SYNTHESIS, CHARACTERISATION AND POTENTIAL APPLICATION OF VANADIUM COMPLEXES

Abstract

Vanadium with atomic number 23 and electronic configuration [Ar]3d 4s , is a soft and silvery gray ductile transition metal. Concentration of vanadium is about 136 ppm in the earth's crust and is nineteenth element in the order of abundance. It is also present at very low concentrations (<10 M) in the cells of plants and animals. Metallic vanadium is not found in nature, but is known to exist in about 65 different minerals. 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. Vanadium exhibits formal oxidation states from +V down to -III. The most stable oxidation states +IV and +V under normal conditions are generally stabilized through V-0 bond and oxocations [VO] , [VO]3+ and [V02]+ are most common for biological systems. Vanadium in these oxidation states comfortably binds with O, N and S donor ligands. Much attention was focused on oxovanadium(IV) complexes in mid 70s. The discovery of vanadium(V) in vanadium based enzymes in 90s, e.g., vanadate-dependent haloperoxidases and vanadium nitrogenase attracted attention of researcher to develop coordination chemistry of vanadium(V) in search of good models for vanadium-containing biomolecules. Studies on the metabolism and detoxification of vanadium compounds under physiological conditions, their stability and speciation in biofluids have further influenced the coordination chemistry of vanadium with multidentate ligands. Medicinal aspects of vanadium compounds were increased with the discovery of insulin-mimetic, antituberculosis and antiamoebic properties of vanadium complexes. Vanadium(IV) and vanadium(V) salts have been extensively tested both in vivo and in vitro in a considerable variety of experimental models of diabetes. A significant effect on the antitumor ii activity of the vanadium complexes by structural modifications on the semicarbazone moiety has been indicated. Recently, several papers have also appeared in the literature on the potential application of vanadium complexes as catalysts for different oxidation reactions [whole issue of Coord. Chem. Rev., 2Z1 (2003) and an issue of Pure Appl. Chem., 81(2009)]. In view of the above it may clearly be conceived that the coordination chemistry of vanadium is of increasing potential interest and therefore was considered desirable to study the coordination chemistry of vanadium that would provide: (i) structural and functional models of haloperoxidases, and (ii) medicinal as well as catalytic potentials. The present thesis is therefore, aimed to describe the coordination chemistry of vanadium considering biologically important 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. The isolated complexes have been screened for their potential catalytic and medicinal applications. For convenient the work embodied in the thesis has been divided into following chapters: First chapter is introductory one and deals with the general remarks on vanadium, their occurrence in nature and biological systems. Applications of vanadium complexes in different areas (biological, medicinal and catalytic) and literature on model studies as well as general coordination chemistry have also been included. The synthesis of dinuclear oxidovanadium(IV) and dioxidovanadium(V) complexes of two hydrazones {CH2(H2sal-nah)2, 2.1} and {CH2(H2sal-inh)2, 2.11} derived from 5,5'-methylenebis(salicylaldehyde) {CH2(Hsal)2} and nicotinic acid hydrazide (nah) or isonicotinic acid hydrazide (inh) is described in second chapter. The compounds are characterized in the solid state and in solution, namely by spectroscopic techniques (IR, UV-Vis, EPR, 'H, l3C and 5IV NMR). It has been demonstrated that the oxidovanadium(IV) complexes [CH2{VIV0(sallii nah)(H20)}2] (2.1) and [CH2{VlvO(sal-inh)(H20)}2] (2.2) are catalyst precursors for the catalytic oxidation, by peroxide, of methyl phenyl sulfide and diphenyl sulfide, yielding the corresponding sulfoxide and sulfone. It has also been shown that the dioxidovanadium(V) complexes K2[CH2{Vv02(sal-nah)}2]-2H20 (2.3), Cs2[CH2{Vv02(sal-nah)}2]-2H20 (2.4) and Cs2[CH2{Vv02(sal-inh)}2]-2H20 (2.5) of 2.1 and 2.II are active in the oxidative bromination of salicylaldehyde, by H202, therefore acting as functional models of vanadium dependent haloperoxidases. Plausible intermediates involved in these catalytic processes are established by UV-Vis, EPR and 51V NMR studies. The