Ru-Based CO releasing molecules with azole ligands: interaction with proteins and the CO release mechanism disclosed by X-ray crystallography

Abstract

fac-[Ru^II(CO)₃Cl₂(N³-Imidazole)] (Ru^IIIM), fac-[Ru^II(CO)₃Cl₂(N³-methyl-imidazole)] (Ru^IIMIM) and fac-[Ru^II(CO)₃Cl₂(N³-methyl-benzimidazole)] (Ru^IIMBI) are three ruthenium based CO releasing molecules (Ru-CORMs) that are cytotoxic towards ovarian and colon carcinoma cell lines. Detailed structural information on the adducts formed upon reaction of Ru^IIIM and Ru^IIMIM with hen egg white lysozyme and of the three Ru-CORMs with bovine pancreatic ribonuclease is provided here by X-ray crystallography. Comparative analysis of seven crystal structures of these adducts allows one to delineate some general trends in the reactivity of these Ru-CORMs with proteins. Indeed, in all cases Ru-CORMs bind these model systems upon detachment of the azole ligand and concomitant coordination to a protein His or Asp residue. Apparently the three Ru-CORMs progressively dissociate losing azoles, chlorides, and one or two CO molecules. Data were compared with those reported in the literature for adducts of the same proteins with other Ru-CORMs and with in-solution data previously obtained on the same systems. These results are potentially useful for a better understanding of the chemistry, potential toxicity and mechanism of actions of these interesting Ru-CORMs and are helpful in defining the molecular mechanisms of CO release.