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

核磁共振波谱是研究分子结构、动力学和化学键的一种强大的分析技术。这项技术在过去几十年的发展使化学和生物科学发生了革命性的变化。然而，大多数成功的核磁共振应用于生物系统，如蛋白质和核酸，主要是基于检测核自旋量子数为1/2的原子核，如1H，13C和15N。另一方面，氧元素是有机和生物分子中含量最丰富的元素之一，目前还不能很容易地通过核磁共振光谱获得。这主要是因为唯一的核磁共振活性氧同位素17O的核自旋量子数为5/2，即所谓的四极核。众所周知，四极核很难用核磁共振进行研究，因为它们通常会产生非常广泛的核磁共振信号。因此，在生物大分子的背景下，17O常常被认为是“核磁共振不可见的”。最近，我们在解决这一具有挑战性的问题上取得了两个突破。首先，我们论证了在固态和水溶液中获得生物大分子高分辨~(17)O核磁共振谱的可行性。其次，我们已经证明了顺磁性化合物的17O核磁共振也是可能的。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核磁共振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)在36T(世界上最强的核磁共振磁体)下分辨率的进一步提高，以及(3)顺磁金属蛋白的研究。我们研究计划的最终目标是使有机和生物分子中的所有主要元素(H、C、N和O)都能通过核磁共振光谱学获得。拟议的研究计划将为培养在国际上具有竞争力的下一代高素质人才提供极好的机会。

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.