Homodinuclear organometallics of ditopic N,N-chelates: Synthesis, reactivity and in vitro anticancer activity

Abstract

In some instances, multimetallic complexes have shown higher anticancer activity than mononuclear analogues, possibly by interacting with target molecules through a different binding mode. Therefore, a series of novel bis-pyridylimine-based homodinuclear MII/III(cym/Cp*)Cl (cym = η6-p-cymene: M = Ru, Os; Cp* = η5-pentamethylcyclopentadienyl: M = Rh, Ir) complexes were synthesized and studied. The dinuclear complexes were characterized by 1H, 13C{1H}, and 31P{1H} NMR spectroscopy, ESI-MS, and elemental analysis. Additionally, the molecular structures of several complexes were investigated by single crystal X-ray diffraction analysis. [{N,N’-(1,4-Phenylene)(bis(1-(pyridin-2-yl)(methanimine)-ᴋ2N,N’))}bis{chlorido(η6-p-cymene)ruthenium(II)}] hexafluorophosphate, 1a, was used in stability and binding studies to 9-ethylguanine (EtG) as a DNA nucleobase model and L-histidine (His), L-cysteine (Cys) and L-methionine (Met) as protein models. However, compared to structurally related Ru(arene) complexes, the investigations were inconclusive in terms of the nature of hydrolysis product(s) and EtG adducts formed, while reactions to His and Cys but not Met were observed for 1a. The in vitro cytotoxicity of the ligands and dinuclear complexes was determined against a small panel of human cancer cell lines. Some of the complexes showed moderate antiproliferative activity but were less potent than the bis-pyridylimine-based bridging ligands.