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Determination of the crystal structure of three organic compounds by X-ray diffraction Schaffrin, Roger Michael 1970

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THE DETERMINATION OF THE CRYSTAL STRUCTURE OF THREE ORGANIC COMPOUNDS BY X-RAY DIFFRACTION BY ROGER MICHAEL SCHAFFRIN M.D., University of Saskatchewan, 1963 B.A., University of Saskatchewan, 1965 A THESIS SUBMITTED IN THE REQUIREMENTS DOCTOR OF PARTIAL; FULFILMENT OF FOR THE.DEGREE OF PHILOSOPHY in the Department of CHEMISTRY We accept this thesis as conforming to the required standard THE UNIVERSITY OF BRITISH COLUMBIA July, 1970 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 representatives. It is understood that copying or publication of this thesis for financial gain shall not be allowed without my written permission. Department of The University of British Columbia Vancouver 8, Canada Date OcJ-cA^,, C . - ii -ABSTRACT Supervisor: Professor James Trotter The crystal structure of dibenzothiophene has been determined by X-ray diffraction. Mo-K scintillation counter data were used for a this analysis; the sulfur atom position was determined by means of a Patterson function; the carbon atoms were located from a Fourier synthesis, and the hydrogen atoms, from a difference synthesis. Refinement of positional and thermal parameters was by least-squares methods. The molecule is slightly folded, the dihedral angles between the five-membered ring and the six-membered rings being 0.4° and 1.2°. The bond distances and valency angles are similar to those in related o molecules. The C-S bond length is 1.740 A, and the C-S-C angle is 91.5°. The crystal structure of DL-ornithine hydrobromide has been determined by means of visual Cu-K data. The bromine ion position a ; was found by Patterson methods; carbon, nitrogen, and oxygen atoms were located on Fourier summations and the hydrogen atoms, on a difference synthesis. The positional and thermal parameters were refined by least-squares. The ornithine molecule is a zwitterion, with both nitrogens accepting protons. The mean bond distances are o , o o C-0, 1.249 A; C-N, 1.469 A; C-C, 1.532 A. The structure is held together by a system of N—H 0 (2.84, 2.84, 2.89 A) and N—H...Br O (3.29, 3.36,.3.46 A) hydrogen bonds. The crystal and molecular structure of histamine diphosphate monohydrate has been determined with scintillation counter Mo-K data. J a - iii -The positions of the phosphorus atoms were determined by Patterson methods; the carbon, nitrogen and oxygen atoms were located by means o Fourier syntheses; the hydrogen atoms were found on a difference synthesis. The thermal and positional parameters were refined by least-squares. The atoms of this histamine cation lie in two almost perpendicular planes, the plane of the imidazole ring and that of the side chain. The bond lengths and angles are similar to the correspond ing values in histidine hydrochloride monohydrate. The dimensions of o o the two P02(OH)2~ ions are P-0 1.51 A, P-OH 1.57 A, O-P-0 115.5°, and HO-P-OH 107.0°. The most important feature of the packing is a complex system of 0-H...0 and N-H...0 hydrogen bonds. - iv -TABLE OF CONTENTS Page TITLE PAGE i ABSTRACT ii TABLE OF CONTENTS iv LIST OF TABLES vLIST OF FIGURES vii ACKNOWLEDGEMENTS viiGENERAL INTRODUCTION 1 PART I. THE DETERMINATION OF THE STRUCTURE OF DIBENZOTHIO-PHENE 2 A. INTRODUCTION , 3 B. THE STRUCTURE OF DIBENZOTHIOPHENE 3 ExperimentalStructure Analysis 5 Results and Discussion 12 PART II. THE DETERMINATION OF THE STRUCTURE OF DL-ORNITHINE HYDROBROMIDE 18 A. INTRODUCTION 9 B. THE STRUCTURE OF DL-ORNITHINE HYDROBROMIDE 19 Experimental 1Structure Analysis 20 Results and Discussion 2 PART III. THE DETERMINATION OF THE STRUCTURE OF HISTAMINE DIPHOSPHATE MONOHYDRATE A. INTRODUCTION B. THE STRUCTURE OF HISTAMINE DIPHOSPHATE MONOHYDRATE Experimental Structure Analysis Results and Discussion BIBLIOGRAPHY - vi -LIST OF TABLES Table Page Dibenzothiophene 1. Final positional and thermal parameters 8 2. Measured and calculated structure factors 10 3. Displacements from mean planes 13 4. Bond distances and angles in dibenzothiophene and related molecules 14 DL-Ornithine Hydrobromide 5. Measured and calculated structure factors 23 6. Final positional and thermal parameters 26 7. Bond lengths and angles 27 8. Hydrogen atoms 28 9. Carbon-oxygen bond lengths in some amino acids 29 10. Carboxylate bond angles in ornithine and lysine derivatives 30 11. Carbon-carbon-nitrogen angles in ornithine and lysine derivatives12. Carbon-carbon-carbon angles in ornithine and lysine derivatives 31 13. Hydrogen bonds 5 Histamine Diphosphate Monohydrate 14. Final positional and thermal parameters 42 15. Measured and calculated structure factors 47 16. Bond distances and angles 50 17. Hydrogen bonds 57 18. Environments of atoms involved in hydrogen bonding... 58 - vii -LIST OF FIGURES Figure Page Dibenzothiophene 1. (a) Perspective drawing showing atom numbering 7 (b) Projected difference synthesis 7 2. Projected electron density distribution .9 3. Packing diagram 17 DL-Ornithine Hydrobromide 4. (a) Projected electron density distribution 24 (b) Perspective drawing showing atom numbering 24 5. Packing diagram 32 Histamine Diphosphate Monohydrate 6. Projected difference synthesis 41 7. Projected electron-density distribution 44 8. Perspective drawing showing atom numbering 45 9. Packing diagram 510. Hydrogen bonding scheme 56 - viii -ACKNOWLEDGEMENTS I want to thank Professor James Trotter for his help and for his great patience. While working under him I grew to respect him very much for his gentle manner and scientific thoroughness. I should like to thank Dr. R.J. Zwarich for suggesting the analysis of dibenzothiophene and for providing me with a sample of this compound. For the assistance which I received from the University of British Columbia Computing Centre I am grateful. Finally I wish to thank the Medical Research Council of Canada for providing Medical Research Fellowships for the academic years 1965-1967. - 1 -GENERAL INTRODUCTION In 1912 von Laue suggested that crystals should diffract X-rays; this was confirmed experimentally by Friedrich and Knipping. Bragg elucidated the mathematical interpretation of X-ray diffraction and determined the first crystal structure by X-ray diffraction in 1913. Since that time X-ray crystallography has been used to investigate the structure of matter on an atomic scale. With the advent of automated spectrogoniometers and digital computers, structures of relatively great size and complexity, such as hemoglobin and myoglobin, have been examined by means of X-ray crystallography. Of the various analytical tools available to the chemist, crystallo graphy is the only one that gives a complete three-dimensional picture of the molecule. The detailed molecular structure, in turn, is often necessary for an understanding of the physical, chemical and biological properties of substances occurring in living organisms. Various amino acids, hormones, enzymes and proteins have been studied by means of X-ray crystallography. It was with the aid of this tool that the Watson-Crick model for DNA was developed. Since then,the molecular approach to biological systems has gained tremendously in favor. This thesis concerns itself with the determination, by single-crystal X-ray diffraction, of the structures of three organic compounds. Since the methods of gathering the data, deriving structure factors,; solving the structures by Patterson and Fourier techniques as well as the subsequent.refinement by least-squares methods are adequately described in many reference books (1,2,3), they will not be described in detail in the thesis. The compounds analysed are listed in order of increasing difficulty and medical importance. PART I THE DETERMINATION OF THE STRUCTURE OF DIBENZOTHIOPHENE - 3 -A. INTRODUCTION In 1955 Burns and Iball (4) reported the crystal and molecular structure of fluorene, C^H^n. Kurahashi et al (5) and Lahiri (6,7) determined the structure of carbazole, C10H N, between 1966 and 1969. Finally, McCullough et al (8) reported the crystal and molecular structure of dibenzoselenophene, C.„H Se, in the winter of 1969. It iz o seemed of interest therefore to determine the structure of dibenzothio phene C^2^gS. B. THE STRUCTURE OF DIBENZOTHIOPHENE Experimental When sublimed at atmospheric pressure in a stream of nitrogen, dibenzothiophene forms thin, colorless plates which are elongated along b, with (102) well developed and smaller (100) and (001) forms. The unit cell parameters and space group were determined from various photographic and diffractometer measurements. o , Crystal data (A, Mo-K = 0.7107 A). Dibenzothiophene, C.