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

## TL;DR

A new compound was developed that responds to visible light and can control cancer cell toxicity, offering a new approach for targeted cancer therapy.

## Contribution

Ester modification at the ortho position enables both visible-light responsiveness and improved thermal stability in azo compounds.

## Key findings

- Ester substitution at the ortho position achieves a λmax redshift to 383 nm with a half-life of up to 4.7 days.
- The compound 5-PS shows visible-light-controlled toxicity in human cancer cells.
- The Z-isomer of 5-PS has significantly lower IC50 values compared to the E-isomer in HepG2 cells.

## 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 λmax (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.

Through ester modification at the ortho position, a dual enhancement of π → π* redshift and extended half-life was achieved. After modification, the compound exhibited potential for visible-light controlled anticancer therapy.