e x t r i n s . I t forms c r y s t a l l i n e i n c l u s i o n complexes w i t h a l a r g e v a r i e t y of l i q u i d guest m o l e c u l e s . So, i t i s r a t h e r d i f f i c u l t t o f i n d a s u i t a b l e noncomplexing s o l v e n t t o d i s s o l v e the d e s i r e d s o l i d s u b s t r a t e which i s t o be i n c l u d e d . Encaged guest m o l e c u l e s such as ar g o n , s u l f u r d i o x i d e , ammonia, benzene, d e c a l i n , and d i - t e r t . - b u t y l n i t r o x i d e have been r e p o r t e d . 9 3 The s t r u c t u r e of t h i s h o s t m o l e c u l e was unambiguously e s t a b l i s h e d by Baker e t a l . 9 * i n the m i d - f i f t i e s . A decade and a h a l f l a t e r , d e t a i l e d X-ray s t u d i e s 9 5 c o n f i r m e d the t r u e cage s t r u c t u r e f o r the c h l o r o f o r m , e t h a n o l and 1-h e p t a n o l complexes, and f o r the u n s o l v a t e d c r y s t a l . As d i s t i n c t from c y c l o d e x t r i n s where i n c l u s i o n complexes and the f r e e h o s t have d i f f e r e n t c r y s t a l 1 65 s t r u c t u r e s , the s t r u c t u r e s of the complexes of D i a n i n ' s compound a r e independent of the encaged o r g a n i c g u e s t s . They b e l o n g t o space group R3, w i t h 18 m o l e c u l e s per u n i t c e l l . 9 3 S i x h o s t m o l e c u l e s of compound [ 3 0 ] , 4-p-hydroxy-p h e n y l - 2 , 2 , 4 - t r i m e t h y l c h r o m a n , a r e r e q u i r e d t o make up the h o u r g l a s s - s h a p e d cage; the ends of each cage a r e formed by t h e i r hydrogen-bonded h y d r o x y l groups, w i t h a l t e r n a t e host m o l e c u l e s p o i n t i n g up and down w i t h r e s p e c t t o the p l a n e of the hexagonal OH r i n g ( F i g . 11-34; A and B ) . The c o n s t r i c t i o n a t the mi d d l e i s formed by s i x i n w a r d - p o i n t i n g methyl groups, one from each of the s i x host m o l e c u l e s . For s m a l l e r guest s u b s t r a t e s such as e t h a n o l or a c e t o n e , two m o l e c u l e s a r e h e l d i n the wider p a r t s of the cage, w h i l e f o r l a r g e r g u e s t s such as benzene, t o l u e n e , or p - x y l e n e the cage i s s i n g l y o c c u p i e d . L i k e the c y c l o d e x t r i n s , the c a v i t y s i z e of t h i s host m o l e c u l e can be a l t e r e d . Removal of the p r o t r u d i n g methyl groups ( F i g . II-34C) c o u l d b r i n g about a marked change t o the c a v i t y , i n which the w a i s t would be c o m p l e t e l y e l i m i n a t e d . I t has been s h o w n 9 6 t h a t removal of e i t h e r g eminal m e t h y l group of host [30] does not l e a d t o a c o l l a p s e of the cage s t r u c t u r e and, a t the same t i m e , the analogues s t i l l r e t a i n the a b i l i t y t o form i n c l u s i o n complexes. Hence, i t i s p o s s i b l e t o study the m o l e c u l a r r e o r i e n t a t i o n of a guest m o l e c u l e w i t h i n t h e s e c a v i t i e s . 166 F i g . 11-34. The s t r u c t u r e s of D i a n i n ' s compound (A and B) and m o d i f i e d D i a n i n ' s compound which l a c k s the 2-methyl groups t r a n s t o the p-hydroxypheny1 s u b s t i t u e n t (C) (from Ref. [ 9 3 ] ) . 11 .8 . S y n t h e s i s In 1914 D i a n i n 9 7 d i s c o v e r e d t h a t compound [30] c o u l d be p r e p a r e d by c o n d e n s a t i o n of phenol (2 mol) and m e s i t y l o x i d e (1 mol) as shown below: HCl 2C 6H 5OH + (CH 3) 2C=CHCOCH 3 > [30] 167 S u b s e q u e n t l y , the f o r m u l a of t h i s compound was e s t a b l i s h e d by Baker and McOmie, 9 8 who a l s o improved on the s y n t h e t i c method. The crude p r o d u c t was r e c r y s t a l l i z e d from e t h a n o l which was then removed by vacuum s u b l i m a t i o n , t o a f f o r d the f r e e h o s t m a t e r i a l . The i n c l u s i o n complexes of benzene [ 3 1 ] , t o l u e n e [ 3 2 ] , and p - x y l e n e [33] were p r e p a r e d by r e c r y s t a l l i z a t i o n of compound [30] from the r e s p e c t i v e l i q u i d - g u e s t compounds. 11.9. R e s u l t s and D i s c u s s i o n I n c l u s i o n complexes [ 3 1 ] , [ 3 2 ] , and [33] were chosen f o r the s t u d y because of t h e i r s i m i l a r i t y t o 2,6-di-O-Me-/3-CD i n c l u s i o n complexes, i n which t h e r e i s one guest m o l e c u l e per c a v i t y . The s o l i d - s t a t e 1 3C-c,p.-m.a.s. s p e c t r a of D i a n i n ' s i n c l u s i o n complexes w i t h nonaromatic guest m o l e c u l e s have been p r e v i o u s l y r e p o r t e d . 9 9 S i m i l a r r e s u l t s were o b t a i n e d i n t h i s s tudy w i t h a r o m a t i c guest m o l e c u l e s , which cause l i t t l e or no p e r t u r b a t i o n of the c r y s t a l s t r u c t u r e of the h o s t ( F i g . 11-35). The asymmetric u n i t i n the u n i t c e l l i s one complete m o l e c u l e ; t h u s , no more than 18 r e s o l v a b l e resonances a r e a n t i c i p a t e d . I t i s not s u r p r i s i n g t h a t sharp peaks a r e o b s e r v e d , as the host m o l e c u l e s a r e merely l i n k e d t o g e t h e r by hydrogen bonding. T h i s i s not t r u e f o r c y c l o d e x t r i n s where d i s t o r t i o n of the g l y c o s i d i c l i n k a g e s may cause s p l i t t i n g s of the carbon r e s o n a n c e s . A c c o r d i n g t o R i p m e e s t e r , 9 9 p a r t i a l assignment of the 168 150 100 50 P-P . m . 0 F i g . 11-35. 1 3C-n.m.r. s p e c t r a of D i a n i n ' s compound and i t s i n c l u s i o n complexes, w i t h o u t and w i t h d i p o l a r d ephasing ( t o p and bottom s p e c t r a , r e s p e c t i v e l y ) : (A) [ 3 0 ] ; ( B ) [ 3 1 ] ; (C) [ 3 2 ] ; (D) [ 3 3 ] . 169 B ~1 150 F i g . 11-35 c o n t ' d J 1 — i — i — | — i — i — i — i — i — i — i — i — ' i 1 • 1 1 r 100 50 p.p.m. 0 170 c F i g . 11-35 c o n t ' d 171 D 172 1 3 C resonances i s made p o s s i b l e by the use of the d i p o l a r d e phasing t e c h n i q u e . The methyl groups (C-17,C-18,C-19) are a s s i g n e d on the b a s i s of t h e i r l o c a t i o n s i n the c r y s t a l l a t t i c e . The lo w e s t f i e l d methyl carbon resonance can be a s s i g n e d to C-17, which i s s i t u a t e d c l o s e t o two p h e n y l r i n g s . Of the two geminal methyl groups, the inward-p o i n t i n g methyl carbon would be d e s h i e l d e d most by the encaged a r o m a t i c s u b s t r a t e s . The h i g h f i e l d methyl resonance, which i s most s e n s i t i v e t o the a r o m a t i c 7 r - c l o u d and r i n g s i z e , i s then a s s i g n e d t o C-18. The r e m a i n i n g e i g h t p r o t o n a t e d r i n g carbons have been a s s i g n e d 1 0 0 by s e l e c t i v e d e u t e r a t i o n of the m o l e c u l e ( F i g . I I - 3 5 A ) . The s p e c t r a of D i a n i n ' s complexes r e v e a l a s m a l l peak c o r r e s p o n d i n g t o C-18 of the f r e e h o s t m o l e c u l e . A l b e i t the host t o guest r a t i o i s g e n e r a l l y 6:1 ( i . e . , 1 guest m o l e c u l e per c a v i t y ) f o r l a r g e r guest s p e c i e s , a r a t i o of 7:1 has been r e p o r t e d i n the l i t e r a t u r e f o r a number of m o l e c u l e s . The method used f o r the a n a l y s i s 9 " of th e s e t h r e e i n c l u s i o n complexes was by l o s s i n weight on h e a t i n g , which was found t o be l e s s a c c u r a t e , e s p e c i a l l y f o r the b o r d e r l i n e c a s e s . Hence, t h e r e i s a p o s s i b i l i t y t h a t some cages a r e c o m p l e t e l y empty, which would then account f o r the above o b s e r v a t i o n . T h i s c o u l d happen t o the analogous c y c l o d e x t r i n complexes d i s c u s s e d e a r l i e r , but the s p e c t r a are t oo c o m p l i c a t e d t o r e v e a l the presence of t h i s phenomenon. I t s h o u l d be noted t h a t the l i n e s h a p e s of the geminal 1 73 methyl carbons a re a f f e c t e d t o d i f f e r e n t e x t e n t by the t h r e e a r o m a t i c guest m o l e c u l e s . The C-18 resonance broadens g r a d u a l l y as the benzene i s r e p l a c e d by t o l u e n e , and then by p - x y l e n e . The l a t t e r spectrum a l s o shows a s l i g h t s p l i t t i n g of the C-19 resonance i n t o a d o u b l e t . T h e r e f o r e , these methyl carbons a r e most s e n s i t i v e t o changes i n l o c a l e n v i ronment. The 1 3 C resonances of the guest m o l e c u l e s a r e s h i f t e d u p f i e l d w i t h r e s p e c t t o t h e i r i s o t r o p i c c h e m i c a l s h i f t v a l u e s measured i n the " f r e e " s t a t e . The a r o m a t i c 7r-cloud of the D i a n i n ' s m o l e c u l e s p r o b a b l y g e n e r a t e s an area of h i g h e l e c t r o n d e n s i t y i n the host c a v i t y and/ t h e r e f o r e , i m p a r t s a s t e r i c c o m p r e s s i o n s h i f t t o the guest m o l e c u l e s . T h i s was not seen i n the analogous complexes of 2,6-di-O-Me-0-CD, i n which the 1 3 C resonances of the g u e s t s a r e not s h i f t e d . The d i p o l a r d e p h a s i n g s p e c t r a of t h e s e complexes i n d i c a t e t h a t the guest m o l e c u l e s a r e undergoing m o l e c u l a r r e o r i e n t a t i o n w i t h i n the c a v i t y of the h o s t . A comparison i s made, of the m o l e c u l a r motion undertaken by benzene and t o l u e n e i n the c a v i t i e s of 2,6-di-O-Me-0-CD and D i a n i n ' s compound. B e f o r e d i s c u s s i n g t h i s s t u d y , i t would be h e l p f u l i f t he o r i e n t a t i o n s of the guest m o l e c u l e s were known i n the l a t t e r compounds. S i n c e X-ray d a t a a re not a v a i l a b l e , one has t o r e l y on o t h e r r e l a t e d c r y s t a l s t r u c t u r e s t o f i x the p o s i t i o n of the a r o m a t i c r i n g w i t h i n the c a v i t y . Most l i k e l y , the r i n g would s t a y i n an u p r i g h t p o s i t i o n as shown 174 i n F i g . 11-36. i • i . i • i , F i g . 11-36. S t r u c t u r e of D i a n i n ' s compound d e p i c t i n g the o r i e n t a t i o n of the a r o m a t i c guest m o l e c u l e . I t has been demonstrated e a r l i e r t h a t the benzene m o l e c u l e w i t h i n the c a v i t y of hos t [4] i s f r e e t o r o t a t e about i t s C 6 a x i s , w i t h f u r t h e r a d d i t i o n a l a n i s o t r o p i c motions suggested f o r i n c l u s i o n i n h o s t [ 3 ] . I n t e r e s t i n g l y , the d e u t e r i u m n.m.r. spectrum of the D i a n i n ' s complex of benzene-dg a f f o r d s a q u a d r u p o l e s p l i t t i n g of 16 kHz. In t h i s c a s e , the benzene r i n g would undergo r a p i d d i f f u s i o n a l r o t a t i o n about i t s C 2 a x i s , i n which case the C-D bonds would be a t 60 ± 1° t o the a x i s of m o t i o n a l a v e r a g i n g . The s p l i t t i n g i s then g i v e n by (assuming >1 = 0) A\)<a, = A\)a (3cos 260° - 1 ) 2 175 which i s about 17 kHz. O p e l l a e t a l . 1 0 1 have d e f i n e d the freq u e n c y e x p r e s s i o n s f o r the s p e c t r a l d i s c o n t i n u i t i e s t o i n c l u d e *j ( F i g . 11-37) . v. = v. = ±v = ± V y y ± 3_ e 2qQ (1 64 h ±V„ ± 3_ e 2qQ (1 - 3"? ) 32 h * Isotropic -200 0 200 kHz F i g . 11-37. T h e o r e t i c a l 2H-N.m.r. s p e c t r a of p o l y c r y s t a l l i n e p h e n y l a l a n i n e - d 5 where e 2qQ/h = 180 kHz and ^ = 0.05. ( B ) , powder . p a t t e r n a v e r a g e d by f a s t 180° f l i p s about the Cp-CV a x i s . ( C ) , powder p a t t e r n a veraged by f a s t r o t a t i o n about the Ca-Cy a x i s (from Ref. [ 1 0 1 ] ) . r B e s i d e s the s p l i t l i n e s h a p e , t h e r e i s a l s o a sharp " i s o t r o p i c " peak h a v i n g a w i d t h of <2 kHz. T h i s c o u l d be due t o a r e s i d u a l amount of " f r e e " benzene, which was not 176 F i g . 11-38. 2H-N.m.r. s p e c t r a of (A) C 6D 6 i n [ 3 1 ] ; (B) C 6H 5CH 2D i n [ 3 2 ] . 177 removed c o m p l e t e l y by d r y i n g the c r y s t a l l i n e sample i n vacuo. S i n c e a r a p i d i s o t r o p i c motion of benzene would p r e c l u d e g e n e r a t i n g i t s 1 3C s i g n a l i n a c.p.-m.a.s. spectrum, i t i s i m p o s s i b l e t o v e r i f y such a f i n d i n g by t h i s method. The d e u t e r i u m spectrum of the e q u i v a l e n t complex of C 6H 5CH 2D r e v e a l s a l i n e s h a p e of w i d t h 35 kHz. I t c o r r e s p o n d s t o f a s t r o t a t i o n of the methyl group, w i t h a d d i t i o n a l f a s t motion about the l o n g a x i s . A g a i n , an i s o t r o p i c peak i s p r e s e n t i n the spectrum. 1 1 . 