„H0S; M = 184.3; mp = 99°C. o Monoclinic, a = 8.67 ± 0.01, b = 6.00 ± 0.01, c = 18.70 ± 0.02 A, 3 = 113.9 ± 0.1°. °3 U = 889.5 A . :.D = 1.35, Z = 4, D = 1.38. m x F(000) = 384. Absorption coefficient for X-rays, u(Mo-K ) = 2.99 cm Absent reflexions: h0>! when £ is odd, 0k0 when k is odd. Space group is-•P21/c (C^, ) . The intensities of all reflexions with 2 6 (Mo-K )< 50° (minimum d, a o 0.84 A) were measured on a G.E. XRD 5 Spectrogoniometer, with single Crystal Orienter, using a scintillation counter, Mo-K^ radiation (zirconium filter and pulse height analyser), and the moving-crystal moving-counter technique of Furnas (9). All the intensities were corrected for background radiation (approximately only a function of 8 ) and the structure amplitudes were derived as usual. The crystal, a square plate measuring 0.58 x 0.53 x 0.20 mm was mounted with b parallel to the axis of the goniostat so that the cross section traversed by the X-ray was 0.58 x 0.20 mm. The following sources of error in the measured structure factors were considered. Firstly, taking the crystal as a cylinder with a mean diameter of 0.39 mm, uR is 0.058 and the absorption correction factor A is 1.10 and constant over the range of 6 = 0-25°; thus the maximum absorption ; error is negligible for the above range of 6 . Secondly, absorption errors due to non-uniformity of crystal dimension were estimated by considering the shortest (0.20 mm) and the longest (0.8 mm) path lengths in the crystal. The absorption corrections for the correspond ing structure factors are exp(2.99 x 0.02/2) and exp(2.99 x 0.08/2) or 1.03 and 1.13 respectively. Therefore, the maximum deviation from the mean correction is less than 5%. Since the total maximum error in F due to absorption is 5% and since most of the errors will be much o • r smaller than this value, no corrections were made for absorption. - 5 -Structure Analysis The position of the sulfur atom was determined from a three-dimensional Patterson synthesis (0.156, 0.167, 0.135) and structure factors were calculated for all the three-dimensional data for sulfur only, using scattering factors from the International Tables for X-ray Crystallography 1962 (10) and an isotropic thermal parameter of 4.0 A . One least-squares refinement reduced R to 0.56. A three-dimensional Fourier series summed with phases based on the sulfur atom revealed the positions of all the carbon atoms. When these were introduced into the structure factor calculations with scattering factors from the °2 International Tables and B = 4.0 A , R dropped to 0.45. Further, refinement of the positional and isotropic thermal parameters together with an overall scale factor, proceeded by the method of block-2 diagonal least-squares, the function minimized being Zw(jFq|-|F£|) . Since the structure factors were considered to be least accurately measured for the very strong reflexions which are affected most by , absorption, and for the very weak and unobserved reflexions the intensities of which are close to that of background radiation , jthe weighting scheme employed was v*w~ = 1 if | Fq | <F , i/w" = | F |/F if |FQ|>F where F was taken as 5. For unobserved reflexions i/w was 0.70. After fourteen isotropic least-squares refinement cycles, R was 0.12 and shifts in positional and thermal parameters were small in magnitude and random in direction, the largest shift being less than ' one fourth of a. standard deviation. Further refinement commenced with anisotropic thermal parameters; seven anisotropic refinement cycles decreased R to 0.10. A three-dimensional difference synthesis summed at this stage of the analysis - 6 -revealed all eight hydrogen atoms (Figure 1). Their peak electron °-3 densities varied between 0.4 and 1.0 eA . When these hydrogen atoms were introduced into the structure factor calculations with scattering °2 factors from the International Tables and B = 4.0 A , R fell to 0.09. During the subsequent three least-squares cycles the shifts of the isotropic thermal parameters of hydrogen atoms 1, 3, and 8 were large and positive. A second difference synthesis was prepared in order to determine the precise positions of hydrogens 1, 3, and 8. A final series of five least-squares cycles completed the refinement. During the last cycle, parameter shifts were small and nonsystematic, the largest shift being one quarter of a standard deviation for the heavier atoms and one half of a standard deviation for the hydrogen atoms. The positional and thermal parameters of all the atoms as derived from the final least-squares cycle are given in Table 1, together with their standard deviations computed from the inverses of the diagonal terms of the matrix of the least-squares normal equations. The atom numbering used is shown in Figure 1. The hydrogen atoms were assigned the numbers of the carbon atoms to which they are bonded. The final three dimensional electron density distribution is shown in Figure 2; °-3 all the heavier atoms are well resolved with peak densities of 10 eA °-3 for carbon atoms and 30 eA for the sulfur atom. The final measured and calculated structure factors are listed in Table 2; R is 0.083 for 1176 observed reflexions. A final three-dimensional difference synthesis was computed and showed random fluctua-°_3 tions in electron density as great as ± 0.6eA (b) Three-dimensional difference synthesis projected along b. The hydrogen atoms have the same number as the carbon atom to which they are bonded. - 8 -Table 1 Final positional (fractional, x 10 for C and S, x 10 for H) and °2 2 ° 2 thermal (A x 10 ; B in A ) parameters, with standard deviations in parentheses. Atom C(l) C(2) C(3) C(4) C(5) C(6) C(7) C(8) S(9) C(10) C(ll) C(12) C(13) -1496(11) -2755(11) -2693(12) -1380(10) 1934(10) 3393(11) 4362(10) 3905(11) 1542( 3) -0163(10) -0082( 8) 1403( 9) 2416( 9) 3036(16) 4659(17) 6565(17) 6938(14) 6997(14) 6675(15) 4800(17) 3197(15) 1674( 4) 3435(14) 5383(13) 5405(13) 3499(13) 0192(5) -0087(5) 0346(5) 1047(5) 2652(5) 3314(5) 3379(5) 2808(5) 1361(1) 0903(5) 1336(4) 2060(4) 2151(4) H(l) -160(22) 173(32) -023(11) 9(5) H(2) -381(11) 409(32) -058( 5) 2(2) H(3) -346(15) 782(23) 011( 8) 5(3) H(4) -126(11) 846(14) 127( 5) 1(2) H(5) 129(11) 823(14) 254( 5) 1(2) H(6) 353(10) 790(16) 357 ( 5) 1(2) H(7) 531(11) 454(16) 388 ( 5) 2(2) H(8) 463(15) 209(24) 275( 7) 5(3) Atom u_ u, „ II. U „ TT Mean 11 12 13 22 23 33 a(U) c(i). 5. 33 -0.49 1. 50 6.03 -0.58 3. 49 0.38 C(2) 4. 69 -0.60 0. 76 6.39 0.17 4. 06 0.40 C(3) 4. 60 0.51 1. 59 6.02 0.73 5. 01 0.40 C(4) 4. 21 0.32 1. 88 4.24 0.04 4. 69 0.33 C(5) 4. 6.3 -0.04 1. 75 4.56 -0.05 4. 01 0.33 C(6) 4. 40 -1.05 1. 38 5.15 -0.83 4. 31 0.36 C(7) 3. 87 -0.91 1. 34 6.74 0.49 4. 61 0.38 C(8) 4. 19 0.43 1. 51 5.19 0.78 4. 80 0.37 C(9) 5. 23 0.75 1. 49 4.49 -0.63 4. 84 0.09 C(10) 4. 62 0.03 1. 71 4.67 -0.14 3. 55 0.32 C(ll) 3. 10 0.04 1. 56 3.95 0.29 3. 72 Q.28 C(12) 3. 44 -0.58 1. 28 3.88 -0.14 3. 23 Q.28 C(13) 3. 28 0.01 1. 59 4.08 0.32 4. 26 0.31 - 10 -Table 2 Measured and calculated structure factors (Unobserved reflexions are indicated by a negative sign in front of |FQ|). 0 -1C - 17.t c It 14.2 -4,4 0 -It) ICC 79.7" 0 16 14. 1 - L 5. 7 c -16 11.4 L2.« c 16 1.4 -8.1 L 0 -1" 1.1 -5.Q 0 16 -1.5 -2.3 0 - 16 16.4 -14.7 c - 16 I 7.P -17.6 c -16 -1.5 -I .2 c - 16 -l.t 2.4 i - 1* -l-l 1 .> c -16 -1.1 l.H 0 IS 12.5 -5.7 c - Ifl i r.) -17.7 a l" 12. 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' -T l.t - 1. t 0 t .. 1 fc.5_ 7 -7 -!:« - 1. 5 1.4 ! 6 "J •VI -9. 7 -5.1 z] uS 2 * "J ft. 1 1 -1. i 2.S ) fa .$ l.\ -fa. i -M IC. 1 13.9 3 fa _. 5 -1 •- 1.4 • 4.4 -1.7 -P 1.7 2.7 5 (. -4 - 1." -0.1 4.1 t. 1 -H 4. r 4. » 1 fa -ft IC.l -10.4 e -i .* -l.h 1 fa 5.*. -p i.i 7.0 2 fa -fa IC. . - J . t i" 9.4 -9.<: 2 « • -1 .<. I . 1 - 12 -Results and Discussion The equations of the mean plane of the individual rings as well as the equation of the mean molecular plane are given in Table 3. The individual five- and six-membered rings are strictly planar, but the molecule as a whole shows a small deviation from exact planarity. The outer atoms of the six-membered rings are displaced from the mean molecular plane (plane 1, Table 3) in the opposite direction to the atoms of the five-membered ring, so that the molecule is folded very slightly. The dihedral angles between the five-membered ring and the six-membered rings are 0.4° and 1.2°. Similar deviations from planarity were reported for dibenzoselenophene (8). The bond lengths and valency angles are listed in Table 4 together with the corresponding bonds and angles of dibenzoselenophene (8) and carbazole (7). The distances and angles are very similar except, of course, those involving unlike atoms. There are small variations in the bond lengths in the six-membered rings, C(10)-C(ll) being the longest, and C(l)-C(2) and C(3)-C(4) the shortest. These variations agree with bond order differences calculated by simple molecular orbital theory (11). The internal angles of the six-membered rings deviate slightly from 120° with angles at C(l) and C(ll) being reduced to about 118° while the other angles are slightly increased. The angles in the five-membered rings of the three molecules show greater differences as a result of the difference in angle at the hetero-atom, the angles being 91.5°, 86.6°, and 108.3°. for dibenzothiophene, dibenzo selenophene, and carbazole respectively. The C-S bond distance in o o dibenzothiophene, 1.740 (a = 0.008)A is close to the mean value of 1.72 A - 13 -Table 3 o Displacements (A) from mean planes (values underlined refer to the atoms used to define the planes) 1 2 3 4 C(l) +0.016 +0.007 +0.015 +0.082 C(2) +0.001 -0.011 +0.006 +0.069 C(3) +0.009 +0.005 +0.025 +0.063 C(4) -0.004 +0.005 +0.017 +0.033 C(5) -0.007 +0.027 +0.022 -0.009 C(6) +0.028 +0.074 +0.059 +0.011 C(7) +0.012 +0.058 +0.036 -0.001 C(8) -0.010 +0.026 +0.003 -0.006 S(9) +0.001 +0.011 +0.001 +0.043 C(10) -0.003 0 +0.001 +0.045 C(ll) -0.019 -0.007 -0.003 +0.014 C(12) -0.015 +0.009 +0.004 +0.001 C(13) -0.014 +0.011 -0.003 +0.004 Equations of planes (X1, Y, ; o in A referred to a, b, c*) 1 -0.7534 X' - 0.4711 Y + 0.4587 Z' = 0.3631 2 -0.7504 X' - 0.4682 Y + 0.4666 Z' = 0.3751 ! 3 -0.7551 X' - 0.4647 Y + 0.4626 Z' = 0.3791 4 -0.7567 X' - 0.4773 Y + 0.4468 Z* = 0.2862 Angles between-plane normals (degrees) 2 3 4 1 0.5 0.4 0.8 . 