Request for a 500 MHz NMR console and nitrogen-cooled cryoprobe

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Abstract This proposal is a request to upgrade the 500 MHz NMR spectrometer that operates in the Eshelman School of Pharmacy at the University of North Carolina at Chapel Hill (UNC Eshelman School of Pharmacy). This facility serves a community of NIH-supported medicinal chemists, chemical biologists, drug delivery scientists, and a molecular imaging methodologist with biological applications. The requested equipment is for a Bruker Neo 500 console with liquid nitrogen cooled cryoprobe and automatic sample changer. The requested upgrade equipment is critical because all of the NMR instruments in the facility are aging Varian spectrometers that have never been upgraded and are no longer supported by the vendor. None of the instruments currently have cryoprobes, and hence the sensitivity is limited, especially for the many routine 13C acquisitions that are needed for small molecule NMR. The work in the School of Pharmacy’s NMR Facility is highlighted by the existence of two centers, the Center for Integrative Chemical Biology and Drug Discovery (CICBDD, led by Dr. Stephen Frye) and the UNC footprint of the Structural Genomics Consortium (SGC-UNC, led by Dr. Tim Willson). These centers produce very large numbers of small molecules that are used in libraries or are tested for activities against a variety of disease-related targets. The syntheses of these molecules require extensive NMR characterization, and there is a large need for high-sensitivity, automated data collection to support this work, as well as the research of the other researchers included in this application. The facility is managed by an experienced manager/director team and further supported by an oversight committee and School administration. There are two locations for the spectrometers in a single building (Marsico Hall, completed in 2014), with the spaces designed specifically for NMR. This is a first-rate facility with excellent infrastructure; however, the age of the spectrometers poses a serious threat of lengthy downtime that may be very challenging to deal with in the event of hardware failure. Furthermore, convenient walk-up access to spectrometers that serve the needs of the users is becoming problematic because of limited automation and low sensitivity of existing probes. This requested equipment is the first step towards modernizing the facility through upgrades that will introduce a highly user-desirable instrument that can be relied upon for the next decade and beyond.