RS Fellow - EPSRC grant (2014): Application of Tandem Non-Covalent Interactions to the Development of New Enantioselective Reactions

有机化学家的主要目标是构建分子，用于药物，新材料和生物分子等多种应用。该领域不断受到对新的，更有效的方法以及以前可能不可能获得分子的方法的需求的驱动。在有机化学家的处置最重要的工具无疑是催化，其中使用少量的定制设计的催化剂可以允许反应发生在比其他更温和的条件下，或者完全打开新的化学途径。因此，催化的创新是有机化学创新的核心。自然界的催化作用是由酶来完成的;进化使它们具有惊人的效率。通常在酶促过程中起主导作用的是“氢键”，这是一种特殊类型的静电吸引，通过使两个分子彼此紧密接近或通过稳定导致产物形成的途径来促进两个分子之间的化学反应。我的研究试图利用这些相同的相互作用，但在小分子的背景下，我们可以很容易地在实验室合成和处理。这种催化方法是非常令人兴奋的，因为它仍处于起步阶段，但为激活和控制提供了令人兴奋的机会。该项目将寻求从化学中一个独特的领域“超分子化学”中获得灵感，该领域探索了使用多个弱“临时”相互作用串联工作的小分子组装的大分子的行为。氢键在这方面非常重要，但还有许多其他关键的相互作用，如离子对和π-阳离子相互作用，这些相互作用已被证明在建立分子结构方面很强大。我们的目标是将这些相互作用中的几种串联在一起来设计新的催化剂，这些催化剂将以非常明确的方向与我们的反应物结合。催化剂还将诱导底物与另一种分子反应，允许选择性合成一种分子的镜像而不是另一种（所谓的对映体）。这在科学上是一个非常重要的追求，因为生物系统固有的“手性”意味着手性分子的不同镜像形式通常在体内具有非常不同的效果。这在制药应用中特别重要。

A primary goal of organic chemists is the construction of molecules for applications as diverse as medicines, new materials and biomolecules. The field is constantly driven by the need for new, more efficient methods as well as ways to access molecules which may have previously been impossible. The most important tool at an organic chemist's disposal is undoubtedly catalysis, whereby the use of a small amount of a custom-designed catalyst can permit a reaction to occur under much milder conditions than otherwise, or opens up new chemical pathways altogether. For this reason, innovation in catalysis is central to innovation in organic chemistry. Nature's catalysis is performed by enzymes; evolution has made them phenomenally efficient. Often playing a leading role in enzymatic processes are 'hydrogen bonds', special types of electrostatic attraction which are important in facilitating the chemical reaction between two molecules by bringing them into close proximity with one another or by stabilising the pathway leading to product formation. My research seeks to employ these same interactions, but in the context of small molecules which we can readily synthesise and handle in the lab. This approach to catalysis is very exciting as it is still in its infancy yet offers exciting opportunities for both activation and control. This project will seek to take inspiration from a distinct field within chemistry called Supramolecular Chemistry, which explores the behavior of large molecules which are assembled from smaller ones using multiple weak 'temporary' interactions working in tandem. Hydrogen bonds are very important in this regard but there are a number of other key interactions such as ion pairs and pi-cation interactions which have been shown to be powerful in building up molecular structures. It is our aim to apply several of these interactions together in tandem to design new catalysts that will bind with our reactant in a very well defined orientation. The catalyst will also induce the substrate to react with another molecule, allowing the selective synthesis of one mirror image of a molecule over the other (so-called enantiomers). This is a very important pursuit in science, since the inherent 'handedness' of biological systems means that the different mirror image forms of chiral molecules often have very different effects in the body. This is of particular importance in pharmaceutical applications.