Meeting the Sensitivity Grand Challenges in Pulsed Electron Magnetic Resonance

迎接脉冲电子磁共振灵敏度的巨大挑战

• 批准号: EP/R013705/1
• 负责人: Graham Smith
• 金额: $ 96.6万
• 依托单位: University of St Andrews
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2017
• 资助国家: 英国
• 起止时间: 2017 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FR013705%2F1
• 关键词: Meeting; Sensitivity; Grand; Challenges; Pulsed

Summary This instrument development project seeks to substantially and dramatically increase the sensitivity and time resolution and capability of electron paramagnetic resonance (EPR) spectrometers and to demonstrate a major impact across biology, chemistry, physics and materials science. One of the fundamental quantum mechanical rules governing the basic structure and organisation of matter, is that electrons like to pair up. However, in many materials there are unpaired electrons left over from this pairing process. Such systems are known as paramagnetic and examples include radicals, many types of metal atoms, and defects in crystals. The reactivity of any given unpaired electron strongly depends on its local atomic environment. Some radicals are so reactive that they are able to tear electrons from any nearby molecules and initiate a destructive cascade of reactions. Indeed, it is the accumulated damage from such free radicals within the body that is believed to underlie our aging process, despite the body evolving many defense mechanisms. Measurements of free radicals in the blood can be health indicators. Other paramagnets can be relatively stable and highly beneficial. Transient paramagnetic species are involved in closely regulated reactions in huge numbers of biological processes. Much of the UK's chemical industry depends on the use of radicals and transition metals to initiate and promote catalytic reactions. Paramagnetic defects in crystals, thin films or at interfaces can determine or strongly affect a material's electronic, magnetic, optical, chemical and mechanical properties and are hugely important in the UK's material science and electronics industries. The sensitivity of NMR or MRI experiments can be dramatically increased by making electron spins interact with local nuclei.Even in systems where there are no naturally occurring unpaired electrons, molecular biologists have developed ways to routinely add free radical (electron) spin labels at specific sites within biomolecules, which can be used as "molecular spies" to understand reactions, interactions, large-scale structure and fast dynamics with a precision not possible with other techniques. Characterisation of such structures and processes can underpin the understanding of the mechanisms behind disease and the development of new drugs. The most important tool in studying and understanding these systems is pulsed electron paramagnetic resonance. This technique involves placing a paramagnetic sample in a large magnetic field and illuminating it with a carefully controlled sequence of rapid high power microwave pulses and monitoring the response of the sample. Until relatively recently, it was widely believed there was little scope to significantly improve the sensitivity of pulsed EPR instruments. Yet ten years ago we demonstrated a significant increase by a factor of between 15 and 30 in concentration sensitivity for common measurements. Today, commercial instruments have nearly but still not caught up. This project now seeks to further increase sensitivity, by another factor of 30. This increase will be achieved by taking advantage of recent advances in fast electronics and by modifying an existing state-of-the-art system using techniques that we have already demonstrated in many proof-of-principle experiments. This would be a major advance, particularly for molecular biology, as for the first time it would allow spin-labeled protein systems to be investigated at natural (in-cell) protein concentrations using electron magnetic resonance. There are also many important electronic, materials and catalytic systems, which involve paramagnetic centres in thin films or at interfaces where sensitivity is paramount.To maximise the impact of the instrument development, the project is linked to a large number of applications and methodology development programmes, with a wide range of local collaborators and co-investigators.

