Abstract

Hydrogen sulfide (H2S) is an important endogenous gasotransmitter, but the bioorthogonal reaction triggered H2S donors are still rare. Here we show one type of bioorthogonal H2S donors, sydnthiones (1,2,3-oxadiazol-3-ium-5-thiolate derivatives), which was designed with the aid of density functional theory (DFT) calculations. The reactions between sydnthiones and strained alkynes provide a platform for controllable, tunable and mitochondria-targeted release of H2S. We investigate the reactivity of sydnthiones‒dibenzoazacyclooctyne (DIBAC) reactions and their orthogonality with two other bioorthogonal cycloaddition pairs: tetrazine‒norbornene (Nor) and tetrazine‒monohydroxylated cyclooctyne (MOHO). By taking advantage of these mutually orthogonal reactions, we can realize selective labeling or drug release. Furthermore, we explore the role of H2S, which is released from the sydnthione-DIBAC reaction, on doxorubicin-induced cytotoxicity. The results demonstrate that the viability of H9c2 cells can be significantly improved by pretreating with sydnthione 1b and DIBAC for 6 h prior to exposure to Dox.

Hydrogen sulfide (H2S) is an important endogenous gasotransmitter, but the bioorthogonal H2S donors are limited. Here, the authors design and synthesize sydnthiones, and investigate their bioorthogonal reactions with strained alkynes for mitochondria-targeted H2S release.

Details

Title
Sydnthiones are versatile bioorthogonal hydrogen sulfide donors
Author
Xu, Wenyuan 1   VIAFID ORCID Logo  ; Tang, Cheng 1 ; Zhao, Ruohan 1 ; Wang, Yajun 1 ; Jiao, Hongyun 1 ; Ang, Han 1 ; Chen, Yinghan 1   VIAFID ORCID Logo  ; Wang, Xin 2   VIAFID ORCID Logo  ; Liang, Yong 3   VIAFID ORCID Logo 

 Nanjing University, State Key Laboratory of Coordination Chemistry, Jiangsu Key Laboratory of Advanced Organic Materials, School of Chemistry and Chemical Engineering, Chemistry and Biomedicine Innovation Center (ChemBIC), ChemBioMed Inter-disciplinary Research Center, Nanjing, China (GRID:grid.41156.37) (ISNI:0000 0001 2314 964X) 
 Henan University, Henan-Macquarie University Joint Centre for Biomedical Innovation, School of Life Sciences, Kaifeng, China (GRID:grid.256922.8) (ISNI:0000 0000 9139 560X) 
 Nanjing University, State Key Laboratory of Coordination Chemistry, Jiangsu Key Laboratory of Advanced Organic Materials, School of Chemistry and Chemical Engineering, Chemistry and Biomedicine Innovation Center (ChemBIC), ChemBioMed Inter-disciplinary Research Center, Nanjing, China (GRID:grid.41156.37) (ISNI:0000 0001 2314 964X); Henan University, Henan-Macquarie University Joint Centre for Biomedical Innovation, School of Life Sciences, Kaifeng, China (GRID:grid.256922.8) (ISNI:0000 0000 9139 560X) 
Pages
10288
Publication year
2024
Publication date
2024
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
3133603535
Copyright
© The Author(s) 2024. This work is published under http://creativecommons.org/licenses/by-nc-nd/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.