Dinuclear ruthenium(II) polypyridyl complexes: Mechanistic study with biomolecules, DNA/BSA interactions and cytotoxic activity

Abstract

The substitution reactions of dinuclear Ru(II) polypyridyl complexes, i.e. [{RuCl(bpy)2}2(μ-pzn)][PF6]2 (1) and [{RuCl(phen)2}2(μ-pzn)][PF6]2 (2) (bpy = 2,2′-bipyridine, phen = 1,10-phenanthroline, μ-pzn = pyrazine), with mononucleotide guanosine-5′-monophosphate (5′-GMP) and sulfur-containing nucleophiles, such as l-methionine (l-Met) and glutathione (GSH) were studied by UV–Vis spectroscopy. The structures of dinuclear Ru(II) complexes 1 and 2 were preserved during the substitution processes and the calculated enthalpies and entropies of activation (ΔH≠ > 0, ΔS≠ < 0) supported an associative mechanism of substitution. The DNA binding affinity of complexes 1 and 2 was evaluated by UV–Vis, fluorescence emission spectroscopy and by viscosity measurements in aqueous phosphate buffer solution (PBS) at pH 7.40. Additionally, competitive binding reactions with an intercalative agent ethidium bromide (EB) and the known minor groove binder Hoechst 33258 were studied as well. The obtained results indicate that complexes 1 and 2 can interact with DNA through the intercalation and/or minor groove binding, where the latest was preferred. This observation is in a good agreement with the results obtained by molecular docking. Furthermore, both complexes strongly quenched the fluorescence of tryptophan residues in serum albumin (BSA) through both static and dynamic quenching (Ksv = 104–105 M−1). In addition, complexes 1 and 2 showed moderate cytotoxic activity against human breast cancer cells (MDA-MB-231), while both were inactive against human colorectal cancer cells (HCT-116).