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Coordination complexes of trivalent non-transition metal ions Smith, Alexis 1988

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COORDINATION COMPLEXES OF TRTVALENT NON-TRANSITION METAL IONS by ALEXIS SMITH B.Sc, University of Guelph, Ontario, Canada - 1985. A THESIS SUBMITTED IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF MASTER OF SCIENCE in THE FACULTY OF GRADUATE STUDIES (Department of Chemistry) We accept this thesis as conforming to the required standard The University of British Columbia July 1988 © Alexis Smith, 1988. 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 C M ^ V V V ^ V ^ f The University of British Columbia 1956 Main Mall Vancouver, Canada V6T 1Y3 DE-6(3/81) ABSTRACT L^thaxride(in) complexes of three potentially heptadentate Schiff base ligands were prepared by addition of lanthanide(III) salts to a solution containing a slight excess of ligand in the presence of poorly coordinating chloride ions or strongly coordinating nitrate ions. The complexes La(hatren), La(datren)(CH30H) and La(trac) were isolated in the presence of chloride ions, and were found to have the ligand bound in a hexadentate or heptadentate fashion. We were unable to isolate analogous complexes with the heavier lanthanides (Ln = Pr, Nd, Gd, Dy, Yb, Lu). The complexes Ln(H3L)(NC>3)3 (Ln = La, Pr, Nd, Gd, Dy, Yb; H 3 L = F^hatren, H3datren) and Ln(H3trac)(NC>3)3 (Ln = Pr, Nd, Gd, Dy, Yb) were isolated in the presence of nitrate ions, and were found to have the Schiff base ligand bound in a tridentate fashion ( where FJ^datren = tris(2'-hydroxy-4',5'-dimethylacetopheniminoethyl)amine; H3trac = tris(3-aza-4-methylhept-4-ene-6-one)amine; and H3hatren = tris(2'-hydroxyacetophenirninoethyl)amine) Al l products were characterized by infrared and mass spectroscopy, and by elemental analysis. ^ - N M R spectroscopy indicated that the complexes were solution labile and dissociated in DMSO to yield free ligand and solvated lanthanide(IU) ions. The crystal structure of Gd(H.3trac)(N03)3 was determined. The gadolinium(III) ion is nine coordinate. H3trac is bound only through its three oxygen donor atoms, and the nitrate ions are bound in a bidentate fashion to the gadolinium center. AlurninumfTH) and gallium(IU) complexes of 2-chloromethyl-5-hydroxy-4H-pyran-4-one (Hck) were isolated from a basic aqueous solution. The complexes Al(ck)3 and Ga(ck)3 were characterized by ^ - N M R (CDCI3), infrared and mass spectroscopy, as well as by elemental analysis. Al(ck)3 was also characterized by 2 7 A1-NMR in CDCI3. i i T A B L E OF CONTENTS page Abstract ii Table of Contents iii List of Tables vi List of Figures viii List of Abbreviations xi Acknowledgements xiii Chapter I: General Introduction 1 Chapter II: Lanthanide(III) Complexes of Potentially Heptadentate Ligands 8 A . Introduction 8 B . Complexes of F^hatren and F^datren 20 1. Isolation of the Lanthanide(III) Adducts 20 2. mfrared Spectra of H3hatren,H3datren and their Lanthanide(III) Adducts 26 3. Mass Spectra of H3hatren, F^datren and their Lanthanide(III) Adducts 31 C . Complexes of H3trac 37 1. Isolation of the Lanthanide(III) Adducts 37 2. Crystal Structure of Gd(H3trac)(N03)3 41 3. Infrared Spectra of H3trac and its Lanthanide(III) Adducts 48 4. Mass Spectra of H3trac and its Lanthanide(III) Adducts 51 D. Experimental 56 i i i 1. General Techniques 56 2. Synthetic Procedure 57 2.1. Synthesis of H3hatren 57 2.2. Synthesis of La(hatren) 57 2.3. Synthesis of Ln(H3hatren)(N03)3 (Ln = La, Pr, Nd, Gd, Dy, Yb) 58 2.4. Synthesis of H3datren 59 2.5. Synthesis of La(datren)(CH3OH) 59 2.6. Synthesis of Ln(H3datren)(NC>3)3 (Ln = La, Pr, Nd, Gd, Dy, Yb) 60 2.7. Synthesis of H3trac 60 2.5. Synthesis of La(trac) 61 2.6. Synthesis of Ln(H3trac)(N03)3 (Ln = Pr, Nd, Gd, Dy, Yb) 62 Chapter LTJ: Aluminum(III) and G a l h u m ( T n ) Complexes of Substituted 3-Hydroxy-4H-pyran-4-ones 63 A. Introduction 63 B. Results and Discussion 66 1. Isolation of the Complexes 66 2. Infrared Spectra of Al(ck)3 and Ga(ck)3 67 3. Mass Spectra of Al(ck)3 and Ga(ck)3 69 4. Nuclear Magnetic Resonance Data 72 C. Experimental 75 1. General Techniques 75 2. Synthetic Procedure 76 2.1. Synthesis of tris(chlorokojato)aliiniinum(III). 76 2.2. Synthesis of tris(chlorokojato)gallium(III).... 76 i v Chapter IV. Conclusions and Perpectives 77 References 79 Appendix 87 A . Infrared Spectra 87 B. Mass Spectra 98 v LIST OF TABLES page Table 2.1. Elemental Analysis Data for Fi^ hatren, La(hatren) ,and 24 Ln(H3hatren)(N03)3 (Ln = La, F T , Nd, Gd, Dy, Yb). Table 2.2. Elemental Analysis Data for H3datren, La(datren)(CH30H), 25 and Ln(Ti3hatren)(N03)3 (Ln = La, Pr, Nd, Gd, Dy, Yb). Table 2.3. Infrared Data on F^hatren, La(hatren), and La(N03)3(H3hatren) 28 Table 2.4. Infrared Data on H3datren, La(datren)(CH3OH), 29 and La(H3hatren)(N03)3 Table 2.5. Mass Spectral Data on H3hatren, La(hatren), and 33 Ln(H3hatren)(N03)3 (Ln = La, Pr, Nd, Gd, Dy, Yb) Table 2.6. Mass Spectral Data on Flatten, La(datren)(CH30H), 34 and Ln(H3hatren)(N03)3 (Ln = La, Pr, Nd, Gd, Dy, Yb) Table 2.7. Elemental Analysis Data for Ffjtrac, La(trac), and 39 Ln(H3trac)(N03)3 (Ln = Pr, Nd, Gd, Dy, Yb) Table 2.8. Crystallographic Bond Lengths (A) (with estimated standard 43 deviations in parentheses) for Gd(H3trac)(N03)3 Table 2.9. Crystallographic Bond Angles (deg) (with estimated standard 44 deviations in parentheses) for Gd(H3trac)(N03)3 Table 2.10. Oxygen-Oxygen Distances (A) in the Coordination Polyhedron 47 of Gd(H3trac)(N03)3 Table 2.11. mfrared Data on FTjtrac, La(trac), and Gd(H3trac)(N03)3 49 Table 2.12. Mass Spectral Data on H3trac, La(trac), and 54 Ln(H3trac)(N03)3 (Ln = Pr, Nd, Gd, Dy, Yb) Table 3.1. Elemental Analysis Data for Hck, Al(ck)3, and Ga(ck)3. 67 Table 3.2. Infrared Data on Hck, Al(ck)3, and Ga(ck)3. 68 vi Table 3.3. EI - Mass Spectral Data on Hck, Al(ck)3, and Ga(ck)3. 70 Table 3.4. FAB - Mass Spectral Data on Hck, Al(ck)3, and Ga(ck)3. 71 Table 3.5. NMR Data on Hck, Al(ck) 3, and Ga(ck)3 73 vii LIST OF FIGURES page Figure 1.1. pyromeconic acid - Hpa, maltol - Hma, kojic acid - Hka, 6 chlorokojic acid - Hck, kojic amine - Hkm Figure 2.1. Cu(II)(salim)2 and Cu(II)(acacen) 9 Figure 2.2. H.3trac, H^hatren and H3datren 10 Figure 2.3. The P-ketoamino, p-ketoimino and P-enolimino tautomers 10 Figure 2.4. pytren, H3saltren and H3pyroltren 11 Figure 2.5. Hsdtpa and FLjdota 13 Figure 2.6. Yb(acac)3(Hacim) 15 Figure 2.7. H.2acacen 15 Figure 2.8. pytame and cage 16 Figure 2.9. dpea 16 Figure 2.10. Macrocyclic hexaimine ligands py2en2 and py2pen2 17 Figure 2.11. Possible binding modes of the potentially heptadentate ligands 18 Figure 2.12. Nitrate ion: free (D3h), monodentate (C2V) and bidentate(C2v) 30 Figure 2.13. ORTEP drawing (above) and stereoview (below) of 40 Gd(H3trac)(N03)3 Figure 2.14. Average bond lengths (A) in the p^ketoarnine moiety of 42 Gd(H3trac)(N03)3 Figure 2.15. Schematic drawing of M(unidentate)3(bidendentate)3, TCPT. 45 Figure 2.16. ORTEP view of the tricapped trigonal prismatic GdOo 46 coordination polyhedron in Gd(H3trac)(N03)3 Figure 3.1. Geometric isomers of an M(A-B)3 system 72 Figure A1 . Jjifrared spectrum (KBr pellet) of the 4000 to 200 cm-1 region of 87 H3hatren Figure A2. Infrared spectrum (KBr pellet) of the 4000 to 200 cm' 1 region of 88 vi i i La(hatren) Figure A3. Infrared spectrum (KBr pellet) of the 4000 to 200 cnr 1 region of 89 La(H3hatren)(N03)3 Figure A4. Irifrared spectrum (KBr pellet) of the 4000 to 200 cm"1 region of 90 H3datren Figure A5. Mrared spectrum (KBr pellet) of the 4000 to 200 cnr 1 region of 91 La(datren)(CH30H) Figure A6. Irifrared spectrum (KBr pellet) of the 4000 to 200 cm"1 region of 92 La(H3datren)(N03)3 Figure A7. Infrared spectrum (neat oil) of the 4000 to 200 cnr 1 region of 93 H3trac Figure A8. Infrared spectrum (KBr pellet) of the 4000 to 200 cm"1 region 94 of La(trac) Figure A9. Infrared spectrum (KBr pellet) of the 4000 to 200 cm"1 region of 95 Gd(H 3trac)(N03)3 Figure A10. Infrared spectrum (KBr pellet) of the 4000 to 200 cm"1 region of 96 chlorokojic acid (Hck) Figure A l l . Infrared spectrum (KBr pellet) of the 4000 to 200 cm- 1 region 97 of Al(ck) 3 Figure A12. E.I. mass spectrum of H3hatren 98 Figure A13. E.I. mass spectrum of La(hatren) 99 Figure A14. E.I. mass spectrum of Nd(H3hatren)(N03)3 100 Figure A15. E.I. mass spectrum of Yb(H3hatren)(NC>3)3 101 Figure A16. E.I. mass spectrum of H3datren 102 Figure A17. E.I. mass spectrum of La(H3datren)(CH30H) 103 Figure A18. E.I. mass spectrum of Nd(H3datren)(N03)3 104 Figure A19. E.I. mass spectrum of Yb(H3datren)(NC>3)3 105 ix Figure A20. E.I. mass spectrum of H3trac Figure A21. E.I. mass spectrum of La(H3trac) Figure A22. E.I. mass spectrum of Gd(H3trac)(N03)3 LIST OF ABBREVIATIONS Abbreviation Meaning atp annpyrine BBB blood brain barrier br broad (NMR and infrared spectroscopy) C.N. coordination number cage l-methyl-4,6,10-(tris-a-pyridyl)-3,5,7,-triazarricyclo[3,3,1,1,3,7]decane 18-crown-6 1,4,7,10,13,16-hexaoxacyclooctadecane CSAP capped square antiprism DMSO dimethylsulphoxide E. I. electron impact ionization (mass spectrometry) F. A.B. fast atom bombardment ionization (mass spectrometry) Hacac 2,4-pentanedione Hacacen 5,8- diaza-4,6-dimethyldodeca-3,9-diene-2,11 -dione Hacim 4-amino-3-pentene-2-one Hck 2-chloromethyl-5-hydroxy-4H-pyran-4-one (chlorokojic acid) H3datren tris(2'-hydroxy-4\5'-dimethylacetopheniminoethyl)amine H4dota l,4,7,10-tetraazacyclododecane-N,N',N",N'"-tetraacetic acid Hsdtpa diethylenetriarmne-N,N,N',NM,N''-pentaacetic acid H4edta ethylenediamine-N,N,N',N'-tetraacetic acid H3hatren ms(2'-hydroxyacetophenimmoemyl)amine Hka 2-hydroxymethyl-5-hydroxy-4H-pyran-4-one (kojic acid) Hkm 2-aminomethyl-5-hydroxy-4H-pyran-4-one (kojic amine) Hma 3-hydroxy-2-methyl-4H-pyran-4-one (maltol) xi Hpa 3-hydroxy-4H-pyran-4-one (pyromeconic acid) H3pyroltren tris(pyrol-2-carboxyaldirnmoethyl)airune Hsalim sahcylaldimine H3saltren tris(saHcylaldimmc«thyl)arnine H3trac iris(3-aza-4-memymept-4-ene-6-one)amine Ln lanthanide m multiplet (NMR spectroscopy) m medium intensity (infrared spectroscopy) NMR nuclear magnetic resonance N 4 O 3 H3trac, H3hatren, and H3datren ligand donor atoms py2C»2 Schiff base condensation product of 2,6-diacetylpyridine and 1,2-diaminoethane (see Figure 2.10) py2pen2 Schiff base condensation product of 2,6-diacetylpyridine and 1,2-diaminopropane (see Figure 2.10) pytame 1,1,1 -nis(pyridine-2-aldirninomethyl)ethane pytren tris(pyricnne-2-carboxyaldmimoethyl)amine r ionic radius s singlet (NMR spectroscopy) sh shoulder (infrared spectroscopy) t triplet (NMR spectroscopy) T i longitudinal relaxation time (NMR spectroscopy) T2 transverse relaxation time (NMR spectroscopy) TCTP tri capped trigonal prism w weak intensity (infrared spectroscopy) 8 chemical shift relative to standard (NMR spectroscopy) V X - Y X -Y stretching vibration (infrared spectroscopy) xii A CKNOWLEDGEMENTS I would like to thank Dr. C. Orvig and the members of his group, past and present, for their support and encouragement throughout this work. I would also like to thank Mr. P. Borda for the elemental analysis of the products and his patience in their determination; Dr. S. Rettig for his prompt determination of the crystal structure of Gd(H3trac)(NC»3)3; the technical staff of the NMR and mass spectroscopy labs and the U B C Chemistry support staff for their expertise. The financial assistance in the form of a University Graduate Fellowship and a Teaching Assistantship is gratefully acknowledged, as is a research grant received from Sigma Xi . Most importantly, I would like to thank Shelley, Robert, Judy, Kathryn, Adam, Mikey, Chris G. and many others for their optimism, and unfailing cheerfulness which contributed to the completion of this work. xiii Chapter I General Introduction Nuclear magnetic resonance has recently emerged as a diagnostic tool in medicine. With this development has come a need for a new series of contrast agents for in vivo NMR imaging. Although the inherent contrast between tissues is large because of both the physical and chemical properties of the medium, targetting of diseased tissue is desirable and can be achieved by the use of tissue-specific paramagnetic agents.1-3 The gadolinium(III) ion (Gd 3 +) is ideal for use as a contrast agent due to the isotropic magnetic field associated with the half-filled 4f shell. The spin and orbital angular momenta of the unpaired electrons on gadolinium(III) combine to generate an isotropic magnetic field in close proximity to the metal ion. The chemical shift of the observed nucleus will not be affected by the presence of the local magnetic field generated around the gadolinium(III) ion. 4 The relaxation rate of nearby nuclei will be affected by the magnetic field and the long electron spin-lattice relaxation time associated with the gadolinium(III) ion, resulting in an overall enhancement of the signal.2'5-6 Nuclear magnetic resonance is an ideal diagnostic tool because it does not damage the tissue being probed. In a NMR imaging experiment, the body is placed in a magnetic field gradient and the degeneracy of the magnetic moments of all species present is lifted. A small oscillating magnetic field corresponding to the water proton resonance frequency is applied perpendicular to the strong magnetic field resulting in excitation of the nuclear magnetic moments associated with the water protons. The water proton resonances are detected giving rise to a series of two-dimensional NMR spectra 2 Differentiation between the local environments of the water protons is achieved using complex pulse sequences. The main contrast parameters in an NMR imaging experiment are the local concentration of the nuclei under observation (usually water 1 protons), and the longitudinal and transverse relaxation times, T i and T2 respectively.7'8 Proximate to a gadolinium ion, the relaxation rate of the water protons is increased due to spin-spin interactions between the nuclear magnetic moments of the water protons and the electronic magnetic moments associated with the unpaired electrons on the gadolinium(ni) ion. This relaxation enhancement can occur either via a contact interaction in which the information is transmitted through bonding electrons, or via a dipolar interaction in which the information is carried through space.9 Even though the magnetic properties of the gadolinium(III) ion appear to be ideal for use as a contrast agent, problems arise when free gadolinium is injected directly into the patient. Free gadolinium(III) is toxic. It will interfere with blood formation and coagulation and is stored over relatively long periods of time in the liver, spleen and muscle with slow excretion. In order to take advantage of the magnetic properties of gadolinium(III), the metal ion must be administered in some non-toxic form.4'5 Inherent toxicity of gadolinium(III) can be overcome by administration of the metal ion in the form of a stable complex. The general requirements for such complexes are specific distribution in vivo, in vivo stability, excretability, and lack of toxicity.10 The metal complexes must also have a high efficiency for enhancement of proton relaxation rates, i.e. high relaxivity values.2 Lanthanide complexes tend to be labile in solution. If one wishes to use a gadolinium complex for in vivo NMR imaging, the complex must be not only thermodynamically stable but also kinetically inert in order to avoid delivery of free gadolinium and free ligand into the local environment. The bonding interaction between the lanthanide ion