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Oxovanadium(IV) and (V) complexes with naturally-occurring molecules Zhou, Ying 1993

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OXOVANADIUM(IV) AND (V) COMPLEXES WITHNATURALLY-OCCURRING MOLECULESbyYING 7J-10UB.Sc. (Honours), Chengdu University of Science and Technology,Chengdu, Sichuan, People's Republic of China, 1990A THESIS SUBMIllED IN PARTIAL FULFILLMENT OFTHE REQUIREMENTS FOR THE DEGREE OFMASTER OF SCIENCEinTHE FACULTY OF GRADUATE STUDIES(Department of Chemistry)We accept this thesis as conformingto the required standardThe University of British ColumbiaApril 1993© Ying Zhou, 1993this thesis inUniversity offor referenceIn presentingdegree at thefreely availablepartial fulfilment of the requirements for an advancedBritish Columbia, I agree that the Library shall make itand study. I further agree that permission for extensivecopying of this thesis for scholarly purposes may be granted by the head of mydepartment or by his or her representatives. It is understood that copying orpublication of this thesis for financial gain shall not be allowed without my writtenpermission.Department of C4 e  The University of British ColumbiaVancouver, CanadaDate  4pi Q 26. I 773DE-6 (2/88)AbstractComplexes with naturally-occurring ligating moieties were prepared and studied aspart of an overall process to understand the coordination chemistry of vanadium.Bis(kojato)oxovanadium(IV), VO(ka)2, bis(3-oxy-1,2-dimethy1-4-pyridinonato)-oxovanadium(IV), VO(dpp)2, bis(2-hydroxymethy1-5-oxy-1-methy1-4-pyridinonato)-oxovanadium(IV), VO(hmp)2, bis[2-(2'-oxypheny1)-2-oxazolinato]oxovanadium(IV),VO(oz)2, bis[2-(2'-oxypheny1)-2-thiazolinato]oxovanadium(IV), VO(thz)2.0.5H20 andbis(benzohydroxamato) oxovanadium(IV), VO(bz)2 were prepared and characterized. Inaddition, two oxovanadium(V) complexes, bis(benzohydroxamato)methoxo-oxovanadium(V), V0(OCH3)(bz)2 and bis(benzohydroxamato)ethoxooxovanadium(V),VO(0C2H5)(bz)2 were also prepared from VO(bz)2. All eight complexes were preparedin one step processes, in particular V0(dpp)2 and V0(hmp)2 which were prepared directlyfrom maltol and kojic acid, respectively, using vanadyl and methylamine in a one-potsynthesis method.All oxovanadium complexes were characterized by infrared spectroscopy, massspectrometry, elemental analyses and room temperature magnetic susceptibilitymeasurements, and whenever possible, by UV-Visible spectrophotometry. 1H and 51VNMR were also used to characterize the two oxovanadium(V) complexes,VO(OCH3)(bz)2 and VO(0C2H5)(bz)2. Single crystal X-ray diffraction studies ofVO(oz)2 and V0(thz)2 were also performed by the departmental facility.Characterization of the oxovanadium(IV) complexes revealed them to be 5-coordinate square pyramidal bis(ligand)oxovanadium(IV) complexes with each ligandbinding in a bidentate fashion to the central vanadium atom. VO(OCH3)(bz)2 andV0(0C2H5)(bz)2 were found to be 6-coordinate bis(ligand)oxovanadium(V) complexes.Comparison of the infrared stretching frequencies of the vanadium-oxo bond revealed thatthe strength of the vanadium-oxo bond in the eight complexes was consistent with bondiiistrength observed in other oxovanadium complexes. Single crystal X-ray diffractionstudies of VO(0z)2 and VO(thz)2 showed them to be isostructural. The bidentate ligandsare bonded to the vanadium center through the phenolate oxygen and the oxazoline orthiazoline ring nitrogen. The two complexes are both regular square pyramids with thebidentate ligands coordinated in a trans fashion. The vanadium atoms in these complexesare elevated by approximately 0.6 A from the basal square planes defined by the fourligand 0 and N donors. The average V=0 bond length is 1.6 A.TABLE OF CONTENTSpageAbstractTable of Contents^  iv^List of Tables   vList of Figures ^  viList of Abbreviations  viiAcknowledgements^  xChapter 1.^General Introduction^  1Chapter 2.^Experimental Details  72.1. Synthesis Material and methods^  72.2. Characterization^  102.2.1 Infrared Spectroscopy ^  112.2.2. Elemental Analyses  122.2.3. 1H NMR Spectroscopy  132.2.4. Variable Temperature 1H NMR Spectroscopy ^ 152.2.5. 51V NMR Spectroscopy ^ 152.2.6. Mass Spectrosmetry  162.2.7. UV-Vis Spectrophotometry^ 172.2.8. X-ray Crystallographic Analysis  18Chapter 3.^Results and Discussion ^  19References   39Appendix A   42Appendix B   49ivLIST OF TABLESpageTable 2.2.1.^Characteristic infrared absorptions ^  11Table 2.2.2.^Results of elemental analyses of the vanadium complexes ^ 13Table 2.2.3.^1H NMR data for the VO(OR)(bz)2 complexes ^ 14Table 2.2.5.^51V NMR data for the VO(OR)(bz)2 complexes  15Table^FAB mass spectral data (m/z) of the vanadium complexes ^ 16Table^El mass spectral data (m/z) of the vanadium complexes ^ 16Table 2.2.7.^UV-Vis spectral data, X, nm (e, M-1cm-1) ^ 17Table 3.1.^Selected bond lengths for VO(oz)2 and VO(thz)2 ^ 30Table 3.2.^Selected bond angles for VO(oz)2 and VO(thz)2  31Table Al^Selected crystallographic data for VO(oz)2 and VO(thz)2 ^ 42Table A2^Final atomic coordinates (fractional) and Beg for VO(oz)2 ^ 43Table A3^Final atomic coordinates (fractional) and Beg for VO(thz)2 ^ 44Table A4^Bond lengths for VO(oz)2 and VO(thz)2 ^ 45Table A5^Bond angles for VO(oz)2 and VO(thz)2  46Table B1^Comparison of the plasma glucose levels between the acutetime course experiments for VO(ma)2 and VO(ka)2 ^ 51VLIST OF FIGURESpageFigure 1.1.^Ligand precursors chosen for thebis(ligand)oxovanadium(IV) complexes ^ 2Figure 1.2.^Structures of the siderophores mycobactin anddeferriferrioxamine B ^  4Figure 2.2.3.^VO(OR)(bz)2 complexes atom labelling used in NMR data ^ 14Figure 3.1.^Bis(ligand)oxovanadium(IV) complexes ^ 19Figure 3.2.^Scheme for the one-pot synthesis of bis(3-oxy-4-pyridinonato)-oxovanadium(IV) complexes ^  20Figure 3.3.^Six possible isomers for VO(OR)(bz)2 complexes ^ 25Figure 3.4.^Structure of bis(benzohydroxamato)chlorooxovanadium(V)complex ^  26Figure 3.5.^ORTEP view of the VO(oz)2 unit ^  28Figure 3.6.^ORTEP view of the VO(thz)2 unit  29Figure 3.7.^Molecular orbital scheme for [VO(H20)521 (C4, symmetry)according to Ballhausen and Gray ^  34Figure 3.8.^Potential "intensity stealing" effect in UV-Visspectrophotometric study of VO(oz)2 and VO(thz)2 ^ 36Figure 3.9.^Splitting of the vanadium d levels ^  37Figure Bl.^Daily average blood glucose levels for the ten STZ-diabeticrats following chronic administration of VO(ka)2 in thedrinking water. ^  52Scheme I   32viLIST OF ABBREVIATIONSAbbreviation^ Meaninga^length of the unit cell along the a axisA angstroma^interaxial angle between unit cell edges b and cb length of the unit cell along the b axis13^interaxial angle between unit cell edges a and cBM Bohr magnetonc^length of the unit cell along the c axis°C degrees Celsiuscm-i^wave number8 chemical shiftDcalc^calculated densitydeg degreese^molar extinction coefficientEl electron-impact ionizationEIMS^electron-impact ionization mass spectrometry+FAB positive ion fast atom bombardment+FABMS^positive ion fast atom bombardment mass spectrometryfw formula weightg^gramsY interaxial angle between unit cell edges a and b67Ga^gallium-67iH protonHbz^benzohydroxamic acidH3DFB deferriferrioxamine BviiviiiHdpp^3-hydroxy-1,2-dimethy1-4-pyridinoneHhmp 2-hydroxymethy1-5-hydroxy-1-methyl-4-pyridinoneHka^kojic acid, 2-hydroxymethy1-5-hydroxy-y-pyroneHoz 2-(2'-hydroxypheny1)-2-oxazolineHthz^2-(2'-hydroxypheny1)-2-thiazolineHz hertzI.P.^intraperitonealIR infraredJab^NMR coupling constant between hydrogens a and bK degrees Kelvinkg^kilogramsL literLL^bidentate ligandX, wavelength, nmmaltol^3-hydroxy-2-methyl-4-pyronemL millilitermmol^millimoleVx-y vibrational stretching modenm^nanometer, 10-9mNMR nuclear magnetic resonanceORTEP^Oak Ridge Thermal Ellipsoid PlotR agreement factorRw^weighted agreement factorSTZ streptozotocinT^temperatureUV-Vis^ultraviolet-visbleVO(bz)2 bis(benzohydroxamato)oxovanadium(IV)ixVO(bz)2C1^bis(benzohydroxamato)chlorooxovanadium(V)VO(dpp)2 bis(3-oxy-1,2-dimethy1-4-pyridinonato)oxovanadium(IV)VO(hmP)2^bis(2-hydroxymethy1-5-oxy-1-methyl-4-pyridinonato)oxovanadium(IV)VO(H20)(C204)2^aquobis(oxalato)oxovanadium(IV)VO(ka)2^bis(kojato)oxovanadium(IV)VO(ma)2 bis(maltolato)oxovanadium(IV)VO(OCH3)(bz)2^bis(benzohydroxamato)methoxooxovanadium(V)VO(0C2H5)(bz)2^bis(benzohydroxamato)ethoxooxovanadium(V)VO(OiPr)(ox)2^isopropoxobis(8-hydroxyquinolinato)oxovanadium(V)VO(OR)(bz)2^bis(benzohydroxamato)alkoxooxovanadium(V)VO(oz)2 bis[2-(2'-oxypheny1)-2-oxazolinato]oxovanadium(IV)VO(thz)2^bisf2-(2'-oxypheny1)-2-thiazolinato]oxovanadium(IV)weighting factorWia^peak width at half peak heightnumber of molecules in the unit cell (excluding solventmolecules of crystallization)ACKNOWLEDGEMENTSI would like to thank Dr. Chris Orvig for his guidance and encouragementthroughout this work.Thanks also to the Orvig team members, past and present, from whom I learned alot. I would like to give my special thanks to Dr. Lucio Gelmini and Ernest Wong for theirhelp on my computer techniques and their patience in reading through this thesis and theirvaluable suggestions.I would also