Mass spectrometry-led catalyst discovery

催化剂提高了化学反应的速率，但在反应过程中本身并不被消耗。它们的工作原理是通过增加步骤为反应提供另一种途径，所有这些步骤都比未催化的反应快，并最终使催化剂再次再生。在各种规模的工业重要反应中，很大一部分都使用催化剂；它们经常使原本不可能实现的转换成为可能；它们使反应更干净、更快；而且它们产生的废物也少得多（它们的“原子经济”，即最终进入产品的原料中原子的比例，通常非常高）。现代催化剂通常非常有效，少量就能产生大量的产物。虽然这种效率无疑是一件好事，但它也带来了一个问题——当只有少量的混合物是有趣的时，我们如何在相关条件下研究催化反应？**我们开发了一种新的方法来研究催化反应，这种技术主要是科学家研究大型生物分子（如蛋白质）的技术：电喷雾电离质谱（ESI-MS）。我们将使用它来研究催化中的难题，通过使用它来检查中间体的身份和丰度，同时使用能够检查溶液中丰富物种（主要是起始材料和产物的数量）的补充方法来测量反应的进展。直接探测中间体的能力也为发现新的催化剂和新的转化开辟了机会。虽然许多其他研究小组都被类似的问题所吸引，但我们的方法将给我们带来相当大的竞争优势：通过使用一套工具来测量主要成分（反应物，产物，通常在摩尔浓度下），而使用ESI-MS来探测次要成分（催化中间体，静息状态，通常在毫摩尔到微摩尔浓度下），我们将能够在六个数量级或更多的动态范围内操作。在此过程中，我们将对反应进行的方式获得前所未有的洞察力，我们将利用我们的理解来合理地改进催化剂，并开发更清洁、更快、更有效的化学转化新方法。

Catalysts increase the rate of chemical reactions, but are not themselves consumed in the process. They work by providing an alternative pathway for reaction through an increased number of steps, all of which are faster than the uncatalyzed reaction and that ultimately regenerate the catalyst again. A huge proportion of industrially-important reactions at all scales use catalysts; they frequently enable transformations that would otherwise be impossible; they make reactions cleaner and faster; and they generate significantly less waste (their "atom economy", or proportion of atoms in starting materials that end up in products, is often very high). Modern catalysts are often extraordinarily effective, with tiny quantities generating enormous amounts of product. While this efficiency is unquestionably a good thing, it also creates a problem - how do we study catalytic reactions under relevant conditions when only a tiny amount of the mixture is interesting?**We have developed novel methodologies to study catalytic reactions using a technique that was principally the preserve of scientists studying large biomolecules such as proteins: electrospray ionization mass spectrometry (ESI-MS). We will use it to study the difficult problems in catalysis by using it to inspect the identity and abundance of intermediates while simultaneously measuring the progress of reactions using complementary methods capable of examining the abundant species in solution (primarily the quantity of starting materials and products). The ability to probe intermediates directly also opens up opportunities for the discovery of new catalysts and new transformations. While numerous other research groups are captivated by similar problems, our approach will give us a considerable competitive advantage: by using one set of tools to measure the major components (reactants, products, typically at molar concentrations) while using ESI-MS to probe the minor components (catalytic intermediates, resting states, typically at milli- to micromolar concentrations), we will be able to operate across six orders of magnitude or more of dynamic range. In doing so, we will obtain unprecedented insight into the way in which reactions proceed, and we will use our understanding to rationally improve catalysts and to develop new ways of transforming chemicals that are cleaner, faster and more efficient.