Purchase of a 700MHz NMR Spectrometer for Liquid Applications Project Summary Solution nuclear magnetic resonance (NMR) spectroscopy is one of the most powerful spectroscopic tools available to the synthetic chemist for the elucidation of the structure of a molecule. Advances in computing power, high-field magnet technology, and improved electronics have dramatically increased both sensitivity and chemical shift dispersion such that detection of low natural abundance nuclei is now routine. Presently in the Chemistry department at the University of Michigan (UM, Ann Arbor) there is a rapidly growing gap between the existing capabilities offered by our aging/obsolete NMR spectrometers and the demands of our NIH-funded investigators. This demand stems from the fact that not only have the molecular systems under investigation grown in size and complexity, the questions being addressed by NMR are also more ambitious and include atomic characterization of molecular configuration, conformation, dynamics, interactions and mechanisms. The availability of a high field, multi-channel NMR spectrometer dedicated to liquid applications will have a significant impact on the investigation of complex natural products bearing multiple stereocenters, determination of relative stereochemistry of 5-membered carbocyclic ring systems such as cyclopentanes, tetrahydrofurans, and pyrrolidines possessing up to 4 stereocenters, characterization of unstable organoboron and organosilicon intermediates, and time-resolved kinetic studies of reactive organometallic intermediates formed in low concentrations. High-resolution structural information will be highly valuable in designing small molecule isoxazolidine transcriptional activators, as well as probing how enzymes use free radicals to catalyze chemically difficult transformations. Progress in these research projects and the training of chemistry students in cutting-edge NMR techniques are hampered due to the lack of an accessible modern high field NMR spectrometer. Therefore, to close this gap, we propose the purchase of a multi-channel 700 MHz NMR spectrometer outfitted with the latest in cryogenically cooled, triple resonance probe technology. Additionally, access to such a state-of-the-art instrument will be made available to NIH-funded chemistry projects at nearby institutions such as the University of Toledo, where significant benefit would be realized in the area of complex carbohydrate synthesis.
The NIH-funded projects described herein will contribute to a greater understanding of areas that impact human health. Advances enabled by the requested instrumentation include the discovery of potential drug leads, the understanding of biological processes involved in disease progression or prevention, and the development of new strategies in synthesis that enable creative solutions to research projects of this type.
