Iridium(III) complexes with five-membered heterocyclic ligands for combined photodynamic therapy and photoactivated chemotherapy

Organometallic iridium complexes have emerged as potent anticancer agents in recent years. In this work, three cyclometalated iridium(III) complexes Ir1–Ir3 containing monodentate five-membered heterocyclic ligands have been synthesized and characterized. Upon visible light (425 nm) irradiation, the five-membered heterocyclic ligands will dissociate from the metal centre. Moreover, Ir1–Ir3 can also act as effective singlet oxygen photosensitizers. Thus, Ir1–Ir3 can exert their light-mediated activation of anticancer effects by dual modes including ligand exchange reactions and generation of singlet oxygen (1O2) upon visible light irradiation. Notably, Ir1 displays a high phototoxicity index of 61.7 against human cancer cells. Further studies show that light-mediated anticancer properties exerted by Ir1–Ir3 occur through reactive oxygen species (ROS) generation, caspase activation, and eventually apoptosis induction. Our study demonstrates that these complexes can act as novel dual-mode light-mediated anticancer agents.