Pure Shift Proton NMR: A Resolution of the Resolution Problem?

质子(氢)核磁共振波谱是化学家用来确定未知化合物分子结构的最广泛的单一工具。这是一个非常通用和灵敏的工具，但它有一个重大缺陷：它很难从分子中不同的氢原子中分离出信号，因为每个原子通常都会产生多个信号。这种多种多样的信号是由于氢核之间的磁相互作用而产生的，它通常导致光谱比如果这些相互作用可以被关闭的情况下的情况更加拥挤大约十倍。不幸的是，虽然在涉及不同类型原子(例如氢和碳)之间的相互作用的情况下，这样的宽带去耦合是例行公事，但对于相同类型的原子之间的相互作用，没有通用的方法来实现它。然而，我们最近表明，通过适当选择实验方法，我们可以在许多情况下逆转相互作用的影响，使我们能够测量纯移位光谱，在该光谱中，一个分子中的每个氢原子都有一个单一的信号。这种技术提供的简单性意味着我们应该能够在比目前情况下更大的物种或更复杂的混合物中解析单个原子的信号。目前，更好地分辨信号的唯一方法是使用更高的磁场来分散信号，但制造更好的磁体的进展极其缓慢--在过去30年里，可用的最高磁场平均每年仅增加几个百分点。用纯粹的移位方法，我们应该能够在几年的时间里获得几乎十倍的改进。在这个项目中，一名博士后研究员和一名研究生将研究将我们最初的原则证明转化为实用工具。如果它们成功了，这些工具最终将被世界各地的化学家、生物化学家和其他科学家使用。

Proton (hydrogen) nuclear magnetic resonance (NMR) spectroscopy is the single tool most widely used by chemists for determining the molecular structures of unknown compounds. It is a wonderfully versatile and sensitive tool, but it has a major drawback: it struggles to separate the signals from the different hydrogen atoms in a molecule, because each atom typically gives rise to multiple signals. This multiplicity of signals arises because of the magnetic interactions between hydrogen nuclei, and it typically leads to spectra being about ten times more crowded than would be the case if these interactions could be switched off. Unfortunately, while such a broadband decoupling is routine where interactions between different types of atom (e.g. hydrogen and carbon) are involved, there is no general way of achieving it for interactions between atoms of the same type. What we have recently shown, however, is that by suitable choice of experimental methods we can in many cases reverse the effects of interactions, allowing us to measure pure shift spectra in which a single signal is seen for each hydrogen atom in a molecule. The simplicity such techniques offer means that we should be able to resolve the signals of individual atoms in much larger species, or in much more complex mixtures, than is currently the case. At the moment the only way to resolve signals better is to spread them out by using a higher magnetic field, but progress in building better magnets is agonisingly slow - over the last 30 years the highest field available has increased on average by just a few per cent each year. With pure shift methods we should be able to get almost a tenfold improvement in the space of a few years. In this project, a postdoctoral research fellow and a postgraduate student will investigate turning our initial proof of principle into practical tools. If they are successful, these tools will end up being used by chemists, biochemists and other scientists all over the world.