The UC Santa Cruz Department of Chemistry and Biochemistry requests funds to purchase a 500 MHz- 11.75 Tesla Nuclear Magnetic Resonance spectrometer. The central instrumentation lab in our Department of Chemistry and Biochemistry provides analytical support for the researchers of the UCSC chemistry and biochemistry community. It is managed by a full-time staff person who provides maintenance, training and advisory services. One 250 MHz NMR spectrometer and one 300 MHz NMR spectrometer are housed in this laboratory and these instruments are used on a round-the-clock basis. While our department does not have a 500 MHz instrument, a triple channel 500 MHz spectrometer, purchased from a Markey Foundation grant, is housed in the UCSC Center for the Molecular Biology of RNA. Unfortunately, essentially no time is available on it for general chemistry use. In this application we outline the benefit that will be derived from the acquisition of an NMR spectrometer with state-of-the art capabilities. Overall, this equipment will support the education and training of more than 10 postdoctorals, 33 graduate student researchers and 10 undergraduates who are involved in the programs of six core research groups. A comparable number of postdoctoral and student researchers are affiliated with the programs of another six secondary user research groups. The six projects of the primary users include: Structural Characterizations of Exotic Marine Sponge Natural Products (Organic Chemistry Prof. Crews), Structural Studies of Partially-Folded Intermediate States of Proteins (Biochemistry Prof. Fink), Synthesis of Complex Molecules (Organic Chemistry Prof. Konopelski), Designed Analogues of Metallobleomycins (Inorganic Chemistry Prof. Mascharak), Nuclear Magnetic Resonance of Peptide Helix Conformations (Physical Biochemistry Prof. Millhauser), and NMR Studies of Lense Transparency (Physical Biochemistry Prof. Schleich).The secondary user research groups include those involved in the follo wing subject areas: three organic, one bioinorganic, one marine chemical toxicology, and one biological NMR. Our faculty has continued to keep abreast of developments in NMR technology. Two of the investigators of this proposal (Crews and Schleich) have extensively obtained and used 500 MHz data in their research. Three others (Konopelski, Millhauser, and Mascharak) each include examples of actual 500 or 600 MHz data in their research descriptions. We desperately need to have a more rapid turn-around time for two-dimensional (2D) experiments.. Neither of the two instruments in the central lab can satisfy the desire to carry out contemporary 2D NMR experiments. These two instruments have very limited INVERSE detection capabilities because both lack the necessary probes and associated hardware for such detection. In addition, the reduced sensitivity at both 250 MHz and 300 MHz make the inverse detection method much more difficult to satisfactorily implement. We need access to rotating frame experiments. As will be noted in the proposal, many important 2D-NMR rotating frame experiments such as TOCSY, ROESY, HMQC-TOCSY or T-ROESY are not available to our researchers. Overall, such a limited capacity does not allow us to rapidly obtain sophisticated NMR data which is a must in structure studies of complex organic, biochemical, and bioinorganic compounds. The additional obvious major problem is that signals can not be resolved when large clusters of protons overlap for the increasingly complex molecules being studied by our researchers. In summary, the instrument we seek will make it possible for our student and faculty researchers to increase their productivity. The use of this new instrument will be overseen by James Loo, who has been the Chemistry NMR lab manager since 1980.
