DNA-encoded libraries (DELs) are a key technology for identifying small-molecule hits in both the pharmaceutical industry and academia, but their chemical diversity is largely limited to water-compatible reactions to aid in the solubility and integrity of encoding DNA tags. To broaden the DEL chemical space, we present a workflow utilizing DNA–cationic surfactant complexation that enables dissolution and reactions on-DNA in anhydrous organic solvents. We demonstrate its utility by developing DEL-compatible photoredox decarboxylative C(sp²)–C(sp³) coupling under water-free conditions. The workflow is optimized for the 96-well format necessary for large-scale DEL productions, and it enables screening and optimization of DEL-compatible reactions in organic solvents.

中文翻译：

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疏水性表面活性剂-DNA 复合物 (Surf-DNA) 可在无水条件下实现 DNA 编码文库兼容的脱羧芳基化


DNA 编码文库 (DEL) 是制药行业和学术界识别小分子命中的关键技术，但其化学多样性很大程度上限于水相容性反应，以帮助编码 DNA 标签的溶解度和完整性。为了拓宽 DEL 化学空间，我们提出了一种利用 DNA-阳离子表面活性剂络合的工作流程，可以在无水有机溶剂中溶解 DNA 并进行反应。我们通过在无水条件下开发 DEL 兼容的光氧化还原脱羧 C(sp ² )–C(sp ³ ) 偶联来证明其实用性。该工作流程针对大规模 DEL 生产所需的 96 孔格式进行了优化，并且能够筛选和优化有机溶剂中的 DEL 兼容反应。