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 (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 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.