美国圣犹达儿童研究医院Blair Daniel J.研究团队报道了化学反应的连续收集分析。相关研究成果发表在2024年12月11日出版的《自然》。

从模块化构建块中自动合成小有机分子，有可能改变人们制造药物和材料的能力。这种分子构建策略的颠覆性加速广泛地释放了其功能潜力，并需要整合许多新的组装化学物质。尽管高通量化学的最新进展可以加快适当合成方法的开发，例如，从广泛的潜在选择中选择适当的化学反应条件，但需要等效的高通量分析方法。

该文中，研究人员报告了一种通过质谱法，快速定量分析化学反应的简化方法。化学构建块的内在碎片特征概括了化学反应的分析，能够实现亚秒级的反应结果读数。

这一进展的核心是确定起始材料碎片模式，作为质谱下游产品分析的通用条形码。将这些特征与声滴喷射质谱结合，可以消除缓慢的色谱步骤，并以多种形式连续评估化学反应。

这使得能够将反应条件分配给，来自超高通量化学合成实验的分子。更一般地说，这些结果表明，化学合成固有的碎片特征可以实现快速的数据丰富实验。

附：英文原文

Title: Continuous collective analysis of chemical reactions

Author: Hu, Maowei, Yang, Lei, Twarog, Nathaniel, Ochoada, Jason, Li, Yong, Vrettos, Eirinaios I., Torres-Hernandez, Arnaldo X., Martinez, James B., Bhatia, Jiya, Young, Brandon M., Price, Jeanine, McGowan, Kevin, Nguyen, Theresa H., Shi, Zhe, Anyanwu, Matthew, Rimmer, Mary Ashley, Mercer, Shea, Rankovic, Zoran, Shelat, Anang A., Blair, Daniel J.

Issue&Volume: 2024-12-11

Abstract: The automated synthesis of small organic molecules from modular building blocks has the potential to transform our capacity to create medicines and materials1,2,3. Disruptive acceleration of this molecule-building strategy broadly unlocks its functional potential and requires the integration of many new assembly chemistries. Although recent advances in high-throughput chemistry4,5,6 can speed up the development of appropriate synthetic methods, for example, in selecting appropriate chemical reaction conditions from the vast range of potential options, equivalent high-throughput analytical methods are needed. Here we report a streamlined approach for the rapid, quantitative analysis of chemical reactions by mass spectrometry. The intrinsic fragmentation features of chemical building blocks generalize the analyses of chemical reactions, allowing sub-second readouts of reaction outcomes. Central to this advance was identifying that starting material fragmentation patterns function as universal barcodes for downstream product analysis by mass spectrometry. Combining these features with acoustic droplet ejection mass spectrometry7,8 we could eliminate slow chromatographic steps and continuously evaluate chemical reactions in multiplexed formats. This enabled the assignment of reaction conditions to molecules derived from ultrahigh-throughput chemical synthesis experiments. More generally, these results indicate that fragmentation features inherent to chemical synthesis can empower rapid data-rich experimentation.

DOI: 10.1038/s41586-024-08211-4

Source: https://www.nature.com/articles/s41586-024-08211-4