MRI: Development of Instrumentation for Dynamic Nuclear Polarization of Organic Solutions

MRI：有机溶液动态核极化仪器的开发

• 批准号: 1229170
• 负责人: Stephen Hill
• 金额: $ 135.27万
• 依托单位: Florida State University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-01 至 2018-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1229170&HistoricalAwards=false
• 关键词: MRI; Development; Instrumentation; Dynamic; Nuclear

With this award from the Major Research Instrumentation Program, Professor Stephen Hill from Florida State University (FSU) and the National High Magnetic Field Laboratory (NHMFL) and colleagues William Brey and Johan van Tol will develop a custom spectrometer equipped with a magnet and probes capable of supporting both high-resolution nuclear magnetic resonance (NMR) and electron paramagnetic resonance (EPR) at relatively high fields and frequencies. The main idea is to combine these methodologies, resulting in a high-field dynamic nuclear polarization (DNP) instrument for organic solutions that would allow the study of samples that are mass limited and thus can only be prepared in very low concentrations. The target is to operate at 14.1 T, requiring nuclear and electron irradiation at 600 MHz and 395 GHz, respectively. The design is based on rapid shuttling inside the NMR magnet between the homogeneity sweet spot, which will be used for the NMR experiments, and a location just above, where the DNP will be performed by microwave irradiation. The new instrument will lead to an enhancement in sensitivity of the typical organic NMR experiment (including essentially any NMR experiment implemented today on molecules dissolved in organic solvent) by over two orders of magnitude. A 50-fold enhancement in sensitivity is expected with successful DNP implementation, with further gains coming from adapting existing NHMFL-based orthogonal technologies utilizing cryogenic high temperature superconducting NMR probe platforms. Such enhancements will open wide new fields of applications in many of areas of interest to NMR spectroscopists. Examples are organic structure determinations, synthesis and screening of pharmaceuticals, elucidation of natural product structures, and metabolomics analyses.The proposed instrument will combine three techniques: nuclear magnetic resonance (NMR), electron paramagnetic resonance (EPR) and dynamic nuclear polarization (DNP). NMR spectroscopy is one of the most powerful tools available to chemists for the elucidation of the structure of molecules. It is used to identify unknown substances, to characterize specific arrangements of atoms within molecules, and to study the dynamics of interactions between molecules in solution. Access to state-of-the-art NMR spectrometers is essential to chemists who are carrying out frontier research. Similarly, an EPR spectrometer yields detailed information on the geometric and electronic structure of molecular and solid state materials. It may also be used to obtain information about the lifetimes of short-lived, highly reactive species involved in important chemical and biochemical processes. DNP utilizes EPR in order to overcome one of NMR's main drawbacks - its inherent low sensitivity. By irradiating stable electron radicals that have been co-mixed with molecular targets of interest with high-power microwaves tuned to the appropriate EPR frequency (395 GHz in this case), polarization can be transferred to the target nuclei via the electron spins. The increased nuclear polarization results in increased sensitivity in NMR experiments and thus improves the chances of using samples that can only be prepared in very low concentrations, e.g., from rare natural products or bioproducts. This research will have a major impact in improving NMR screening capabilities and will catalyze pharmaceutical development, while also training the next generation of instrumentalists by combining the expertise of chemists, physicists and biochemists.

有了这项重大研究仪器计划的奖项，来自佛罗里达州立大学（FSU）和国家高磁场实验室（NHMFL）的Stephen Hill教授及其同事William Brey和Johan货车Tol将开发一种定制光谱仪，该光谱仪配备有磁体和探针，能够在相对较高的场和频率下支持高分辨率核磁共振（NMR）和电子顺磁共振（EPR）。其主要思想是联合收割机这些方法，导致在高场动态核极化（DNP）仪器的有机溶液，将允许研究的样品是质量有限，因此只能在非常低的浓度制备。目标是在14.1 T下工作，分别需要600 MHz和395 GHz的核和电子辐照。该设计基于NMR磁体内部的均匀性最佳点（将用于NMR实验）和正上方的位置（将通过微波辐射进行DNP）之间的快速穿梭。新仪器将使典型的有机NMR实验（包括今天对溶解在有机溶剂中的分子进行的任何NMR实验）的灵敏度提高两个数量级以上。成功的DNP实施预计灵敏度将提高50倍，进一步的收益来自于利用低温高温超导NMR探针平台调整现有的基于NHMFL的正交技术。这种增强将在NMR光谱学家感兴趣的许多领域中打开广泛的新应用领域。例如有机结构测定、药物的合成和筛选、天然产物结构的阐明和代谢组学分析。拟议的仪器将结合联合收割机三种技术：核磁共振（NMR）、电子顺磁共振（EPR）和动态核极化（DNP）。核磁共振波谱学是化学家用来阐明分子结构的最有力的工具之一。它用于识别未知物质，表征分子内原子的特定排列，并研究溶液中分子之间相互作用的动力学。对于从事前沿研究的化学家来说，使用最先进的NMR光谱仪是必不可少的。类似地，EPR光谱仪产生关于分子和固态材料的几何和电子结构的详细信息。它也可用于获得有关重要化学和生物化学过程中所涉及的短寿命、高活性物种的寿命的信息。DNP利用EPR来克服NMR的主要缺点之一-其固有的低灵敏度。通过用调谐到适当EPR频率（在这种情况下为395 GHz）的高功率微波照射已经与感兴趣的分子靶共混合的稳定电子自由基，可以经由电子自旋将极化转移到靶核。增加的核极化导致NMR实验中增加的灵敏度，从而提高了使用仅能以非常低的浓度制备的样品的机会，例如，稀有天然产品或生物产品。这项研究将对提高NMR筛选能力产生重大影响，并将促进药物开发，同时通过结合化学家，物理学家和生物化学家的专业知识来培训下一代仪器。

项目成果

Time domain measurement of electron spin relaxation at high fields and dynamic nuclear polarization at sub-millimeter wavelengths

• DOI: 10.1109/mwsym.2017.8058878
• 发表时间: 2017-06
• 期刊: 2017 IEEE MTT-S International Microwave Symposium (IMS)
• 作者: Thierry Dubroca;J. McKay;Xiaoling Wang;J. van Tol