CO release by redox stimuli and HSA interaction: Planning new CORMs based on µ-oxo triruthenium carbonyl clusters

Abstract

Hydrogen peroxide promoted the release of carbon monoxide through the oxidation of the [Ru₃O(CH₃COO)₆(L)₂CO]⁰ complexes (L = pyridine (1a), dimethylpyrazine (2a) and 4-tert-butylpyridine (3a)). For 1a, a two-step reaction was observed in acetonitrile, with pseudo-first order rate constants k^obs₁ = (10.9 ± 2.9) × 10⁻³ s⁻¹ and k₂ = (11.8 ± 0.8) × 10⁻⁴ s⁻¹, assigned to the oxidation reaction Ru^III,III,II/Ru^III,III,III followed by the substitution of the coordinated CO by a solvent molecule. In acetate buffer, only one-step was observable. Comparison of the reaction rate of three related clusters suggested a dependence of the rate constants with the basicity of the ligands. The 4-tert-butylpyridine ligand increases the oxidative-induced CO release, since σ-donation of electronic density by the more basic ligand facilitates the oxidation of the Ru(II) ion to Ru(III). We also addressed the possibility of interaction with a relevant biological target, using 1a as example. It is suggested that 1a interacts with human serum albumin (HSA) by the static mechanism, while the interaction of [Ru₃O(CH₃COO)₆(pyridine)₂H₂O]⁺ (1b), the reaction product of 1a oxidation, also has a contribution from the dynamic mechanism. This implies that weak interactions play a major role, since the labile point does not seem to favour adduct formation by coordinative bonding.