500 MHz NMR Spectrometer Upgrade and Cryoprobe

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PROJECT SUMMARY/ABSTRACT We request the funding to purchase a Bruker NEO 500 MHz NMR spectrometer, equipped with a Prodigy (nitrogen boiloff) cryoprobe and a SampleCase 24-position sample changer. The existing NMR capabilities at the University of Washington, Seattle (UW) are increasingly both obsolete and unreliable, and indeed we recently had to decommission one instrument where neither the electronics nor magnet could be economically repaired. The technical limitations of much of our remaining instrumentation are slowing or blocking many lines of investigation on NIH-funded research in multiple departments. The proposed system will simultaneously improve reliability and efficiency by replacing our fastest-failing instrument and expand our research capabilities with advances in NMR technology that our decades-old equipment cannot provide. These include: (1) drastically increased sensitivity, 2-3 fold, across a range of nuclei ranging from 15N to 19F – an enhancement particularly valuable for 31P and 19F, nuclei of wide- ranging research utility that are badly underserved with existing equipment, and for which this will become the most sensitive instrument available on campus by a wide margin; (2) a combination of an automatic sample changer, automatic probe tuning and shimming, and automation software, which collectively provide users with highly efficient, hands-off sample handling to supply continued, productive instrument use during unattended hours; and (3) dynamic, wide-ranged temperature control, with experimental variability over a broad range to study reaction dynamics, and 0.1°C-precision stability to hold delicate biochemical samples at a safe, consistent temperature during storage and data acquisition. From small molecules to large proteins, NMR is a vital tool for determining structure, kinetics, and molecular interactions, relied upon by dozens of research groups on campus. This instrument will supply crucial support to full range of projects related to human health, including the development of new biomedical screening technologies, new synthetic pathways for pharmaceutical developments, mechanistic investigations of enzymatic tumor suppressors, metabolomic nutritional studies bolstering the recovery of critically ill patients, and many more.