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Abstract Hydrogen sulfide (H 2 S) is an important endogenous gasotransmitter, but the targeted delivery and real‐time feedback of exogenous H 2 S are still challenging. With the aid of density functional theory (DFT) calculations, we designed a new 1,3‐dithiolium‐4‐olate (DTO) compound, which can react with a strained alkyne via the 1,3‐dipolar cycloaddition and the retro‐Diels–Alder reaction to generate carbonyl sulfide (COS) as the precursor of H 2 S, and a thiophene derivative with turn‐on fluorescence. Moreover, the diphenylamino substituent in DTO greatly increases the mitochondrial targeting of this H 2 S delivery system. Such a bioorthogonal click‐and‐release reaction has integrated three functions in one system for the first time: (1) in situ controllable H 2 S release, (2) concomitant fluorescence response, and (3) mitochondria‐targeted delivery. In addition, we investigated the mitochondrial membrane potential loss alleviation by using this system in H9c2 cells under oxidative stress.
Chen et al. (Mon,) studied this question.