Yu Xuanchi, Zhang Chenyu, Dong Dongfang, Liu Bing, Wang Dali, Li Tao
School of Chemistry and Chemical Engineering, Shanghai Jiao Tong University Shanghai 200240 China
State Key Laboratory of Synergistic Chem-Bio Synthesis, Shanghai Key Laboratory of Electrical Insulation and Thermal Aging, Shanghai Jiao Tong University Shanghai 200240 China.
Chem Sci. 2025 Jul 21. doi: 10.1039/d5sc03275j.
As a class of universal light-responsive units, most azo compounds require ultraviolet (UV) excitation. Most conventional π → π* redshift strategies, while enabling visible-light excitation, often compromise the thermal stability of the -isomer. Herein, we designed a series of -substituted indoleazopyrazoles that simultaneously achieve visible-light responsiveness and exceptional thermal stability. Notably, ester substitution at the position (relative to the azo group) of the indoleazopyrazole exhibits a (π → π*) redshift to 383 nm while maintaining a half-life of up to 4.7 days. Following water-soluble modification, the optimized ester substitution derivative 5-photosurfactant (5-PS) demonstrates visible-light-controlled bioactivity, switching between low toxicity (-isomer) and high toxicity (-isomer) in three human cancer cell lines. Remarkably, the half-maximal inhibitory concentration (IC) of the -isomer is approximately threefold higher than that of the -rich isomer in HepG2 cells. This strategy achieves the dual enhancement of π → π* redshift and half-life, opening a new avenue for visible-light-controlled targeted anticancer therapy.
作为一类通用的光响应单元，大多数偶氮化合物需要紫外线（UV）激发。大多数传统的π→π红移策略虽然能实现可见光激发，但往往会损害反式异构体的热稳定性。在此，我们设计了一系列α-取代的吲哚偶氮吡唑，它们同时实现了可见光响应性和出色的热稳定性。值得注意的是，吲哚偶氮吡唑的α位（相对于偶氮基团）进行酯取代时，会出现π→π红移至383 nm，同时保持高达4.7天的半衰期。经过水溶性修饰后，优化的酯取代衍生物5-光表面活性剂（5-PS）在三种人类癌细胞系中表现出可见光控制的生物活性，在低毒性（反式异构体）和高毒性（顺式异构体）之间切换。值得注意的是，在HepG2细胞中，反式异构体的半数抑制浓度（IC）比富含顺式异构体的约高三倍。该策略实现了π→π*红移和半衰期的双重增强，为可见光控制的靶向抗癌治疗开辟了新途径。
