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

Abstract

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