The principal aim of this proposal is the development of basic methods and theory for using solid state nuclear magnetic resonance (SSNMR) techniques in relevant biomedical problems using the C-13 and N-15 magnetic isotopes. SSNMR is becoming an increasingly important tool in almost all branches of chemistry and biology. Theoretical computations tie experimental data to structure and allow the influence of hydrogen bonding, conformation and stereo-chemistry to be systematically evaluated through analysis of hypothetical model compounds. New HETCOR, INADEQUATE, FIREMAT, and TIGER methods will be used. As many biomolecules have very low solubility, SSNMR methods offer an important way to investigate these systems. This allows x-ray powder diffraction (XRPD) to be combined with SSNMR in obtaining lattice structure. While diffraction methods characterize long range microcrystalline lattice arrays, SSNMR focuses with greater accuracy on short range order especially when studying proton positions in powders. XRPD finds considerable success when Z = 1 and when the molecular weight is not overly high. If Z e 2, the Rietveld structural fit of diffraction histograms tends to break down without independent information such as SSNMR initial structures. Thus, we intend to study a number of important bio-systems: flavenoids such as catechin (Z =2), Taxol. (Z =2x1/2). Actinomycin D has a doubling of two half molecules, The available single crystal structures for actinomycin D take advantage of the known lattice structure to aid in developing methods for the combined use of SSNMR and XRPD in powders. Catechin (powerful anti-oxidant) found in chocolate and the recently developed, stable Taxol. polymorph have never been obtained in single crystal form. Taxol. is one of the leading anti-carcinogen agents used to treat many different forms of cancer in our country at the present time, Structural information on Taxol. and its tubuline peptide could be of great health consequence. The N-15 applications include natural products, pharmaceuticals, nucleosides, peptides and related derivatives, etc. SSNMR is also proving to give reliable information on antioxidants from polyphenolic flavenoids.
We are using solid state NMR methods to study structure of biomedical systems that can be studied in no other manner. When combined with additional quantum chemical calculations, X-ray (both single crystal and microcrystalline powders approaches), density measurements, etc. structural information is obtained that can be gained in no other manner. Modern Biomedical work has become very dependent upon this type of data. Our focus is on new and powerful techniques. The applications include drug and pharmaceutical agents, several antioxidant flavonoids. Specifically, we have made considerable progress in the structure of Taxol., catechin, and a variety of new bioactive and potential drugs from plants, and chitisan, chitin which are derivatives of the very common natural polymer: glucosamine.
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