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

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.