SHARPER NMR: fast and accurate analysis of molecules, reactions and processes

更清晰的 NMR：快速准确地分析分子、反应和过程

• 批准号: EP/S016139/1
• 负责人: Dusan Uhrin
• 金额: $ 46.48万
• 依托单位: University of Edinburgh
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2019
• 资助国家: 英国
• 起止时间: 2019 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FS016139%2F1
• 关键词: SHARPER; NMR; fast; accurate; analysis

Nuclear Magnetic Resonance (NMR) spectroscopy is a very useful analytical technique, which has applications across the range of sciences, including medicine, biology, geosciences, physics and chemistry. It can be performed on living organisms, solid state materials, or molecules dissolved in liquids. This proposal focusses on the solution state NMR spectroscopy.Solution state NMR is a bread and butter technique for chemists. It has been around for 70 years, but does not show any sign of slowing down in its development, improvement, and increased efficiency. What distinguishes NMR from other spectroscopies is the longevity of the excited states of nuclei (or spins, as we often called them) that are subjects of NMR experiments. Their lifetime on the order of milliseconds to seconds allows scientists to design elaborate ways of spin manipulation before, or these days also during, signal acquisition. The purpose of these manipulations is to obtain specific information about the structure or the chemical state of the molecule, including interactions with other molecules.Such manipulations are important for several reasons: (i) sometimes there is too much to see and we need to simplify NMR spectra in order to access the information we require. (ii) NMR is a relatively insensitive technique and compared to other analytical techniques, such as for example mass spectrometry (MS), requires large amounts of material (typically milligram quantities, compared to micro, nano grams or even pico grams that are sufficient for MS). (iii) In its standard implementation, NMR can be too slow to monitor fast processes that are occurring on millisecond to second times scales. (iv) Ideally, solution state NMR is performed on homogeneous samples and standard techniques struggle to provide high quality information about heterogeneous system, e.g. characterisation of processes taking place at the interface of two immiscible liquids, or when a gas is bubbled through a solution.This proposal addresses the difficulties outlined above and aims to design novel NMR techniques that allow information to be obtained under circumstances where this is not as yet possible (e.g. heterogeneous systems), or bring evident improvements to existing techniques in terms of efficiencies (time saving) and quality of information obtained. Accuracy of NMR parameters, that are ultimately interpreted to provide chemical structures, characterise chemical reactions, or determine molecular sizes, will be improved. The focus is on (i) monitoring of fast chemical reactions and (ii) characterising molecular sizes and (iii) going beyond the primary structure of molecules (the order in which the individual atoms are connected to each other) to how the atoms are arranged in the three-dimensional space (conformation, tertiary structure). Such information is crucial to our ability to rationalise intermolecular interactions (e.g. interactions of drugs with biomacromolecules). Another important aspect of the proposed techniques is that they can be applied to complex systems. NMR has traditionally been very good in studying pure compounds, but to this day struggles to study them as part of mixtures. In real life situations it is not always possible to separate out individual molecules from mixtures, and many industries must learn how to deal with mixtures efficiently. We will work with a manufacture of benchtop NMR spectrometers to bring the developed techniques directly into fume hoods and production lines, out of the specialised NMR laboratories. We anticipate that the new methods we will develop will be applied across a wide spectrum of academic and industrial research.

核磁共振（NMR）光谱是一种非常有用的分析技术，在整个科学范围内都有应用，包括医学，生物学，地球科学，物理和化学。它可以在溶于液体中的生物体，固态物质或分子上进行。该建议的重点是溶液状态NMR光谱。解决状态NMR是化学家的面包和黄油技术。它已经存在了70年，但没有显示出放慢其发展，提高和提高效率的任何迹象。 NMR与其他光谱镜的区别是核的激发态的寿命（或我们通常称为它们的旋转）是NMR实验的受试者。他们在毫秒到几秒钟的命令上的寿命使科学家可以在恢复信号获取之前或这些天设计精心的旋转操作方式。这些操作的目的是获取有关分子的结构或化学状态的特定信息，包括与其他分子的相互作用。操纵很重要，原因是多种原因：（i）有时候有太多的观察，我们需要简化NMR光谱以访问我们所需的信息。 （ii）NMR是一种相对不敏感的技术，与其他分析技术（例如质谱（MS））相比，需要大量材料（通常是毫克数量，与微型，纳米rams相比，甚至是毫无疑问的Pico grams，甚至是MS的PICO gram）。 （iii）在其标准实现中，NMR可能太慢，无法监视以毫秒至第二次尺度发生的快速过程。 （iv）理想情况下，解决方案状态NMR是在均质样本上进行的，标准技术很难提供有关异质系统的高质量信息，例如在两种不混溶液体的界面或通过解决方案冒泡时发生的过程的表征。该建议解决上述困难，并旨在设计新型的NMR技术，在这种情况下允许在这种情况下尚无可能在可能的情况下获得信息（例如，在各种系统中可以保存的质量及时及时的质量，都可以在可能的情况下获得。最终解释为提供化学结构，表征化学反应或确定分子大小的NMR参数的准确性将得到改善。重点放在（i）监测快速化学反应和（ii）表征分子大小和（iii）超出分子的主要结构（彼此相互连接的顺序）到原子如何在三维空间（构象，三级结构）中排列的。此类信息对于我们合理化分子间相互作用的能力至关重要（例如，药物与生物ac纤维分子的相互作用）。提出的技术的另一个重要方面是它们可以应用于复杂的系统。传统上，NMR在研究纯化合物方面一直非常出色，但是直到今天，它一直在努力研究它们作为混合物的一部分。在现实生活中，并非总是有可能将单个分子与混合物分开，许多行业必须学习如何有效地处理混合物。我们将使用台式NMR光谱仪的制造，以将开发的技术直接从专门的NMR实验室中带入烟雾罩和生产线中。我们预计我们将开发的新方法将在各种各样的学术和工业研究中应用。

项目成果

Monitoring off-resonance signals with SHARPER NMR - the MR-SHARPER experiment.

使用 SHARPER NMR 监测非共振信号 - MR-SHARPER 实验。

• DOI: 10.1039/d2an00134a
• 发表时间: 2022
• 期刊: The Analyst
• 作者: Davy M

SHARPER-DOSY: Sensitivity enhanced diffusion-ordered NMR spectroscopy.

• DOI: 10.1038/s41467-023-40130-2
• 发表时间: 2023-07-21
• 期刊: NATURE COMMUNICATIONS
• 影响因子: 16.6
• 作者: Peat, George;Boaler, Patrick J.;Dickson, Claire L.;Lloyd-Jones, Guy C.;Uhrin, Dusan
• 通讯作者: Uhrin, Dusan