Harnessing Electrostatics to Unlock Cage Catalysis: A Combined Experimental Computational Approach

将一种分子转化为另一种分子的能力是社会经济进步的核心。它允许石油或煤炭等原材料转化为高效用产品，如药品、燃料和塑料。然而，大多数分子不容易将自己转化为其他分子，而需要使用催化剂。这些物种极大地加速了一个分子向下一个分子的转化，因此，例如，通常需要数百万年的化学反应只需要几秒钟。催化剂还可以有其他好处，比如它们可以非常有选择性，使用一种催化剂可以产生单一的产品，但通常会形成许多产品。这对于制药行业的应用尤其重要。我们日常使用的许多催化剂都是人造的。然而，大自然已经提供了一系列被称为酶的催化剂，这些催化剂使生命所依赖的化学过程成为可能。尽管合成催化剂和酶具有加速化学反应的共同功能，但它们的工作方式却截然不同。人工催化剂通常依赖于稀有的金属元素，这些元素是很好的催化剂，但通常很难使用，因为它们在空气中不稳定。相比之下，酶也是很好的催化剂，主要使用“有机元素”(碳、氢、氮、氧)，因此它们完全稳定，因为它们需要在体内发挥作用。在这项研究中，我们的目标是制造模仿酶工作方式的催化剂。这是一项艰巨的任务，因为酶是一种大聚合物，含有数千个原子，以复杂的三维结构组织起来。酶的活性部分也隐藏在一个半中空的内部。因此，我们将设计具有中空内部的合成催化剂，这样它们就可以复制酶的活性部分，然而，它们也更简单和更容易制备，因为当简单的积木(如乐高积木)混合在一起时，它们会自发组装。一旦分子结合在这些组装的催化剂中，它们就会被激活，并进行化学反应，选择性地生成产品。开发一种具有生物催化剂或“常规”催化剂的熟练程度的简单、“用户友好”的新型催化剂，有可能为高效用产品提供具有成本效益的途径，从而提供显著的社会经济效益。

The ability to convert one molecule into another is central to socioeconomic progress. It allows raw materials, such as oil or coal, to be converted into high utility products, such as drugs, fuels and plastics. Most molecules, however, do not readily transform themselves into others and instead require the use of a catalyst. These species dramatically speed up the conversion of one molecule into the next, so, for example, a chemical reaction that would normally take millions of years only takes a few seconds. Catalysts can also have other benefits, such as they can be very selective, wherein using a catalyst produces a single product whereas often many are formed. This is especially important for applications in the pharmaceutical industry. Many of the catalysts we use on a day-to-day basis are man-made. However, nature already provides a wide range of catalysts, known as enzymes, which make possible the chemical processes upon which life depend. Despite their common function of speeding up chemical reactions, synthetic catalysts and enzymes work in fundamentally different ways. Artificial catalysts often rely on rare, metallic elements, which are excellent catalysts but are often difficult to work with because they are not stable in air. In contrast, enzymes, which are also excellent catalysts, principally use "organic elements" (carbon, hydrogen, nitrogen, oxygen) so they are completely stable as they need to function in the body. In this research, we aim to make catalysts that mimic the way that enzymes work. This is a difficult task because enzymes are large polymers, containing thousands of atoms organised in complex three-dimensional structures. The active part of the enzyme is also hidden away in a semi-hollow interior. We will thus design synthetic catalysts that also possess a hollow interior, so they can replicate the active part of an enzyme, however, they are also much simpler and easier to prepare because they spontaneously assemble when simple building blocks (like Lego pieces) are mixed together. Once the molecules are bound inside these assembled catalysts, they become activated and undergo a chemical reaction to selectively generate the product. The development of a new class of simple and "user-friendly" catalysts that possess the proficiency of either biological or "conventional" catalysts has the potential to deliver cost-effective routes to high utility products and thus provide significant socioeconomic benefits.