Rationally designed photosensitizers with enhanced spin–orbit coupling for high quantum yield and potent antibacterial activity

As a novel approach to killing bacteria, photodynamic therapy holds great potential in antibacterial treatment. However, the majority of traditional photosensitizers exhibit relatively low reactive oxygen species (ROS) quantum yield. Therefore, it is essential to develop photosensitizers with high ROS quantum yield to effectively kill bacteria. Herein, we propose a molecular design approach to enhance the spin-orbit coupling (SOC) and improve the ROS quantum yield by introducing carbonyl groups into a donor-acceptor (D-A) system. In the meantime, we also introduced membrane-anchoring functional groups to the photosensitizer to anchor on the bacterial surface for improved antibacterial treatment. In this design, two D-A photosensitizers (CTI-1-anchor and CTI-2-anchor) were synthesized by linking membrane-anchoring functional groups to carbazole and indanedione derivatives. Notably, the resulting CTI-1-anchor exhibited a significantly enhanced ROS generation capability, and its ROS quantum yield can reach 87%. Moreover, the CTI-1-anchor demonstrated superior antibacterial performance against Gram-positive bacteria (<i>S. aureus</i>) and Gram-negative bacteria (<i>E. coli</i>). The antibacterial efficacy of CTI-1-anchor reached 97.7% and 73.4% for <i>S. aureus</i> and <i>E. coli</i>, respectively. This study is expected to inspire further molecular designs of photosensitizers, ultimately contributing to the development of efficient antibacterial therapy.