Disulfide-Bridged Cationic Dinuclear Ir(III) Complex\nwith Aggregation-Induced Emission and Glutathione-Consumption Properties\nfor Elevating Photodynamic Therapy

The ability of photosensitizers\n(PSs) to generate reactive oxygen\nspecies (ROS) is crucial for photodynamic therapy (PDT). However,\nmany traditional PSs face the drawbacks that aggregation-caused quenching\n(ACQ) and highly expressed glutathione (GSH) in the tumor microenvironment\nseriously limit their ROS generation ability. Herein, we report two\ncationic dinuclear iridium complexes, <b>Ir–C–C–Ir</b> and <b>Ir–S–S–Ir</b>, which possess aggregation-induced\nemission (AIE). <b>Ir–S–S–Ir</b> was constructed\nfor GSH consumption by introducing a disulfide linkage between the\ntwo auxiliary ligands with imine units. Quantum chemical calculations\nrevealed that <b>Ir–C–C–Ir</b> and <b>Ir–S–S–Ir</b> possess many degenerate states,\nwhich provide more channels for singlet-to-triplet exciton transitions,\nand then the intersystem crossing rate is increased due to the heavy\natom effect of the iridium and sulfur atoms. The ROS production experiments\nindicated that the singlet oxygen yield of <b>Ir–S–S–Ir</b> was 33 times more than that of the ACQ mononuclear iridium complex <b>Ir–C</b>. Most importantly, <b>Ir–S–S–Ir</b> consumed GSH through a thiol–disulfide exchange reaction,\nas demonstrated by mass spectrometry and high-performance liquid chromatography.\nCell experiments testified that <b>Ir–S–S–Ir</b> consumes GSH in tumor cells, possesses good ROS production capacity,\nand exhibits an extraordinary PDT effect. This is the first report\nof an AIE dinuclear iridium complex with a GSH-consuming function.