Work

Biocompatible decarboxylative coupling enabled by N-hydroxynaphthalimide esters

Year: 2025

Type: article

Abstract: 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. Achieving selective and precise modification of macromolecules under biocompatible conditions (such as aqueous solutions, mild temperatures, and neutral pH) remains a significant technical challenge. Here, the authors develop a photoinduced coupling reaction based on N-hydroxy naphthalimide esters, which is effective in biologically relevant conditions.

Source: Nature Communications

DOI: 10.1038/s41467-025-65244-7