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

• Published in: Dalton transactions : an international journal of inorganic chemistry Vol. 42; no. 48; p. 16796
• Main Authors: Santos, Rodrigo Luis Silva Ribeiro, van Eldik, Rudi, de Oliveira Silva, Denise
• Format: Journal Article
• Language: English
• Published: England 28-12-2013
• Subjects: Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Ascorbic Acid - metabolism; Carboxylic Acids - chemistry; Carboxylic Acids - pharmacology; Glutathione - metabolism; Kinetics; Reducing Agents - metabolism; Ruthenium - chemistry; Ruthenium - pharmacology
• ISSN: 1477-9234
• DOI: 10.1039/c3dt51763b

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 [Ru2(RCOO)4](+) paddlewheel framework by using the non-drug, diaqua complex ion [Ru2(CH3COO)4(H2O)2](+). In the presence of the reducing agents, the diaqua-Ru2 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 Ru2(5+) to Ru2(4+) and the reducing agent is oxidized. Product analyses were performed with the application of ESI-MS and (1)H-NMR techniques. Rate and activation parameters are reported for the different reaction steps.