Complex formation between Ru(η6-p-cym)(H2O)3]2+ and (O,O) donor ligands with biological relevance in aqueous solution

Abstract

The interaction between [Ru(η⁶-p-cym)(H₂O)₃]²⁺ and (O,O) type chelators with different basicity of the donor atoms was studied using combined pH-potentiometric, ¹H-NMR and ESI-TOF-MS techniques. The studied nine ligands are building blocks of reported complexes with antitumor activity or may model (O,O) donor serum components capable of interacting with the administered half-sandwich ruthenium(II) type drug. Composition and stability constants of the [Ru(η⁶-p-cym)(O,O)Y] type species (Y: H₂O or OH⁻) were determined (T = 25.0 °C; I = 0.20 M (KCl)) and the metal ion binding strengths of the ligands are discussed. It was found that ligands with two low basicity O donors (oxalic and cyclobutane-1,1-dicarboxylic acid) bind the metal ion at acidic conditions but are not able to prevent the hydrolysis at physiologically relevant conditions. Ligands with one low and one high basicity O donor (lactic and salicylic acid) are weak binders for Ru(η⁶-p-cym)(H₂O)₃]²⁺. Pyrone or pyridinone based ligands are capable of binding the metal ion over a wide pH range and no hydrolysis product is detectable at pH = 7.4. The obtained speciation models may help in the rationalization of the biological activity of such complexes and provide a deeper insight into the solution behaviour of half-sandwich Ru(II) complexes with potential anticancer activity.