Visible-light-responsive indoleazopyrazole photoswitches: dual enhancement of redshift and half-life by ester modification at the ortho position

Abstract

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 Z-isomer. Herein, we designed a series of ortho-substituted indoleazopyrazoles that simultaneously achieve visible-light responsiveness and exceptional thermal stability. Notably, ester substitution at the ortho position (relative to the azo group) of the indoleazopyrazole exhibits a λ_max (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 (E-isomer) and high toxicity (Z-isomer) in three human cancer cell lines. Remarkably, the half-maximal inhibitory concentration (IC₅₀) of the E-isomer is approximately threefold higher than that of the Z-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.