New Horizons in the High Field NMR Interrogation of Transients: Techniques to Assemble Pulse and Analyse in Under One-Hundredth of a Second

对化学物质浓度随时间变化的分析称为“反应动力学”。测量反应动力学，识别反应过程中产生的任何短寿命物质，是理解化学反应如何工作（称为“机制”）的重要组成部分。机制知识具有强大的推动作用：它可以加速或减缓化学反应，使其更加环保，并扩大生产现代社会所依赖的药品、农用化学品、智能材料等。核磁共振（NMR）是研究液体反应机理最常用的技术（在学术界和工业界）。核磁共振提供了反应物质及其浓度的独特而精致的结构信息水平，允许深入深入的研究。然而，目前可用的常规核磁共振技术需要在外部启动反应，然后加载到仪器中进行分析。因此，该技术不适用于反应完成的时间少于将其装入仪器所需的时间（通常是几分钟）。该研究项目通过一种新的微型反应器设计来解决这一挑战，该设计允许正在研究的过程在装载到核磁共振仪器后开始，而不是事先开始。反应堆的设计是这样的，在反应开始后的百分之几秒内就可以分析反应，而不是目前需要的几秒或几分钟。实现这一目标在工程、电子和仪表控制方面带来了巨大的挑战。建设和试验两种小型反应堆设计方案。我们将与我们的项目伙伴Ute Hellmich教授博士（德国）合作，应用它们分析被忽视的热带病，包括非洲昏睡病所涉及的酶。到目前为止，目前的核磁共振技术对这种酶的短寿命物种（酶/抑制剂遇到复合物）的产生“一无所知”，通过这次合作对它们的检测将清楚地证明这项研究的突破性性质。

The analysis of the changes in the concentrations of chemical species with time is termed 'reaction kinetics'. Measuring reaction kinetics, and the identification of any short-lived species generated during a reaction, is an essential component in the understanding of how the chemical reaction works (termed 'mechanism'). Knowledge of mechanism is powerfully enabling: it allows chemical reactions to be accelerated, or slowed down, made more environmentally friendly, and scaled up to produce the pharmaceuticals, agrochemicals, smart materials, etc. that modern society relies upon.Nuclear Magnetic Resonance (NMR) is the most frequently-applied technique (in academia and industry) for the study of reaction mechanisms in liquids. NMR provides unique and exquisite levels of structural information on the reacting species, and their concentrations, allowing deeply-insightful investigations.However, the routine NMR techniques that are currently available require a reaction to be started externally and then loaded into the instrument for analysis. The technique is thus not applicable to reactions that have finished in less time than it takes to load them into the instrument - usually a matter of minutes.This research project addresses this challenge through a new design of mini-reactor that allows the process being studied to be started after it has been loaded into the NMR instrument, instead of beforehand. The design of the reactor is such that the reactions can be analysed just a few hundredths of a second after they have been started, rather than the seconds or minutes currently required. Achieving this brings substantial challenges in terms of engineering, electronic, and instrument control.We will build and test two designs of mini-reactor. We will apply them in collaboration with our project partner Prof Dr Ute Hellmich (Germany) to analyse enzymes involved in neglected tropical diseases, including African Sleeping Sickness. Current NMR techniques have thus far been 'blind' to the generation of short-lived species (enzyme/inhibitor encounter complexes) for this enzyme and their detection through this collaboration will clearly demonstrate the breakthrough nature of this research.