Nickel(ii)–naproxen mixed-ligand complexes: synthesis, structure, antioxidant activity and interaction with albumins and calf-thymus DNA

Abstract

The nickel(II) complexes with the non-steroidal anti-inflammatory drug naproxen (Hnap) were prepared in the absence or presence of the nitrogen-donor heterocyclic ligands 2,2′-bipyridine (bipy), 1,10-phenanthroline (phen), 2,2′-bipyridylamine (bipyam), 2,2′-dipyridylketone oxime (Hpko) or pyridine (py) and were characterized by diverse techniques. The crystal structures of complexes [Ni(nap-O)(nap-O,O′)(bipy)(MeOH)], 2 and [Ni(nap-O)(nap-O,O′)(phen)(H₂O)] 3 were determined by X-ray crystallography. The antioxidant activity of the complexes was evaluated in vitro by examining their ability to scavenge 1,1-diphenyl-picrylhydrazyl, 2,2′-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) and hydroxyl radicals and to inhibit soybean lipoxygenase. The ability of the complexes to intercalate to calf-thymus DNA was monitored by diverse techniques (UV-vis spectroscopy, cyclic voltammetry, viscosity measurements) and competitive studies with ethidium bromide. The interaction of the complexes with serum albumins was studied by fluorescence emission spectroscopy and the corresponding binding constants were calculated. The bio-activity of the complexes was compared to previously reported metal–naproxen complexes and the structural factors responsible for enhanced activity are discussed.