Coordination Complexes of Vanadium Featuring O-N-O and O-N-S Donor Ligands: Study of Reactivity and Solution Behavior

Abstract

The presence of transition metals in our body in form of metallo-proteins and metallo-enzymes has motivated researchers to find its potential in field of pharmaceutical industry. Among the transition metals, the chemistry of vanadium and its complexes has become a fascinating area of research after the discovery of vanadium as a bio-essential element and its presence in many naturally occurring compounds. It has stimulatory effect on the growth of algae and plants, participating in various enzymatic reactions like, the inhibitory action of vanadate(V) on Na, K-ATPase, haloperoxidases and some nitrogenases in nitrogen-fixing Azotobacter. Vanadium is also under research for its probable anti-cancer therapeutics due to its long proven insulin-like behavior and reported reduction of hyperlipidemia and hypertension to suppress tumor cell growth. Keeping these factors in mind, in this dissertation the chemistry of a wide variety of new versatile variable valence mono-/di-nuclear non-oxido and oxido vanadium(IV/V) complexes of some tridentate binegative ONO or ONS donor Schiff base as main and neutral N,N-donor as co-ligand systems are reported, with special reference to their pharmacological activity and solution property. All the synthesized ligands and their corresponding metal complexes have been successfully characterized by several physicochemical (elemental analysis), spectroscopic (UV-vis, IR, NMR and EPR), spectrometric (ESI‒MS) and electrochemical (cyclic voltammetry) methods. The exact geometry of the complexes was further confirmed by single crystal X-ray diffraction (SC-XRD) analysis. In order to get additional information, molecular structure and spectroscopic properties such as UV-vis and EPR of some of the above complexes was simulated by DFT (density functional theory) methods. With a view to evaluate the biological activity, interaction with DNA and several proteins (HSA, BSA, cytochrome c, ubiquitin and lysozyme) through analytical and molecular docking approaches and in vitro antiproliferative activity against different cancer cell lines [ovarian (A2780), prostate (PC3), cervical (HeLa) and colon (HT-29)] as well as non-cancerous cell lines [mouse embryonic fibroblast (NIH-3T3) and normal fibroblasts (V79)] of some of the above complexes was studied. The results indicated that some of the complexes showed significant binding affinity towards both DNA and proteins. In vitro antiproliferative activities of the studied complexes reveal them to be potential lead molecules for drug designing and also the complexes studied herein showed similar, or in some cases improved in vitro cytotoxicity (IC50 values in the range 1.1−42.7 μM) as compared to the various clinically reported prevalent chemotherapeutic drugs. Apart from that, the solution behavior of the synthesized mono- and di- nuclear vanadium(IV/V) compounds has also been studied in order to understand their transformation, interconversion, changes in coordination geometry, nuclearity and redox processes and mode of interaction with the biological systems and mechanistic action under physiological conditions which were not explored earlier. Finally, a plausible mechanism of such solution behavior has also been discussed in details.