Regioisomerization Strategy in Iridium(III) Complexes Achieving Enhanced Type I Photosensitization and Tumor Photoimmunotherapy

While molecular isomers exhibit nearly identical compositions, their spatial arrangement often dictates distinct physicochemical properties. We present a regioisomer engineering strategy to construct two iridium(III) complexes (<b>Ir1</b> and <b>Ir2</b>) through precise positioning of triphenylamine electron donors relative to the metal chelation core. Compared to <b>Ir1</b>, <b>Ir2</b> features strategically displaced donors that create a contracted bandgap, reduced oxidation potential, and amplified spin-orbit coupling (SOC). These electronic modifications synergistically enable <b>Ir2</b> to achieve superior type I photodynamic activity and thus generate O₂^•- and •OH radicals after 633 nm irradiation even under hypoxic conditions. The sustained reactive oxygen species (ROS) production induces potent immunogenic cell death (ICD), ultimately stimulating dendritic cell maturation and antitumor immunity. This regioisomeric design paradigm establishes a molecular blueprint for oxygen-tolerant photosensitizers, addressing the critical challenge of hypoxia in photoimmunotherapy applications.