{"title":"DNA-Compatible Photoredox Atom Transfer Radical Addition to Alkynes with Thiosulfonates","authors":"Cong Wang, Yinghui Lu, Zhiyuan Peng, Chi Zhang, Qingchao Liu, Xue-Qiang Wang, Tiezheng Jia","doi":"10.31635/ccschem.024.202404703","DOIUrl":null,"url":null,"abstract":"<p>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<sup>2</sup>–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 <i>E</i>-β-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.</p>","PeriodicalId":9810,"journal":{"name":"CCS Chemistry","volume":"1 1","pages":""},"PeriodicalIF":9.4000,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"CCS Chemistry","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.31635/ccschem.024.202404703","RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, MULTIDISCIPLINARY","Score":null,"Total":0}
引用次数: 0
Abstract
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 Csp2–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-β-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.
随着DNA编码文库(DEL)和核酸适配体技术的蓬勃发展,DNA兼容反应越来越受到制药业和学术界的关注。在这方面,通过 Csp2-S 键在 DNA 上结合有机硫支架具有优势,但仍未得到广泛应用。在此,我们报告了一种温和、高效的光氧化原子转移自由基加成(ATRA)方法,在有机光催化剂的催化下,将硫代磺酸盐与末端和内部炔烃进行加成,从而以优异的区域和立体选择性生成了多种 E-β-芳基硫醇-乙烯基砜。机理研究表明,磺酰基可能是这一转化过程中的关键中间体。利用其广泛的官能团耐受性以及温和的生物友好型条件,该方案可同时在 DNA 上安装砜和硫化物。更重要的是,氧化还原反应荧光探针(10-乙基-2-磺酸-吖啶酮,ESAC)可以方便地引入到两种常用的适配体(AS1411 和 Sgc8c)上,从而可以对一系列人类肿瘤细胞系进行后续成像研究。值得注意的是,共聚焦显微镜和流式细胞仪技术都捕捉到了ESAC-适配体进入细胞的过程,其中大部分ESAC-适配体在被细胞吸收后发出绿色荧光,小部分留在外膜上的ESAC-适配体则发出蓝色荧光。
期刊介绍:
CCS Chemistry, the flagship publication of the Chinese Chemical Society, stands as a leading international chemistry journal based in China. With a commitment to global outreach in both contributions and readership, the journal operates on a fully Open Access model, eliminating subscription fees for contributing authors. Issued monthly, all articles are published online promptly upon reaching final publishable form. Additionally, authors have the option to expedite the posting process through Immediate Online Accepted Article posting, making a PDF of their accepted article available online upon journal acceptance.