Biocompatible 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.
Authors
- Shuai Liu (ORCID: https://orcid.org/0000-0002-8405-6743)
- Zhiyou Su
- Yongjun Zhou (ORCID: https://orcid.org/0000-0002-3005-2843)
- Hongrui Zhu (ORCID: https://orcid.org/0000-0001-6823-6827)
- Hou‐Wen Lin (ORCID: https://orcid.org/0000-0002-7097-0876)
- Wei‐Hua Jiao (ORCID: https://orcid.org/0000-0003-4835-4775)
- Hongze Liao (ORCID: https://orcid.org/0000-0003-1340-6811)
- Jia Zhang (ORCID: https://orcid.org/0000-0002-1433-6651)
- Shuping Wang (ORCID: https://orcid.org/0000-0001-8120-4213)
- Lei Li (ORCID: https://orcid.org/0000-0001-9887-0175)
- Fan Sun (ORCID: https://orcid.org/0000-0001-8483-152X)
- Zhizhen Zhang (ORCID: https://orcid.org/0000-0002-8290-3507)
- M. Z. Fan (ORCID: https://orcid.org/0009-0003-6452-7696)
Institutions
- Shenyang Pharmaceutical University (CN)
- Shanghai Jiao Tong University (CN)
- Renji Hospital (CN)
- Liaoning University of Traditional Chinese Medicine (CN)
- Zhejiang Ocean University (CN)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-11-24
- DOI
- https://doi.org/10.1038/s41467-025-65244-7
- Primary Topic
- Radical Photochemical Reactions
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- National Natural Science Foundation of China
- East China University of Science and Technology
- Science and Technology Commission of Shanghai Municipality
- Natural Science Foundation of Shandong Province
- National Key Research and Development Program of China