and the ligand is electrostatic, analogous to binding in alkali and alkaline earth metal ions. Phosphate and carbonate ions have a high affinity for the trivalent metal ions,1 1 as does transferrin, an iron transport protein.12'13 In vivo, these may act as sequestering agents for free gadolinium ions. Lability of the complex would only compound the toxicity problem observed for free gadolinium since the ligand would also 2 act as a metal ion scavenger. Dissociation of the complex may lead to binding of the chelating agent to calcium(JJ) ions, thus causing a depletion of this ion in the body.2 A certain degree of versatility within the ligand system with respect to substitution would also be desirable; the targetting properties of the system could be modulated by the presence of either hydrophobic or hydrophilic groups. The manner in which the complex is excreted from the body is also highly dependent upon the solubility of such complexes. Complexes which are hydrophobic are usually taken up by the liver and undergo hepatobiliary excretion, whereas complexes which have low molecular weights and are hydrophilic are usually filtered out non-specifically by the kidneys. It is therefore desirable to have a balance between hydrophilic and hydrophobic properties if one wishes to target a given tissue prior to excretion via the hepatobiliary or the urinary route.2 A number of chelating agents have been studied over the years, but to date only two ligands afford physiologically inert complexes with gadolinium.1-2 Both of these are polyamino polycarboxylic acids. Diethylenetriamine-N,N,N',N",N"-pentaacetic acid (H5dtpa) is an open-chained analogue and 1,4,7,10-tetraazacyclododecane-N,N',N",N"'-tetraacetic acid (FUdota) is a macrocyclic analogue of ethylenediamine-N,N,N',N'-tetraacetic acid (H4edta). Gadolinium complexes of both these ligands (Hsdtpa, FLtdota) are currently undergoing clinical investigation for use as NMR contrast agents.1'2 The association constants for [Gd(dtpa)(H20)]2~ and [GdCdota)^©)] 1" are extremely high, the logKML values being 22.46 and 24.7 respectively.14 Both these ligands lead to charged hydrophilic complexes of the divalent gadolinium ion. Ionic complexes require a carrier mediated transport system in order to cross membrane lipid bilayers; that is, they must interact with membrane proteins. No such transport system appears to be available for either complex, and they localize in the intravascular and interstitial compartments. These complexes are non-specific with respect to extracellular distribution, and undergo renal excretion. They are currently used as contrast agents for imaging of the kidneys15 and in the detection of lesions in the brain.16 3 Brain lesions generally lead to breakdown of the blood brain barrier allowing [Gd(dtpa)(H20)]-2 or [Gd(dota)(H20)]-l to enter the interstitial areas of the brain.16 There is a need for other physiologically stable gadolinium complexes for use as contrast agents if this field is to be developed further. The H.5dtpa and FLjdota chelators afford stable but charged and hydrophilic complexes with gadolinium(III) ions. Development of neutral and hydrophobic complexes would be of interest2 We were interested in the possibility of forming inert gadolinium(III) complexes with potentially heptadentate ligands based on the Schiff base condensation of one equivalent of tris(2-aminoethyl)amine with three equivalents of a ($-diketone or a (3-hydroxyketone. These ligands would afford neutral complexes with trivalent metal ions and the complexes would exhibit a possible coordination site opposite the bridging tertiary nitrogen, thus allowing inner-sphere interactions of the gadolinium(III) ion with water molecules.17 We chose to look at three such ligand systems. Two of the ligands are based on 2'-hydroxyacetophenone which exhibits a certain degree of flexibility with respect to substitution on the phenyl ring system. The third ligand is based on the simplest (J-diketone, namely 2,4-pentanedione. It was hoped that the high denticity of these ligands would be a major driving force for the formation of stable complexes. Isolation and characterization of the lanthanide(III) adducts of these three ligands will be discussed in chapter TJ. Two other metal ions, aluminum and gallium, are also of biomedical interest. Aluminum is the most abundant metal in the earth's crust and is present in a variety of products ingested daily by the majority of the population. In the recent past, aluminum was believed to be non-toxic. Under normal circumstances most of the ingested aluminumfJII) will be excreted in the form of insoluble aluminum(ni) hydroxy compounds.18 Some of the ingested aluminum(TII) may be absorbed and enter the blood stream. Once in the blood stream aluminum(III) can compete with iron(III) for the two binding sites on the iron-transport protein, transferrin. The stability constants for aluminum(III) binding to 4 transferrin (log K i = 12.9; log K 2 = 12.3) are lower than those for iron(III) (log K i = 22.5; log K 2 = 21.4).19 These stability constants indicate that the binding of aluminum(III) will not be favoured over binding to iron(UI). This assumption ignores the fact that only 30% of the sites on transferrin are occupied by iron(III). The uptake of aluminum(ILT) by transferrin occurs if the bivalent metal ion enters the blood stream.20 Evidence as to the involvement of aluminum in neurological dysfunctions and bone disorders is slowly accumulating.21 The involvement of aluminum in Alzheimer's disease, for instance, has been the subject of much controversy in recent years.22 The presence of aluminum in the nuclei of neurons bearing neurofibrillary tangles found in the brain of Alzheimer patients raises questions as to the role, direct or indirect, of aluminum in this disease.2-^24 The blood brain barrier (BBB) is the term given to the intricate capillary system which maintains homeostasis in the brain when fluctuations in the extracellular concentrations of hormones, amino acids, and ions occur. Essential nutrients cross the BBB aided by specific transport systems. Neutral low molecular weight compounds can cross the BBB by passive diffusion.25 Determination of the source and transport system which allows aluminum(III) ions to cross the BBB of Alzheimer patients requires a better knowledge of the coordination chemistry of aluminum(III) at physiological pH. 2 0 The aqueous coordination chemistry of gallium(III), another group 13 metal, at physiological pH is also of interest because of the existence of two radioisotopes used in nuclear medicine. The development of 6 7 G a (ti/2 = 78.1 h; y = 93.3, 185, 300 keV; accelerator product) and 6^Ga (t\/2 = 68.3 min; y= 511 keV from 6+-annihilation; generator product) radiopharmaceuticals has been the focus of some research in recent years.26 In order to be of use as a radiopharmaceutical, the gauium(LTJ) complexes must be thermodynamically stable and kinetically inert under physiological conditions. The stability constants for gallium(UI) binding to transferrin (log K i = 20.3, log K 2 = 19.319) are much 5 greater than those for aluminum(III) and transferrin wil l readily bind to any free gaUium(ni) present in the blood. 1 9 Our group has been interested in the development of a series of aluminum(III) and gallium(in) chelate complexes of several 3-hydroxy-4H-pyran-4-one derivatives (Figure l . l ) . 2 7 The aluminum(III) complex of 3-hydroxy-2-methyl-4H-pyran-4-one (Hma) was administered intracranially in rabbits and found to be highly neurotoxic.28 The fact that the Al(ma)3 complex was stable under physiological conditions in the brain and crosses brain cell membranes prompted an investigation into the chemistry of aluminum(III) and gallium(III) chelates of close analogues of Hma, namely 2-chloromethyl-5-hydroxy-4H-pyran-4-one (commonly known as chlorokojic acid - Hck) and 2-aminomethyl-5-hydroxy-4H-pyran-4-one (kojic amine - Hkm). Riv^ ^ Q ^ . ^^-2 ' O H ] o 1 (Ri = H , R 2 = H) 2 ( R i = H , R 2 = C H 3 ) 3 (Ri = C H 2 O H , R 2 = H) 4 (Ri = CH 2 C1, R 2 = H) 5 (Ri = C H 2 N H 2 , R 2 = H) Figure 1.1. pyromeconic acid - Hpa (1), maltol - Hma (2), kojic acid -.Hka (3) chlorokojic acid - Hck (4), kojic amine - Hkm (5). Substitution on the basic 3-hydroxy-4H-pyran-4-one moiety will impart different properties to the chelate complexes formed with aluminum(in) or gallium(LTI) and can be used to manipulate the in vivo targetting properties of the resulting complexes. We were particularly interested in Hkm as a ligand for alurriinum(rn) and galliumtTH) ions because of its amine functionality, a moiety found in neurotransmitters (e.g. dopamine) and drugs (e.g. amphetamine) which cross the B B B . 2 9 Isolation and characterization of the 6 alurninum(III) and gallium(lTI) complexes of Hck will be discussed in chapter III. We were unable to isolate the aluminum(LTJ) and gallium(m) complexes of Hkm. 7 Chapter II Lanmamde(IIT) Complexes of Potentially Heptadentate Ligands A. Introduction The interest in the coordination chemistry of the lanthanides stems from their distinct chemical and physical properties, which result from shielding of the partially filled 4f orbitals by the filled 5s and 5p orbitals and from the ineffective nuclear shielding by the 4f electrons.30-31 The coordination chemistry of the lanthanides is analogous to that of alkali and alkaline earth metal ions in that the interaction between the lanthanide ion and ligand donor atoms is essentially electrostatic. Lanthanide(HT) ions (Ln 3 +) are often used as probes in solution studies of Ca(II)-binding proteins because of the similarities in the metal ion size and bonding interactions.32 The ionic radii progressively decrease along the series as a result of the ineffective shielding of the nucleus. This decrease in ionic radii is commonly termed the "lanthanide contraction" (e.g. for CN = 6: L a 3 + , r = 1.17; L u 3 + , r = 1.00).30 The charge density of the trivalent cations increases along the series as a result of this contraction.30'33 Some ligands will bind preferentially to the lighter lanthanides because of the need for larger radii for complete and unstrained binding of the ligand. Other ligand systems will bind preferentially to the heavier lanthanide(III) ions because of the higher charge densities and smaller ionic radii of these metal ions. Development of sequestering agents for the separation of lanthanides is based on these trends within the series.34 The ligand field restrictions encountered with transition metal ions are not a major factor when one approaches the design of a chelating agent for the lanthanide(HI) ions because of the lack of covalency in the bonding interaction.35 The coordination mode and the conformation of a given ligand system depend on factors such as the size and charge 8 density of the lanthanide(III) ion, the nature of the ligand donor atoms, and the steric constraints imposed by ligand-ligand interactions.36 The nature of the adduct formed is also dependent on the solvent and other species present during the synthesis.37 The electrostatic non-directional bonding coupled with the size of the metal cations leads to the formation of complexes with coordination numbers of up to twelve and allows an investigation into high coordinate structures, permitting comparisons between idealized and actual polyhedra.36 Schiff bases derived from the reaction of an aldehyde or ketone with a primary amine afford versatile ligands which have been studied extensively for many years. The first metal complex was isolated in 1840 from the reaction of cupric acetate, salicylaldehyde and aqueous ammonia, yielding bis(salicylaldimino)copper(II), Cu(II)(salim)2 (6). The first (3-ketoamine metal complex, (5,8-diaza-4,6-dimethyldodeca-3,9-diene-2,l 1-diono)copper(n), Cu(II)(acacen) (7), was prepared in 1889.38 Figure 2.1. Cu(H)(salim)2 (6) and Cu(II)(acacen) (7) Although numerous transition metal complexes of such ligands have been studied over the years, very few lanthanide(m) complexes have been isolated. The objective of this work was to investigate the solid state and solution chemistry of lanthanide(III) complexes of three potentially heptadentate ligands based on this ligand chemistry. The novel ligands are condensation products of tris(2-aminoethyI)amine, commonly known as tren, and three equivalents of a conjugated ketone. The three ligands are tris(3-aza-4-6 7 9 methylhept-4-ene-6-one)amine, tris(2'-hycb:oxyacetopheniminoethyl)amine and tris(2'-hydroxy-4\5'-dimethylacetophenirmnoemyl)amine and shall be referred to from here on as H3trac (8), H3hatren (9) and H3datren (10) respectively. 8 9 (R = H) 10 (R = C H 3 ) Figure 2.2. H3trac (8), H3hatren (9) and H3datren (10) The three Schiff base derivatives can each exist in three tautomeric forms, namely as the P-ketoamino (11), the P-ketoimino (12) and the P-enolimino (13) tautomers. The P-ketoimino tautomer is the least favoured and is rarely observed. Schiff bases derived 11 12 13 Figure 2.3. The P-ketoamino (11), p-ketoimino (12) and P-enolimino (13) tautomers from P-diketones have been shown to be predominantly in their P-ketoamino tautomeric f o r m 3 9 ' 4 0 whereas those derived from P-phenolicketones are predominantly in the P-enolimino form 4 1 - 4 2 and are therefore depicted as such, although the other tautomeric form may also be present to a lesser extent 10 A series of analogous ligands, condensation products of tren and a variety of aldehydes, have been synthesized over the past couple of decades. The idea of using the tetradentate tripod-like ligand tren as a bridging group in the formation of multidentate chelating agents was first developed in 1968 independently by two research groups.43-44 The Schiff bases derived from the reaction of tren with pyridine-2-carboxyaldehyde (pytren) (14), 4 5 salicyladehyde (H3saltren) (15) 4 6 and pyrol-2-carboxyaldehyde (H3pyroltren) (16) 4 7 form stable complexes with a variety of transition metal ions. A series of such complexes were isolated and their crystal structures determined.45^7 Figure 2.4 : pytren (14), H3saltren (15) and H3pyroltren (16) There was great interest in the effect of the ligand bridging group on the geometry of the metal chelates. The crystal structures indicated that the interaction between the tertiary bridging nitrogen and the metal center was repulsive in most cases. The lone pan-on the tertiary nitrogen was directed toward the metal center and the interaction between the lone pair and the predominantly metal al orbital leads to distortions from the ideal sp3 hybridization angles for the tertiary amine toward sp 2 hybridization angles. These complexes have been recendy reviewed.48-49 The effect of the ligand field in lanthanide coordination chemistry is, in general, two orders of magnitude smaller than that observed for transition metal ions, and is not significant when compared to the effects of spin-orbit coupling and interelectronic repulsion.35 The large size of the lanthanide(III) ions and the lack of ligand field 14 15 16 1 1 restrictions on the coordination sphere allow lanthanide(IU) ions to form high coordinate complexes.36 It was hoped that the H3trac, H3hatren, and H3datren ligands would bind in a seven coordinate manner to the larger lanthanide ions, no repulsive interaction between the lone pair on the tertiary nitrogen and the metal ion orbitals being expected. The solid state structure of lanthanide(ILT) complexes depends mainly on ligand-ligand interactions and on the size of the metal ion. Distortions from idealized polyhedra are usually the result of steric constraints imposed on the structure by the bridging moieties or bulky groups present in the ligand.36 The structure of the heptadentate complexes was expected to be that of a slightly distorted capped trigonal antiprism, based on the distorted trigonal antiprismatic structures observed for the H3saltren (see Figure 2.4) transition metal complexes.46 The possibility of an eighth coordination site being occupied by a solvent molecule was also considered. Lanthanide(III) complexes of the chloro or nitro substituted H3saltren (see Figure 2.4) ligands have been isolated.50 Infrared spectroscopy and elemental analysis of the amorphous powders indicated the presence of lattice water. The complexes were insoluble in most organic solvents, and all solution studies were performed in DMSO. Complexes of the unsubstituted H3saltren chelator were found to be hydrolytically unstable and could not be isolated. Lanthanide(UI) complexes tend to be solution labile51 and nuclear magnetic resonance spectra of the Ln(3,5-diClsaltren) complexes (Ln = Pr, Nd, Sm) were recorded in order to determine whether the complexes dissociate in DMSO, a polar solvent which has a high affinity for lanthanide(III) ions. Large dipolar shifts were observed relative to the chemical shifts of the H3(3,5-diClsaltren) ligand, indicating that the ligand competes with DMSO for the sites on the lanthanide(ILT) ions.5 0 b Alyea and coworkers concluded that variations on the ligand system may afford soluble and inert paramagnetic compounds with potential as shift reagents in routine analysis of complex NMR spectra of organic Lewis bases.50b 12 LanthanideCLTJ) complexes tend to be solution labile due to the electrostatic nature of the bonding interactions. The lability of a given complex in solution is dependent on the nature of the ligand donor atoms. Lanthanide(ITI) ions wil l bind preferentially to ligands containing oxygen donor atoms, leading to relatively inert complexes. 