Ultrahigh resolution NMR: citius, altius, fortius

了解分子的结构和行为对于理解我们周围的世界，以及利用化学帮助我们在这个世界上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波谱。分子中的每个氢原子——大多数分子包含许多氢原子——会产生一系列被称为多重信号的信号。多重体在光谱中的位置（化学位移）取决于原子的局部化学环境；多重结构取决于它与附近原子的磁相互作用（标量耦合）。随着我们对化学和生物化学理解的进步，我们需要研究的物种的大小和复杂性也在增加。核磁共振信号的数量相应增加，导致非常拥挤的核磁共振光谱难以甚至不可能解释。化学家和生命科学家一直在为从大多数核磁共振光谱中发现的复杂的重叠多胞胎中提取结构信息而斗争。本提案描述了一系列新的实验方法，通过建立“纯移位”核磁共振的最新发展，提高了核磁共振的速度、效率和范围，这种方法抑制了磁相互作用的影响，从而大大简化了光谱。在大多数情况下，新方法以灵敏度为代价（随着仪器仪表的最新进步，灵敏度不再是大多数样品的限制因素），以速度为代价，提高了使用光谱仪时间的效率，并能够获得化学系统的详细结构信息，这些化学系统目前过于复杂，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上——增加单位时间内可获得的结构信息的数量。最终的结果将是在现有的光谱仪资源范围内提供更多的化学信息，并使在实际的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的控制和定制的数据采样。这两种技术都开始在化学核磁共振波谱中得到应用，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得到开发。结合起来，它们将提高世界各地工业和学术界实验室的化学核磁共振的吞吐量和能力。这些新方法将广泛应用于学术研究领域和工业部门，包括化学、生物化学、生物学、制药、医疗保健、农用化学、香料和香料。

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.