Synthesis, structure and biological activity of nickel(II) complexes with mefenamato and nitrogen-donor ligands

Abstract

Six novel nickel(II) complexes with the non-steroidal anti-inflammatory drug mefenamic acid (Hmef) with the nitrogen-donor heterocyclic ligands 2,2′-bipyridine (bipy), 2,2′-bipyridylamine (bipyam), 1,10-phenanthroline (phen), 2,2′-dipyridylketone oxime (Hpko) or pyridine (py) and/or the oxygen-donor ligands CH3OH or H2O were synthesized and characterized by physicochemical and spectroscopic techniques. The crystal structures of [Ni(mef-O)2(bipy)(CH3OH)2] (1), [Ni(mef-O)2(phen)(CH3OH)2] (2), [Ni(mef-O,O′)2(bipyam)] (3) and [Ni(mef-O)2(Hpko)2]∙CH3OH (4·CH3OH) were determined by X-ray crystallography. The ability of the complexes to scavenge 1,1-diphenyl-picrylhydrazyl, 2,2′-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) and hydroxyl radicals was investigated and the in vitro inhibitory activity against soybean lipoxygenase was evaluated; complexes 3 and 4 were the most active compounds. Spectroscopic (UV and fluorescence), electrochemical (cyclic voltammetry) and physicochemical (viscosity measurements) techniques were employed in order to study the binding mode of the complexes to calf-thymus (CT) DNA and to calculate the corresponding binding constants; for all complexes, intercalation was the most possible mode of DNA-binding. The interaction of the complexes with serum albumins was studied by fluorescence emission spectroscopy and the values of the albumin-binding constants were determined.