Design and Development of a Bioorthogonal, Visualizable and Mitochondria‐Targeted Hydrogen Sulfide (H2S) Delivery System. (20th December 2021)

• Record Type: Journal Article
• Authors: Chen, Yinghan; Zhao, Ruohan; Tang, Cheng; Zhang, Chun; Xu, Wenyuan; Wu, Luyan; Wang, Yuqi; Ye, Deju; Liang, Yong
• Is Part Of: Angewandte Chemie. Volume 134:Number 6(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2021-12-20
• Subjects: bioorthogonal reaction -- click-and-release -- fluorescence turn-on -- hydrogen sulfide (H2S) -- mitochondria-targeted; Chemistry -- Periodicals; 540
• DOI: 10.1002/ange.202112734
• Languages: English
• ISSNs: 0044-8249

Abstract

Abstract: Hydrogen sulfide (H2 S) is an important endogenous gasotransmitter, but the targeted delivery and real‐time feedback of exogenous H2 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 H2 S, and a thiophene derivative with turn‐on fluorescence. Moreover, the diphenylamino substituent in DTO greatly increases the mitochondrial targeting of this H2 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 H2 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. Abstract : Reported herein is a triple‐functional H2 S delivery system, which is triggered by the bioorthogonal click‐and‐release reaction between a newly designed diphenylamino‐substituted 1, 3‐dithiolium‐4‐olate (DTO) and a strained alkyne. This COS‐based H2 S release platform can realize in‐mitochondria H2 S release in a controllable manner, and provide a concomitant fluorescence for spatiotemporal feedback of the exogenous H2 S in cells.