Clearing the undergrowth: new NMR techniques for high dynamic range mixtures

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Nuclear magnetic resonance (NMR) spectroscopy is one of the most useful methods for studying the structures and behaviours of molecules, and of critical importance both in understanding the world around us and in developing new technologies. It is a particularly powerful tool for determining the chemical structures of pure compounds. However, Nature is more complicated, and some of the most interesting scientific challenges present themselves as complex mixtures. These often have very crowded NMR spectra, due to the presence of many species with many different concentrations, and the spectra are therefore very difficult (sometimes impossible) to interpret. Chemists and life scientists fight a continual battle to extract qualitative and quantitative information from the multiple overlapping signals that are found in most NMR spectra of complex mixtures. New NMR methods are urgently needed to allow us to address a wider range of scientific problems, and to reduce the time and effort needed to extract chemical and biological information from mixtures.This proposal describes a series of novel NMR methods that address some of the most challenging problems in the field of mixture analysis, especially those of high dynamic range mixtures. We will demonstrate how ultraclean spectra, free of extraneous signals (e.g. satellites and artefacts), can be obtained, allowing us to identify and quantify components at least down to the 0.1% level (the current regulatory limit in the pharmaceutical industry). We will also show how - by reducing the complexity of NMR spectra, using "pure shift" methods that collapse multiplet signals into singlets and/or "spectral editing" methods that pick out the signals of individual components - structure determination of the components of intact mixtures can be achieved simply and efficiently. The common thread is that all these new methods are focused on increasing the amount of qualitative, quantitative and structural information obtainable from the spectra of intact mixtures. These new methods will have direct applications across a wide range of academic and industrial research areas, including chemistry, biochemistry, biology, pharmacy, petrochemistry, agrochemistry, healthcare, and flavours and fragrances.