Intramolecular Thiol‐Promoted Decomposition of Cysteine Ester (ITPDC): A General Platform for Controllable Release of Reactive Sulfur Species
Abstract
Abstract Endogenously generated reactive sulfur species (RSS) play critical roles in various physiological processes. RSS donors can enhance our understanding of RSS chemical biology and open new avenues for treating RSS‐associated diseases. Nevertheless, general strategies for the controllable release of distinct RSS remain lacking. Herein, we present the first general platform for controllable release of RSS with sulfur oxidation states ranging from −2 to +4, based on the intramolecular thiol‐promoted decomposition of cysteine ester ( ITPDC ). We first rationally designed ITPDC ‐based hydrogen sulfide (H 2 S) donors that avoid electrophilic byproducts and exhibit high H 2 S release efficiencies (>50%). Mechanistic investigations and density functional theory calculations elucidated the detailed pathways of pH‐controllable H 2 S release from ITPDC , and computational studies also predicted other H 2 S‐related RSS release from the ITPDC ‐based motifs. Importantly, we developed a series of ITPDC ‐based donors capable of releasing various RSS, including persulfide, hydrogen persulfide, sulfenic acid, sulfinic acid, and sulfur dioxide (SO 2 ). Moreover, fluorescent imaging demonstrated the successful cellular delivery of H 2 S, persulfide, and SO 2 from these donors, and the ITPDC ‐based motif was employed to create a light‐triggered donor. We anticipate that these innovative chemistries will provide valuable tools for studying sulfur biology and for developing new RSS donors and bio‐orthogonal cleavage techniques.
Article Details
Authors (14)
Yalun Dong
State Key Laboratory of Organic‐Inorganic Composites and Beijing Key Lab of Bioprocess Beijing University of Chemical Technology Beijing 100029 P.R. China
Haishun Ye
State Key Laboratory of Organic‐Inorganic Composites and Beijing Key Lab of Bioprocess Beijing University of Chemical Technology Beijing 100029 P.R. China
Baifan Wang
State Key Laboratory of Elemento‐Organic Chemistry, College of Chemistry Nankai University Tianjin China
Dejun Ma
State Key Laboratory of Elemento‐Organic Chemistry, College of Chemistry Nankai University Tianjin China
Xueying Kang
State Key Laboratory of Organic‐Inorganic Composites and Beijing Key Lab of Bioprocess Beijing University of Chemical Technology Beijing 100029 P.R. China
Wenfang Liang
State Key Laboratory of Organic‐Inorganic Composites and Beijing Key Lab of Bioprocess Beijing University of Chemical Technology Beijing 100029 P.R. China
Xuekang Cai
State Key Laboratory of Organic‐Inorganic Composites and Beijing Key Lab of Bioprocess Beijing University of Chemical Technology Beijing 100029 P.R. China
Shanshan Liu
Chenyang Jiang
Wenhao Du
Huatang Zhang
Hongyan Sun
Zhen Xi
State Key Laboratory of Elemento‐Organic Chemistry, College of Chemistry Nankai University Tianjin China
Long Yi
State Key Laboratory of Extreme Photonics and Instrumentation College of Optical Science and Engineering Zhejiang University Hangzhou 310027 China