2 0.4 1.3 3 1.2 - 14 -Table 4 o Bond distances (A) and angles (degrees) in dibenzothiophene and related molecules Dibenzothiophene o(C-•S) = o 0.008 A a(C-S-C) = 0.4° o(C-•C) = 0.011 a(S-C-C) = 0.6 CT(C-C-C) = 0.7 a(C-•H) ~ 0.1 c(C-C-H) ~ 6 Dibenzothiophene g Dibenzoselenophene Carbazo! X=S X=Se X=NH C(l)-C(2) 1.396 1.384 1.371 1.390 C(7)-C(8) 1.371 C(2)-C(3) 1.390 1.385 1.377 1.398 C(6)-C(7) 1.380 C(3)-C(4) 1.361 1.370 1.380 1.395 C(5)-C(6) 1.379 C(4)-C(ll) 1.391 1.392 1.395 1.400 C(5)-C(12) 1.393 C(10)-C(ll) 1.408 1.409 1.398 1.404 C(12)-C(13) 1.409 C(l)-C(10) 1.384 1.386 1.395 1.395 C(8)-C(13) 1.387 C(ll)-C(12) 1.441 1.441 1.453 1.467 C(10)-X(9) 1.734 1.740 1.899 1.414 C(13)-X(9) 1.746 C(l)-C(2)-C(3) 121.1 . 121.6 121.1 121.3 C(6)-C(7)-C(8) 122.0 C(2)-C(3)-C(4) 121.1 120.5 120.6 120.4 C(5)-C(6)-C(7) •• 119.8 C(3)-C(4)-C(ll) 119.5 120.0 120.3 119.5 C(12)-C(5)-C(6) 120.4 C(4)-C(ll)-C(10) 119.2 118.7 118.1 118.8 C(5)-C(12)-C(13) 118.1 - 15 -Table 4 (Continued) X=S X=Se X=NH C(ll)-C(10)-C(l) 121.6 121.6 121.6 122.3 C(8)-C(13)-C(12) 121.5 C(10)-C(l)-C(2) 117.4 117.8 118.7 117.7 C(7)-C(8)-C(13) 118.1 C(ll)-C(10)-S(9) 112.8 112.3 112.4 108.8 C(12)-C(13)-S(9) 111.8 C(10)-C(ll)-C(12) 111.4 111.9 114.3 107.1 C(ll)-C(12)-C(13) 112.4 C(4)-C(ll)-C(12) 129.3 129.4 127.6 134.1 C(ll)-C(12)-C(5) 129.4 C(l)-C(10)-X(9) 125.6 126.2 126.0 128.9 C(8)-C(13)-X(9) 126.7 C(10)-X(9)-C(13) 91.5 91.5 86.6 108.3 Dibenzothiophene C(l)-H 1.09 H-C(l)-C(2,10) 114,128 C(2)-H 1.06 H-C(2)-C(l,3) 112,126 C(3)-H 0.99 H-C(3)-C(2,4) 120,117 C(4)-H 0.99 H-C(4)-C(3,ll) 117,122 C(5)-H 0.90 ' H-C(5)-C(6,12) 126,114 C(6)-H 0.85 H-C(6)-C(5,7) 104,135 C(7)-H 0.98 H-C(7)-C(6,8) 118,120 C(8)-K 0.95 H-C(8)-C(7,13) 126,114 - 16 -found for related conjugated heterocyclic molecules (12). The hydrogen atoms have been located with less precision. The o C-H bond lengths range between 0.85 and 1.09 (a = 0.12) A with a mean o value of 0.97 A. The H-C-C valency angles vary from 104 to 135 (a = o 6) with a mean value of 120°. The packing of molecules in the unit cell is shown in Figure 3. The shortest heavy-atom intermolecular distance is a C(5)...C(11) o distance of 3.57 A. Since only C(5) carries a hydrogen atom, there is no steric interaction. The shortest hydrogen-hydrogen intermolecular o distance is 2.39 A and involves the hydrogens of C(2) and C(7). Since o the van der Waal radius of hydrogen in 1.2 A, there is no steric strain. Figure 3. Projection of the structure along b. PART II THE DETERMINATION OF THE STRUCTURE OF DL-ORNITHINE HYDROBROMIDE - 19 -A. INTRODUCTION L-ornithine H2N(CH2)3CH(NH2)COOH is the key amino acid of the Krebs-Henseleit, or ornithine cycle in the mammalian liver. The highly toxic ammonia produced by the deamination of amino acids is converted into the much less toxic urea by means of the ornithine cycle. Urea, the chief nitrogen end product in mammals, is then, eliminated via the kidneys. Thus, although ornithine is not a consti tuent amino .acid of proteins, it is one of the more important amino acids in protein metabolism. B. THE STRUCTURE OF DL-ORNITHINE HYDROBROMIDE Experimental DL-ornithine hydrobromide was recrystallized from water and a small single crystal was cut from a large crystalline mass. The crystal appeared to be stable at room temperature. Unit cell and space group data were determined from rotation, Weissenberg, and precession photographs. o o Crystal data (X, Cu-K = 1.5418 A, X, Mo-K = 0.7107 A). —i a a DL-ornithine hydrobromide, C^^N^Br; M = 213.1; m.p. 223°. 0 Monoclinic, a = 12.18 ± 0.02, b = 7.88 + 0.02, c = 11.61 ± 0.02 A, 6 = 133° 39' ± 20'. °3 U = 806.3 A , D =1.74 (floatation), Z = 4, D = 1.75. m x F(000) = 432. Absorption coefficient for X-rays, uCCu-K^) = 72 cm \ u(Mo-K^) = 53 cm \ Absent reflexions: h0£ when £ is odd, OkO when k is odd. - 20 -5 Space group is P2^/c (C2n)* The intensities of the reflexions were estimated visually from Cu-K^ equi-inclination Weissenberg films of the h0£-h7£ layers; the layers were correlated with intensities measured from Mo-K precession a films of the hkO and hkh zones. The crystal used measured 0.25 x 0.38 x 0.50 mm and was approximately a right-angled parallelepiped. Of the possible 2171 independent reflexions within the copper sphere , 1559 were observed. The intensities were corrected for Lorentz and polarization effects, but not for absorption. Structure amplitudes were derived as usual. The bromide ion was located by means of a three-dimensional Patterson function (0.0458, 0.1271, 0.1875). Structure factors were calculated for all the three-dimensional data for bromine alone. The scattering factor for Br was obtained from the curve for the uncharged bromine atom from the International Tables for X-ray Crystallography (10) by comparison with the differences in the values of X and X (X = F, CI, I) and was corrected for anomalous dispersion according to the expression using the values Af' and Af" given in the International Tables. The isotropic thermal parameter, B, was taken as 4.0 A . The discrepancy factor was 0.39. A three-dimensional Fourier series was summed with Structure Analysis - 21 -phases based on the bromide ion; in this electron-density distribution, all the carbon, nitrogen, and oxygen atoms were identified. These were introduced to the structure factor calculations with scattering °2 factors from the International Tables and B = 4.0 A . During the first least-squares refinement cycle R dropped to 0.27. A second Fourier synthesis gave well-resolved peaks for each of the ten heavy atoms. Further refinement of the positional and isotropic thermal parameters, together with an overall scale factor proceeded by the block-diagonal least-squares method, the function minimized being 2 Zw(j F |—|F |) . As the structure factors are least accurate for the very strong reflexions which are difficult to estimate visually, the weighting scheme employed was = 1 for |FQ|<F' and = F /|F | II*''* for |Fo|>F , where F was taken as 9. After four cycles of isotropic least-squares refinement, R was 0.20. At this point the intensities of a few reflexions with very marked |F |-|F | differences were re-estimated visually. After an additional six cycles of isotropic,, refinement, R was 0.15 and the parameter shifts were small in magnitude and random in direction. Subsequent anisotropic cycles of refinement reduced R to 0.14. At that point the thirteen hydrogen atoms of the molecule were located by means of a difference synthesis. The hydrogen atoms are °-3 moderately well-resolved with peak densities of 0.7-1.3 eA . The hydrogen atoms were introduced into the structure factor calculations °2 with scattering factors from the International Tables and B = 4.0 A . During the final three cycles of least-squares refinement, the thermal parameters of the hydrogen atoms were refined isotropically while those of the heavier atoms were refined anisotropically. All the parameter shifts were small and nonsystematic; the largest parameter shift during the last cycle being one-third of a standard deviation for the non-hydrogen atoms and three quarters of a standard deviation for hydrogen atoms. The final observed and calculated structure factors are listed,in Table 5; R is 0.13 for the 1559 observed reflexions. The final three-dimensional Fourier synthesis is shown in Figure 4. The atoms are °-3 well resolved with peak densities of 70 eA for the bromide ion, ° ~* 3 °™3 °~3 16 eA for oxygen atoms, 12 eA for nitrogen atoms, and 10 eA for carbon atoms. These high peak densities may be the result of high absorption. The final three-dimensional difference synthesis revealed random fluctuations in electron density distribution as great as 1 1 eA . However, in the vicinity of the bromide ion there is a 3 eA , °-3 peak flanked on two sides by troughs at 2 eA and on each of the : °-remaining opposing sides by a peak of 1 eA The final positional and thermal parameters of the non-hydrogen atoms are in Table 6. The bond lengths and valency angles are in Table 7. The positional parameters of the hydrogen atoms which have been determined with much less accuracy are listed in Table 8, together with a summary, of the molecular dimensions involving hydrogen atoms. Results and Discussion Due to the presence of a centre of symmetry, the unit cell contains two of each of. the optical isomers of ornithine hydrobromide. The standard molecule in this analysis happens to be the D-isomer. The - 23 -Table 5 Measured and calculated structure factors (Unobserved reflexions are indicated by a minus sign in front of JF |). h k 1 •iii Ii ;• iiii iii i i iii iiii :jj j i ii;! |j ; i iii iii \ fi i;': -\t ii ii iii ii ii 1 '»il_ 1.0 i 1 | j| i * i «ii •»! i ! jji* -jjii 1 0 - -ft) |-i iii ii.i if" !" :j i i.t .iii [ t (»i» 11 !! It!' 'i ji'i '\'\ j ti i t V 1 .J v :| i iii ii !:» 1: i 'ii> J>i. i iii; ;!.;.: :i! ii iiii -iii :;; ; i;i .i;i il i 1 1' " :i iii; Ii \ i ii; 2ii 1 E |i i >.l 77* ;• i iiii ~K TW a jjlt i 1—a—•!:; t »ii :j | 'iii: 'ii:: •ii \ i 'ii i:i 1 •iii iiii 1 ! loit i * ~-W.\ ii "ii i J!J ;i-1 fill II.I i \ jp |i ii iii; 1'. • i i iii jjii Mil i -*_ _ _Jll|_ ill* ;• i iii i.i-1. t *'•> :;; * io!» lo'.b \ ii;i :i;i Ii if i | iiii •iii :i j iii •mi i 'iii 1 -t j 1S»1_ Ii i i :l ->.'< i t'a w ii i \ iiit iiii J i "'• iilii ij ;i:; 'ii: -• ;i ii -J_ _. L Itij I; ii iii \ si; rS 1 Iii ii: ;< - 1— -I. |;i -ii iii ;jii ill'. \ j ijjj |: • n. -lis -iii 1 • jjii |*io ii r;.i iii iiii ii • \a -j ii; «:] .J M ; i i'; •. :i; i iiii n'.l M'.l -ij :i [ iiii iiii j :*:; ; iiii ii; -! I 3 iiii iiii ; 1? 0 iiii iii;! :i:I •! i ii: ":* I S3 "B: .-; — j'ii M.. ° i & is!; ;| .j : i I'i I; I tie ij i £ "i -\'.' '!;* : L 4l!« •II • il'i H'» i iii' -Jii' i ;ii iii' iii iii 1 i ii iii :| !;" :J 1..4 -11.' ii Ii lti( "i-io i u!»_ jjii 3— i iiii ;|i i i ii ;i \ i is il: i I -i't -j'.t "J ii;! 1 j j • ^il 'r'ii :| III:! : ':! . i*:p -I.N iii I § :!jii 1 ,:i; si; ii ,1 iii -Ii:' i •i;i s •i. J».o 11.' "If"ii • j «ij _-t la iV.o J.ii ;'i iii iii -10 ! iil^l: l w Ii 1 j iii ii i •I «: i ioi! I": - J L. Iii) :J :* II «I i iiii iiiii :ii 1i| iii 1 i Ii 1 :|! ii H; iiii :i *: • I -l -ii.'i iii ii iiii iii :; iii iiiii ii '; iii; iiii j i !jij |j iiii iiii. -a. "rl! -ill ii iii* ill's :| ii't '''4 ;i i j ;i;i :i;i .