like to thank Mr. P. Borda for the elemental analysis of the productsand his patience in their determination; Dr. S. Rettig for his prompt determination of thecrystal structures; the technical staff of the NMR and mass spectroscopy facility and theUBC Chemistry support staff for their expertise.I would like to extend my thanks to Dr. J. McNeill and his group at UBCPharmaceutical Sciences Department for supplying the data of VO(ka)2 in animal studies.Financial support in the form of a Teaching Assistantship is gratefullyacknowledged.To my parents and my sisters who always support me with their love.xi1Chapter 1. General IntroductionVanadium is a widely distributed first row transition metal and is the nineteenthmost abundant element in the earth's crust. Research into the chemistry and biologicalimportance of vanadium has been in progress since its discovery by N. G. Sefstrom in1831,1 however, interest in vanadium intensified after the discovery of the inhibitoryactions of orthovanadate ion (VO43-) in sodium-potassium pump in 19772 and thediscovery of the insulin mimicking properties of vanadate in 1980.3,4 Much progressconcerning the chemistry and biological relevance of vanadium has been made during thepast decade. It is known that the biological role of vanadium encompasses stimulatory,regulatory and inhibitory functions.1 Vanadium has also been recognized as anendogenous component present in trace quantities in tissues of higher animals and issuspected to be essential for growth and development in many organisms. Whethervanadium is essential for humans remains unclear, although mounting evidenceincreasingly suggests that vanadium is most likely an essential trace element.5,6,7Research into this suggestion has led to numerous studies which have examined thebehaviour of vanadium within the human body. For example, the binding of V(IV) andV(V) to human serum transferrin has been well documented.8 In addition, the discoveryof vanadate as a possible insulin mimicking agent has also stimulated research into thesynthesis of new vanadium compounds and the study of their properties in vivo.Vanadium is of course found in numerous other biological systems besides humans.Recently, vanadium has been recognized as a part of the catalytically active center in thenitrogenase system of a special strain of Azotobacter chroococcum9 and in thevanadate(V)-dependent haloperoxidases of several marine algae.10 However, much workis still required before the precise functions of vanadium in these and other biologicalsystems can be fully understood.Although much effort has been expended studying the behaviour and function of2vanadium in naturally-occurring systems, there is also much interest in studying theproperties of synthetic vanadium compounds and their possible applications. For example,the discovery of the insulin mimicking properties of vanadate has accelerated the searchfor vanadium compounds which could replace insulin in the treatment of diabetes.3ADiabetes is a condition in which the level of glucose in the blood plasma of mammals isabnormally high.11 Present diabetic treatment often involves twice daily injections ofinsulin, a hormone which regulates the utilization and storage of basic human nutrients.Since insulin is not orally active, there is tremendous interest in developing an orallyactive vanadium compound as a replacement for insulin.HO00/OHX=0 HozX=S HthzHIcaNHO 'HR2=CH3, R6=H^Hdpp^ HbzR2=H, R6=CH2OH HhmpFigure 1.1. Ligand precursors chosen for the bis(ligand)oxovanadium(IV) complexes.3In order to better understand the biological role of vanadium, the relevantcoordination chemistry of vanadium needs to be thoroughly investigated. Vanadium existsin a number of oxidation states, but only oxidation states +3, +4 and +5 are important inbiological systems.12 Compounds of oxovanadium(IV) are of particular interest to usbecause oxovanadium(IV) compounds are less toxic in the rabbit, rat, mouse, and guineapig than vanadate(V) compounds, and, furthermore, several studies have indicated that theinsulin-like actions of vanadate are also found with the vanadyl form and that theformation of vanadyl from vanadate in vitro coincided with the appearance of effects thatare similar to those observed with insulin.13The V02+ moiety is known to bond effectively to electronegative donor atomssuch as fluorine, chlorine, oxygen and nitrogen. Complexes with fluorine and oxygendonor atoms are known to be especially stable.14 Examples of the V02+ moiety bondingto sulfur and phosphorus atoms are also known.14 In this study of the coordinationchemistry of vanadium, potential bidentate ligands with oxygen-oxygen or oxygen-nitrogen donor atoms were chosen to coordinate to the V02+ moiety. It was our desire toutilize naturally-occurring compounds or ligating moieties as a basis for choosing potentialligands of interest. The ligands in this study of the coordination behaviour ofoxovanadium(IV) are illustrated in Figure 1.1.The coordination of oxovanadium(IV) with benzohydroxamic acid (Hbz), 2-(2'-hydroxypheny1)-2-oxazoline (Hoz) and 2-(T-hydroxypheny1)-2-thiazoline (Hthz) werestudied because the ligating moieties of these ligands can be found in certain classes ofmicrobial iron chelators (i.e. the siderophores). For example, the binding groups in thesiderophore mycobactin consists of two hydroxamic acid residues and a 2-(2'-hydroxypheny1)-2-oxazoline residue. Two examples of siderophores (mycobactins anddeferriferrioxamine B) containing the 2-(2'-hydroxypheny1)-2-oxazoline residue and thehydroxamic acid residues are shown in Figure 1.2.15,16,17 It is of interest to determinehow the ligating moieties in these ligands would bind to oxovanadium(IV).4Mvcobactin R4^4^ Rl, R4 = Me, Et, or long chain0 R1^R2, R3, R5 =H or Me1N .,.,,,"...,,...„. N^0OHHON11\2^CONH^CONH/^'''), /^".>(CH2)5^(CH2)2 kCH2)5^(CH2)2 (CH2)5^CH3\ /^\ /^\ /N—C N—C N—CI^II^I^II I^IIOHO OHO^OHODeferriferrioxamine B (H3DFB)Figure 1.2. Structure of the siderophores mycobactin and deferriferrioxamine B (H3DFB)Over the past several years, the coordination of the a-hydroxyketone moiety withvarious metal centers has been investigated in this lab. Initial investigation focused onligands containing the a-hydroxyketone moiety derived from 3-hydroxy-4-pyrones and 1-alky1-3-hydroxy-4-pyridinones. Aluminium, gallium, indium, rhenium, and technetiumcomplexes with these pyrone and pyridinone ligands have been prepared and studied.17,18Coordination of these ligands to Al, Ga, and In resulted in 6-coordinate tris(ligand) metalcomplexes. For Tc and Re, 6-coordinate bis(ligand) complexes containing a metal oxobond were formed. As a continuation of this work, the coordination of the a-hydroxyketone moiety to oxovanadium(IV) was studied. Kojic acid (Hka), a naturally-occurring compound which contains the a-hydroxyketone moiety was chosen as one of thepotential ligands for this study. In addition, 3-hydroxy-1,2-dimethy1-4-pyridinone (Hdpp)5and 2-hydroxymethy1-5-hydroxy-1-methyl-4-pyridinone (Hhmp), which also contain thea-hydroxyketone unit, also were chosen as potential ligands for coordination withoxovanadium(IV).A unique combination of biologically relevant properties (water solubility,hydrolytic stability and lipophilicity) has made pyrone and pyridinone complexesparticularly interesting with respect to their possible medical application. For example,the tris(maltolato)aluminium complex has been used widely in the study of Alneurotoxicity.19 Another example is the 67Ga complex tris(1-p-methoxypheny1-2-methyl-3-oxy-4-pyridinonato)gallium(III), which is a potential heart imaging agent.20 Thesepyrone and pyridinone ligands are non-toxic, naturally-occurring or easily synthesized andthe properties of their complexes can be altered by changing the substituents on theligands. With such favorable ligand properties, oxovanadium(IV) complexes of theseligands may prove to have interesting potential medical applications considering theinsulin mimicking properties of some vanadium compounds.Coordination of six different bidentate ligands to oxovanadium(IV) were studied.For each ligand, 5-coordinate bis(ligand) complexes with a V02+ core were synthesizedand characterized. The characterization of these complexes involved the use of infraredspectroscopy, mass spectrometry, elemental analyses, magnetic susceptibilitymeasurements and ultraviolet-visible spectrophotometry when possible. X-raycrystallographic analyses of bis[2-(2'-oxypheny1)-2-oxazolinato]oxovanadium(IV),VO(oz)2, and bis[2-(2'-oxypheny1)-2-thiazolinatoloxovanadium(IV), VO(thz)2, were alsoobtained. Besides the oxovanadium(IV) complexes, two V(V) derivatives of VO(bz)2,VO(OCH3)(bz)2 and VO(0C2H5)(bz)2 which are 6-coordinate oxovanadium(V)complexes were also synthesized. In addition to the techniques used to characterized thesix oxovanadium(IV) complexes, 1H and 51V NMR were also used to studyVO(OCH3)(bz)2 and VO(0C2H5)(bz)2. The preparation and characterization of the eightvanadium complexes are summarized in Chapter 2. It is the belief that by studying the6coordination of vanadium with ligating moieties of biological or medical significance, abetter understanding of the general roles or behaviour of vanadium in nature can beachieved. As a secondary objective, some of these oxovanadium complexes could also beevaluated as potential replacement for insulin in the treatment of diabetes (see AppendixB).7Chapter 2. Experimental Details2.1 synthesis Material and MethodsAll chemicals were reagent grade and were used as received without furtherpurification: kojic acid (2-hydroxymethy1-5-hydroxy-y—pyrone), maltol (3-hydroxy-2-methy1-4-pyrone) and benzohydroxamic acid (Hbz, Sigma), VOSO4-5H20 andVOSO4•3H20 (Aldrich), Na0Ac-3H20 (Fisher). 