dioxidovanadium(V) complexes along with ligands 2.1 and 2.II were also screened against HM1:1MSS strains of Entamoeba histolytica, the results showed that the IC50 value of compound 2.3 and 2.5 are less than the IC50 value of metronidazole. The toxicity studies against human cervical (HeLa) cells line showed that the compounds 2.3 and 2.5 are toxic as compared to metronidazole. Third chapter describes the interaction of binucleating hydrazones CH2(H2sal-bhz)2 (3.1) and CH2(H2sal-fah)2 (3.II), derived from 5,5'- methylbis(salicylaldehyde) and benzoylhydrazide or 2-furoylhydrazide with [VIV0(acac)2] to give dinuclear VlvO-complexes [CH2{VIV0(sal-bhz)(H20)}2] 3.1 and [CH2{VlvO(sal-fah)(H20)}2] (3.4), respectively. In the presence of KOH or CsOHH20, oxidation of (3.1) and (3.4) results in the formation of dioxidovanadium(V) complexes, K2[CH2{Vv02(sal-bhz)}2]-2H20 (3.2), K2[CH2{Vv02(sal-fah)}2]-2H20 (3.5), Cs2[CH2{Vv02(sal-bhz)}2]-2H20 (3.3) and Cs2[CH2{Vv02(sal-fah)}2]-2H20 (3.6). These complexes have also been prepared by aerial oxidation of in situ prepared oxidovanadium(IV) complexes 3.1 and 3.4. The compounds were characterized by IR, electronic, EPR, H, C and V NMR spectroscopy, elemental analyses and thermogravimetric patterns. Single crystal X-ray analysis of Cs2[CH2{Vv02(sal-bhz)}2]-2H20 (3.3) confirms the coordination of the ligand in the dianionic (ONO2) enolate tautomeric form. The IV Vv02-complexes were used to catalyze the oxidative bromination of salicylaldehyde, therefore acting as functional models of vanadium dependent haloperoxidases, in aqueous H202/KBr in presence of HC104 at room temperature. It has been shown that the VlvO-complexes [CH2{VIV0(sal-bhz)(H20)}2] (3.1) and [CH2{VlvO(sal-fah)(H20)}2] (3.4) are catalyst precursors for the catalytic oxidation of organic sulphides using aqueous H202. Plausible intermediates involved in these catalytic processes have been established by UV-Vis, EPR and 51V NMR studies. The vanadium complexes along with ligands CH2(H2sal-bhz)2 (3.1) and CH2(H2sal-fah)2 (3.II) have also been screened against HM1:1MSS strains of Entamoeba histolytica, the results showing that the IC50 values of compounds Cs2[CH2{Vv02(sal-bhz)}2]-2H20 (3.3) and Cs2[CH2{Vv02(salfah)} 2]-2H20 (3.6) are lower than that of metronidazole. The toxicity studies against human cervical (HeLa) cancer cell line also showed that although compounds 3.3 and 3.6 are more toxic than metronidazole towards this cell line, the corresponding IC50 values are relatively high, the cell viability therefore not being much affected. Syntheses of dinuclear oxidovanadium(IV) and dioxidovanadium(V) complexes of two thiohydrazones {CH2(H2sal-sbdt)2, 4.1} and {CH2(H2sal-smdt)2, 4.11} derived from 5,5'-methylenebis(salicylaldehyde) {CH2(Hsal)2} and Sbenzyldithiocarbazate (sbdt) or S-methyldithiocarbazate (smdt) have been described in Chapter 4. Reactions of [VO(acac)2] with CH2(H2sal-sbdt)2 or CH2(H2sal-smdt)2 in 2:1 molar ratio in refluxing methanol gave the dinuclear oxidovanadium(IV) complexes [CH2{VO(sal-sbdt)(H20)}2] (4.1) and [CH2{VO(sal-smdt)(H20)}2] (4.2), respectively. Oxidation of [CH2{VO(salsbdt)( H20)}2] and [CH2{VO(sal-smdt)(H20)}2] in the presence KOH or CsOH gave the corresponding dioxidovanadium(V) species K2[CH2{V02(salsbdt) 2}]-2H20 (4.3), Cs2[CH2{V02(sal-sbdt)2}]-2H20 (4.4), K2[CH2{V02(salsmdt) 2}]-2H20 (4.5) and Cs2[CH2{V02(sal-smdt)2}]-2H20 (4.6), respectively. These complexes can also be isolated directly by the reaction of [VO(acac)2] with CH2(H2sal-sbdt)2 or CH2(H2sal-smdt)2 in 2:1 ratio in refluxing methanol followed by aerial oxidation in the presence of corresponding hydroxides. These compounds have been characterized in the solid state and in solution by spectroscopic techniques (IR, UV-Vis, 'H, and 5IV NMR). Complexes Cs2[CH2{V02(sal-sbdt)2}]-2H20 (4.4), Cs2[CH2{V02(sal-smdt)2}]-2H20 (4.6) have been used as catalysts for the oxidation and oxidative bromination of organic substrates in the presence of H202. Reactivity of these complexes with H202 and HCl has been studied to obtained possible intermediate involved in catalytic reactions. Oxidovanadium(IV) and dioxidovanadium(V) complexes along with ligands 4.1 and 4.II have also screened against HM1:1MSS strains of Entamoeba histolytica and results showed that metallation of ligands reduced the IC50 value considerably and all dioxidovanadium(V) complexes have IC50 value much less than the IC50 value of metronidazole.