Sulfur‐π Interaction: A New Strategy for Designing NIR‐II AIE Photosensitizer for Wound Healing

Abstract Noncovalent interactions (NCIs) play a pivotal role in tuning the photophysical properties of functional materials, yet their potential in optimizing photosensitizers remains underexplored. In this study, a molecular design strategy is presented that integrates sulfur‐π (S‐π) interactions with aggregation‐induced emission (AIE) to enhance the performance of near‐infrared II (NIR‐II) photosensitizers for biomedical applications. Unlike conventional π‐π stacking, which often leads to aggregation‐caused quenching (ACQ), S‐π interactions provide directional molecular packing without significant fluorescence quenching. Four AIE molecules (P‐THX, T‐THX, TP‐THX, and TT‐THX) are synthesized with systematic phenyl‐to‐thiophene substitution to modulate S‐π interactions precisely. These interactions lower the singlet‐triplet energy gap (Δ E _ST ), extend π‐conjugation, and facilitate intersystem crossing (ISC), thereby boosting the generation of reactive oxygen species (ROS). Single‐crystal analysis revealed that S‐π interactions create continuous electronic coupling networks with advantages over conventional π‐π stacking arrangements. The thiophene‐substituted TT‐THX exhibits superior photophysical properties, demonstrating potent photodynamic antibacterial activity against Staphylococcus aureus ( S. aureus ) and methicillin‐resistant S. aureus (MRSA). When formulated as nanoparticles, TT‐THX enables effective wound healing, underscoring the therapeutic potential of S‐π interaction‐engineered AIE photosensitizers. This study establishes a new molecular design paradigm, unlocking advanced NIR‐II phototheranostics strategies with promising applications in infection treatment, cancer therapy, and biosensing.