An E/Z isomer strategy of photosensitizers with tunable generation processes of reactive oxygen species

Abstract

Designing type I photosensitizers (PSs) with ease and precision is a promising approach to address the limitations of traditional photodynamic therapy (PDT) within the hypoxic tumor microenvironment. An effective strategy to achieve type I PSs involves adjusting the energy levels of triplet (T₁) states to inhibit type II PDT, ensuring they are lower than those required for singlet oxygen (¹O₂) production. Herein, we report an E/Z isomer strategy to precisely regulate the type of reactive oxygen species (ROS) generated, thereby promoting the generation of type I PDT. Two pairs of E/Z isomers of tetraphenyl-1,3-butadiene (TPB) derivatives have been synthesized, which serve as the core of aggregation-induced emission (AIE) materials, exhibiting a typical donor–π–acceptor structure. These isomers were obtained successfully via silica gel column chromatography. The E isomer demonstrated superior ROS generation efficiency compared with the Z isomer, attributed to its higher intersystem crossing (ISC). Meanwhile, the T₁–S₀ energy gap of the E isomer was smaller than that of O₂, effectively preventing the generation of ¹O₂ through the type II process. The E/Z isomer strategy represents a promising avenue for the facile preparation of type I PDT agents and contributes to our understanding of the underlying mechanisms.