Ru(CO)x-core complexes with selected azoles: Synthesis, X-ray structure, spectroscopy, DFT analysis and evaluation of cytotoxic activity against human cancer cells

The reaction of [RuII(CO) Cl ], 1, in methanol with azoles affords complexes that contain the fac-{RuII 262 (CO)3}2+-core. The complexes presented in this paper have the general formula fac-[RuII(CO)3Cl2L], with a molecule L of imidazole (IM), 2, or N-methyl-imidazole (MIM), 3, as a ligand in the pseudo-octahedral coor- dination sphere that is completed by two chlorido ligands cis to each other. The compounds show an appre- ciable solubility in water (up to ca 1 g/L) at 25 °C, and are well soluble in other solvents, such as alcohol, acetone, dicholoromethane, dimethylsulfoxide, and in mixtures of solvents. In the case where water is pres- ent in the medium (10% v/v or higher), significant dissociation of the Ru–N bond that is trans to a carbonyl ligand occurs, and a series of substitutions and other types of reactions may take place afterwards, depend- ing on the reactants and the applied experimental conditions. The synthesis and isolation of single crystals of 2 was performed by reacting the starting dimer 1 with 1-acetylimidazole in alcohol medium. DFT structure simulations/optimizations were carried out at Becke3lyp level of theory by using several basis sets up to 6-311++G⁄⁄ for C, H, Cl, N and O atoms, and the Lanl2DZ pseudo-potential for Ru. In vitro cytotoxicity tests for 2, 3 and fac-[RuII(CO)3Cl2(THZ)] (THZ = 1,3-thiazole), 4, showed IC50 values mostly in the range 100–200 lM in CH1 (ovarian carcinoma) and SW480 (colon carcinoma) cell lines. ESI-MS studies revealed the ability of these complexes to link the model proteins Lysozyme and Cytochrome c and similar binding patterns are highlighted; interestingly, protein binding is accompanied by a partial release of the original ligands. Fragments of the type [RuII(CO)2]2+ or [RuII(CO)]2+ are found associated to the proteins.