Exploring the singlet oxygen generation of iridium(III) complex containing phenothiazine for photodynamic therapy

As a photochemical-based treatment approach, photodynamic therapy (PDT) relies on a photosensitiser (PS) that produces reactive oxygen species (ROS) after irradiation, which lead to irreparable cell damage and hence cell death. Cyclometalated iridium(III) complexes are often used in the development of PSs attributed to their rich photophysical properties with high quantum yields, large Stokes shifts, long-lived phosphorescence and good photostability. In addition, phenothiazine has excellent electron-donating ability and good rigid structure, its derivatives have been shown to possess activity against bacteria, malignant cells, and protozoa. In this work, we designed and synthesized two iridium(III) complexes DF-Ir-CHO and DF-Ir-PTZ. The DF-Ir-PTZ contains a novel ligand functionalized with phenothiazine. DF-Ir-PTZ has a better singlet oxygen (¹O₂) production quantum yield of 0.357 upon light irradiation and negligible dark cytotoxicity, suggesting that its biological safety is favorable. In addition, DF-Ir-PTZ was able to generate ¹O₂ and ROS in cancer cells under light conditions, leading to cell apoptosis of MCF-7.