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

•Novel nickel(II) complexes with the NSAID mefenamic acid were characterized.•The crystal structures of four Ni-mefenamato complexes were determined.•The complexes can bind to human or bovine serum albumins.•The complexes bind to DNA via intercalation.•The complexes show noteworthy antioxidant activity.

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.

Graphical abstractNickel(II) complexes with mefenamato and nitrogen–donor ligands exhibit enhanced antioxidant activity and DNA– and albumin–binding affinity compared to free mefenamic acid.Figure optionsDownload full-size imageDownload as PowerPoint slide