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

• Published in: Journal of Inclusion Phenomena and Macrocyclic Chemistry Vol. 71; no. 3-4; pp. 371 - 379
• Main Authors: Mulyana, Yanyan, Collins, Grant, Keene, Richard
• Format: Journal Article
• Language: English
• Published: Dordrecht Springer Netherlands 01.12.2011
• Subjects: Chemistry; Chemistry and Materials Science; Crystallography and Scattering Methods; Food Science; Organic Chemistry; Original Article; Oligonuclear; Cytotoxicity; Ruthenium; Polypyridyl; DNA binding; Labile ligands
• ISSN: 0923-0750; 1573-1111
• DOI: 10.1007/s10847-011-0036-1

We report the synthesis, nucleic acid binding and cytotoxicity of the complexes [Ru(terpy)(Me 2 bpy)Cl] + , [Ru(terpy)(phen)Cl] + and dinuclear [{Ru(terpy)Cl} 2 (μ-bb n )] 2+ {where Me 2 bpy = 4,4′-dimethyl-2,2′-bipyridine; phen = 1,10-phenanthroline; and bb n  = 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)Cl 3 ] 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 1 H NMR and 31 P NMR experiments, which also demonstrated that the complex bound to the N7 guanine was the major product. The UV–Visible and 1 H 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-bb n )] 2+ complexes were significantly more cytotoxic than mononuclear [Ru(terpy)(Me 2 bpy)Cl] + . The [{Ru(terpy)Cl} 2 (μ-bb 14 )] 2+ complex appeared to be the most active (IC 50  = 4.2 μM).