Design and Development of a Bioorthogonal, Visualizable and Mitochondria‐Targeted Hydrogen Sulfide (H<sub>2</sub>S) Delivery System
Yinghan Chen, Ruohan Zhao, Cheng Tang, Chun Zhang, Wenyuan Xu, Luyan Wu, Yuqi Wang, Deju Ye, Yong Liang
Abstract
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.