Oxidization enhances type I ROS generation of AIE-active zwitterionic photosensitizers for photodynamic killing of drug-resistant bacteria

Abstract

Type I photosensitizers (PSs) with an aggregation-induced emission (AIE) feature have received sustained attention for their excellent theranostic performance in the treatment of clinical diseases. However, the development of AIE-active type I PSs with strong reactive oxygen species (ROS) production capacity remains a challenge due to the lack of in-depth theoretical studies on the aggregate behavior of PSs and rational design strategies. Herein, we proposed a facile oxidization strategy to enhance the ROS generation efficiency of AIE-active type I PSs. Two AIE luminogens, MPD and its oxidized product MPD-O were synthesized. Compared with MPD, the zwitterionic MPD-O showed higher ROS generation efficiency. The introduction of electron-withdrawing oxygen atoms results in the formation of intermolecular hydrogen bonds in the molecular stacking of MPD-O, which endowed MPD-O with more tightly packed arrangement in the aggregate state. Theoretical calculations demonstrated that more accessible intersystem crossing (ISC) channels and larger spin–orbit coupling (SOC) constants provide further explanation for the superior ROS generation efficiency of MPD-O, which evidenced the effectiveness of enhancing the ROS production ability by the oxidization strategy. Moreover, DAPD-O, a cationic derivative of MPD-O, was further synthesized to improve the antibacterial activity of MPD-O, showing excellent photodynamic antibacterial performance against methicillin-resistant S. aureus both in vitro and in vivo. This work elucidates the mechanism of the oxidization strategy for enhancing the ROS production ability of PSs and offers a new guideline for the exploitation of AIE-active type I PSs.