High‐Throughput Optimization of Photochemical Reactions using Segmented‐Flow Nanoelectrospray ‐ Ionization Mass Spectrometry**
High‐Throughput Optimization of Photochemical Reactions using Segmented‐Flow Nanoelectrospray ‐ Ionization Mass Spectrometry**
复制标题
使用分段流纳电喷雾-电离质谱法对光化学反应进行高通量优化**
DOI：
10.1002/anie.202301664
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发表时间：
2023
期刊：
影响因子：
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通讯作者：
Kennedy, Robert T.
中科院分区：
文献类型：
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作者：
Sun, Alexandra C.;Steyer, Daniel J.;Robinson, Richard I.;Ginsburg‐Moraff, Carol;Plummer, Scott;Gao, Jinhai;Tucker, Joseph W.;Alpers, Dirk;Stephenson, Corey R. J.;Kennedy, Robert T.
在药物发现领域，高通量实验技术可以快速优化反应，加快药物化合物库的生成，用于生物学和药代动力学评估。在本文中，我们报告了一个基于分段流动质谱的平台的开发，以实现对早期药物发现的光氧化还原反应的快速探索。具体而言，将基于微孔板的光化学反应屏幕重新格式化为分段流格式，以实现纳米电喷雾电离-质谱分析。这种方法被证明用于复杂药物支架的后期修饰，以及合成类似物的后续结构-活性关系评估。该技术有望通过实现高通量文库多样化来扩展光氧化还原催化在药物发现中的强大能力。
Within the realm of drug discovery, high‐throughput experimentation techniques enable the rapid optimization of reactions and expedited generation of drug compound libraries for biological and pharmacokinetic evaluation. Herein we report the development of a segmented flow mass spectrometry‐based platform to enable the rapid exploration of photoredox reactions for early‐stage drug discovery. Specifically, microwell plate‐based photochemical reaction screens were reformatted to segmented flow format to enable delivery to nanoelectrospray ionization‐mass spectrometry analysis. This approach was demonstrated for the late‐stage modification of complex drug scaffolds, as well as the subsequent structure–activity relationship evaluation of synthesized analogs. This technology is anticipated to expand the robust capabilities of photoredox catalysis in drug discovery by enabling high‐throughput library diversification.