2-(2'-Hydroxypheny1)-2-oxazoline(Hoz)21, and 2-(2'-hydroxypheny1)-2-thiazoline (Hthz)22 were prepared according to theliterature and were used without further purification. Water was deionized (BarnsteadD8902 and D8904 cartridges) and distilled (Corning MP-1 Megapure still). The yields arefor analytically pure compounds and they are calculated based on vanadium. The meltingpoints were measured with a Mel-Temp aparatus; however, all the vanadium complexeswere non-volatile, charring and decomposing above 120°C. Room temperature (293.5 K)magnetic susceptibilities were measured on a Johnson Matthey magnetic susceptibilitybalance, using Hg[Co(NCS)41 as the susceptibility standard. Diamagnetic correctionswere estimated by using Pascal's constants23.8Bis(kojato)oxovanadium(IV), VO(ka)z. VOSO4.5H20 (2.50 g, 9.88 mmol) was dissolvedin 10 mL hot water and the solution was degassed with As for 10 minutes. The solutionwas then added to 10 mL of a degassed aqueous solution of kojic acid (2.88 g, 20.3 mmol)and Na0Ac.3H20 (2.97 g, 21.8 mmol). After refluxing under Ar overnight, a blue solidwas collected by vacuum filtration using a Schlenk filtering funnel and dried overnight invacuo. The yield was 2.69 g (78%). The solid state magnetic moment was 1.76 BM.Bis(3-oxy-1.2-dimethy1-4-pyridinonato)oxovanadium(IV). VOldpgq To a solution ofmaltol (2.10 g, 16.7 mmol) and V0SO4-5H20 (2.01 g, 8.0 mmol) in 20 mL hot water wasadded 20 mL 40% methylamine in water (26 mmol) and the pH of the solution wasdecreased from 11.7 to 9.9 by addition of 2 N H2SO4. The solution was refluxed for 8hours. A gray blue solid was collected by filtration and washed several times with hotwater. The yield was 2.56 g (94%). The solid state magnetic moment was 1.77 BM.Bis(2-hydroxymethy1-5-oxy- 1 -methyl-4-pyridinonato)oxovanadium(IV). VO(hmpla. Toa solution of kojic acid (2.80 g, 19.7 mmol) in 40 mL hot water was added 20 mL 40%methylamine in water (26 mmol) and V0SO4-5H20 (2..47 g, 9.8 mmol) in 20 mL hotwater. The pH of the solution was decreased from 12.8 to 11.0 by addition of 2 N H2SO4.The solution was refluxed under Ar for 8 hours. A blue solid was collected by filtrationand washed several times with hot water. The yield was 2.45 g (67%). The solid statemagnetic moment was 1.74 BM.Bis12-(2'-oxypheny1)-2-oxazolinatoloxovanadium(IV), VO(oz)z. To a solution of Hoz(0.31 g, 1.90 mmol) and Na0Ac.3H20 (0.27 g, 1.95 mmol) in CH3OH (10 mL) was addedV0SO4.3H20 (0.20 g, 0.92 mmol) in 11 mL of CH3OH:H20 (10:1) solution. A gray-bluesolid immediately precipitated and was collected by filtration. Recrystallization of the9solid from CH2C12 yielded large blue crystals. The yield was 0.27 g (75%). The solidstate magnetic moment was 1.84 BM.B is12-(2'-oxypheny1)-2- thiazolin atol oxovanadium(IV), VO(thz)224L5..tiz11. Thepreparation was as for VO(oz)2. V0SO4.3H20 (0.20 g, 0.92 mmol), Hthz (0.34 g, 1.90mmol) and Na0Ac-3H20 (0.27 g, 1.95 mmol) were employed. Recrystallization fromCH2C12 yielded large yellow-green crystals. The yield was 0.32 g (82%). The solid statemagnetic moment was 1.80 BM.Bis(benzohydroxamato)oxovanadium(IV). VO(bz). VOSO4.3H20 (0.20 g, 0.92 mmol)in 10 mL water was added dropwise to a solution of benzohydroxamic acid (0.26 g, 1.90mmol) in 20 mL hot water. A purple solid precipitated. The pH of the suspension wasraised from 1.7 to 7.4 by the slow addition of 0.5 N NaOH. The suspension was thenstirred for 1.5 hours. The purple solid was collected by filtration yielding 0.22 g (71%) ofthe product. The solid state magnetic moment was 1.72 BM.Bis(benzohydroxamato)methoxooxovanadium(V). VO(OCH2)(bz)z. VO(bz)2 (0.11 g,0.32 mmol) was dissolved in 10 mL -35°C methanol and then stirred for 2 hours. Abrick-red microcrystalline solid precipitated after the addition of 10 mL water. Theproduct was collected by filtration and washed several times with water. The yield was0.065 g (54%).Bis(benzohydroxamato)ethoxooxovanadium(V). V0(0C21_1.5.1.(1L)z. VO(bz)2 (0.10 g,0.30 mmol) was dissolved in 10 mL hot ethanol and stirred for 2 hours. A golden-redsolid precipitated upon slow evaporation of solvent. The product was collected byfiltration and washed several times with water. The yield was 0.058 g (52%).102.2. CharacterizationThe bis(ligand)oxovanadium(IV) complexes were characterized by infrared (IR)spectroscopy, positive ion fast atom bombardment mass spectrometry (+FABMS) orelectron-impact ionization mass spectrometry (EIMS), UV-visible spectrophotometry(UV-Vis), elemental analyses, and in some cases, X-ray crystallograghy. In addition to theabove methods, the six-coordinate bis(ligand)alkoxooxovanadium(V) complexes were alsocharacterized by 1H NMR and 51V NMR.IR spectra were recorded as KBr disk in the range 4000-400 cm-1 on a Perkin-Elmer PE783 spectrophotometer and were referenced to polystyrene. The mass spectrawere obtained with an AEI MS9 (FABMS) spectrometer, or a Kratos MS50 (EIMS)instrument by the UBC mass spectrometry service. Elemental analyses were performed byMr. Peter Borda of the Microanalytical Laboratory of this department. 1H NMR spectra,recorded on a Varian XL-300 instrument, are reported in ppm downfield oftetramethylsilane (TMS) as the internal standard. 51V NMR spectra were recorded on aVarian XL-300 instrument and are referenced to external VOC13. The UV-Vis spectrawere recorded from 900-200 nm with a Shimadzu UV-2100 spectrophotometer. Bothcrystal structures reported in this thesis were determined with a Rigaku AFC6Sdiffractometer by Dr. Steven J. Rettig of the UBC Structural Chemistry Laboratory.112.2.1 Infrared SpectroscopyThe relevant IR data is summarized in Table 2.2.1. All compounds exhibit a strongV=0 stretching frequency in the region from 960 to 995 cm-1.Table 2.2.1 Characteristic IR absorptions (cm-1).All bands are sharp and strong except where noted.*Assignment VO(ka)2 VO(dpp)2 VO(hmp)21610 1605 1610(m)vc.0 and 1550 1550 1560(m)vc.c(ring) 1500 1490 15101470 1450 14501430(w)vv.o 980 965 970VC-N(ring) 1300Assignment VO(0z)2 VO(thz)2VC.N 1620 1600VC=C(aroma tic) 1595(w) 15701540vv.° 990 98012Assignment^VO(bz)2^VO(OCH3)(bz)2^VO(0C2H5)(bz)21600^1600^1600vc.0 and^1570 1520(b)^1550(b)Vc.C(aromatic)^1510^ 1520(b)1480 1480^14901440^1440 1450vv.o^995^960^970VN-H 3200(b)^3200(b)^3200(b)* w, weak; m, medium; b, broad.2.2.2. Elemental AnalysesSatisfactory elemental analyses were obtained for all complexes (refer to Table2.2.2). Prior to analysis, each sample was purified by recrystallization when possible anddried at —65°C in vacuo for at least 24 hours.13Table 2.2.2Results of elemental analyses of the vanadium complexes(Calculated[Found])Compound^Formula %C %H %NyO(ka)2 C12111009\1 41.28[41.06] 2.89[2.89]VO(dpp)2 C141116N205V 48.99[48.56] 4.70[4.65] 8.16[8.38]VO(hmp)2 C141116N207V 44.81[45.00] 4.30[4.39] 7.47[7.47]VO(oz)2 C181-1 16N205V 55.25[55.12] 4.12[4.17] 7.16[7.08]VO(thz)2.0.5H20 C181-117N203.5S2V 50.00[50.42] 3.98[3.83] 6.48[6.47]VO(bz)2 C141112N205V 49.57[49.37] 3.57[3.66] 8.26[8.02]VO(OCH3)(bz)2 C151115N206V 48.66[48.46] 4.08[4.03] 7.57[7.54]VO(0C2H5)(bz)2 C161117N206V 50.01[50.32] 4.46[4.54] 7.29[7.16]2.2.3. 11-1 NMR Spectroscopy1H NMR spectral data of the two vanadium(V) complexes are listed in Table 2.2.3.Both spectra exhibit a doublet and two triplets for the phenyl hydrogens and characteristicsignals for the alkoxy hydrogens.214R=CH3f^VO(OCH3)(bz)2R=CH2gCH3h VO(0C2H5)(bz)2Figure 2.2.3. VO(OR)(bz)2 complexes atom labelling used in NMR data.Table 2.2.3. 111 NMR chemical shifts (8) for the VO(OR)(bz)2 complexes (PPn1).aRefer to Figure 2.2.3. for atom labelling.VO(OCH3)(bz)2 VO(0C2H5)(bz)2Ha,e (d) 7.73(2H, J=7.1 Hz) 7.78(2H, J=7.2 Hz)Hb,d (t) 7.40(2H, J=7.5 Hz) 7.43(2H, J=7.5 Hz)He (t) 7.49(1H, J=7.5 Hz) 7.52(1H, J=7.4 Hz)CH3f (s) 3.34(3H)CH2g (q) 3.60(2H, J=7.1 Hz)CH3h 1.17(3H, J=7.1 Hz)a in CD3ODAbbreviations: s=singlet d=doublet t=triplet q=quartet152.2.4. Variable Temperature  1H NMR SpectroscopyThe variable low temperature 1H NMR spectra for VO(OCH3)(bz)2 andVO(0C2H5)(bz)2 in CD3OD were recorded over the range -80°C to 25°C. The lowtemperature 111 NMR spectra did not differ significantly from the spectrum obtained atroom temperature except for a slight broadening of the signals.2.2.5. 51V NMR Spectroscopy51V NMR data for VO(OCH3)(bz)2 and VO(0C2H5)(bz)2, recorded in CH2C12and C2H5OH respectively, are given in Table 2.2.5. Both complexes yielded one sharpsingle resonance, as expected for single species.Table 2.2.5. 