Ruthenium (II) complexes of 4-nitroimidazoles: their characterization, solution chemistry, and radiosensitizing activity

A series of ruthenium(II) complexes of formulation RuCl 2 (dmso) 2 L n , where dmso = S-bonded dimethylsulfoxide, L is a 4-nitroimidazole derivative, and n = 1 or 2, have been synthesized and characterized by spectroscopic methods, particularly 1 H nmr and X-ray photoelectron spectroscopy. With L = 4-nitroimidazole itself (4-NO 2 Im), RSU-1170, -3083 or -3100, n = 2 and the six-coordinate complexes are considered to be of cis,cis,cis-geometry. The N-methyl-4-nitroimidazole (NMe-4-NO 2 Im) ligand (n = 1) chelates through the imidazole-N and the oxygen of NO 2 . The RSU-3159 ligand (n = 1) binds through the sulfur and may be chelated. The complexes are of interest because of their radiosensitizer properties toward hypoxic tumour cells; the RuCl 2 (dmso) 2 (NMe-4-NO 2 Im) complex has a higher sensitizing enhancement ratio than the free imidazole ligand, and shows no cytoxicity in vitro, and these data are compared to those reported previously for RuCl 2 (dmso) 2 (4-NO 2 Im) 2 . Some aspects of the aqueous solution chemistry of the complexes (aquation via loss of chloride, pK a of coordinated water) are discussed in relation to their biological activities.