Ultrahigh resolution NMR: citius, altius, fortius

了解分子的结构和行为对于了解我们周围的世界以及利用化学帮助我们在那个世界中生存和繁荣至关重要。确定分子结构的唯一最有用的方法是核磁共振光谱学。分子中的每个氢原子--大多数分子都含有许多--会产生一系列被称为多重态的信号。多重态在光谱中的位置(化学位移)取决于原子的局部化学环境；多重态结构取决于它与附近原子的磁性相互作用(标量耦合)。随着我们对化学和生物化学的理解的进步，我们需要研究的物种的规模和复杂性都在增加。核磁共振信号的数量相应地增加，导致非常拥挤的核磁共振谱，可能很难甚至不可能解释。化学家和生命科学家一直在为从大多数核磁共振谱中发现的复杂的重叠多重态集合中提取结构信息而战。这一提议描述了一系列新的实验方法，这些方法通过建立在“纯位移”核磁共振的最新发展基础上，抑制了磁相互作用的影响，从而极大地简化了谱。在大多数情况下，新方法以灵敏度为代价来换取速度，提高了使用光谱仪时间的效率，并能够获得有关化学体系的详细结构信息，目前这些化学体系过于复杂，无法通过溶液状态核磁共振进行研究。共同的主线是，所有这些发展都集中在增加核磁共振实验的信息带宽--增加单位时间可获得的结构信息量。最终的结果将是在现有的光谱仪资源内提供更多的化学信息，并使在实际时间框架内解决最具挑战性的结构问题成为可能。将使用的关键工具是耦合交互控制和量身定制的数据采样。这两种技术都开始在化学核磁共振光谱学中找到应用，但都没有接近实现其全部潜力，它们之间的协同作用几乎完全没有开发出来。这些新方法将在包括化学、生物化学、生物、制药、保健、农用化学以及香料和香料在内的广泛的学术研究领域和工业部门得到广泛的应用。

Understanding the structures and behaviour of molecules is of critical importance in understanding the world around us, and in using chemistry to help us survive and prosper in that world. The single most useful method for determining molecular structure is NMR spectroscopy. Every hydrogen atom in a molecule - and most molecules contain many - produces a family of signals known as a multiplet. The position of the multiplet within the spectrum (the chemical shift) depends on the local chemical environment of the atom; the multiplet structure depends on its magnetic interactions (scalar couplings) with nearby atoms. As our understanding of chemistry and biochemistry advances, the species we need to study increase in size and complexity. The number of NMR signals grows accordingly, leading to very crowded NMR spectra that can be difficult or even impossible to interpret. Chemists and life scientists fight a continual battle to extract structural information from the complex sets of overlapping multiplets that are found in most NMR spectra.This proposal describes a family of new experimental methods that enhance the speed, efficiency, and scope of NMR, by building on recent developments in "pure shift" NMR, which suppresses the effects of magnetic interactions and hence greatly simplifies spectra. For the most part the new methods trade sensitivity, which with recent advances in instrumentation is no longer a limiting factor for most samples, for speed, improving the efficiency with which spectrometer time is used, and enabling detailed structural information to be obtained on chemical systems that currently are too complex to be studied by solution state NMR. The common thread is that all these developments are focused on increasing the information bandwidth of NMR experiments - increasing the amount of structural information obtainable per unit time. The net result will be both to enable more chemical information to be delivered within existing spectrometer resources, and to make it possible to attack the most challenging structural problems within practical timeframes. The key tools that will be used are control of coupling interactions and tailored data sampling. Both technologies are beginning to find application in chemical NMR spectroscopy, but neither has come close to realising its full potential, and synergies between them are almost entirely unexploited. In combination they should enhance both the throughput and the power of chemical NMR in laboratories world-wide, in both industry and academia.These new methods will find use across a wide range of academic research areas and industrial sectors including chemistry, biochemistry, biology, pharmaceuticals, healthcare, agrochemistry, and flavours and fragrances.