Synthesis, Structure−Property Relationships, and Photodynamic Activity of Heavy-Atom-Free BODIPY Photosensitizers Based on Spin−Orbit Charge Transfer
Huang Chen, Wei Luo, Xiaoqiang Wu, Zhiqiang Yang, Yanyan Lin, Chenyi You, Ye Lu, Shuping Huang, Feng-Xiang Tang, Mei-Rong Ke, Jian-Dong HuangAbstract
The geometrically orthogonal donor−acceptor (D−A) architecture, which favors spin−orbit charge-transfer intersystem crossing (SOCT-ISC), has emerged as a promising strategy for developing heavy-atom-free photosensitizers. However, systematic structure−property relationship (SPR) studies for such systems remain limited. In this work, we designed and synthesized 18 orthogonal D−A BODIPY derivatives modified with diverse electron-donating and electron-withdrawing groups. SPR investigation established that the meso-anthryl moiety and quaternary ammonium groups at the 3,5- and 2,6-positions significantly enhanced D−A interaction, reduced ΔEST, strengthened spin−orbit coupling (SOC), and thereby promoted SOCT-ISC, leading to markedly increased ROS generation (∼20-fold vs Chlorin e6). Importantly, the optimized compound An-DQA-OM, formulated as nanoparticles (ADO NPs), exhibited potent oxygen-independent photocytotoxicity (IC50 ≈ 0.39 μM in normoxia and 0.79 μM in hypoxia) and strong in vivo antitumor efficacy. This work presented a SPR paradigm for the rational design of efficient, heavy-atom-free BODIPY photosensitizers via the SOCT-ISC mechanism.