Tuning of Redox Properties for the Design of Ruthenium Anticancer Drugs:  Part 2. Syntheses, Crystal Structures, and Electrochemistry of Potentially Antitumor [Ru^III/IICl_6-n(Azole)_n]^z (n = 3, 4, 6) Complexes

Abstract

A series of mixed chloro-azole ruthenium complexes with potential antitumor activity, viz., mer-[RuIIICl3(azole)3] (B), trans-[RuIIICl2(azole)4]Cl (C), trans-[RuIICl2(azole)4] (D), and [RuII(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 RuIII/RuII 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 EL parameters were estimated for 1 (EL = 0.06 V), 3 (EL = 0.10 V), 4 (EL = 0.17 V), and 5 (EL = 0.18 V). The EL 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 RuIII/RuII 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 RuIII/RuII 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.

Synthesis, Reactivity, X‐ray Crystal Structures and Electrochemical Behaviour of Water‐Soluble [Tris(pyrazolyl)borato]ruthenium(II) Complexes of 1,3,5‐Triaza‐7‐phosphaadamantane (PTA)

“…Indeed, the estimated Ru III/IV oxidation potentials (approx. 2.4 V vs. SCE), by application of a proposed version of Lever's relationship in which S M = 1.03 and I M = 1.68 V vs. NHE, [28] are much higher than the experimentally measured ones.…”

Characterization of Coordination Compounds by Electrochemical Parameters

“…Nevertheless, Equation (15) is valid for allenylidenes and alkynyls. [28,36,42] ( 15) E L values are already known for a wide variety of ligands, [13][14][15][16][28][29][30]36,41,57,64,[70][71][72][73][74][75] including an extensive list of recently estimated values by the current author [36] for many carbyne, carbene, vinylidene, allenylidene and alkynyl ligands. Examples are given in Table 1.…”

“…[28,64] Normally, the redox centres are six-coordinate, with the exception of the four-and five-coordinate Rh II/I , [28,64] and in particular the five-coordinate Fe III/II [13] and Mn II/III [13] cases. The parameters usually have been obtained in organic media, but different values are observed in water where solvation effects and the complex charge can play a relevant role, as observed for Cr III/II , [13] Fe III/II , [13] Ru III/II (2+/1+), [13] Ru III/II (1-/2-) [71,75] and Os III/II [13] systems. The charge effect has been studied [75] particularly for the Ru III/II system.…”

“…The parameters usually have been obtained in organic media, but different values are observed in water where solvation effects and the complex charge can play a relevant role, as observed for Cr III/II , [13] Fe III/II , [13] Ru III/II (2+/1+), [13] Ru III/II (1-/2-) [71,75] and Os III/II [13] systems. The charge effect has been studied [75] particularly for the Ru III/II system. Moreover, particular sets of S M and I M values, different from the general ones but that better fit an expression of the type (14), have been proposed [26,27] for certain series of complexes.…”

The Complexes [OsCl2(azole)2(dmso)2] and [OsCl2(azole)(dmso)3]: Synthesis, Structure, Spectroscopic Properties and Catalytic Hydration of Chloronitriles

“…and their basicity [pK a (Hind) Ͻ pK a (Hpz) Ͻ pK a (Hbzim) Ͻ pK a (Him) [23] ). The responses are reversible or quasi-reversible and are characterised by a peak-to-peak separation (∆E p ) of 60-70 mV and an anodic peak current (i pa ) that is almost equal to the cathodic peak current (i pc ) (or slightly different), as expected for reversible electron-transfer processes.…”