Unveiling Volcano-Type Trends in SOCT-ISC Photosensitization: Energy Gap Law-Guided Strategy for Efficient...

The development of high-performance heavy-atom-free photosensitizers requires deep insight into their excited-state dynamics. We report a series of cyanine-based compounds functionalized at the C2 position that operate through spin-orbit charge transfer intersystem crossing (SOCT-ISC). A pronounced "volcano-type" relationship between photo-induced electron transfer (PeT) efficiency and singlet oxygen quantum yield was uncovered. Femtosecond transient spectroscopy and quantum chemical calculations reveal that this trend stems from a dynamic competition between S₁ and T₂ intersystem crossing from the charge-separated (CS) state and CS-state charge recombination via internal conversion. The CS-state energy serves as a key descriptor dictating this balance. By modulating the donor strength of the substituents, we optimized the CS-state energy and identified TCy-Pyr, a molecule near the volcano apex. TCy-Pyr exhibits outstanding photodynamic performance, with in vitro and in vivo anticancer efficacy surpassing conventional benchmarks. It also displays aggregation-induced targeting behavior, promoting selective tumor accumulation. This work elucidates the excited-state dynamics in SOCT-ISC systems and establishes a rational design strategy to overcome performance bottlenecks in photosensitizer development.