Development of a Dynamic Nuclear Polarisation based NMR techniques for the rapid detection and characterisation of reaction intermediates.

摘要过渡金属元素化合物介导的催化是无机化学中一个极其重要的领域，几乎是整个化学工业的基石。精炼和优化任何催化系统的核心能力是对反应进行的途径的详细了解。在研究这类反应和观察催化中间体中常用的一种技术是核磁共振（NMR）光谱。这项技术利用核磁现象来探测含有具有磁性活性原子核的原子的分子。因此，同位素如1H、13C、15N和31P的原子核可以被认为是微小的条形磁铁。当放置在强磁体的磁场中，例如在核磁共振光谱仪中发现的磁场，条形磁铁可以对齐以加强或反对主磁场，结果产生不同的能量状态。这些状态之间的转换可以通过吸收射频信号来实现。这些频率是原子核化学环境的一个特征，最终可以用来识别起作用的化合物。然而，这种技术的灵敏度受到很大的限制。在这个项目中，我们将利用一种名为动态核极化（DNP）的新技术，将核磁共振方法的灵敏度提高一个接近10,000的系数，并允许检测和表征低浓度的活性化合物，否则将无法观察到。我们的目标是建立程序和方法，使我们能够通过DNP敏化随后发生化学反应的合适前体底物化合物，使用NDP衍生的信号作为探针来检测底物通过参与反应机制的瞬态中间体的通道。这将使我们能够跟踪它们的反应性，并了解催化循环中涉及的基本反应步骤的顺序。然而，为了实现这一目标，必须设计新的核磁共振实验，以便有效地利用DNP方法产生的信号，包括实施最先进的快速扫描（与以色列魏茨曼研究所的Frydman教授合作）和选择性观察方法。我们还需要设计和建立一个采样处理系统，将DNP敏化材料与研究反应中涉及的其他化合物混合，并以受控的方式将反应混合物输送到将进行测量的核磁共振光谱仪区域。我们将首先以含金属化合物的简单反应为目标，这些反应产生稳定的产物，作为这些新技术的试验场，然后将继续研究催化反应。我们最初选择的体系是被广泛使用的由Grubb催化剂（Nobel prize 2005）催化的烯烃复分解反应，使用DNP敏化烯烃来探测催化反应机理中涉及的金属化合物。一些中间产物已经被观察到并确定，但仍有许多工作要做。因此，该系统作为这些方法的理想试验场。后续将扩展到另一个高值反应——Heck反应，重点研究含P， c -钯环配合物催化的体系。在这里，人们对催化剂的确切作用机制或激活途径知之甚少。这项工作将产生重大影响，不仅在直接催化化学社区，但所开发的技术也将有衍生应用在其他领域，如生物核磁共振研究和其他领域的分析化学，有限的样本量是一个主要问题。

Project SummarySummary Catalysis mediated by compounds of the transition metal elements is an extremely important area of inorganic chemistry and is the corner stone of virtually the entire chemicals industry. Central to the ability to refine and optimise any catalytic system is a detailed knowledge of the pathways by which the reaction proceeds. One technique commonly used in the study of these types of reaction and for the observation of catalytic intermediates is nuclear magnetic resonance (NMR) spectroscopy. This technique utilises the phenomenon of nuclear magnetism to detect molecules containing atoms with magnetically active nuclei. Nuclei of isotopes such as 1H, 13C, 15N and 31P can therefore be thought of as tiny bar magnets. When placed in the field of a strong magnet, such as that found inside an NMR spectrometer, the bar magnets can either align to reinforce or oppose the main field with the result that states of differing energies are produced. Transitions between these states can be achieved by the absorption of radio frequency signals. These frequencies are a characteristic feature of the chemical environment of the nuclei and ultimately can be used to identify the contributing compound. The sensitivity of this technique is however greatly limited.In this project we will utilise a new technique called dynamic nuclear polarisation (DNP) to increase the sensitivity of the NMR method by a factor that will approach 10,000 and allow the detection and characterisation of low concentration reactive compounds that would otherwise not be observable. Our aim is to established procedures and methodologies that will allow us to sensitise by DNP a suitable precursor substrate compound that subsequently undergoes chemical reactions, using the NDP derived signals as a probe to detect that passage of the substrate through transient intermediates involved in the reaction mechanism. This will enable us follow their reactivity and gain an understanding of the sequence of fundamental reaction steps involved in the catalytic cycle.In order to achieve this however, new NMR experiments must be designed in order to efficiently utilise the signal generated by the DNP method involving the implementation of state-of-the-art rapid scan (in collaboration with Prof Frydman of the Weizmann Institute, Israel) and selective observation methods. We will also need to design and build a sampling handling system that mixes the DNP sensitised materials with other compounds involved in the reaction of study and delivers the reaction mixture in a controlled manner into the region of the NMR spectrometer where measurements will be taken.We will first target simple reactions involving metal containing compounds that yield stable products as a testing ground for these new techniques and will then follow onto to study catalytic reactions. Our initial choice of system is the widely used alkene metathesis reaction catalysed by Grubb's catalyst (Nobel prize 2005) using DNP sensitised alkenes to probe the metallic compounds involved in the catalytic reaction mechanism. Some of the intermediates have already been observed an identified but much work can still be achieved. Therefore this system acts as an ideal proving ground for these methods. Later will be extend our study to another high value reaction, the Heck reaction and focus on the system catalysed by palladium containing P,C-palladcyclic complexes. Here, very little is known about the exact mechanism of operation or the route by which the catalyst is activated.This work will have significant impact, not only on the immediate catalytic chemistry community, but the techniques developed will also have spin-off applications in other fields such as biological NMR research and other areas of analytical chemistry where limited sample size is a major problem.