Reaction monitoring on micro-second timescales by nuclear magnetic resonance: aiming for a paradigm shift in the study of reaction mechanisms

我们都熟悉赢得自行车比赛的必备条件的概念，简单地说就是先冲过终点线。然而，当我们反思这一过程时，我们可能会对这一事件提出许多潜在的问题。这些问题包括，当时有多少参与者，他们是否都在同一时间点出发，他们是否都遵循相同的路线，他们的平均速度是多少，他们是否都到达相同的终点，自行车的效果如何，如果是在接近终点的情况下，谁确实是第一个。如果我们要检查过渡金属催化的反应，那么会产生一系列类似的问题。在当今高科技世界，过渡金属催化的反应被用来产生许多我们认为理所当然的化学物质。然而，现在参与者的规模要小得多，需要非常特殊的方法来查看它们。此外，如果我们要准确地了解反应的效率，我们仍然需要发令枪，事实上，就像在自行车比赛中一样，如果我们努力训练并设计出最好的催化剂(自行车)，我们就可以以理想的方式影响结果。在这里，这可能只是为了减少能源需求，或者确实是为了增加所需产品(产率)的比例，如果该反应以100万吨的规模完成，这对于最大限度地减少浪费至关重要。在化学中，有一种非常特殊的方法，称为核磁共振光谱(核磁共振)，它允许我们对这样一个过程中的参与者拍照，但它通常在几秒钟内测量其信息，而且它比其他一些方法需要更多的材料。我们克服了这一限制，通过同时查看多达100万个相同分子的拷贝，以产生其反应。即使到那时，一些测量可能需要几天时间才能完成。在这个项目中，我们的目标是开发一种新的方法，使用核磁共振来检查分子在催化反应中转化为高价值产品时所采取的路线。我们计划利用这些信息以积极的方式改善反应的结果。我们将使用来自激光的光开始比赛，并使用一种特殊形式的氢，称为仲氢，使我们能够将核磁共振测量的灵敏度提高到一个水平，使我们能够在千分之一秒到百万分之一秒的时间段内完成对反应的监测。仲氢实际上是航天飞机的燃料。在这里，人们可能会认为它的作用就像一个分子摄像机，同时从旁观者(溶液中存在的其他分子)中去除(过滤)任何不需要的信号。我们将通过拍摄核磁共振照片来建立我们对反应路线的理解，其中包含关于比赛开始后不同时间参与者(分子)身份的准确信息。我们将在不同的条件下多次监测相同的过程，以便产生必要的分子水平图像，最终使我们能够优化我们选择的催化过程。这一过程带来的理解水平的提高将使科学家能够以一种以前不可能实现的方式开发和优化催化过程，从而对社会做出更积极的贡献。为了实现这一目标，我们首先必须开发这种新方法，然后建立对其工作原理的严格理解。当实现了这一点后，我们可以开始选择具体的反应。我们将致力于设计并优化新的催化剂，以通过我们方法实现的更好的理解来改进现有的催化剂。我们希望，新方法最终将在其他地方使用，从而在学术界和工业界产生重大影响。

We are all familiar with the concept of what is necessary to win a cycle race, simply to cross the finish line first. When we reflect on this process, however, there are lots of potential questions we might ask about the event. These include, how many participants were there, did they all start at the same point in time, did they all follow the same route, what was their average speed, did they all end up at the same finish-point, what was the effect of the bike, and then in the event of a close finish who indeed was first.A similar range of questions would result if we were to examine transition metal catalysed reactions that are used to produce many of the chemicals we take for granted in today's high-tech world. Now, however, the participants are much smaller and very special methods are needed to view them. Furthermore, we still need a starting gun if we are to learn precisely about the efficiency of the reaction and indeed, just like in the cycle race, if we train hard and design the best catalyst (bike) we can influence the outcome in a desirable way. Here, this might simply be to reduce the energy need or indeed to increase the proportion of desired product (yield) which is vital to minimise waste if the reaction is completed on a 1,000,000 tonne scale. In Chemistry, there is a very special method called nuclear magnetic resonance spectroscopy (NMR) that allows us to take a picture of the participants in such a process but it normally measures its information over a period of seconds and it requires a larger amount of material than some other methods. We overcome this limitation by viewing as many as a million million million copies of the same molecule simultaneously in order to produce its response. Even then, some measurements can take days to complete. In this project we aim to develop a new method using NMR to examine the route taken by molecules during their conversion to high value products in catalytic reactions. We plan to use this information to improve on the reactions' outcomes in a positive way. We will use light from a laser to start the race and employ a special form of hydrogen, known as parahydrogen to enable us to increase the sensitivity of the NMR measurement to a level that will allow us to complete the monitoring of reactions within time periods from a thousandth to a millionth of a second. Parahydrogen was actually the fuel of the space shuttle. Here, one might view it as acting like a molecular video camera whilst at the same time removing (filtering) any unwanted signals from the spectators (other molecules present in the solution). We will build-up our understanding of the reaction's route by taking our NMR picture which contains precise information about the identity of the participants (molecules) at different times after the start of the race. We will monitor the same process several times under different conditions in order to produce the necessary molecular level picture that will ultimately allow us to optimise our chosen catalytic process. The enhanced level of understanding that will result from this process will enable scientists to develop and optimise catalytic processes in a way that was previously impossible and hence contribute more positively to society.In order to achieve this goal, we will first have to develop this new method and then build up a rigorous understanding of how it works. When that has been achieved, we can start to select specific reactions. We will aim to design and then optimise new catalysts to improve on those currently available through the improved understanding achieved by our methods. We hope that ultimately the new method will be used elsewhere and hence have a substantial impact in both academia and industry.