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Updated: Oct 19, 2025

Free Radicals in Chemical Biology: from Chemical Behavior to Biomarker Development
Published on: April 15, 2013
Enhancing the Potential of Miniature-Scale DNA-Compatible Radical Reactions via an Electron Donor-Acceptor Complex
Bizhen Lin1, Weiwei Lu2, Zhen-Yu Chen3
1Guangdong Provincial Key Laboratory of Chiral Molecules and Drug Discovery, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China.
Abstract:
DNA-encoded library (DEL) technology is a powerful tool in the discovery of bioactive probe molecules and drug leads. Mostly, the success in DEL technology stems from the molecular diversity of the chemical libraries. However, the construction of DELs has been restricted by the idiosyncratic needs and the required low concentration (∼1 mM or less) of the library intermediate. Here, we report visible-light-promoted on-DNA radical coupling reactions via an electron donor-acceptor (EDA) complex and a reversible adsorption to solid support (RASS) strategy. This protocol provides a unique solution to the challenges of increasing the reactivity of highly diluted DNA substrates and reducing the residues of heavy metals from photocatalysts. A series of on-DNA indole sulfone and selenide derivatives were obtained with good to quantitative conversions. It is anticipated that these mild-condition on-DNA radical reactions will significantly improve the chemical diversity of DELs and find widespread utility to DEL construction.
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