Nickel(II) coordination compounds of 4'-chloro-fenamic acid: characterization and biological activity.

Abstract

With the aim of investigating whether the coordination of fenamates to Ni(II) affects the biological profile, a chloro-derivative of fenamic acid (4'-chloro-fenamic acid) was synthesized and used as a ligand for the synthesis of seven nickel(II) complexes in the absence or presence of the nitrogen-donors pyridine, β-picoline, 1H-imidazole, 1,10-phenanthroline, 2,9-dimethyl-1,10-phenanthroline, and 2,2'-bipyridylamine. The characterization of the resultant Ni(II) complexes was performed with diverse techniques (elemental analysis, molar conductivity measurements, mass spectrometry, IR and UV-vis spectroscopy, and single-crystal X-ray crystallography). The compounds were evaluated for their in vitro biological activity in terms of the antioxidant activity via free radical scavenging and H₂O₂ reduction, the antimicrobial activity against two Gram-positive and two Gram-negative bacterial strains, the interaction with calf-thymus DNA, the cleavage of supercoiled pBR322 plasmid DNA (pDNA) in the dark or under UVB/UVA/visible light irradiation, and the binding affinity toward bovine and human serum albumins. The antioxidant activity of the compounds is noteworthy against 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) radicals and H₂O₂, and comparable with that of the reference compounds. The complexes exhibit notable antimicrobial activity against the strains tested. The compounds interact with calf-thymus DNA via intercalation with binding constants of 10⁵-10⁶ M^-1 magnitude. The pDNA-cleavage ability of the compounds is significantly enhanced under irradiation. All the compounds can bind tightly and reversibly to both albumins tested.