51V NMR chemical shifts (8) for the VO(OR)(bz)2 complexes (Ppm).complex^chemical shift. (ppm)^line width (W112, Hz)VO(OCH3)(bz)2a^-425^ 222VO(0C2H5)(bz)2b -411 543a in CH2C12, b in C2H5OH162.2.6. Mass SpectrometryThe mass spectra of the complexes showed the HVOL2+, and/or VOL2+ fragmentswhen recorded in the positive ion FAB mode, or the VOL2+, VOL+, and L+ fragments inthe El mode. The results are listed in Table for positive ion FAB mode and inTable for the El mode.Table FAB mass spectral data (m/z) of the vanadium complexes.HVOL2+ VOL2+VO(ka)2 350* 349VO(bz)2 340 339*VO(dpp)2 344* 343VO(hmp)2 376* 375VO(OCH3)(bz)2 339VO(0C2H5)(bz)2 339* indicates the base peak.Table El mass spectral data (m/z) of the vanadium complexes.The relative intensities of the peaks are included in the parentheses.VOL2+^VOL+^L+VO (0z)2 391(100) 229(17.9) 163(88.9)v0(thz)2 423(100) 245(11.4) 179(5.2)172.2.7. UV-Vis ^m tr .The UV-Visible spectral data which were obtained at room temperature aresummarized in Table 2.2.7. Data for VO(dpp)2, VO(hmp)2 and VO(bz)2 were notobtained either due to their very limited solubility in various solvents or due to the reactionof the complexes with the solvents.Table 2.2.7. UV-Vis spectral data, X, nm (c, M-1cm-1).complex^solvent Amax (E)1 II In otherv0(ka)2^H20 842(30) 612(15) 223(34200)VO(oz)2^CH2C12 597(47) 543(45) 409(sh*, 111) 331(12000)239(63700)VO(thz)2^CH2C12 595(53) 537(66) 437(sh, 179) 346(11200)242(56500)VO(OCH3)(bz)2 CH3OH 441(2000)222(22200)203(25600)VO(0C2H5)(bz)2 C2H5OH 446(2400)222(25600)204(29700)* sh=shoulder182.2.8. X-ray Crystallographic AnalysesThe solid state structures of VO(oz)2, and VO(thz)2 were established by singlecrystal X-ray diffraction studies at 21°C. Single crystals of thebis(ligand)oxovanadium(IV) complexes were grown by slow evaporation from saturatedmethylene chloride solution. Crystallographic data, final atomic coordinates andequivalent isotropic thermal parameters Beg for VO(oz)2 and VO(thz)2 are given inAppendix A as Tables Al, A2 and A3. The complete list of bond lengths and bond anglesare summarized in Tables A4 and A5 in Appendix A.x=o vo(oz)2X=S VO(thz)22vo(ka)2•I■0IIV\,1-/ CH3 12019Chapter 3. Results and DiscussionThe coordination chemistry of oxovanadium(IV) was studied with kojic acid(Hka), 3-hydroxy-1,2-dimethy1-4-pyridinone (Hdpp), 2-hydroxymethy1-5-hydroxy-1-methyl-4-pyridinone (Hhmp), 2-(2'-hydroxypheny1)-2-oxazoline (Hoz), 2-(2'-hydroxypheny1)-2-thiazoline (Hthz) and benzohydroxamic acid (Hbz) as potential ligandsfor binding to the V02+ moiety. The ligands used in this study were chosen because theyall possess qualities which are desirable for bonding to oxovanadium(IV). All of these2 R2=CH3, R6=H VO(dpp)2R2=H, R6=CH2OH VO(hmp)2 VO(bz)2Figure 3.1. Bis(ligand)oxovanadium(IV) complexes.1 12CH3NH2-2H202 _R62R2V02+OH -2H+ _11VIMP20potential ligands when deprotonated behave as bidentate Lewis bases.24,25 The V02+cation is classified as a hard Lewis acid,26 therefore, according to hard soft acid basetheory,26 the V02+ cation should bind favorably to donor atoms which are hard Lewisbases. In the case of Inca, Hdpp, Hhmp and Hbz, the deprotonated hydroxy oxygen andthe carbonyl oxygen act as donor atoms, each donating an electron pair to theoxovanadium(IV) center. For Hoz and Hthz, the donor atoms are the deprotonatedhydroxy oxygen and the oxazoline or thiazoline ring nitrogen. The hydroxy oxygen, thecarbonyl oxygen and the ring nitrogen within these ligands can be classified as relativelyhard bases.25 Binding of the hard Lewis acid, V02+, to the hard Lewis base donor atomsresulted in bis(ligand) metal complexes of neutral charge. Each ligand binds to the centralvanadium atom to form 5 or 6-membered chelate rings (refer to Figure 3.1.). The chelateeffect contributes to the overall thermodynamic stability of these bis(ligand)oxovanadium(IV) complexes.R2=CH3, R6=H maltolR2=H, R6=CH2OH kojic acidFigure 3.2. Scheme for the one-pot synthesis of bis(3-oxy-4-pyridinonato)oxovanadium(IV)complexesThe synthesis of oxovanadium(IV) complexes with the {0, 0} or {0, N} bidentatemonobasic ligands were straightforward and gave relatively high yields (67%-94%). Theratio of ligand precursor to V02+ used was 2:1 with a slight excess of ligand precursor21used to force the reaction to completion. In the synthesis of VO(dpp)2 and VO(hmp)2, aone pot synthetic method was utilized.27 The synthesis involves the conversion of themetal coordinated pyrone precursor to the corresponding coordinated pyridinone metalcomplex. The traditional method of synthesis for 3-hydroxy-4-pyridinone involves theamination of the analogous 3-hydroxy-4-pyrone.27 To carry out this conversion, protectedpyrone precursors are usually utilized in a multistep process. The overall conversion istime consuming and rigorous. On the other hand, one pot synthesis of VO(dpp)2 andVO(hmp)2 took only a single step and gave yields of 94% and 67%, respectively. The onepot synthetic process begins by the in situ formation of the metal-pyrone complex. This isthen followed by the insertion of a primary amine into the pyrone ring to form theappropriate pyridinonate complex. Figure 3.2. outlines the synthetic scheme for the one-pot synthesis of the oxovanadium pyridinonate complexes.Recrystallization of the oxovanadium(IV) complexes was not always possible dueto the limited solubility of some of these complexes in common solvents or due to theoxidation of the complex by oxygen within the solvent. For example, purple VO(bz)2dissolves in methanol to give a light orange solution which quickly changes colour to darkred. Addition of water to this solution yields microcrystalline VO(OCH3)(bz)2, anoxovanadium(V) species. Dissolving VO(bz)2 in ethanol produces similar results; theoxovanadium(V) complex, VO(0C2H5)(bz)2 was obtained.All the oxovanadium(IV) complexes were found to be air stable and exhibit amagnetic moment at room temperature in the solid state. Vanadium(IV) has an electronconfiguration of [Ad3d1 and hence has a single unpaired electron. Assuming that themagnetic moment has contribution from only the spin angular momentum of the unpairedelectron, the spin only formula predicts a magnetic moments of 1.73 for a d1 system. Thesix oxovanadium(IV) complexes possess solid state magnetic moment of 1.72 to 1.84 BMat room temperature. The observed magnetic moment for the six oxovanadium(IV)complexes is within the range of values commonly found for many vanadium(IV)22complexes and indicates the presence of a single unpaired electron.28 VO(OCH3)(bz)2and VO(0C2H5)(bz)2 are oxovanadium(V) species with an electron configuration of1Arl3d0. The two oxovanadium(V) complexes showed no solid state magnetic momentsince they possess no unpaired electron.Infrared measurements for each of the oxovanadium complexes are summarized inChapter 2, Table 2.2.1. The infrared spectral pattern of the ligands is preserved in thesecomplexes with a general bathochromatic shift upon coordination to the oxovanadiumcenter. In the infrared spectra of the eight oxovanadium complexes, the absorptionassociated with the characteristic V=0 stretching frequency is of particular interest. Thestretching frequencies of the V=0 bond in oxovanadium complexes are generally observedaround 930 cm-1 to 1030 cm-1.14 For the eight oxovanadium complexes synthesized inthis study, vv.() was observed to range from 965 to 995 cm-1.The oxovanadium(V) complexes, VO(OCH3)(bz)2 and VO(0C2H5)(bz)2, showedDv.0 at 960 cm-1 and 970 cm-1 respectively. The Dv.° for VO(OCH3)(bz)2 andVO(0C2H5)(bz)2 were 35 cm-1 and 25 cm-1 lower than Dv.° in the oxovanadium(IV)complex VO(bz)2 (995 cm-1). This indicates that the vanadium oxo bond in theVO(OR)(bz)2 complexes is weaker than the vanadium oxo bond in VO(bz)2. This may beexplained as follows.The V=0 bond is a multiple covalent bond involving pit-dir electron donation fromthe oxygen to the vanadium center which has empty acceptor orbita1.29 This electrondonation through the it bond is superimposed upon a a bond. Changes in the electronaccepting ability of the vanadium center causes changes in the strength of the vanadiumoxo bond, which is reflected in changes in the V=0 stretching frequency. Coordinatedligands which donate electron density to the vanadium center will increase the electrondensity in the vanadium d orbitals. This increased electron density in the vanadium dorbitals reduces the electron accepting ability of the vanadium atom, therefore reducing theV=0 pit-d/c electron donation. The degree of reduction in the V=0 pit-dn electron23donation depends on the electron donating ability of the ligands. It is not unreasonable toassume that the total electron accepting ability of a metal ion in a particular valence state iscertain.30 When a V4+ complex oxidises to a V5+ complex, the vanadium ion increases itselectrophilicity. At this stage, when a monodentate negative group reaches thecoordination zone, it may or may not exactly counterbalance the increased electrophilicitya V5+. If the donor property of the new ligand is greater