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

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• 批准号: EP/K003674/1
• 负责人: Steven Brown
• 金额: $ 49.58万
• 依托单位: University of Warwick
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2012
• 资助国家: 英国
• 起止时间: 2012 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FK003674%2F1
• 关键词: Switchable; Biomimetic; Self; Assembly; Guanosines

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.

自然界利用有机分子之间的相互作用来执行生命的功能，例如，通过阅读我们DNA的密码来制造蛋白质，或者通过细胞膜上的离子通道将金属离子泵入或泵出细胞。化学家们正在努力了解如何模拟这种对分子间相互作用的精细控制，这种相互作用驱动特定分子如何组装在一起。该项目的重点是基于DNA成分之一的鸟苷的合成衍生物。在过去的15年里，世界各地的实验室已经合成了各种各样的此类化合物，这些化合物表现出丰富多样的纳米结构。这些系统具有作为新型材料开发的潜力，例如，在分子电子器件中，或者提取特定的离子，例如，放射性铯，或在仿生离子通道的建设。特别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改变，例如，分析工具的可用性，以查看特定的分子间相互作用是一个先决条件，为知情的设计新材料和仿生系统。至关重要的是所谓的氢键，其中氢原子（H）在受体原子（例如，氧（O）或氮（N）和供体基团，例如，OH或NH。观察这样的相互作用是特别具有挑战性的鸟苷衍生物，通常是由一个刚性的核心与连接的柔性链，其动态阻止使用广泛采用的方法的X-射线衍射的3D结构的测定，而基于表面的成像技术缺乏分辨率来查看分子间的相互作用的固态。相反，该项目利用核磁共振（NMR）技术，该技术利用原子核的固有磁性。在比地球磁场强几十万倍的非常强的磁场中，可以利用与特定频率的无线电波相关的能量来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关于原子核的电子环境及其化学结构的复杂细节，第二，不同的磁矩是如何排列的，从而可以非常精确地测量原子之间的距离。虽然大多数核磁共振实验是在液体样品上进行的，其中分子的翻滚增加了不同光谱线的分辨率，但固态样品可以使用一种称为魔角旋转（MAS）的方法进行分析，其中样品绕着与外部磁场倾斜54.7度的轴快速旋转。在初步工作中，使用MAS固态NMR，沃里克小组已经表明，鸟苷衍生物表现出的两种不同类型的自组装，即带状和四元体状排列，可以区分。本项目将与在合成鸟苷衍生物研究领域处于领先地位并处于展示新应用前沿的两个海外领先团队合作，系统地研究改变溶剂、pH或温度如何影响所展示的自组装。一个特别的重点将是衍生物，表现出可调的自组装和形成仿生离子通道。实验将使用最先进的基础设施进行，包括英国850 MHz固态NMR设施。通过将固态NMR提供的新见解与以前在溶液状态和表面上获得的见解进行比较，将阐明决定自组装如何在不同相（固体与溶液）和体积与表面效应之间控制的相似性和差异性的因素。通过建立结构-性能关系，这将使设计更好的新材料成为可能。

项目成果

Interplay of Noncovalent Interactions in Ribbon-like Guanosine Self-Assembly: An NMR Crystallography Study

• DOI: 10.1021/acs.cgd.5b01440
• 发表时间: 2015-11
• 期刊: Crystal Growth & Design
• 影响因子: 3.8
• 作者: G. N. M. Reddy;Andrew Marsh;Jeffery T. Davis;S. Masiero;S. Brown

Cover Picture: Co-existence of Distinct Supramolecular Assemblies in Solution and in the Solid State (Chem. Eur. J. 10/2017)

封面图片：不同超分子组装体在溶液和固态中的共存（Chem. Eur. J. 10/2017）

• DOI: 10.1002/chem.201605967
• 发表时间: 2017
• 期刊: Chemistry - A European Journal
• 作者: Reddy G

Magic-angle spinning NMR spectroscopy provides insight into the impact of small molecule uptake by G-quartet hydrogels

• DOI: 10.1039/d0ma00475h
• 发表时间: 2020-10
• 期刊: Materials Advances
• 影响因子: 5
• 作者: G. N. Manjunatha Reddy;G. Peters;Benjamin J. Tatman;Teena S. Rajan;Si Min Kock;Jing Zhang;B. Frenguelli;Jeffery T. Davis;Andrew Marsh;S. Brown

Coexistence of Distinct Supramolecular Assemblies in Solution and in the Solid State

不同超分子组装体在溶液和固态中的共存

• DOI: 10.1002/chem.201605975
• 发表时间: 2017
• 期刊: Chemistry - A European Journal
• 作者: Reddy G

Combining heteronuclear correlation NMR with spin-diffusion to detect relayed Cl-H-H and N-H-H proximities in molecular solids

将异核相关 NMR 与自旋扩散相结合，检测分子固体中中继的 Cl-H-H 和 N-H-H 邻近性

• DOI: 10.1016/j.ssnmr.2022.101808
• 发表时间: 2022
• 期刊: Solid State Nuclear Magnetic Resonance
• 影响因子: 3.2
• 作者: Raval P