biostudies-literatureUnknown16(1)Liao HThis study develops a catalyst-free, light-induced decarboxylative coupling utilizing N-hydroxynaphthalimide esters (NHNI esters) as multifunctional reagents, acting as photosensitizers, oxidants, and redox-active esters. In cell lysates, this method efficiently enabled Csp3-Csp3 coupling reactions with silyl enol ethers or Michael acceptors. Substrates with donor-acceptor (D-A) frameworks are found to significantly enhance reaction efficiency, with photophysical characterization showing that efficient D-A framework promotes the formation of charge transfer state (CT), thus improving coupling efficiency. The system was further demonstrated in peptide labeling and DNA-encoded library (DEL) technology for the introduction of diverse alkyl groups. Notably, the successful application of this methodology in live cells is confirmed through confocal microscopy and HRMS, providing an efficient tool for chemical modification in biological systems.Nature communications10342https://www.ebi.ac.uk/biostudies/studies/S-EPMC12644656biostudies-literatureBiocompatible decarboxylative coupling enabled by N-hydroxynaphthalimide esters.PMC12644656Zhu HRZhang JZhou YJLiu SLi LLin HWZhang ZLiao HFan MJSun FSu ZWang SPJiao WfalseBiocompatible decarboxylative coupling enabled by N-hydroxynaphthalimide esters.This study develops a catalyst-free, light-induced decarboxylative coupling utilizing N-hydroxynaphthalimide esters (NHNI esters) as multifunctional reagents, acting as photosensitizers, oxidants, and redox-active esters. In cell lysates, this method efficiently enabled Csp3-Csp3 coupling reactions with silyl enol ethers or Michael acceptors. Substrates with donor-acceptor (D-A) frameworks are found to significantly enhance reaction efficiency, with photophysical characterization showing that efficient D-A framework promotes the formation of charge transfer state (CT), thus improving coupling efficiency. The system was further demonstrated in peptide labeling and DNA-encoded library (DEL) technology for the introduction of diverse alkyl groups. Notably, the successful application of this methodology in live cells is confirmed through confocal microscopy and HRMS, providing an efficient tool for chemical modification in biological systems.2025-01-01T00:00:00Z2025 Nov2026-06-05T19:07:14.335Z2026-05-20T03:14:46.367ZS-EPMC126446564128571510.1038/s41467-025-65244-7