DNA-Compatible Photoredox Atom Transfer Radical Addition to Alkynes with Thiosulfonates

Wang, Cong1; Lu, Yinghui1,2; Peng, Zhiyuan1; Zhang, Chi3,4; Liu, Qingchao2; Wang, Xue-Qiang3,4; Jia, Tiezheng1,3,4,5

2024-09-01

10.31635/ccschem.024.202404703

CCS CHEMISTRY   影响因子和分区

2096-5745

With the blossom of DNA encoded library (DEL) and nucleic acid aptamer techniques, DNA-compatible reactions draw increasing attention in both the pharmaceutical industry and academia. In this regard, the incorporation of organosulfur scaffolds on DNA via the Csp(2)-S bond exhibits advantages but remains underrepresented. Herein, we report a mild and efficient photoredox atom transfer radical addition (ATRA) to terminal and internal alkynes with thiosulfonates catalyzed by organic photocatalyst, furnishing a wide array of E-beta-arylthiol-vinyl sulfones with excellent regio- and stereoselectivity. Mechanistic investigations demonstrate that sulfonyl radical likely served as the key intermediate in this transformation. Leveraging the broad functional group tolerance and the mild and biofriendly conditions, this protocol could be adapted to simultaneously install sulfones and sulfides on DNA. More importantly, a redox-responsive fluorescent probe (10-ethyl-2-sulfonate-acridone, ESAC) could be conveniently introduced on two commonly used aptamers (AS1411 and Sgc8c), allowing their subsequent imaging studies across a series of human tumor cell lines. Remarkably, the process of ESAC-aptamers entering the cells was captured by both confocal microscopy and flow cytometry techniques, whereby most of the ESAC-aptamers exhibited green fluorescence after their cellular uptake, with the small portion remaining in the outer membrane emitting blue fluorescence.

on-DNA reaction photoredox atom transfer radical addition thiosulfonates alkynes

ESCI

英语

第一 ; 通讯

Guangdong Basic and Applied Basic Research Foundation, China["2021B1515120046","2022B1515120075"] ; Science and Technology Innovation Commission of Shenzhen Municipality, China["JCYJ20220818101404010","20220815113214003"] ; High-Level of Special Funds, China[G03050K003] ; National Natural Science Foundation of China[22078263] ; National Key R&D Program of China[2022YFC2106100] ; Hunan Provincial Science Foundation for Distinguished Young Scholars, China[2022JJ10005] ; Key Science and Technology project of Hunan Province, China[2021SK1020]

Chemistry

Chemistry, Multidisciplinary

WOS:001320335700001

CHINESE CHEMICAL SOC

Web of Science

1.Southern Univ Sci & Technol, Res Ctr Chem Biol & Om Anal, Dept Chem, Shenzhen 518055, Guangdong, Peoples R China
2.Northwest Univ, Coll Chem Engn, Dept Pharmaceut Engn, Xian 710069, Shaanxi, Peoples R China
3.Hunan Univ, Coll Chem & Chem Engn, Coll Biol, Mol Sci & Biomed Lab MBL,State Key Lab Chemo Biose, Changsha 410082, Peoples R China
4.Hunan Univ, Aptamer Engn Ctr Hunan Prov, Changsha 410082, Peoples R China
5.Chinese Acad Sci, Key Lab Biomed Imaging Sci & Syst, Shenzhen 518000, Peoples R China

Wang, Cong,Lu, Yinghui,Peng, Zhiyuan,et al. DNA-Compatible Photoredox Atom Transfer Radical Addition to Alkynes with Thiosulfonates[J]. CCS CHEMISTRY,2024.

Wang, Cong.,Lu, Yinghui.,Peng, Zhiyuan.,Zhang, Chi.,Liu, Qingchao.,...&Jia, Tiezheng.(2024).DNA-Compatible Photoredox Atom Transfer Radical Addition to Alkynes with Thiosulfonates.CCS CHEMISTRY.

Wang, Cong,et al."DNA-Compatible Photoredox Atom Transfer Radical Addition to Alkynes with Thiosulfonates".CCS CHEMISTRY (2024).