* .si; iii iii % 11 a! :1i —i»tf~ nii S ! (til 4- i ii ii -10 ; Ii 1 • 1 ;i 1 j 1 ii - 1 i if"!" i !__ Ijij.. | 4-:', 'iiihiii ;i i iii Iii :i 11 iiii ;j -j I:! "it III* - •i .', I II'N i'i' 1 til -l.t -!' 1 •' -11 \ Hi: iiiii il i iii |i 1 1 | 1 iii -il i fi:! a J,i. • • -i _ _ 1 I j jl« i o 4 A Figure 4(a). Sections of the final electron-density distribution parallel to °-3 (010). Contours at intervals of 2 eA , exceDt at Br where °-3 contours are at intervals of 10 eA (b). A perspective drawing of the molecule as viewed along the b-axis, showing atom numbering used. - 25 -final three-dimensional electron density distribution is shown in Figure 4 together with a drawing of the molecule giving the atom numbering used in this analysis. The compound is a zwitterion, -+ + -Br NH3(CH2)3CH(NH3)COO , with both nitrogens accepting protons to form tetrahedral C-NH3+ groups. The molecule is composed of two approximately planar groupings of atoms, a carboxyl group and an aliphatic side chain terminating in nitrogen atoms. The equation of the mean plane through 0(1), 0(2), C(l), C(2) is -0.3206 X' + 0.9459 Y - 0.0501 Z' = 1.2152 O where X', Y, Z' are coordinates in A with reference to orthogonal axes a, b, and c*. The deviations of the atoms from the plane are: o o o o 0(1), +0.005 A; 0(2), +0.005 A; C(l), -0.014 A; and C(2), +0.003 A. o The a-nitrogen atom, N(l), lies 0.823 A out of the plane as compared o o to a value of 0.436 A for L-glycine (13), 0.446 A for L-lysine o hydrochloride dihydrate (14) and 0.838 A for L-ornithine hydrochloride (15). The aliphatic side-chain is fully extended; its mean plane has the equation: 0.8133 X' + 0.4790 Y - 0.3302 Z' = 2.5741 o o The deviations from the plane are N(l), -0.074 A; C(2), +0.086 A; boo o C(3), +0.069 A; C(4), -0.116 A; C(5), -0.029 A; and N(2), +0.050 A. o C(l) is displaced +1.399 A. The dihedral angle between the two planes is 77.9° as compared to 78.7° for ornithine hydrochloride (15) and 71.4° for lysine (14). The two C-0 distances are equal within experimental error, the o mean value being 1.249 A. Table 6 4 ° 2 2 Final positional (fractional x 10 ) and thermal (A x 10 ) parameters, with standard deviations in parentheses Atom X y z C(l) 4628(15) 3446(22) 2064(16) C(2) 3243(12) 2833(22) 1749(15) C(3) 2284(13) 4375(23) 1371(14) C(4) 3073(14) 5464(26) 2857(15) C(5) 2141(13) 7068(23) 2421(14) N(l) 2316(13) 1615(21) 0435(15) N(2) 3032(12) 8259(22) 3772(13) 0(1) 5823(11) 3692(15) 3481(13) 0(2) 4434(11) 3710(16) 0873(12) Br 0447(1) 1279(2) 1891(2) Atom U-,., U, ^ 11 12 13 22 23 33 C(l) 2.56 0.55 1.75 2.98 0.27 3.33 C(2) 2.20 -0.16 1.98 2.77 0.01 3.72 C(3) '2.37 -0.41 1.92 3.18 -0.51 3.23 C(4) 3.41 0.35 2.32 4.48 -0.47 3.36 C(5) 2.80 0.06 1.94 3.08 -0. 32 2.90 N(l) 3.32 -0.06 2.31 2.90 -0.05 4.31 N(2) 2.96 -0.11 2.05 4.16 -0.58 3.36 0(1) 2.45 -0.25 2.18 4.00 0.27 4.37 0(2) 4.11 0.09 3.25 5.06 0.81 4.19 Br 3.20 -0.10 2.22 3.85 -0.09 3.66 Mean a: C,N,0 0.35 0.44 0.23 0.85 0.44 0.35 Br 0.05 0.04 0.04 0.14 0.05 0.06 - 27 -Table 7 o o Bond distances (A) and angles (degrees) (a = 0.02 A and 1.5°) C(l)-C(2) 1.537 C(l)-C(2)-C(3) 108.3 C(2)-C(3) 1.525 C(2)-C(3)-C(4) 111.2 C(3)-C(4) 1.532 C(3)-C(4)-C(5) 110.1 C(4)-C(5) 1.533 Mean C-C-C 109.9 Mean C-C 1.532 C(l)-C(2)-N(l) 112.6 C(2)-N(l) 1.465 C(3)-C(2)-N(l) 109.6 C(5)-N(2) 1.473 C(4)-C(5)-N(2) 109.9 Mean C-N 1.469 Mean C-C-N 110.7 C(l)-0(1) 1.249 C(2)-C(l)-0(1) 116.8 C(l)-0(2) 1.248 C(2)-C(l)-0(2) 116.9 Mean C-0 1.249 Mean C-C-0 116.9 0(l)-C(l)-0(2) 126.2 - 28 -Table 8 Hydrogen atoms 3 ° Positional parameters (fraction x 10 ; a ^ 0.25 A; the mean B being o 2 o o 1.3 A ), bond lengths (A, a ^ 0.25 A), and valency angles (degrees, a ^ 15 - 20°) Atom Bonded to x y z H(l) N(l) 269 077 049 H(2) N(l) 185 205 -055 H(3) N(l) 157 098 013 H(4) N(2) 393 832 411 H(5) N(2) 360 762 494 H(6) N(2) 260 903 369 H(7) C(2) 358 250 284 H(8) C(3) 217 517 031 H(9) C(3) 123 398 093 H(10) C(4) 470 563 381 H(ll) C(4) 283 493 374 H(12) C(5) 192 752 152 H(13) C(5) 155 725 256 N-H 0.8-1.1, mean 0.9 C-H 0.9-1.4, mean 1.1 C-N-H 107-130, mean 117 H-N-H 86-124, mean 101 C-C-H, 78-127, mean 108 N-C-H H-C-H 111-120, mean 114 - 29 -Table 9 Carbon-oxygen bond lengths in some amino acids Amino Acid C(l)-0(1) C(l)-0(2) Mean DL-ornithine hydrobromide 1.249 A O 1.248 A 1.249 A L-ornithine hydrochloride 1.257 1.245 1.251 L-lysine hydrochloride dihydrate 1.250 1.246 1.248 L-alanine 1.247 1.256 1.253 As shown in Table 9, these values agree well with the corresponding internuclear distances of other amino acids. The two C-NH^"*" bonds also are equal within experimental error (Table 7); the average value o o of 1.469 A is similar to that of 1.482 A for L-lysine (14), and that o of 1.492 A for ornithine hydrochloride (15), these differences probably not being significant. The C-C bond lengths do not differ significantly from each other (Table 7). The mean C-C distance of 1.532 A agrees, well with the single bond length of 1.533 proposed by Bartell (16) on the basis of electron diffraction studies of normal hydrocarbons butane through heptane. The mean C-C distance is similar to the '.' o ; o analogous values of 1.524 A for lysine (14), 1.525 A for L-alanine (17), o and 1.530 A for ornithine hydrochloride (15). The bond angles of the carboxylate group are equal within the limits of experimental error to the analogous'angles in lysine (14), and ornithine (15). - 30 -Table 10 Carboxylate bond angles in ornithine and lysine derivatives Angle Compound Ornithine HBr Ornithine HC1 Lysine HC1-2H20 0(l)-C(l)-0(2) 126.2° 126.6° 125.5° C(2)-C(l)-0(1) 116.8 116.0 116.8 C(2)-C(l)-0(2) 116.9 117.0 117.7 Similarly, the C-C -N angles of the above compounds resemble one another; however, the agreement is not so good as in the case of the carboxylate group angles. Table 11 Carbon-carbon-nitrogen angles in ornithine and lysine derivatives Angle Compound Ornithine HBr Ornithine HC1 Lysine HC1-2H20 C(l)-C(2)-N(l) 112.6° 110.3° 109.7° C(3)-C(2)-N(l) • 109.6 107.8 111.8 C(4)-C(5)-N(2). 109.9 110.4 C(5)-C(6)-N(2).; 110.9 The C-C-C angles of the three amino acids are similar and close to the tetrahedral value of 109.5, - 31 -Table 12 Carbon-carbon-carbon angles in ornithine and lysine derivatives Angle Ornithine HBr Compound Ornithine HC1 Lysine HC1-2H20 C(l)-C(2)-C(3) 108.3° 110.2° 109.8° C(2)-C(3)-C(4) 111.2 112.4 114.6 C(3)-C(4)-C(5) 110.1 109.0 110.0 C(4)-C(5)-C(6) 111.5 The visual data are not sufficiently accurate to yield reliable values for the hydrogen parameters. The average N-H bond length of o o o 0.89 A is close to the value of 0.94 A for lysine (14), and 0.95 A for ornithine hydrochloride (15). On the other hand, all these bonds o are somewhat shorter than the standard N-H bond distance of 1.03 A o for the ammonium ion and that of 1.01 A for ammonia. However, these differences are not significant. o The mean C-H bond length of 1.14 A is insignificantly longer o than the analogous mean values of 1.06 and 1.05 A for lysine (14) and ornithine (15) respectively. A projection of the structure is shown in Figure 5. The most significant feature of the packing is a system of three N-H...0 and three N-H...Br hydrogen bonds involving all six active hydrogen atoms. The terminal nitrogen atom, N(2), donates three protons, one to the bromide ion of the standard molecule at [010], another to the carboxylate 0(2) of the nearest screw-axis-generated molecule at [111] and the last gure 5. Projection of the structure along b; broken lines are hydrogen bonds. - 33 -proton to the carboxylate 0(1) of the adjacent center-of-symmetry-generated molecule at [111], The side-chain nitrogen atom, N(l), also donates three protons, one to the carboxylate 0(1) of the closest screw-axis-generated molecule at [101] and the remainder to nearby bromide ions. The hydrogen bond distances and angles are in Table 13. One of the C-N...Br angles is 155°, but the other C-N...0,Br angles are all in the range 95-109°. The positions of the hydrogen atoms support the hydrogen bond assignments; the H...0 distances are about o o 2.0 A, the H...Br distances 2.6 A, and the bonds all show the i usual deviations from exact linearity, the H-N...0, Br angles varying from 7° to 25°. There is one further short N(2)...0(2) internuclear o contact of 2.97 A, but the C-N...0 angle is 166° and there is no o intervening hydrogen atom, the shortest H...0 distance being 2.6 A, so that this contact does not represent a hydrogen bond. The N-H...0 distances (2.84, 2.84, 2.89 A) and the N-H...Br distances (3.29, 3.36, o 3.46 A) are close to the values usually found in these types of systems (18). The bromide ion acts as an acceptor for three hydrogen bonds, the N...Br ...N angles being 91, 91, and 139°. 0(1) accepts two protons, the C-0...N angles being 124° and 127°, and the N...0...N angle 108°. . 