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Authors: Kumar, Amit
Issue Date: 2006
Abstract: Vanadium is atrace element that occurs in concentrations ranging from 0.1 to 3 nmol/g in the most mammalian cells. Its concentration is about 136 ppm in the earth's crust and is nineteenth element in the order of abundance. Vanadium has been reported to be an essential bio-element for certain organisms, including tunicates, bacteria and some fungi. The physiological role of vanadium is not known but its importance has been indicated for the normal growth and development. The role of vanadium in biochemistry has attracted attention for the last two decades. It could be used as inhibitor for nucleases and phosphatases. Vanadium was widely used as a therapeutic agent in the late I8lh century, treating a variety of disease including anemia, tuberculosis, rheumatism and diabetes. Several nutritional studies have revealed that the deficiency of vanadium may impediment the proper growth and development of chick and rat. Vanadium with atomic number 23 and electronic configuration [Ar]3d34s2, can exits in at least six oxidation states. Oxidation states +IV and +V are generally stabilized through V-0 bond, and oxocations [VO]2+, [VO]3+ and [V02]+ are most common for biological systems. Vanadium chemistry has attracted attention of scientists worldwide due to its medicinal interest. The vanadium(IV) state is proposed to be apossible active form of vanadium in mimicking or enhancing insulin action by interacting with the glucose transporter. Thus, several types of neutral and low molecular weight vanadium(IV) complexes with organic ligands have been designed and investigated in animal model systems for the treatment of diabetes. The presence of vanadium in vanadium based enzymes e.g. vanadatedependent haloperoxidases and vanadium nitrogenases attracted attention of researchers to develop coordination chemistry of vanadium in search of good models for these enzymes. In fact, the development of structural and functional model complexes of vanadium haloperoxidases is the key motive of vanadium coordination chemistry. Several compounds have been reported but still scientists are in search of new mimic having more efficacy. Vanadium complexes have also been found to catalyze the oxidation and epoxidation of various organic substrates. Studies on the ill metabolism and detoxification of vanadium compounds under physiological conditions, stability as well as speciation of vanadium complexes in biofluides have further influenced the coordination chemistry of vanadium. 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 in oxidation states IV and V. The present thesis is, therefore, aimed to describe the coordination chemistry of vanadium with biologically relevant ligands. Their characterization, stability and reactivity studies have been carried out. Some of the complexes reported in second and third chapter can be considered to be structural models of haloperoxidases. The model character also extends to functional similarities, in that they catalyse the oxidation, by oxidant, of sulfoxide, styrene, cyclohexene, phenol, trans-stilbene etc. Some of the complexes have also been tested for their antiamoebic activity. For convenience, the present thesis has been divided into four chapters. The first chapter is introductory one and deals with the historical overview of vanadium chemistry developed during the past three decades and their potential biological, medicinal and catalytic aspects. Second chapter is based on the model character of vanadium haloperoxidases. Thus, reaction between [VO(acac)2] and the ONN donor Schiff base Hsal-ambmz (I) (Hsal-ambmz = Schiff base obtained by the condensation of salicylaldehyde and 2-aminomethylbenzimidazole) resulted in the formation of the complexes [VlvO(acac)(sal-ambmz)] (1), [Vv02(acac-ambmz)] (2) (Hacac-ambmz = Schiff base derived from acetylacetone and 2-aminomethylbenzimidazole) and the known complex [VlvO(sal-phen)] (3) (M2sal-phen =Schiff base derived from salicylaldehyde and o-phenylenediamine). Similarly/[VlvO(acac)(sal-aebmz)] (7) has been isolated from the reaction with Hsal-aebmz (II) (Hsal-aebmz derives from salicylaldehyde and 2-aminoethylbenzimidazole). Aerial oxidation of the methanolic solutions/suspensions of1and 7 yielded the dioxovanadium(V) complexes [V02(salambmz)] (4) and [V02(sal-aebmz)] (8), respectively. Reaction ofVOS04 with II gave [{VlvO(sal-aebmz)}2S04] (9) and [VlvO(sal-aebmz)2] (10) along with 3and 8. Under IV similar reaction conditions, I gave only [{VIV0(sal-ambmz)}2S04] (5) and 3as major products. Treatment of1and 7with benzohydroxamic acid (Hbha) yielded the mixed chelate complexes [VvO(bha)(sal-ambmz)] (6) and [VvO(bha)(sal-aebmz)] (11). The crystal and molecular structures of 2, 3Y2DMF, 7-lAH20, 8, 9-2H20, 10 and 11 have been determined, confirming the ONN binding mode of the ligands. In complex 10, one of the ligands is coordinated through the azomethine nitrogen and phenolate oxygen only, leaving the benzimidazole group free. In the dinuclear complex 9, bridging functions are the phenolate oxygens from both of the ligands and two oxygens of the sulfato group. The unstable oxoperoxovanadium(V) complex [VvO(02)(sal-aebmz)] (12) has been prepared by treatment of 7with aqueous H202, the formation ofwhich has also been monitored