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

佛罗里达州立大学(FSU)和国家强磁场实验室(NHMFL)的Stephen Hill教授及其同事William Brey和Johan van Tol获得了重大研究仪器计划的这一奖项，他们将开发一种定制的光谱仪，配备磁铁和探测器，能够在相对较高的磁场和频率下支持高分辨率核磁共振(NMR)和电子顺磁共振(EPR)。主要的想法是将这些方法结合起来，产生一种用于有机溶液的高场动态核极化(DNP)仪器，该仪器将允许研究质量有限的样品，因此只能在非常低的浓度下制备。目标是在14.1T下运行，需要分别在600兆赫和395兆赫进行核辐射和电子辐照。该设计是基于在核磁共振磁铁内部快速穿梭，在用于核磁共振实验的均质最佳点和上面的位置之间快速穿梭，在那里将通过微波辐射进行DNP。新仪器将使典型的有机核磁共振实验(包括今天对溶解在有机溶剂中的分子进行的任何核磁共振实验)的灵敏度提高两个数量级以上。随着DNP的成功实施，灵敏度有望提高50倍，进一步的收益来自于利用低温高温超导核磁共振探针平台采用现有的基于NHMFL的正交技术。这样的增强将在核磁共振光谱学家感兴趣的许多领域开辟广泛的应用新领域。例如有机结构测定、药物的合成和筛选、天然产物结构的确定和代谢组学分析。建议的仪器将结合三种技术：核磁共振(核磁共振)、电子顺磁共振(EPR)和动态核极化(DNP)。核磁共振波谱是化学家用来阐明分子结构的最强大的工具之一。它被用来识别未知物质，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。对于正在进行前沿研究的化学家来说，获得最先进的核磁共振光谱仪是必不可少的。同样，EPR光谱仪可以提供有关分子和固态材料的几何和电子结构的详细信息。它还可以用来获取有关重要化学和生化过程中涉及的短寿命、高活性物种的寿命的信息。DNP利用EPR来克服核磁共振的主要缺点之一--其固有的低灵敏度。通过用调到适当的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目标共混的稳定的电子自由基，可以通过电子自旋将极化转移到目标核。核极化的增加导致核磁共振实验的灵敏度增加，从而增加了使用只能在非常低的浓度下制备的样品的机会，例如从稀有的天然产品或生物产品中制备的样品。这项研究将对提高核磁共振筛选能力产生重大影响，并将促进制药发展，同时还将通过结合化学家、物理学家和生物化学家的专业知识来培训下一代仪器专家。

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.