A heterocyclic strategy for regulating the proportion of type I and type II photodynamic therapy

Abstract

Type I photosensitizers (PSs) used in photodynamic therapy (PDT) offer advanced capabilities because they can generate cytotoxic reactive oxygen species (ROS) through electron transfer, even in hypoxic environments. However, this process is more challenging compared to the type II process via energy transfer. Herein, we present a facile and effective strategy to regulate the proportion of the two types of PSs by converting type II PSs to type I PSs through the introduction of heterocyclic rings. Three tetraphenyl-1,3-butadiene (TPB) derivatives were synthesized, each incorporating a different “bridge” molecule: benzene (TPP), thiophene (TPS), and furan (TPO), forming typical D–A structures. Compared with TPP, the electron-rich heterocyclic derivatives TPS and TPO produce more ROS, with type I ROS accounting for a higher proportion. This enhancement is attributed to the lone pair of electrons in the heterocyclic rings, which enhances the intersystem crossing and electron transfer. Systematic and detailed experimental and theoretical calculations prove our findings: (yield of ROS)_TPO > (yield of ROS)_TPS > (yield of ROS)_TPP, and (proportion of type I ROS)_TPO > (proportion of type I ROS)_TPS > (proportion of type I ROS)_TPP. This strategy not only provides a pathway for developing new PSs, but also lays the foundation for designing pure type I PSs.