spectrophotometrically. Acidification of methanolic solutions of 7 and 10 lead to (reversible) protonation of the bemzimidazole, while 8 was converted to an oxo-hydroxo species. Complexes 2, 4 and 8 catalyze the oxidation ofmethyl phenyl sulfide to methyl phenyl sulfoxide and methyl phenyl sulfone, a reaction mimicking the sulfideperoxidase activity of vanadate-dependent haloperoxidases. These complexes are also catalytically active in the oxidation of styrene to styrene oxide, benzaldehyde, benzoic acid and 1- phenylethane-1,2-diol. Amoebosis is chronic disease and thousands ofpeople die every year from this epidemic. Metronidazole (MNZ) is an important drug which is commercially available in the market and being used to control and cure for this epidemic. But this causes neurological alterations due to interaction of the drug with the central nervous system. According to the International Agency for Research on Cancer (IARC), metronidazole is classified in the 2B group, i.e. potentially carcinogenic to humans, and proved carcinogenic to animals. In search of novel vanadium complexes with pharmacologically interesting properties, chapter third deals with the synthesis and characterization of neutral dioxovanadium (V) complexes of the type [V02(HL)] (H2L = I: 1, H2L = II: 3, H2L = III: 5, H2L = IV: 7, and fl2L - V: 9; H2L are H2pydxsbdt, I, H2pydx-smdt, II H2pydx-tsc (III), H2pydx-chtsc (IV) and H2pydx-clbtsc (V); pydx = pyridoxal, sbdt = S-benzyldithiocarbazate, smdt = S-methyldithiocarbazate, tsc = thiosemicarbazide, chtsc = N4-cyclohexylthiosemicarbazide and clbtsc = N4-(2-chloro)benzylthiosemicarbazide ). Heating of the methanolic solutions of these complexes yield the oxo-bridged binuclear complexes [{VO(pydx-sbdt)}2//-0] (2), [{VO(pydx-smdt)}2/y-0] (4), [{VO(pydx-tsc)}2/u-0] (6), [{VO(pydx-chtsc)}2/y-0] (8) and [{VO(pydx-clbtsc)}2//-0] (10). The crystals and molecular structures of 1, 31.5H20 and 4-2CH3OH have been determined, confirming the ONS binding mode of the dianionic ligands in their thioenolate form. The ring nitrogen of the pyridoxal moiety is protonated in complexes of the type [V02(HL)] (H2L = ligand). On acidification of [V02(HL)] with HC1 dissolved in methanol afforded oxohydroxo complexes, while in methanolic KOH solution, the corresponding dioxo species K[V02(HL)] are formed. Treatment with H202 yields (unstable) oxoperoxovanadium(V) complexes, the formation of which has been established spectrophotometrically. In vitro antiamoebic activities (against HML1MSS strain of Entamoeba histolytica) were established for all of the dioxo- and oxovanadium (V) complexes. The complexes 1, 2, 4, 5, 6, 7, 8, 9 and 10 were more effective than metronidazole, suggesting that oxovanadium (V) complexes may open a new dimension in the therapy of amoebiasis. Within the series, complex 8 showed the most promising amoebicidal activity (/C50 = 0.5 /M versus 7C50 = 1.8 of metronidazole). Fourth chapter describes the catalytic applications of vanadium complexes in oxidation reactions. Five polymeric oxovanadium(IV) complexes, [-CH2{VO(salen)}- ]„ (1), [-CH2{VO(sal-l,2-pn)Hn (2), [-CH2{VO(sal-l,3-pn)}-]n (3), [>CH2{VO(saldach). DMF}-]n (4) and [-S2{VO(sal-dach).DMF}-]n (5) of the polymeric Schiff bases derived from 5,5'-methylebis(salicylaldehyde)[CH2(Hsal)2] or 5,5'- dithiobis(salicylaldehyde) )[S2(Hsal)2] and 1,2-diaminoethene (en), 1,2- diaminopropane (1,2-pn), 1,3-diaminopropane (1,3-pn) and 1,2-diaminocyclohexane (1,2-dach) have been isolated and characterized by various physico-chemical techniques. All these complexes are insoluble in common solvents and are paramagnetic. IR spectral data confirm the coordination of ligands through the azomethine nitrogen and the phenolic oxygen atoms to the metal ion. EPR spectra of VI these complexes reveal paramagnetic nature of the complexes, and anisotropic axial patterns and the Hamiltonian parameters predict a square pyramidal geometry around vanadium ions in these complexes. Complexes 1, 2 and 3 exhibit good catalytic activity towards the liquid phase hydroxylation of phenol into a mixture of catechol and hydroquinone using H202 as oxidant. Under the optimized reaction conditions, the selectivity towards the formation of catechol and hydroquinone are about 90 - 98 and 2-10 %, respectively. Oxidative bromination of salicylaldehyde using these complexes range between 83 - 86 % with ca. 95 % selectivity towards 5- bromosalicylaldehyde. Complexes 4 and 5 exhibjt good catalytic activity towards the oxidation of styrene, cyclohexene and /ra/is-stilbene using terf-butylhydroperoxide as an oxidant. Concentration of the oxidant and reaction temperature has been optimised for the maximum oxidation of these substartes. Under the optimized conditions, oxidation of styrene gave a maximum of 76 % (with 4) or 85 % (with 5) conversion having following products in order of selectivity: benzaldehyde > styreneoxide > 1- phenylethane-l,2-diol > benzoic acid. A maximum of 98 % conversion of cyclohexene was obtained with both the catalysts where selectivity of cyclohexeneoxide varied in the order: 5 (62 %) > 4(45 %). With the conversion of 33 % (with 4) and 47 % (with 5), oxidation of tows-stilbene gives benzaldehyde, benzil and fra«s-stilbeneoxide as major products.
Other Identifiers: Ph.D
Appears in Collections:DOCTORAL THESES (chemistry)

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