0(2) accepts one hydrogen bond, and the C-0...N angle is 118°. The above system of hydrogen bonds is complex in that the five heavier atoms of the standard molecule participate in twelve hydrogen bonds which involve the corresponding atoms [N(l), N(2), 0(1), 0(2), Br] in twelve different molecules. The structure of DL-ornithine hydrobromide is similar to that of L-ornithine hydrochloride. Layers of L-ornithine molecules parallel - 34 -to the ab plane are almost identical in the structures. In L-ornithine o hydrochloride these layers are stacked along c, giving a c-axis of 5 A; in DL-ornithine hydrobromide, the layers of L-ornithine molecules are related by the c glide plane to layers of D-molecules (Figure 5) resulting in a c-axis of about double the length. - 35 -Table 13 o Distances (A) and angles (degrees) in the hydrogen bonds, N-H...A (A = 0 or Br) Bond C-N...A N(l)-H(l)...0(1), IV[101] N(l)-H(2)...Br, II[001] N(l)-H(3)...Br, III[000] 2.84 3.46 3.36 105 109 155 N(2)-H(4)...0(2), IV[111] N(2)-H(5)...0(1), III[111] N(2)-H(6)...Br, I[010] 2.84 2.89 3.29 99 106 95 Equivalent positions are I x IIIII -x IV -x - y -y + y + z -z together with translation in a, b, and c indicated in square brackets. PART III THE DETERMINATION OF THE STRUCTURE OF HISTAMINE DIPHOSPHATE MONOHYDRATE - 37 -A. INTRODUCTION Histamine, one of the most important autacoids in the human body, is synthesized in vivo by the enzymatic decarboxylation of histidine. Almost all mammalian tissues contain histamine and are capable of synthes ing it. The histamine which is released by injured body tissues gives rise to many of the signs and symptoms of trauma and allergy. B. THE STRUCTURE OF HISTAMINE DIPHOSPHATE MONOHYDRATE Experimental Histamine diphosphate was recrystallized from water. The resultant colorless, transparent, needle-shaped crystals are elongated along a and appear to be stable in room air; no radiation damage was observed. The unit cell parameters and space group were determined from various rotation, Weissenberg and precession films. The melting point could not be determined as the crystal began to lose water of hydration at 88° and became completely liquid at 118°C. o Crystal data (A, Mo-K = 0.7107 A). — a 4-(2-aminoethyl)-imidazole diphosphate monohydrate, C<.H.j^N30gP2; M = 325.2.-; O Monoclinic, a =.7.99 + 0.01, b = 13.17 ± 0.01, c = 13.19 ± 0.01 A, 3 = 111.2 ± 0.1°. °3 ; :' U = 1294 A , D. = 1.669 (floatation), Z =4, D = 1.668. m x F(000) = 680 . Absorption coefficient for X-rays, u(Mo-K ) = 3.90 cm \ a Absent reflexions: hOfc when % is odd, OkO when k is odd. Space group P2^/c (C^). The intensities of all reflexions with 26(Mo-K ) less than 46° a - 38 -were measured on a G.E. XRD-5 Spectrogoniometer, with Single Crystal Orienter, using a scintillation counter, Mo-K^ radiation (zirconium filter and pulse height analyzer), and the moving-crystal moving-counter technique (9). The corresponding minimum interplanar spacing o is 0.91 A. All the intensities were corrected for background and the structure amplitudes were derived as usual. The crystal, measuring 0.5 x0.5 x 2.0 mm, was mounted with a* parallel to the goniostat axis. Possible errors in the measured structure factors were examined. Considering the crystal as a cylinder of mean diameter 0.5 mm, uR is 0.0975 and hence the absorption correc-tion factor A is 1.10 and constant in the range 9 = 0-40°; therefore, the error due to absorption is negligible. In addition, absorption errors due to non-uniformity of crystal dimension were estimated by considering the longest and shortest path lengths in the cross-section of the crystal. The absorption corrections for the corresponding structure factors are exp (3.9 x 0.07/2) and exp (3.9 x 0.05/2), that is 1.15 and 1.10 respectively. Thus the maximum deviation from the mean correction of 1.125 is 0.025 or 2.2%. Since the cumulative possible maximum error in F due to absorption is less than 2.3% and since the o majority of errors will be much smaller than this value, no correction o was made for absorption. 1747 reflexions in the range 0 < 26 < 46 were observed; 1554 (89%) had intensities above background. Structure Analysis The positions of the two phosphorus atoms were determined from a three-dimensional Patterson synthesis (P-l, 0.333, 0.125, 0.370; P-2, 0.740, 0.290,.0.216) and structure factors were calculated for all the 39 -three-dimensional data for phosphorus only using scattering factors from the International Tables for X-ray Crystallography, 1962 (10) °2 and isotropic thermal parameters of 4.0 A . The discrepancy factor, R, was 0.57 for the observed reflexions. A three-dimensional Fourier synthesis with the phase angles based on the phosphorus atoms revealed the positions of all the non-hydrogen atoms. When these were introduced into the structure factor calculations with scattering factors from the °2 International Tables and B = 4.0 A , R dropped to 0.32. Subsequent refinement of the positional and isotropic thermal parameters together with an overall scale factor, was carried out by means of the block-diagonal least-squares method, the function minimized being 2 Ew(|F |-|F I) . Since the structure factors were considered to be 1 o 1 1 c ' least accurately measured for the strong reflexions which are most affected by absorption as well as for the weak reflexions whose intensities are similar to that of background radiation, the following weighting scheme was employed: r •• 1 where F* = 16 and G* = 26. This scheme gives = 0.80 for |F | =1, maximum i^w = 1 for | FQ | = 16 and thereafter decreasing weights so that at |F | =42, for example, •w = 0.71. Unobserved reflexions were assigned •w = 0.29. After seven isotropic least-squares refinement cycles, R was 0.12; shifts in positional parameters were about one-third of a standard deviation while - 40 -thermal parameter shifts were of the order of one standard deviation. The parameter shifts of the water oxygen atom, however, were larger. Therefore, its position was redetermined on an additional difference synthesis. Six anisotropic refinement cycles reduced R to 0.09. Thereafter, a difference synthesis was summed and all 17 hydrogen atoms (with peak °-3 values of 0.5-0.7 eA ) were located (Figure 6). The hydrogen atoms were included in subsequent structure factor calculations with °2 scattering factors from the International Tables and B = 4.0 A . After six refinement cycles in which the thermal parameters of the heavy atoms were refined anisotropically while those of the hydrogens were refined isotropically, R was 0.07. However, as the temperature factors of the water hydrogens were too high at this point, their positions were redetermined on a difference synthesis. At the completion of the final series of eight least-squares refinements, the positional parameter shifts were small and nonsystematic, the largest shift being one-sixth of a standard deviation for the heavy atoms and one-third of a standard deviation for the hydrogen atoms. The positional and anisotropic thermal parameters of the heavier atoms from the.final least-squares cycle are given in Table 14, together with their standard deviations computed from the inverses of the diagonal terms of the matrix of the least-squares normal equations. Also listed in Table 14 are the hydrogen atom positional and isotropic thermal parameters together with their standard deviations. The final electron-density distribution is shown in Figure 7, the atom numbering used in Figure 8. - 42 -Table 14 Final positional parameters (fractional, x 10^ for P, 0, N, and C; 3 0 2 2 0 2 x 10 for H) and thermal parameters (U.. in A x 10 ; B in A ), with p 2 their standard deviations in parentheses [a(B) for hydrogen=3-4 A ]. Atom x v z B P(l) 3466(4) 1287(2) 3749(2) P(2) 7489(4) 2879(2) 2299(2) 0(3) 1917(11) 1800(7) 2789(6) 0(4) 2743(11) 0259(7) 4005(6) 0(5) 3879(11) 1925(7) 4759(6) 0(6) 4989(11) 1139(7) 3351(7) 0(7) 5669(11) 2715(7) 2463(7) 0(8) 7098(11) 2715(7) 1062(7) 0(9) 8026(12) 3965(7) 2565(7) 0(10) 8852(11) 2118(7) 2915(7) N(ll) 2734(14) 4402(9) 1352(8) C(12) 1971(17) 4447(12) 2232(10) C(13) 3389(19) 4695(12) 3299(11) C(14) 2775(16) 4695(10) 4246(10) 0(15) .: 2361(17) 5467(10) 4782(10) N(16) 2046(14) 5058(8) 5662(8) 0(17) '2231(16) 4070(10) 5648(9) N(18) 2659(14) 3819(8) 4790(8) 0(w,19) ' 9536(15) 1440(13) 4990(9) H(20) 363(23) 379(13) 166(13) 3.8 H(21) 187(17) 433(10) 065(10) 1.3 H(22) 323(22) 504(13) 121(13) 3.7 H(23) 117(18) 375(11) 226(11) 1.5 H(24) 099(18) 500(11) 208(11) 1.7 H(25) 424(17) 407(11) 338(10) 1.3 H(26) 394(19) 540(11) 319(11) 2.3 H(27) 234(13) 624(8) 461(8) 1.0 H(28) 204(18) 542(11) 628(11) 2.0 H(29) 196(13) 355(8) 615(8) 1.0 H(30) 295(18) 315(11) 469(11) 1.7 H(31) 894(25) 167(15) 430(15) 5.5 H(32) 870(25) 160(15) 540(15) 5.5 H(33) 084(22) 192(13) 296(13) 3.7 H(34) , 561(22) 212(13) 283(13) 3.7 H(35) 612(21) 278(13) 076(13) 3.2 H(36) "• 753(24) 485(14) 151(14) 4.7 - 43 -Table 14 (Continued) Atom Ull U12 U13 U22 U23 U33 P(D 2. 53(12) 0.06(12) 1. 43(9) 2. 69(16) -0. 06(12) 2. 80(12) P(2) 2. 78(13) 0.64(12) 1. 43(10) 2. 43(15) 0. 43(12) 3. 10(13) 0(3) 3. 36(38) 1.17(40) 1. 50(28) 5. 57(55) 0. 64(39) 2. 87(36) 0(4) 4. 55(40) -1.11(39) 2. 22(29) 3. 61(47) -0. 36(37) 3.62(37) 0(5) 3. 53(40) 0.20(37) 1. 31(30) 3. 50(46) -0.91(37) 3. 49(38) 0(6) 3. 38(37) 0.39(36) 2. 08(29) 3. 45(47) 0.40(38) 4. 40(40) 0(7) 4. 56(40) 1.72(41) 3. 54(32) 4. 78(54) 2. 18(44) 6. 57(47) 0(8) 3. 39(40) 0.55(38) 1. 19(31) 4. 05(48) -0. 76(39) 3. 59(40) 0(9) 6. 24(51) 0.05(42) 2. 07(35) 3. 07(47) 0. 05(39) 3. 78(41) 0(10) 3.45(40) 0.62(40) 1. 58(31) 4. 43(51) 1. 21(41) 4. 16(41) N(ll) 4. 74(53) -0.18(51) 2. 26(37) 4. 47(65) -0. 60(48) 3. 63(47) C(12) 3. 77(62) 0.12(62) 1. 48(45) 5. 43(84) 0. 26(61) 3. 26(57) C(13) 4. 64(64) -0.47(67) 2. 09(46) 5.63(87) 0. 39(65) 3. 95(60) C(14) 3. 13(56) -0.15(55) 1. 39(43) 4. 03(72) 0. 36(56) 3. 48(57) C(15) 3. 91(58) -0.09(55) 1. 68(44) 3. 34(67) 0. 22(55) 3. 66(57) N(16) 4. 25(51) 0.19(47) 1. 61(36) 3. 62(58) -0. 37(44) 2. 99(45) C(17) 3. 55(57) 0.20(54) 1. 28(42) 3. 62(67) 1. 09(52) 2. 78(51) N(18) 4. 60(54) 0.02(47) 1. 86(40) 2. 78(54) -0. 36(46) 4. 05(51) 0(19) 7. 66(60) 7.99(69) 4. 36(45) 18. 55(121) 6. 73(70) 7. 