than the increased acceptorproperty of the metal ion, there will be an overall accumulation of increased electrondensity around the vanadium ion. This would greatly affect V=0 bond, the stretchingfrequency of which would certainly be lowered. This is what is found in the complexesVO(bz)2 and VO(OR)(bz)2 (R=methyl or ethyl).Analyses for carbon, hydrogen and, when appropriate, nitrogen were carried outfor each oxovanadium complex. The results are summarized in Table 2.2.2. The data areconsistent with the formulation of bis(ligand) oxovanadium complexes. With theexception of VO(thz)2, no solvate water was observed in these complexes. Attempts toremove the solvated water in VO(thz)2 by drying at approximately 65°C in vacuo (< 0.3Torr) for a minimum of 24 hours were not successful.The eight synthesized oxovanadium complexes were examined by massspectrometry. The data are summarized in Chapter 2, Tables and Themass spectra of VO(oz)2 and VO(thz)2 were obtained using electron impact ionization (El)while the mass spectra of the other complexes were obtained using positive ion fast atombombardment (+FAB). The spectra of VO(oz)2 and VO(thz)2 showed strong signalscorresponding to VOL2+, VOL+ and L+ fragments. For VO(ka)2, VO(bz)2, VO(dpp)2 andVO(hmp)2, the mass spectra revealed very strong signals corresponding to HVOL2+ andVOL2+ fragments. The results for these complexes are consistent for a VOL2 formulation.In the case of VO(OCH3)(bz)2 and VO(0C2H5)(bz)2 complexes, VO(OR)(bz)2+ andHVO(OR)(bz)2+ fragments were not the dominant fragments. The base peak in theobserved mass spectra corresponds instead to VOL2+. The alkoxy group was lost during24the fragmentation process in the mass spectrometer. This would suggest that the alkoxygroup is bonded less strongly to the vanadium(V) center compared to the other oxygendonor atoms within the complexes.1H NMR data for VO(OCH3)(bz)2 and VO(0C2H5)(bz)2 were recorded inCH3OD and are presented in Table 2.2.3. The assignments and integrations of the Hsignals are consistent with the coordination of two bidentate ligands to the oxovanadiumcore. 1H signals due to the phenyl ring hydrogens of the two benzohydroxamato ligandssuggest that the phenyl rings of the two ligands are in the same chemical environment.Low temperature 1H NMR of both complexes were carried out and the spectra at differenttemperatures show only slight broadening of the signals. No emergence of any additional1 H resonances was observed even at -80°C.Six isomers are possible for the VO(OR)(bz)2 complexes. These possible isomersare illustrated in Figure 3.3. Isomers I and II have the alkoxy group trans to the V=0 bondwhereas isomers III to VI have the alkoxy group cis to the V=0 bond. At roomtemperature, the 1H NMR spectra shows the hydrogens on the two phenyl rings associatedwith the two benzohydroxamate ligands to be in the same chemical environment. Thiswould suggest that the oxovanadium complex has assumed a trans configuration where thehydrogens in the two phenyl rings are chemically equivalent (I or II). However, fastexchange of the two benzohydroxamate ligands in a cis configuration (III to VI) wouldalso show equivalent phenyl ring hydrogens. If such an exchange process is occurring,lowering the temperature might slow down the rate of exchange and allow the observationof two sets of inequivalent hydrogens on each of the benzohydroxamate ligands.However, variable temperature 1H NMR experiments (as low as -80°C) did not produceany significant changes in the H NMR spectra. This may suggest that the oxovanadiumcomplexes are indeed in a trans configuration. However, the possibility of the complexesin a cis configuration can not be ruled out on the basis of the results from the variable0C v^CH N...O/I O NH‘°0RU,,,. II %%0,N0/1^CoNfr. ‘C0,, ll 0....N.11c o-- ,...11,v^IH NI0 /IN0 C' 025IIIII^ IV^RO„,. 11^c^*V*^I0N /'C V^ VIFigure 3.3. Six possible isomers for V0(OR)(bz)2 complexes.26temperature H NMR experiments. It may be that the rate of exchange of thebenzohydroxamate ligands is faster than the NMR time scale; then the stereochemistry atthe vanadium metal center would not be elucidated using H NMR.A crystal structure of bis(benzohydroxamato)chlorooxovanadium(V), VOC1(bz)2(Figure 3.4.) was reported by Raymond et al.3 1 In this crystal structure, theoxovanadium(V) complex assumes a cis configuration cooresponding to the stereoisomerIII in Figure 3.3 with the chlorine atom cis to the vanadium oxo bond. Similar structures0Cl„ II10 C/0NFigure 3.4. Structure of bis(benzohydroxamato)chlorooxovanadium(V) complex.31have been observed in aquobis(oxalato)oxovanadium(IV), VO(H20)(C204)232 andisopropoxobis(8-hydroxyquinolinato)oxovanadium(V), VO(OiPr)(ox)2.33 Theseoxovanadium(V) complexes exhibit the trans influence which refers to the ability of oneligand to lengthen (and apparently weaken) the bond to the ligand trans to it.34 It waspredicted that a multiply bonded ligand (e.g. V=0) will preferentially weaken other ligandbonds in the trans position.34 Thus, ligands that tend to form strong bonds willpreferentially occupy a position cis to the vanadium oxo bond.31 In 6-coordinateoxovanadium complexes with both bidentate and monodentate ligands, it is likely that one27donor atom of the bidentate ligand would occupy the trans position with the monodentateligand occupying the cis position. This could be attributed to the chelate effect of thebidentate ligand, since the extra thermodynamic stability caused by the positive enthalpychange after chelation might overcome the trans influence from the vanadium oxogroup.24 The trans influence of the oxo group within VO(bz)2C1, VO(H20)(C204)2 andVO(OiPr)(ox)2 causes the chlorine, the water and the isopropoxy group to assume aposition cis relative to the vanadium oxo bond. In our example, VO(OR)(bz)2, it issuspected that the trans influence of the oxo group would also cause the alkoxy group totake up a cis position relative to the oxo bond. However, we have been unable to obtainevidence which supports this conclusion in the VO(OR)(bz)2 complexes. Hence, in theabsence of any concrete evidence in solid state or in solution, the possibility of the alkoxygroup being trans to the oxo group cannot be entirely ruled out.Single crystal X-ray diffraction studies of VO(oz)2 and VO(thz)2 were performed.The analyses show unequivocally that the complexes are indeed the expected bis(ligand)oxovanadium(IV) complexes. The crystal structure of VO(oz)2 was found to beisostructural with VO(thz)2. Computer generated ORTEP diagrams of VO(oz)2 andVO(thz)2 are presented in Figures 3.5. and 3.6.. Selected bond lengths and bond anglesare summarized in Tables 3.1. and 3.2. respectively. X-ray diffraction studies revealedboth VO(oz)2 and VO(thz)2 to be 5-coordinate square pyramidal oxovanadium(IV)complexes, with the oxo group in the axial position. This structure is common for manyoxovanadium(IV) complexes.10 The 2-(2'-oxypheny1)-2-oxazolinate and 2-(2'-oxypheny1)-2-thiazolinate ligands are coordinated to the vanadium center via the phenolateoxygen and the oxazoline or thiazoline ring nitrogen. The two oxazolinate or thiazolinateligands are found to be trans to one another and cis to the oxo group.The vanadium oxo bond lengths in VO(oz)2 and VO(thz)2 are observed to be1.594(1) A and 1.591(3) A, respectively, and are typical for V=0 bond lengths inoxovanadium(IV) complexes (1.52 A-1.68 A).29 Within the six-membered chelate ring01H204C14 H13C15H10H728Figure 3.5. ORTEP view of the VO(oz)2 unit.29Figure 3.6. ORTEP view of the VO(thz)2 unit.30Table 3.1.^Selected Bond Lengths (A) for V0(oz)2 and V0(thz)2 with EstimatedStandard Deviations in ParenthesesVO(oz)2 VO(thz)2Atoms Distance Atoms DistanceV(1)-0(2) 1.931(1) V(1)-0(2) 1.903(3)V(1)-0(4) 1.926(1) V(1)-0(4) 1.900(3)V(1)-0(5) 1.594(1) V(1)-0(5) 1.591(3)V(1)-N(1) 2.068(1) V(1)-N(1) 2.083(3)V(1)-N(2) 2.061(1) V(1)-N(2) 2.083(3)0(1)-C(1) 1.347(2) S(1)-C(1) 1.757(4)0(1)-C(2) 1.460(2) S(1)-C(2) 1.790(5)0(2)-C(5) 1.315(2) 0(2)-C(5) 1.330(4)0(3)-C(10) 1.346(2) S(2)-C(10) 1.761(4)0(3)-C(11) 1.458(2) S(2)-C(11) 1.788(5)0(4)-C(14) 1.319(2) 0(4)-C(14) 1.328(4)N(1)-C(1) 1.284(2) N(1)-C(1) 1.295(5)N(1)-C(3) 1.472(2) N(1)-C(3) 1.479(5)N(2)-C(10) 1.287(2) N(2)-C(10) 1.291(4)N(2)-C(12) 1.472(2) N(2)-C(12) 1.474(5)31Table 3.2.