1 0 . Summary and C o n c l u s i o n s C y c l o d e x t r i n s a r e p r o b a b l y the most i m p o r t a n t example of compounds t h a t e x h i b i t s the " h o s t - g u e s t " r e l a t i o n s h i p . A v a r i e t y of o r g a n i c m o l e c u l e s has been used i n the s y n t h e s i s of t h e s e complexes w i t h host m o l e c u l e s [3] and [ 4 ] . S i n c e c r y s t a l s t r u c t u r e s a r e not a v a i l a b l e f o r e i t h e r of the two h o s t m o l e c u l e s or f o r t h e i r i n c l u s i o n complexes, the s t u d i e s r e p o r t e d here p r o v i d e new i n f o r m a t i o n f o r t h e s e systems as d i s c u s s e d i n t h i s c h a p t e r . However, the i n t e r p r e t a t i o n s g i v e n here have been f a c i l i t a t e d by comparison w i t h the 1H- and 1 3C-n.m.r. s t u d i e s of t h e s e complexes i n s o l u t i o n , and w i t h the X-ray data of the guest m o l e c u l e s themselves and of r e l a t e d g u e s t - h o s t complexes. I t was found t h a t the sugar resonances of c y c l o d e x t r i n s a r e r e l a t i v e l y b r o a d, and a r e o f t e n c o m p l i c a t e d by the s u b s t a n t i a l s p l i t t i n g s induced by the 178 presence of the guest m o l e c u l e s . R e c i p r o c a l s h i f t s are induced f o r the g u e s t s ; those of the s m a l l e r guest m o l e c u l e s were found t o be l e a s t a f f e c t e d by the c a v i t y s i z e of the host m o l e c u l e [ 3 ] , and t h e i r i s o t r o p i c c h e m i c a l s h i f t v a l u e s are s i m i l a r t o t h o s e measured f o r s o l u t i o n s . Those m o l e c u l e s which undergo a n i s o t r o p i c motion w i t h i n the c a v i t y , c o u l d be d e t e c t e d by the d i p o l a r dephasing t e c h n i q u e . Deuterium q u a d r u p o l e echo s p e c t r o s c o p y p r o v i d e d d i r e c t e v i d e n c e c o n c e r n i n g the m o l e c u l a r motion of the guest m o l e c u l e s and c o u l d be i n t e r p r e t e d by comparison w i t h r e s u l t s r e p o r t e d i n the l i t e r a t u r e f o r o t h e r systems. The n o v e l a s p e c t of t h i s study i s t h a t i t draws q u a l i t a t i v e c o n c l u s i o n s about the a n i s o t r o p i c m o t i o n a l b e h a v i o r of s e v e r a l guest m o l e c u l e s i n the c a v i t i e s of host c y c l o d e x t r i n s [ 3 ] and [ 4 ] . I t s h o u l d be noted t h a t i n t e r p r e t i n g of 2H l i n e s h a p e s of the guest m o l e c u l e s i n some i n t e r m e d i a t e s t a t e of the h o s t / g u e s t environments may, i n g e n e r a l , be q u i t e d i f f i c u l t . However, the p r e s e n t study s u p p o r t s p r e v i o u s r e p o r t s 7 8 ' 8 1 t h a t the d e u t e r i u m q u a d r u p o l e method can p r o v i d e u s e f u l i n f o r m a t i o n p e r t a i n i n g t o m o l e c u l a r motion of complex o r g a n i c systems; t h i s p o t e n t i a l i s f u r t h e r enhanced by the ease, and low c o s t w i t h which s p e c i f i c d e u t e r a t i o n can be a c h i e v e d . As a r e s u l t of i n s t r u m e n t a l l i m i t a t i o n s a t U.B.C. d u r i n g the time of t h i s r e s e a r c h , i t was not easy t o expand t h i s work f u r t h e r t o i n c l u d e o t h e r i n t e r e s t i n g i n c l u s i o n 179 complexes. N e v e r t h e l e s s , s u f f i c i e n t d a t a of i n t e r e s t have been c o l l e c t e d f o r the s e c y c l o d e x t r i n s and t h e i r i n c l u s i o n complexes. S i n c e the c a v i t y of hos t m o l e c u l e [4] c o u l d o n l y t r a p s m a l l a r o m a t i c m o l e c u l e s , the number of complexes formed i s s e v e r e l y l i m i t e d . S e v e r a l p o t e n t i a l host m o l e c u l e s ( o t h e r c y c l o d e x t r i n d e r i v a t i v e s ) c o u l d have been s y n t h e s i z e d whereby the c a v i t y s i z e i s changed g r a d u a l l y . For i n s t a n c e , 6 - d e o x y - / 3 - c y c l o d e x t r i n may be used t o p r e p a r e h e p t a k i s ( 6 - d e o x y - 2 - 0 - m e t h y l ) - / 3 - c y c l o d e x t r i n and 6-deoxy-/3-c y c l o d e x t r i n p e r a c e t a t e . Here, the c a v i t i e s [of the C(6) s i d e ] a re e x p e c t e d t o be l a r g e r than those of compounds [3] and [ 4 ] . Thus, l a r g e r o r g a n i c m o l e c u l e s , which c o u l d not be t r a p p e d e a r l i e r , would p r o b a b l y f i n d some s u c c e s s w i t h t h e s e m o d i f i e d , p o t e n t i a l h o s t m o l e c u l e s . The i n c l u s i o n of d a t a from the r e s u l t i n g complexes would have been a bonus t o the d i s c u s s i o n on the r e l a t i o n s h i p between m o t i o n , s t r u c t u r e and s t a b i l i t y . C l e a r l y t h e n , c y c l o d e x t r i n s r e p r e s e n t c a r b o h y d r a t e systems which can be e x c i t i n g and v a l u a b l e t o s t u d y . I t i s hoped t h a t more a t t e n t i o n w i l l be f o c u s s e d on the use of m o d i f i e d c y c l o d e x t r i n s i n m i c r o -e n c a p s u l a t i o n of s e n s i t i v e a r o m a t i c s u b s t a n c e s , p h a r m a c e u t i c a l s , h e r b i c i d e s and i n s e c t i c i d e s . 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I n t r o d u c t i o n The a b i l i t y of sugars and t h e i r d e r i v a t i v e s t o s e q u e s t e r m e t a l s i s of i n t e r e s t t o the p o s s i b l e development of n o v e l c l a s s e s of metal-based a f f i n i t y chromatography m a t e r i a l s , 1 of c h i r a l homogeneous c a t a l y s t s , 2 of m e t a l -c h e l a t o r s f o r c l i n i c a l u s e , 3 and of models f o r b i o l o g i c a l l y i m p o r t a n t c h e l a t e s . " Other ongoing i n t e r e s t s i n c l u d e n.m.r. i n v e s t i g a t i o n s of m e t a l i o n b i n d i n g t o s u g a r s . As an e x t e n s i o n of a l o n g - s t a n d i n g i n t e r e s t i n our own l a b o r a t o r y i n h i g h - r e s o l u t i o n n.m.r. s t u d i e s of "metal c o n j u g a t i o n " by s u g a r s , i t was a p p r o p r i a t e then t o examine th e s e complexes i n the s o l i d s t a t e . The metal-complexes i n v o l v e d here can be c l a s s i f i e d i n t o two c l a s s e s , those which a r e d i a m a g n e t i c and o t h e r s which a re p a r a m a g n e t i c . The study of paramagnetic m o l e c u l e s by n.m.r. has had a tremendous impact on the c h e m i c a l and b i o l o g i c a l s c i e n c e s . A l t h o u g h t h i s f i e l d o r i g i n a t e d i n the e a r l y 1950's, t h e r e was i n i t i a l l y doubt of i t s p o t e n t i a l because i t was f e a r e d t h a t paramagnetic compounds would f u r n i s h n.m.r. s p e c t r a t h a t were broadened too e x t e n s i v e l y t o be of any s i g n f i c a n c e . In 1975, a w e l l - r e s o l v e d spectrum of n i c k e l o c e n e , [Ni ( C 2 H 5 ) 2 ] , was r e p o r t e d by McC o n n e l l and Holm. 5 S i n c e t h e n , the use of n.m.r. s p e c t r o s c o p y f o r s t u d y i n g such complexes has s u r p a s s e d the i n t e r e s t shown f o r the d i a m a g n e t i c c o u n t e r p a r t s . A n a l y s i s of paramagnetic s h i f t s and r e l a x a t i o n r a t e s p r o v i d e s u s e f u l i n f o r m a t i o n about the m o l e c u l a r geometry of the complex, i t s dynamic 190 b e h a v i o r , and/or the d i s t r i b u t i o n of u n p a i r e d e l e c t r o n s i n the l i g a n d s k e l e t o n of paramagnetic metal i o n complexes i n the s o l u t i o n s t a t e . N e v e r t h e l e s s , o p t i m a l development of t h i s f i e l d has been s e v e r e l y hampered by the e v i d e n t l a c k of any source of a c l e a r d e s c r i p t i o n of the p h y s i c a l p r i n c i p l e s of the phenomenon, or of the i n t e r p r e t a t i o n of the r e s u l t i n g magnetic resonance p a r a m e t e r s . 6 The l a t t e r r e q u i r e s knowledge of the l i g a n d f i e l d t h e o r y , of e l e c t r o n paramagnetic resonance, of magnetic s u s c e p t i b i l i t y , and of the o p t i c a l p r o p e r t i e s of t r a n s i t i o n m e tal complexes. In t h i s a r e a of s t u d y , the s y n t h e s i s of s p e c i f i c monomeric, m e t a l - s u g a r compounds was i n i t i a l l y u n d e r t a k e n . S c h i f f ' s base l i g a n d s were o b t a i n e d by combining amino sugars w i t h a r o m a t i c a l d e h y d e s , f o l l o w e d by c o m p l e x a t i o n w i t h s u i t a b l e m e tal i o n s . S u b s e q u e n t l y , s t u d i e s were made of the c h e l a t i n g p o l y m e r s , c h i t i n and a l g i n a t e , which can be o b t a i n e d i n enormous q u a n t i t i e s from n a t u r a l s o u r c e s . Then, f o l l o w i n g o t h e r r e c e n t a t t e m p t s t o improve the m e t a l -c h e l a t i n g c a p a b i l i t y by c h e m i c a l d e r i v a t i z a t i o n of the n a t i v e p o l y m e r , 7 c h i t o s a n S c h i f f ' s bases were s t u d i e d . A l t h o u g h t h i s study r e p r e s e n t s o n l y a b e g i n n i n g , i t c l e a r l y w a r r a n t s f u r t h e r e v a l u a t i o n of the m e r i t s of u s i n g s o l i d -s t a t e 1 3C-n.m.r. methods. 191 111 .2 . Paramagnet i c s i n S o l u t i o n  111.2.1. R e l a x a t i o n P r o c e s s e s C o n s i d e r i n g a paramagnetic i o n i n s o l u t i o n , the s p i n energy l e v e l s i n an e x t e r n a l f i e l d , B 0, can be w r i t t e n a s 6 E T = g/SBoS* - q„P„B0Iz + a I z S z (1) where "g" and "0" a r e the e l e c t r o n i c s p e c t r o s c o p i c s p l i t t i n g f a c t o r and Bohr magneton, r e s p e c t i v e l y , "a" i s the h y p e r f i n e c o u p l i n g c o n s t a n t , "g^" and ")3 N" a r e the n u c l e a r "g" v a l u e and magneton, r e s p e c t i v e l y , "Sz." i s the z-component of the e l e c t r o n s p i n , and " I z n i s the z-compqnent of the n u c l e a r s p i n . The a l l o w e d n u c l e a r t r a n s i t i o n s A I Z = ±1 and A I S = 0 a r e shown as v e r t i c a l arrows i n F i g . 111 — 1. The two l i n e s would be obse r v e d i n the n.m.r. spectrum w i t h f r e q u e n c i e s hV, = g„/3„B0 - l / 2 ( a ) (2) hv* = g„/3*B0 + l / 2 ( a ) (3) and t h e i r s e p a r a t i o n i s e q u a l t o " a " . R e l a x a t i o n of n u c l e i i n t h i s k i n d of s o l u t i o n i s o f t e n dominated by the h y p e r f i n e i n t e r a c t i o n between the n u c l e a r s p i n and the u n p a i r e d e l e c t r o n s p i n . The s t r o n g l o c a l f i e l d produced by the e l e c t r o n can be c o u p l e d t o the n u c l e i by s i m p l e " d i p o l a r " i n t e r a c t i o n and the "Fermi h y p e r f i n e c o n t a c t " i n t e r a c t i o n . S i n c e the e l e c t r o n r e l a x a t i o n or 1 92 ELECTRON ZEEMAN NUCLEAR ZEEMAN HYPERFINE j{q$+trH)B._ j<q)3+1^ )3,-1 o 4 4 > -l(gg-tytl)BrT(^-"tiyN'^T° , i _ i v -7<gMyN)B.-j<g/9+fyN)B.-jo F i g . 111 — 1. Energy l e v e l s f o r a p r o t o n w i t h weak h y p e r f i n e c o u p l i n g t o an e l e c t r o n . V e r t i c a l arrows r e p r e s e n t a l l o w e d n u c l e a r t r a n s i t i o n s (from Ref. [ 6 ] ) . e l e c t r o n exchange i s so r a p i d on the n.m.r. time s c a l e , the d o u b l e t s h o u l d c o l l a p s e i n t o a s i n g l e peak. The r e s u l t a n t peak i s not c e n t e r e d midway between the components of the d o u b l e t , but i s s l i g h t l y s h i f t e d due t o the unequal p o p u l a t i o n s of the e l e c t r o n s p i n s t a t e s , by the c o n t a c t s h i f t . The e x p e c t e d case of two s h i f t e d peaks has never been observed s i n c e f o r such slow e l e c t r o n r e l a x a t i o n , p r o t o n s m a g n e t i c a l l y c o u p l e d t o the e l e c t r o n s w i l l be r e l a x e d v e r y e f f i c i e n t l y g i v i n g r i s e t o broad resonance l i n e s t h a t c o u l d not be d e t e c t e d . E l e c t r o n s r e l a x i n g w i t h e x a c t l y the same freq u e n c y as 193 the h y p e r f i n e c o u p l i n g c o n s t a n t , a/h ( i n H z ) , a r e most e f f i c i e n t a t broade n i n g the spectrum. The l i f e t i m e of an e l e c t r o n s p i n s t a t e i s r e l a t e d t o T, e, the e l e c t r o n - s p i n r e l a x a t i o n t i m e , which i s a measure of the time taken f o r energy t o be t r a n s f e r r e d between a p a i r of l e v e l s such as the 1+1/2, -1/2> and | - l / 2 , - l / 2 > . T* e, the e l e c t r o n exchange t i m e , i s c h a r a c t e r i s t i c of the time spent by the l i g a n d a t the p a r t i c u l a r m e t a l s i t e . 8 I f 1/T i e >> a/h or 1/T*e >> a/h, the resonance s i g n a l would appear a t a p o s i t i o n which i s the average of the two f r e q u e n c i e s and V 2 w e i g h t e d by the p o p u l a t i o n s of the two e l e c t r o n s p i n s t a t e s . a/h i s t y p i c a l l y 10 8 Hz, w h i l e T i e i s g e n e r a l l y i n the range of 10~ 9 t o 1 0 ~ 1 1 s, so t h a t i n p r a c t i c e , 1/T,e >> a/h. Thus, the average t r a n s i t i o n energy i s g i v e n b y 6 = /[(g^Bo) - l / 2 ( a ) ] + f [(g„0NBo) + i / 2 ( a ) ] U J-i (4) where f, and / are the f r a c t i o n s of the m o l e c u l e s i n the |+1/2> and |-l/2> e l e c t r o n s p i n s t a t e s , r e s p e c t i v e l y . S i n c e the n u c l e i a r e d i v i d e d between the l e v e l s a c c o r d i n g t o the Boltzmann d i s t r i b u t i o n , i t f o l l o w s t h a t L- 1 + (g/3B0/kT) - 1 (2 + g/3B 0/kT)~ 1 (-g/JBo/kT) (2 - g/3B0/kT) - 1 ( 5 ) (6) 1 94 so t h a t Eq.(4) becomes h%) = 4 g N f i , B„ + qgB 0a/kT a g N0„B o + q<3B0a (4 - g 2 0 2 B o 2 / k 2 T 2 ) 4kT (7) s i n c e the q u a n t i t y g 2/3 2B 0 2 / k 2 T 2 i s n e g l i g i b l e . The i s o t r o p i c s h i f t (or c o n t a c t s h i f t ) i s then g i v e n by where AS) i s the s h i f t from the c o r r e s p o n d i n g p o s i t i o n i n the d i a m a g n e t i c complex, and V 0 i s the i r r a d i a t i n g f r e q u e n c y . The d i r e c t i o n of the s h i f t depends on the s i g n The r e l a x a t i o n t i m e s T, and T 2 of n u c l e i bound t o , or n e a r , a p aramagnetic c e n t e r , a r e u s u a l l y w e l l r e p r e s e n t e d by the c l a s s i c a l Solomon-Bloembergen e q u a t i o n s . 9 ' 1 0 These e x p r e s s i o n s a r e based on a n a l y s i s of the d i p o l e - d i p o l e i n t e r a c t i o n between the e l e c t r o n and n u c l e a r s p i n s , and of the i s o t r o p i c n u c l e a r - e l e c t r o n s p i n exchange i n t e r a c t i o n . More r e c e n t l y , t h e r e have been s e v e r a l developments i n the t h e o r y of n u c l e a r s p i n r e l a x a t i o n i n paramagnetic systems. S a b i r o v 1 1 has r e v i e w e d the case by c o n s i d e r i n g a l l p o s s i b l e t r a n s i t i o n s caused by e l e c t r o n - n u c l e a r i n t e r a c t i o n . A s i m i l a r approach has been developed by Bergen et a l . , 1 2 who have d e r i v e d a n a l y t i c a l e x p r e s s i o n s f o r e l e c t r o n and n u c l e a r r e l a x a t i o n t i m e s i n the g e n e r a l c a s e , where the g-f a c t o r may be a n i s o t r o p i c and the n i n e h y p e r f i n e (8) of "a I! 1 95 i n t e r a c t i o n t e n s o r components may a l l be d i f f e r e n t . I l l . 2 . 2 . E l e c t r o n - S p i n R e l a x a t i o n I t has been mentioned e a r l i e r t h a t T i e s h o u l d be of the o r d e r of 10" 1 1 s or l e s s i f w e l l - r e s o l v e d n.m.r. s p e c t r a a r e t o be o b t a i n e d f o r paramagnetic complexes. However, the observed t r a n s i t i o n s a re not as s h a r p as those o b s e r v e d f o r the d i a m a g n e t i c e q u i v a l e n t s . S e v e r a l f a c t o r s which can l e a d t o s h o r t e l e c t r o n r e l a x a t i o n t i m e s were d i s c u s s e d e x t e n s i v e l y d u r i n g the 1 9 6 0 s . 