Molecular Engineering of D‐π‐A Conjugate with N‐Heterocycle Purine for Enhanced ROS Generation and Photodynamic Therapy

Abstract The efficient generation of reactive oxygen species (ROS) is crucial for the photodynamic therapy (PDT) effect. The D‐π‐A molecular engineering strategy can effectively separate the highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO) distribution to achieve a smaller energy gap thereby facilitating ROS generation of photosensitizers (PSs). Incorporating heterocycles as π‐bridges can not only extend the conjugation system with improving the degree of π‐delocalization but also effectively accelerate the intersystem crossing process. Herein, a N‐heterocycle purine is innovatively integrated into the D‐π‐A structure as a π‐bridge, which significantly enhances the photodynamic performance by achieving high levels of Type I and Type II ROS generation. The most potent TPM‐QN2 is obtained by modulating the electron‐withdrawing ability of the acceptor (quinolinium), with a ¹O₂ yield of 9.32, which is the highest yield reported to date. Furthermore, these purine‐based PSs exhibit excellent capabilities in promoting cell photodynamic ablation and inhibiting tumor tissue growth. This novel approach of introducing natural heterocycles provides a promising avenue for developing high‐performance PSs and promoting tumor phototherapy.