Influence of Oxygenation on the Reactivity of Ruthenium-Thiolato Bonds in Arene Anticancer Complexes: Insights from XAS and DFT

Thiolate ligand oxygenation is believed to activate cytotoxic half-sandwich [(eta(6)-arene)Ru(en)(SR)](+) complexes toward DNA binding. We have made detailed comparisons of the nature of the Ru-S bond in the parent thiolato complexes and mono- (sulfenato) and bis- (sulfinato) oxygenated species including the influence of substituents on the sulfur and arene. Sulfur K-edge XAS indicates that S-3p donation into the Ru-4d manifold depends strongly on the oxidation state of the sulfur atom, whereas Ru K-edge data suggest little change at the metal center. DFT results are in agreement with the experimental data and allow a more detailed analysis of the electronic contributions to the Ru-S bond. Overall, the total ligand charge donation to the metal center remains essentially unchanged upon ligand oxygenation, but the origin of the donation differs markedly. In sulfenato complexes, the terminal oxo group makes a large contribution to charge donation and Oven small electronic changes in the thiolato complexes are amplified upon ligand oxygenation, an observation which carries direct implications for the biological activity of this family of complexes. Details of Ru-S bonding in the mono-oxygenated complexes suggest that these should be most susceptible to ligand exchange, yet only if protonation of the terminal oxo group can occur. The potential consequences of these results for biological activation, are discussed.