^Selected Bond Angles (deg) for VO(oz)2 and VO(thz)2 with EstimatedStandard Deviations in Parentheses.Atoms Anglevo(oz)2 v0(thz)20(2)-V(1)-0(5) 108.41(5) 115.2(1)0(4)-V(1)-0(5) 108.81(5) 114.9(1)0(5)-V(1)-N(1) 104.73(6) 99.1(1)0(5)-V(1)-N(2) 103.79(5) 99.4(1)0(2)-V(1)-N(1) 85.28(5) 86.8(1)0(2)-V(1)-N(2) 85.25(5) 86.4(1)0(4)-V(1)-N(1) 85.23(5) 85.5(1)0(4)-V(1)-N(2) 86.21(5) 85.7(1)0(2)-V(1)-0(4) 142.79(5) 129.9(1)N(1)-V(1)-N(2) 151.47(5) 161.4(1)formed by the coordination of the phenolate oxygen and the ring nitrogen to the vanadiumcenter, the average vanadium phenolate oxygen bond length is 1.928(1) A and 1.901(3) Afor VO(oz)2 and VO(thz)2 respectively. The average vanadium ring nitrogen bond lengthis 2.064(1) A for the oxazolinate complex and is 2.083(3) A for the thiazolinate complex.The V-0 and V-N bond lengths fall in the range of V-0 and V-N bond lengths observedfor many oxovanadium Schiff base complexes.35 The average V-0 bond length in bothcomplexes are shorter than the observed V-N bond lengths. In the complexes M(oz)3(M=A13+, Ga3+ and In3+), the M-0 bonds were also found to be shorter than the M-Nbonds.1732Examination of one of the oxazoline rings in VO(oz)2 (Figure 3.5.) shows theC(1)-0(1) bond length of 1.347(2) A to be significantly shorter than the C(2)-0(1) bondlength of 1.460(2) A. Also the C(1)-N(1) bond length (1.284(2) A) is shorter than theC(3)-N(1) bond length (1.472(2) A). The average bond length of a carbon oxygen singlebond is 1.45 A while a typical carbon oxygen double bond has a bond length of about 1.25A. A typical carbon nitrogen single bond has bond length of about 1.47 A.36 Comparisonof the observed C-N and C-0 bond lengths with typically observed bond lengths suggeststhat some of the C-N and C-0 bonds exhibit double bond character. This can berationalized using resonance structures (see Scheme 0.17,37For the complex VO(thz)2, similar double bond character was observed for the C-N bonds of the thiazoline rings. However, very little double bond character, if any wasobserved for the C-S bonds in the thiazoline rings. Hence no resonance structures like theones in Scheme I can be given for the thiazoline rings of the VO(thz)2 complex. OH OHScheme IIn the structure of both VO(oz)2 and VO(thz)2, the vanadium atom is displacedtoward the oxo group and away from the least-square basal plane defined by the fourligating atoms, Ni, N2, 02 and 04 (refer to Figures 3.5. and 3.6.). This displacement ofthe vanadium atom is observed in many oxovanadium(IV) complexes. The displacementof the vanadium atom was observed to be 0.57 A in VO(oz)2 and 0.60 A in VO(thz)2.These observed displacements are close to those commonly observed in other similar33oxovanadium(IV) complexes.35,38Ultraviolet-visible spectra of VO(ka)2, VO(oz)2, VO(thz)2, VO(OCH3)(bz)2 andVO(0C2H5)(bz)2 were recorded in appropriate solvents. A summary of the observedabsorbances for the oxovanadium(IV) complexes are listed in Chapter 2, Table 2.2.7.Oxovanadium(IV) complexes typically exhibit three d-d or ligand field bands in the UV-Visible spectra.14,39,40,41,42,43 These three bands, band I, band II, and band III areobserved in the regions of 900 to 625 nm, 690 to 520 nm and 470 to 330 nm respectively.The extinction coefficient of the observed bands range from 5 to 100 M-1cm-1. Band IIIwhose absorbance is of the highest energy is frequently obscured by the strong chargetransfer bands in the ultraviolet region of the spectra. When band III is observable, itoften appears as a shoulder on one of the charge transfer bands so that its maximumposition is known with the least accuracy among the three bands.40 Oxovanadium(IV)complexes commonly exhibit coordination numbers of 5 or 6 with observed coordinationgeometries of square pyramid or distorted octahedron.10 However, due to the presence ofa dominant axial field, the energy level diagrams associated with each coordinationgeometry do not differ very much from each other.42 Hence, the bands of both 5-coordinate and 6-coordinate oxovanadium(IV) complexes can be assigned on the basis ofthe same energy level scheme.42Ballhausen and Gray have proposed a energy level diagram for VO(H20 )52+.41The orbital transformation scheme for the C4v species VO(H20)52+ defines: (i) a strong a-bond of al symmetry between the (3dz2+4s) hybrid on vanadium and the spa oxygenhybrid; (ii) two e symmetry 7c-bonds lying between the vanadium dxz and dyz orbitals andthe 2px and 2py orbitals of oxygen; (iii) formation of four a—bonds between the spahybrids (on the equivalent water oxygens) and the vanadium (4s-3d2) (ai symmetry), 4Pxand 4py (e symmetry), and 3d2_2 (bi symmetry) orbitals; (iv) the sixth ligand forming aa—bond with the 4pz vanadium orbital; and (v) a nonbonding b2 symmetry 3dxy orbital ofvanadium.40 Figure 3.6. illustrates the proposed energy level diagram.38•,. ,s„^• ,^ ,*.•., ', ... .. ,.......:-ebEit1:, ......•,. „ • • it (oxide)34Vanadium orbitals^M.O. Levels^Oxygen orbitalsea',• • ••^,•‘ ;. /^,-'.,'...11:1 '.^‘Ia*i ..• 1 .,\ \ ',..b*i \ '‘,......,^',,.'.sse*n',•',s• ',,-' ss,,,,‘^...,.%, • •^,• s;,^*. •, ,• • %,••st^., i3d ^i''..s*-..:" \^b2^':'. ; \•...:,^ro'.^I,. .^rb^..'-re^'.., . ,..^Mal', ,..:\ ,,,eb  :,/■,`,,V,.:^..,,•- ,,,,'^'..^a ^.‘ ,^b^/^‘b ^b1 ^nal^.. .1 ____.--....1121%^...."-a (water) a (oxide)Figure 3.6. Molecular orbital scheme for [VO(H20)52+] (C4v symmetry) according toBallhausen and Gray4135With reference to the energy level diagram in Figure 3.7., the three observed bandswere assigned by Ballhausen and Gray as follows: (a) band I, electronic transition from b2to en* or 2B2 to 2E(I) (b) band II, electronic transitions from b2 to bl* or 2B2 to 2Bi (c)band III, electronic transitions from b2 to Iai* or 2B2 to 2A1.41 The second transitionmaximum yeilds the value of 10Dq directly.39 The intense higher energy bands that areobserved out to 200 nm are assumed to be charge transfer in origin.39,40,41 Even thoughin some cases, distortion from C4v symmetry occurred (especially where LL is a bidentateligand in common complexes of the type VO(LL)2), the three observed bands wereassigned in the same way as that for C4v species by the comparison of the energies andintensities with the C4v species.41 However, it should be noted that there is still no realagreement on the ordering of the energy levels.39In our study, the UV-Visible spectrum of the complex VO(ka)2 shows only twobands in the region of 330-900 nm. The lowest energy band observed at 842 nm isassigned to the b2 to en* transition while the band observed at 612 nm is assigned to the b2to 1)1* transition. The band corresponding to the higher energy b2 to Iai* transition (orband III) is obscured by the low energy tail of the intense charge transfer band in the UVregion of the spectra. In the case of VO(oz)2 and VO(thz)2, the higher energy band IIIwhich could be assigned to b2 to Iai* transition was observed as a shoulder of the chargetransfer band at 409 nm and 437 nm, respectively. In addition, band I for these complexeswas observed at approximately 595 nm, which falls slightly out of the region where band Iis commonly observed for previously reported oxovanadium(IV) complexes.The intensity of band I is commonly observed to be greater than the intensity (i.e.extinction coefficient) of band II for many oxovanadium(IV) complexes. For VO(ka)2,band I is observed to have an extinction coefficient of 30 while band II has an extinctioncoefficient of 15. These observed intensities and extinction coefficients are consistentwith the fact that the b2 to en* transition is partially allowed (allowed xy)40 while the36, .-oo000°'ogoo4-c )0o'.8'o^■  ■ a .     ■       ....   ■   . ■,•■•• . • • • ■ . • .... .......... .,,A4\114. 0o800^900 ooFigure 3.8. Potential "intensity stealing" effect in UV-Vis spectrophotometric study ofVO(oz)2 and VO(thz)2.dz2dx 2 _y 2 (or d„y)1 dxz, dyzdxy (or dx2 _y 2)I.^.4^:^;Ial^I^II^I^.lb I:I 11dxy d2 III id22II37transitions corresponding to the other bands are totally forbidden. However, thisphenomenon of band I having a greater intensity than band II is not found in VO(oz)2 andVO(thz)2. This is particularly true for VO(thz)2 where the intensity of band II isabnormally higher than band I. The greater intensity of band II is probably due to the"intensity stealing" effect of band II. Figure 3.8. illustrates the intensity stealing effect ofband II.C4v symmetry^Low symmetryFigure 3.9. Splitting of the vanadium d levels (b2, e and b1 considered mainly as V orbitals)It should be noted that for some oxovanadium(IV) complexes, four distinct bandsare observed in the UV-Visible spectra. This is attributed to a lowering of the symmetryof the complexes. A lowering of symmetry would result in the lifting of the degeneracy ofthe en* orbital. This would change the molecular orbital diagram to that shown in Figure3.9.14 With this lowering of symmetry, four bands are expected in the UV-Visiblespectrum. Low symmetry oxovanadium(IV) complexes involving tartrate, lactate,mandelate or malate groups have UV-Visible spectra showing four well defined absorptionbands in the region of 1000 to 380 nm.43 For the oxovanadium(IV) complexesinvestigated in our study, the highest possible symmetry of the VOL2 complex (L is a38bidentate ligand) is C2. The symmetry of VO(oz)2 and VO(thz)2, in the solid state, wasshown by single crystal X-ray diffraction studies to be C2 (refer to Figure 3.5. and 3.6.).However, the complexes studied in this thesis all showed less than four bands. It isassumed that the splitting of the eic* level caused by the lowering of symmetry is simplytoo small to be observed experimentally.40Vanadium(V) has a d0 configuration and as such does not exhibit d-d transition.The two oxovanadium(V) complexes, VO(OCH3)(bz)2 and VO(0C2H5)(bz)2 do not showd-d transitions in the UV-Vis spectra. Only high intensity ligand to metal charge transferbands, which are allowed transitions, are observed in the UV portion of the optical spectra.UV-Visible spectra of freshly prepared solutions of VO(bz)2 in methanol or ethanol showno d-d transition bands. This is because the reaction of VO(bz)2 with solvent molecules(methanol or ethanol) produces VO(OCH3)(bz)2 or VO(0C2H5)(bz)2 extremely rapidly.In conclusion, some new oxovanadium complexes have been prepared and therelevant coordination chemistry observed in these complexes is consistent with thatexpected from examining the literature. Naturally-occurring ligating moieties were usedto coordinate to V02+ because of the potential application of their oxovanadiumcomplexes in the treatment of diabetes. An evaluation of VO(ka)2 as a potential insulinmimicking agent has been performed and preliminary data are presented in the appendixB.39REFERENCES1. Rehder, D. Biometals 1992, 5, 3.2. Cantley Jr., L. C.; Cantley, L. G.; Josephson, L. J. Biol. Chem. 1978, 253, 7361.3. Dubyak, G. R.; Kleinzeller, A. J. Biol. Chem. 1980, 255 , 5306.4. Shechter, Y.; Karlish, S.J. D. Nature 1980, 284, 556.5. Post, R. L. Proceedings of the 2nd International Conference on the Properties andFunctions of Na, K-ATPase: Academic: New York, U. S. A., 1979; p.389-4016. Nechay, B. R. J. Ann. Rev. Pharmacol. 