Redirecting Excited‐State Energy Flow Through Programmed Supramolecular Confinement in Twisted Photosensitizers

Programmed supramolecular confinement is introduced as a physical strategy to investigate aggregation-enhanced reactive oxygen species (ROS) generation in twisted intramolecular charge transfer (TICT)-active twisted photosensitizers without changing the conjugated photosensitizing unit. In this design, TICT functions as a confinement-sensitive regulator of excited-state energy dissipation, while cell membranes (CM) serve as supramolecular platforms that confine photosensitizers within their compact phospholipid bilayer architectures. Through alkyl-chain engineering, the obtained photosensitizers exhibit similar photophysical properties but tunable interactions with phospholipids, resulting in programmed confinement states within CMs. Experimental and theoretical studies reveal that supramolecular confinement suppresses TICT-mediated non-radiative relaxation by reducing excitation-induced donor-acceptor torsional change and restricting intramolecular rotation, thereby redirecting excited-state energy flow toward radiative emission and intersystem crossing-mediated ROS generation. Accordingly, stronger confinement induces higher enhancements in fluorescence and ROS generation, establishing a supramolecular confinement-dependent correlation among TICT restriction, fluorescence, and ROS generation. Finally, the optimized CM-photosensitizer assemblies are applied as photodynamic systems and display effective performance in cancer immunotherapy. By coupling TICT restriction with ROS generation, this work establishes supramolecular confinement as a physical strategy for redirecting excited-state energy flow and provides direct insight into how aggregation enhances ROS generation in twisted photosensitizers.