Design and investigation of photoactivatable platinum(iv) prodrug complexes of cisplatin

Abstract

Platinum(IV) carboxylate scaffolds have garnered considerable research interest because they can be engineered to function as prodrugs of clinical platinum(II) anticancer drugs. These platinum(IV) prodrug complexes are stable and tunable, and activated by reduction to release their cytotoxic platinum(II) cargo. Here we propose new platinum(IV) prodrug complexes designed to release cisplatin via photoreduction upon UV irradiation. The central strategy is to utilise aryl carboxylate ligands on the axial positions of that platinum(IV) scaffold that confer significant UV absorption and would stabilise carboxyl radical formation, thus favouring homolytic Pt–O bond cleavage. We isolated and identified aryl carboxyl radicals via spin-trapping and showed that the photoreduced platinum species mirror cisplatin reactivity toward DNA bases, thereby validating the efficacy of this approach.