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.
Mato et al. (Sat,) studied this question.