Tuning of redox properties for the design of ruthenium anticancer drugs:: Part 2.: Syntheses, crystal structures, and electrochemistry of potentially antitumor [RuIII/IICl6-n(Azole)n]z (n=3, 4, 6) complexes

A series of mixed chloro-azole ruthenium complexes with potential antitumor activity, viz., rner-[(RuCl3)-Cl-III(azole)(3)] (B), trans[(RuCl2)-Cl-III(azole)(4)]Cl (C), trans-[(RuCl2)-Cl-II(azole)(4)] (D), and [Ru-II(azole)(6)](SO3CF3)(2) (E), where azole = 1-butylimidazole (1), imidazole (2), benzimidazole (3), 1-methyl-1,2,4-triazole (4), 4-methylpyrazole (5), 1,2,4-triazole (6), pyrazole (7), and indazole (8), have been prepared as a further development of anticancer drugs with the general formula [RuCl4(azole)(2)](-) (A). These compounds were characterized by elemental analysis, IR spectroscopy, electronic spectra, electrospray mass spectrometry, and X-ray crystallography. The electrochemical behavior has been studied in detail in DMF, DMSO, and aqueous media using cyclic voltammetry, square wave voltammetry, and controlled potential electrolysis. Compounds B and a number of C complexes exhibit one Ru-III/Ru-II reduction, followed, at a sufficiently long time scale, by metal dechlorination on solvolysis. The redox potential values in organic media agree with those predicted by Lever's parametrization method, and the yet unknown E-L parameters were estimated for 1 (E-L = 0.06 V), 3 (E-L = 0.10 V), 4 (E-L = 0.17 V), and 5 (E-L = 0.18 V). The E-L values for the azole ligands 1-8 correlate linearly with their basicity (pK(a) value of the corresponding azolium acid H2L+). In addition, a logarithmic dependence between the homogeneous rate constants for the reductively induced stepwise replacement of chloro ligands by solvent molecules and the Ru-III/Ru-II redox potentials was observed. Lower E-1/2 values (higher net electron donor character of the ligands) result in enhanced kinetic rate constants of solvolysis upon reduction. The effect of the net charge on the Ru-III/Ru-II redox potentials in water is tentatively explained by the application of the Born equation. In addition, the pH-dependent electrochemical behavior of trans-[RuCl2(1,2,4-triazole)(4)]Cl is discussed.