title: Tuning of redox potentials for the design of ruthenium anticancer drugs -- an electrochemical study of [trans-RuCl(4)L(DMSO)](-) and [trans-RuCl(4)L(2)](-) complexes, where L = imidazole, 1,2,4-triazole, indazole.
abstract: The electrochemical behavior of [trans-RuCl(4)L(DMSO)](-) (A) and [trans-RuCl(4)L(2)](-) (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 Ru(III)/Ru(II) reduction involving, at a sufficiently long time scale, metal dechlorination on solvolysis, as well as, in organic media, one single-electron reversible Ru(III)/Ru(IV) 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 E(L) parameter) are proposed, for the first time, for negatively (1-) charged complexes with the Ru(III/II) redox couple center in aqueous phosphate buffer (pH 7) medium and for complexes with the Ru(III/IV) couple in organic media. The E(L) 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 E(L)) of the neutral ligands (DMSO < indazole < triazole < imidazole) and with the basicity of the ligated azole, factors that destabilize the Ru(II) relative to the Ru(III) 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 (Ph(3)PCH(2)Ph)[trans-RuCl(4)(Htrz)(DMSO)], [(Ph(3)P)(2)N][trans-RuCl(4)(Htrz)(DMSO)], (H(2)ind)[trans-RuCl(4)(Hind)(DMSO)], and [(Hind)(2)H][trans-RuCl(4)(Hind)(2)].
authors.affiliation: Centro de Química Estrutural, Complexo I, Instituto Superior Técnico, Av. Rovisco Pais, 1049-001 Lisbon, Portugal.
authors.forename: Erwin
authors.initials: E
authors.lastname: Reisner
authors.forename: Vladimir B
authors.initials: VB
authors.lastname: Arion
authors.forename: M Fátima C
authors.initials: MF
authors.lastname: Guedes da Silva
authors.forename: Roman
authors.initials: R
authors.lastname: Lichtenecker
authors.forename: Anna
authors.initials: A
authors.lastname: Eichinger
authors.forename: Bernhard K
authors.initials: BK
authors.lastname: Keppler
authors.forename: Vadim Yu
authors.initials: VY
authors.lastname: Kukushkin
authors.forename: Armando J L
authors.initials: AJ
authors.lastname: Pombeiro
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D004121:Dimethyl Sulfoxide; D015195:Drug Design; D004563:Electrochemistry; D007093:Imidazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D007191:Indazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D008968:Molecular Conformation; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D010084:Oxidation-Reduction; D012428:Ruthenium / Q000737:chemistry*; D013237:Stereoisomerism; D014230:Triazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D007093:Imidazoles; D007191:Indazoles; D009942:Organometallic Compounds; D014230:Triazoles; C029899:imidazole; D012428:Ruthenium; D004121:Dimethyl Sulfoxide