02(58) - 44 -Figure 8. Drawing of the structure viewed along a and showing the atom numbering used. - 46 -The final measured and calculated structure factors are given in Table 15; R is 0.072 for 1554 independent observed reflexions. A final three-dimensional difference synthesis was computed and showed °-3 random fluctuations as high as ± 0.6 eA , Results and Discussion The structure contains a histamine cation, two H„P0, anions and 2 4 a molecule of water. The imidazole ring of histamine appears to be planar within the limits of experimental error. The equation of the mean plane is 0.8206 X' + 0.0908 Y + 0.5642 Z' = 3.659 O where Xf, Y, and Z' are coordinates in A referred to the orthogonal axes a, b, and c . The deviations of the atoms from the mean plane are: C(14), +0.009 A; C(15), -0.008 A; N(16), +0.004 A; C(17), +0.002 A; and N(18), 0 -0,007 A, The deviations of the corresponding hydrogen atoms from the o o plane of the imidazole ring are: H(27), +0.02 A; H(28), +0.23 A; H(29), o o -0.08 A; and H(30), +0.08 A. Thus the hydrogens lie in the plane of the heterocyclic ring within the limits of accuracy of the method. The deviations of the side chain atoms from the imidazole plane are: C(13), o o o +0.12 A; C(12), -1.16 A; and N(ll), -0.93 A; all highly significant displacements. The ethylamine side chain is approximately planar; the equation of the mean plane through N(ll), C(12), C(13), C(14) being: -0.1541 X1 + 0.9743 Y - 0.1643 Z' = 5.159 O with deviations of +0.021, -0.018, -0.024, and +0.021 A respectively. The dihedral angle between the plane of the ring and the plane of the side, chain is 82.5°. However, the plane of the chain does not bisect the ring, instead it is rotated toward N(18) so that - 47 -Table 15 Measured and calculated structure factors (Unobserved reflexions are indicated by a negative sign in front of JF j). kl /FD/FC h=0 0 2 5B.2 -51,9 0 4 6 7.6 62.lt 8 I 37.7 -38.1 8 3 28.0 20.1 7 -11 4.1 2 7 11 11.a -14 a 8 0 5 -11 15.0 15.4 11 17.7 15.9 4-8 4.7 2.1 4 8 14.9 16.7 4 4 37.6 37 4 -5 9.9 a 4 7 5.4 -5 4 -7 10.4 12 4 <i -'l.l 0 1 2 TT 0 7 0 2 8 24 2 -10 15 2 10 12 2 -12 32 .8 -2 .8 -15 .4 12 .2 J2 .0 .9 .8 .5 It / 45.4 46.5 8 9 22.4 -22.b 8 11 6.6 -7.1 9 2 37.5 37.0 9 4 10.5 10.2 B -2 -t.7 -5 tt 2 47.9 50 2 43.7 44.0 -2 22-6 20-4 4 16.6 -19.1 -4 9.3 9.2 6 B.l T.7 4 10 9.6 10.1 4 -12 U.O -12.a 5 -1 7.5 10.0 5 1 33.2 30.4 5 -3 -1.5 1.8 8 -4 2J.5 22 B 4 17.0 16 8 -6 39.J 42 8 b 12.2 -3J 8 -8 13.6 -12 8 B 6.9 -6 3 5 5 3 1 4-9 5.7 b 4 -11 7.8 -7 4 11 5.4 2 4 -13 14.6 -8 5 0 31.1 -30 5 2 6.5 8 3 -1 4U 3 I 10 J -3 48 3 J 42 3-5 4 . 7 49 .4 -9 .2 -45 . J 40 .2 0 .9 .6 .2 .0 0 6 50.3 -47.9 0 8 62.J 63.1 0 10 -2.0 -2.9 0 12 -2.3 -7.2 t I 17.9 -11.7 1 3 96.2 35.8 9 6 23.3 -24.0 9 8 16.0 -6.9 9 10 6.5 10 9 7.5 -J.6 10 1 10.1 1.7 10 1 31.2 -31.1 -6 37.1 3B.Y 7 8 -2.1 0.1 -6 4.5 -2.0 -10 6.0 -3.4 10 7.3 -6.5 7 -12 -2.4 -4.t 5 3 3B.0 -J7.5 5 -5 8.7 -7.8 5 5 44,4 43.9 5 -7 25.2 -26.5 5 7 12.2 -13.3 5 -9 24.6 24.6 8 -10 12.9 -U a io 10.7 IT 9 -I 62.1 65 9 1 37.2 -36 9 -3 12.9 -12 9 1 15.1 -14 0 2 3 5 1 I 5 -2 25.9 -24 5 4 -1.7 -I 5 -4 14.J 15 5 6 9.0 9 5-6 3.7 -0 5 » 26.3 -28 9 a t 9 0 J -7 15 3 7 31 3,-9 9 3 9 0 3 -TL B .9 17 .3 11 .a a . 1 -8 . 7 -20 .5 .1 .0 .3 1 5 b.l 6.0 1 7 26.5 -26.6 1 9 45.2 -•.8.4 1 11 '16.3 17.2 1 1) -2.4 6.6 10 5 49.2 4 5.0 10 7 -2.2 -D.4 11 2 35.4 37.0 11 4 6.7 6.3 11 6 8.7 -9.1 11 8 12.5 10.a B 1 40.5 40.9" B -1 23.2 24.0 B 3 14.9 -15.4 b -3 8.8 -9.9 8 5 10.2 10.7 8 -5 -1.9 -5.1 5 9 17.9 18.5 5 -11 10.B -11.4 5 -13 6.2 J.O 6 0 7.8 3.1 6 -2 16.7 15.1 6 2 5.8 5.7 9 -5 10.7 11 9 5 2t.8 -21 9 -7 27.0 -28 9 7 29.7 30 9 -9 14./ 13 9 9 12.4 -11 2 6 0 7 7 5 -8 26.4 -78 5 -10 35.6 -37 5 10 23.0 24 5-12 15.J 15 6 1 8.7 -9 6 -1 46.4 50 0 8 I 4 0 7 4-2 tl 4 2 48 4-4 6 4 4 15 .6 I .7 14 . 6 -47 .9 -5 .3 14 . 1 .2 .5 . J .0 .a .6 .0 . 7 .1 .5 2 2 ,92.H A9.8 2 4 92.5 -92.1 2 6 16.1 17.5 2 8 30.9 -13.7 2 10 ' 5.6 -7.0 2—T2 rBT8 11 .4 12 I 15.7 -15.1 12 1 7.0 1.0 12 5 7.2 -i.5 12 7 6.6 5.2 13 2 6. 1 0.1 13 4 7.4 -5.9 (j 1 I>6.4 -27.6 6 -7 11.4 -12.2 b 9 25.B 25,0 B -9 30.5 30.7 B -11 20.1 -20.6 9 0 34.0 -11.4 6 -4 25.6 25.7 6 4 4.0 -2.B 6 -6 5.6 -4.4 b 6 10.1 10.0 6 -8 29.1 29.7 b 8 4.8 0.0 0 0 -1.9 2 0 -2 4.4 -4 0 2 16.0 -16 0 -4 12.1 11 0 4 16.7 -16 0 -6 16.4 -17 t 9 5 7 3 2 6 3 18.1 -19 6 -J 26.4 -2B 6 5 27.1 -29 6 -5 26.1 -26 6 7 36.4 15 6 -7 12.0 -12 6 0 4 b -2 4 -a 56 4 8 6 4 -10 5 4 10 9 .0 0 .4 -53 .0 5 . 3 6 .4 -9 .4 19 3 1 111.1 105.1 3 3 39.0 -26.8 J 5 45.0 45.5 ) 7 10.a -10.7 3 9 20.1 21.1 14 1 11.1 12.0 h=1 H 2 9.4 8.7 9 -2 39.0 38.2 9 4 21.1 21.0 9 -4 -1.9 4.4 9 6 27.4 26.1 1 -6 -2.0 3.1 b -10 6.7 -4.7 b 10 6.5 3,6 5-12 6.1 L.L 0 6 -2,2 -5 0 -8 6.2 5 0 8 6.4 -4 0 -10 16.2 -15 1 -I b.4 -7 7 3 1 2 7 -1 9.8 -10.4 1 26.4 -27.2 7 - 3 a.o -a.o 6 9 9.4 6 6-11 11.1 -10 7 0 -1.7 D 7 2 4.8 -5 9 0 7 3 5-1 51 5 1 31 5-1 13 5 114 5-5 5 .6 -51 . 1 31 .5 - 12 .0 - 1 . J 2 .2 .8 i 13 10.2 9.3 4 0 16.1 15.4 4 2 32.3 -12.5 4 4 -1.4 11.0 4 6 53.4 -55.5 0 0 65 0 -2 Bi .0 -53.6 .6 -77.3 .6 90.4 .0 54.1 .9 69.3 *» 8 13.9 -12.5 9 -B 2J.5 -24.1 7 3 JO.4 2U.7 7 -5 11.fl 13.8 7 5 40.9 -42.2 7 -7 30.7 12.5 7 7 -2.1 J.O 3 -4 49 3 4 70 1 -1 8.J 9 1 3 10.1 11 I -5 29.6 11 15 9.1-7 1 -7 16.1 17 1 7 24.4 -25 2 9 2 9 0 9 -10 5.2 2.3 0 -9 13.J -11.4 0 1 4.4 2.1 7 -2 52.4 51 7 4 -1.9 0 7 -4 G.6 B 7 6 4.5 4 7-6 4.1 2 1 B 5.0 -3 B 2 9 6 3 9 5 5 -1 5-7 15 5 7 17 5 -9 24 5 9 9 5 -11 30 .9 2 . 1 15 . 1 -19 .0 2 .1 . 5 .0 .0 4 8 12.b -2b.9 * 10 10.5 <}.-4 12 li.J 10.t 5 1 28.a -26.7 5 3 24.6 -20.8 5 5 48.J -46.1 5 7 44.7 4b.7 5 9 3B.1 -40.8 6 15 a 2a -10 11 3 10 51 .0 -15.9 .3 - 1. 1 ,0 -29.H 6 -34.0 .4 5J.1 0 -1 5.3 -7.1 0 J 11.5 U.4 0 -1 14.0 -13.a 0 5 44.9 -44.2 0 -5 U.O -15.5 0 7 11.4 U.7 7 -9 27.8 -26.9 7 9 6.J -5.4 7 -tl 11.4 10.3 1 -9 9.4 -12 11 5.7 3 2 0 15.0 15 2 -2 29.2 JL 2 2 24.6 -24 1 7 9 2 3 0 6.9 8.0 a -2 -1.8 -2.5 8 2 60.9 -60.3 7 -8 23.0 -24 7 -10 22.6 -23 1 10 17.5 IT 7-12 11.3 9 B 1 19.4 38 9 2 3 B 5 -1J 7 6 0 19 6-2 6 6 2 -I 6-4 -1 .2 5 .4 17 . 1 . J .1 .5 .2 D -12 19 3 12 -2 -I 54 1 12 -3 6 J J? .1 -16.4 .4 12.'. 7 49.2 .a -11.7 .6 -5.1 .7 -JV7T 0 -7 2J. 7 23,7 1 -8 12.9 12.0 1 0 12.2 5.7 I 2 49.7 -51.1 I -2 24.2 -24.J 8 -4 13.5 14.0 8 4 14.5 14.2 B -6 18.1 -20.6 B 6 24.0 2J.0 8 -B B.l -4.7 B 8 -2.1 6.4 6 0 10.7 -B.4 6 2 19.9 38.2 6 4 -1,6 -4.0 6 6 -I.8 9.0 6 G b.H -7.9. 2 4 19.4 -20 2 -6 8.2 5 2 6 -2.4 -0 3 -1 5.1 -6 J I 5.1 -5 5 0 6 5 4 C 3 22.2 -20 8 -3 15.2 17 8 5 24.6 25 8 -5 4.2 5 8 7 26.0 -25 2 2 1 7 0 6-6 9 6 6 11 6 -B -2 6 8 a 6 -to a .5 4 .4 3 .0 - J . a 8 .2 -a .4 .8 .0 .3 .7 -5 8 1 4b -7 19 7 51 -9 7 9 -2 .6 -4B,4 .6 -fcl.2' . J 55.1 .0 -2.1 I -4 26.8 26.5 1 6 8.9 -9.6 1 -6 21.9 -23,2 2 1 7.7 U.2 2 -1 0.4 -B.6 B -10 9.4 B.6 9 -1 28,6 -28.0 9 I 14.8 15.7 7 -3 -1.9 -1.1 9 1 -2.0 2.1 9 -5 -2.0 6.6 6 12 -2.4 -0.9 7 1 13.2 12.6 7 3 5.2 -5.9 7 5 31.3 32.7 7 7 44.5 -42 .7 J 3 6.4 -1 3 -5 9.2 6 4 0 8.5 1 4 -2 -2.4 4 J .9 2 1 1 9 B H 9 7.5 5 8 -9 21.6 -23 8-11 13.4 -13 9 0 14.9 14 9 2 21.J -21 8 2 I -1 12 7 1 34 7 - J 10 7 J JL 7 -5 IB . 1 11 .9 -3D . 1 tl Tfr .0 -11 It 11 -2 - 13 11 0 12 -2 4 1 2 19 .4 -10.8 2 -1.'7 .8 -12.0,' .5 10.5. .8 41.7. .2 -n.r 2 -3 6.0 1.4 2 5 8.2 6.3 2 -5 5.1 -l.t 2 -7 11.0 -U.9 3 0 14.4 -12.1 9 5 12.5 -11.a > -7 4.7 6.6 7 9 to. r n.i 7 11 13,4 -13.6 b 11 2«.6 25. 1 1 0 1U.) 7 I 2 9B.4 -96 9 -9 16.6 19.2 9-11 13.2 -13.4 10 0 15.1-1J.4 9 4 31.4 -32 9 -4 20.0 -20 9 6 -2.2 -1 9 -6 -2.0 0 9 8 15.6 14 2 7 7 / -7 14 7 7 11 7-9 15 7-11 14 8 0 18 • il -14 .2 13 .5 13 . 3 .2 .6 .9 « 4 4>>.7 -44.6 -4 19 4 23 .9 18.9-.6 2".'. 7 .5 -2.6 .6 -J6.4 .5 -12.f .0 54.5 1 4 . 27^6 29 1 -4 68.0 6B 3 -2 -2.3 5.0 ) 4 21.4 -20.9 3 -4 25.1 -24.1 3 -6 19.2 18.7 4 1 22.9 -24.6 10 -2 16.i 15.8 10 2 14.1 13.1 10 -4 18.2 -20.1 10 4 27.7 -JO.6 10 -6 3B.6 39.5 10 6 9.4 9.4 a 8 •-2.1 9. / 8 10 6.3 -2.0 9 1 9.5 -9.2 9 1 13.2 33.B •Y 5 4.4 0.1 9 7 -7.1 -0.3 6 J5 -a I J 6 11 1 6 20.7 -72 1 -6 6J.5 -65 1 8 17.7 -IB I -8 37.5 40 1 -10 -2.0 2 I 10 4.7 -4 2 5 9 -10 5.2 '1 10 -9 16.4 -18 10 1 25.9 -25 10 -1 12.6 12 L(J 3 28.6 28 3 0 0 a -2 4 a 2 7 a -4 a a 4 21 8-6 12 3 6-2 .6 -a .4 -9 .0 -21 .9 -13 .2 -2 . 1 . 1 .a -10 25 10 34 -12 2 7 2 12 21 J -1 10a 1 1 B6 .6 24.5 .1 -J5.7 .6 -27.2 . B 73.7 .1 -105.6-.i HI .6 4 -1 13.8 11.5 10 -Q 6.2 3.6 10 -10 9.J 8.4 11 '-1 14.8 15.0 11 1 35.4 -35.9 11 -J 13.8 15.3 9 9 ii, J - IS.0 10 0 IB.2 13.9 10 2 16.0 -IB. v 10 4 13.6 ii.L 10 6 I 7. J -17.1 10 B 1.2 -6.9 1 12 9.8 B 2 I 3B.I J5 2 -1 17.5 -14 2 J 25.1 -25 2 -3 74.5 -73 6 1 3 5 10 6 9.2 -9 10 -5 26.0 26 10 7 11.8 -8 10 -7 -2.2 1 tl -8 14.J 11 3 7 7 9 8 8 1 o a -io ii 9-1 J9 9 I 11 9 -J li .0 5 . J 11 . 9 -40 . 1 13 .2 14 .1 .2 .4 . 1 .a - 3 70 3 J 12 1 -5 5 5 25 1-7 9 t 19 .9 7 1'. 4' .6 -lf.2' .9 5.7 .9 26.1 .3 &. ) .2 -40. r 0 0 207.7 -214.1 0 -2 121.6 124.4 11 -5 12.4 U.2 It 5 10.3 9.B 11 -7 10.2 -9.4 11 -9 -2.4 -t .3 12 0 2b,0 26.9 12 -2 7 9.9 - 28.1 11 I 17.7 17.5 11 i 2 I.i -27.7 11 5 70.1 -23.6 11 7 7.1 -7.1 12 0 SB.2 -56.1 12 2 14.6 16.1 2 -5 6.5 6 2 7 20.4 19 2 -7 24.4 24 2 9 10.4 JL 2 -9 4.8 4 6 5 7 2 6 2 86.9 -92.2 0 -4 21.6 20.1 0 4 13.5 -11.6 0 -6 I0J.0 100.6 0 b 62.5 b5.9 0 -8 36.6 -36.4 11 2 10.2 -11 I I -2 6.6 6 It 4 16.3 -17 II -4 16.9 IB 11 b U.2 10 2 1 J 9 0 9 3 -2 9 -4 -i 9 5 25 9-7 2 1 9 7b 9-9 15 . 1 - 1 .a I .6 27 .2 22 . 5 1 .0 .5 -9 20 1 9 30 1 -11 5 3ii a 1-13 14 ? 0 .6 -21.1. .6 32.7. .4 -1.5. . o b. 7-.2 11.» . 2 2T<T M i &.ft a.i 12 -4 IB. 1 20.0 12 4 B.J 7.4 12 -6 9.0 0.4 13 -1 8.2 5.7 1J 1 10.5 10.1 12 4 -2.2 -3.7 12 fc 9.8 0.5 13 1 1.2 1.4 13 3 a.2 -7.5 13 5 -2.4 -6.2 14 0 26.2 6.8 2 -11 21.U -21 2 11 10.6 -11 2 -1J -14.4 -12 3 0 149. 1 -148 3 2 23.7 -22 3 -2 8 7.J B5 2 2 0 0 18.5 -1B.4~ 0 -10 26.0 27.0 0 10 14.0 -14.7 12 1 -2.2 I 12 -1 6.0 -4 12 3 7.3 -5 12 -J 1J.2 -13 12 5 -2.4 -2 7 9 5 9-11 9 10 0 18 10 -2 11 LO 2 5 10 -4 16 10 4 26 .4 tO . i -19 .3 11 .9 4 .2 -17 . 1 25 .3 .2 .3 . -2 20 4 2 -1 -4 52 4 4U fc -6 10 .0 -17.4 . 1 J . 4 .5 -42.7 .9 -4?,5 .7 1.2' 0 -12 17.4 18.5 0 -14 13.7 -14.8 1 -1 57.2 -51,7 11 -1 15.2 13.6 11 3 6.6 -8.5 13 -5 7.6 4.8 14 2 16,1 -14.9 3 4 68.1 65 J -4 17.4 16 J 6 32.8 34 3 -6 2 7. 