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

Lead Research Organisation: University of Edinburgh
Department Name: Sch of Chemistry

Abstract

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.

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