Ligand-driven redox behavior of gold(III) complexes: electrochemical insights into stability and biological potential

Gold(III) compounds are an important class of experimental drugs with potential use in the treatment of cancer. It is believed that the remarkable oxidizing nature of the gold(III) centre, which is variably modulated by the metal ligands, may play a key role in determining their reactivity with biomolecules and, hence, their mode of action. Here, we present a systematic electrochemical investigation of five structurally diverse mononuclear gold(III) complexes (i.e. Auen, Audien, Aucyclam, Aubipy and Aubipyc) the chemical and cytotoxic properties of which have previously been determined in our laboratory. The electrochemical profiles of the panel compounds were comparatively investigated by cyclic voltammetry (CV) both in aqueous solution and in DMSO to explore solvent-dependent redox behavior under biologically relevant conditions. The results highlight the influence of ligand denticity and coordination flexibility on the stabilization of the Au(III) center and the accessibility of redox processes of the redox processes within the biological environment. The electrochemical profiles obtained for this panel of gold(III) complexes are analyzed and compared with their known biological and antiproliferative profiles to explore possible structure-activity relationships within a unified interpretative framework. Overall, these findings highlight the delicate balance between stability and reactivity required for gold-based drugs to achieve their therapeutic effect, and suggest that electrochemical profiling can inform the rational design of redox-activated anticancer agents.