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

我们都很熟悉赢得自行车比赛的必要条件，仅仅是第一个冲过终点线。然而，当我们反思这个过程时，我们可能会问很多关于这个事件的潜在问题。这些问题包括，有多少参与者，他们是否都在同一时间点出发，他们是否都走同样的路线，他们的平均速度是多少，他们是否都到达了相同的终点，自行车的影响是什么，以及在接近终点的情况下谁确实是第一名。如果我们要研究过渡金属催化反应，也会产生类似的问题。过渡金属催化反应用于生产许多我们在当今高科技世界中习以为常的化学品。然而，现在的参与者要小得多，需要非常特殊的方法来观察它们。此外，如果我们要准确地了解反应的效率，我们仍然需要一支发令枪。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），我们就能以一种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，或者实际上是为了增加所需产品的比例（产量），如果反应以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叫做核磁共振波谱（NMR），它允许我们在这样一个过程中拍摄参与者的照片，但它通常在几秒钟内测量其信息，并且比其他方法需要更多的材料。我们克服了这一限制，通过同时观察相同分子的多达一百亿亿个拷贝来产生它的反应。即便如此，一些测量可能需要几天才能完成。在这个项目中，我们的目标是开发一种新的方法，利用核磁共振来检查分子在催化反应中转化为高价值产物的路线。我们计划利用这些信息以积极的方式改善反应的结果。我们将使用激光开始比赛，并使用一种特殊形式的氢，称为对氢，使我们能够提高核磁共振测量的灵敏度，使我们能够在千分之一秒到百万分之一秒的时间内完成对反应的监测。对氢实际上是航天飞机的燃料。在这里，人们可以把它看作是一个分子摄像机，同时从旁观者（溶液中存在的其他分子）那里去除（过滤）任何不需要的信号。我们将通过在比赛开始后的不同时间拍摄包含参与者（分子）身份的精确信息的核磁共振图像来建立我们对反应路线的理解。我们将在不同条件下多次监测同一过程，以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。从这一过程中产生的更高水平的理解将使科学家能够以一种以前不可能的方式开发和优化催化过程，从而为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。当达到这个目标时，我们可以开始选择特定的反应。我们的目标是设计并优化新的催化剂，通过我们的方法获得的更好的理解来改进目前可用的催化剂。我们希望这种新方法最终能在其他地方得到应用，从而对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.