Acceptor Engineering‐Mediated Charge‐Transfer Control: A Hierarchical Framework for Predictive Design of High‐Performance Type I AIE Photosensitizers

ABSTRACT This study presents a hierarchical multi‐parameter framework for designing hypoxia‐tolerant Type I aggregation‐induced emission (AIE) photosensitizers through acceptor engineering. Enhancing electron‐withdrawing capacity strengthens intramolecular charge transfer (ICT) in singlet excited states (S n ), enabling a direct charge transfer‐mediated intersystem crossing (ISC) pathway. Key parameters—favorable singlet‐triplet gap (ΔE > 0, thermodynamic prerequisite), low reorganization energy (λ, kinetic driver), and strong spin‐orbit coupling (SOC, ISC activator)—optimize ISC efficiency, an exceptionally high S 1 →T 1 ISC rate of 2.94 × 10 7 s −1 for DPCMQ. This high ISC efficiency populates the T 1 state, where DPCMQ benefits from optimal descriptors (lowest E b and λ T1 ) for efficient electron transfer. Its performance is further boosted in aggregates by restricted molecular motion and a hydration‐promoted microenvironment. This design selectively promotes hydroxyl radical (•OH) generation over oxygen‐dependent superoxide pathways, while low triplet energy suppresses Type II activity. The framework provides a predictive blueprint for advanced photodynamic therapy optimized for hypoxic conditions.