摘要 该仪器开发项目旨在大幅提高电子顺磁共振 (EPR) 波谱仪的灵敏度、时间分辨率和能力，并展示对生物学、化学、物理学和材料科学的重大影响。控制物质基本结构和组织的基本量子力学规则之一是电子喜欢配对。然而，在许多材料中，配对过程中留下了不成对的电子。这种系统被称为顺磁性系统，例子包​​括自由基、许多类型的金属原子和晶体中的缺陷。任何给定的不成对电子的反应性很大程度上取决于其局部原子环境。一些自由基的反应性非常强，它们能够从附近的分子中撕下电子，并引发破坏性的级联反应。事实上，尽管人体进化出了许多防御机制，但人们认为体内自由基的累积损伤才是我们衰老过程的基础。血液中自由基的测量可以作为健康指标。其他顺磁体相对稳定并且非常有益。瞬态顺磁物质参与大量生物过程中受到严格调控的反应。英国的大部分化学工业依赖于使用自由基和过渡金属来引发和促进催化反应。晶体、薄膜或界面中的顺磁性缺陷可以决定或强烈影响材料的电子、磁性、光学、化学和机械性能，并且在英国的材料科学和电子行业中非常重要。通过使电子自旋与局部原子核相互作用，可以显着提高 NMR 或 MRI 实验的灵敏度。即使在不存在自然存在的不成对电子的系统中，分子生物学家也开发出了在特定位点常规添加自由基（电子）自旋标记的方法它可以用作“分子间谍”，以其他技术无法达到的精度来理解反应、相互作用、大规模结构和快速动力学。这些结构和过程的表征可以巩固对疾病背后机制和新药开发的理解。研究和理解这些系统的最重要工具是脉冲电子顺磁共振。该技术包括将顺磁性样品放置在大磁场中，并用仔细控制的快速高功率微波脉冲序列对其进行照射，并监测样品的响应。直到最近，人们普遍认为显着提高脉冲 EPR 仪器的灵敏度的空间很小。然而十年前，我们证明了常见测量的浓度灵敏度显着提高了 15 至 30 倍。如今，商业工具已经几乎但仍未赶上。该项目现在寻求将灵敏度进一步提高 30 倍。这种提高将通过利用快速电子学的最新进展以及使用我们已经在许多原理验证实验。这将是一个重大进步，特别是对于分子生物学而言，因为它将首次允许使用电子磁共振在天然（细胞内）蛋白质浓度下研究自旋标记蛋白质系统。还有许多重要的电子、材料和催化系统，其中涉及薄膜中或灵敏度至关重要的界面处的顺磁中心。为了最大限度地发挥仪器开发的影响，该项目与大量应用和方法开发计划相关联，拥有广泛的当地合作者和共同研究人员。

项目成果

High-sensitivity Gd3+-Gd3+ EPR distance measurements that eliminate artefacts seen at short distances

高灵敏度钆

• DOI: http://dx.10.5194/mr-1-301-2020
• 发表时间: 2020
• 期刊: Magnetic Resonance
• 作者: EL Mkami H

Large cross-effect dynamic nuclear polarisation enhancements with kilowatt inverting chirped pulses at 94 GHz.

通过 94 GHz 千瓦反相啁啾脉冲增强大交叉效应动态核极化。

• DOI: http://dx.10.1038/s42004-023-00963-w
• 发表时间: 2023
• 期刊: Communications chemistry
• 影响因子: 5.9
• 作者: Zhao Y

Design of the elusive proteinaceous oxygen donor copper site suggests a promising future for copper for MRI contrast agents.

难以捉摸的蛋白质氧供体铜位点的设计表明铜用于 MRI 造影剂的前景广阔。

• DOI: http://dx.10.1073/pnas.2219036120
• 发表时间: 2023
• 期刊: Proceedings of the National Academy of Sciences of the United States of America
• 影响因子: 11.1
• 作者: Shah A

Orientation selection in high-field RIDME and PELDOR experiments involving low-spin CoII ions.

涉及低自旋 CoII 离子的高场 RIDME 和 PELDOR 实验中的方向选择。

• DOI: http://dx.10.1039/c7cp07248a
• 发表时间: 2018
• 期刊: PCCP
• 作者: Giannoulis A

A Gadolinium Spin Label with Both a Narrow Central Transition and Short Tether for Use in Double Electron Electron Resonance Distance Measurements

具有窄中心跃迁和短系链的钆自旋标签，用于双电子电子共振距离测量

• DOI: http://dx.10.1021/acs.inorgchem.8b02892
• 发表时间: 2019
• 期刊: Inorganic Chemistry
• 影响因子: 4.6
• 作者: Shah A