Development of Solid State NMR Methods and Technology

固态核磁共振方法和技术的发展

• 批准号: 8741375
• 负责人: ROBERT TYCKO
• 金额: $ 45.81万
• 依托单位: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8741375
• 关键词: Accounting; Address; Area; Biopolymers; Calmodulin; Chemical Structure; Dependence; Development; Dimensions; Electron Transport; Electrons; Equipment; Goals; Imaging technology; Magic; Magnetic Resonance Imaging; Measurement; Measures; Methods; Microscopy; Noise; Nuclear; Pathway interactions; Peptides; Physiologic pulse; Population; Proteins; Protons; RF coil; Resolution; Rotation; Sampling; Sapphire; Series; Signal Transduction; Solubility; Source; System; Techniques; Technology; Temperature; Testing; Three-Dimensional Image; Time; Torsion; amyloid fibril formation; base; cold temperature; design; design and construction; improved; irradiation; magnetic field; microwave electromagnetic radiation; nitroxyl; protein complex; prototype; radiofrequency; research study; solid state nuclear magnetic resonance; submicron; theories

Progress in FY2013 was made in the following areas: (1) LOW-TEMPERATURE DYNAMIC NUCLEAR POLARIZATION (DNP). DNP is a phenomenon in which irradiation of electron spin transitions with microwaves leads to enhancements of nuclear spin polarizations, and hence enhancements of NMR signals. We have constructed a new magic-angle spinning probe with DNP capabilities that operates down to 20 K. DNP enhancements greater than 20X have been achieved, with microwave powers around 30 mW, at 20-25 K and with MAS at 7 kHz. With a new "extended interaction oscillator" (EIO) source that produces 700 mW of microwave power, DNP signal enhancements up to 200X have been achieved. This technology now permits solid state NMR studies of a variety of systems that were previously inaccessible due to low signal-to-noise. Demonstrations and tests on transient intermediate species in amyloid fibril formation pathways and peptide/protein complexes (M13/calmodulin) have been performed and will be pursued further in FY14. (2) THEORY OF DNP. We have developed the first comprehensive theoretical understanding of dynamic nuclear polarization under magic-angle spinning (MAS). The theory takes into account the periodic time dependence of nuclear and electron spin energy levels due to sample rotation and shows that DNP (i.e., transfer of electron spin polarizations to nuclear spins) occurs through a series of population transfers at time-dependent level crossings. The theory also predicts that MAS alone can perturb nuclear spin polarizations in nitroxide-radical-doped samples, with application of microwaves. This effect has been verified by experiments. (3) DEVELOPMENT OF TRIRADICAL POLARIZING AGENTS FOR DNP. We have synthesized and tested a series of tri-nitroxide compounds with related chemical structures and varying solubilities, as well as bi-nitroxide and tetra-nitroxide compounds. We find that tri-nitroxide compounds produce the largest DNP enhancements at temperatures around 25 K under MAS, and thus are the preferred compounds for our DNP experiments. (4) DNP-ENHANCED MRI MICROSCOPY. We have initiated a project to design and construct a magnetic resonance imaging system capable of sub-micron resolution. This MRI system will operate at low temperatures (<10 K) and use dynamic nuclear polarization to enhance proton NMR signals, ultimately enabling signals from voxels with < 1 micron dimensions to be detected. A prototype has been constructed and tested at room temperature, based on a surprisingly simple design in which magnetic field gradient coils and RF coils are mounted on a series of stacked sapphire plates. 3D images of "phantom" samples have been obtained successfully, so far with spatial resolution of approximately 5 microns in each direction. Attempts to reach 2 micron resolution at room temperature are in progress, which would represent a world record for MRI microscopy. Low temperature experiments will be performed in FY14.

2013财政年度在以下方面取得了进展： (1)低温动态核极化（DNP）。 DNP是这样一种现象，其中用微波照射电子自旋跃迁导致核自旋极化的增强，并因此导致NMR信号的增强。 我们已经建造了一个新的魔角旋转探头与DNP能力，工作低至20 K。 DNP增强大于20倍已经实现，微波功率约30 mW，在20-25 K和MAS在7 kHz。 通过一个新的“扩展相互作用振荡器”（EIO）源，产生700 mW的微波功率，DNP信号增强高达200倍。 这项技术现在允许固态核磁共振研究的各种系统，以前无法访问，由于低信噪比。 已经对淀粉样蛋白原纤维形成途径和肽/蛋白质复合物（M13/钙调蛋白）中的瞬时中间物质进行了演示和测试，并将在2014财年进一步进行。 (2)DNP理论 我们已经开发了第一个全面的理论理解下魔角旋转（MAS）的动态核极化。 该理论考虑了由于样品旋转引起的核和电子自旋能级的周期性时间依赖性，并表明DNP（即，电子自旋极化到核自旋的转移）通过在时间相关的能级交叉处的一系列布居转移发生。 该理论还预测，MAS单独可以扰动氮氧自由基掺杂的样品中的核自旋极化，与微波的应用。 这一效应得到了实验的验证。 (3)DNP三自由基偏振剂的研制。 我们已经合成并测试了一系列具有相关化学结构和不同溶解度的三氮氧化合物，以及二氮氧化合物和四氮氧化合物。 我们发现，三硝基氧化合物产生最大的DNP增强在25 K左右的温度下MAS，因此是我们的DNP实验的优选化合物。 (4)DNP增强MRI显微镜检查。 我们已经启动了一个项目，设计和构建一个磁共振成像系统能够亚微米分辨率。 该MRI系统将在低温（<10 K）下运行，并使用动态核极化来增强质子NMR信号，最终能够检测到尺寸< 1微米的体素的信号。 一个原型已经构建和测试在室温下，基于一个令人惊讶的简单的设计，其中磁场梯度线圈和RF线圈安装在一系列堆叠的蓝宝石板。 已经成功地获得了“体模”样品的3D图像，到目前为止，每个方向的空间分辨率约为5微米。 在室温下达到2微米分辨率的尝试正在进行中，这将代表MRI显微镜的世界纪录。 低温实验将在2014财年进行。