1 3 Only a b r i e f summary of some g e n e r a l o b s e r v a t i o n s 6 based on f i r s t row t r a n s i t i o n metal i o n systems i s g i v e n h e r e . For those s p e c i e s c o n t a i n i n g a s i n g l e u n p a i r e d e l e c t r o n (S = 1/2) such as o r g a n i c f r e e r a d i c a l s , broad n.m.r. s p e c t r a a re ob s e r v e d because t h e r e i s no z e r o f i e l d s p l i t t i n g ( z . f . s . ) t o cause e f f i c i e n t e l e c t r o n - s p i n r e l a x a t i o n . E x c e p t i o n s occur f o r complexes (S ^ 1) w i t h t r i p l y degenerate (T) ground s t a t e s , where the presence of s m a l l low-symmetry d i s t o r t i o n s , or s p i n - o r b i t c o u p l i n g , produces l o w - l y i n g e x c i t e d s t a t e s which g r e a t l y d i m i n i s h T i e . These i n c l u d e o c t a h e d r a l complexes h a v i n g the f o l l o w i n g c o n f i g u r a t i o n s : d 2 , low s p i n - d " , low s p i n - d 5 , h i g h s p i n - d 6 , and h i g h s p i n - d 7 . When l a r g e d i s t o r t i o n s from o c t a h e d r a l symmetry e x i s t i n the complexes, the T s t a t e s a r e s p l i t and the n.m.r. s p e c t r a o f t e n become br o a d e r . T e t r a h e d r a l complexes w i t h T ground s t a t e s a l s o r e s u l t i n sh a r p n.m.r. s p e c t r a ; t h i s i s t y p i c a l of Co 2* systems. 196 T a b l e 111 -1 summarizes the r e s u l t s p r e s e n t e d i n e a r l i e r i n v e s t i g a t i o n s on e l e c t r o n r e l a x a t i o n . The e n t r i e s i n t h i s t a b l e a r e g e n e r a l l y c o n s i s t e n t w i t h the c o n c l u s i o n s made on the b a s i s of the a n t i c i p a t e d e l e c t r o n - s p i n r e l a x a t i o n mechanism. 111.2.3. I s o t r o p i c S h i f t s I n t e r a c t i o n s between n u c l e i and u n p a i r e d e l e c t r o n s a r e c a p a b l e not o n l y of a f f e c t i n g n u c l e a r r e l a x a t i o n t i m e s , but a l s o of p r o d u c i n g s h i f t s of many o r d e r s of magnitude g r e a t e r than those a r i s i n g from s h i e l d i n g e f f e c t s i n d i a m a g n e t i c m o l e c u l e s . I t i s i m p o r t a n t t o a p p r e c i a t e t h a t the o bserved s h i f t can have c o n t r i b u t i o n s from at l e a s t t h r e e e f f e c t s : c o n t a c t s h i f t , 1 " d i p o l a r s h i f t , 1 5 and c o m p l e x a t i o n (or d i a m a g n e t i c ) s h i f t . Hence, c o r r e c t i o n f o r the s m a l l d i a m a g n e t i c s h i f t i s n e c e s s a r y b e f o r e h a n d i n o r d e r t o show the presence of a paramagnetic induced s h i f t . The c o n t a c t s h i f t , AVC , i s sometimes r e f e r r e d t o as the Fermi or i s o t r o p i c c o n t a c t s h i f t . T h i s i n t e r a c t i o n i s g e n e r a l l y t r a n s m i t t e d t h r o u g h c h e m i c a l bonds t o the a p p r o p r i a t e n u c l e u s and, t h e r e f o r e , i t i s d i r e c t l y r e l a t e d t o the amount of u n p a i r e d s p i n t h a t i s d e l o c a l i z e d onto the l i g a n d . A c o n t a c t s h i f t i s o b s e r v e d when the e l e c t r o n i c r a d i a l wave f u n c t i o n has a f i n i t e v a l u e a t a g i v e n n u c l e u s . Assuming an i s o t r o p i c g v a l u e f o r the system, Eq. (8) can be w r i t t e n i n the f o l l o w i n g form 197 Geometry S p i n s t a t e d 1 d 2 d 3 d" d 5 d 6 d 7 d 8 d 9 High + - + + 0 + + Low + + b -* T d High -* 0* +* + 0 + • + + + P l a n a r High + +* +* + c 0 F i v e -c o o r d i n a t e H i g h -* 0* 0* + + +* + + 0 Table 111 — 1. Ground s t a t e s of t r a n s i t i o n m e t a l i o n s as a f u n c t i o n of d c o n f i g u r a t i o n , geometry, and s p i n s t a t e (from Ref. [ 6 ] ) . P l u s (+) i n d i c a t e s T,e i s u s u a l l y s h o r t enough t o y i e l d narrow n.m.r. l i n e s ; minus (-) i n d i c a t e s T,e i s g e n e r a l l y too l o n g t o y i e l d u s e f u l n.m.r. s p e c t r a ; z e r o (0) i n d i c a t e s b o r d e r l i n e c a s e s ; a s t e r i s k (*) i n d i c a t e s p r e d i c t e d q u a l i t y of as an y e t unobserved c o n f i g u r a t i o n . bDiamagnet i c . c L o w - s p i n , d i a m a g n e t i c . 1 98 /A\ g/3S(S+1 ) = /A\ \f\j 3 k T 7 v I ft/ <S Z> (9) where S i s the t o t a l e l e c t r o n s p i n , and 7^ i s the magnetogyric r a t i o of the n u c l e u s ( d e r i v e d from g N/3 N = 'fiyhl). " a " , which i s f o r o n e - e l e c t r o n systems, has been r e p l a c e d by "A" f o r the m a n y - e l e c t r o n system. <S Z> i s the average v a l u e of Sz over the s p i n l e v e l s , and i t i s u s u a l l y r e f e r r e d t o as the averaged e l e c t r o n s p i n p o l a r i z a t i o n . Another mechanism, which can produce c h e m i c a l s h i f t s , i s the pseudocontact or d i p o l a r s h i f t , AVpC; i t i s a through-space i n t e r a c t i o n between l i g a n d n u c l e i and u n p a i r e d e l e c t r o n s on the metal i o n . T h i s s h i f t i s o n l y o b s e r v e d i f the magnetic f i e l d produced by the l a t t e r i s not averaged t o z e r o , t h a t i s , i t i s a n i s o t r o p i c . Thus, the e q u a t i o n f o r t h i s s h i f t depends on the symmetry of the g-f a c t o r and t a k e s i t s s i m p l e s t form f o r d i s s o l v e d complexes w i t h a x i a l l y symmetric g - t e n s o r s ( i . e . , g x = g t g z ) . 8 d i s t a n c e , and 6 i s the a n g l e between the e l e c t r o n - n u c l e a r v e c t o r and the symmetry a x i s of the g - f a c t o r . The ps e u d o c o n t a c t term c o n t a i n s i n f o r m a t i o n r e l a t i n g t o (10) where g z = g and g x = g x , r i s the e l e c t r o n - n u c l e a r 199 m o l e c u l a r geometry and t h i s has been r i g o r o u s l y e v a l u a t e d . I f the g - f a c t o r i s i s o t r o p i c , then t h e r e w i l l be no s h i e l d i n g e f f e c t a r i s i n g from the d i p o l a r i n t e r a c t i o n s w i t h the u n p a i r e d e l e c t r o n . The t o t a l observed i s o t r o p i c s h i f t i s the a l g e b r a i c sum of t h e s e two s h i f t s : 8 In most complexes, both A V t and AVpc c o n t r i b u t e t o the t o t a l o b s e r v e d s h i f t , but i t i s p o s s i b l e t o d e s i g n systems such t h a t one of the i n t e r a c t i o n s dominates. For e x a m p l e , 1 6 o c t a h e d r a l N i ( I I ) and t e t r e h e d r a l C o ( I I ) a r e m a g n e t i c a l l y i s o t r o p i c , t h e r e f o r e , the c o n t r i b u t i o n from A V p c i s s m a l l . In the case of l a n t h a n i d e complexes, the u n p a i r e d e l e c t r o n s a r e d e e p l y b u r i e d i n the 4f o r b i t a l s , w i t h v e r y l i t t l e d e l o c a l i z a t i o n onto the l i g a n d s . Hence, the c o n t r i b u t i o n from AVc t o the o b s e r v e d s h i f t would be n e g l i g i b l e . L i n e b r o a d e n i n g of l i g a n d s i g n a l s i s commonly a s s o c i a t e d w i t h paramagnetic m e t a l complexes i n s o l u t i o n -s t a t e n.m.r. s t u d i e s . In o r d e r t o observe t h e s e s i g n a l s , i t i s n e c e s s a r y , i n most c a s e s , t o use low c o n c e n t r a t i o n s of the paramagnetic i o n r e l a t i v e t o the l i g a n d . T h i s c r e a t e s a s m a l l number of o b s e r v e d n u c l e i i n the "M" environment ( c o o r d i n a t i o n sphere) compared t o t h a t i n the "0" AV; ISO A V C + A V p c (11) 200 environment ( o u t s i d e ) , and the r e s u l t a n t observed spectrum e s s e n t i a l l y c o n s i s t s of a s i n g l e peak f o r the p a r t i c u l a r k i n d of n u c l e u s . S w i f t and C o n n i c k 1 7 have developed e q u a t i o n s f o r such a s i t u a t i o n ; the l i n e w i d t h of t h i s peak, T / i ' T ^ o b s d , and i t s f r e q u e n c y s h i f t , A u M ( i n a n g u l a r f r e q u e n c y t e r m s ) , r e l a t i v e t o the fr e q u e n c y of the 0 environment, a r e g i v e n by T2j> 1 = T 2 o b s d " 1 ~ T 2 o ~ 1 (T 2 M- 1 + TM~ 1 )T Z W- 1 + AOJM 2 (12) 2~ T M (T l M- 1 + T M " 1 ) + pq Aw M (13) where p i s the r a t i o of m e t a l - t o - l i g a n d c o n c e n t r a t i o n s , q i s the number of c o o r d i n a t e d l i g a n d s per m e t a l i o n , and T M i s the l i f e t i m e of the l i g a n d i n the c o o r d i n a t i o n sphere. T 2 Q and T 2 |^ a r e the r e l a x a t i o n t i m e s of the n u c l e i i n the f r e e l i g a n d and i n the c o o r d i n a t i o n s p h e r e , r e s p e c t i v e l y . The l a t t e r i s d e r i v e d from the Solomon-Bloembergen e q u a t i o n . The a d j u s t e d r e l a x a t i o n r a t e , T 2 p ~ 1 , and i s o t r o p i c s h i f t , Au>p, measure t h e paramagnetic c o n t r i b u t i o n t o t h e s e o b s e r v e d p a r a m e t e r s . 201 111.3. Paramaqnetics i n the S o l i d S t a t e 111.3.1. C h a r a c t e r i s t i c s of Paramagnetic S p e c t r a I n t r o d u c t i o n of a s m a l l amount of a paramagnetic " i m p u r i t y " has been w i d e l y used i n the s o l i d s t a t e t o de c r e a s e p r o t o n r e l a x a t i o n t i m e s . 1 8 ' 1 9 The use of paramagnetic r e a g e n t s t o induce c h e m i c a l s h i f t d i s p e r s i o n i s s t i l l l a r g e l y u n e x p l o r e d . 2 0 T h i s i s because a paramagnetic m o l e c u l e , or i o n , has d i f f i c u l t y i n d i f f u s i n g r a p i d l y among m o l e c u l e s of i n t e r e s t t o g i v e a f a s t exchange-averaged r e s u l t a n t s h i f t , t he magnitude of which would be governed by the c o n c e n t r a t i o n of the paramagnetic s p e c i e s . The same l a c k of r a p i d m o l e c u l a r t u m b l i n g a l s o a l l o w s the f u l l development of v a r i o u s t y p e s of magnetic a n i s o t r o p y i n the s o l i d s t a t e which can c o m p l i c a t e the observe d l i n e - s h a p e s and s p e c t r a l r e s o l u t i o n . The c o m p e t i t i o n between p a r a m a g n e t i c a l l y i n d u c e d - s h i f t and -r e l a x a t i o n u l t i m a t e l y d e c i d e s the r e s o l u t i o n o b t a i n a b l e f o r the spectrum. E l e c t r o n s p i n r e l a x a t i o n i s n o r m a l l y r a p i d i n s o l i d t r a n s i t i o n m e t a l complexes and the n u c l e a r s p i n s e x p e r i e n c e an averaged e l e c t r o n p o l a r i z a t i o n , <S Z>. <S Z> = qgB 0S(S+1) (14) 3kT S i n c e the d i p o l a r and Fermi c o n t a c t i n t e r a c t i o n s a r e p r o p o r t i o n a l t o <S Z>, the observ e d s h i f t s i n c r e a s e l i n e a r l y 202 w i t h the i n v e r s e of t e m p e r a t u r e . W e l l - r e s o l v e d s p e c t r a a re observ e d when the s h i f t s become l a r g e compared w i t h the i n t r i n s i c l i n e w i d t h of the i n d i v i d u a l t r a n s i t i o n . Hence, low-temperature n.m.r. i n v e s t i g a t i o n s can p r o v i d e v a l u a b l e i n f o r m a t i o n about t h e s e i n t e r a c t i o n s . 2 1 As mentioned e a r l i e r , the d i p o l a r i n t e r a c t i o n depends on the geometric f a c t o r (1 - 3 c o s 2 0 ) / r 3 ; t h u s , by measuring the d i p o l a r terms, i t i s p o s s i b l e t o det e r m i n e the r e l a t i v e p o s i t i o n s of the n u c l e i i n the l i g a n d s w i t h r e s p e c t t o the c e n t r a l paramagnetic i o n . A l t h o u g h the d i p o l a r i n t e r a c t i o n f a l l s o f f as 1 / r 3 , i t i s s t i l l p o s s i b l e f o r n e i g h b o r i n g e l e c t r o n s p i n s t o p a r t i c i p a t e i n t h i s i n t e r a c t i o n . The resonance s h i f t f o r a d i l u t e paramagnetic s o l i d i s g i v e n b y 6 where 8 i s the a n g l e between the v e c t o r c o n n e c t i n g the e l e c t r o n and n u c l e a r s p i n , and the e x t e r n a l magnetic f i e l d B 0. The o t h e r symbols have been d e f i n e d e a r l i e r . In c o n c e n t r a t e d paramagnetic samples, a g i v e n n u c l e a r s p i n i n t e r a c t s not o n l y w i t h the e l e c t r o n s p i n on the p a r e n t m o l e c u l e , but a l s o w i t h n e i g h b o r i n g e l e c t r o n s p i n s as w e l l . Eq. (15) must then c o n s i d e r a l l p o s s i b l e i n t e r m o l e c u l a r and i n t r a m o l e c u l a r c o n t r i b u t i o n s t o the e l e c t r o n - n u c l e a r i n t e r a c t i o n s . 2 2 203 < Vo / 'so = - <Sz > Bo 9*2 (1 - 3 c o s2 0 i ) 7-—3 + <S Z> J A 7 WB 0 f f i (16) The f i r s t term of Eq. (16) r e p r e s e n t s the a n i s o t r o p i c c o n t r i b u t i o n t o the s h i f t , and i t c o n t a i n s a summation over a s e r i e s of a n g l e s and d i s t a n c e s . The second term b e l o n g s t o the Fermi c o n t a c t i n t e r a c t i o n , i n which the i s o t r o p i c h y p e r f i n e c o u p l i n g c o n s t a n t i s n o r m a l l y dominated by the i n t r a m o l e c u l a r term. However, i n some c a s e s , a n e i g h b o r i n g m o l e c u l e may c o n t r i b u t e t o t h i s c o u p l i n g c o n s t a n t . 111. 3. 2. S p e c t r a l Assignments C.p.