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

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 (Sn), 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 S1→T1 ISC rate of 2.94 × 107 s-1 for DPCMQ. This high ISC efficiency populates the T1 state, where DPCMQ benefits from optimal descriptors (lowest Eb and λT1) 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.