This application targets the acquisition of a new console for our 600 MHz NMR spectrometer, a cryogenically-cooled probe, three high-power lasers (25 W frequency-tunable Argon ion, excimer, and Ti-Sapphire) for photo-CIDNP-mediated ultrasensitive NMR and laser-initiated chemistry, and flow and sample-changer automation. The above instrumentation will provide unique capabilities to the UW- Madison and entire US research community. The requested equipment will be located in the Paul Bender Chemistry Instrument Center (PBCIC) within the Department of Chemistry at the University of Wisconsin-Madison. All instrumentation will be housed in a dedicated room that has excellent temperature and humidity control already in place, and will be overseen by experienced personnel with a proven track record for spectrometer method development, supervision, safe operation and technical support. The laser-enhanced spectrometer will be available for use to both on- and off-campus researchers. The requested instrumentation will provide crucial support for a variety of hypothesis-driven health-related research and method development that should benefit the NMR community at large. Major research projects that will be enabled by the requested equipment include: (1) photochemically-induced dynamic nuclear polarization (photo-CIDNP) method development and applications;(2) structural studies on molecular chaperone-substrate complexes;(3) NMR analysis of photo-initiated chemical reactions;(4) NMR-detected high-throughput screening of novel compounds for biomedically valuable activities;(5) structural characterization and screening of protein-like foldamers;(6) exploration of the molecular basis of carbohydrate-mediated intercellular recognition;and (7) development of ligands that intercept inter-bacterial communication (quorum sensing) and elucidate host-microbe signaling. The high-power lasers and flow accessories will provide unprecedented capabilities and flexibility for cutting-edge high-sensitivity laser-enhanced NMR. Progress on fundamental scientific challenges such as signal-to-noise enhancement in NMR spectroscopy, elucidation of reaction mechanisms, and characterization of RNA and protein folding processes in real time will be enabled. The synergism between photo-CIDNP-enhanced NMR and the cryogenic probe will enable collecting crucial biological data on samples that require rapid, ultrasensitive data collection (e.g., aggregation-/degradation-prone systems), and pave the way to augment the intrinsically poor sensitivity of NMR spectroscopy. Finally, the automated sample-changing capabilities will enable high-throughput screening within the PBCIC, with significant advancements for health-related research.
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