-m.a.s. 1 3C-n.m.r. s p e c t r o s c o p y has been a p p l i e d t o paramagnetic complexes, but the s p e c t r a a r e u s u a l l y broad and more d i f f i c u l t t o i n t e r p r e t 2 0 than t h e i r d i a m a g n e t i c c o u n t e r p a r t s . I t i s o n l y i n s i t u a t i o n s where T i e i s e x t r e m e l y s h o r t t h a t s h a r p resonances a r e o b s e r v e d . However, the br o a d e n i n g e f f e c t s can be of a i d i n making assignments of 1 3 C reso n a n c e s . More i m p o r t a n t l y , i f some e s t i m a t e of the p r o x i m i t y of v a r i o u s n u c l e i t o the paramagnetic c e n t e r can be d e r i v e d from the l i g a n d geometry, then assignments may be made on the b a s i s of r e l a t i v e l i n e w i d t h s , p r o v i d e d the d i f f e r e n c e s i n v o l v e d a r e a p p r e c i a b l e . When t h i s i s used as an a i d t o s p e c t r a l a s s i g n m e n t s f o r paramagnetic systems, comparison w i t h the analogous d i a m a g n e t i c s p e c i e s i s o f t e n made. 204 111 • 4. S y n t h e s i s 111.4.1 . S c h i f f ' s Base F o r m a t i o n S c h i f f ' s bases a r e compounds which c o n t a i n the azomethine group; they are u s u a l l y formed by the c o n d e n s a t i o n of a p r i m a r y amine w i t h an a c t i v e c a r b o n y l compound. The compound of the l a t t e r type c o n s i d e r e d here i s m a i n l y 2-hydroxybenzaldehyde ( s a l i c y l a l d e h y d e ) [ l ] . In 1922 I r v i n e and E a r l 2 3 f i r s t r e p o r t e d the s y n t h e s i s of s a l i c y l a l d i m i n e compounds ( S c h i f f ' s bases formed from s a l i c y l a l d e h y d e or s u b s t i t u t e d s a l i c y l a l d e h y d e compounds) from glucosamine (2-amino-2-deoxy-a,/3-D-glucopyranose) h y d r o c h l o r i d e [ 2 ] . NHjCl [1] [2] Not s u r p r i s i n g l y , " b l o c k e d " glucosamine d e r i v a t i v e s such as methyl 3 , 4 , 6-tri-0-acetyl-2-amino-2-deoxy-/3-D-g l u c o p y r a n o s i d e hydrobromide [ 3 ] 2 * and 1,3,4,6-tetra-O-a c e t y l - 2 - a m i n o - 2 - d e o x y - 0 - D - g l u c o p y r a n o s e [ 4 ] 2 5 a l s o r e a c t w i t h s a l i c y l a l d e h y d e t o a f f o r d the c o r r e s p o n d i n g S c h i f f ' s bases [5] and [6] as shown below. Compounds [5] and [6] a r e c r y s t a l l i n e , b r i g h t y e l l o w , s t a b l e d e r i v a t i v e s . However, they a r e a c i d - and base-l a b i l e ; f o r these r e a s o n s , a r o m a t i c a l d e h y d e s are 205 c o n v e n i e n t l y used as amino b l o c k i n g groups f o r amino s u g a r s . They a r e s t a b l e t o c o l d , anhydrous a c y l a t i n g r e a g e n t s , and hence the amino sugar [ 4 ] 2 5 can be p r e p a r e d by t h i s approach: a n i s a l d e h y d e (p-methoxybenzaldehyde) [8] was used as an amino b l o c k i n g group t o y i e l d the S c h i f f ' s base [ 9 ] , which was s u b s e q u e n t l y a c e t y l a t e d and c l e a v e d as shown (see Pg. 206). 111.4.2. S c h i f f ' s Base M e t a l Complexes For m e t a l c o m p l e x a t i o n t o o c c u r w i t h t h e s e S c h i f f ' s b a s e s , the h y d r o x y l f u n c t i o n on the a r o m a t i c r i n g must be brought i n t o c l o s e p r o x i m i t y w i t h the n i t r o g e n atom of the 206 Ml] [6] sugar m o i e t y , p r e f e r a b l y by s t r o n g hydrogen bonding. I t i s known 2 6 t h a t c y c l o h e x y l s a l i c y l a l d i m i n e can form b i s -s t r u c t u r e complexes [11] w i t h s e v e r a l d i v a l e n t m e t a l s . The analogous sugar d e r i v a t i v e s [5] and [6] were t h e r e f o r e e x p e c t e d t o s e r v e as p o t e n t i a l l i g a n d s as w e l l . When a m e t h a n o l i c s o l u t i o n of c u p r i c a c e t a t e was added t o a hot 207 m e t h a n o l i c s o l u t i o n of compound [ 5 ] , the brown c o p p e r ( l l ) sugar complex [12] c r y s t a l l i z e d r e a d i l y i n good y i e l d . [13] R, = Me, R 2 = H , M = Zn [14] R, = Me, R 2 =H, M = Co [15] R, = Ac, R2 =H, M = Cu [16] R, =Me, R 2=Br, M = Cu S i m i l a r l y , b oth z i n c and c o b a l t o u s a c e t a t e have been shown t o form complexes w i t h l i g a n d [ 5 ] , but i n low y i e l d s . 2 7 The sugar s a l i c y l a l d i m i n e l i g a n d [6] a l s o forms a c o p p e r ( I I ) complex [ 1 5 ] , Cu(Sug I I - s a l ) 2 ; however, at t e m p t e d c o m p l e x a t i o n of l i g a n d [6] w i t h z i n c and c o b a l t o u s a c e t a t e s f a i l e d t o y i e l d any p r o d u c t . T h i s c o p p e r ( I I ) complex was o b t a i n e d as s h i n y o l i v e green c r y s t a l s when hot e t h a n o l i c s o l u t i o n s of c u p r i c a c e t a t e and l i g a n d [6] were mixed and a l l o w e d t o c o o l g r a d u a l l y . 208 C h i t o s a n [ 1 8 ] , a polymer of gl u c o s a m i n e , condenses r e a d i l y w i t h a r y l a l d e h y d e s f o l l o w i n g the methods of Nud'ga et a l . 2 8 and H i r a n o e t a l . 2 9 t o g i v e the c o r r e s p o n d i n g S c h i f f ' s b ases. The polymer was f i r s t d i s s o l v e d i n a m i x t u r e of methanol and 1-10 % aqueous a c e t i c a c i d a t room temperature t o a f f o r d a v i s c o u s s o l u t i o n , which was then t r e a t e d w i t h a s o l u t i o n of an a r y l a l d e h y d e . A f t e r a few h o u r s , the r e s u l t a n t g e l was fragmented, and suspended s u c c e s s i v e l y i n methanol, e t h a n o l , and e t h e r over a p e r i o d 209 of 1 d t o remove a c e t i c a c i d and a l d e h y d e . The f i l t e r e d g e l was a i r - d r i e d i n i t i a l l y and f i n a l l y i n vacuo a t 56°C f o r 1 d. The N - s a l i c y l i d e n e c h i t o s a n s , l i k e t h e i r monomeric c o u n t e r p a r t s , r e a d i l y r e a c t w i t h c o p p e r ( I I ) a c e t a t e i n m e t h a n o l i c s o l u t i o n t o a f f o r d c o l o r e d complexes, which have been c h a r a c t e r i z e d by e . s . r . s p e c t r o s c o p y . 3 0 They are a l s o s u i t a b l e f o r c h e l a t i o n of a wide range of m e t a l s o t h e r than copper. 111.5. R e s u l t s and D i s c u s s i o n The c.p.-m.a.s. 1 3C-n.m.r. spectrum of the z i n c sugar complex [ 1 3 ] , Zn(Sug I - s a l ) 2 , a l o n g w i t h t h a t of the p a r e n t l i g a n d [5] a r e shown i n F i g . 111-2. A l t h o u g h the l i n e w i d t h s of the resonances a r e narrow and the peaks w e l l r e s o l v e d , t h e r e i s s t i l l some a m b i g u i t y i n the assignment of i n d i v i d u a l resonances i n the s o l i d s t a t e , even when the s e assignments a r e based on s o l u t i o n s p e c t r a of t h e s e , and r e l a t e d m o l e c u l e s . The presence of the z i n c atom n i c e l y d i s p e r s e s the a r o m a t i c r e g i o n , but o n l y the two n o n p r o t o n a t e d carbons can be d i f f e r e n t i a t e d from the r e s t by the d i p o l a r d ephasing t e c h n i q u e . 3 1 The assignments f o r the p r o t o n a t e d carbons must be c o n s i d e r e d t e n t a t i v e . Not s u r p r i s i n g l y , s m a l l changes o c c u r i n the sugar r e g i o n i n comparison w i t h t h a t of the f r e e l i g a n d . The broad s i g n a l a t 75.82 p.p.m. i s a s s i g n e d t o C-2, and i t i s suggested t h a t the b r o a d e n i n g i s caused by q u a d r u p o l a r i n t e r a c t i o n 210 CH, OCH, SSB -| 1 r 111-2 _j j p- ~i 1 1 r~ 150 100 50 p . p m . 1 3C-C.p.-m.a.s. s p e c t r a of methyl 3 , 4 , 6 - t r i - O -a c e t y l - 2 - d e o x y - 2 - s a l i c y l ideneamino-/3-D-g l u c o p y r a n o s i d e and i t s complex: TA) f r e e l i g a n d [ 5 ] ; (B) d i a m a g n e t i c z i n c ( I I ) complex [ 1 3 ] ; (C) D i p o l a r d ephasing spectrum of the z i n c ( I I ) complex. 21 1 w i t h the 1"N n u c l e u s , not averaged by magic a n g l e s p i n n i n g . 3 2 S u r p r i s i n g l y , m e tal i o n c h e l a t i o n a t the C-1 oxygen and the C-2' n i t r o g e n has no pronounced e f f e c t s on the c h e m i c a l s h i f t s of C-1 and C-2'. I t may be t h a t an up-f i e l d s t e r i c c o m p r e s s i o n s h i f t 3 3 c o u n t e r a c t s the a n t i c i p a t e d l o w - f i e l d s h i f t . The methyl carbon atoms of the a c e t o x y l m o i e t i e s appear as a d o u b l e t of a p p r o x i m a t e l y 2:1 p r o p o r t i o n s , one of which i s u n a f f e c t e d by m e t a l - i n d u c e d s h i f t s . E q u i v a l e n t s p l i t t i n g s of the c a r b o n y l resonances may be o b s c u r e d by the c o m p l e x i t y of t h a t s p e c t r a l r e g i o n . I t has been r e p o r t e d e a r l i e r 2 7 t h a t the 1H-n.m.r. s o l u t i o n - s t a t e spectrum of t h i s complex shows some f r e e l i g a n d which c o u l d not be removed by r e c r y s t a l l i z a t i o n , and i f t h i s complex decomposes i n s o l u t i o n , the p r o p o r t i o n of f r e e l i g a n d i n c r e a s e s and can be m o n i t o r e d . The s i g n a l s from the r e s i d u a l , f r e e l i g a n d a r e marked by a s t e r i s k s . M i c r o a n a l y s i s of the sample used here r e v e a l e d a n e g l i g i b l e amount of f r e e l i g a n d ; t h u s , the s p l i t t i n g of the methyl resonances cannot be a t t r i b u t e d t o resonances from the f r e e 212 l i g a n d . P o s s i b l y i t i s due t o a c r y s t a l l o g r a p h i c e f f e c t . A p a r t from these o b s e r v a t i o n s , n o t h i n g more can be c o n c l u d e d from the s p e c t r a of the f r e e l i g a n d or i t s complex. As s t a t e d e a r l i e r , the observed l i n e w i d t h s of the carbon-13 resonance a r e dependent on T 1 e , which i n t u r n i s dependent on the c o o r d i n a t i o n geometry about the paramagnetic i o n . 6 The s h o r t e r the T, e, the narrower the l i n e w i d t h ; f u r t h e r m o r e , i t i s known t h a t c o p p e r ( l l ) i o n s w i t h a square p l a n a r geometry have a l o n g e r T i e than complexes w i t h a more t e t r a h e d r a l c o o r d i n a t i o n . In g e n e r a l , the former geometry i s f a v o r e d ; i n t h a t geometry the e x c i t e d s t a t e s a re w e l l s e p a r a t e d as a r e s u l t of the Jahn-T e l l e r e f f e c t . A l t h o u g h the complex Cu(Sug I I - s a l ) 2 , [ 1 5 ] , i s c l o s e r t o a square p l a n a r geometry than the Cu(Sug I -s a l ) 2 , [ 1 2 ] , they are b o t h e s s e n t i a l l y b o r d e r l i n e c a s e s i n s o l u t i o n , as e v i d e n c e d from the i . r . s t u d i e s r e p o r t e d e a r l i e r . 2 7 1 3C-C.p.-m.a.s. s p e c t r a of complexes [12] and [15] a r e shown i n F i g . 111-3. No s i g n a l s whatsoever were o b s e r v e d f o r the square p l a n a r complex [ 1 5 ] , because the c o p p e r ( I I ) e l e c t r o n r e l a x a t i o n r a t e i s so slow. On the o t h e r hand, the use of a v e r y s h o r t c o n t a c t time (0.1 ms) i n the c.p.-m.a.s. experiment r e v e a l e d some broad 1 3C resonances f o r the p s e u d o t e t r a h e d r a l complex [ 1 2 ] ; o n l y those sugar resonances which are r e l a t i v e l y remote from the m e t a l c e n t e r were observed. The l i n e b r o a d e n i n g e f f e c t of the 213 F i g . 111-3 . 1 3C-N.m.r. s p e c t r a of paramagnetic c o p p e r ( I I ) complexes: (A) [ 1 5 ] ; (B) and (C) [ 1 2 ] , w i t h c o n t a c t t i m e s of 0.1 and 1 ms, r e s p e c t i v e l y . 214 c o p p e r ( I I ) i o n i s a r e s u l t of the s p i n - s p i n r e l a x a t i o n t i m e , T 2, t o which the l i n e w i d t h i s i n v e r s e l y p r o p o r t i o n a l . I f the e l e c t r o n - t o - c a r b o n - 1 3 d i p o l a r i n t e r a c t i o n i s dominant, T 2 v a r i e s d i r e c t l y w i t h the s i x t h power of the m e t a l - t o - c a r b o n d i s t a n c e ; hence, resonances of carbon atoms c l o s e s t t o the me t a l b i n d i n g s i t e s a r e broadened most. I t s h o u l d be noted t h a t the i s o t r o p i c n u c l e a r - e l e c t r o n s p i n exchange i n t e r a c t i o n need not be l o c a l i z e d t o the donor s i t e , but can a l s o e x t e n d around the a r o m a t i c r i n g , which c o u l d f u r t h e r reduce the T 2 v a l u e s . Thus, the d i s a p p e a r a n c e of the a r o m a t i c resonances i n d i c a t e s extreme b r o a d e n i n g and the b i n d i n g of c o p p e r ( I I ) i o n t o the C-1 oxygen and the C-2' n i t r o g e n . Only the a c e t y l groups of the sugar r i n g s can be observed c l e a r l y , and the o t h e r carbon-13 s i g n a l s appear as a s i n g l e , broad peak t h a t cannot be a s s i g n e d . A l t h o u g h the l i n e w i d t h s a r e r e l a t i v e l y broad i n comparison w i t h those of the d i a m a g n e t i c z i n c ( I I ) complex [ 1 3 ] , the d o u b l e t s f o r the c a r b o n y l and methyl carbon atoms of the a c e t o x y l m o i e t i e s a r e w e l l r e s o l v e d ; t h e i r s e p a r a t i o n s a r e a p p r o x i m a t e l y 7.3 and 10.2 p.p.m., r e s p e c t i v e l y . The e f f e c t of m etal i o n s , paramagnetic or n o t , on the i s o t r o p i c s h i f t s i s n i c e l y i l l u s t r a t e d by these complexes. When the c o n t a c t time was i n c r e a s e d t o 1 ms, a l l of the sugar s i g n a l s d i s a p p e a r e d ; t h i s s u g g e s t s t h a t the s p l i t t i n g s of the a c e t o x y l resonances a re not caused by the presence of f r e e l i g a n d s , which s h o u l d be q u i t e remote from the n e a r e s t m e t a l c e n t e r . T h i s a l s o r u l e s out the 215 p o s s i b i l i t y t h a t such s p l i t t i n g s a r e due t o paramagnetic a n i s o t r o p i c e f f e c t s 2 0 because t h e i r s e p a r a t i o n s a r e c o m p a r a t i v e l y s m a l l and, moreover, the i n t e g r a l r a t i o of the two s i g n a l s i s s i m i l a r t o t h a t measured f o r the analogous d i a m a g n e t i c , z i n c - s u g a r complex. Changing the s u b s t i t u e n t on the anomeric carbon of the sugar r i n g , has a v e r y s u b s t a n t i a l impact on the observed spectrum; compare, f o r example, complexes [12] and [ 1 5 ] . T h i s i s due t o a g e o m e t r i c e f f e c t on the c o n f i g u r a t i o n of the complex. S i m i l a r l y , broad s i g n a l s were obse r v e d f o r Cu(Sug I - x s a l ) 2 , [ 1 6 ] , o n l y f o r c o n t a c t times s e t s h o r t e r than those used f o r complex [12] ( i . e . t c p ^ 0.05 ms); t h i s s u g g e s t s t h a t the g e o m e t r i c a l s t r u c t u r e and T,e, of [16] a r e i n t e r m e d i a t e between those of complexes [12] and [ 1 5 ] . I t i s a p p r o p r i a t e now t o r e v i e w b r i e f l y the ways whereby the r e l a x a t i o n induced by the c o p p e r ( I I ) i o n s , r e s u l t i n the o b s e r v e d e f f e c t s . T h i s i s based most a p p r o p r i a t e l y on the matched Hartmann-Hahn c o n d i t i o n , 3 " a c c o r d i n g t o which, the carbon-13 m a g n e t i z a t i o n grows as M ( t c p ) = C X ~ 1 { 1 - e x p - ( X t C p / T C H ) } e x p ( - t C p / T | f H ) r ' r J (17) where X = 1 + TCH " T CH rp C m H T,j c i s the carbon r o t a t i n g frame r e l a x a t i o n t i m e , and " c " i s a p r o p o r t i o n a l i t y c o n s t a n t . The o t h e r symbols have the u s u a l meanings as d e f i n e d on Pg. 32. Eq. (17) may be s i m p l i f i e d t o g i v e 216 M ( t C p ) = c X " 1 X t C p [ l - tc£_l (18) T C H T , j « T h i s e x p r e s s i o n shows t h a t the carbon m a g n e t i z a t i o n r i s e s w i t h a r a t e , V T C N , and f a l l s o f f as S i n c e T C H i s of the o r d e r of the c a r b o n - p r o t o n T 2 as a r e s u l t of mutual c a r b o n - p r o t o n s p i n f l i p s under the Hartmann-Hahn c o n d i t i o n , t h i s e x p r e s s i o n i s v a l i d when T,^c > T,j >> T C H . For a s u f f i c i e n t l y l o n g v a l u e of T i e (such as f o r complex [ 1 5 ] ) , two p o s s i b l e mechanisms may be i n v o l v e d i n the c o u r s e of the 1 3C-c.p.