STUDIES ON OXO-, DIOXO- AND OXOPEROXOVANADIUM(V) COMPLEXES OF POLYDENTATE LIGANDS

Abstract

Vanadium is believed to be a trace element in most higher animals and known to be essential to some organisms, including tunicates and mushrooms(^4wa«/7fl muscaria). The structural analogy between vanadate (H^O/junder physiological conditions) and phosphate (HP042) possibly is the basis for many regulatory, inhibitary and stimulating functions of vanadium towards phosphate metabolising. In addition, vanadate-dependent haloperoxidases and nitrogenases are currently the only enzymes which require vanadium for catalytic activity. Haloperoxidases catalyze the oxidation of a halide (i.e. chloride, bromide or iodide) by hydrogen peroxide, which results in the halogenation of organic substates. Enzyme nitrogenase catalyzes the reduction of atmospheric N2 to NH3. Vanadium bromoperoxidase (V-BrPO) has been isolated from many species of marine algae and terrestrial lichen. Vanadium-chloroperoxidase (V-CIPO) has recently been discovered in terrestrial fungi. The active site structures of the vanadate-dependent haloperoxidase have been revealed by X-ray diffraction studies. Accordingly, vanadium ion (in oxidation V) is in an 04N-coordination and is distorted towards a trigonal pyramid, thus providing the fifth coordination site, which is coordinated to the imine nitrogen atom of the histidine. The coordination ofthe amine nitrogen ofhistidine to Vivn in the V-Fe cofactor ofthe Mcluster of vanadium-nitrogenase from azotobacter has also been confirmed. In vanadiumnitrogenase, homocitrate and three bridging sulphides further complement the coordination sphere. Sulphur coordination through cysteinate has also been observed in vanadate-derivatised tyrosine phosphatase. The X-ray structures of the peroxide form of V-CIPO reveals a distorted tetragonal pyramid geometry in which vanadium(V) is coordinated by peroxide in an n2 fashion, by histidine nitrogen atom and an oxygen atom at the basal plane, and by an oxo ligand in the axial position. Ill The coordination chemistry of vanadium has attracted increasing interest during the last few years, due to the model character of many vanadium complexes for the biological functions of vanadium. Catalytic activity and therapeutic applications such as the treatment of the diabetes types I(insulin deficiency) and II(insulin resistance) of vanadium complexes have further stimulated the coordination chemistry of vanadium . Aconsiderable amount of work dealing with the solid state and solution studies on the structure of vanadium coordination compounds has been carried out which model: (i) the vanadium binding sites in enzymes, the geometrical and electronic aspects of vanadium coordination of biogenic molecules and (ii) the function of vanadium in its active domains. Oxovanadium(IV) and vanadates(V) are mainly present in biofluids under physiological conditions and these bind with low molecular mass components present in biofluids. Enzymes such as xylose, isomerase, ribonuclease(Rnase), adenosinetriphosphatase(Atpase), carboanhydrase, glyceraldehyde-3-phosphate dehydrogenase etc. all coordinate to oxovanadium(IV) and oxovnadium(V). The interaction of peptide and oligopeptides with these metal ions in solution has also been reported. Model complexes have also isolated and studied to understand the interaction of vanadate and vanadyl ions with protein and peptides. All these clearly indicate that the coordination chemistry of vanadium is of increasing potential interest and it was considered desirable to study the coordination chemistry of vanadium. The present thesis is, therefore, aimed to describe the coordination chemistry of vanadium with biologically relevant ligands in biologically relevant oxidation states. Stability, structural and reactivity studies have been carried out to model the role of vanadium in vanadium based enzymes e.g. vanadate-dependent haloperoxidases and nitrogenase. For convenience the work embodied in the thesis is presented in the following chapters: IV First chapter of the thesis is introductory one, dealing with the general remarks on vanadium found in naturally occurring system and interaction of vanadium with proteins/peptides, biofluids and enzymes. Applications of vanadium complexes and literature on model studies and general coordination chemistry of vanadium have been