1984, 24, 501.7. Simons, T. J. B. Nature, 1979, 281, 337.8. Chasteen, N. D.; Grady, J. K.; Holloway, C. E. Inorg. Chem. 1986, 25 , 2754.9. Robson, R. L.; Eady, R. R.; Richardson, T. J.; Miller, R. W.; Hawkins, M.;Postgate, T. J. Nature 1986, 322, 388.10. Weyer, R.; Drenn, B. E. In Vanadium in Biological Systems : VanadiumHaloperoxidases; Chasteen, N. D., Ed.; Kluwer Academic Publishers:Dordrecht,1990; p. 8111. Atkinson, M. A.; Maclaren, N. K. Sci. Am. 1990, 263, 62.12. Butler, A.; Carrano, C. J. Coord. Chem. Rev. 1991, 109, 61.13.^Ramanadham, S.; Brownsey, R. W.; Cros, G. H.; Mongold, J. J.; McNeill, J. H.Metabolism 1989, 38, 1022, and references therein.14^Wilkinson, G.; Gillard, R. D.; McCleverty, J. A. Comprehensive CoordinationChemistry Volume 3: Pergamon Press: New York, U. S. A., 1987; p. 455, and 488.15. Miller, M. J. J. Am. Chem. Soc. 1983, 105, 240.16. Crumbliss, A. L. Coord. Chem. Rev. 1990, 105,155.17. Hoveyda, H. R.; Karunaratne, V. Rettig, S. J.; Orvig, C. Inorg. Chem. 1992, 31,5408.18. Luo, H.; Rettig, S. J.; Orvig, C. Inorg. Chem. in press.4019. Hewitt, C. D.; Herman, M. M.; Lopes, M. B. S.; Savory, J.; Wills, M. R.Neuropath. App!. Neurobiol. 1991, 17, 47 and references therein.20. Zhang, Z.; Lyster, D. M.; Webb, G. A.; Orvig, C. Nucl. Med. Biol. 1992, 19, 327.21. Black, D.; Wade, M. J. Aust. J. Chem. 1972, 25, 1797.22. Hoveyda, H. R.; Orvig, C. Unpublished results.23. Mabbs, F. E.; Machin, D. J. Magnetism and Transition Metal Complexes,Chapman and Hall: London, Great Britian, 1961; p.5.24. Cotton, F. A.; Wilkinson, G. Advanced Inorganic Chemistry, A ComprehensiveText, 4th Ed.; John Wiley and Sons: New York, U. S. A., 1980; p.63 and 7125. Cotton, F. A.; Wilkinson, G. Basic Inorganic Chemistry, John Wiley and Sons:New York, U. S. A., 1976; p.131, 170 and 21126. Huheey, J. E. Inorganic Chemistry, 3rd Ed.; Harper and Row: New York, U. S. A.,1983; p.31427. Zhang, Z.; Hui, T.; Orvig, C. Can. J. Chem. 1989, 67, 1708, and references therein.28. Drago, R. S. Physical Methods in Chemistry, W. B. Saunders Company:Philadelphia, U. S. A., 1977; p.42529. Caira, M. R.; Haigh, J. M.; Nassimbeni, L. R. J. Inorg. Nucl. Chem. 1972, 34,3171.30. Dutta, R. L.; Lahiry, S. Jour. Indian Chem. Soc. 1964, 41, 546.31. Fisher, D. C.; Barclay-Peet, J.; Balfe, C. A.; Raymond, K. N. Inorg. Chem. 1989,28, 4399.32. Oughtred, R. E.; Raper, E. S.; Shearer, H. M. M. Acta Crystallogr. Sect. B 1976,B32, 82.33. Scheidt, W. R. Inorg. Chem. 1973, 12, 1758.34. Nugent, W. A.; Mayer, J. M. Metal-Ligand Multiple Bonds; John Wiley and sons:New York, U. S. A., 1988, p156-157.4135. Carrano, C. J.; Nunn, C. M.; Quan, R.; Bonadies, J. A.; Pecoraro, V. L. Inorg.Chem. 1990, 29, 944.36. Weast, R. C. C.R.C. Handbook of Chemistry and Physics, 54th Ed.; C.R.C. Press:Ohio, U. S. A., 1973; p.F19637. Eng-Wilmot, D. L.; van der Helm, D. J. Am. Chem. Soc. 1980, 102, 7719.38. Cooper, S. R.; Koh, Y. B.; Raymond, K. N. J. Am. Chem. Soc. 1982, 104, 5092.39. Bonadies, J. A.; Carrano, C. J. J. Am. Chem. Soc. 1986, 108, 4088.40. Selbin, J. Chem. Rev. 1965, 65, 153.41. Ballhausen, C. J.; Gray, H. B. Inorg. Chem. 1962, 1, 111.42. Sacconi, L.; Campigli, U. Inorg. Chem. 1965, 5 , 606.43.^Lever, A. B. P. Inorganic Electronic Spectroscopy, 2nd Ed.; Elsevier SciencePublishers B.V.: Amsterdam, 1984, p.385-39242Appendix ATable Al Selected Crystallographic Data for VO(oz)2 and VO(thz)2.complex^VO(oz)2^v0(thz)2formula^C181116N205V^C181116N203S2Vfw 391.28^423.40crystal system^triclinic orthorhombicspace group P1^ Pbcaa,A^10.408(1)^12.331(2)b,A 11.282(1) 26.090(2)c, A^7.666(1)^11.125(2)a, deg 103.78(1)0, deg^109.64(1)7, deg 84.75(1)V, A3^823.3(2)^3579.3(9)Z 2 8Dcalc, g/cm3^1.578^1.571T, °C 21 21radiation (k, A)^Mo Ka (0.71069)^Mo Koc (0.71069)[t(MoKa) cm-1 6.14^ 7.80transmission factor^0.92-1.00 0.82-1.00R^ 0.034^0.035Rw 0.035 0.03043Table A2 Final atomic coordinates (fractional) and Beg (A2) for V0(oz)2.Atom^x^Y^z^BegV(1) 0.27964(3) 0.46204(2) 0.12244(4) 2.351(8)0(1) 0.2143(1) 0.7491(1) 0.5528(2) 3.41(4)0(2) 0.4605(1) 0.5193(1) 0.2775(1) 2.79(3)0(3) 0.4041(1) 0.1095(1) -0.1073(2) 3.42(4)0(4) 0.1376(1) 0.3577(1) 0.1060(2) 3.05(4)0(5) 0.2300(1) 0.5241(1) -0.0560(2) 3.16(4)N(1) 0.2157(1) 0.5813(1) 0.3285(2) 2.62(4)N(2) 0.3771(1) 0.3041(1) 0.0311(2) 2.55(4)C(1) 0.2793(1) 0.6769(1) 0.4406(2) 2.50(5)C(2) 0.0801(2) 0.6965(2) 0.5014(3) 4.18(7)C(3) 0.0860(2) 0.5753(2) 0.3635(3) 3.45(6)C(4) 0.4150(1) 0.7131(1) 0.4626(2) 2.52(5)C(5) 0.5005(1) 0.6279(1) 0.3840(2) 2.45(5)C(6) 0.6357(2) 0.6628(2) 0.4224(2) 3.12(5)C(7) 0.6814(2) 0.7763(2) 0.5293(3) 3.84(7)C(8) 0.5959(2) 0.8606(2) 0.6204(3) 3.80(6)C(9) 0.4645(2) 0.8287(1) 0.5705(2) 3.27(6)C(10) 0.3223(2) 0.1989(1) -0.0510(2) 2.57(5)C(11) 0.5362(2) 0.1640(2) -0.0636(3) 3.44(6)C(12) 0.5210(2) 0.2953(2) 0.0397(2) 2.90(5)C(13) 0.1823(2) 0.1673(1) -0.0884(2) 2.72(5)C(14) 0.0972(2) 0.2502(1) -0.0059(2) 2.60(5)C(15) -0.0380(2) 0.2150(2) -0.0460(3) 3.29(6)44C(16) -0.0859(2)^0.1052(2)^-0.1638(3)^4.28(7)C(17) -0.0022(2)^0.0242(2)^-0.2450(3)^4.57(7)C(18)^0.1306(2)^0.0548(2)^-0.2070(3)^3.71(6)Table A3. Final atomic coordinates (fractional) and Beg (A2) for VO(thz)2.Atom^x^Y^z^BeqV(1) 0.44725(6) 0.35945(2) 0.40706(6) 2.89(3)S(1) 0.53110(11) 0.47063(5) 0.71884(11) 4.95(7)S(2) 0.27819(10) 0.22705(5) 0.19962(12) 4.57(7)0(2) 0.3157(2) 0.39716(10) 0.4207(3) 3.6(1)0(4) 0.4955(2) 0.30099(10) 0.4937(2) 3.5(1)0(5) 0.5296(2) 0.38000(10) 0.3081(2) 3.9(1)N(1) 0.5023(3) 0.40147(13) 0.5541(3) 3.2(2)N(2) 0.3596(2) 0.30771(12) 0.3027(3) 2.9(2)C(1) 0.4587(3) 0.44201(15) 0.6006(4) 3.1(2)C(2) 0.6426(4) 0.4276(2) 0.6984(4) 4.9(3)C(3) 0.6046(4) 0.3859(2) 0.6131(4) 4.3(2)C(4) 0.3560(3) 0.46407(15) 0.5638(4) 3.0(2)C(5) 0.2891(3) 0.4402(2) 0.4778(4) 3.0(2)C(6) 0.1880(4) 0.4621(2) 0.4510(4) 3.5(2)C(7) 0.1551(4) 0.5065(2) 0.5064(5) 4.4(3)C(8) 0.2201(4) 0.5304(2) 0.5904(5) 5.1(3)C(9) 0.3193(4) 0.5097(2) 0.6170(4) 4.1(2)C(10) 0.3619(3) 0.2582(2) 0.3049(4) 3.1(2)C(11) 0.2258(4) 0.2873(2) 0.1495(4) 5.0(3)45C(12) 0.2914(3)^0.3290(2) 0.2060(4) 4.0(2)C(13) 0.4290(2)^0.22764(15) 0.3840(4) 3.1(2)C(14) 0.4925(3)^0.2508(2) 0.4746(4) 3.1(2)C(15) 0.5560(4)^0.2194(2) 0.5486(4) 4.3(2)C(16) 0.5585(4)^0.1673(2) 0.5324(5) 5.2(3)C(17) 0.4972(4)^0.1444(2) 0.4440(5) 5.2(3)C(18) 0.4330(4)^0.1737(2) 0.3714(4) 4.4(3)Table A4. Bond Lengths (A) for VO(oz)2 and VO(thz)2 with Estimated StandardDeviations in ParenthesesVO(oz)2 vO(thz)2Atoms Distance Atoms DistanceV(1)-0(2) 1.931(1) V(1)-0(2) 1.903(3)V(1)-0(4) 1.926(1) V(1)-0(4) 1.900(3)V(1)-0(5) 1.594(1) V(1)-0(5) 1.591(3)V(1)-N(1) 2.068(1) V(1)-N(1) 2.083(3)V(1)-N(2) 2.061(1) V(1)-N(2) 2.083(3)0(1)-C(1) 1.347(2) S(1)-C(1) 1.757(4)0(1)-C(2) 1.460(2) S(1)-C(2) 1.790(5)0(2)-C(5) 1.315(2) 0(2)-C(5) 1.330(4)0(3)-C(10) 1.346(2) S(2)-C(10) 1.761(4)0(3)-C(11) 1.458(2) S(2)-C(11) 1.788(5)0(4)-C(14) 1.319(2) 0(4)-C(14) 1.328(4)N(1)-C(1) 1.284(2) N(1)-C(1) 1.295(5)46N(1)-C(3) 1.472(2) N(1)-C(3) 1.479(5)N(2)-C(10) 1.287(2) N(2)-C(10) 1.291(4)N(2)-C(12) 1.472(2) N(2)-C(12) 1.474(5)C(1)-C(4) 1.451(2) C(1)-C(4) 1.450(5)C(2)-C(3) 1.526(3) C(2)-C(3) 1.518(6)C(4)-C(5) 1.415(2) C(4)-C(5) 1.410(5)C(4)-C(9) 1.405(2) C(4)-C(9) 1.404(5)C(5)-C(6) 1.411(2) C(5)-C(6) 1.404(5)C(6)-C(7) 1.374(2) C(6)-C(7) 1.372(6)C(7)-C(8) 1.391(3) C(7)-C(8) 1.380(6)C(8)-C(9) 1.372(2) C(8)-C(9) 1.370(6)C(10)-C(13) 1.448(2) C(10)-C(13) 1.447(5)C(11)-C(12) 1.526(2) C(11)-C(12) 1.495(6)C(13)-C(14) 1.414(2) C(13)-C(14) 1.411(5)C(13)-C(18) 1.405(2) C(13)-C(18) 1.417(5)C(14)-C(15) 1.409(2) C(14)-C(15) 1.400(5)C(15)-C(16) 1.370(2) C(15)-C(16) 1.373(6)C(16)-C(17) 1.389(3) C(16)-C(17) 1.377(6)C(17)-C(18) 1.372(3) C(17)-C(18) 1.365(6)Table A5. Bond Angles (deg) for VO(oz)2 and VO(thz)2 with Estimated StandardDeviations in Parentheses.VO(Oz)2^ VO(thz)2Atoms^Angle^Atoms^Angle47O(2)-V( 1)-0(5) 108.41(5) 0(2)-V(1)-0(5) 115.2(1)0(4)-V(1)-0(5) 108.81(5) 