Project Summary This major instrumentation proposal requests funds for the purchase of a JEOL 500 MHz NMR spectrometer to support a large user base of NIH-funded researchers at the Johns Hopkins School of Medicine (JHSOM). Re- searchers supported by the JHSOM NMR facility come from diverse clinical and basic science departments and are funded by numerous NIH institutes (NIGMS, NCI, NIAID, NIDDK, NIDA, NINDS, NIA, NIBIB, NEI, and NIMH). This new state-of-the-art spectrometer package consists of a 11.7T, shielded, 54 mm bore magnet, a spectrom- eter console with an RF generation system, preamplifiers, power amplifiers, digital receivers, and a field gradient system. The requested 5 mm FG/RO HFX digital autotune probe and 24 slots autosampler are essential features to support characterization of small molecules studied by our user base and to maximize throughput and ease- of-use. The new Dell Precision Workstation and the pulse programmer controlled by the Delta FT-NMR software provide a friendly user interface that will facilitate the achievement of research goals. Since the previous sub- mission, due to frequent and expensive repairs and crippling service disruptions, our previous 500 MHz Bruker system was replaced with the JEOL 500 MHz spectrometer described above. We are currently using the JEOL system under a negotiated evaluation agreement with an option to pay and own, extend the lease, or return without full payment by May 10, 2024. For 23 years this NMR core resource, which is managed and supported by the Department of Pharmacology and Molecular Sciences (DPMS), has been key in supporting biomedical chemistry research at the school of medicine. The health-related goals of the supported projects range from development of new imaging agents, new drug discovery for cancer and neurological diseases, and basic inves- tigations into cellular metabolomics and drug metabolism. The facility provides an essential resource for syn- thetic chemistry, drug development and basic science research efforts at the medical school campus. It provides the main tool for our chemists to assess the outcome of chemical transformations (1D 1H, 31P, 13C and 19F NMR spectra). Our research spans all classes of organic molecules of biomedical interest, including bioactive probes, drugs, and polymer conjugated molecules. In addition, the capabilities of this moderately high-field instrument allow for more sophisticated homonuclear and heteronuclear experiments to elucidate the structure of challeng- ing small molecules, nucleic acids, small proteins, and peptides (2D COSY, TOCSY, HSQC, HMBC, NOESY). Thus, this facility has contributed to biomedical research in a unique way over the past 23 years and will continue in this role with this new, very needed instrumentation upgrade.