SHARPER NMR: fast and accurate analysis of molecules, reactions and processes

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Nuclear Magnetic Resonance (NMR) spectroscopy is a very useful analytical technique, which has applications across the range of sciences, including medicine, biology, geosciences, physics and chemistry. It can be performed on living organisms, solid state materials, or molecules dissolved in liquids. This proposal focusses on the solution state NMR spectroscopy.Solution state NMR is a bread and butter technique for chemists. It has been around for 70 years, but does not show any sign of slowing down in its development, improvement, and increased efficiency. What distinguishes NMR from other spectroscopies is the longevity of the excited states of nuclei (or spins, as we often called them) that are subjects of NMR experiments. Their lifetime on the order of milliseconds to seconds allows scientists to design elaborate ways of spin manipulation before, or these days also during, signal acquisition. The purpose of these manipulations is to obtain specific information about the structure or the chemical state of the molecule, including interactions with other molecules.Such manipulations are important for several reasons: (i) sometimes there is too much to see and we need to simplify NMR spectra in order to access the information we require. (ii) NMR is a relatively insensitive technique and compared to other analytical techniques, such as for example mass spectrometry (MS), requires large amounts of material (typically milligram quantities, compared to micro, nano grams or even pico grams that are sufficient for MS). (iii) In its standard implementation, NMR can be too slow to monitor fast processes that are occurring on millisecond to second times scales. (iv) Ideally, solution state NMR is performed on homogeneous samples and standard techniques struggle to provide high quality information about heterogeneous system, e.g. characterisation of processes taking place at the interface of two immiscible liquids, or when a gas is bubbled through a solution.This proposal addresses the difficulties outlined above and aims to design novel NMR techniques that allow information to be obtained under circumstances where this is not as yet possible (e.g. heterogeneous systems), or bring evident improvements to existing techniques in terms of efficiencies (time saving) and quality of information obtained. Accuracy of NMR parameters, that are ultimately interpreted to provide chemical structures, characterise chemical reactions, or determine molecular sizes, will be improved. The focus is on (i) monitoring of fast chemical reactions and (ii) characterising molecular sizes and (iii) going beyond the primary structure of molecules (the order in which the individual atoms are connected to each other) to how the atoms are arranged in the three-dimensional space (conformation, tertiary structure). Such information is crucial to our ability to rationalise intermolecular interactions (e.g. interactions of drugs with biomacromolecules). Another important aspect of the proposed techniques is that they can be applied to complex systems. NMR has traditionally been very good in studying pure compounds, but to this day struggles to study them as part of mixtures. In real life situations it is not always possible to separate out individual molecules from mixtures, and many industries must learn how to deal with mixtures efficiently. We will work with a manufacture of benchtop NMR spectrometers to bring the developed techniques directly into fume hoods and production lines, out of the specialised NMR laboratories. We anticipate that the new methods we will develop will be applied across a wide spectrum of academic and industrial research.