Synthesis, nucleic acid binding and cytotoxicity of oligonuclear ruthenium complexes containing labile ligands

Abstract

We report the synthesis, nucleic acid binding and cytotoxicity of the complexes [Ru(terpy)(Me2bpy)Cl]+, [Ru(terpy)(phen)Cl]+ and dinuclear [{Ru(terpy)Cl}2(μ-bbn)]2+ {where Me2bpy = 4,4′-dimethyl-2,2′-bipyridine; phen = 1,10-phenanthroline; and bbn = bis[4(4′-methyl-2,2′-bipyridyl)]-1,n-alkane, with n = 7, 10, 12, 14}. The complexes were isolated from the reaction of the [Ru(terpy)Cl3] precursor with the respective bidentate and di-bidentate bridging ligands. The time-course UV–Visible spectroscopy of the reaction of the mono- and dinuclear complexes with guanosine 5-monophosphate (GMP) showed the movement of the metal-to-ligand charge transfer (MLCT) band to lower wavelengths, accompanied by a hypochromism effect. The formation of the aqua complex and phosphate-bound intermediates in the reaction were detected by the time-course 1H NMR and 31P NMR experiments, which also demonstrated that the complex bound to the N7 guanine was the major product. The UV–Visible and 1H NMR studies showed no evidence of the interaction of the complexes with both adenosine 5-monophosphate (AMP) and cytidine 5-monophosphate (CMP). Cytotoxicity studies of these complexes against a murine leukemia L1210 cell line revealed that the dinuclear [{Ru(terpy)Cl}2(μ-bbn)]2+ complexes were significantly more cytotoxic than mononuclear [Ru(terpy)(Me2bpy)Cl]+. The [{Ru(terpy)Cl}2(μ-bb14)]2+ complex appeared to be the most active (IC50 = 4.2 μM).