also included. Second chapter described the isolation of dioxovanadium(V) complexes M[V02(L)so/v] (2, 5, 6) along with dimeric, oxo-bridged monooxovanadium complexes of composition [{VOL}2u-0] (1, 4), and characterisation by their spectral and thermogravimetric properties and reactivity patterns. H2L is the hydrazone H2[(R-sal)-INH] (sal derives from salicylaldehyde (R = H) or p-Clsalicylaldehydehyde (R = CI)) or H2hap-INH, where hap is the o-hydroxyacetophenone moiety, and INH stands for isonicotinic acid hydrazide. In the isolated potassium (M = K) complexes 2a, 5 and 6, solv is a water molecule, which is exchanged, as evidenced by 51V NMR, by methanol or DMSO in the respective solutions. Treatment of the dimeric (1 and 4) or anionic complexes (2a and 5) with H202 yields (unstable) oxo-peroxovanadium complexes K[VO(02)L] (7, 8). Acidification of 1 and 4 affords oxo-hydroxo complexes. 2a dissolved in methanol partly deoxygenises to form [VO(OMe)(HOMe)L] (9), the crystal and molecular structures of which have been determined, confirming the ONO binding mode of L in its enolate form. Oxoanadium(V) complexes, [VOL(hq)] (1 - 4), prepared by the reaction of [VO(acac)2] and ligands LH2 in the presence of 8-hydroxyquinoline (Hhq) are described in the third chapter. LH2 is the dibasic tridentate ONO Manmch base (X-H2glysal, S-H2alasal, S-H2leusal and .V-H2ileusal), obtained by the reduction of the Schiff bases of salicylaldehyde and amino acids, glycine, DL-alanine, leucine and isoleucine, respectively. Spectral studies favour an octahedral structure for these complexes. These complexes exhibit a single 51V NMR signal due to the existence ofa single isomeric species in solution. The complexes 1 (as = glycine) and 4(as =isoleucine) show reversible redox behaviour in the presence of Lascorbic acid in air, as monitored by electronic absoiption studies. Synthesis, characterisation and reactivity of oxo, -dioxo, and oxoperoxovanadmm(V) complexes of biomimetic ONN hydrozonate ligands are described in the fourth chapter. [VO(acac)2] reacts with ligands LH (LH is the hydrazone Hacpy-INH, where acpy derives from acetylpyridine and INH stands for isonicotimc acid hydrazide or Hacpy-BHZ where BHZ is benzoylhydrazide) in dry methanol to give [VO(acac)L] (1, 3) winch on aerial oxidation gives dioxovanadmm(V) complexes [V02L] (2, 4). Treatment of oxovanadium(IV) complexes (1 and 3) or dioxovanadium(V) complexes (2 and 4) with H202 yields oxoperoxovanadium(V) complexes [VO(02)L] (5, 6). In presence of catechol or benzohydroxamic acid 1and 3gives mixed chelate complexes [VOL(cat)] (7,8) or fVOL(bha)] (9, 10). The peroxo complexes 5, and 6undergo oxygen transfer reaction with PPh3 in DMF. Stability of mixed chelate complexes, 7, 8, 9and 10 in dry and wet DMF/DMSO indicates the slow conversion into the correspndmg dioxo species. Acidification of 2and 4affords oxo-hydroxo complexes while reaction of 7with L-ascorbic acid shows its reduction with the removal of catechol and then reoxidation to the corresponding dioxo species. Fifth chapter deals with vanadium complexes having [VO]2t [VO]3+- [V02]+ and [VO(02]+ cores with the ligands derived from 2-acetyl pyridine and Sbenzyldithiocarbazate (Hacpy-SBDT) or S-methldithiocarbazate (Hacpy-SMDT). The dioxovanadium(V) complexes [V02L] (2, 5)(LH =ligand) were isolated by the reaction between ligand and the oxidized solution of [VO(acac)2] ,n presence of air and KOH in dry methanol while reaction of Hacpy-SMDT with the above oxidized species in wet methanol gave malonato coordinated complex [VO(acpy- SMDTXmalonate)] (6). Under anaerobic reaction condition [VO(acac)2] and ligands gave monoacetylacetonato cordinated oxovandium(IV) complexes [VO(acac)L](l, 4). Treatment of these complexes with H202, catechol or benzohydroxamic acid yielded oxoperoxo vanadium complexes [VO(02)L] (3, 7), v VI catecholate coordinated complexes [VOL(cat)] (8, 9) or benzohydroxamate coordinated complexes [VOL(bha)] (10, 11), respectively. Acidification of 2 with HC1 dissolved in methanol affords oxo-hydroxo complex. Complexes 8 and 11 undergo reduction in presence of L-ascorbic acid in air. These reduced species slowly oxidize to the corresponding dioxo complexes 2 and 5, respectively. The crystal structures of 2 and 6 have been determined, confirming NNS binding mode of both the ligands and malonate coordination in 6.