3 28 1 8 8.0 -3 3 -8 26.2 -27 9 I 5 t I 53.7 -52.0 1 -3 64.2 -B3.0 1 3 42.4 -42.2 I -5 30.0 -2».l 1 5 33.2 -34.4 1 -7 17.1 17.0 12 -5 -2.J I 12 -7 11.3 10 13 0 13.8 -11 13 2 10.6 -8 13 -2 10.4 8 13 -4 7.5 4 9 8 B 10-6 7 10 6 5 10 -8 16 10 -10 22 T 1 -1 5 11 1 0 .3 -3 .6 21 .5 8 .5 .9 .0 .9 .5 1 2 4 3.2 39. 1 1 4 26.8 -24.3 1 6 11.4 H .9 \ i, 24 -8 20 a 26 -10 10 10 9 -12 10 .'- 11.0. .0 19.1 .5 -25.6 .b 3.9 .1 -9.7 .2 -9.0 I 0 57.6 51.4 1 2 6 7.4 66.3 1 -2 2.4 2.6 t 4 15.7 -17.8 -4 11.1 9.6 I 10 ?!l 7.5 1 12 15.2 15.7 1 -8.5 -7.6 2 1 71.7 -72.h 2 5 44.5 46.1 1 - 10 8.5 -4 J 10 4.a -5 3 -12 10.6 9 3 12 11.9 12 4 1 55.8 14 4 -1 IB.2 -17 8 n t 0 I 7 u.a -i2.i 1 -9 2B.3 27.4 1 9 32.9 16,t I -11 42.8 -44.2 1 11 8.1 5.0 1 -13 -2.1 -1.9 11 -3 22 11 3 5 11 -5 17 IT 5 b LI -7 U I t -9 B ,0 -22 . 1 -5 .5 -17 .6 -5 .6 13 .6 10 . 1 .3 .9 .8 .1 12 U -L 25 > 1 11 -3 54 1 52 •> -5 11 .0 -13.B 3 20.a . 0 - J t: 4 .4 49'.2 .2 Si".* .9 JO,i 6 31.J 34.3 1 -6 34.9 34.1 8 -2.0 -3.2 1 -B 31.0 31.1 1-10 -1,8 -0.2 t io i.a 8.4 2 9 -U9 2.2 2 11 19.'» -21.1 2 13 11.7 11.1 3 2 60.B 18.9 J 4 1.7 -3.0 4 3 64.4 -64 4 -3 6.9 5 4 5 7.7 4 4 -5 9.4 -7 4 7 22.1 -21 4 -7 to.a 10 2 9 4 2 6 71.5 -65.1 2 -2 57.4 -57.1 2 2 55.7 -55.0 2 -4 11.0 11.6 2 4 13.6 15.7 2 -6 5.9 l.l 0 0 72.0 7 0 -2 96.9 104 B 12 0 19 12 -2 14 12 2 b 12 -4 14 12 -6 17 13 -1 -2 . 1 -IB .4 4 .5 14 .'4 -2 . 3 5 44 -7 4 5 7 b -9 7 9 8 .7 '-4J.0 .0 6.2 0 4.9 2 - 7.2 -14 12.3 -12.1 2 1 99.4 -94 .4 1 -1 -1.1 -0.5 2 3 28.6 31.5 -3 34,6 - 12 .4 0 -4 97.5 -97 0 4 43.5 -43 0 -6 71.6 73 0 6 4.2 -6 0 -B 4.1 -5 5 2 1 9 1 8 14,7 -14.7 i 10 14.9 15.2 1 12 B.l -0.2 4 t »9.J )5.i 4 3 17.4 - 1'. . 9 4 9 20.1 20 4-9 4 3.1 44 4 -11 12.5 -11 4 11 15.4 -16 4 -11 12.4 11 0 0 0 4 2 6 5.6 -5.5 2 -8 7.7 6.J 2 B 14.1 14.9 2 -10 14.1 -14,6 2 10 12.2 12.5 13 1 -2 IJ - 3 8 11-5 7 1 0 J 1 2 4 1 -2 7 t 4 22 I -4 25 1 6 -1 .4 -2 .4 - 10 .7 .0 -1 . 1 7 .5 8 . J 23 .9 -25 . 1 .5 .3 .8 .5 .2 .9 . J ill 7 - 11 10 0 25 -2 JO 2 6 • fl 12; b .4 -0.4 3 B.l 2 17. o 7 -13.7 9 5. J 2 5 5.9 10.0 2 -5 23.9 25.B 2 7 2B.9 -29.4 2 -7 32.1 -32.3 ? 9 19.8 -20.1 2 -9 1.9 0.7 0 a 51.4 52 0 -10 44.2 46 0 10 9.8 -5 0 -12 16.5 -TO 0 -14 17.2 15 2 0 a 2 4 5 12.4 -U.O 4 7 17.5 19.1 4 9 -2.U 0.5 4 11 1.6 7.6 5 2 40.2 -51.1 5 4 15.0 14.7 5 0 40.0 40 5 2 21.4 20 5 -2 29.6 -29 4 4 13.6 14 5 -4 26.4 25 5 & 12.3 -LI 0 5 3 7 2 -12 18.5 -19.8 2 -14 5.1 0.4 J -1 4B.2 45.9 3 I 22.5 -23.2 3 -3 61.2 64.1 J 1 19.5 - 19.0 -6 13 6 - 1 -B 6 8 -2 J 15.7 7 -3.6 2 -b.r 9 3.9 .8 '4.0 I -0.2, -11 5.4 -4.1 11 14.4 11.4 -13 28.3 27.5 0 62.0 56.9 2 17.0 -17.0 -2 5.9 -5.1 I t 14.4 -14 1 -1 10.0 -8 1 1 21.0 -22 1 -5 J9.2 37 1 5 40.2 41 1 -7 4.9 1 0 5 7 7 5 5 t -I.I 6.4 5 a -1.9 2.4 5 10 47.1 -45.9 5 12 10.6 a.L 6 1 70.1 71.5 6 1 19.5 14.6 "6 5 2 r.H-~-"2TT4-6 7 3 7.7 - 39. 3 6 9 19.2 15.7 5 -6 14.4 15 5 8 25.1 26 b -6 21.5 23 5-10 b.3 -7 5 10 14.9 12 5 -12 18.0 -17 4 5 1 6 J -5 a.5 -9.7 J 5 14.7 14.7 3 -7 46.8 45.1 3 7 24.8 25.4 3 -9 9.3 6.3 J 9 16.9 -16.9 1 8 -2 1-8 37 1 - 10 4 .8 -J' . 7 -5 'I 10 -2 - 12 10 1 3ll b h. 7 0 -5.4 5 10.5 4 10.7 4 30.3 -29. 1 -4 12.5 -14.5 6 5.7 -6.2 -6 16.1 -16.7 8 48.9 50.7 -8 -1.7 0.5 1 7 22.3 -23 1 -9 3.8 4 1 9 20.9 -21 1 -11 25.1 25 1 -13 10.b It 2 0 6.6 -4 7 9 0 7 t 10 12 1 -12 4 1 -14 21 2 1 11 2-1 12 2 3 -1 .9 11 .5 -2 .4 20 . 3 10 .5 I J . 6 -0 .4 .0 . 5 .2 1 10 - 3 9 6 6 40.6 -41 70.0 6b 66.5 65 47.1 47 30.8 29 8. J -7 J 1 9 3 -11 29.6 10,3 3 11 8.4 6,6 1 -13 15.2 -15.2 4 0 50.1 -46.6 4 -2 11.0 -10.B 4 2 4.6 -0.6 6 11 14.1 -1i.9 / 2 8.4 6.B 7 4 22.2 21-0 -5 46 5 29 -7 6 7 7 -9 -2 0 -48.1 1 29.1 8 1.6 8 7 1 1.4 - 10 14.5 12.7 10 17.5 -1B.1 -17 5.7 2.7 1 12.9 13.5 -I 42.J 38.8 2 -2 64.& -64 2 2 12.1 -12 2 -4 4t.O 40 2 4 34.5 -lb 2 -6 13.9 -13 a 5 j 4 2 -3 22 2 5 -1 2-5 3 2 7 19 2-7 49 2 9 IJ 2-9 2 3 .4 20 .8 -2 .5 20 .2 -50 .tt - 14 .0 2J . 7 .0 ""/ 6 15.6 15.9 7 II 24.2 -21.9 6 -6 2B.9 29 -l.B 3 18.0 -20 a 6 1 4 -4 29.4 2B.6 4 4 24.9 24.7 4 -h 17.1 1HO 9 b 1 4.b 6 -9 14.4 -14 4 6 21.2 -23.7 -i -L.*4 -2^1 2 -a 31.3 31 ) - 48 -Table 15 (Continued) 1,1.2 -47.9 14.5 20.0 -34.6 -12.0 U.4 15.T 5 -12 4.4 lb.2 lb.5 42. J -42.0 t> 3 14.9 15.2 -1.7 -0.6 -2.0 -3.0 6 -5 71 .6 23.5 30.4 -33.5 tt -7 7.3 ID.O 15.0 11.5 4. 7 -5.0 20.5 -2 1.6 24.6 29.0 7 5.6 4.0 18.2 -1T.B 7 -2 78. 7 -28.b 27.1 -28.4 t -4 2 7.6 -27.b 10.2 -B. 5 7 -6 ?b.b -29.2 6 5 .a 1 -0 5.5 - 3.8 -10 74."* 26.1 -12 a. 4 -9.1 a 1 75. b -25.5 - 1 1 7.4 -19.1 12. 3 - 1 15.0 15.) -2.1 1.1 -5 1 2 .9 -12.5 a T 4. h 9. 7 8 -7 1. 1 8.9 -9 20.2 -26.9 B - 11 20.6 IB. b 0 it.'t 2 20.9 19.9 9 -2 2 7.1 -24.b 9 7.6 7.9 7 7.4 27 .8 - If.. 7 9 B.S lb.9 17.0 -10 1 KB -12.4 25.9 25.6 10 -1 i i!« - 3. ) 14.3 ID 1 '21 -16.9 10 5 b. 1 6.2 -5 -2.1 -O.b 10 -7 24. 5 -24.4 1 1 -B 15.4 -14.a 0 12.4 -1 1.4 1 l 2 2b. 7 27.4 11.3 11.0 1 1 4 -2.9 1 1 -4 22.4 -22. 7 I | -6 71. 1 21.1 r a.9 B. 1 -2.3 2.0 12 7 . 5 12 -3 10.8 12.0 12 -5 14. 1 14.4 17 -7 5.4 1.0 1 3 0 16.5 16.9 1 ) -2 6.5 3.9 1 3 -4. -2.4 4.0 h=4 • 0 bO. T 61 .4 0 50-1 -51 .8 0 40.9 43,b 0 14.0 -1 I .6 0 *1.9 41 .8 0 4.4 -4,4 0 34.7 -16.8 0 -1.7 20.4 0 8.8 -7.9 0 7.2 -6.2 0 28.7 27. 7 0 -14 1 7.0 12.1 1 33.4 15. 1 1 47.7 48.3 21.2 22.2 30.4 -29.4 I 12.1 12.7 21.4 - IB.4 -2.2 9. J t -1.8 4 ,0 4.3 -2.1 1 - 11 16.0 16.4 11.7 21.4 24.5 44. 5 19.B -17.9 22.1 -24.4 17.5 23.7 -2.0 21.0 16.6 19.7 -2.2 -2.2 9.2 14.1 -2.1 -20.1 ~TB~rr 14.5 12.4 -14.4 16.4 25.8 22.0 23.1 -72.2 19. a 24.3 15.9 -15.1 h=5 30. 9 7b.0 21.0 3a. 1 14.7 4.0 11.0 27.2 -2b. * I 1.0 _-U--* 59.2 -10.2 -27.0 73.7 2.5 ~670' 12.b 1 i.u 38.6 6.3 20.0 41.fl 15.9 37.4 *5.l 14.0 9.4 22.0 12.9 41.0 29.4 15.9 15.4 8.0 35..B 21.7 13.0 36.1 -45.7 -14.5 9.1 ^rrTT -11.9 -41.1 33.1 lb.7 12.a 18.3 -0.7 15.1 -6.2 -3b.6 16.6 23.7 —-b.V -16.5 7.6 21.? 14.9 16.6 -11.5 •10.2 -2.9 30. I -2.1 35.1 8.4 2b.0 24.8 8.4 ~V779--14.0 34.4 11.0 19.9 21.4 IB. 7 25.6 IB.6 12.2 19.4 35. I 15. 1 4T4~" 6.1 2B. 1 43. 4 11.2 27.0 37.6 -12.5 19.7 -777B -8.5 12.2 b -3 2 1."2" ' -25.6 2 8 5 5.4 4.2 2 a -5 11.6 10. 0 i a -7 9.a -9.8 1 a -9 16.2 15.0 3 8 -11 16.3 -15.9 3 9 0 10.6 9.3 9 2 -2. 3 -2.1 9 -2 8.5 10.7 9 4 16.1 -15.1 j 9 -4 17.9 -IB.5 1 9 -6 13.2 13.7 i, 9 -8 4.7 10.4 9 -10 -2.4 3.0 10 1 6.4 -3.6 10 -I 24.5 -22.4 4 10 -3 16.0 16.5 10 -5 7.2 5.6 <, 10 -7 7.4 -6.3 4 1 1 0 16.5 11.4 11 -2 5.3 -3.7 11 -4 6.5 -5.2 5 11 -6 10.7 -9.7 5 h=6 48.5 -49 20. 1 28. 3 20.2 23.8 12.9 6.0 35.0 11.4 . 8.9 6.2 11.3 19.5 21.7 -2.2 15.4 -2.2 U.C -11.5 21.2 -23.9 •17.6 39.0 13.6 22.8 10.2 15.2 -8.0 -15.1 24.b 11.9 •^5675" -8.7 12.8 28. 7 53.2 38. 1 23.1 - 19.1 -23.7 h=7 21.5 -20.1 - 49 -O the distance between N(18) and the plane is 1.20 A whereas that of o C(15) is only 0.95 A. The bond distances and valency angles of the histamine ion are given in Table 16, together with the corresponding values obtained by Donohue and Caron (19) for histidine. The bond lengths of the two analyses are in good agreement except for the C(12)-C(13) bond in histidine which is significantly longer than the analogous bond in histamine. Since the carboxyl group is attached to the C(12) of histidine, the increase in the C(12)-C(13) bond is not surprising. Considering the hydrogen bonding scheme, the probable tautomers of the imidazole ring are: I II III IV V Upon applying the carbon-nitrogen bond-order-length equation (20) rx = rl " (rl " r2)(3x)/(2x + 1) where r.. = single bond length, r = double bond length, r = observed X. Z. X bond length, and x = percent double bond.character to the observed carbon-nitrogen bond lengths in the imidazole ring, the C(14)-N(18), C(15)-N(16), C(17)-N(16), and C(17)-N(18) bonds were found to have - 50 -Table 16 o Bond distances (A) and valency angles (degrees) Standard deviations a(P-O) 0.009 a(O-P-O) 0.5 a(C-N) 0.018 a(< at C,N) 1.0-1 o(C-C) 0.020 a(C-H) a(X-Y-H) 9 a(N-H) 0.15 a(H-X-H) 12 a(O-H) Histamine ion Histidine C(12) -N(ll) 1.494 1.495 C(12) -C(13) 1.490 1.527 C(13) -C(14) 1.498 1.508 C(14) -C(15) 1.346 1.358 C(14) -N(18) 1.379 1.386 C(15) -N(16) 1.383 1.359 C(17) -N(16) 1.311 1.314 C(17) -N(18) 1.336 1.319 N(ll) -C(12) -C(13) 111.0 C(12) -C(13) -C(14) 114.9 C(13) -C(14) -C(15) 130.9 C(i3) -C(14) -N(18) 122.5 0(15) -C(14) -N(18) 106.4 C(14: -C(15) -N(16) 107.5 C(15] -N(16) -C(17) 108.6 C(14) -N(18) -C(17) 108.6 N(16) -C(17) -N(18) 108.8 N(ll] -H(20) 1.06 N(II; -H(21) 0.94 N(ll) -H(22) 0.98 c(i2: -H(23) 1.13 C(12] -H(24) 1.04 C(13} -H(25) 1.05 C(13: -H(26) 1.06 C(15} -H(27) 1.04 N(16; -H(28] 0.95 -H(29) 1.03 N(18] -H(30] 0.93 C(12; -N(ll) -H(20) 98 c(i'2; )-N(ll] -H(21) 114 c(i2; >-N(ll} -H(22) 115 H(.2O; -N(ll) -H(21) 117 H(20: )-N(II; -H(22) 118 H(2I; )-N(II; -H(22) 96 N(ii; >-c(i2; -H(23) 113 N(:ll] )-c(i2: -H(24) 112 - 51 -Table 16 (Continued) C(13) -C(12) -H(23) 113 C(13) -C(12) -H(24) 107 H(23) -C(12) -H(24) 100 C(12) -C(13) -H(25) 100 C(12) -C(13) -H(26) 106 C(14) -C(13) -H(25) 108 C(14) -C(13) -H(26) 113 H(25) -C(13) -H(26) 115 C(14) -C(15) -H(27) 128 N(16) -C(15) -H(27) 125 C(15) -N(16) -H(28) 126 C(17) -N(16) -H(28) 123 N(16) -C(17) -H(29) 127 N(18) -C(17) -H(29) 124 C(14) -N(18) -H(30) 131 C(17) -N(18) -H(30) 120 Phosphate groups P(D -0(3) 1.568 P(l) -0(4) 1.556 P(D -0(5) 1.507 P(i) -0(6) 1.502 P(2.) -0(7) 1.560 P(2) -0(8) 1.561 P(2) -0(9) 1.498 P(2) -0(10) 1.487 0(3) -H(33) 0.98 0(4) -H(36) 0.83 0(7) -H(34) 0.93 0(8) -H(35) 0.74 0(3:) >-P(l)-0(4) 107.7 0(3) -P(l)-0(5) 109.3 0(3) -P(l)-0(6) 106.1 0(4) -P(l)-0(5) 105.9 0(4) -P(l)-0(6) 112.0 0(5) -P(l)-0(6) 115.8 0(7) -P(2)-0(8) 106.3 0(7) -P(2)-0(9) 107.6 0(7) )-P(2)-0(10) 111.5 0(8) -P(2)-0(9) 108.0 0(8) -P(2)-0(10) 108.0 0(9) -P(2)-0(10) 115.2 - 52 -Table 16 (Continued) P(l)-0(3)-H(33) 113 P(l)-0(4)-H(36) 114 P(2)-0(7)-H(34) 114 P(2)-0(8)-H(35) 109 Water molecule 0(19)-H(31) 0.91 0(19)-H(32) 1.02 H(31)-0(19)-H(32) 105 - 53 -21, 20, 54, and 