# Photoredox Unmasking of Aromatic C–H Bonds in Living Environments Enabled by Thianthrenium Salts

## TL;DR

A new method uses light to activate antifungal drugs inside living cells by unmasking their chemical bonds.

## Contribution

A novel photoredox uncaging strategy for aromatic C–H bonds using thianthrenium salts is introduced.

## Key findings

- Photoredox activation of thianthrenium salts generates aryl radicals in living cells.
- Endogenous bioreductants rapidly reduce radicals to restore native C–H bonds.
- The method successfully modulates antifungal agent activity in a proof-of-concept study.

## Abstract

Prodrug strategies traditionally rely on masking polar
functional
groups of bioactive molecules with protecting units that can be removed
by specific stimuli in biological settings. Here, we introduce an
alternative uncaging approach that bypasses the need for heteroatom
handles, based on reversible masking of aromatic C–H bonds
with thianthrenium groups. Unmasking is triggered by low-energy photoredox
activation, which generates aryl radicals that are rapidly reduced
by endogenous bioreductants to restore the native C–H bond.
Beyond establishing the feasibility of photoredox radical chemistry
in living cells, we demonstrate a proof-of-concept application of
this strategy for the modulation of activity of antifungal agents.