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，以及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。对机理的了解具有强大的能力：它可以加速或减慢化学反应，使其更环保，并按比例放大以生产现代社会所依赖的药物，农用化学品，智能材料等。核磁共振（NMR）是研究液体反应机理的最常用技术（学术界和工业界）。NMR提供了反应物种及其浓度的独特而精细的结构信息，允许深入深入的研究。然而，目前可用的常规NMR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，该技术不适用于那些反应完成的时间比加载到仪器中所需的时间更短（通常是几分钟）的反应。本研究项目通过一种新设计的微型反应器来解决这一挑战，该反应器允许研究过程在加载到NMR仪器后开始，而不是预先开始。反应器的设计使得反应可以在开始后的百分之几秒内进行分析，而不是目前所需的秒或分钟。实现这一目标在工程、电子和仪器控制方面带来了巨大的挑战。我们将建造和测试两种微型反应堆设计。我们将与我们的项目伙伴Ute Hellmich博士（德国）合作，分析与被忽视的热带疾病（包括非洲昏睡病）有关的酶。目前的NMR技术迄今为止对这种酶的短寿命物种（酶/抑制剂遭遇复合物）的产生是“盲目的”，通过这种合作进行检测将清楚地表明这项研究的突破性。

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.