0(4)-V(1)-0(5) 114.9(1)0(5)-V(1)-N(1) 104.73(6) 0(5)-V(1)-N(1) 99.1(1)0(5)-V(1)-N(2) 103.79(5) 0(5)-V(1)-N(2) 99.4(1)0(2)-V(1)-N(1) 85.28(5) 0(2)-V(1)-N(1) 86.8(1)0(2)-V(1)-N(2) 85.25(5) 0(2)-V(1)-N(2) 86.4(1)0(4)-V(1)-N(1) 85.23(5) 0(4)-V(1)-N(1) 85.5(1)0(4)-V(1)-N(2) 86.21(5) 0(4)-V(1)-N(2) 85.7(1)0(2)-V(1)-0(4) 142.79(5) 0(2)-V(1)-0(4) 129.9(1)N(1)-V(1)-N(2) 151.47(5) N(1)-V(1)-N(2) 161.4(1)C(1)-0(1)-C(2) 106.7(1) C(1)-S(1)-C(2) 91.6(2)V(1)-0(2)-C(5) 129.80(9) V(1)-0(2)-C(5) 133.2(3)C(10)-0(3)-C(11) 107.0(1) C(10)-S(2)-C(11) 90.7(2)V(1)-0(4)-C(14) 130.4(1) V(1)-0(4)-C(14) 134.6(3)V(1)-N(1)-C(1) 125.6(1) V(1)-N(1)-C(1) 127.5V(1)-N(1)-C(3) 125.9(1) V(1)-N(1)-C(3) 118.8(3)C(1)-N(1)-C(3) 108.4(1) C(1)-N(1)-C(3) 113.7(4)V(1)-N(2)-C(10) 126.4(1) V(1)-N(2)-C(10) 128.7(3)V(1)-N(2)-C(12) 125.0(1) V(1)-N(2)-C(12) 117.3(3)C(10)-N(2)-C(12) 108.6(1) C(10)-N(2)-C(12) 113.9(4)0(1)-C(1)-N(1) 116.4(1) S(1)-C(1)-N(1) 115.8(3)0(1)-C(1)-C(4) 116.9(1) S(1)-C(1)-C(4) 119.1(3)N(1)-C(1)-C(4) 126.7(1) N(1)-C(1)-C(4) 125.1(4)0(1)-C(2)-C(3) 104.3(1) S(1)-C(2)-C(3) 107.0(3)N(1)-C(3)-C(2) 103.4(1) N(1)-C(3)-C(2) 110.1(4)C(1)-C(4)-C(5) 119.3(1) C(1)-C(4)-C(5) 121.8(4)C(1)-C(4)-C(9) 120.4(1) C(1)-C(4)-C(9) 120.0(4)C(5)-C(4)-C(9) 120.2(1) C(5)-C(4)-C(9) 118.2(4)0(2)-C(5)-C(4) 123.7(1) 0(2)-C(5)-C(4) 123.6(4)0(2)-C(5)-C(6) 118.7(1) 0(2)-C(5)-C(6) 117.6(4)C(4)-C(5)-C(6) 117.6(1) C(4)-C(5)-C(6) 118.9(4)C(5)-C(6)-C(7) 120.9(2) C(5)-C(6)-C(7) 120.8(4)C(6)-C(7)-C(8) 121.2(2) C(6)-C(7)-C(8) 120.9(4)C(7)-C(8)-C(9) 119.4(2) C(7)-C(8)-C(9) 119.1(4)C(4)-C(9)-C(8) 120.7(2) C(4)-C(9)-C(8) 122.1(4)0(3)-C(10)-N(2) 116.2(1) S(2)-C(10)-N(2) 115.8(3)0(3)-C(10)-C(13) 117.0(1) S(2)-C(10)-C(13) 119.0(3)N(2)-C(10)-C(13) 126.7(1) N(2)-C(10)-C(13) 125.2(4)0(3)-C(11)-C(12) 104.4(1) S(2)-C(11)-C(12) 108.3(3)N(2)-C(12)-C(11) 103.5(1) N(2)-C(12)-C(11) 109.9(4)C(10)-C(13)-C(14) 119.9(1) C(10)-C(13)-C(14) 121.0(4)C(10)-C(13)-C(18) 120.2(1) C(10)-C(13)-C(18) 120.5(4)C(14)-C(13)-C(18) 119.9(1) C(14)-C(13)-C(18) 118.5(4)0(4)-C(14)-C(13) 123.7(1) 0(4)-C(14)-C(13) 123.5(4)0(4)-C(14)-C(15) 118.6(1) 0(4)-C(14)-C(15) 117.7(4)C(13)-C(14)-C(15) 117.8(1) C(13)-C(14)-C(15) 118.7(4)C(14)-C(15)-C(16) 121.0(2) C(14)-C(15)-C(16) 120.9(5)C(15)-C(16)-C(17) 121.1(2) C(15)-C(16)-C(17) 120.8(5)C(16)-C(17)-C(18) 119.4(2) C(16)-C(17)-C(18) 119.9(4)C(13)-C(18)-C(17) 120.8(2) C(13)-C(18)-C(17) 121.2(4)4849Appendix BMillions of people suffer from a mammalian condition known as diabetes. Peoplesuffering from diabetes have an abnormally high level of glucose in their blood plasma.'Diabetes can be life-threatening and can lead to a number of medical complications suchas atheosclerosis, microangiopathy, kidney disorders, renal failure, cardiac disease,diabetic retinopathy and other ocular disorders including blindness.2 There are a variety ofways to control diabetes but the primary method is the daily administering of insulin.Insulin is a hormone that is normally produced naturally in the pancreas and is primarilyresponsible for signaling the utilization or storage of basic nutrients. In general, insulinactivates the enzymes that are involved in intracellular utilization and storage of basicnutrients such as glucose, amino acids and fatty acids.3 It is also involved in the inhibitionof processes which breakdown glycogens, fats and proteins. In diabetic individuals, thereis insufficient insulin present in the body or the body is tolerant to insulin, resulting in thebody requiring an abnormally high dose of insulin to cause the desired effect. The use ofinsulin in treating diabetics involves the daily injection of the hormone. Insulin must beinjected since it is not orally active and is known to decompose before or during passagethrough the gastrointestinal tract.In 1980, it was discovered that vanadate simulated the action of insulin in glucoseoxidation in rat adipocytes.4,5 The years following this discovery revealed that vanadatewas able to mimic nearly all or most of the documented actions of insulin. Interest in theinsulin mimicking action of vanadate rose even higher when McNeill et al reported thatvanadate, administered to diabetic rats through drinking water caused a decrease inelevated blood glucose.6 Unfortunately, vanadate has the disadvantage of being poorlyabsorbed from the gastrointestinal tract. An even greater disadvantage of vanadate is thatit must be administered at near toxic levels before any insulin mimicking effects areobserved. Nevertheless, the work by McNeill et al showed that it may be possible to50utilize orally active vanadium compounds as a substitute for insulin. There has beeninterest in the insulin-mimetic effects of both vanadate and vanadyl since Sakurai et. al.showed that vanadate is reduced in vivo to vanady1.7Recently, our group in collaboration with Dr. McNeill of the Faculty ofPharmceutical Sciences at UBC has been studying the feasibility of usingbis(maltolato)oxovanadium(IV) as an insulin mimicking agent.2 As a continuation of thiswork, the feasibility of bis(kojato)oxovanadium(IV) as an insulin mimic was alsoinvestigated.Bis(kojato)oxovanadium(IV), VO(ka)2, was prepared according to the proceduredescribed in Chapter 2. Initial investigations into the feasibility of using VO(ka)2 asinsulin mimicking agent involved laboratory rats that were made diabetic by the injectionof streptozoticin (STZ). VO(ka)2 was administered by intraperitoneal injection as asuspension in 1% methyl cellulose or orally administered by gavage. Of the diabetic ratswhich were given 0.063 mmol/kg of VO(ka)2 by injection, 60% showed decrease bloodglucose levels within 24 hours. Of the diabetic rats which were given 0.55 mmol/kg ofVO(ka)2 by gavage, 57% showed reduced blood glucose level within 24 hours. Similarexperiments were also carried out using bis(maltolato)oxovanadium(IV), VO(ma)2. Inexperiments involving the administering of VO(ma)2 by injection and by oral gavage, 50%of the rats showed reduced blood glucose level within 24 hours. A higher percentage ofrats responding to the oxovanadium compound was observed with VO(ka)2 compared toVO(ma)2 in both cases when the oxovanadium compound was administered either byinjection or by oral gavage. The results of the studies using VO(ka)2 and VO(ma)2 aresummarized in Table Bl.A drinking water pilot study with VO(ka)2 was also performed on 10 diabetic rats.Administration of VO(ka)2 was done using aqueous solutions in the concentration range of1.43 to 3.58 mM. The rats received doses in the range of 0.41 to 0.91 mmol/kg. Onaverage, a reduced blood glucose level was observed in the diabetic rats. This is51Table B1^Comparison of the plasma glucose levels (mmol/L) between the acute timecourse experiments for bis(maltolato)oxovanadium(IV) (n=8) andbis(kojato)oxovanadium(IV) (n=10)Bis(maltolato)oxovanadium(IV)^Bis(kojato)oxovanadium(IV)I.P. Injection^Oral Gavage^I.P. Injection^Oral Gavage(0.063 mmol/kg) (0.55 mmol/kg)^(0.063 mmol/kg) (0.55 mmoVkg)TIME DTR DTN DTR DTN DTR DTN DTR DTN(Hrs) (50%) (50%) (50%) (50%) (60%) (40%) (57%) (43%)0 17.51 19.42 18.09 19.31 17.94 20.86 15.75 23.08±0.8 ±0.15 ±0.72 ±0.35 ±0.41 ±0.28 ±0.55 ±1.271 14.77 18.82 14.55 18.05 14.75 18.55 12.5 21.18±2.0 ±0.8 ±1.96 ±0.46 ±0.44 ±0.42 ±1.46 ±1.452 12.65 18.51 13.13 17.57 10.17 16.62 10.1 21.51±2.33 ±0.79 ±2.04 ±0.5 ±0.47 ±0.65 ±0.99 ±1.724 10.6 17.94 11.68 16.92 9.26 17.37 7.96 20.57±2.39 ±0.85 ±2.07 ±0.35 ±0.32 ±0.23 ±0.26 ±1.076 10.28 18.08 9.47 16.43 8.73 16.62 6.6 18.2±1.76 ±0.48 ±2.58 ±0.43 ±0.17 ±0.35 ±0.35 ±0.898 9.08 17.77 9.27 15.02 7.4 15.49 6.87 19.06±1.06 ±0.59 ±2.27 ±1.13 ±0.12 ±0.65 ±0.33 ±0.9612 9.38 19.07 7.01 17.17 10.37 18.24 6.01 18.81±0.96 ±0.37 ±0.57 ±0.6 ±0.46 ±0.45 ±0.25 ±00.3324 7.15 19.01 6.31 18.07 13.28 18.77 6.74 25.0±1.51 ±0.21 ±0.57 ±0.74 ±0.83 ±0.49 ±0.05 ±0.4DTR-Diabetic Treated RespondersDTN-Diabetic Treated Non-responder3052.^I^I^15 1 0 1 5Time (Days)120^25Figure Bl. Daily average blood glucose levels for the ten STZ-diabetic rats followingchronic administration of VO(ka)2 in the drinking water. Time 0 is the dayof treatment started.53illustrated in Figure Bl.Initial studies into the feasibility of VO(ka)2 as an orally active insulin mimickingagent have given promising results. It appears that VO(ka)2 gives the same, if not, betterperformance than VO(ma)2 in reducing blood glucose level in diabetic rats. The resultsfrom these preliminary experiments justify more in depth studies into the possibility ofusing VO(ka)2 as an insulin mimicking agent.1) Atkinson, M. A.; Maclaren, N. K. Sci. Am.. 1990, 263, 62-71.2) McNeill, J. H.; Yuen, V. G.; Hoveyda, H. R. ; Orvig, C. J. Med. Chem.. 1992, 35,1489.3) Weyer, R.; Drenn, B. E. Vanadium in Biological Systems Kluwer AcademicPublishers: Norwell, 1990, p. 129.4) Shechter, Y.; Karlish, S. J. D. Nature 1980 , 284, 556-558.5) Dubyak, G. R.; Kleinzeller, A. J. Biol. Chem. 1980, 255 , 5306.6) Heyliger, C. E.; Tahiliani, A. G. ; McNeill, J. H. Science 1985, 227, 1474-1477.7)^Sakurai, H.; Shimomura, S.; Fukuzawa, K.; Ishizu, K. Biochem. Biophys. Res.Commun. 1980, 96, 293-298


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