-m.a.s ex p e r i m e n t : 1) The p r o t o n m a g n e t i z a t i o n decays so r a p i d l y d u r i n g the onset of s p i n l o c k i n g t h a t none remains f o r t r a n s f e r t o the carbon n u c l e i , whose s i g n a l s a r e , t h e r e f o r e , e l i m i n a t e d from the spectrum. 2) The T^" i s so s h o r t e n e d t h a t c r o s s - p o l a r i z a t i o n between s p i n s o c c u r s r a p i d l y , d e c a y i n g as a f u n c t i o n of 1/T,jT . A g r a d u a l d e c r e a s e i n T ^ can r e s u l t i n the appearance of some r e a s o n a b l y broad 1 3 C r e s o n a n c e s , o b s e r v a b l e f o r v e r y s h o r t c o n t a c t t i m e s . Presumably, t h i s l o n g (moderate) T,e modulates the c.p. r a t e (see Pg. 212), which i s s u b s e q u e n t l y d e c r e a s e d . For s i t u a t i o n s where T 1 H (and T i e.) i s of i n t e r m e d i a t e range, c o n v e n t i o n a l s i n g l e - p u l s e 1 3 C n.m.r. w i t h h i g h -power, gated d e c o u p l i n g of the p r o t o n s p i n s can a l s o be used t o o b t a i n the spectrum of complex [12] ( F i g . 111-4). I t s T 1 c and T 2 C a r e r e a s o n a b l y s h o r t ; the d i p o l a r - c a r b o n - 1 3 d i p o l a r i n t e r a c t i o n i s not c o m p l i c a t e d by the s p i n 218 d i f f u s i o n e f f e c t s d i s c u s s e d e a r l i e r . However, no s i g n a l s were obse r v e d f o r complex [15] p r o b a b l y due t o e x t r e m e l y s h o r t r e l a x a t i o n t i m e s . C o b a l t ( l l ) t e t r a h e d r a l or square p l a n a r complexes have the s h o r t T 1 c r e q u i r e d t o produce narrow n.m.r. l i n e s . 6 However, atte m p t e d c o m p l e x a t i o n of l i g a n d s [5] and [6] w i t h t h i s m e t al i o n f a i l e d t o y i e l d the e x p e c t e d p r o d u c t s . A l t h o u g h the complex [14] was p r e p a r e d s u c c e s s f u l l y by Adam, 2 7 i t s s t r u c t u r e was not examined by n.m.r. s p e c t r o s c o p y . S o l i d - s t a t e n.m.r. s t u d i e s of t h i s complex would have o f f e r e d a b e t t e r e v a l u a t i o n of the b e h a v i o r of paramagnetic i o n s w i t h t h e s e sugar l i g a n d s . [17] We have seen i n the p r e c e d i n g d i s c u s s i o n t h a t T 1 e governs the r e s o l u t i o n of the 1 3C-n.m.r. s p e c t r a of paramagnetic s p e c i e s . O r g a n i c f r e e r a d i c a l s r e p r e s e n t a 219 s p i n d o u b l e t system (S = 1/2) i n which T i e i s v e r y l o n g , and t h e i r e . s . r . s p e c t r a are u s u a l l y w e l l r e s o l v e d . 6 Most of them p o s s e s s o r b i t a l l y nondegenerate ground s t a t e s , and f o r those w i t h degenerate ground s t a t e s , the s p i n - o r b i t c o u p l i n g i s s t i l l i n s u f f i c i e n t t o g r e a t l y d i m i n i s h T 1 e . The s p i n - l a b e l l e d sugar complex [ 1 7 ] , which has a sugar moiety i d e n t i c a l t o t h a t of complex [ 1 2 ] , was chosen t o i l l u s t r a t e t h i s p o i n t . L i k e complex [ 1 5 ] , no s i g n a l s can be d e t e c t e d from i t s c.p.-m.a.s. spectrum. A B F i g . I I I - 5 . R e p r e s e n t a t i o n of p o l y m e r i c s t r u c t u r e s : (A) a l g i n a t e ; (B) c h i t o s a n . E x t e n s i o n of t h i s work i n the c o n t e x t of p o l y s a c c h a r i d e s such as c h i t o s a n and a l g i n a t e ( F i g . I I I - 5 ) i s most a p p r o p r i a t e . F i r s t , we note t h a t the m e t a l b i n d i n g s i t e s can be e i t h e r c l o s e l y or d i s t a n t l y spaced, depending on the k i n d of p o l y s a c c h a r i d e i n v o l v e d . The carbon atoms of 220 the polymers which a r e l o c a t e d c l o s e t o the m e t a l - l o c u s , s h o u l d behave s i m i l a r l y t o those of the monomeric, m e t a l -sugar complexes. Those of a d i s t a n t sugar moiety can behave d i f f e r e n t l y , s i n c e t h i s moiety may remain f a r from the m e t a l - b i n d i n g s i t e s . However, the c r y s t a l l i n e or amorphous p a c k i n g of the sample may b r i n g the two zones i n t o c l o s e p r o x i m i t y . Thus, s o l i d - s t a t e n.m.r. t e c h n i q u e s may be u s e f u l not o n l y f o r s t u d i e s of p a r a m a g n e t i c a l l y i n d u c e d -s h i f t s and - r e l a x a t i o n phenomena, but a l s o f o r d e t e r m i n a t i o n of the p r i m a r y s t r u c t u r e of some p o l y s a c c h a r i d e s and t h e i r c h e m i c a l d e r i v a t i v e s . The 1 3C-n.m.r. s p e c t r a of c h i t o s a n [18] and i t s S c h i f f ' s base d e r i v a t i v e s are shown i n F i g . 111-6. Depending on the commercial b a t c h of c h i t o s a n used, the r e s i d u a l amount of N - a c e t y l groups can v a r y by up t o 15 % due t o i n c o m p l e t e h y d r o l y s i s . A h i g h a c e t y l - c o n t e n t can e a s i l y be d e t e c t e d by the presence of the a p p r o p r i a t e carbon r e s o n a n c e s ; t h e i r absence from the spectrum as shown i n F i g . I I I - 6 A , i s i n d i c a t i v e of almost complete d e a c e t y l a t i o n . The 1 3C-n.m.r. spectrum of an amorphous sample of s a l i c y l i d e n e c h i t o s a n [ 1 9 ] , r e v e a l s broad peaks r e f l e c t i n g a d i s p e r s i o n of c h e m i c a l s h i f t s , and the a s s i g n m e n t s of i t s resonances a r e made by comparison w i t h those f o r the r e s p e c t i v e carbon n u c l e i of the s t a r t i n g m a t e r i a l s . The c o p p e r ( I I ) s a l i c y l i d e n e c h i t o s a n complex i s analogous t o Cu(Sug I I - s a l ) 2 i n terms of i t s deep-green c o l o r , and i t s c h a r a c t e r i s t i c e . s . r . spectrum which 221 150 100 50 p. p.m. 0 I I I - 6 . 1 3C-N.m.r. s p e c t r a of c h i t o s a n and i t s S c h i f f ' s base d e r i v a t i v e s : (A) c h i t o s a n [ 1 8 ] ; (B) s a l i c y l i d e n e c h i t o s a n [ 1 9 ] ; (C) 4 - n i t r o -b e n z y l i d e n e c h i t o s a n [ 2 1 ] , 222 i n d i c a t e s a t r u e c h e l a t e . 3 0 A low c a p a c i t y f o r c h e l a t i o n was r e p o r t e d e a r l i e r f o r t h i s polymer, i n t h a t o n l y 20 % of the b i n d i n g s i t e s were o c c u p i e d by c o p p e r ( I I ) i o n s a f t e r a 12 h e q u i l i b r a t i o n w i t h t h e s e i o n s . T h i s i s presumably due t o the low p o r o s i t y of the polymer and i t s i n a b i l i t y t o s w e l l i n aqueous or a l c o h o l i c s o l u t i o n . In t h i s work, an i n c r e a s e i n the c o p p e r - c h e l a t i n g c a p a c i t y was a c h i e v e d [3.29 mmol of c o p p e r ( I I ) per g; 87.4 % of the t h e o r e t i c a l v a l u e ] u s i n g the m o d i f i e d r e a c t i o n procedure g i v e n i n the E x p e r i m e n t a l S e c t i o n . The absence of d e t e c t a b l e carbon resonances can be i n t e r p r e t e d as a r i s i n g from the dense d i s p e r s i o n of c o p p e r ( I I ) i o n s i n the polymer " m a t r i x " ; t h i s causes the resonances of n o n - m e t a l l a t e d monomeric u n i t s t o e x p e r i e n c e a T i e, comparable t o t h a t e x p e r i e n c e d by those which a r e m e t a l l a t e d . T h i s p o i n t i s f u r t h e r i l l u s t r a t e d by the s u b s t a n c e , [ 2 0 ] , p r e p a r e d by r e a c t i n g c h i t o s a n w i t h a m i x t u r e of benzaldehyde and s a l i c y l a l d e h y d e . The c o l o r of the mixed polymer i s l i g h t e r , w i t h or w i t h o u t c o p p e r ( I I ) i o n s when compared t o s a l i c y l i d e n e c h i t o s a n . The r a t i o of b e n z y l i d e n e t o s a l i c y l i d e n e m o i e t i e s i s e s t i m a t e d t o be 2:1 from F i g . 111-7. In the presence of c o p p e r ( I I ) i o n s (2.09 mmol of c o p p e r ( I I ) per g ) , the carbon s i g n a l s of s a l i c y l i d e n e c h i t o s a n d i s a p p e a r e d and those of b e n z y l i d e n e -c h i t o s a n were broadened s i g n i f i c a n t l y ; the l a t t e r p r o b a b l y does not p a r t i c i p a t e i n metal c h e l a t i o n . By s e t t i n g a l o n g e r c o n t a c t time (3 ms), r e a s o n a b l y sharp s i g n a l s were 223 A — i — i — i — i — i — [ — i — i — i — i — i — i — i — ' i r 150 100 50 C F i g . 111-7. 1 3C-N.m.r. s p e c t r a of mixed S c h i f f ' s bases of b e n z y l i d e n e c h i t o s a n and s a l i c y l i d e n e c h i t o s a n [20] w i t h and w i t h o u t c o p p e r ( l l ) i o n s : (A) f r e e l i g a n d ; (B) and (C) copper complexed, w i t h c o n t a c t t i m e s s e t a t 0.5 and 3 ms, r e s p e c t i v e l y . 224 o b t a i n e d , c o r r e s p o n d i n g t o " f r e e " b e n z y l i d e n e c h i t o s a n u n p e r t u r b e d by the d i s t a n t paramagnetic i o n s . I t i s now a p p r o p r i a t e t o c o n s i d e r what e f f e c t s c o p p e r ( I I ) i o n s have on polymers which l a c k any major l o c u s f o r s t r o n g m e t a l c h e l a t i o n . For such compounds i t has been shown 3 5 i n the s o l i d s t a t e t h a t (1/T,) ©CN.a.D., where "N" i s the number of paramagnetic n u c l e i per u n i t volume, "a" i s the d i s t a n c e between n u c l e i , and "D" i s the s p i n -d i f f u s i o n c o n s t a n t d e r i v e d from the s p i n f l i p - f l o p between n u c l e i . At low c o n c e n t r a t i o n s of c o p p e r ( I I ) i o n s i n the polymer m a t r i x , the carbon resonances are e x p e c t e d not t o be s h i f t e d or broadened t o any s i g n i f i c a n t e x t e n t . 4-N i t r o b e n z y l i d e n e c h i t o s a n , [ 2 1 ] , produces a c o p p e r ( l l ) complex which i s b l u e , and which b i n d s 0.74 mmol of c o p p e r ( I I ) per g of the polymer (21.8 % of the t h e o r e t i c a l v a l u e ) . The s p e c t r a i n F i g . I I I - 8 i n d i c a t e t h a t the c o p p e r ( l l ) i o n s d e c r e a s e the r e l a x a t i o n t i m e s of the polymer, but t o a l e s s e r e x t e n t than f o r the s a l i c y l i d e n e -c o p p e r ( I I ) complexes d i s c u s s e d above. S l i g h t amounts of l i n e b r o a d e n i n g were obse r v e d because of the h i g h c o p p e r ( I I ) i o n c o n c e n t r a t i o n , but no measurable s h i f t s were d e t e c t e d f o r the carbon r e s o n a n c e s . Reducing the c o n t a c t time f u r t h e r , t o 0.1 ms o n l y d e c r e a s e d the i n t e n s i t i e s of the n o n p r o t o n a t e d carbon-13 s i g n a l s of the a r o m a t i c r i n g ; t h i s o b s e r v a t i o n would be u n l i k e l y f o r a t r u e m e t a l c h e l a t e . Hence, we c o n c l u d e t h a t the paramagnetic i o n s a r e d i f f u s e d t h r o u g h the m a t r i x , and a r e weakly bound t o the 225 A T I I | I I I I | 1 1 1 1 1 1 1 1 1 p 150 100 50 0 p.p.m. F i g . I I I - 8 . , 3C-N.m.r. s p e c t r a of [ 2 1 ] , "doped" w i t h c o p p e r ( I I ) i o n s . C o n d i t i o n s were: (A) 3 ms and (B) 0.1 ms c o n t a c t t i m e s . 226 m a t r i x by some long-range bonding t o the h y d r o x y l groups. A l g i n a t e may be c o n s i d e r e d as a l i n e a r , b l o c k copolymer of f>-D-mannuronic a c i d and °<-L-guluronic a c i d r e s i d u e s , the r e l a t i v e amounts of which v a r y g r e a t l y f o r a l g i n i c a c i d s from d i f f e r e n t s p e c i e s of a l g a e . 3 6 The s t r u c t u r e c o n s i s t s of t h r e e t y p e s of b l o c k s : homopolymeric b l o c k s of mannuronic a c i d (MM) and of g u l u r o n i c a c i d (GG), and b l o c k s w i t h an a l t e r n a t i n g sequence (MG). I t has been suggested t h a t the metal i o n s a r e s e l e c t i v e l y bound i n the lo n g sequences of GG b l o c k s , and we had hoped t h a t c h e l a t i o n of c o p p e r ( I I ) would e l i m i n a t e the 1 3 C resonances of those b l o c k s , l e a v i n g the o t h e r s s t i l l d e t e c t a b l e . The absence of carbon s i g n a l s i n the spectrum of the copper-a l g i n a t e complex (2.58 mmol of c o p p e r ( I I ) per g ) , suggests t h a t not o n l y the copper( 1 1 ) - c o m p l e x e d r e g i o n s , but r a t h e r the whole p o l y m e r i c u n i t e x p e r i e n c e s a l o n g T1(Z.. T h i s can be e x p l a i n e d by two models: the polymer c o u l d be r i c h i n L -g u l u r o n i c a c i d r e s i d u e s , or the D-mannuronic a c i d r e s i d u e s c o u l d have some a f f i n i t y f o r the me t a l i o n s and/or have been brought c l o s e r t o the b i n d i n g s i t e s by m o l e c u l a r p a c k i n g . I t was d e c i d e d not t o pursue t h i s q u e s t i o n f u r t h e r . I I . 