Acceptor Engineering-Mediated Charge-Transfer Control: A Hierarchical Framework for Predictive Design of...

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 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 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.