Synthetic Optimization of Organic Radicals for Dynamic Nuclear Polarization

描述（由申请人提供）：核磁共振（NMR）光谱法特别适用于提供有关非结晶材料的结构和动力学的信息;这些材料包括生物相关材料，如非结晶蛋白质、膜结合蛋白质、淀粉样蛋白、肽、胶束和囊泡。因此，这项技术有望揭示与糖尿病、阿尔茨海默病和帕金森病等疾病有关的许多病理过程。然而，由于这些NMR技术通常涉及对具有低平衡极化的低伽马核的观察，因此NMR实验中的灵敏度固有地低，并且实验必须艰苦地长。已经发现了许多在NMR实验中增加核灵敏度的方法，但也许最普遍适用的方法是微波驱动的动态核极化（DNP）。在DNP增强的NMR实验中，稳定的有机自由基和感兴趣的分子的混合物在特定的微波频率下照射。辐射导致极化从自由基电子转移到极化程度较低的原子核，从而增强NMR信号强度。 直到最近，DNP实验还使用传统的稳定有机自由基作为极化电子的来源。由于这些自由基不是专门设计用于DNP过程，信号增强达不到理论最大值。该提案旨在通过设计和合成专门用作DNP试剂的自由基来改善DNP实验中的整体信号增强。 提出的策略包括：1）调整自由基电子g值，以精确匹配操作DNP机制的理想条件。这将通过将重原子和过渡金属结合到已知自由基DNP试剂的电子结构中来实现; 2）优化电子自旋-晶格弛豫时间以减少核极化所需的建立时间。这可以通过使自由基的外围组分官能化来实现;以及3）使电子-电子偶极耦合最大化，同时使交换耦合最小化以进一步增加极化。优化耦合将需要分析结合两个自由基的潜在连接单元的数量。有机和无机合成方法将提供访问所提出的自由基，和合成自由基的电子和磁性的详细调查将通知进一步的设计。任何这些策略的成功都有助于提高DNP试剂的增强因子，从而使先进的NMR技术更适合于研究关键的人类健康问题。

DESCRIPTION (provided by applicant): Nuclear magnetic resonance (NMR) spectroscopy is uniquely suited to provide information about the structure and dynamics of non-crystalline materials; these include biologically relevant materials like non-crystalline proteins, membrane-bound proteins, amyloids, peptides, micelles and vesicles. Consequently, this technique promises to shed light on a number of pathological processes implicated in diseases including diabetes, Alzheimer's and Parkinson's, among many others. Because these NMR techniques generally involve observation of low-gamma nuclei with low equilibrium polarization, however, sensitivity in the NMR experiment is inherently low and experiments must be arduously long. A number of means to increase nuclear sensitivity in NMR experiments have been discovered, but perhaps the most generally applicable method is microwave-driven dynamic nuclear polarization (DNP). In a DNP-enhanced NMR experiment, mixtures of stable organic radicals and a molecule of interest are irradiated at particular microwave frequencies. The irradiation causes polarization to be transferred from the radical electrons-which are naturally more polarized-to the less polarized nuclei, resulting in enhanced NMR signal intensity. Until recently, DNP experiments have made use of conventional stable organic radicals as a source of polarized electrons. Because these radicals are not specifically designed for use in the DNP process, signal enhancements fall short of the theoretical maximum values. This proposal aims to improve overall signal enhancement in DNP experiments by design and synthesis of radicals specifically tailored for use as DNP agents. The strategies proposed include: 1) tuning radical electron g-values to precisely match the conditions ideal for the operative DNP mechanisms. This will be accomplished by incorporating heavy atoms and transition metals into the electronic structure of known radical DNP agents; 2) optimizing the electron spin-lattice relaxation times in order to reduce the necessary build-up time for nuclear polarization. This can be achieved by functionalizing the peripheral components of the radicals; and 3) maximizing electron-electron dipolar coupling while simultaneously minimizing exchange coupling to further increase polarization. Optimizing couplings will require assaying a number of potential linking units binding two radicals. Organic and inorganic synthetic methods will provide access to the proposed radicals, and detailed investigation of the electronic and magnetic properties of the synthesized radicals will inform further design. Success with any of these strategies stands to improve enhancement factors of DNP agents, thus rendering advanced NMR techniques more amenable for the investigation of crucial human health issues.