Nickel(II) complexes of the non-steroidal anti-inflammatory drug tolfenamic acid: Synthesis, structure, antioxidant activity and interaction with albumins and calf-thymus DNA

Abstract

The reaction of NiCl2·6H2O with the non-steroidal anti-inflammatory drug tolfenamic acid (Htolf) in the absence or presence of a nitrogen-donor heterocyclic ligand such as 2,2′-bipyridine (bipy), 1,10-phenanthroline (phen), 2,2′-bipyridylamine (bipyam), 2,2′-dipyridylketone oxime (Hpko) and pyridine (py) led to the formation of six novel Ni(II) mononuclear complexes. The complexes were characterized by physicochemical and spectroscopic techniques and the crystal structures of complexes [Ni(tolf-O)2(bipy)(MeOH)2], 2 and [Ni(tolf-O)2(Hpko-N,N′)2], 5 were determined by X-ray crystallography. The in vitro investigation of the ability of the complexes to scavenge 1,1-diphenyl-picrylhydrazyl, 2,2′-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) and hydroxyl radicals and to inhibit soybean lipoxygenase revealed their potential antioxidant activity. The interaction of the complexes to calf-thymus DNA was monitored by diverse techniques (UV spectroscopy, cyclic voltammetry, viscosity measurements) revealing intercalation as the most possible mode of binding. Competitive studies of the complexes with ethidium bromide were monitored by fluorescence emission spectroscopy. The interaction of the complexes with serum albumins was studied by fluorescence emission spectroscopy and the binding constants of the compounds to the albumins were calculated.