Exploring new frontiers of oxygen-17 NMR spectroscopy for chemical and biological applications

探索氧 17 NMR 光谱在化学和生物应用中的新领域

• 批准号: RGPIN-2016-05251
• 负责人: Wu, Gang
• 金额: $ 5.46万
• 依托单位: Queen's University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2016
• 资助国家: 加拿大
• 起止时间: 2016-01-01 至 2017-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=615586
• 关键词: Exploring; new; frontiers; oxygen; 17

Nuclear magnetic resonance (NMR) spectroscopy is a powerful analytical technique for studying molecular structure, dynamics, and chemical bonding. The development of this technique over the past several decades has revolutionized chemical and biological sciences. However, most successful NMR applications to biological systems such as proteins and nucleic acids are primarily based on detection of atomic nuclei with a nuclear spin quantum number of 1/2 such as 1H, 13C, and 15N. On the other hand, the oxygen element, being one of the most abundant in organic and biological molecules, has not yet been readily accessible by NMR spectroscopy. This is principally because the only NMR-active oxygen isotope, 17O, has a nuclear spin quantum number of 5/2, known as a quadrupolar nucleus. Quadrupolar nuclei are notoriously difficult to study by NMR because they often give rise to very broad NMR signals. As a result, 17O is very often considered to be “NMR invisible” in the context of biological macromolecules. Recently, we have made two breakthroughs to solve this challenging problem. First, we have demonstrated the feasibility of obtaining high resolution 17O NMR spectra for biological macromolecules both in the solid state and in aqueous solution. Second, we have shown that 17O NMR is also possible for paramagnetic compounds. The primary objective of our proposed research program for the next 5 years is to apply these new 17O NMR methods to solve important problems in the following three major areas: (1) detection of unstable reaction products, (2) further improvement of resolution at 36 T (the strongest NMR magnet in the world), and (3) studies of paramagnetic metalloproteins. The ultimate goal of our research program is to make all major elements (H, C, N, and O) found in organic and biological molecules equally accessible by NMR spectroscopy. The proposed research program will provide excellent opportunities for training of the next generation of highly qualified personnel to be competitive at the international level.

核磁共振 (NMR) 光谱是一种用于研究分子结构、动力学和化学键合的强大分析技术，该技术在过去几十年的发展已经彻底改变了化学和生物科学，然而，最成功的 NMR 应用是在生物系统中。因为蛋白质和核酸主要基于对核自旋量子数为 1/2 的原子核的检测，例如 1H、13C 和 15N。另一方面，氧元素是最丰富的元素之一。有机和生物分子尚未通过 NMR 光谱轻易获得，这主要是因为唯一的 NMR 活性氧同位素 17O 的核自旋量子数为 5/2，被称为四极核。由于 17O 经常产生非常宽的 NMR 信号，因此很难通过 NMR 研究。我们在解决这一具有挑战性的问题上取得了两项突破：首先，我们证明了获得固态和水溶液中生物大分子的高分辨率 17O NMR 谱的可行性。我们提出的未来 5 年研究计划的主要目标是应用这些新的 17O NMR 方法来解决以下三个主要领域的重要问题：（1）不稳定反应产物的检测， (2) 进一步提高 36 T 的分辨率（世界上最强的 NMR 磁体），以及 (3) 顺磁性金属蛋白的研究 我们研究计划的最终目标是制造所有主要元素（H、C、N 和）。 O）在有机和生物分子中同样可以通过核磁共振波谱法发现。拟议的研究计划将为培训下一代高素质人才提供极好的机会，使其在国际水平上具有竞争力。