Tuning of Redox Potentials for the Design of Ruthenium Anticancer Drugs − an Electrochemical Study of [trans-RuCl4L(DMSO)]- and [trans-RuCl4L2]- Complexes, where L = Imidazole, 1,2,4-Triazole, Indazole

The electrochemical behavior of [trans-RuCl4L(DMSO)]- (A) and [trans-RuCl4L2]- (B) [L = imidazole (Him), 1,2,4-triazole (Htrz), and indazole (Hind)] complexes has been studied in DMF, DMSO, and aqueous media by cyclic voltammetry and controlled potential electrolysis. They exhibit one single-electron RuIII/RuII reduction involving, at a sufficiently long time scale, metal dechlorination on solvolysis, as well as, in organic media, one single-electron reversible Ru III/RuII oxidation. The redox potential values are interpreted on the basis of the Lever's parametrization method, and particular forms of this linear expression (that relates the redox potential with the ligand EL parameter) are proposed, for the first time, for negatively (1-) charged complexes with the RuIII/IV redox couple center in aqueous phosphate buffer (pH 7) medium and for complexes with the Ru III/IV couple in organic media. The EL parameter was estimated for indazole showing that this ligand behaves as a weaker net electron donor than imidazole or triazole. The kinetics of the reductively induced stepwise replacement of chloride by DMF were studied by digital simulation of the cyclic voltammograms, and the obtained rate constants were shown to increase with the net electron donor character (decrease of EL) of the neutral ligands (DMSO <indazole <triazole <imidazole) and with the basicity of the ligated azole, factors that destabilize the RuII relative to the RuIII form of the complexes. The synthesis and characterization of some novel complexes of the A and B series are also reported, including the X-ray structural analyses of (Ph3PCH 2Ph)[trans-RuCl4(Htrz)(DMSO)], [(Ph3P) 2N][trans-RuCl4(Htrz)(DMSO)], (H2ind)-[trans- RuCl4(Hind)(DMSO)], and [(Hind)2H][trans-RuCl 4(Hind)2].