3 1 Complexes of ligands containing only nitrogen donor atoms tend to be solution labile . 5 2 - 5 3 For example, Forsberg and coworkers isolated complexes <0f the tetradentate tris(2-aminoethyl)amine ligand from an acetonitrile solution under rigorously anhydrous conditions. 5 4 Kinetic studies of these complexes in acetonitrile indicated the highly labile nature of the complexes and the exchange process was studied in acetonitrile using N M R spectroscopy.55 These complexes could not be isolated in the presence of water and they decomposed readily upon exposure to air. 5 4 Multidentate ligands containing a combination of nitrogen and oxygen donor atoms have been found to form kinetically inert and thermodynamically stable lanthanide (III) complexes. The most widely studied lanthamde(III) complexes of this type are those formed by open-chained and macrocyclic polyamino polycarboxylic acids. 1 4 - 5 6 The stability of these complexes is due to a combination of the high affinity of the lanthanide (III) ion for the carboxyl oxygen donor atoms, the high denticity of the ligands, and the ideal fit between the cavity created by the ligands and the size of the lanthanide(m) ion. The gadolinium(III) complexes of diethylenetriamine-N,N,N',N",N"-pentaacetic 17 18 Figure 2.5. Hsdtpa (17) and FLtdota (18) 13 acid, Hsdtpa (17), and 1,4,7,10-tetraazacyclododecane-N,N',N",N'"-tetraacetic acid, H4dota (18) are highly inert and are the only two gadolinium(III) complexes currently undergoing clinical tests as in vivo NMR contrast agents.1-2 The possibility of forming lanthanide(ffl) adducts of H3trac was alluded to by various authors5 0-5 7 but resulted in the isolation of unstable oily products when attempted.5015 Some lanthanidetTTI) complexes (Ln = Pr, Eu and Yb) of highly fluorinated analogues of H3trac have been formed in situ and evaluated as NMR shift reagents for substrates containing oxygen and nitrogen donor atoms. The results indicate that the cage-like ligands partially encapsulate the lanthanide ions inhibiting the formation of complexes with multiple stoichiometrics and affording relatively inert complexes compared to other shift reagents investigated.58 The results of these studies were discussed at an ACS meeting in Las Vegas in 1980.58a A personal communication from Sievers and coworkers581* indicated that these complexes have been neither isolated nor structurally analysed. A bidentate analogue of H3trac, the Schiff base condensation product of 2,4-pentanedione and ammonia (Hacim), was found to complex quite readily with the heavier lanthanide(ITI) ions to yield Ln(acac)3(Hacim) (Ln = Yb, Lu). 5 9 These complexes could be recrystallized from 2,4-pentanedione, a surprising result in view of the high stability of Ln(acac)3(Hacac) type species. The crystal structure of Yb(acac)3(Hacim) (19) was determined and the ytterbium center found to be seven-coordinate, with the three acetylacetonato ligands bound in a bidentate fashion, and the Hacim ligand bound only through the oxygen atom59 (see Figure 2.6). The Hacim ligand exists in its 4-amino-3-pentene-2-one tautomeric form when bound to the ytterbium center. The stability of the complex is attributed to the possibility of intermolecular hydrogen bonding between the amino group of the bound Hacim and an acetylacetonato moiety bound to a neighboring ytterbium center. The fact that this complex 14 3 19 Figure 2.6. Yb(acac)3(Hacim) (19) can be recrystallized from 2,4-pentanedione was attributed to the lower solubility of Yb(acac)3(Hacim) complex as compared to that of the Yb(acac)3(Hacac) species.59 Lanthanide(III) adducts of the tetradentate analogue of H3trac, 5,8-diaza-4,6-dimethyldodeca-3,9-diene-2,l 1-dione, H2acacen (20), have been isolated.6 0'6 1 The nature Figure 2.7. Fl^acacen (20) of the adduct formed depends upon the ratio of metal to ligand used in preparing them and upon the size of the lanthanide(III) ion. Adducts having formulae [Ln(FJ.2acacen)2]X3 (Ln = La, Ce, FT, Nd, Sm; X" = Or, NO3-, SCN") and [Ln2(H2acacen)3]X6 (Ln = Gd, Dy, E r ; X" = Cl", NO3") were formed when the metal to ligand ratio was L 3 . 6 0 Adducts of general formula [Ln(FJ.2acacen)Cl3] were obtained when the metal to ligand ratio was kept at 1:1.61 These complexes were found to dissociate in aqueous solution with hydrolysis of the C=N bond. 6 0 Attempts6 2 at isolating lanthanide(III) complexes of the Schiff base ligand 1,1,1-tris(pyridine-2-aldiminomethyl)ethane, pytame (21), were unsuccessful and led to polymeric products. The ligand was found to exist as two possible structural isomers. The 20 15 first i s the e x p e c t e d o p e n - c h a i n e d i s o m e r a n d the s e c o n d i s the s tab le c a g e - l i k e 1-methyl-4,6,10-(tri-a-pyTidyl)-3,5,7-triazatricyclo[3,3,1,1,3J]decane Figure 2.8. pytame (21) and cage (22) isomer, cage (22). The cage isomer is the predominant species in solution and will bind to a lanthanide(III) ion in a bidentate or monodentate fashion, thus allowing a second or even third metal ion to bind, producing polymeric products.62 Hart and coworkers successfully isolated lanthanide(III) complexes of the tetradentate analogue of pytame, l,2-bis(pyridme-a-aldimino)ethane, dpea (23)63 and 23 Figure 2.9. dpea(23) obtained the crystal structure of Gd(NC»3)3(dpea).64 The gadolinium(III) ion is ten coordinate, the teffairriine ligand is bound in a tetradentate fashion, and the nitrate ions are all bound in a bidentate fashion. The complexes were found to be soluble in water, but on standing precipitation of Ln(OH)3 occurs indicating the dissociation and hydrolysis of the Schiff base in aqueous medium.63 1 6 Macrocyclic analogues of the dpea ligands yielded very stable complexes with the lighter but larger lanthanide(ffl) ions. The ligands are condensation products of 2,6-diacetylpyridine with a variety of diamines such as 1,2-diaminoethane, py2en2 (24), and 1,3-diaminopropane, py2pen2 (25). 6 5 - 6 7 Figure 2.10. Macrocyclic hexaimine ligands py2en2 (24) and py2pen2 (25). Ln(NC>3)3(py2en2 ) (Ln = La, Ce) complexes were isolated from a template reaction in methanol and once formed were inert to dissociation or metal ion exchange in aqueous medium. 6 5 Complexes of heavier lanthanide(flT) ions could only be isolated in a metal exchange reaction with Ba(ClC»4)2(py2en2); these complexes were labile and dissociated in aqueous solution. The ideal fit between the lighter lanthanide(IH) ions and the cavity of the py2en2 ligand caused the Ln(NC»3)3(py2en2) (Ln = La, Ce) complexes to be highly inert to transmetallation and dissociation.65 There is a large entropic gain involved in the formation of neutral complexes of the type L n L where the ligand L is bound in a hexadentate or heptadentate fashion. The chelate effect6 8 and the neutralization of charge 6 9 will be the main driving forces in the formation of complexes H3hatren, H3datren, or H3trac ligands with the trivalent lanthanide ions. The phenolic and the keto oxygens will bind strongly to the lanthanidetJU) ion even in the presence of other strong donors. The lanthanide(IH) ions have a low affinity for imino 24 25 17 donor atoms but will bind to them if the electropositive lanthanide ions fit the cavity created by the polydentate ligand. The question arises as to whether the entropic gain achieved in the formation of the LnL species will be great enough to overcome any steric restrictions enforced by the ligand system. Opposing the formation of LnL (L = hatren, datren, trac) complexes in the absence of other strong donor species is the possibility of steric interactions between the three ligand arms and of distortions of the sp3 geometry of the tertiary nitrogen due to an unfavourable fit between ligand and metal ion. Two modes of binding of the H3trac, H3hatren, and H3datren ligands can be envisaged (Figure 2.11). The first mode (type 1) would involve binding of all six or seven donor atoms to the metal center. The second mode (type2) would involve binding of the N 4 O 3 ligand in a tridentate O3 fashion, the other coordination sites on the lanthanide(III) ion being occupied by solvent molecules or other anions present during the isolation procedure. Typel complexes would have the formulation LnL and would contain the triply deprotonated (trianionic) N4O3 ligand. Type2 complexes would involve the fully typel type2 Figure 2.11. Possible binding modes of the potentially heptadentate ligands. 18 protonated ligand. Whether the complexes isolated are typel or type2 depends on the nature of the other species present in solution during the isolation of the adducts and on the size and charge density of a given lanthanide(lTJ) ion. 1 9 B. Complexes of Fhhatren and rfrdatren 1. Isolation of the LanthanidedTl') Adducts The synthetic procedure used to isolate the lanthanidefTrj) adducts of both H3hatren and F^datren was analogous to the procedure used previously to isolate lanthanide(III) complexes of Schiff base ligands.60-61 Slow addition of hydrated lanthanide(ITJ) chloride salts to a hot ethanolic solution containing a slight excess of Fhhatren or H3datren resulted in the immediate precipitation of amorphous powders. The molecular ion peaks due to [Ln(hatren)] + and [Ln(datren)] + were present in the mass spectra of all products isolated, and the fragmentation patterns were analogous to those observed for the substituted H3saltren products isolated by Alyea and coworkers.501* The infrared spectra of the adducts isolated were superimposable for a given ligand and the band patterns in the 1600-1500 cm"l region were different from the pattern observed in the ligand spectra. The crude complexes analysed as LnLxHCl ( Ln = La, Pr, Nd, Gd, Dy, Yb, Lu; L = hatren, datren and x= 0 to 3). We concluded that the products isolated were made up of a mixture of different adducts due to the non-integral number of chloride ions detected in the analysis. The products were soluble in strong donor solvents such as DMSO or pyridine,70 but ligand precipitation from the DMSO solution and the iH-NMR of the products in either DMSO or pyridine indicated that the complexes dissociate in the presence of these solvents to form solvated LnSm type species (S= DMSO, pyridine) and free ligand. The adducts were insoluble in all other solvents with lower solvating ability70 with the exception of methanol, and therefore methanol was the solvent of choice for further treatment of the products in an attempt to isolate complexes of the type Ln(hatren) or Ln(datren). La(datren)(CH30H) precipitated out upon slow cooling of a hot saturated methanolic solution of the crude product, and La(hatren) was isolated from a methanolic 20 solution of the crude product upon addition of diethyl ether. The recrystallized products were both microcrystalline in solution but lost their crystallinity upon removal from the mother liquor; the loss probably being due to evaporation of weakly bound lattice methanol. In the La(darren)(CH30H) complex, the methanol molecule is believed to be tightly bound to the lanthanum center opposite the bridging nitrogen atom, since the product still analysed for the presence of one molecule of methanol even after drastic drying of the sample. Problems arose when similar procedures were used to isolate analogous complexes with the heavier lanthanide(III) ions (Ln= Pr, Nd, Gd, Dy, Yb and Lu). The degree of chloride ion "contamination" varied from one recrystallization attempt to the next for a given lanthanide(III) ion and ligand system. Successive recrystallizations of the crude products finally resulted in product decomposition rather than isolation of the desired Ln(hatren) or Ln(datren) (Ln= Pr, Nd, Gd, Dy, Yb and Lu) adducts. The amount of chloride present in the adducts isolated for the heavier lanthanide(IIT) ions appears to be dependent to a great extent on the amount of chloride ion "contamination" in the crude adducts. In order to determine the role of the solvent in complex formation, the synthesis was attempted in methanol, isopropanol, and tetrahydrofuran to see if formation of LnL species (L= hatren, datren) would be favoured over the formation of the other species and whether the desired complex could be isolated directly from these solvents. The amorphous powders isolated from the synthesis in these solvents were analogous to those isolated in ethanol and contained variable equivalents of chloride ions. The synthesis and the recrystallization procedures were attempted under anhydrous conditions in order to determine whether the presence of water was a factor in the isolation of the chloride "contaminated" products. Under anhydrous conditions, the products isolated did not differ from those isolated in the presence of residual water and therefore the 21 residual water does not seem to be the cause of the difficulties encountered in isolating the desired LnL (L= hatren, datren) complexes. The hydrogen bonding between the ligand oxygen and imino nitrogen donor atoms must be disrupted in order to get the ligand to bind in a N4O3 fashion. The stability imparted to the ligand system by this hydrogen bonding interaction may interfere in the complexation of the ligand in a heptadentate fashion. Synthesis of the compounds by addition of a variety of bases was attempted in order to get the ligand in the L?