While platinum drugs remain central to chemotherapy, their limitations in toxicity, drug resistance, and poor tumour selectivity have driven the exploration of gold-based metallodrugs that exploit oxidation-state chemistry to access new modes of biological action.[1] This work focuses on controlling gold oxidation states, from well-defined AuI systems to unusual [2] AuII, and mixed-valent AuI/III species, and extends these principles to heterometallic Au–Pt complexes as chemically robust platforms for developing next-generation cancer therapies.
Using an integrated approach encompassing synthetic inorganic chemistry, electrochemistry, structural characterisation, and biological evaluation,[2] this study demonstrates how oxidation-state control and ligand design translate into promising anticancer activity, including activity in drug-resistant cancer models. Rational ligand design is employed to modulate coordination geometry, electronic structure, and redox behaviour, thereby enabling biological responses beyond those of classical DNA-targeting platinum drugs.
Representative frameworks include acridone-functionalised gold(I) amide complexes of general formula [Au(LX)(PR3)], where LX = acridone (LH) or 2-Br acridone (LBr) and R = Ph, (4-C6H4F), or (4-C6H4OMe), as well as mononuclear gold(I) amidinate–phosphine complexes of general formula [Au(L)(PR3)], where L = {ArN=C(H)NAr} and PR₃ = PPh3, P(p-F-C6H4)3, P(p-OMe-C6H4)3, or 1,3,5-triaza-7-phosphaadamantane (PTA). In addition, dinuclear Au(II) complexes of the type [Au2X2(μ-ArPEt2)2] (X = Cl, Br, I) are examined as rare and underexplored oxidation-state platforms.
Collectively, this work demonstrates how oxidation-state-controlled gold- and platinum-based systems can serve as metallodrug platforms with clear therapeutic relevance and translational potential.