39 percent double bond character, respectively. This implies 66 percent double bond character for C(14)-C(15) and, at the same time a total contribution of tautomers I and II of about 60%. The preponderance of these tautomers is expected because they do not involve charge separation. The internal angles of the imidazole ring are equal to one another within the accuracy of the method. o The N(ll)-C(12) bond length of 1.494 A is slightly greater than the standard value of 1.479 A, but agrees well with the a-carbon-amino-nitrogen bond lengths described for other amino acids;these range o o from 1.46 to 1.52 A, the majority being close to 1.51 A in length. The carbon-carbon bond lengths of the side chain have an average value of 1.494 A which is significantly shorter than the standard paraffinic o bond length of 1.541 A. The bond lengths and valency angles of the E^PO^ ions also are listed in Table 16. The mean P-0 and P-OH distances of 1.561 and o o 1.499 A (with a standard error of the mean of 0.005 A) are in agreement with those observed in similar compounds (21-25). The bond lengths are also in good agreement with those predicted by iT-bonding theories for ions of this type (23). Cruickshank (23) pointed out that the bond lengths for E^PO^ in a crystal are close to the average of those in -3 PO^ and those in P02(0R)2 where R = alkyl. Presumably the deviation from the P02(0R)2 bond length is due to hydrogen bonding of H^PO^ _ o in the crystal. The predicted values for E^PO^ °^ 1-50 A for P-0 and o 1.59 A for P-OH are close to the observed values. Robinson (26) has used correlations between i.r. stretching frequencies and bond lengths o _ to predict P-0 and P-OH bond lengths of 1.48 and 1.58 A for the H P0. ion. The mean 0-P-0 angle of 115.5° differs significantly from the mean H0-P-0H angle of 107.0°. This deviation from a tetrahedral configura tion would be expected on the basis of the electron-pair repulsion theory (27). The values are close to those observed for the H^PO^ ion in KH2P04, namely, 115.4 and 105.5° respectively (21). The small differences among the various O-P-OH angles are possibly due to crystal packing. o The mean 0-H bond length in the H^PO^ ion is 0.87 A with a range o o o of 0.74-0.98 A (a 0.15 A). The difference between 0.87 A and the o 1.04 A obtained for the same bond by means of neutron diffraction (21) is thought to be due to a nuclear displacement from the centre of the hydrogen electron cloud. The P-O-H angles with a mean of 112 - 9° range from 109 to 114°. o o The mean 0-H bond length in the water molecule is 0.97 A (a 0.15 A) and the H-0-H angle 105°, both as expected. The high temperature factors of the water molecule may be the result of weak hydrogen bonding or a slight variation in the water content. The structure may be thought of as a leaning stack of histamine ions surrounded by a cylinder of H„P0, ions and water molecules as 2 4 shown in Figure 9. The significant features of the complex hydrogen bonding scheme which includes six 0-H...0 and five N-H...0 bonds and involves every active hydrogen atom, are outlined in Figure 10 and Tables 17 and 18. The observed bond angles and bond lengths of the hydrogen bonding system suggest that all the hydrogen bonds have been correctly assigned. In addition to those assigned, N(ll) has a further two near oxygen Figure 9. Projection of structure along a. - 56 -- 57 -Table 17 Distances (A) and angles (degrees) in the hydrogen bonds X-H. . .0 (X = 0 or N) Bond X. . .0 X-H H. . .0 H-X. . , .0 Donor Acceptor (X) 0(3)-H(33). . .O(K)1) [100] 2.55 0.98 1.59 9 OH 0 0(4)-H(36). . .0(9IV)[101] 2.58 0.83 1.75 2 OH 0 0(7)-H(34). . .0C61)[000] 2.54 0.93 1.62 9 OH 0 0(8)-H(35). . .0(5I][)[001] 2.57 0.74 1.84 10 OH 0 0(19)-H(31) . . .0(101)[000] 2.74 0.91 1.90 19 H20 0 0(19)-H(32) . . .0(8i:c) [000] 3.00 1.02 2.01 10 H20 OH N(ll)-H(21) . . .0(19n) [101] 2.77 0.94 2.02 31 NH3+ H90 N(ll)-H(22) . ..0(6IV)[111] 2.86 0.98 1.96 19 NH3+ 0 N(ll)-H(20) .. .0(7I)[000] 3.18 1.06 2.13 6 NH3+ 0H N(16)-H(28) . . .0(9m) [111] 2.69 0.95 1.74 2 NH 0 N(18)-H(30) . . .0(5!)[000] 2.68 0.93 1.76 8 NH 0 Equivalent positions are shown by superior Roman numerals: I X y z II X l/2-y 1/2+z III -X -y z IV -X -l/2+y -1/2-z together with translation in a, b, and c indicated in square brackets. - 58 -Table 18 Environments of atoms involved in hydrogen bonding Atoms involved Angle in degrees P(l)-0(3)...0(10) 121 P(l)-0(4)...0(9) 114 P(l)-0(5)...0(8) 123 P(1)-0(5)...N(18) 125 0(8)...0(5)...N(18) 96 P(l)-0(6)...0(7) 113 P(l)-0(6)...N(ll) 128 0(7)...0(6)...N(11) 119 P(2)-0(7)...0(6) 123 P(2)-0(7)...N(ll) 114 0(6)... .0(7). . .N(ll) 123 P(2)-0(8)...0(5) 117 P(2)-0(8)...0(19) 121 0(5)...0(8)...0(19) 106 P(2)-0(9)...0(4) 119 P(2)-0(9)...N(16) 125 0(4)...0(9)...N(16) 108 P(2)-0(10)...0(3) 127 P(2)-0(10)...0(19) 127 0(3)...0(10)...0(19) 99 N(ll)...0(19)...0(8) 117 N(ll)...0(19)...0(10) 126 0(8)...0(19)...0(10) 115 C(15)-N(16)...0(9) 128 C(17).-N(16)...0(9) 122 C(15)-N(16)-C(17) 109 C(14)-N(18)...0(5) 133 C(17)-N(18)...0(5) 117 C(14)-N(18)-C(17) 109 C(12)-N(ll)...0(6) 106 C(12)-N(ll)...0(7) 96 C(12)-N(ll)...0(19) 89 0(6)...N(ll)...0(7) 100 0(6)...N(ll)...0(19) 143 0(7)...N(ll)...0(19) 112 - 59 -o o neighbours: 0(4) at 3.13 A and 0(5) at 3.11 A. Since the corresponding N-H...0 angles are 156 and 148° respectively, they are not likely to be bonded to N(ll). Mo reover, the position of H(20) favors the 0(7) bond. As indicated in Figure 10, the water molecule is linked via two 0-H...0 hydrogen bonds to the phosphate network. The water molecule accepts one hydrogen from the terminal nitrogen of histamine. The four 0-H...0 bonds between the phosphate ions are typical of the distances reported for inorganic acids (18). The hydrogen bonds formed by the o water as a donor are 2.74 and 3.00 A, also within the usual range, (18). The histamine ion acting as a donor forms a total of five N-H...0 o bonds which range from 2.66 to 3.18 A in length and involve four different phosphate ions and one water molecule (Figure 10). Except o for the N(18)-H(30) . . .0(5) bond length of 3.18 A, the bonds are in •• the usual range (24). The geometry of this long bond is otherwise quite acceptable. The N(ll) atom is roughly in a tetrahedral configuration although the 0(6)...N(ll)...0(19) angle of 143° (Table 18) does deviate appreciably from the tetrahedral value. The hydrogens of N(ll) approach a tetra hedral arrangement much closer (Table 16). Oxygens (3) and (4) take part in only one hydrogen bond each. All other oxygen atoms participate in two hydrogen bonds. The arrangement of covalent and hydrogen bonds around the oxygen atoms approximates planarity with the sum of the sets of three angles ranging between 344 and 360°. The hydrogen bonds show the usual deviation (28) from 180°, of up to about 30° as indicated in Table 17. - 60 -There are only two other short intermolecular distances in the o structure. One is an N(16)...N(16) distance of 3.10 A across the centre of symmetry; the contact is between two molecules whose planes are parallel, and is slightly longer than the sum of the van der Waals radii o (3.0 A). The second contact is a C(17)-H(29)...0(3) interaction O (Figure 10). The C...0 distance is 3.14 (a 0.017) A, the H...0 O distance is 2.22 (a 0.15) A, and the H-C...0 angle 22°. Donohue. (28), who has described similar contacts, concluded that they did not represent hydrogen bonds in the same sense as 0-H...0 or N-H...0 bonds. - 61 -BIBLIOGRAPHY 1. G.H. Stout and L.H. Jensen, "X-Ray Structure Determination. A Practical Guide", Macmillan, New York, 1968. 2. M.J. Buerger, "Crystal Structure Analysis", Wiley, New York, 1960. 3. S.C. Nyburg, "X-Ray Analysis of Organic Structures", Academic Press, New York, 1961. 4. D.M. Burns and J. Iball, Proc. Roy. Soc. , 227A, 200, 1955. 5. M. Kurahashi, M. Fukuyo, A. Shimada, A. Furusaki, and I. Nitta, Bull. Chem. Soc. Japan, 39, 2564, 1966. 6. B.N. Lahiri, Z. Kristallogr. , 127_, 456, 1968. 7. B.N. Lahiri, Acta Cryst., A25, 5127, XIII-4, 1969. 8. J.D. McCullough, C. Knobler, and H. Hope, American Crystallographic Association, Winter Meeting, Seattle, Washington, 1969, Program and Abstracts, p. 52, H4. 9. T.C. Furnas, "Single-Crystal Orienter Instruction Manual", Milwaukee, General Electric Company, 1957. 10. "International Tables for X-ray Crystallography", Kynoch Press, Birmingham, volume III, 1962. 11. "Dictionary of ir-Electron Calculations", W.H. Freeman, San Francisco, p. 344, 1965. 12. Chem. Soc. Special Publ., number 11, 1958 and number 18, 1965. 13. R.E. Marsh, Acta Cryst., 11, 654, 1958. 14. D.A. Wright and R.E. Marsh, Acta Cryst., 15, 54, 1962. 15. A. Chiba, T. Ueki, T. Ashida, Y. Sasada, and M. Kakudo, Acta Cryst., 22., 863, 1967. 16. L.S. Bartell, J. Amer. Chem. Soc, 81, 3497, 1959. 17. H.J. Simpson and R.E. Marsh, Acta Cryst., 20, 550, 1966. 18. G.H. Stout and L.H. Jensen, "X-ray Structure Determination. A Practical Guide", Macmillan, New York, p. 303, 1968. - 62 -19. J. Donohue and A. Caron, Acta Cryst., 17_, 1178, 1964. 20. J. Donohue, L.R. Lavine, and J.S. Rollett, Acta Cryst., 9_, 655, 1956. 21. G.E. Bacon and R.S. Pease, Proc. Roy. Soc, A230, 359, 1955. 22. J.D. Dunitz and J.S. Rollett, Acta Cryst., £, 327, 1956. 23. D.W.J. Cruickshank, J. Chem. Soc, 5486, 1961. 24. G.H. McCallum, J.M. Robertson, and G.A. Sim, Nature, 184, 1863, 1959. 25. D.E.C. Corbridge, Topics in Phosphorus Chem., _3, 57, 1966. 26. E.A. Robinson, Canad. J. Chem., 41_, 3021, 1963. 27. R.J. Gillespie and R.S. Nyholm, Quart. Rev., 11, 339, 1957. 28. J. Donohue, in "Structural Chemistry and Molecular Biology", ed. A. Rich and N.Davidson. Freeman, San Francisco, p. 433, 1968. 

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