~ form prior to the addition of metal chloride but resulted in either ligand precipitation or precipitation of Ln(OH)3. With lanthanum, the slightly larger ionic size30 of the metal ion appears to be ideal for binding of the N4O3 ligand in a hexadentate or heptadentate fashion. The strain imposed on the ligand due to possible distortions of the sp3 geometry of the apical nitrogen coupled with the possible steric interaction between the ligand arms appears to play an important role when one attempts to form complexes with the heavier but smaller lanthanide(ffl) ions in the presence of other donor species. During the synthesis of these complexes, the ligand H3L, chloride ions, solvent, and some residual water are present in solution. From the attempts to isolate complexes in solvents other than ethanol, and under anhydrous conditions, it appears that the chloride ions present in solution are the main competitor for the sites on the lanthanide(lTI) ion. Solution studies have shown that the species present in aqueous solutions of lanthanide(ni) ions containing chloride ions is Ln(H20)x3+ with x = 8,9.71 The chloride ion cannot compete with the water molecules for the coordination sites on the metal center. The lanthanide(ni)-chloride ion interaction is essentially outer-sphere; that is, the chloride ions are separated from the lanthanide ions by a layer of water molecules.72 Very few solution studies for determination of Ln-Cl interactions have been performed in solvents other than water, but 1 3 9 La-NMR 7 3 and X-ray diffraction74 studies have shown that inner-sphere La-Cl interactions are relatively strong in methanolic 22 solutions, and the main species present is the [LaCl2(CH30H)5]2 dimer. Methanol shows a lower nucleophilicity than water toward the lanthanide(III) ions and thus chloride ions can compete with the solvent for the metal coordination sites even in the presence of residual water (studies done in 97% methanol73). In the absence of data regarding the Ln-Cl interaction in non-aqueous solvents other than methanol, we will assume that in other solvents such as ethanol and isopropanol,70 the interactions between the lanthanide(III) ions and the chloride ions are inner-sphere. In order to investigate the effect of the counter ions in solution, the synthesis of lanthanide complexes by addition of hydrated lanthanide(III) nitrate salts to an ethanolic solution of ligand was attempted. Solution studies have shown that the interaction between the lanthanide(III) and nitrate ion in an aqueous solution is inner-sphere;75 the interaction between nitrate and lanthanide(III) ions must therefore be stronger than Ln-Cl interaction. In an ethanolic solution, the nitrate ions will compete strongly with the N4O3 chelating agent for the metal binding sites. The nature of the product isolated in the presence of nitrate ions may help elucidate the problems involved in isolating products in the presence of chloride ions. The crude products obtained upon addition of the lanthanide(III) nitrate salts to an ethanolic solution of either t^hatren or H3datren were amorphous powders and were insoluble in most common organic solvents, with the exception of DMSO. Their infrared spectra were analogous to those of the adducts isolated in the presence of chloride ions except for bands which indicated bound nitrate ions. The mass spectra of these complexes were nearly superimposable on the spectra obtained for the chloride species. These products analyzed as Ln(H3L)(N03)3 (L = hatren, datren) after several washes with hot methanol. The synthesis was attempted in a variety of solvents in order to investigate the effect of the solvent on complex formation. Upon addition of the hydrated lanthanidefTfl) nitrate salts to a solution of H3hatren or H3datren in acetonitrile, a powder appeared. The powder then redissolved upon stirring 23 Table 2.1. Elemental Analysis Data for F^hatren , La(hatren) and Ln(H3hatren)(N03)3 (Ln = La , Pr, Nd, Gd, Dy, Yb) Compound calculated expected C H N C H N H3hatren 71.97 7.25 11.19 71.78 7.35 11.05 La(hatren) 56.61 5.23 8.80 56.76 5.46 8.63 La(H3hatren)(N03)3 43.65 4.40 11.88 43.69 4.40 11.85 Pr(H3hatren)(N03)3 43.54 4.38 11.85 43.31 4.59 12.12 Nd(H3hatren)(N03)3 43.37 4.37 11.80 43.40 4.32 11.82 Gd(H3hatren)(N03)3 42.70 4.30 11.62 42.34 4.49 11.33 Dy(H3hatren)(N03)3 42.43 4.27 11.55 42.80 4.41 11.44 Yb(H3hatren)(N03)3 41.91 4.22 11.40 41.74 4.29 11.32 and a crystalline solid slowly precipitated out of solution. The products were insoluble in most organic solvents. They were slightly soluble in water, but formation of a gel-like precipitate indicated dissociation and formation of Ln(OH)3. The crystalline products analysed as L n ( H 3 L ) ( N 0 3 ) 3 (Ln = La, Pr,.Nd, Gd, Dy, Yb; L = hatren, datren) without further purification. In these complexes, the H 3 L is believed to be bound to the lanthanide(III) ion in a tridentate fashion through the phenolic oxygens (type2 in Figure 2.11), the other sites on the lanthanide(IJJ) ion being occupied by the nitrate ions. The strong interaction between the lanthanide(III) and nitrate ions excludes the possibility of binding between the imine donor atoms of the H 3 L (L= hatren, datren) and the lanthanide(UI) ions. Comparison between the products formed in the presence of the nitrate ions and the products formed in the presence of chloride ions leads us to believe that the "contaminated" chloride complexes 24 Table 2.2. Elemental Analysis Data for H3datren La(datren) and Ln(H3datren)(N03)3 (Ln = La , F T , Nd, Gd, Dy, Yb) Compound calculated expected C H N C H N H3datren 73.94 8.27 9.58 73.96 8.28 9.78 La(datren)(CH3OH) 59.04 6.56 7.44 59.40 6.70 7.44 La(H3datren)(NC>3)3 47.53 5.32 10.78 47.00 5.49 10.60 Pr(H3datren)(N03)3 47.42 5.31 10.75 47.70 5.09 10.60 Nd(H3datren)(N03)3 47.25 5.29 10.71 47.30 5.40 10.40 Gd(H3datren)(N03)3 46.59 5.21 10.56 46.33 5.29 10.70 Dy(H3datren)(N03)3 46.33 5.18 10.51 45.99 5.19 10.70 Yb(H3datren)(N03)3 45.81 5.13 10.39 45.64 5.05 10.28 are actually a mixture of LnL and Ln(H3L)Cl3 ( L = hatren, datren) species and the relative amount of each species is dependent upon the size of the lanthanide(III) ion and upon the stoichiometry of each species in solution. The elemental analysis data for FJ^hatren, La(hatren) and the Ln(hatren)(N03)3 adducts are given in table 2.1, and those for H^datren, La(datren)(CH30H) and the Ln(datren)(N03)3 species are given in table 2.2. The infrared and mass spectra of the two novel ligands and of their lanthanide adducts are discussed below. Shifts in the D C = N , t > C = C > V C - O . m ^ VCS frequencies on complexation to the lanthanide(III) ion and the presence of molecular ion peaks in the mass spectra of the lanihanide(rfl) adducts confirm the formulation given for the complexes. 25 2. Infrared Spectra of Khhatren. Ffedatren and their LanthanidedID Adducts Table 2.3 lists the main bands in the infrared spectra of H3hatren, La(hatren) and La(H3hatren)(N03)3, and table 2.4 lists the main bands in the infrared spectra of H3datren, La(datren)(CH30H) and La(H3datren)(NC>3)3. The infrared spectra of only two of the Ln(H3L)(N03)3 (Ln = La, Pr, Nd, Gd, Dy, Yb; H 3 L = H3hatren and H3datren) adducts are listed because the spectra of the nitrate adducts are independent of the lanthanide(III) ion. This indicates that the metal-ligand interactions are essentially identical within the sensitivity of the infrared spectrometer. A broad band of weak intensity is observed in the 2700 to 2200 cm~l region of the ligand spectra. The low intensity and low frequency of the O-H stretching modes has been observed previously for salicylalclimines and is attributed to strong intramolecular hydrogen bonding which weakens the phenolic O-H bond.5 0 b The broad band at 3600 to 3400 cnr* in the ligand spectra and those of their lanthanide(III) adducts results from the "uo-H of water present in the KBr used to make up the sample, or of the bound methanol molecule in the case of La(datren)(CH30H). Very little information can be drawn from this region of the spectra. In the double bond stretching region of the spectra, the overall band pattern changes on complexation to the lanthanide(LTI) ion. An exact assignment of such bands to either UC=C o r UC=N is not possible because of the high degree of vibrational coupling between these modes. 1 ^ -labelling studies have shown the higher frequency band to have more uc=N character.76 The double bond character of the C=N bond is reduced by hydrogen bonding and resonance which explains the low frequency of the C=N stretch. In the spectrum of H3hatren, one can distinguish four bands in the 1630 to 1500 cm~l region: a sharp band of strong intensity at 1615 cm"l, two sharp bands of medium intensity at 1580 and 1505 cm~l, and a weak band at 1545 cm~l. In the spectrum of La(hatren), one observes a broad band of strong intensity at 1635 to 1610 cm - 1 , no band in 26 the 1580 cm-1 region, a band at 1535 cirri, a broad band of medium intensity at 1510 cm"l. In the spectra of the Ln(H3hatren)(NC»3)3 adducts, one observes a band at 1610 cm'l with a shoulder at 1625 cirri, n o band at 1585 cm~l, and a sharp band at 1540 cm"l. The presence or absence of a band at 1510 cirr * cannot be commented on, as the region is obscured by a broad band at 1475 cm"l associated with the bound nitrate ion. Three sharp bands at 1620,1570 and 1510 cm - 1 and a weak band at 1530 cm - 1 are observed in the double bond stretching region of the spectrum of H3datren. In the spectrum of La(datren)(CH30H), the i>c=N and vc=C appear at 1620, 1530, and 1515 cm - 1. In the spectra of the Ln(H3datren)(NC»3)3 adducts, three bands are also observed in this region: two sharp bands at 1620 and 1535 cnrl a band at 1505 cnrl which is slightly obscured by the presence of a broad nitrate peak at 1460 cm" 1. Even though the La(hatren) and La(datren)(CH30H) complexes are believed to be bound in a typel (Figure 2.11) and the La(H3L)(N03)3 (L = H.3hatren, H^datren) species are bound in a type2 (Figure 2.11) manner, the effects of either mode of binding on the C=C and C=N stretching modes appear to be comparable. Shifts in the uc=N and t)c=c frequencies and changes in the overall band pattern in this region on coordination to the lanthanide(TII) ions indicate that binding to the metal ion has indeed occured. In the 1350 to 1190 cm"l region of the ligand spectra, one can observe various bands of weak to medium intensity which are assigned to either C-O or C-N stretching modes.7 7 The Drj-O and "Oc-N band pattern also changes on complexation to the lanthahide(III) ion. vc-0 and t>C-N are observed at 1310, 1270 and 1240 cm"l in the spectrum of H3hatren and at 1335, 1280, 1245 and 1200 cm - 1 in the spectrum of H3datren. On complexation to the lanthanide(LTJ) ion, uc-0 and Dc-N shift to higher frequency; analogous shifts were observed for salicylaldimines and their copper(II) complexes.76 The Ln-0 stretching modes are expected in the 300-500 cm - 1 region of the spectra.5015 A broad band of medium intensity at 400 cm" 1 with a shoulder at 425 cm"l in 27 T a b l e 2 . 3 . Infrared Data on Htyiatren , La(hatren), and La(H3hatren)(N03)3 Assignment3 H3hatrenb (cnr1) La(hatren)b (cm-1) La(H3hatren)(N03)3b (cm-1) UO-H 2700-2300w _ 3100-2780 3100-2700 3100-2700 UC=N/C=C 1615s 1635s.sh 1630s.sh 1580m.br 1610s 1610s 1545w.br 1535m 1545s 1505m.br 1510m -V4(N03) - - 1475s.br v(free NO3) - - 1385w 0)l(NO3) - - 1300s.br VC-O/C-N 1310m 1345m 1350s 1270mw 1260mw 1265s.sh 1240w 1210m 1220s D2(N03) - - 1030m 0*C-N=C 738s 760-745m.br 765s 710w 750s.sh 735m.sh 720w "UM-O - 400w.br 405m.br a) D = stretching, a = bending deformation modes b) s = strong, m = medium, w = weak intensity; sh = shoulder, br = broad band. the spectrum of La(hatren) and the weak bands at 435, 405 cm"1 in the spectra of the Ln(H3hatren)(NC»3)3 adducts are absent in the ligand spectrum and can be attributed to the Ln-O stretching mode. The bands at 405 cnr1 in the spectrum of La(datren)(CH30H) and at 490 and 410 cm'1 in the spectra of the Ln(H3datren)(NC>3)3 adducts are absent in the ligand spectrum and can be assigned to this mode. Ln-N stretching modes are expected in the 300 to 200 cm-1 region5* but are not observed for either ligand system. 28 Table 2.4. Infrared Data on H3datren , La(datren),(CH30H), and La(H3datren)(N03)3 Assignment3 H3datrenD (cnr1) La(datrenXCH30H)b (cm*1) La(H3datren)(N03)3 (cm"1) VO-U 2700-2200w 3660-3100m -Vrj-H 3040-2800 3080-2800 3000-2800 C^=N/C=C 1620s 1620s.br 1620s.br 1575s 1530s.br 1530s 1530w 1515m.sh -1510m 0)4(NO3) - - 1460s.br -u(free NO3) - - 1385w i ) l (N0 3 ) - - 1300s.br UC-O/C-N 1335m 1335w _ 1280s 1300m 1275s.sh 1245m 1275s 1230s 1200m 1195m.br 1195ms \)2(N0 3) - - 1035s 0"C=N-C 860m.br 870m.br 875m.br DM-O 405w.br 490m 410m.br a) u = stretching, o = bending deformation modes b) s = strong, m = medium, w = weak intensity; sh = shoulder, br = broad band. The spectra of both the Ln(H3hatren)(N03)3 and Ln(H3datren)(N03)3 (Ln = La, Pr, Nd, Gd, Dy, Yb) give little information as to the mode of binding of the nitrate ions. Ionic nitrate ions have D3h symmetry and exhibit three infrared active modes which occur at -1385, ~820, and ~730 cm"l . Upon complexation in a bidentate or monodentate 29 fashion, the symmetry of the nitrate ion is reduced to C2v and one can in general observe six infrared active modes.75 In the spectra of the Ln(H3L)(NC>3)3 adducts, a band of weak intensity is present at 1385 cm*1. A band in this region is also observed in the spectra of H3hatren and H^datren. Free nitrate ions usually absorb strongly in this region75 and the weak band at 1385 cnr1 is probably a result of ligand vibrations. In the spectra of the Ln(H3hatren)(N03)3, only three modes associated with bound nitrate ions (C2 V symmetry) were observed at 1300 ( D I ) , 1475(1)4) and 820(1)6) cm - 1 . The bands expected75 at 1030(1)2), 740(1)3) and 710(1)5) cnr* could not be assigned due to the presence of ligand bands in these regions. In the spectra of the Ln (datren) (NO3) 3 species, only three bands due to bound nitrate ions can be assigned. These bands occur at 1300 (ui), 1460(1)4) and 820 (D6) cm"1. The bands expected at 1030 (i)2), 740(1)3) and 710 (1)5) cm - 1 are either obscured by the presence of ligand bands or are not present in the spectra. 0 o c. 1 \ / \ N N—O—M O—N M free monodentate bidentate Figure 2.12. Nitrate ion: free (E>3h), monodentate (C 2 v) bidentate (C2 V) Nitrate ions bound in a bidentate or monodentate fashion can be differentiated using infrared spectroscopy if combination bands are present in the 1800 to 1700 cm"l region of the spectrum.78 No such bands are present in the spectra of the Ln(H3hatren)(N03)3 and Ln(H3datren)(NC»3)3 species. The high coordination numbers expected for lanthanide(HI) ions would suggest that the nitrate ions are bound in a bidentate rather than monodentate fashion. 3 0 3. Mass Spectra of the Fhhatren and Fhdatren and their LanthanidedLT) Adducts The mass spectra of both H3hatren and H3datren exhibit low intensity molecular ion peaks at mle = 500 and mle = 584 respectively. The inconsistent appearance of peaks at mle = 554 and mle = 638 in some of the ligand spectra indicate that partial hydrolysis of the imine bonds occurs upon standing, leading to the following molecular ions: R = H , m/e = 554 C H 3 , m/e = 638 The most intense peaks in the ligand spectra result from cleavage of the carbon-carbon bond of one of the ethyl arms of the tren moiety: R = H , m/e = 500 R = H , m/e = 352 C H 3 , m/e = 584 C H 3 , m/e = 408 The alternative cation from this fragmentation mode is also observed but rapidly undergoes rearrangement and subsequent loss of H2 to yield a more stable cation: 3 1 + R = H , m/e = 148 R = H , m/e = 146 C H 3 , m/e = 176 C H 3 , m/e = 174 This rearrangement has been noted previously for salicylaldimines.50b>79 Cleavage of the carbon-imino nitrogen bond giving rise to relatively stable radical cations is also observed: R = H , m/e = 365 C H 3 , m/e = 421 The relative intensities of the main fragments observed in the mass spectrum of H3hatren and in those of its lanthanide(LTI) adducts are given in table 2.5; the relative intensities of the main fragments in the mass spectrum of H3datren and in the mass spectra of its lanthanide(in) adducts are given in table 2.6. The monomelic character of the La(hatren) and La(datren)(CH30H) species is indicated by the presence of the low intensity molecular ion peaks. 