Grant: Discovery Grants Program - Individual

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 1 H, 13 C, and 15 N. 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, 17 O, 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, 17 O is very often considered to be NMR invisible in the context of biological macromolecules. Recently, we have made two breakthroughs tosolve this challenging problem. First, we have demonstrated the feasibility of obtaininghigh resolution 17 O NMR spectra for biological macromolecules both in the solid state and in aqueous solution. Second, we have shown that 17 O 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 17 O 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.