6 . Summary and C o n c l u s i o n s The amino sugars d e s c r i b e d i n t h i s c h a p t e r a re b i o l o g i c a l l y s i g n i f i c a n t i n t h e i r own r i g h t and a l s o as models f o r the amino sugar c o n s t i t u e n t s of a l a r g e number 227 of a n t i b i o t i c s . I t might be e x p e c t e d t h a t the combined presence of sugar- and m e t a l - m o i e t i e s would g i v e these compounds i n t e r e s t i n g b i o l o g i c a l p r o p e r t i e s . Compounds [ 5 ] and [ 6 ] have been known f o r over f i f t y y e a r s and were p r e p a r e d r e a d i l y i n h i g h y i e l d . I t was e x p e c t e d t h a t t h e s e compounds would form m e t a l sugar complexes; however, t h i s o n l y o c c u r r e d r e a d i l y w i t h c o p p e r ( I l ) i o n s . S i m i l a r l y , amino s u g a r - c o n t a i n i n g p o l y s a c c h a r i d e s would be e x p e c t e d t o r e a c t w i t h the same me t a l t o produce a n a l o g s of the monosaccharide complexes. These complexes o f t e n have i n t r a c t a b l e p r o p e r t i e s , and the s o l i d - s t a t e 1 3C-n.m.r. method has been used t o h e l p c h a r a c t e r i z e them. The i s o t r o p i c s h i f t s of d i a m a g n e t i c m e t a l - s u g a r complexes are c l o s e l y s i m i l a r t o those measured f o r the uncomplexed s u g a r - 1 i g a n d s . On the o t h e r hand, b i n d i n g of paramagnetic i o n s has a p r o f o u n d e f f e c t on the o b t a i n a b l e r e s o l u t i o n of the 1 3 C spectrum. H i g h c o n c e n t r a t i o n s of the paramagnetic m e t a l r e s u l t i n broad f e a t u r e l e s s s p e c t r a . I n t e r p r e t a t i o n of the mechanism f o r t h o s e e f f e c t s i s c o m p l i c a t e d by s p i n d i f f u s i o n of the p r o t o n s ; however, the major f a c t o r s appear t o be the T 1 e and the inter-moment d i s t a n c e s as d i s c u s s e d i n t h i s c h a p t e r . S i n c e i t o n l y r e p r e s e n t s an e x t e n s i o n of the 1 3C-c.p.-m.a.s. methods t o the study of m e t a l c h e l a t e s , we b e l i e v e t h a t f u r t h e r i n v e s t i g a t i o n s a r e w a r r a n t e d i n coming t o some g e n e r a l c o n c l u s i o n s . 228 R e f e r e n c e s 1. B. L o n n e r d a l , J . C a r l s s o n , J . P o r a t h , FEBS L e t t . , 75, 89(1977); J . P. L e b r e t o n , i b i d . , 80, 351(1977). 2. W. R. C u l l e n , Y. S u g i , T e t r a h e d r o n L e t t . , 1978, 1635. 3. M. N. Hughes, The I n o r g a n i c C h e m i s t r y of B i o l o g i c a l  P r o c e s s e s , W i l e y , New York, 1974. 4. Y. A. Zhdanov, 0. A. O s i p o v , V. P. G r i g o r i e v , A. D. Garnovsky, Yu F. A l e x e e v , V. G. A l e x e e v a , N. M. Gontmacher,.P. A. Per o v , V. G. Z a l i o t o v , V. N. Formina, T. A. Useman, 0. N. Nechaeva, V. N. M i r n y , Carbohydr. Res., 38, C1(1974). 5. H. M. M c C o n n e l l , C. H. Holm, J . Chem. Phys., 27, 314(1957). 6. G. N. La Mar, W. D. H o r r o c k s , R. H. Holm, NMR of  Paramagnetic M o l e c u l e s , Academic P r e s s , New York, 1973. 7. R. A. A. M u z z a r e l l i , C h i t i n , Pergamon, O x f o r d , 1977. 8. E. Deboer, H. van W i l l i g e n , P r o g . N u c l . Magn. Reson. S p e c t r o s c , 2, 1 1 1 ( 1967); R. S. Drago, J . I . Z i n k , R. M. Richman, W. D. P e r r y , J . Chem. Educ., 5J_, 371(1974). 9. I . Solomon, Phys. Rev., 99, 559(1955). 10. N. Bloembergen, J . Chem. Phys., 27, 572, 595(1957). 11. R. Kh. S a b i r o v , Paramagn. Rezon., J_2, 49(1976). 12. H. A. Bergen, R. M. G o l d i n g , L. C. Stubbs, M o l . Phys., 37, 1371(1979). 13. N. Bloembergen, L.O. Morgan, J . Chem. Phys., 34, 842(1961); A. C a r r i n g t o n , G. R. L u c k h u r s t , M o l . Phys., 8, 125(1964); W. B. L e w i s , L. 0. Morgan, T r a n s i t i o n 229 M e t a l C h e m i s t r y , V o l . 4, Dekker, New York, 1968. 14. H. M. M c C o n n e l l , D. B. C h e s t n u t , J . Chem. Phys., 28, 107(1958). 15. H. M. M c C o n n e l l , R. E. R o b e r t s o n , i b i d . , 29, 1361(1958). 16. W. D. H o r r o c k s , I n o r g . Chem., 9, 690(1970). 17. T. J . S w i f t , R. E. Co n n i c k , J . Chem. Phys., 37, 307(1962) . 18. N. Bloembergen, P h y s i c a (Amsterdam) , J_5, 386(1949). 19. P-G. Gennes De, Phys. Chem. S o l i d s , 7, 345(1958). 20. V. P. Chacko, S. Ganapathy, R. G. B r y a n t , J . Am. Chem. Soc . , J_05, 5491 ( 1 983) . 21. T. S a n d r e c z k i , D. O n d e r c h i n , R. W. K r e i l i c k , i b i d . , 101, 2880(1979). 22. T. S a n d r e c z k i , D. O n d e r c h i n , R. W. K r e i l i c k , J . Magn. Reson., 34, 171 ( 1979) . 23. J . C. I r v i n e , J . C. E a r l , J . Chem. S o c , 121, 2376(1922). 24. J . C. I r v i n e , D. M c N i c o l l , A. Hynd, J . Chem. S o c , 99, 250(1911). 25. M.Bergmann, L. Z e r v a s , Chem. B e r . , 64B, 975(1931). 26. R. H. Holm, G. W. E v e r e t t , J r . , A. C h a k r a v o r t y , Prog. I n o r g . Chem., 7, 83(1966). 27. M. J . Adam, L. D. H a l l , J . Chem. Soc. Chem. Comm., 1979, 234. 28. L. A. Nud'ga, E. A. P l i s k o , S. N. D a n i l o v , Zh. Obshch. Khim., 43, 2752(1973). 230 29. S. H i r a n o , N. Matsuda, 0. M i u r a , H. I w a k i , Carbohydr. Res., 7J_, 339( 1979). 30. L. D. H a l l , M. Y a l p a n i , Carbohydr. Res., 83, C5(1980). 31. S. J . O p e l l a , M. H. F r e y , J . Am. Chem. S o c , 101, 5854(1979). 32. S. J . O p e l l a , J . G. Hexem, M. H. F r e y , T. A. C r o s s , P h i l . T r a n s . Roy. Soc. A, 299, 665(1981). 33. D. M. G r a n t , B. V. Cheney, J . Am. Chem. S o c , 89, 5315(1967). 34. L. B. Alemany, D. M. G r a n t , R. J . Pugmire, T. D. A l g e r , K. W. Z i l m , J . Am. Chem. S o c , 105, 2133(1983) and r e f e r e n c e s t h e r e i n . 35. S. Ganapathy, A. N a i t o , C. A. McDowell, J . Am. Chem. Soc . , J_03, 601 1 ( 1 981 ). 36. D. W. Drummond, E. L. H i r s t , E. P e r c i v a l , J . Chem. S o c , 1 962, 1208. CHAPTER IV EXPERIMENTAL 232 IV. 1 . N u c l e a r Magnetic Resonance IV.1.1. Measurements i n the S o l u t i o n S t a t e Most of s p e c t r a were measured at room temperature u s i n g a Bruker WH-400 (9.4 T) h i g h r e s o l u t i o n s p e c t r o m e t e r equipped w i t h an Aspect 2000 computer, o p e r a t i n g a t 400 MHz f o r 'H and a t 100.6 MHz f o r 1 3 C , and l o c a t e d i n the Department of C h e m i s t r y , U n i v e r s i t y of B r i t i s h Columbia. Some of the 'H-n.m.r. s p e c t r a were a l s o r e c o r d e d a t 270 MHz w i t h a h o m e - b u i l t s p e c t r o m e t e r based on a Bruk e r WP-60 c o n s o l e , a N i c o l e t 1180 computer (32K), a N i c o l e t 293B p u l s e programmer, a D i a b l o d i s k d r i v e (model 3 1 ) , and an Ox f o r d I n s t r u m e n t s s u p e r c o n d u c t i n g s o l e n o i d magnet w i t h a 54 mm. bore s i z e . Samples f o r n.m.r. s p e c t r a were p r e p a r e d i n c o n c e n t r a t i o n s of 0.1 t o 0.4 M. A l l d e u t e r a t e d s o l v e n t s were o b t a i n e d from Merck Sharp and Dohme Canada L t d . and t e t r a m e t h y l s i l a n e (TMS) was used as an e x t e r n a l s t a n d a r d . Data were accumulated i n q u a d r a t u r e d e t e c t i o n mode and s t o r e d on 1 Mbyte d i s k s f o r subsequent p r o c e s s i n g . P r i o r t o F o u r i e r t r a n s f o r m a t i o n , a l l the d a t a were m u l t i p l i e d by an e x p o n e n t i a l l i n e b r o a d e n i n g f u n c t i o n (0.1 Hz f o r 1H and 0.5 Hz f o r 1 3 C ) . IV.1.2. Measurements i n the S o l i d S t a t e A l l s p e c t r a were d e t e r m i n e d i n the F o u r i e r mode u s i n g a Bruker CXP-200 s p e c t r o m e t e r , o p e r a t i n g a t the resonance 233 f r e q u e n c i e s of 200 MHz f o r 'H, 50.3 MHz f o r 1 3 C , and 30.7 MHz f o r 2H. An Aspect 2000 computer was used t o a c q u i r e the d a t a . 1 3C-C.p.-m.a.s. s p e c t r a were o b t a i n e d a t room temperature u s i n g a s i n g l e - c o i l , d o u b l y tuned probe. S p i n -l o c k e d c r o s s - p o l a r i z a t i o n was e s t a b l i s h e d by the s i n g l e -c o n t a c t Hartmann-Hahn p r o c e d u r e , u s i n g a p p l i e d 1H and 1 3 C r . f . f i e l d s of 15 and 60 G, r e s p e c t i v e l y . The p r o t o n d e c o u p l i n g f i e l d was m a i n t a i n e d a t 15 G u s i n g a 1 kW power a m p l i f i e r . In g e n e r a l , a s p e c t r a l w i d t h of 40 kHz, which s e t s up a c o m p u t e r - c o n t r o l l e d f i l t e r bandwidth of 50 kHz, was observed i n 16K d a t a p o i n t s u s i n g an approximate p u l s e a n g l e of 90° (5 ^ s ) and 4K a c q u i s i t i o n . For d i a m a g n e t i c o r g a n i c s o l i d s and s o l i d p o l y m e r s , c o n t a c t times were o p t i m i z e d by measuring the m a g n e t i z a t i o n response t o v a r i a b l e s p i n l o c k i n g t i m e s ( t C p ) r when i n t e g r a t i o n of the carbon resonances was d e s i r e d . The s e t t i n g s , which v a r i e d from 0.5 t o 5 ms, were much l o n g e r than those used f o r the paramagnetic c o u n t e r p a r t s ( t c p ^  0.5 ms). A w a i t i n g time of 12 yu.s, w i t h c o n c o m i t a n t d e c o u p l i n g , between the end of the c r o s s - p o l a r i z a t i o n s t e p and the s t a r t of d a t a a c q u i s i t i o n was used. The r e c e i v e r was b l a n k e d u n t i l the s t a r t of d a t a a c q u i s i t i o n , and an a c q u i s i t i o n time of 50 ms (one d w e l l time) was employed; a t t h a t t i m e , the d e c o u p l i n g power was gated on. In most c a s e s , many a c q u i s i t i o n s (1,000-3,000 t r a n s i e n t s ) were r e q u i r e d t o enhance the s i g n a l - t o - n o i s e r a t i o of low i n t e n s i t y peaks, and r e c y c l e t i m e s of 10-30 s 234 were used. Quadrature d e t e c t i o n and phase a l t e r n a t e d p u l s e s (90°x and 90°-x) were i n c l u d e d i n the e x p e r i m e n t . The l a t t e r t e c h n i q u e was used t o i n v e r t the p r o t o n s p i n temperature so as t o e l i m i n a t e e x p e r i m e n t a l a r t i f a c t s , and t o s i m p l i f y the d a t a a n a l y s i s . Magic a n g l e s p i n n i n g was c a r r i e d out u s i n g an Andrew-Beams r o t o r s made from D e l r i n . I t s s p i n n i n g f r e q u e n c y , e s t i m a t e d from the s p i n n i n g s i d e b a n d s , was 4.2 ± 0.3 kHz. The s u p e r c o n d u c t i n g s o l e n o i d was o p e r a t e d w i t h o u t f i e l d - f r e q u e n c y l o c k because the d r i f t was s m a l l enough t o g i v e a c c u r a t e s h i f t measurements. Thus, the 1 3C-n.m.r. s i g n a l of l i q u i d benzene was used as an e x t e r n a l r e f e r e n c e t o determine the c h e m i c a l s h i f t s , which were s u b s e q u e n t l y e x p r e s s e d as p.p.m. d o w n f i e l d from TMS (benzene i s 128.5 p.p.m. d o w n f i e l d from t h i s r e f e r e n c e ) . For a c c u r a t e r e a d i n g s , i n some c a s e s , c o r r e c t i o n s were made t o the observed c h e m i c a l s h i f t s by m o n i t o r i n g the d r i f t p e r i o d i c a l l y . I n i t i a l l y , the n o n s p i n n i n g 'H f . i . d . of benzene, c o n t a i n e d i n a 10-mm o.d. sample tu b e , was p r o p e r l y shimmed t o a f f o r d a l i n e w i d t h of 10-15 Hz. The d e c o u p l e r o f f s e t was then s e t e x a c t l y on the p r o t o n resonance. Next, the 1 3 C -n.m.r. spectrum of benzene was a c q u i r e d and s t o r e d on a d i s k . The Hartmann-Hahn c o n d i t i o n was a d j u s t e d u s i n g a n o n s p i n n i n g sample of adamantane. S i n c e t h i s i s a s m a l l , " s p h e r i c a l " m o l e c u l e w i t h a h i g h m o b i l i t y i n the c r y s t a l l i n e s t a t e , narrow l i n e w i d t h s a r e e x p e c t e d ; as a r e s u l t , adamantane undergoes r e l a t i v e l y l i t t l e c r o s s -235 p o l a r i z a t i o n , but i t s s i g n a l i s v e r y s e n s i t i v e t o the Hartmann-Hahn match, which i s u s e f u l f o r o p t i m i z i n g t h a t c o n d i t i o n . Hexamethylbenzene was chosen f o r the magic a n g l e adjustment because i t has two e q u a l s e t s of c a r b o n s . The an g l e of the sample s p i n n i n g a x i s r e l a t i v e t o B 0 was a d j u s t e d t o m i n i m i z e the l i n e w i d t h of the a r o m a t i c c a r b o n s , whose l a r g e c h e m i c a l s h i f t a n i s o t r o p y makes them more s e n s i t i v e t o magic-angle m i s s e t t i n g than the methyl c a r b o n s . Two i s o t r o p i c peaks of almost e q u a l i n t e n s i t y were observed when a l o n g e r s p i n l o c k i n g time (5-8 ms) was s e t . Once the c.p.-m.a.s. c o n d i t i o n s were s a t i s f i e d , the r o t o r c o n t a i n i n g hexamethylbenzene was r e p l a c e d . A l l e x p e r i m e n t a l samples (200-300 mg) were spun w i t h compressed a i r i n the D e l r i n r o t o r . 2H-N.m.r. s p e c t r a were r e c o r d e d on the same i n s t r u m e n t u s i n g a 10-mm o.d. sample tube and a quadrupole echo p u l s e sequence. The s p e c t r o m e t e r was a d j u s t e d u s i n g a D 20 sample, and the r . f . f i e l d was then a p p l i e d on resonance. In o r d e r t o ensure minimum d i s t o r t i o n s of the s p e c t r a , phase c o r r e c t i o n s were a l s o c a r r i e d o u t . The r . f . p u l s e w i d t h v a r i e d between 2.5 and 6.0 /<s, depending on the s i z e of the s p e c t r a l w i d t h . A p u l s e s p a c i n g of 100-240 fMS, and r e c y c l e t i m e s of 0.5-1.0 s were used. A l l d a t a were a c q u i r e d i n q u a d r a t u r e w i t h a 0.25-MHz d i g i t i z a t i o n r a t e . S i n c e the exp e r i m e n t s were performed on resonance, F o u r i e r t r a n s f o r m a t i o n r e s u l t e d i n the n e g a t i v e f r e q u e n c i e s of the symmetric spectrum b e i n g f o l d e d over on t o p of t h e p o s i t i v e 236 f r e q u e n c i e s , t h e r e b y i n c r e a s i n g the s i g n a l - t o - n o i s e r a t i o by a f a c t o r of N / 2 . 1 Even so, a g r e a t number of scans (10,000-50,000) were needed t o g i v e a good spectrum. Most of the e x p e r i m e n t s were a l s o performed as a f u n c t i o n of t e m p e r a t u r e . The probehead and the a i r f l o w h e a t i n g system p r o v i d e d by Bruker were used. The temperature at the sample was c o n t r o l l e d w i t h a f l o w of compressed a i r or N 2 gas, and s t a b i l i z e d w i t h a Bruker temperature c o n t r o l u n i t (model B VT 1000), w i t h a p r e c i s i o n of r o u g h l y ±1.5°C. IV.2. G e n e r a l S y n t h e t i c P r o c e d u r e s A l l m e l t i n g p o i n t s were r e c o r d e d u s i n g a F i s h e r - J o h n s m e l t i n g p o i n t a p p a r a t u s and a r e u n c o r r e c t e d . A l l s o l u t i o n s were e v a p o r a t e d u s i n g a Buchi r o t a r y e v a p o r a t o r . T h i n l a y e r chromatography ( t . l . c . ) was performed on 7.5 x 2.5 cm B a k e r - f l e x ( J . T . Baker Chemical Co. N.J.) p r e c o a t e d s i l i c a g e l p l a t e s . The f o l l o w i n g s o l v e n t systems were used: (A) 1:3 v/v m e t h a n o l : e t h y l a c e t a t e ; (B) 1:4 v/v m e t h a n o l : e t h y l a c e t a t e ; (C) 1:1 v/v t o l u e n e : e t h y l a c e t a t e ; (D) 1:4 v/v methanol:benzene. V i s u a l i z a t i o n was e f f e c t e d by s p r a y i n g w i t h 30 % s u l f u r i c a c i d i n e t h a n o l , and h e a t i n g . A l l s o l v e n t s used were of s p e c t r o or reagent grade and, i n most c a s e s , were used w i t h o u t f u r t h e r t r e a t m e n t . For r e a c t i o n s r e q u i r i n g anhydrous ( d r y ) s o l v e n t s , the s o l v e n t s were d r i e d by s t a n d a r d methods, then d i s t i l l e d and s t o r e d under a n i t r o g e n atmosphere. 