5 0 b The molecular ion will rapidly undergo fragmentation to yield the following cation: R = H , m/e = 488 C H 3 , m/e = 544 32 Table 2.5. Mass Spectral Data on H3hatren , La(hatren) and Ln(H3hatren)(N03)3 (Ln = La, Pr, Nd, Gd, Dy, Yb) ADDUCT mle relative intensity H3hatren 500 2.2 365 59.8 352 83.9 230 100.0 148 28.7 146 30.5 139La(hatren) 636 1.2 488 1.9 352 9.4 223 100.0 139La(H3hatren)(N03)3 636 6.9 488 27.3 352 13.0 223 100.0 141Pr(H3hatren)(N03)3 638 28.3 490 96.5 352 12.0 223 100.0* l42Nd(H3hatren)(N03)3 639 4.3 491 13.0 352 12.1 223 100.0 158Gd(H3hatren)(N03)3 655 2.4 507 8.0 352 0.6 223 100.0* 164Dy(H3hatren)(N03)3 661 32.1 513 100.0* 352 6.6 174Yb(H3hatren)(N03)3 671 44.3 523 100.0 352 2.4 * most intense peak in spectrum if the peak at mle = 30 ( NO + , relative intensity = 100.0) is ignored when relative intensity calculations were performed. 33 Table 2.6. Mass Spectral Data on H3datren , La(datren)(CH30H) and Ln(H3datren)(N03)3 (Ln = La, Pr, Nd, Gd, Dy, Yb) ADDUCT mle relative intensity H3datren 584 7.8 421 51.0 408 100.0 176 40.9 174 57.6 l39La(datren)(CH3OH) 720 0.3 544 0.7 408 26.7 279 100.0 139La(H3datren)(N03)3 720 12.8 544 45.7 408 32.7 174 100.0 141Pr(H3datren)(N03)3 722 14.5 546 12.9 408 10.3 174 100.0 l42Nd(H3datren)(N03)3 723 4.3 547 13.9 408 45.6 174 100.0* i58Gd(H3datren)(N03)3 739 42.3 563 100.0 408 15.2 164Dy(H3datren)(N03)3 745 39.2 569 100.0 408 24.7 174Yb(H3datren)(N03)3 755 48.2 579 100.0 408 0.8 * most intense peak in spectrum if the peak at mle = 30 ( NO+, relative intensity = 100.0) is ignored when relative intensity calculations were performed. 3 4 The peaks at m/e = 488 and m/e = 544 are present at low intensity in the spectra of both La(in) adducts. The more intense peaks in the mass spectra of the adducts are due to fragments which no longer contain the metal ion, an indication of the lack of thermal stability in these metal complexes when ionized. The molecular ion for the Ln(H3L)(NC»3)3 (Ln = La, Pr, Nd, Gd, Dy, Yb; L= hatren, datren) adducts cannot be detected. Rapid loss of the three nitrate ions occurs upon ionization of the complexes. A peak for the [LnL]+ species is present in the mass spectra of all lanthanide adducts at medium to low intensity. The most abundant metal-containing ions for all species corresponds to the fragments observed for the La(hatren) species at m/e = 488 and for the La(datren)(CH30H) at m/e = 544 which result from the cleavage of one ethyl arm of the tren moiety. The relative intensities of these peaks increase quite drastically in the mass spectra of the nitrate species as one goes from the lighter lanthanide(III) adducts (Ln = La, Pr, Nd) to the heavier lanthanide(III) adducts (Ln = Gd, Dy, Yb). This increase in the stability of the metal-containing fragments is probably a result of the increased charge density as one goes to the heavier but smaller lanthanide(JJI) ions. The fragments containing the metal ion can easily be recognized in the mass spectra of the neodymium, gadolinium, dysprosium, and ytterbium adducts because of their characteristic isotope pattern.80 Only the relative intensities of the peaks corresponding to the most abundant metal isotope are given in table 2.5 and 2.6. A peak at m/e = 30 is sometimes the most intense peak in the spectra of the Ln(H3L)(N03)3 adducts and is attributed to the NO + cation (the presence of this peak is indicated in table 2.5 and table 2.6). The relative intensities of the ligand peak at m/e = 352 for the H3hatren species and at m/e - 408 for the H3datren species are also given as an indication of the stability of the metal-containing fragments. The most intense peaks in the mass spectra of La(hatren), La(datren)(CH30H), and Ln(H3L)(N03)3 (Ln = La, Pr, Nd, Gd; L= hatren; Ln = La, Pr, 35 Nd; L = datren) correspond to ligand fragments whereas those in the mass spectra of Ln(H3L)(N03)3 (Ln = Dy, Yb; L= hatren; Ln = Gd, Dy, Yb; L = datren) correspond to the metal-containing fragments. 36 C. Complexes of Fhtrac 1. Isolation of the Lanthanide(TJD adducts Schiff bases are obtained from the condensation of a primary amine and an aldehyde or ketone (equation 2.1). The mechanism of imine formation is well known. The reversible reaction is acid catalysed and is usually driven in the desired direction by removal of water from the reaction mixture. The formation of hydrolytically stable imines is favoured by the presence of aryl substituents on the ketone or aldehyde. Schiff base formation does not occur as readily when aryl substitution is not present, and the products, when isolated, tend to be unstable and prone to hydrolysis or polymerization.81 RR'C=0 + R"NH2 = RR'C=NR" + H2O (2.1) H3trac was prepared in benzene. Water was removed azeotropically using a Dean-Stark trap. The ^ - N M R spectrum of H3trac indicated that the P-ketoamino tautomer was the predominant isomeric form in chloroform and in methanol.3 9-4 0 The resonance of the methylene protons attached to the amine nitrogen appeared as a multiplet because of coupling to the adjacent methylene and amine protons. The ^ - N M R spectrum also indicated that the crude oil was relatively clear of proton containing impurities. We were unable to isolate pure H3trac. Lanthanide(ffl) ions have been frequently used as templating agents.65"67 In these reactions, the metal center has an organizational role in the formation of the macrocyclic ligands. We hoped that the metal ion would extract the H3trac from the crude ligand oil. The synthesis of lanthanide(iri) adducts of H3trac was undertaken using the crude oil. The synthetic procedures employed to isolate the lanthanide(in) adducts of H3trac were analogous to the procedures used to isolate complexes of H3hatren and F^datren. 37 Addition of hydrated lanthanum(ffl) chloride to an ethanolic solution containing a slight excess of H3trac resulted in slow precipitation of a white crystalline product: .N + La ,3+ EtOH -La ,N The product was recrystallized from ethanol and dried in vacuo at 45°C to yield La(trac). The solid is crystalline in solution but readily loses lattice solvent upon removal from the mother liquor. La(trac) has a low melting point but decomposed when sublimation was attempted. The product is soluble in water but the slow formation of a gel-like precipitate upon standing indicates complex dissociation, ligand hydrolysis and the formation of insoluble La(OH)3. The product slowly decomposes upon exposure to air due to hydrolysis of the imine bond, and must be stored under an inert atmosphere. When similar synthetic procedures were used to isolate the Ln(trac) (Ln = Pr, Nd, Gd, Dy, Yb, Lu) adducts, oily products were obtained. The synthesis was attempted in other solvents with analogous results. The fit between the lanthanide(III) ion and the H.3trac ligand is apparently more favourable in the case of the lanthanum(III) ion. Addition of hydrated lanthanide nitrate salts to an acetonitrile solution of H3trac resulted in slow precipitation of Ln(H3trac)(NC>3)3 (Ln = Pr, Nd, Gd, Dy, Yb). The lanthanum(LTI) analogue could not be isolated using this synthetic procedure, suggesting the delicate balance between the size of the lanmanide(ILT) ion and other factors such as the nature of other species in solution and the solvent used in the isolation of the lanthanide adducts. Unlike the H3hatren and H3datren complexes, none of the Ln(H3trac)(N03)3 adducts could be isolated from an ethanolic or methanolic solution. 38 The Ln(H3trac)(N03)3 products do not melt but decompose at temperatures greater than 200°C. They are soluble in water but slow formation of a gel-like Ln(OH)3 precipitate indicated dissociation and ligand hydrolysis. These products are not prone to decomposition upon exposure to atmospheric moisture and can be stored in a dessicator over long periods of time. Table 2.7. Elemental Analysis Data for H3trac, La(trac) and Ln(H3trac)(NC»3)3 (Ln = Pr, Nd, Gd, Dy, Yb) Compound calculated expected C H N C H N La(trac) 47.72 6.30 10.60 47.96 6.25 10.57 Pr(H3trac)(N03)3 35.06 5.04 13.63 34.89 5.00 13.54 Nd(H 3trac)(N0 3)3 34.90 5.02 13.56 34.79 5.00 13.80 Gd(H 3trac)(N0 3)3 34.28 4.93 13.33 34.35 4.94 13.43 Dy(H3trac)(N03)3 34.04 4.90 13.23 33.75 5.00 13.26 Yb(H 3trac)(N0 3)3 33.56 4.83 13.04 33.70 4.84 13.20 Gd(H3trac)(NC»3)3 precipitated out of the reaction mixture in crystalline form and its crystal structure was determined by Dr. Steve Rettig of this department. The crystal structure (see Figure 2.13) showed that the H3trac ligand was bound to the metal ion in a tridentate fashion and that the ligand is indeed in its P-ketoamino tautomeric form. 3 9 Figure 2.13. ORTEP drawing (above) and stercoview (below) of Gd(H3trac)(N03)3 40 2. Crystal Structure of GdfH^tracVNO^ The gadolinium(nr) ion in Gd(H3trac)(NC>3)3 is nine-coordinate (see Figure 2.13). The H3trac ligand is bound to the metal center solely through the oxygen donor atoms and the nitrate ions are bound in a bidentate fashion. The three ligand arms of H3trac approach the gadolinium center forming a left-handed screw and the nitrate ions form a right-handed screw in its approach to the metal center. The crystal structure consists of discrete molecules linked along the c-axis by C-H - O hydrogen bonds [C(8)-H(8b)-0(8) (x,y_,l+z); H-0 = 2.31 A, C - 0 = 3.275(4) A and C-H-O = 168°]. The chains are cross-linked by weak C-H-0 interactions [C(16)-H(16b)-0(4) (x,l-y,l/2-z); H-0 = 2.53 A, C - O = 3.438 A and C-H-O = 155°]. The bridging nitrogen of the H3trac ligand is tucked in with its lone pair directed towards the gadolinium center. The H3trac ligand system is unstrained and the geometry of the apical nitrogen is that of an sp3 hybridized nitrogen;48-82 the angles between C(l)-N(l)-C(8), C(l)-N(l)-C(15) and C(8)-N(l)-C(15) are 113.7°, 113.0° and 113.7° respectively. The pVketoamine groups within each of the three H3trac ligand arms are linked by hydrogen bonding between the keto oxygen and amine hydrogen. This hydrogen bonding leads to the formation of nearly planar six-membered rings within the ligand arms. The Yb(acac)3(Hacim) complex isolated by Richardson et al. 5 9 exhibits analogous hydrogen bonding between the keto oxygen bound to the metal center and the hydrogen of the amino group of the 4-amino-3-pentene-2-one ligand. Bond lengths show that the three |3-ketoamine moieties (see Figure 2.14 and Table 2.8) are quite delocalized, although the protons are definitely located on the nitrogen atoms. The carbon-oxygen lengths are much closer to that of the C=0 lengths in Hacac than those for C-O 8 3 , i.e. the double bond is localized. The C-O lengths are equal to that found for the C-O bond length (1.26(3) A) in the Hacim moiety of the Yb(acac)(Hacim) complex59 41 but are significantly less than the average values found in eight metal structures of the H2acacen ligand. 8 4 The C-N bond lengths are the same as those found in Yb(acac)3(Hacim)59 and the averaged F^acacen84 structures within experimental error. The two C-C distances within the P-ketoamine moiety are not significantly different and this can be explained by delocalization and intramolecular hydrogen bonding. All distances (see Table 2.8 and Figure 2.14) show a higher degree of delocalization within the P-ketoamine portion of the H3trac arm than found in the metal complexes of H2acacen. Figure 2.14. Average bond lengths (A) in the P-ketoamine moiety of Gd(H3trac)(N03)3 Complexes of the general formula M(unidentate)3(bidentate)3 have been isolated and structurally analysed by several groups. Two restrictions on the formation of high coordinate complexes are the metal ion size and ligand-ligand repulsive/steric interactions. All nine-coordinate species studied previously involve a lanthanide metal center and nitrate ions bound in a bidentate fashion. The lanthanide(rn) ions have large ionic radii and can accommodate the nine donor atoms within their coordination sphere. The nitrate ion, when bound in a bidentate fashion, reduces possible repulsive interactions between ligand species due to its relative compact size and small bite angle.36 42 Table 2.8. CrystaUographic Bond Lengths (A) (with estimated standard deviation in parentheses) for Gd(NC»3)3(H3trac) Bond L e n g t h ( A ) Bond L e n g t h ( A ) Gd -0(1) 2.344(2) N( 1 )-C(15) 1.457(6) Gd -0(2) 2.342(2) N (2)-C (2) 1.459(5) Gd -0(3) 2.337(2) N ( 2 ) - C ( 3 ) 1.322(5) Gd - 0 ( 4 ) 2 .516(3) N ( 3 ) - C ( 9 ) 1.450(5) Gd - 0 ( 5 ) 2.515(2) N(3)-C(1 0 ) 1 . 323(4 ) Gd - 0 ( 7 ) 2.524(2) N(4)-C( 1 6 ) 1.462(5) Gd - 0 ( 8 ) 2.444(2) N ( 4 ) - C ( 1 7 ) 1.310(5) Gd -0(10) 2.472(3) C( 1 )-C(2) 1.520(5) Gd - 0 ( 1 1 ) 2.527(2) C ( 3 ) - C ( 4 ) 1.406(5) 0 ( 1 ) - C ( 5 ) 1.274(4) C ( 3 ) - C ( 7 ) 1.505(5) 0(2)-C(1 2 ) 1.274(3) C ( 4 ) - C ( 5 ) 1 .394( 5) 0(3)-C(19) 1 . 280(4 ) C ( 5 ) - C ( 6 ) 1.496(6) 0 ( 4 ) - N ( 5 ) 1.263(4) C (8)-C (9) 1 .531(7) 0 ( 5 ) - N ( 5 ) 1.267(4) C( 10)-C(11) 1.392<5) 0 ( 6 ) - N ( 5 ) 1.218(4) C( 10)-C(14) 1.506(4) 0 ( 7 ) - N ( 6 ) 1.267(3) C( 1 1 )-C(12) 1.392(4) 0 ( 8 ) - N ( 6 ) 1.267(4) C ( 1 2 ) - C ( 1 3 ) 1.498(5) 0(9)-N(6) 1.210(3) C( 1 5)-C(16) 1.529(6) 0 ( 1 0)-N(7) 1.260(5) C( 17)-C(18) 1.407(6) 0 ( 1 1)-N(7) 1.261(5) C(17)-C ( 2 1 ) 1.494(5) 0 ( 1 2)-N(7) 1.221(4) C(18)-C ( 1 9 ) 1.397(5) N (1)-C (1) 1 .471(4) C(19)-C (20) 1.494(6) N (1)-C (8) 1.464(5) 43 Table 2.9. Crystallographic Bond Angles (deg) (with estimated standard deviation in parentheses) for Gd(NC»3)3(H3trac) Bonds Angle(deg) Bonds Angle(deg) 0(1] -Gd -0 2) 79.78(8) Gd -0(11)-N(7) 95.0 2) 0(1 ) -Gd -0 3) 79.76(8) C( 1)~N(1)-C(8) 113.71 3) 0( 1 -Gd -0 4) 148.33(8) C( 1 )-N(1)-C(15) 113.0< 3) 0(1 -Gd -0 5) 151.04(9) C( 8)-N(l)-C(l5) 113.7 3) 0( 1 ) -Gd -0 7) 72.12(7) C( 2)-N(2)-C(3) 125.3 3) 0(1] -Gd -0 8) 123.02(8) C( 9)-N(3)-C(10) 125.81 3) 0( 1 -Gd -0 10) 94.50(11) C( 16)-N(4)-C(17) 126.0( 3) 0(1 -Gd -0 11) 82.34(9) 0( 4)-N(5)-0(5) 116.1 3) 0(2 -Gd -0 3) 79.71(8) 0( 4)-N(5)-0(6) 122.0 4) 0(2 -Gd -0 4) 80.86(8) 0( 5)-N(5)-0(6) 121.9 3) 0(2 -Gd -0 5) 86.19(9) 0( 7)-N{6)-0(8) 115.0 2) 0(2 -Gd -0 7) 148.19(7) 0( 7)-N(6)-0(9) 122.5 3) 0(2> -Gd -0 8) 152.13(10) 0< 8)-N(6)-0(9) 122.5 [3) 0(2] -Gd -0 10) 127.64(9) 0( 10)-N(7)-0(11) 116.3 3) 0(2 -Gd -0 1 1 ) 77.01(9) 0( 10)-N(7)-0(12) 121.6 4) 0(3 -Gd -0 4) 72.28(8) 0( 11)-N(7)-0(12) 122. 1 4) 0(3 -Gd -o 5) 122.60(9) N< 1)-C(1)-C(2) 1 10.9 3) 0(3 -Gd -0 7) 80.88(8) N( 2)-C(2)-C(1 ) 110.3 3) 0(3] -Gd -o 8) 88.42(9) N( 2)-C(3)-C(4) 1 22.4 3) 0(3 -Gd -0 10) 150.95(9) N( 2)-C(3)-C(7) 118.9 3) 0(3 -Gd -0 1 1 ) 152.75(9) C< 4)-C(3)-C(7) 118.7 4) 0(4 -Gd -0 5) 50.54(8) C( 3)-C(4)-C(5) 125.2 3) 0(4 -Gd -0 7) 116.51(8) 0< 1)-C(5)-C(4) 1 23.6 3) 0(4 -Gd -0 8) 71.50(9) 0< 1)-C(5)-C(6) 119.2 3) 0(4 -Gd -0 10) 117.17(11) C< 4)-C(5)-C(6) 117.2 3) 0(4 -Gd -0 1 1 ) 117.16(10) N< 1)-C(8)-C(9) 113.0 r3) 0(5 -Gd -0 7) 125.58(8) N 3)-C(9)-C(8) 110.3 3) 0(5 -Gd -o 8) 79.10(9) N< 3)-C(10)-C(11) 122.2 3) 0(5 -Gd -0 10) 74.26(11) N< 3)-C(10)-C(14) 119.2 3) 0(5 -Gd -0 1 1 ) 69.81(10) C< 11)"C(10)-C(14) 118.5 3) 0(7 -Gd -0 8) 50.94(8) C( 10)-C(11)-C(l2) 125.5 3) 0(7 -Gd -0 10) 70.31(9) 0( 2)-C(12)-C(1l) 122.8 3) 0(7 -Gd -0 1 1 ) 112.79(10) 0< 2)-C(12)-C(13) 119.3 3) 0(8 -Gd -0 10) 70.77(11) C( 11)-C(12)-C(13) 117.9 (3) 0(8 -Gd -0 1 1 ) 118.65(10) N 1)-C(15)-C(16) 111.9 3) 0(10)-Gd -0(11) 50.73(10) N( 4)~C(16)-C(15) 111.1 3) Gd -0(1) -c 5) 139.5(2) N 4)-C(l7)-C(18) 122.5 [3) Gd -0(2) -c 12) 148.4(2) N( 4)-C(17)-C(21) 1 19. 