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.