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

核磁共振（NMR）波谱是研究分子结构和行为最有用的方法之一，在了解我们周围的世界和开发新技术方面都至关重要。它是测定纯化合物化学结构的特别有力的工具。然而，大自然更复杂，一些最有趣的科学挑战表现为复杂的混合物。这些通常有非常拥挤的核磁共振光谱，由于存在许多不同浓度的物种，因此光谱很难（有时不可能）解释。化学家和生命科学家一直在为从复杂混合物的核磁共振光谱中发现的多个重叠信号中提取定性和定量信息而斗争。我们迫切需要新的核磁共振方法来解决更广泛的科学问题，并减少从混合物中提取化学和生物信息所需的时间和精力。本文介绍了一系列新的核磁共振方法，这些方法解决了混合物分析领域中一些最具挑战性的问题，特别是那些高动态范围混合物的问题。我们将演示如何获得无外部信号（例如卫星和人工制品）的超净光谱，使我们能够识别和量化至少低至0.1%水平的成分（制药行业当前的监管限制）。我们还将展示如何-通过降低核磁共振光谱的复杂性，使用“纯移位”方法，将多路信号分解成单线和/或“光谱编辑”方法，挑选出单个成分的信号-完整混合物成分的结构确定可以简单有效地实现。共同的主线是，所有这些新方法都集中在增加从完整混合物光谱中获得的定性，定量和结构信息的数量。这些新方法将直接应用于广泛的学术和工业研究领域，包括化学、生物化学、生物学、制药、石油化学、农业化学、医疗保健、香料和香料。

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.