1 '4) Gd -0(3) -c 19) 140.5(2) C< 18)-C(17)-C(21) 118.3 4) Gd -0(4) -N 5) 96.7(2) C( 17)-C(18)-C(19) 1 25.4 3) Gd -0(5) -N 5) 96.6(2) 0< 3)-C(l9)-C(l8) 122.4 3) Gd -0(7) -N 6) 94.8(2) 0< 3)-C(l9)-C(20) 118.2 3) Gd -0(8) -N 6) 98.7(2) C( 18)-C(19)-C(20) 1 19.4 3) Gd -0(10)-N(7) 97.7(2) 44 Nine coordinate complexes are usually described in terms of two idealized polyhedra, namely the tricapped trigonal prism (TCTP) and the capped square antiprism (CSAP). The structures of M(DMSO)3(N03)3 (M = Lu, Er and Yb), Nd(atp)3(N03)336 and Gd(H20)3(N03)3(18-crown-6)85 have been determined and are analogous to the structure of Gd(H3trac)(NC»3)3. The coordination sphere of these complexes can be described in terms of a distorted TCTP polyhedron.36'86-88 The bidentate ligands span the three edges defined by one of the capping positions and a position on one of the triangular faces. The unidentate ligands occupy the three positions on the opposite triangular face of the distorted TCTP polyhedron as depicted in figure 2.15.36 In the structure of Gd(H3trac)(N03)3, the keto oxygens of the H3trac occupy the three positions on one of the triangular faces of a distorted TCTP; the other six positions are occupied by the bidentate nitrate ions. Figure 2.15. Schematic drawing of M(unidentate)3(bidendentate)3, TCPT. An alternative description of the coordination polyhedron would be that of an octahedron with the nitrate ions occupying a single site. In this description the complex could be described as the pseudo-facial isomer (see Figure 2.16) The bond angles verify this description of the coordination sphere around the Gd atom (e.g O(3)-Gd-O(10) = 151°, 0(3)-Gd-0(ll) = 153°, O(10)-Gd-O(ll)=51°, the three angles total 354°). 45 Figure 2.16. ORTEP view of tricapped trigonal prismatic GdOg coordination polyhedron in Gd(H3trac)(NC»3)3 46 Ideally the structure would have C3 symmetry but the deviations between equivalent atom parameters are too great for C3 symmetry to be assigned. Two of the nitrate ions show statistically, but not chemically significant, deviations from planarity, N(5) and N(6) are displaced by 0.010(3) and 0.014(3) A from their respective O3 planes. The gadolinium atom is displaced by 0.9616(1), 0.7090(1) and 0.9381(1) A from the N(2)-C(3)-C(4)-C(5)-0(l) portion and the corresponding groups containing 0(2) and 0(3) of the H3trac ligand. The gadolinium center (CN = 9, r = 1.11 A89) is not very crowded. Very few of the interligand oxygen distances (see table 2.10) are within the contact range (2.79-2.90 A85). The triangular face occupied by the H3trac keto oxygens has dimensions of 2.999, 3.001 and 3.005 A; the triangular face occupied by the non-capping oxygen atoms of the nitrate ions has dimensions of 2.846, 3.010 and 3.158 A. Table 2.10. Oxygen-Oxygen Distances in the Coordination Polyhedron of Gd(H3trac)(N03)3 atom3 distance atom3 distance (A) (A) 0(l)-0(2) 3.005 0'(4)-0"(5) 2.148 0(l)-0(3) 3.001 0'(7)-0"(8) 2.138 0(2)-0(3) 2.999 O"(10)-O'(H) 2.142 0(l)-0'(7) 2.869 0(1)-0'(H) 3.209 0(2)-0'(H) 3.035 0(2)-0'(4) 3.153 0(3)-0'(4) 2.866 0(3)-0'(7) 3.157 O(l)-O"(10) 3.537 0'(4)-0"(8) 2.898 0(2)-0"(5) 3.321 0"(5)-0'(H) 2.885 0(3)-0"(8) 3.335 O'(7)-O"(10) 2.877 0"(5)-0"(8) 3.158 0'(4)-0'(7) 4.286 O"(5)-O"(10) 3.010 0'(4)-0'(H) 4.303 O"(8)-O"(10) 2.846 0*(7)-0'(H) 4.207 a) 0=trac oxygen, 0'=capping nitrate oxygen, 0"= non-capping nitrate oxygen 47 The bond lengths between the gadolinium(III) and keto oxygens of the H3trac vary from 2.337(2) to 2.344(2) A. The Gd-0 (nitrate ion) bond lengths vary from 2.444(2) to 2.527(2) A and are analogous to the Gd-0 (nitrate ion) bond lengths (2.411(11) to 2.533(13) A) in Gd(H20)3(N03)3(18-crown-6)85. The structure of Gd(H3trac)(NC»3)3 is analogous to the structure of Gd(H20)3(N03)3(18-crown-6)85. In this complex, the gadolinium ion is also nine coordinate; the gadolinium is bound to three water molecules and to the three nitrate ions (the crown ether is not bound directly to the gadolinium(UI) ion but is held in the crystal lattice by hydrogen bonding to the three water molecules).85 3. Infrared Spectra of H3trac and its LanthanidefllT) Adducts The main bands in the infrared spectra of H3trac, La(trac) and Gd(H3trac)(N03)3 are listed in table 2.11. The infrared spectra of the Ln(H3trac)(NC»3)3 (Ln = Pr, Nd, Gd, Dy, Yb) adducts are superimposable indicating that the metal-ligand interactions are essentially identical within the sensitivity limitations of the infrared spectra. Two broad bands of medium intensity are present in the 3600-3300 cnr 1 region of the ligand spectrum. Two bands in this region have often been observed in the spectra of liquid secondary amines; the band at higher frequency is assigned to the N-H stretching mode, and the second band arises from an overtone of an N-H bending mode which is intensified by coupling to the N-H stretch (Fermi resonance).90 The spectra of La(trac) and Ln(H3trac)(NC>3)3 exhibit a band at 3660-3300 cnr1 which is attributed to Do-H of water in the KBr used to make up the sample. The nature of the band at 3210 cnr 1 in the spectrum of La(trac) is unknown but may be due to U N - H or vo-H of partially hydrolysed La(trac). The band at 3250 cm - 1 in the spectrum of Gd(H3trac)(N03)3 is assigned to D N - H of the bound H3trac moiety. Vibrational coupling between the C=0 and C=C stretching modes makes any assignment of bands in the 1620 to 1500 cm*1 region tentative. The uc=N of the minor 4 8 Table 2.11. Infrared Data on H3trac , La(trac), and Gd(H3trac)(NC>3)3. Assignment3 H3tracb (cm-l) La(trac)b (cnr 1) Gd(H3trac)(N0 3 ) 3 b (cnr 1 ) 3600-3400m 3400-3000m 3280-3140m 3250s DC-H 3080 - 2840 3005-2820 3010-2830 combination(N03) - - 2500w 2320w combination(N03) - - 1780w 1740w uc=o 1615-16108^1* 1605s 1605s.br 1>C=C 1585-1565s .br« 1540s 1550s.br 1>C=N 1520m.sh3 1515m -u 4 ( N 0 3 ) - - 1520-1440s Dl(N03) - - 1330-1370s UC-N 1355ms 1360m.sh 1370m vc-c 1295s.br 1300s.br 1275s, sh UC-CH3 1250m.sh 1230w.sh 1210w 1210s D 2 ( N 0 3 ) - 1035s D 6 ( N 0 3 ) - - 820m OC-H 820-770m.sh 740s.br 850-780m.sh 755m.br 810m 770s 745s 420-400m 430-410m 350w 330w a) x> = stretching, a = bending deformation modes b) s = strong, m = medium, w = weak intensity; sh = shoulder, br = broad band c) values taken from spectrum in ecu. 49 (3-enolimino tautomer (Figure 2.3) and an N-H bending mode are also expected in this r e g i o n . 9 0 - 9 1 The double bond character of the C=0 bond is reduced by strong intramolecular hydrogen bonding and resonance between the forms:77 This explains the low frequency of the C=0 stretching mode. The band at 1585-1565 cm - 1 is tentatively assigned to C=C stretch and the band at 1520 cm - 1 to the strongly hydrogen bonded C=N stretching mode of the P-enolimino tautomer.92'93 Al l three bands undergo bathochromic shifts and sharpen considerably upon coordination to the lanthanide (III) ion in a typel or type2 fashion (Figure 2.11). In the spectra of the Ln(H3trac)(N03)3 adducts, the 1520 to 1440 cm - 1 region of the spectra is obscured by a broad nitrate band. Bands in the 1500 to 600 c m - 1 region of the spectrum were assigned by comparison with the infrared spectra of other Schiff bases derived from pV-diketones and diamines 6 0 ' 6 1 ' 9 2 - 9 4 and the assignments are tentative. Most bands in this region shift on coordination to the lanthanide(III) ion. Ln-O stretching vibrations usually occur in the 500 to 300 cm-1 region, and Ln-N stretching modes occur in the 300 to 200 cm"1 region. 5 0 b The band at 420-400 cnr 1 in the spectrum of La(trac) and the band at 430-410 cm"1 in the spectrum of Gd(H3trac)(NC>3)3 are assigned to U M - 0 of the bound H3trac. The bands at 350 and 330 cm - 1 in the spectrum of Gd(H3trac)(NC»3)3 are assigned to the Ln-O(nitrate) stretching vibration because the spectrum of La(trac) exhibits no band in this region. The bands attributed to the nitrate ions of the Ln(H3trac)(NC»3)3 adducts have greater diagnostic value. The bands at -1480 (x>4, Bi), -1300 (DI , A i ) , 1035 (\)2, B 2 ) cm - 1 are characteristic75 of nitrate ions with C 2 v symmetry (see Figure 2.12); that is, all three nitrate ions are bound in a bidentate or monodentate fashion. Free nitrate ions (E>3h 50 symmetry) have three infrared active modes which occur at -1385 (D3, E), -820 ("02, A 2 ) and -730 (1)4, E) cm" 1 . 7 5 The band at -1385 cnr 1 is characteristic of ionic nitrate ions 7 5- 9 3 and is not present in the spectra of the Ln(NC>3)3(H3trac) adducts, indicating again that all three nitrate ions are bound. The presence of two combination bands ( D 1+1)4 in D3h symmetry) in the 1800 to 1750 c m - 1 region of the spectrum is characteristic of bound nitrate ions. These combination bands are separated by 5-26 cm - 1 for nitrate ions bound in a monodentate fashion and separated by 20-66 cm - 1 for bidentate nitrate ions. 7 8 In the spectra of the Ln(H3trac)(N03)3 species, two bands are present in this region and are separated by ~40cm_1. All three nitrate ions are therefore bound in a bidentate fashion. 3. Mass Spectra of Fhtrac and its Lanthanide(HI) Adducts The molecular ion peak ( M + ) is present in the mass spectrum of H3trac, but at very low intensity. The molecular ion is unstable and will rapidly undergo fragmentation. A tetradentate analogue of H 3trac, 3,5-diaza-4,9-dimethyldodeca-3,9-diene-2,ll-dione (H2acacen), exhibits a characteristic fragmentation pattern. The predominant species in the mass spectrum of H2acacen was shown to result from cleavage of the carbon-carbon bond of the diamine bridging group:95 1 • + mle =224 mle =112 51 H3trac exhibits analogous fragments. Cleavage of one of the ethyl bridging groups of the tren moiety results in a relatively intense peak at m/e = 280 and a peak of medium intensity at m/e = 112. m/e = 392 m/e = 280 A second intense peak occurs at m/e = 265 and results from fragmentation of two (3-ketoamine moieties yielding the following fragment: m/e =265 The most intense peak in the spectrum results from subsequent cleavage of the 13-ketoamino moiety and loss of H2 to yield the following fragment: N = C H C H 3 m/e =222 In the spectrum of La(trac), the molecular ion peak at m/e = 528 for [La(trac)] + is more intense than the molecular ion peak for H3trac. The lanthanum ion imparts a certain degree of stability to the (3-ketoarnine ligand. The fragmentation pattern of [La(trac)] + is 52 analogous to the fragmentation pattern of the free ligand and can also be explained in terms of cleavage of the carbon-carbon bond of one of the bridging ethyl groups . The most intense peak resulting from a metal-containing fragment occurs at mle = 416 and corresponds to the fragment: mle =416 A second, relatively intense peak occurs at mle = 403 and corresponds to cleavage of two of the P-ketoamine moieties yielding the following ion: CHCH2 mle =403 The most intense peak in the mass spectrum of La(trac) corresponds to the ligand fragment at mle = 280 indicating that the molecular ion is thermally unstable and loss of the metal ion occurs readily. The fragmentation patterns of the Ln(H3trac)(NC>3)3 (Ln = Pr, Nd, Gd, Dy, Yb) complexes are analogous to those observed for La(trac). In the case of the neodymium, gadolinium, dysprosium, and ytterbium adducts, the fragments containing the metal ion are easily recognized by their characteristic isotope pattern.80 Only the fragments containing the most abundant isotope are given in table 2.12. 53 Table 2.12. Mass Spectral Data on H3trac, La(trac) and Ln(H3trac)(NC>3)3 (Ln = Pr.Nd, Gd, Dy, Yb) ADDUCT mle relative intensity H3trac 392 1.0 280 79.5 262 63.3 222 100.0 112 23.8 139La(trac) 528 2.8 416 4.9 403 2.6 280 100.0 222 70.1 141Pr(H3trac)(N03)3 530 28.7 418 100.0 405 47.5 280 36.9 142Nd(H3trac)(N03)3 531 45.8 419 100.0 406 57.3 280 69.6 158Gd(H3trac)(N03)3 547 46.5 435 100.0 422 57.3 280 20.0 164Dy(H3trac)(N03)3 553 38.3 441 100.0 428 53.9 280 5.8 174Yb(H3trac)(N03)3 563 43.3 451 100.0 438 49.6 280 10.7 54 The most intense peaks in the spectra of Ln(H3trac)(N03)3 adducts correspond to the analogous fragments at m/e =416 and m/e = 403 in the mass spectrum of La(trac). The stability of the metal-containing fragments does not appear to be dependent on the size and charge density of the lanthanide(III) ion, unlike the stability of the metal-containing fragments of the nitrate adducts of FJ^hatren and H3datren. The molecular ion peak corresponding to [Ln(H3trac)(N03)3]-+ is not observed. The three nitrate ions are rapidly lost upon ionization and volatilization of the complex. The ion peaks corresponding to [Ln(trac)]+ are present at medium intensity in the spectra of all the Ln(H3trac)(N03)3 adducts indicating rapid rearrangement of the molecular ion to the more stable [Ln(trac)]+ cation. The free ligand fragment is observed at m/e = 280 although at much lower intensity than in the spectrum of La(trac). The main fragments observed in the mass spectra of H 3trac, La(trac) and Ln(H3trac)(NC>3)3 are described in table 2.12. The relative intensity of the fragments resulting from loss of the metal ion are much lower in the spectra of the Ln(H3trac)(NC»3)3 than in that of La(trac). The relative intensity of the m/e = 280 fragment is given for all species as a reference. The fragmentation pattern of these species is analogous to those exhibited by many multidentate P-ketoamino ligands and their corresponding metal chelates. The main fragmentation mode involves cleavage of the carbon-carbon bond of a bridging ethyl arm or cleavage of the P-ketoamine moiety. 9 5' 9 6 The presence of the peak corresponding to [Ln(trac)]+ indicates that the complexes are monomelic. 55 D. Experimental 1. General Techniques All chemicals were reagent grade and were used as received; methanol was distilled from Mg(OCH3)2 under N 2 . Lanthanide salts were obtained from Alfa or BDH; 2'-hydroxyacetophenone was obtained from Eastman, 2'-hydroxy-4',5'-dimethylacetophenone from Aldrich, 2,4-pentanedione from Fisher; tris-(2-aminoethyl)amine (98+%) was a gift from the Hampshire Organic Chemicals Division of W. R. Grace and Co. The analyses for C, H , Cl , and N were performed by Mr. Peter Borda of this department. The J H - N M R spectra (300MHz) of the products were recorded by the U.B.C. NMR service on a Varian XL-300 and the chemical shifts were measured relative to TMS. The infrared spectra were recorded on a Perkin-Elmer PE783 spectrophotometer using the 1601 cm - 1 band in the spectrum of polystyrene as the reference. The samples were introduced as KBr pellets with the exception of the H3trac ligand for which the spectra of the neat oil and dilute sample (l:10/oil: CCI4) were recorded between KBr disks. The KBr was stored at 90°C prior to use. The mass spectra were recorded by the U.B.C. mass spectrometry service using a Kratos MS50 (electron impact ionization, EI). The intensity of a given peak is stated relative to the most intense peak in the spectrum. The crystal structure of Gd(H3trac)(N03)3 was determined by Dr. Steve Rettig of this department 56 2. Synthetic Procedure 2.1. Synthesis of Fhhatren To a 250 mL ethanolic solution of 19.38 g (0.14 mol) 2'-hydroxyacetophenone was added 6.904 g (0.047 mol) tris(2-aminoethyl)amine. Molecular sieves were added and the solution was refluxed for 1 hour. The deep yellow solution was filtered hot. Upon cooling, a yellow solid formed. The reaction mixture was stored at -20°C overnight, and the solid mass of bright yellow H^hatren was filtered and set to dry overnight at room temperature, yielding 20.3 g (86%) pure H3hatren, mp = 118-120°C. The product is a bright yellow flaky solid which was stored in a dessicator in the presence of Drierite until further use. *NMR data (CDCI3): 5 7.25 (3H, m, (j>-H); 7.22 (3H, m, <)>-H), 6.85 (3H, m, (|>-H), 6.60 (3H, m, <)>-H), 3.65 (6H, t, J = 7 Hz, =NCH2CH2N), 3.03 (6H, t, J = 7 Hz, =NCH2CH2N), 2.23 (9H, s, CH3ON). The product may slowly hydrolyse; a simple recrystallization from ethanol prior to use yields the pure ligand. The product is very soluble in many organic solvents such as CHCI3, CH2CI2, benzene, toluene, DMSO, pyridine, hot CH3OH, CH3CH2OH, and isopropanol. It is sparingly soluble in cold CH3OH, CH3CH2OH, isopropanol and insoluble in H2O. 2.2. Synthesis of La(hatren) To a solution of 0.641 g (1.28 mmol) H3hatren in 50 mL boiling ethanol was added 0.468 g (1.26 mmol) of LaCl3-7H20. A bright yellow solid formed immediately upon addition of the hydrated lanthanum chloride salt to the ligand solution. The solution was stirred hot for 10 minutes and stored at - 20°C overnight. The precipitate was filtered, rinsed with ethanol, and dried overnight in vacuo to yield 0.732 g (91%) of crude product. 