Exploring the binding and cleavage activities of nickelII complexes towards DNA and proteins

Abstract

The present study documents the first investigation into the relationship between the binding and cleavage activity of nickel complexes towards DNA and proteins. Here, three different Ni^II complexes of the general type [Ni(nal)₂diimine] (1a and 1b) and [Ni(8-Hq)₂(bpy)] 1c (nal = nalidixic acid, diimine = 2,2′-bipyridine (bpy) or 1,10-phenanthroline (phen), and 8-Hq = 8-hydroxyquinolone) have been isolated. The structural X-ray analysis clearly showed that all complexes possess cis octahedral geometry around the Ni atoms. The interaction of the complexes with proteins (BSA/HSA) and calf thymus (CT)-DNA was followed via a series of spectroscopic measurements. The observed results for the proteins revealed that the complexes quench the intrinsic fluorescence in static quenching mode with an excellent binding affinity towards both BSA and HSA. The DNA binding studies showed that the complexes readily bind with DNA via intercalative and minor groove modes with excellent binding affinities (1b > 1c > 1a). To understand the binding process of the complexes towards proteins and DNA, the thermodynamic Gibbs free energy (ΔG°), enthalpy (ΔH°) and entropy (ΔS°) parameters were also calculated and the obtained results indicated that the process is spontaneous and electrostatic. Moreover, the variation in the abilities of the complexes to cleave proteins and DNA have been explored via electrophoretic mobility spectrometry studies and the results revealed that all of the complexes exhibit excellent cleavage properties. Docking analysis with the crystal structures of BSA (4F5S), HSA (1AO6) and CT DNA (1BNA) was employed to study the ability of the complexes 1a–1c to bind to these target macromolecules. Finally, the in vitro anticancer activity of all three complexes was evaluated using the MTT assay against human lung (A-549) and breast (MCF-7) tumor cells for 24 h incubation times.