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

凭借这项来自主要研究仪器项目的奖励，来自佛罗里达州立大学（FSU）的Stephen Hill教授和国家高磁场实验室（NHMFL）及其同事William Brey和Johan van Tol将开发一种定制光谱仪，该光谱仪配备了磁铁和探针，能够在相对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）。主要想法是将这些方法结合起来，产生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14.1 T下运行，分别需要600兆赫和395千兆赫的核和电子辐照。该设计基于在核磁共振磁体内部的均匀性最佳点（将用于核磁共振实验）和正上方的位置（将通过微波照射进行DNP）之间的快速穿梭。新仪器将使典型的有机核磁共振实验（包括目前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。通过DNP的成功实施，灵敏度有望提高50倍，并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，进一步提高灵敏度。这种增强将在核磁共振波谱学家感兴趣的许多领域开辟广泛的新应用领域。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。该仪器将结合三种技术：核磁共振（NMR）、电子顺磁共振（EPR）和动态核极化（DNP）。核磁共振光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，以及研究溶液中分子之间相互作用的动力学。获得最先进的核磁共振光谱仪是必不可少的化学家谁正在进行前沿研究。类似地，EPR光谱仪可以获得分子和固态材料的几何和电子结构的详细信息。它还可用于获取有关重要化学和生物化学过程中短命、高活性物质的寿命的信息。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。用调谐到适当EPR频率（本例中为395 GHz）的高功率微波照射与目标分子共混的稳定电子自由基，极化可以通过电子自旋转移到目标原子核上。核极化的增加增加了核磁共振实验的灵敏度，从而提高了使用只能在极低浓度下制备的样品的机会，例如，从稀有的天然产物或生物制品中制备的样品。这项研究将对提高核磁共振筛选能力产生重大影响，并将催化药物开发，同时通过结合化学家、物理学家和生物化学家的专业知识，培养下一代仪器学家。

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.