57 The product was dissolved in methanol. Diethyl ether was added until the solution turned slightly cloudy, and the solution was stored at -20°C for a period of two days. The solvent was removed by decantation and the product rinsed out with ethanol. The product (0.581 g, 72% yield; mp > 200°C dec) was dried in vacuo over P4O10 at 85°C for 2 days. Crystalline products can be obtained from a dilute methanolic solution of La(hatren) upon addition of diethyl ether. The flat crystals lose weakly bound lattice solvent molecules upon removal from the mother liquor and could not be isolated intact for crystal structure analyses. 2.3. Synthesis of Ln(r^hatren)(NO^ (Ln = La. Pr. Nd. Gd. Dv. Yb) The Ln(H3hatren)(NC»3)3 adducts were isolated in high yields (82 to 93%) using procedures analogous to the one outlined below for Nd(H3hatren)(NC»3)3. All products precipitated out of solution in a microcrystalline form. The Ln(H3hatren)(NC»3)3 adducts were soluble in DMSO and sparingly soluble in acetonitrile, nitromethane, and pyridine. The products did not melt, but decomposed at temperatures greater than 220°C. To a boiling solution of 1.06 g (2.12 mmol) H3hatren in 80 mL C H 3 C N were added 0.869 g (2.06 mmol) Nd(N03)3-6H20. The solution turned turbid immediately upon addition of the hydrated neodymium nitrate salt, but the solid slowly went back into solution upon stirring. The solution was refluxed for 15 minutes and a crystalline solid slowly precipitated out of solution. The solution was filtered hot. The green crystalline product was dried overnight to yield 1.58 g (92%) pure Nd(H3hatren)(N03)3, mp > 220°C dec. Crystals were grown in a saturated acetonitrile solution, but were of insufficient quality for X-ray analysis. 58 2.4. Synthesis of Khdatren A n 80 mL ethanolic solution of 1.696 g (10.2 mmol) 2'-hydroxy-4',5'-dimethylacetophenone and 0.5032 g (3.4 mmol) tris(2-aminoethyl)amine was refluxed for 4 hours. The bright yellow solution was filtered hot. The product would not precipitate out of the solution upon cooling and hexanes were added to the reaction mixture at room temperature until the solution turned slightly turbid. The solution was stored at -20°C overnight. The bright yellow precipitate was filtered and dried overnight in vacuo to yield 1.73 g (88%) H3datren. The product was recrystallised from isopropanol to yield pure H3datren (mp 127-130°C). The product is a bright yellow flaky solid which was stored in a dessicator in the presence of Drierite until further use. *NMR data (CDCI3): 8 6.96 (3H, s, <|>-H); 6.62 (3H, s, <t>-H), 3.60 (6H, t, J = 7Hz, =NCH2CH 2 N), 2.96 (6H, t, J = 7 Hz, =NCH2CH2N), 2.20 (18H, s, CH3C=N and/or 0-CH3), 2.10 (9H, s, C H 3 O N and/or <|>-CH3). The product may slowly hydrolyse but a simple recrystallization from isopropanol prior to use yields the pure ligand. The product is very soluble in many organic solvents such as benzene, toluene, D M S O , pyridine, CHCI3, CH2CI2, hot CH3OH, hot CH3CH2OH, and hot isopropanol and was sparingly soluble in cold CH3OH, CH3CH2OH, isopropanol and insoluble in H2O. 2.5 Synthesis of La(datren)(CH^OH) To a solution of 0.587 g (1.00 mmol) H3datren in 20 mL boiling ethanol were added 0.361 g (0.97 mmol) LaCl3-7H20. A yellow precipitate formed immediately upon addition of the lanthanum salt to the ligand solution. The solution was stirred for 5 minutes and the product collected by suction filtration. The product was dried overnight in vacuo 0.481 g (70% yield). The product was recrystalized using freshly distilled methanol under 59 inert atmosphere. The recrystallized product precipitated immediately out of the hot methanolic solution upon cooling and was filtered after being stored at -20°C overnight. The product (0.326 g, 51%; mp > 200°C dec) was dried overnight in vacuo over P2O5 at 60°C for 3 days. The product is insoluble in water and most organic solvents and is sparingly soluble in methanol and very soluble in DMSO and pyridine. 2.6. Synthesis of Ln(H^datren)(NO^ (Ln = La. FT. Nd. Gd. Dv. Yb) The Ln(H3datren)(N03)3 complexes were isolated in high yields (78 to 89%) by procedures analogous to the procedure outlined below for Nd(N03)3(Ff3datren). The microcrystalline products were soluble in DMSO, but insoluble in all other common organic solvents. All products decomposed at temperatures greater than 220°C. To a boiling solution of 0.807 g (1.38 mmol) H3datren in 80 mL C H 3 C N were added 0.580 g (1.38 mmol) Nd(N03)3-6H20. The solution turned turbid immediately upon addition of the hydrated neodymium nitrate salt but the solid redissolved upon stirring. The solution was refluxed for 15 minutes and a microcrystalline solid slowly precipitated out of solution. The solution was filtered hot and the yellow product was dried overnight to yield 1.09 g (86%) pure Nd(H3datren)(N03)3, mp > 230°C dec. The product lost its crystallinity upon removal from the mother liquor. This is believed to be due to evaporation of weakly bound acetonitrile molecules within the crystal lattice. 2.7. Synthesis of Fhtrac A solution of 8.43 g (0.058 mol) tris(2-aminoethyl)amine in 60 mL benzene was added to 17.31 g (0.17 mol) 2,4-pentanedione. The solution was refluxed for 90 min using a Dean-Stark trap and 3 mL H2O were collected. The benzene was removed under reduced pressure. The orange oil was rinsed 4 times with 20 mL hexanes in order to remove any 60 unreacted starting material. The oil was then dried in vacuo overnight. *NMR data (CDCI3) : 6 10.8 (3H, br, N-H); 4.93 (3H, s, CCHC) , 3.38 (6H, m, H N C H 2 C H 2 N ) , 2.78 (6H, t, J = 7 Hz, H N C H 2 C H 2 N ) , 2.00 (9H, s, C H 3 C ) , 1.96 (9H, s, C H 3 C ) . The oil slowly decomposes upon standing; this can be avoided by storing the product in the dark in a chloroform solution. The chloroform is removed under reduced pressure prior to use. The oil is insoluble in hexanes but soluble in most other organic solvents such as benzene, diethyl ether and methanol and is also soluble in water although product hydrolysis occurs. 2.8. Synthesis of La(trac) To an 120 mL ethanolic solution of 0.926 g (2.36 mmol) H3trac were added 0.802 g (2.16 mmol) LaCl3-7H20. The solution was stirred at room temperature for three hours and stored at - 20°C overnight. The white precipitate was filtered, rinsed with ethanol and set to dry in vacuo overnight, yielding 0.925 g (81%) of crude La(trac). The product was recrystalized from 95% ethanol and dried for 2 days in vacuo at 45°C. The product (0.725 g, 64 % yield) analyzed as La(trac), (mp = 98 - 105°C). The product is insoluble in most organic solvents such as benzene, chloroform and acetonitrile. It is sparingly soluble in ethanol at room temperature. The product is very soluble in water, DMSO, pyridine, methanol, and hot ethanol. Crystals of the product can be grown by slow cooling of a saturated ethanolic solution of the product in the presence of excess ligand. The crystals could not be isolated intact because of loss of crystallinity upon removal from the mother liquor. 61 2.9. Synthesis of Ln(H?trac)(NO^ (Ln = Pr. Nd. Gd. Dv. Yb) Analogous procedures to the one outlined below for the synthesis of Gd(H3trac)(NC»3)3 were used to isolate the Ln(H3trac)(NC»3)3 adducts. The lighter lanthanides (Pr, Nd) tend to form slowly and yield glassy type products. These are isolated from the mother liquor by decanting the supernatant C H 3 C N solution and rinsing the product out with diethyl ether. A l l products (except Gd(H3trac)(NC»3)3) were formed in low yields (44-71%). The complexes decomposed at temperatures greater than 200°C and were soluble in water, DMSO, and pyridine, but insoluble in all other common organic solvents. To a solution of 0.807 g (2.05 mmol) H3trac in 100 mL C H 3 C N were added 0.916 g ( 2.03 mmol) Gd(N03)3-6H20. The solution was stirred for 20 minutes at room temperature. A white crystalline precipitate formed slowly. The solution was stored at -20°C overnight. The product was removed by suction filtration, rinsed with C H 3 C N , and dried overnight in vacuo to yield 1.25 g (84%) pure Gd(H3trac)(N03)3, mp = 210°C dec. Crystals for X-ray analysis were obtained by slow cooling of the mother liquor. 62 Chapter in AluminumffTO and GaHiumfHI") Complexes of  Substituted 3-Hvdroxv-4H-pvran-4-ones A. Introduction The coordination chemistry of aluminum(III) and gallium(III) has been poorly developed because of the hydrolytic behaviour of these metal ions in aqueous solution. In acidic solution (pH < 3), aluminum(III) will exist in the form of the octahedral hexahydrate, [A1(H20)6]3+. As the pH of the solution increases, deprotonation occurs to produce species such as [Al(H20)s(OH)]2+ and [Al(H20)4(OH)2]+ (equations 3.1 and 3.2)97 [Al(H20)6p+ = [Al(H20)5(OH)]2+ + H + (3.1) [Al(H20)5(OH)]2+ = [Al(H20)4(OH)2]++ H+ (3.2) The relative concentration of all species in solution is dependent not only on the pH of the solution but also on the total concentration of aluminum(III) ions. For example, the Al(H20)5(OH)+2 species has been detected in dilute solution but rapidly dimerizes in more concentrated solution (equation 3.3).97 At physiological pH, the concentration of free H 2 [Al(H20)5(OH)]2+ = [(H 20) 4AlN o^>l(H20)4] 4 + (3.3) H 6 3 alurninum(TII) will be limited by the formation and precipitation of aluminum hydroxide, Al(OH)3. The two main species in dilute solution at physiological pH, in the absence of other hard donors, will be the tetrahedral [Al(OH)4J- anion and insoluble Al(OH)3. 2 0 The aqueous coordination chemistry of gallium(III) is also pH and concentration dependent. The gallate ion, [Ga(OH)4]-, is the main species in dilute solution at physiological p H . 9 8 Formation of polymeric species, [Ga4o ( O H ) i o o ] 2 0 + and [Ga26(OH)65] 1 3 + occurs at high concentration.98 Aluminum(III) and gallium(III) hydroxides are amphoteric, that is, they will act as both acid and base (equations 3.4 and 3.5). 9 7 M(OH)3(s) = MO2- + H+ + H 2 0 (3.4) M(OH)3(s) = M 3+ + 3 OH- (3.5) Our research group has been interested in the aqueous coordination chemistry of aluminum(III) and galUum(III)27>lu2>103. The ct-hydroxyketo group of the 3-hydroxy-4H-pyran-4-ones 2 7' 9 9 and 3-hydroxy-4(lH)-pyridin-4-ones100 will bind strongly to both trivalent aluminum(HI) and galUum(lTI) ions. The tris chelates of maltol and kojic acid (see Figure 1.1), two naturally occuring 3-hydroxy-4H-pyran-4-ones, were isolated from a slightly basic aqueous solution. 2 7' 9 9 The monobasic ligands yield neutral, water soluble complexes. These underwent further studies in order to determine their neurotoxicity.28 We were interested in the effect of ring-substituents on the stability and the lipophilicity of the aluminum(III) and gallium(III) complexes.2 7 The syntheses of chlorokojic acid (Hck) and kojic acid (Hkm) have been published. 1 0 1 - 1 0 3 Reaction of kojic acid with thionyl chloride yields chlorokojic acid. 1 0 1 Further treatment of chlorokojic acid with sodium azide in D M F yields azidokojic ac id 1 0 2 which is subsequently treated with HBr in a mixture of acetic acid and phenol to yield the dibromide salt of kojic amine.1 0 3 64 physiological pH, kojic amine is neutral and has been shown to cross the B B B . 1 0 3 It exhibits skeletal muscle relaxant and anticonvulsant activity in mice 1 0 3 and causes dose dependent hypotension and bradycardia in rats. 1 0 5 65 B. Results and Discussion 1. Isolation of the Complexes The synthetic procedure employed to isolate the aluminum(III) and gallium(III) complexes of chlorokojic acid (Hck) was analogous to the procedure employed to prepare the tris(kojato)aluminum(III) complex. 1 0 6 The pH of a solution containing the metal ion and a three-fold excess of chlorokojic acid was raised slowly by dropwise addition of a solution of sodium hydroxide. The hydroxy group on the 4H-pyran ring has phenolic character and Hck is a weak monoprotic ac id . 1 0 7 Deprotonation of the hydroxy group occurs upon raising the pH of the solution, leading to the formation of a hard base. Aluminum(III) and gallium(III) ions are hard acids 9 7 and will bind readily to the chlorokojato anion. At pH = 8.7, a white solid precipitates out of solution: Hck M(ck) 3 (M = Al , Ga) Tris(chlorokojato)aluminum(III) is soluble in chlorinated solvents such as CHCI3 and C H 2 C I 2 , but insoluble in polar protic solvents. Al(ck)3 was recrystallized from a chloroform/petroleum ether solution. Tris(chlorokojato)galliurn(TII) was only sparingly soluble in chloroform and was purified by continuous extraction with C H C 1 3 using a Soxhlet apparatus. Both products were characterised by infrared and mass spectroscopy. Elemental analysis data was consistent with the M(ck)3 (M = A l , Ga) formulation for the two products (see table 3.1). The 1 H - or 2 7 A 1 - N M R spectra were recorded in chloroform. 