Molecular Design toward Heavy-Atom-free Photosensitizers Based on the C= S Bond and their Dual Functions in Hypoxia Photodynamic Cancer Therapy and ClO-Detection

Abstract

In this article, we designed and synthesized the thionated NpImidazole derivatives BS and NS, new heavy-atom-free photosensitizers, which efficiently generate a triplet excited state with high singlet oxygen quantum yield. The introduction of the C= S bond to the NpImidazole core is essential for increasing spin-orbit coupling (SOC). The fluorescence emission of BS and NS was quenched at standard ambient temperature, accompanied with the increase in the ISC process from the singlet states to triplet excited states via thionation. BS and NS showed negligible dark cytotoxicity against HeLa cells in working concentration. In contrast, BS and NS rapidly induced cell death under blue light irradiation both under normoxia and hypoxia conditions. Our current study demonstrates that the C= S group can play an important role in type I ROS generation of PSs, which are unprecedented in the previous reports. Finally, the photophysical changes were assigned to the oxidative desulfurization of the C= S group of BS and NS to the C= O group of the corresponding BO and NO via hypochlorite. The combined results demonstrated the dual function of BS and NS as a fluorescent imaging agent for ClO- and an anti-cancer therapeutic by PDT that showed the potential strategy for "one-for-all"and multifunctional agents. © 2021 American Chemical Society.