The effect of incorporating carboxylic acid functionalities into 2,2′-bipyridine on the biological activity of the complexes formed: synthesis, structure, DNA/protein interaction, antioxidant activity and cytotoxicity

Abstract

In order to find out the influence of carboxylic acid functionalities (COOH) present at different positions in 2,2′-bipyridine on various biological activities such as DNA/protein binding, antioxidant activity and cytotoxicity, three new ruthenium(II) complexes [RuCl₂(bpy)(S-DMSO)₂] (1) (bpy = 2,2′-bipyridine), [RuCl₂(H₂L1)(S-DMSO)₂] (2) (H₂L1 = 2,2′-bipyridine-4,4′-dicarboxylic acid) and [RuCl₂(H₂L2)(S-DMSO)₂] (3) (H₂L2 = 2,2′-bipyridine-5,5′-dicarboxylic acid) have been synthesized and structurally characterized by analytical and spectral methods. The structures of 1 and 3 have been determined by single crystal X-ray diffraction studies, which revealed that both are a roughly regular octahedron with bipyridine/bipyridine dicarboxylic acid as neutral bidentate donors with the involvement of both the nitrogen atoms of the bipyridine ring. In vitro DNA binding studies of the complexes were carried out employing absorption titrations, fluorescence spectra, thermal melting, viscosity and circular dichroic measurements, which disclosed that all the complexes bind to CT-DNA via groove binding. The interactions of the complexes with bovine serum albumin (BSA) were also investigated using UV-visible, fluorescence and synchronous fluorescence spectroscopic measurements. The results indicated that the new complexes quench the intrinsic fluorescence of BSA protein in a static quenching mode. The assessment of free radical scavenging ability involving the DPPH radical, hydroxyl radical, nitric oxide radical, superoxide anion radical, and hydrogen peroxide and a metal chelating assay showed that the new complexes 2 and 3 possess excellent radical scavenging properties over 1 and standard antioxidants vitamin C and BHT. The in vitro cytotoxic activity of the new ruthenium complexes has been validated against HCT-15, HeLa, SKOV3, MCF7 and SKMel2 human cancer cells by SRB assay and cytotoxic selectivity has been examined against NIH 3T3 and HEK 293 normal cells by MTT assay and compared with that of the ruthenium anticancer drug NAMI A and standard platinum drug, cisplatin. The results indicated that the new complexes 2 and 3 displayed substantial cytotoxic specificity towards cancer cells only. Incorporation of a carboxylic acid group in the bipyridine moiety has resulted in showing differences in DNA/protein binding affinity, efficiency in antioxidant activity and cytotoxicity.