66 Table 3.1: Elemental Analysis Data for Hck, Al(ck)3, and Ga(ck)3. Compound calculated found C H a C H a Hck 44.88 3.14 22.08 44.71 3.10 21.95 Al(ck) 3 42.76 2.39 21.03 43.00 2.28 20.78 Ga(ck) 3 39.42 2.21 19.39 39.45 2.20 18.79 Dark brown insoluble precipitates were formed when analogous procedures were used in attempts to isolate the aluminum(III) and gallium(III) complexes of kojic amine (Hkm). Even in the absence of metal ion, precipitation of dark brown solids from an aqueous solution of kojic amine occurs upon standing. In the presence of the trivalent metal ions, precipitation of these insoluble brown solids occurs more readily. The presence of the metal ion in solution appears to catalyse the polymerization of Hkm or other side reactions. The nature of the precipitate has not been determined. The synthesis of Al(km)3 was attempted in ethanol with similar results. No further attempts were made at the synthesis of either Al(km)3 or Ga(km)3 because of previous experience in this laboratory with respect to the synthesis and isolation of aluminum(III) complexes of the catecholamines.1 0 8 The catecholamines also possess an amine functionality analogous to kojic amine. Attempts at isolating aluminum(lTI) and gallium(III) complexes of the catecholamines also resulted in the precipitation of unidentifiable brown precipitates.108 3. Infrared spectra of A K c k h and Ga(ckh Table 3.2 lists the main bands in the infrared spectra of Hck, Al(ck)3 and Ga(ck)3. The infrared spectrum of Hck exhibits a broad band at 3240 c m - 1 which is assigned to the 67 hydrogen bonded ' U O H of the cc-hydroxyketo moiety. The broad band at 3450 cm - 1 in the spectra of Al(ck)3 and Ga(ck)3 results from the presence of water in the KBr used to prepare the sample. Table 3.2: Main Infrared Data on Hck, Al(ck)3, and Ga(ck)3. assignment3 Hckb Al(ck)3b Ga(ck) 3 b (cm-1) (cm-1) (cm-1) •00-H(ring) 3240m, br _ _ uc=o 1655s 1575s 1570s uc=c 1625s 1601m 1615s 1585m 1525m 1515s 1455m 1470m 1470s 0"OH 1370s - -UC-OCring) 1287m 1305m 1310s 1230s 1275w 1270w 1210s 1240w 1250s 0"C-H(out-of-plane) 955s 955m 960m 885s 890w 890w "0C-C1 745m 745m 745m -uM-0 455m 305m 425m 290m a) D = stretching, a = bending deformation modes; b) s = strong, m = medium, w = weak intensity The double bond character of the C=0 and C=C bonds is reduced by intramolecular hydrogen bonding and resonance between the following forms: 1 0 9 68 Four bands characteristic of 3-hydroxy-4H-pyran-4-ones are observed in the 1660 to 1450 cm' 1 region of the ligand spectrum.1 1 0 The band at 1655 cnr 1 is usually attributed to t)c=o whereas those observed at 1625, 1585 and 1455 c m - 1 are assigned to VQ=C- A l l four bands shift and the energy ordering of the uc=c and uc=o changes upon complexation. Binding of the ligand to the trivalent metal ion weakens the C=0 bond. The Dc=0 undergoes the largest bathochromic shift (At) = 75 cm"1, Al(ck)3; At) = 80 cm' 1 , Ga(ck)3). Similar shifts were observed for the lanthanide(III) complexes of H c k . 1 1 1 The band at 1370 c m - 1 in the ligand spectrum is not present in the spectra of the M(ck)3 ( M = A l , Ga) complexes. This band is assigned to the O-H deformation mode. 1 1 2 The absence of this band confirms that binding occurs through the oxygen of the phenolic hydroxy group. Even though ligand bands occur in the lower frequency region of the spectrum, comparison between the spectra of Hck, Al(ck)3 and Ga(ck)3 allows one to assign the bands at 455 and 425 cm' 1 (Al(ck)3) and 305 and 290 cnr 1 (Ga(ck)3) to V M - O -These assignments are tentative; O-M-0 chelate ring motions and ring deformation modes also occur in this region. 2. Mass Spectra of A K c k h and Ga(ckh The main fragments observed in the E.I. mass spectra of chlorokojic acid (Hck), Al(ck)3 and Ga(ck)3 are listed in table 3.3. The main fragments in the F .A.B. mass spectra of the Al(ck)3 and Ga(ck)3 are listed in table 3.4. The E.I. mass spectrum of the ligand exhibits an intense molecular ion peak at mle = 160/162. Loss of the chlorine atom occurs readily and results in the observation of a peak at mle = 125. The E.I. mass spectrum of Al(ck)3 exhibits a weak molecular ion peak at mle = 504/506/508 (the fourth peak at mle = 510 is also present but at very low intensity). Loss of a chlorine atom results in the observed fragment at m/e = 469/471/473. The most 69 intense peak in the spectrum of Al(ck)3 occurs at m/e = 345/347/349 and corresponds to the loss of one ligand unit to yield [Al(ck)2]+. This characteristic peak has been observed Table 3.3. EI - Mass Spectral Data on Hck, Al(ck)3,and Ga(ck)3 compound m/e relative intensity assignment Hck 162 30.51 Hck + 160 93.98 125 100.0 Hck + - Cl-Al(ck)3 510 0.16 Al(ck)3-+ 508 0.88 506 2.98 504 3.09 349 11.60 Al(ck)2+ 347 65.11 345 100.0 Ga(ck)3 550 0.34 Ga(ck)3-+ 548 0.72 546 0.32 391 32.9 Ga(ck)2+ 389 85.2 387 63.7 125 100.0 ligand peak for the tris(maltolato)aluminum(III) and tris(kojato)aluminum(III) species isolated previously.106 The F.A.B. mass spectrum of Al(ck)3 exhibited a characteristic peak at m/e = 856 corresponding to the [Al2(ck)s]+ species.27 This peak is present at weak intensity and the isotope pattern for the five chlorine atoms present cannot be distinguished from background 70 noise. The fragment results from the cationization of Al(ck)3 by attachment of the Al(ck)2+ fragment (equation 3.6). Al(ck) 3 + [Al(ck)2]+ = [Al2(ck)5]+ (3.6) T a b l e 3.4. F .A.B - Mass Spectral Data on Hck, Al(ck)3, and Ga(ck)3 compound m/e relative intensity assignment Al(ck) 3 856 12.32 Al 2(ck) 5+ 511 0.88 HAl (ck ) 3 + 507 6.36 505 3.53 349 14.50 Al (ck) 2 + 347 57.54 345 100.0 Ga(ck) 3 937 12.22 Ga2(ck)5+ 902 4.06 552 3.77 HGa(ck)3+ 549 4.12 547 2.01 391 20.74 Ga(ck) 2 + 389 100.0 387 85.72 The E . I . mass spectrum of Ga(ck)3 is analogous to that of Al(ck)3. The isotope pattern of the fragments containing gallium and chlorine yield interesting isotope patterns and the assignments of the [Ga(ck)2]+ and [Ga(ck)3]+ fragments were verified by comparison with computed peak intensity simulation. A single peak due to the characteristic [Ga2(ck)s]+ fragment in the F .A.B. mass spectrum was present at mle = 959. 2 7 71 The E.I. mass spectrum of kojic amine exhibits a molecular ion peak at mle =141. Peaks at higher mle values can also be detected at low intensity indicating that oligomerization of the ligand may be the source of the problem encountered in the attempts at isolating M(km)3 ( M = A l , Ga). The most intense peak in the spectrum of H k m occurs at mle =112 and corresponds to the loss of the methylamine side-arm. 4. Nuclear Magnetic Resonance Data Table 3.5 describes the J H - N M R of chlorokojic, Al(ck)3, and Ga(ck)3, and the 2 7 A 1 - N M R data for Al(ck)3. The assignments were made according to previous ! H - N M R s tud ies . 1 1 3 The aromatic character of the 3-hydroxy-4-pyrones is indicated by the downfield shift observed for the ring protons. The chemical shift data gives little information as to the mode of binding of the three unsymmetric bidentate ligands. A single set of resonances is observed in the ^ - N M R of the complexes, indicating that the chlorokojate ligands are in equivalent environments. A n M(A-B)3 (where A - B is an asymmetric bidentate ligand) system can occur as two distinct optimal isomers (A and A ) , 1 1 4 and two geometric isomers (fac and mer in Figure 3 . 1 ) . 1 1 5 The optical isomers cannot be distinguished in a standard N M R experiment but the geometrical isomers can sometimes be resolved. fac mer Figure 3.1. Geometric isomers of an M(A-B) system 72 In the facial arrangement, all protons have the same chemical environment and one would expect a single set of proton resonances for the three chlorokojato ligands. If the meridional isomer is present in solution, the three ligands would experience a slightly different environment from one another and three sets of signals would be expected. Whether one set of signals is observed in the NMR spectra of both Al(ck)3 and Ga(ck)3 is a result of rapid interligand exchange, or of the fact that the complex is present as the facial isomer in solution, cannot be determined from this data. Table 3.5. NMR Data on Hck, Al(ck) 3 and Ga(ck)3. assignt3 Hck Al(ck)3 Ga(ck)3 !H-NMR b Ha 4.37 4.43 4.41 Hb 6.58 6.87 6.84 He 8.09 8.26 7.90 27A1-NMRC Al 41 (W1/2=650MHz) a) all spectra were recorded in CDC1 3 b) *H chemical shifts in ppm downfield from TMS c ) 2 7 A l chemical shift in ppm donwfield from Al(C10 4)3inD20. 73 The 2 7A1-NMR spectrum of Al(ck)3 in CHCI3 exhibits a single resonance at 41 ppm indicating the presence of a single species in solution. Resonances of the 2 7 A l nucleus (I = 5/2) tend to be broad because of its quadrupole moment (Q = 0.149 x IO - 2 8 m2). 2 7A1-NMR can be a useful probe because of the high natural abundance (100%) and sensitivity (0.206 relative to !H) of the 2 7 A1 nucleus.116 2 7A1-NMR has been used to study the solution chemistry of aluminum(III) at different pH. 2 7 > 1 0 0 ' 1 1 7 Its usefulness is hampered in the case of Al(ck)3 by the insolubility of the product in non-chlorinated solvents. C. Experimental 1. General Techniques A l l chemicals were reagent grade and were used as received. A1C13-6H20 was obtained from B D H ; Ga ingots from Alfa; kojic acid from Sigma and chlorokojic acid was prepared as described by Yabuta. 1 0 1 Water was deionized (Barnstead D8902 and D8904 cartridges) and distilled (Corning MP-1 Megapure still). A 1.37 M solution of GaCl3 in HC1 was prepared by dissolving Ga ingots (9.561 g) in 70 mL of HC1 with heating over 4 days and with periodic additions of HC1. This solution was cooled, diluted to 100 mL, and standardized by EDTA titration. The analyses for C, H and N were performed by Mr. Peter Borda of this department. The ! H - N M R spectra (80MHz) of the products were recorded by the U.B.C. N M R service on a Bruker WP-80 and the chemical shifts were measured relative to TMS. The 2 7 A 1 - N M R spectrum (78.16 MHz) of Al(ck)3 was recorded at 25°C on a Varian XL-300 by W. O. Nelson of this laboratory. The spectrum was referenced to 0.20 M A1(C104)3 in 0.10 M HCIO4 with D2O added as a lock signal. The downfield chemical shifts were taken to be positive. The infrared spectra were recorded on a Perlrin-Elmer PE783 spectrophotometer using the 1601 c m - 1 band in the spectrum of polystyrene as the reference. The K B r was stored at 90 °C prior to use. The mass spectra were recorded by the U.B.C. mass spectrometry service using a Kratos MS50 (electron impact ionization, EI) or an A E I MS 9 (fast atom bombardment ionization, FAB) instrument. The intensity of a given peak is stated relative to the most intense peak in the spectrum. 2. Synthetic Procedure 2.1. Synthesis of tris(chlorokojato)aluminum(TII) Chlorokojic acid (2.564 g, 16.0 mmol) and AICI3.6H2O (0.966 g, 4.0 mmol) were dissolved in 50 mL of water The pH was adjusted to 8.8 by dropwise addition of 2N NaOH and an off-white solid precipitated. The precipitate was removed by suction filtration, washed with acetone, and recrystallized from cWoroform/petroleum ether to yield 1.564 g (78%) of a white microcrystalline solid, mp 310 °C dec. Al(ck)3 was soluble in C H 2 C 1 2 , CHCI3 . 2.2. Synthesis of tris(chlorokojato)gallium(in) Chlorokojic acid (1.528 g, 9.52 mmol) was dissolved in 40 mL of 1:1 water/ethanol, and 1.37 M GaCl3 (1.67 mL, 2.25 mmol) was added. The pH was adjusted to 8.7 by dropwise addition of 2N NaOH, and an off-white solid precipitated and was removed by filtration. The product was extracted in a Soxhlet apparatus with 300 mL of C H C I 3 overnight. The CHCI3 solution was reduced in volume to 50 ml, and when petroleum ether was added and the mixture cooled (-20°C), a white solid appeared. This was removed by filtration and washed with ethanol to yield 1.178 g (95%) of product, mp 270°C dec. Ga(ck)3 was sluggishly soluble in CH3CI and C H 2 C L 2 . 7 6 Chapter IV Conclusions and Perspectives The lanthanide(III) complexes were characterized in the solid state by elemental analysis, infrared and mass spectroscopy. The formation of typel (Figure 2.11) complexes is restricted to the lightest and largest lanthanum(ffl) ion in the presence of poorly coordinating anions (eg. Cl"). Steric restrictions imposed by the ligands favour binding in a tridentate fashion as the ionic radii of the metal ions decreases resulting in mixed products in the presence of chloride ions. When nitrate ions are present, the potentially heptadentate ligands bind in a type2 (Figure 2.11) fashion. The strong Ln-NC»3 interaction limits binding of the lanthanide(III) ions to the ligand oxygen donor atoms. The lack of solubility of all complexes in common organic solvents restricted the study of their solution chemistry. The proton nuclear magnetic resonance ^H-NMR) spectra of the La(hatren), La(datren)(CH30H) and La(trac) complexes in DMSO-d6, pyridine-d5 and CD3OD were superimposable on the !H-NMR spectra of the ligands. Slight broadening of the resonances was observed in CD3OD. The iH-NMR spectra of the Ln(N03)3(H3L) (Ln = La, Pr, Nd, Yb; L = H3harren, H3datren, H3trac) in DMSO-d6 did not differ from the spectra of the ligands indicating that the complexes are labile in solution and dissociate to yield free ligand and solvated lanthanide(III) ions in solution. The isolation of the adducts was possible because of their low solubility in ethanol and acetonitrile once formed. The lability of these complexes precludes the possibility of their use as NMR contrast agents for in vivo studies. A next step in the isolation of inert complexes would be to encapsulate the metal ion completely by Schiff base condensation with a second tren moiety in a template reaction. Attempts at the total encapsulation of the metal ion were undertaken, but were unsuccessful. 7 7 In the case of the I-^ hatren type adducts, alkyl substitution on the phenyl ring of the 2'-hydroxyacetophenone moieties may improve the solubility properties of the resulting complexes in non-polar solvents, thus allowing an investigation of ligand exchange processes occuring in solution. The tris(chlorokojato)alurninum(ni) and tris(chlorokojato)gallium(III) complexes were characterized by elemental analysis, infrared and mass spectroscopy, and by NMR spectroscopy. Although the 3-hydroxy-4H-pyran-4-ones afford stable complexes with aluminum(IH) and gallium(III), subsequent work by other members of this research group has shown that N-substituted-3-hydroxy-4-pyridinones are better candidates for biomedical use. The latter ligands exhibit a greater degree of flexibility with respect to substitution and also yield stable complexes with aluminum(IU) and gallium(III). 78 References 1. 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Inorg. Chem. 1969, 8, 789. 85 116. Harris, R.B.; Mann, B.E.; Eds. "NMR and the Periodic Table"; Academic Press: London, 1978. pp.5-7 and 279-283. 117. Greenaway, F T . Inorg. Chim. Acta 1986,116, L21 86 APPENDIX Figure Al. Infrared spectrum (KBr pellet) of the 4000 to 200 cm"1 region of gharri Figure A 2 . Infrared spectrum (KBr pellet) of the 4000 to 200 cm"1 region of La(hatren) Figure A 3 . Infrared spectrum (KBr pellet) of the 200-4000 cm"1 region of La(H3hatren)(N03)3 Figure A5 . Infrared spectrum (KBr pellet) of the 4000 to 200 cnr 1 region of La(datren)(CH3OH) Figure A7. Infrared spectrum (neat oil) of the 4000 to 200 cnr 1 region of H 3 t r a c NOISSIMSNttU % Figure A 9 . Infrared spectrum (KBr pellet) of the 200-4000 cm"1 region of Gd(H3trac)(NC»3)3 ure A12. EI mass spectrum of H3hatren © x i i i r in <a - is I i r I B g> co vfi i/i ** m N « « a « • at 0 ) fft 0> yO Ui « B ) 0 ) m M — 98 Figure A13. EI mass spectrum of La(hatren) o CN X I T T I I I I 0 * Aitsuaiin dArjcpj 99 Figure A14. EI mass spectrum of Nd(H3hatren)(N03)3 © x S I I I I I I I I I I I r r I I I I I i i \e ^ CB 16 • » IM • * CM 100 101 relative intensity £(£ON)(u9-nBM£H)<LA. j o u m n M d s s s m n 13 * C J V 3Jn3ij ure A16. EI mass spectrum of H3datren 102 ure A17. EI mass spectrum of La(datren)(CH3OH) 0t CD U0 V rsi ^ (Dlfl « IM CD. OD \0 «r N EJ) CD O) * N 1 0 3 Figure A18. EI mass spectrum of Nd(H3datren)(NC»3)3 « o as I I II II I M I N I M I B) -ui N - BJ - a> BI I II II II I! as _ BI BI V 0 T T Bl SI BI » « « CO US w IM 5 * 104 Figure A19. EI mass spectrum of Yb(H3datren)(NG*3)3 « i i I i 1 i i i i I O S I I I I I II I I I 03 _ Bi 81 - N I r r T T «9 B) B) 09 at I II I I I I I I IB BI BI s * « « ts a t£ Xjisuajur S A p B j a i 105 u r e A20. EI mass spectrum of H3trac o « f- • i—i—r " i — i — i — i — i — i — r gg IS in •» rsj — • • o> as ao on cn n ^ ID ui «cn csj — 106 Figure A21. EI mass spectrum of La(trac) A J I S U 3 J U I SAp^ia i 107 Figure A22. EI mass spectrum of Gd(H3trac)(NC>3)3 108 

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