Kinetic and mechanistic studies on reactions of diruthenium(II,III) with biologically relevant reducing agents

Diruthenium(II,III)-tetracarboxylates have shown promising anticancer properties as metallotherapeutics. On the basis of the role that bio-reducing agents may play on the mode of action of ruthenium-based anticancer drugs, we performed detailed kinetic studies on the reaction of ascorbic acid and glutathione with the {[}Ru-2(RCOO)(4)](+) paddlewheel framework by using the non-drug, diaqua complex ion {[}Ru-2(CH3COO)(4)(H2O)(2)](+). In the presence of the reducing agents, the diaqua-Ru-2 species first undergo a ligand substitution reaction by which the axially-coordinated water is displaced by the reducing agent. In both cases, this reaction is followed by an intra-molecular electron transfer process during which the metal-metal center is reduced from Ru-2(5+) to Ru-2(4+) and the reducing agent is oxidized. Product analyses were performed with the application of ESI-MS and H-1-NMR techniques. Rate and activation parameters are reported for the different reaction steps. (AU)