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

作者：Feng Chen, Haitao Ma, Guoqing Wen, Xuan Wu, Xintong Lin, Dan Li, Deliang Wang, Anyi Dao, Huaiyi Huang, Pingyu Zhang · 发表于：Journal of Medicinal Chemistry · 年份：2025 · DOI：10.1021/acs.jmedchem.5c01006 · 被引用次数：9 · 研究领域：Nanoplatforms for cancer theranostics、Photodynamic Therapy Research Studies、Click Chemistry and Applications

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 ( Ir1 and Ir2 ) through precise positioning of triphenylamine electron donors relative to the metal chelation core. Compared to Ir1, Ir2 features strategically displaced donors that create a contracted bandgap, reduced oxidation potential, and amplified spin–orbit coupling (SOC). These electronic modifications synergistically enable Ir2 to achieve superior type I photodynamic activity and thus generate O 2 •− 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.