237 M i c r o a n a l y s e s of the samples were c a r r i e d out by Mr. P. Borda, M i c r o a n a l y s i s L a b o r a t o r y , U n i v e r s i t y of B r i t i s h C o l umbia. Copper m i c r o a n a l y s i s was performed by Canadian M i c r o a n a l y t i c a l S e r v i c e L t d . (Vancouver) u s i n g n i t r i c a c i d d i g e s t i o n of the p o l y s a c c h a r i d e s and atomic a b s o r p t i o n . A l l u l t r a v i o l e t measurements were performed u s i n g a G i l f o r d I nstrument (model 2530). IV.3. Chapter II_ IV.3.1. Sources of M a t e r i a l s a- and /3-cyclodextr i n s were purchased from Sigma Chemical Company, St L o u i s , MO. Sources f o r the c h e m i c a l s , which were used as p o t e n t i a l guest m o l e c u l e s f o r 1 3 C measurements, were as f o l l o w s : benzene (Eastman); t o l u e n e (BDH C h e m i c a l s ) ; e t h y l b e n z e n e (Eastman); c h l o r o b e n z e n e (Matheson Coleman and B e l l ) ; bromobenzene (Eastman); p-x y l e n e (Matheson Coleman and B e l l ) ; p - d i - t e r t . - b u t y l b e n z e n e ( A l d r i c h ) ; b i p h e n y l ( M a l l i n c k r o d t ) ; 4 , 4 ' - d i m e t h y l b i p h e n y l was p r e p a r e d u s i n g the proc e d u r e of Gilman and L i c h t e n w a l t e r ; 2 c y c l o h e x a n e (Matheson Coleman and B e l l ) ; m e t h y l c y c l o h e x a n e ( A l d r i c h ) p-bromotoluene (Eastman); p-h y d r o x y t o l u e n e (Eastman); p - t o l u i d i n e ( A l d r i c h ) ; b e n z o i c a c i d ( M a l l i n c k r o d t ) ; p y r i d i n e ( M a l l i n c k r o d t ) ; durene ( A l d r i c h ) ; naphthalene ( A l d r i c h ) . D i a n i n ' s compound [30] was k i n d l y donated by Henmi Wong. 238 IV.3.2. S y n t h e s i s P r e p a r a t i o n of 2, 6-di-0-Me-/3-CD [ 3 ] . The t i t l e compound was p r e p a r e d by a d a p t i n g the proced u r e of S z e j t l i e t a l . . 3 To a s t i r r e d s o l u t i o n of j3-c y c l o d e x t r i n (9 g) i n 1:1 v/v DMSO-DMF (300 ml) was added g r a d u a l l y a m i x t u r e of BaO (78 g) and Ba(OH) 2.8H 20 (78 g ) . The m i x t u r e was m a i n t a i n e d below 20°C d u r i n g the a d d i t i o n of d i m e t h y l s u l p h a t e (100 ml) i n s m a l l p o r t i o n s over a p e r i o d of 2 h w i t h i n t e n s i v e s t i r r i n g . The m i x t u r e was s t i r r e d f o r another 4 d a t room temperature and then warmed to 85°C f o r 30 min. A f t e r c o o l i n g , c o n c e n t r a t e d NH 40H (105 ml) was added t o decompose the exc e s s d i m e t h y l s u l p h a t e and the m i x t u r e was s t i r r e d f o r an a d d i t i o n a l 4 h at room te m p e r a t u r e . The p r e c i p i t a t e was a l l o w e d t o s e t t l e i n t o "clumps" o v e r n i g h t b e f o r e d e c a n t i n g the f i l t r a t e . The s o l i d was washed s e v e r a l t i m e s w i t h c h l o r o f o r m t o ensure maximum r e c o v e r y of the p r o d u c t . The s o l u t i o n was then e v a p o r a t e d (temperature 60°C) t o a t h i c k s y r u p which c r y s t a l l i z e d on c o o l i n g . The crude p r o d u c t was d i s s o l v e d i n a minimum volume of c h l o r o f o r m and the s o l u t i o n passed t h r o u g h a column of s i l i c a g e l ( K i e s e l g e l 60) p r e v i o u s l y e q u i l i b r a t e d w i t h the e l u a n t , m e t h a n o l - e t h y l a c e t a t e (1:1 v / v ) . The p u r i f i e d compound [3] was then c r y s t a l l i z e d from hot water (85°C) t o produce n e e d l e - l i k e c r y s t a l s i n 70 % y i e l d , m.p. 309-311°C ( l i t . v a l u e 310-312°C). M i c r o a n a l y s i s , c a l c u l a t e d : C 50.50, H 7.42, 0 42.06; found: 239 C 50.50, H 7.50, 0 42.00 %. P r e p a r a t i o n of 2 , 3 , 6 - t r i-0-Ac-/3-CD [ 4 ] . P e r - a c e t y l a t i o n of /3-cyclodextr i n was c a r r i e d out a c c o r d i n g t o the proce d u r e of S t o f f y n e t a l . . * |3-C y c l o d e x t r i n (5 g) was added t o a s o l u t i o n of a c e t i c a n h y d r i d e (25 g) i n dry p y r i d i n e (32.5 g ) . The s u s p e n s i o n was s t i r r e d a t 48°C u n t i l the c y c l o d e x t r i n had d i s s o l v e d , and the s o l u t i o n was m a i n t a i n e d a t t h i s t e mperature f o r 18 h. The s o l u t i o n was c o o l e d and then poured w i t h s t i r r i n g i n t o 100 ml of i c e and water; the crude p r o d u c t p r e c i p i t a t e d out i m m e d i a t e l y . I t was f i l t e r e d , r e d i s s o l v e d i n c h l o r o f o r m (50 m l ) , and washed w i t h s a t u r a t e d copper s u l p h a t e s o l u t i o n . The o r g a n i c l a y e r was then s e p a r a t e d , d r i e d over magnesium s u l f a t e , and e v a p o r a t e d t o a t h i c k s y r u p ( t e m p e r a t u r e 35°C). The s y r u p was d i s s o l v e d i n e t h a n o l (10 ml) and a g a i n poured i n t o i c e and water t o r e g e n e r a t e the pure p r e c i p i t a t e . The pr o d u c t was s u c t i o n f i l t e r e d , washed w i t h i c e - c o l d w a t e r , and f i n a l l y d r i e d i n vacuo a t 56°C t o a c h i e v e a 90 % y i e l d , m.p. 150-152°C. M i c r o a n a l y s i s , c a l c u l a t e d : C 50.00, H 5.60, 0 44.40; found: C 49.75, H 5.56, 0 44.69 %. P r e p a r a t i o n of a - d t - t o l u e n e (CH^D-benzene). 5 A s o l u t i o n of f r e s h l y d i s t i l l e d b e n z y l c h l o r i d e (9 ml) i n 20 ml of anhydrous e t h e r was added t o c l e a n , d r y magnesium t u r n i n g s (2.5 g ) . The r e a c t i o n was i n i t i a t e d by a 240 s m a l l c r y s t a l of i o d i n e and the m i x t u r e was a l l o w e d t o r e f l u x g e n t l y . An a d d i t i o n a l 20 ml of e t h e r was added and b o i l i n g under r e f l u x was c o n t i n u e d f o r 30 min. The r e a c t i o n m i x t u r e was c o o l e d i n an i c e - b a t h and d e u t e r i u m o x i d e (10 ml) was added c a u t i o u s l y t o the s t i r r e d m i x t u r e , f o l l o w e d by 30 % d e u t e r i u m c h l o r i d e - d e u t e r i u m o x i d e s o l u t i o n (5 ml) b e f o r e r e f l u x i n g f o r another 1 h. The crude p r o d u c t was o b t a i n e d by c o o l i n g the m i x t u r e p r i o r t o f i l t e r i n g o f f the p r e c i p i t a t e . The s o l u t i o n was then d i s t i l l e d t o g i v e the a- d , - t o l u e n e i n a y i e l d of 69.4 %, b.p. 109-111°C ( l i t . v a l u e 110.6°C). P r e p a r a t i o n of 0 - d , - e t h y l b e n z e n e . (2-Bromoethyl)benzene (14.0 ml, 102 mmol) was used and the y i e l d of 0 - d , - e t h y l b e n z e n e was 75.0 %, b.p. 133-135°C. P r e p a r a t i o n of a-CD-DMSO-</6-H^O complex. M e t h y l s u l f o x i d e - d g (0.5 m l , 7.0 mmol) was added t o anhydrous a - c y c l o d e x t r i n (0.5 g, 0.5 mmol) and w i t h d r o p w i s e a d d i t i o n of water (2 ml) and h e a t i n g , a s a t u r a t e d s o l u t i o n was o b t a i n e d . Slow c o o l i n g a t room tem p e r a t u r e y i e l d e d c o l o r l e s s n e e d l e - l i k e c r y s t a l s which were then f i l t e r e d by s u c t i o n . Washing was done t h o r o u g h l y w i t h i c e -c o l d water t o remove the " f r e e " methyl s u l f o x i d e - d 6 m o l e c u l e s and the p r o d u c t was e i t h e r a i r - d r i e d f o r 24 h or d r i e d i n vacuo a t room t e m p e r a t u r e . 241 P r e p a r a t i o n of a-CD-DMSCW6 -MeOH-HgO complex. 6 Anhydrous a - c y c l o d e x t r i n (0.5 g, 5.1 mmol) was added t o a s o l u t i o n of methyl s u l f o x i d e - d ^ (1.0 ml, 14.1 mmol) and methanol (2.0 m l , 49.4 mmol). G r a d u a l l y , water (2 d rops) was added t o g i v e a s a t u r a t e d s o l u t i o n . The complex was a l l o w e d t o c r y s t a l l i z e i n the f r e e z e r f o r 2 d b e f o r e f i l t e r i n g and washing w i t h i c e - c o l d w a t e r . The n e e d l e - l i k e c r y s t a l s were d r i e d by the procedure above. P r e p a r a t i o n of a-CD-Me^Oc^-H^O complex. A c e t o n e - d 6 (0.5 ml, 6.8 mmol) was added t o the anhydrous a - c y c l o d e x t r i n (0.5 g, 5.1 mmol) and the proc e d u r e f o r the analogous methyl s u l f o x i d e - d 6 complex was f o l l o w e d . P r e p a r a t i o n of / 3 - c y c l o d e x t r i n i n c l u s i o n complex. j3-CD-DMSO-<^-H20 complex was p r e p a r e d from a s o l u t i o n of / 3 - c y c l o d e x t r i n (0.5 g, 0.4 mmol), methyl s u l f o x i d e - d 6 (0.5 ml, 7.0 mmol) and water (7 ml) by a d a p t i n g the proc e d u r e d e s c i b e d f o r a - c y c l o d e x t r i n . C o l o r l e s s c u b i c c r y s t a l s were formed d u r i n g s t o r a g e of the s o l u t i o n a t room temp e r a t u r e f o r 1 d. S i m i l a r l y , /3-CD-Me^CO-^-H^O complex was a l s o p r e p a r e d by t h i s p r o c e d u r e . 242 P r e p a r a t i o n of 2,6-di-O-Me-0-CD i n c l u s i o n c o m p l e x e s . 7 2,6-di-O-Me-0-CD-benzene complex was pr e p a r e d as f o l l o w s : 1) Benzene (2.5 ml, 28.0 mmol) was added g r a d u a l l y t o the sugar (0.5 g, 0.4 mmol) w i t h h e a t i n g of the m i x t u r e . The complex was l e f t t o c r y s t a l l i z e o v e r n i g h t from the c o n c e n t r a t e d s o l u t i o n , y i e l d i n g r o d - l i k e c r y s t a l s . The pro d u c t was f i l t e r e d , washed t h o r o u g h l y w i t h i c e - c o l d methanol and d r i e d i n vacuo e i t h e r a t room temperature or a t 56°C. 2) A d d i t i o n of methanol (2.0 ml, 49.4 mmol) t o the m i x t u r e of host m o l e c u l e (0.5 g, 0.4 mmol) and benzene (0.5 ml, 5.6 mmol) and h e a t i n g a f f o r d e d the same p r o d u c t . The second method, which i s s u i t a b l e f o r most guest m o l e c u l e s , was adopted f o r the s y n t h e s i s of i n c l u s i o n complexes w i t h host m o l e c u l e s [3] and [ 4 ] , F u r t h e r m o r e , o n l y minimum amounts of guest m o l e c u l e s ( e s p e c i a l l y c r i t i c a l f o r d e u t e r a t e d samples) a r e r e q u i r e d and the complexes r e a d i l y s e p a r a t e from the s o l u t i o n as c o l o r l e s s c r y s t a l s . P r e p a r a t i o n of 1 , 2 : 3 , 4 - d i - 0 - i s o p r o p y l i d e n e - 6 - 0 - p -t o l y l s u l f o n y l - a - D - g a l a c t o p y r a n o s e . 8 p - T o l u e n e s u l f o n y l c h l o r i d e (5.5 g, 28.8 mmol) was added t o a s o l u t i o n of p y r i d i n e (15 ml) c o n t a i n i n g 1,2:3,4-d i - O - i s o p r o p y l i d e n e - a - D - g a l a c t o p y r a n o s e (2.5 g, 9.6 mmol) w i t h s t i r r i n g a t room t e m p e r a t u r e . The r e a c t i o n m i x t u r e was 243 a l l o w e d t o s t i r f o r 24 h and then c o l d 2 M - h y d r o c h l o r i c a c i d (50 ml) was added b e f o r e e x t r a c t i o n of the pr o d u c t w i t h e t h e r . The e t h e r e a l e x t r a c t was f u r t h e r washed w i t h a c i d ( t o remove any r e s i d u a l p y r i d i n e ) f o l l o w e d by sodium b i c a r b o n a t e s o l u t i o n u n t i l i t was n e u t r a l . The e t h e r was removed t o a f f o r d a l i g h t y e l l o w s y r u p (4.0 g, 9.7 mmol), which when c r y s t a l l i z e d from aqueous e t h a n o l , gave c o l o r l e s s c r y s t a l s i n 85 % y i e l d , m.p. 102-103°C ( l i t . v a l u e 104-105°C). S i m i l a r l y , 1 , 2 : 5 , 6 - d i - 0 - i s o p r o p y l i d e n e - 3 - 0 - p - t o l y l -s u l f o n y l - a - D - g l u c o f u r a n o s e was p r e p a r e d i n a h i g h y i e l d . P r e p a r a t i o n of 1 , 2 : 3 , 4 - d i - O - i s o p r o p y l i d e n e - 6 - O - p -t o l y l s u l f o n y l - a - D - g a l a c t o p y r a n o s e - 6 , 6 ' -d^. 1 , 2 : 3 , 4 - D i - O - i s o p r o p y l i d e n e - a - D - g a l a c t o p y r a n o s e (7.0 g, 26.9 mmol) was o x i d i z e d t o the c o r r e s p o n d i n g a c i d (4.8 g, 17.5 mmol) u s i n g b a s i c permanganate s o l u t i o n a c c o r d i n g t o a proce d u r e d e s c r i b e d i n the l i t e r a t u r e . 9 The d r i e d a c i d (2.0 g, 7.3 mmol) was then reduced by l i t h i u m a luminium d e u t e r i d e i n anhydrous t e t r a h y d r o f u r a n u s i n g the method of Brown e t a l . 1 0 t o a f f o r d the crude s t a r t i n g m a t e r i a l (1.8 g, 6.9 mmol), which i s d e u t e r a t e d a t the C--6 p o s i t i o n . I t was used w i t h o u t f u r t h e r p u r i f i c a t i o n t o pr e p a r e the t o s y l a t e d s u g a r . R e c r y s t a l l i z a t i o n of the crude pr o d u c t from aqueous e t h a n o l gave the d e s i r e d compound (1.7 g, 4.1 mmol), m.p. 102-103°C. 244 IV.4. Chapter I I I IV.4.1. Sources of m a t e r i a l s M a t e r i a l s f o r the s t u d i e s d e s c r i b e d h e r e i n were e i t h e r o b t a i n e d c o m m e r c i a l l y , or s y n t h e s i z e d i n t h i s l a b o r a t o r y . Sources f o r c h e m i c a l s were as f o l l o w s : g l u cosamine h y d r o c h l o r i d e (Sigma); carbobenzoxy c h l o r i d e ( A l d r i c h ) ; a n i s a l d e h y d e (Eastman); s a l i c y l a l d e h y d e (Eastman); 5-bromo-2-hydroxybenzaldehyde (Eastman); z i n c a c e t a t e ( F i s h e r ) ; c u p r i c a c e t a t e ( F i s h e r ) ; c h i t o s a n (Sigma); benzaldehyde (Eastman); p - n i t r o b e n z a l d e h y d e (Matheson Coleman and B e l l ) ; sodium a l g i n a t e ( K e l c o ) . The s p i n - l a b e l l e d sugar complex [17] e x i s t e d as a pure s t o c k sample i n the l a b o r a t o r y . IV.4.2. P r e v i o u s Work The monosaccharide s y n t h e s e s have e i t h e r been documented i n our own l a b o r a t o r y or r e p o r t e d e l s e w h e r e . A b r i e f summary w i l l be g i v e n , and any changes i n the p r o c e d u r e s w i l l be noted. The g l y c o s i d e m e t h y l 3 , 4 , 6 - t r i - 0 - a c e t y l - 2 - a m i n o - 2 -deoxy-/3-D-glucopyranoside hydrobromide [3] was p r e p a r e d by a c o m b i n a t i o n of methods from C h a r g a f f , 1 1 G r o s s , 1 2 and I r v i n e and E a r l . 