Flow-tolerant NMR experiments

If successful, this work will allow the full range of NMR experiments to be available at full sensitivity even for convecting and flowing systems. Why does this matter? Liquid state NMR is an essential analytical tool for chemists as NMR is arguably the most powerful method available for accessing information about the structures and dynamics of molecules in solution, and for monitoring reactions. It underpins research and development across the EPSRC remit and is critical in many areas of chemistry and materials. This proposal will produce a new set of NMR experiments that significantly increase the performance of current NMR instrumentation. Low sensitivity is intrinsic to the NMR technique and in some cases, this is exacerbated by motion within the liquid sample. Many of the most powerful NMR methods use pulsed field gradients (PFGs) to ensure clean spectra by removing spurious signals. Almost all of these methods currently require that the sample liquid remain absolutely stationary. The liquid motion can arise from intentional flow - e.g. for reaction monitoring, where a sample is recirculated from a reactor - or unintentional convection, which occurs in nearly all samples. Flowing a sample through an NMR spectrometer allows real-time analysis, with minimal perturbation, in reaction monitoring and chromatography. This is an area of steadily growing importance and has become available to a larger audience thanks to modern less expensive, and more portable, low-field instruments. Convection affects almost all samples and is of particular concern for systems that use cryogenically cooled detectors 'cryoprobes' which are susceptible to temperature gradients and the sensitivity of this expensive equipment is usually not realised. The big temperature gradients in cryoprobes leads to rapid convection in the sample liquid. Similar losses happen in normal probes with room temperature coils if the sample is maintained at a temperature above or below that of the probe. Such "variable temperature" or "VT" experiments are in everyday use for studying the rates of chemical processes, and for measuring spectra of samples such as polymers that need to be heated to dissolve. In both cases, the new family of flow tolerant NMR experiments to be developed in this proposal will be transformative. Current NMR equipment will be enabled to operate at its maximum and intended sensitivity, and the full range of modern NMR methods will become accessible in real-time reaction monitoring. This project will develop new flow-tolerant PFG NMR methods for chemists that reverse the effects of sample motion on the NMR signal, restoring lost sensitivity and enabling the full range of powerful PFG experiments to be used both in cryoprobes and variable temperature experiments, and in flowing samples. The impacts will be felt in a wide range of academic and industrial research areas, including pharmaceutical and natural product chemistry, biochemistry, biology, pharmacy, petrochemistry, agrochemistry, healthcare, and flavours and fragrances.