Switchable & Biomimetic Self-Assembly of Guanosines: Characterising the Interplay of Structure-Directing Non-Covalent Interactions by Solid-State NMR

大自然利用有机分子之间的相互作用来执行生命的功能，例如，通过读取我们DNA的密码来制造蛋白质，或者通过细胞膜中的离子通道将金属离子泵入和泵出细胞。化学家们正在努力理解如何模仿这种对分子间相互作用的精细控制，这些相互作用推动着特定分子如何组装在一起。这个项目的重点是基于鸟苷的合成衍生品，鸟苷是DNA的一种成分。在过去的15年里，世界各地的实验室合成了种类繁多的此类化合物，这些实验室展示了丰富多样的纳米结构。这些体系有可能被开发为新材料，例如在分子电子器件中，或提取特定离子，例如放射性铯，或在构建仿生离子通道中。特别令人感兴趣的是智能材料，其中采用的自组装可以通过外部刺激(例如光)来改变。可用的分析工具来观察特定的分子间相互作用是新材料和仿生系统知情设计的先决条件。关键的重要性是所谓的氢键，其中氢原子(H)在受主原子(例如氧(O)或氮(N))和给体原子(例如OH或NH)之间共享。对于鸟苷衍生物来说，在固态下观察这种相互作用尤其具有挑战性，因为鸟苷衍生物通常由连接了柔性链的刚性核组成，其动力学特性阻止了广泛使用的X射线衍射方法来确定3D结构，而基于表面的成像技术缺乏观察分子间相互作用的分辨率。相反，这个项目利用了核磁共振技术，这项技术利用了原子核的固有磁性。在比地球磁场强几十万倍的非常强的磁场中，利用与特定频率的无线电波相关的能量，可以诱导核磁矩改变其相对于外部磁场的排列。测量这些频率揭示了有关原子核的电子环境和化学结构的复杂细节，其次，不同的磁矩是如何排列的，从而能够非常准确地测量原子之间的距离。虽然大多数核磁共振实验都是在液体样品上进行的，其中分子的翻滚提高了不同谱线的分辨率，但固态样品可以使用一种名为魔角旋转(MAS)的方法进行分析，即样品绕与外部磁场成54.7度角倾斜的轴快速旋转。在初步工作中，使用MAS固体核磁共振，Warwick小组已经证明了鸟苷衍生物表现出的两种不同类型的自组装，即带状和四重组状排列。这个项目将与两个领先的海外研究小组合作，他们开创了合成鸟苷衍生物的研究领域，并走在了展示新应用的前沿，该项目将系统地研究改变溶剂、pH或温度对展示的自组装的影响。一个特别的焦点将是表现出可调自组装和形成仿生离子通道的衍生物。实验将使用最先进的基础设施进行，包括英国850 MHz固态核磁共振设施。通过将固态核磁共振提供的新见解与先前在溶液状态和表面上获得的洞察力进行比较，将阐明决定自组装如何在不同阶段(固体与溶液)以及本体与表面效应之间控制的异同的因素。通过建立结构-性能关系，这将使设计出更好的新材料成为可能。

Nature exploits the interactions between organic molecules to perform the functions of life, e.g., the manufacture of proteins by reading the code of our DNA or the pumping of metal ions in and out of a cell through ion channels in the cellular membranes. Chemists are striving to understand how to mimic this fine control over the intermolecular interactions that drive how specific molecules assemble together. This project focuses on synthetic derivatives based on guanosine that is one of the constituents of DNA. Over the last 15 years, a wide variety of such compounds have been synthesised in laboratories across the world which exhibit a rich diversity of nanostructures. These systems have the potential to be exploited as novel materials, e.g., in molecular electronic devices, or to extract specific ions, e.g., radioactive caesium, or in the construction of biomimetic ion channels. Of particular interest are smart materials, where the adopted self-assembly can be altered by an external stimulus, e.g.,light.The availability of analytical tools to view specific intermolecular interactions is a pre-requisite for the informed design of new materials and biomimetic systems. Of key importance are so-called hydrogen bonds where a hydrogen atom (H) is shared between an acceptor atom, e.g., oxygen (O) or nitrogen (N) and a donor group, e.g., OH or NH. Observing such interactions is particularly challenging in the solid state for guanosine derivatives which are usually composed of a rigid core with attached flexible chains whose dynamics prevents the determination of the 3D structure using the widely employed method of X-ray diffraction, while surface-based imaging techniques lack the resolution to view the intermolecular interactions. Instead, this project makes use of the technique of nuclear magnetic resonance (NMR), which exploits the inherent magnetism of atomic nuclei. In very strong magnetic fields that are a few hundred thousand times stronger than the Earth's magnetic field, the nuclear magnetic moments can be induced to change their alignment with respect to the external magnetic field using the energy associated with radio waves of a specific frequency. Measuring these frequencies reveals intricate details about, first, the electronic environment of an atomic nucleus and hence its chemical structure and, second, how the different magnetic moments are arranged, allowing distances between atoms to be measured very accurately. While most NMR experiments are performed on liquid samples, where the tumbling of the molecules increases the resolution of different spectral lines, solid-state samples can be analysed using a method called magic-angle spinning (MAS) whereby the sample is rotated rapidly around an axis inclined at an angle of 54.7 degrees to the external magnetic field. In preliminary work, using MAS solid-state NMR, the Warwick group have shown that two different types of self-assembly exhibited by guanosine derivatives, namely ribbon-like and quartet-like arrangements, can be distinguished. Working together with two leading overseas groups who pioneered the research field of synthetic guanosine derivatives and are at the forefront of demonstrating new applications, this project will systematically investigate how changing the solvent, pH, or temperature affects the exhibited self-assembly. A particular focus will be derivatives that exhibit tunable self-assembly and form biomimetic ion channels. Experiments will be carried out using state-of-the-art infrastructure including the UK 850 MHz solid-state NMR facility. By comparing the new insight provided by solid-state NMR to that obtained previously in the solution-state and on surfaces, the factors determining similarities and differences between how self-assembly is controlled in different phases (solid vs.solution) and bulk vs surface effects will be elucidated. By establishing structure-property relationships, this will enable the design of better new materials.