1 3 F i r s t , the carbobenzoxy d e r i v a t i v e of glucosamine was p r e p a r e d a c c o r d i n g t o the r e c i p e of C h a r g a f f ; 1 1 one e q u i v a l e n t of glucosamine h y d r o c h l o r i d e was added t o two e q u i v a l e n t s of sodium b i c a r b o n a t e i n water, f o l l o w e d by p o r t i o n - w i s e a d d i t i o n of one e q u i v a l e n t of 245 carbobenzoxy c h l o r i d e (CBZ c h l o r i d e ) . The p r e c i p i t a t e d p r o d u c t was f i l t e r e d and d r i e d t o a f f o r d a y i e l d of about 95 %. Next, the g l y c o s y l bromide was p r e p a r e d by the method of Gross et a l . . 1 2 A m i x t u r e of a c e t i c a c i d and a c e t i c anhydride/HBr (3:2 by weight) was added i n p o r t i o n s t o the CBZ glucosamine a t 0°C and, a f t e r 30 min, HBr gas was bubbled r a p i d l y through the r e a c t i o n m i x t u r e u n t i l the temperature was r a i s e d by about 10°C. E t h e r was added and a f t e r r e f r i g e r a t i o n f o r a few hours t o induce f u r t h e r c r y s t a l l i z a t i o n , the p r o d u c t was f i l t e r e d . The g l y c o s y l bromide was then r e c r y s t a l l i z e d from c h l o r o f o r m / e t h e r . The methyl g l y c o s i d e was f i n a l l y o b t a i n e d f o l l o w i n g the p r o c e d u r e of I r v i n e and E a r l . 1 3 A 5 % s o l u t i o n of the g l y c o s y l bromide i n anhydrous methanol c o n t a i n i n g 1 % of dry p y r i d i n e , was a l l o w e d t o s t a n d o v e r n i g h t . The m i x t u r e was e v a p o r a t e d t o a s m a l l volume and e t h e r added. Upon r e f r i g e r a t i o n the crude methyl g l y c o s i d e was o b t a i n e d . I t was then f i l t e r e d , d r i e d and used w i t h o u t f u r t h e r pur i f i c a t i o n . The t e t r a - O - a c e t y l - g l u c o s a m i n e d e r i v a t i v e [4] was p r e p a r e d by the method of Bergman, 1 4 u s i n g a n i s a l d e h y d e as the amino p r o t e c t i n g group. The S c h i f f ' s base was formed by combining glucosamine h y d r o c h l o r i d e and a n i s a l d e h y d e i n water w i t h one e q u i v a l e n t of sodium b i c a r b o n a t e . The compound p r e c i p i t a t e d r e a d i l y on v i g o r o u s s t i r r i n g and was then f i l t e r e d and d r i e d . The next s t e p i n v o l v e d the a c e t y l a t i o n of t h i s m a t e r i a l i n a 1:1 v/v m i x t u r e of a c e t i c 246 a n h y d r i d e and p y r i d i n e t o y i e l d the t e t r a - a c e t a t e . The S c h i f f ' s base was then c l e a v e d i n a d i l u t e s o l u t i o n of HCl i n aqueous a c e t o n e . The u n h y d r o l y z e d , sugar a c e t a t e s t a r t i n g m a t e r i a l and a n i s a l d e h y d e were then e x t r a c t e d w i t h c h l o r o f o r m . Sodium b i c a r b o n a t e was then added t o the aqueous l a y e r u n t i l i t was n e u t r a l b e f o r e e x t r a c t i n g a g a i n w i t h c h l o r o f o r m t o g i v e the " f r e e " amino sugar. The s t a r t i n g m a t e r i a l , which was r e c o v e r e d from the f i r s t c h l o r o f o r m e x t r a c t i o n , was t r e a t e d a g a i n w i t h a c i d and the e x t r a c t i o n scheme was r e p e a t e d . The crude p r o d u c t was then r e c r y s t a l l i z e d from aqueous e t h a n o l - w a t e r m i x t u r e ; m.p. 137-139°C. The sugar s a l i c y l a l d i m i n e s [5] and [6] were r e a d i l y p r e p a r e d by a d a p t i n g the method of I r v i n e and E a r l . 1 5 S a l i c y l a l d e h y d e was added t o the a p p r o p r i a t e amino sugar i n aqueous methanol, w i t h one e q u i v a l e n t of sodium b i c a r b o n a t e added i n the p r e p a r a t i o n of the former compound. The r e a c t i o n m i x t u r e s were s t i r r e d v i g o r o u s l y f o r a few hours b e f o r e f i l t e r i n g the p r o d u c t s . R e c r y s t a l l i z a t i o n from e i t h e r e t h a n o l or methanol gave the pure compounds i n g r e a t e r than 70 % y i e l d . P r e p a r a t i o n of S c h i f f ' s base m e t a l complexes [ 1 2 ] , [ 1 3 ] , and [ 1 5 ] . The S c h i f f ' s base metal complexes from l i g a n d s [5] and [6] v e r e r e a d i l y p r e p a r e d by the o r i g i n a l method of S c h i f f and r e p e a t e d by r e f e r e n c e t o H o l m . 1 6 The l i g a n d s were f i r s t 247 d i s s o l v e d i n hot e t h a n o l and an e t h a n o l i c s o l u t i o n of the a p p r o p r i a t e metal a c e t a t e added w i t h s t i r r i n g . On c o o l i n g , the metal-complex s e p a r a t e d as f i n e c r y s t a l s and the pr o d u c t was then f i l t e r e d . R e c r y s t a l l i z a t i o n from e i t h e r acetone (complex [ 1 2 ] ) , a c e t o n e / c h l o r o f o r m (complex [ 1 3 ] ) , or e t h a n o l (complex [15]) gave the pure compounds i n good y i e l d s , except f o r the Z n ( I I ) sugar complex. P r e p a r a t i o n of b i s - { ( - N - m e t h y l 3 , 4 , 6 - t r i - 0 - a c e t y l - 2 -d e o x y - 0 - D - g l u c o p y r a n o s y l - 2 - ( 4 - b r o m o - s a l i c y l a l d i m i n o ) } C u ( 1 1 ) [ 1 6 ] . The c o p p e r ( I I ) complex [16] was o b t a i n e d i n 85 % y i e l d and was a n a l y t i c a l l y pure when i s o l a t e d d i r e c t l y from the r e a c t i o n m i x t u r e . Slow c r y s t a l l i z a t i o n from an a c e t o n e / e t h a n o l m i x t u r e y i e l d e d dark brown c u b i c c r y s t a l s , m.p. 243-244°C. M i c r o a n a l y s i s , c a l c u l a t e d : C 45.06, H 4.35, N 2.60; found: C 45.28, H 4.46, N 2.63 %. N - A r y l i d e n e c h i t o s a n g e l s were p r e p a r e d by the methods documented i n our own l a b o r a t o r y . 1 7 P r e p a r a t i o n of [ N - s a l i c y l i d e n e ] c h i t o s a n [ 1 9 ] . P u r i f i e d c h i t o s a n (2 g, 12 mmol) was d i s s o l v e d w i t h s t i r r i n g i n a m i x t u r e (1:1 v/v, 120 ml) of methanol and 10 % aqueous a c e t i c a c i d . To the r e s u l t i n g v i s c o u s s o l u t i o n was added w i t h v i g o r o u s s t i r r i n g , a m e t h a n o l i c s o l u t i o n (40 ml) of s a l i c y l a l d e h y d e (1.4 ml, 14 mmol) f o l l o w e d by s a t u r a t e d sodium b i c a r b o n a t e s o l u t i o n (8 m l ) . A t h i c k g e l 248 was formed w i t h i n minutes and a f u r t h e r e q u a l p o r t i o n of s a l i c y l a l d e h y d e i n methanol was added, f o l l o w e d by methanol (320 ml) and sodium b i c a r b o n a t e s o l u t i o n (4 m l ) . A f t e r 2 h the s o l v e n t s were decanted and the r i g i d g e l was broken up i n t o s m a l l e r p i e c e s . These were suspended i n methanol (600 m l ) , e t h a n o l (300 m l ) , and d i e t h y l e t h e r (300 ml) over a p e r i o d of 1 d. The f i l t e r e d , s o l i d p r o d u c t o b t a i n e d was f i r s t a i r - d r i e d f o r s e v e r a l hours and f i n a l l y d r i e d i n vacuo at 56°C. A b r i g h t y e l l o w p r o d u c t w i t h d.s. 1.0 was o b t a i n e d (28 g ) . M i c r o a n a l y s i s f o r ( C 1 3 K 1 5 N 0 5 ) 0.5 H 20, c a l c u l a t e d : C 56.92, H 5.88, N 5.11; found: C 56.91, H 5.81, N 5.35 %. P r e p a r a t i o n of [ m i x e d ( N - b e n z y l i d e n e and N-s a l i c y l i d e n e ) ] c h i t o s a n [ 2 0 ] . To c h i t o s a n (2 g, 12 mmol), d i s s o l v e d i n a m i x t u r e of methanol and 10 % aqueous a c e t i c a c i d , was added w i t h v i g o r o u s s t i r r i n g , a m e t h a n o l i c s o l u t i o n (40 ml) of benzaldehyde (4 ml, 39 mmol). A s a t u r a t e d sodium b i c a r b o n a t e s o l u t i o n (8 ml) was added and w i t h i n minutes a v e r y s o f t , c o l o r l e s s , and s e m i - t r a n s p a r e n t g e l was formed. S a l i c y l a l d e h y d e (1.4 ml, 14 mmol) i n methanol (40 ml) was added i m m e d i a t e l y r e s u l t i n g i n a f u r t h e r s t i f f e n i n g of the g e l , t o which was then added methanol (320 ml) and sodium b i c a r b o n a t e s o l u t i o n (4 m l ) . The "mixed" g e l o b t a i n e d was l i g h t e r i n c o l o r compared w i t h the pure (N-s a l i c y l i d e n e ) c h i t o s a n . The p r o d u c t , [ 2 0 ] , had a 249 b e n z y l i d e n e - t o - s a l i c y l i d e n e r a t i o o f . 2:1 ( e s t i m a t e d from 1 3C-n.m.r. i n t e g r a t i o n ) . M i c r o a n a l y s i s f o r ( C , 3 H , 5 N 0 5 ) 0 . 3 3 ( C , 3 H , 5 N 0 « ) 0 . 6 7 0.7 H 20, c a l c u l a t e d : C 58.45, H 6.19, N 5.24; found: C 58.48, H 6.10, N 5.51 %. S i m i l a r l y , [ N - ( 4 - n i t r o b e n z y l i d e n e ) ] c h i t o s a n [21] was p r e p a r e d by condensing c h i t o s a n (2 g, 12 mmol) w i t h p-n i t r o b e n z a l d e h y d e (2.1g, 14 mmol) t o g i v e a l i g h t brown, r i g i d g e l w i t h i n minutes ( d . s . 1.0). M i c r o a n a l y s i s f o r (C,3H,flN20„) 1.0 H 20, c a l c u l a t e d : C 50.00, H 5.16, N 8.97; found: C 50.00, H 4.92, N 8.85 %. Copper c o m p l e x a t i o n r e a c t i o n s The wet g e l s (used w i t h o u t d r y i n g from the above p r e p a r a t i o n s ) were complexed by v i g o r o u s s t i r r i n g o v e r n i g h t i n a s a t u r a t e d , m e t h a n o l i c s o l u t i o n of c u p r i c a c e t a t e . The fragmented g e l s were f i l t e r e d , washed (500 ml methanol) and d r i e d i n vacuo a t 56°C f o r 1 d. Copper d e t e r m i n a t i o n s were o b t a i n e d by n i t r i c a c i d d i g e s t i o n of the c h i t o s a n samples f o l l o w e d by atomic a b s o r p t i o n measurements. 2 5 0 R e f e r e n c e s 1. J . H. D a v i s , K. R. J e f f r e y , M. Bloom, M. I . V a l i c , T. P. H i g g s , Chem. Phys. L e t t . , 42, 390(1976). 2. H. Gi l m a n , M. L i c h t e n w a l t e r , J . Am. Chem. S o c , 61 , 957(1939). 3. J . S z e j t l i , A. L i p t a k , I . J o d a l , P. F u g e d i , P. N a n a s i , A. N e s z m e l y i , S t a r k e , 32, 165(1980). 4. P. J . S t o f f y n , R. W. J e a n l o z , J . Am. Chem. S o c , 80, 5690(1958). 5. H. C. Brown, G. A. R u s s e l l , i b i d . , 7_4, 3995(1952). 6. K. H a r a t a , B u l l . Chem. Soc. J p n . , 5J_, 1644(1978). 7. B. Casu, M. R e g g i a n i , G. R. Sanderson, Carbohydr. Res., 76, 59(1979). 8. K. Freudenberg, R. M. H i x o n , B e r . , 56, 2119(1923). 9. H. O h l e , G. Berend, i b i d . , 58, 2577(1925). 10. H. C. Brown, P. M. Weissman, N. M. Yoon, J . Am. Chem. S o c , 88, 1458(1966). 11. E. C h a r g a f f , M. B o v a r n i c k , J . B i o l . Chem., 118, 421(1937). 12. G. Fodor, L. Otvos, Ann. Chem., 604, 29(1957). 13. J . C. I r v i n e , D. M c N i c o l l , A. Hynd, J . Chem. S o c , 99, 250(1911). 14. M. Bergmann, L. Z e r v a s , Chem. Be r . , 64B, 975(1931). 15. J . C. I r v i n e , J . C. E a r l , J . Chem. S o c , 121, 2376(1922). 16. R. H. Holm, K. Swaminathan, I n o r g . Chem., 2, 181(1963). 17. M. Y a l p a n i , Ph. D. t h e s i s , U n i v e r s i t y of B r i t i s h Columbia, (1980). 252 Appendix I_ D i p o l e - D i p o l e I n t e r a c t i o n of N u c l e i I t i s u s e f u l t o t r a n s f o r m the e q u a t i o n o b t a i n e d f o r d i p o l e - d i p o l e i n t e r a c t i o n t o s p h e r i c a l p o l a r c o o r d i n a t e s . Eq. [4] (see Chapter I ) i s o b t a i n e d , where the s i x terms A t o F a r e shown below: His = r ' 3 7 j 7 s h 2 [ A + B + C + D + E + F)^> [4] A = - I I t I S t ( 3 c o s 2 0 - 1 ) B = 1 / 4 { [ I 1 + I s _ + I x . I 3 * ] ( 3 c o s 2 0 - 1)} C = -3/2{ [ I I x I s + + I I t ISz ]sin0cos0exp(-itf>)} D = - 3 / 2 { [ l l z I s _ + Ix_ I S z ] s i n 0 c o s 0 e x p ( i<t>)} E = - 3 / 4 { l I + I S j . s i n 2 0 e x p ( - 2 i 0 ) } F = - 3 / 4 { I j . Is- s i n 2 0 e x p ( 2 i 0 ) } Each of t h e terms A t o F c o n t a i n s a s p i n f a c t o r and a g e o m e t r i c a l f a c t o r . 253 Appendix 11 The E f f e c t s of R a p i d Sample R o t a t i o n S e v e r a l i n t e r a c t i o n s of i n t e r e s t f o r n.m.r. of s o l i d s c o n t a i n the term ( 3 c o s 2 0 - 1 ) , where 6 i s the a n g l e between a p a r t i c u l a r d i r e c t i o n r (example, the d i s t a n c e between n u c l e i ) and the s t a t i c magnetic f i e l d 6 0 . An example i s the d i p o l a r i n t e r a c t i o n between two n u c l e i , i n which the e x p r e s s i o n s f o r terms A and B are g i v e n i n Appendix I . I t i s n e c e s s a r y t o know how such f u n c t i o n s a r e a f f e c t e d by r a p i d sample r o t a t i o n of about an a x i s f i x e d i n space r e l a t i v e t o B c . C o n s i d e r a u n i t v e c t o r OD i n d i r e c t i o n X r o t a t i n g about a x i s S, which i s i n c l i n e d a t a n g l e 0 t o the d i r e c t i o n Bo. L e t the a n g l e between r and S be a and the a n g l e between r and Bo be 6. Then the r e q u i r e d c o s i n e i s g i v e n by OB. Now OE = c o s a OA = OEcos0 = cosacos/3 A l s o ED = s i n a EC = s i n a c o s ^ AB = sinasin0cos<£ s i n c e AEC = 90° - AEO = EOA = 0 [note t h a t the DEC p l a n e i s p e r p e n d i c u l a r t o the p l a n e c o n t a i n i n g 8 0 and s ] OB = OA + AB = cosacos/5 + sinasin/3cos0 In the case of r o t a t i o n about s a t r a t e o>, the a n g l e <t> = u>t 254 i f r i s i n the p l a n e of B0 and S a t time t = 0. Thus co s f l = cosacos/3 + sinasin/Jcoscot a t time t . Hence <cos 20> = c o s 2 / 3 c o s 2 a + 2sin/3cos/3sinacosa<cosa)t> Now <cosa)t> = 0 and <cos 2wt> = 1/2 <cos 20> = c o s 2 / 3 c o s 2 a + l / 2 s i n 2 / 3 s i n 2 a = c o s 2 / 3 c o s 2 a + 1/2(1 - cos 2/3)(1 - c o s 2 a ) = 1/3 + 1/6(3cos 2/3 - 1 ) ( 3 c o s 2 a - 1) <3cos 20 - 1) = 1/2(3COS2/3 - l ) ( 3 c o s 2 a - 1) [ n o t e t h a t the extrema of t h e a n g l e 6 a r e c l e a r l y /3 - a and 0 + a] + s i n 2 0 s i n 2 a < c o s 2 o t > Bo r s / / / B A O 

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