The Chemistry and Analytical Core will provide support for the individual research projects. The Core consists of two components: the Synthesis Laboratory and the Mass Spectrometry Facility. The Synthesis Laboratory will be responsible for providing, on a continuing basis, specific compounds for which need has been established by the Program Projects. Compounds synthesized by the Core will be used as standards in quantitation, for in vitro formation of DNA and protein adducts for in vivo dosing protocols. The availability of standards multiply labeled with stable isotopes from the Synthesis Laboratory will crucial to the development of isotope dilution methods for ultra-trace analysis of metabolites and DNA and protein adducts by the Mass Spectrometry Facility. Specific classes of compounds for which synthetic needs have been established are: Project 1, tricyclic nucleobases, deoxynucleosides and deoxynucleotides; protein adducts of malondialdehyde and 4-hydroxynon-2-enal; cysteine contual basis for dosing protocols; Projects 3 and 8, S-phenyl-d5-cysteine and mercapturic acid; Project 4, fungal metabolites of PAH and Project 5, 13C-labeled PAH phenoles. Synthesis Laboratory will also be available for consultation on questions involving structural characterizations, and application of spectroscopic techniques to problems of quantitation and characterization. Other areas where Core expertise may be useful to Program Projects are in the application of structure-activity relationships to direct efforts in isolation and characterization of products of metabolism or non-enzymatic decay. The Core has access to 500 and 500 MHz NMR spectrometers with multinuclear and variable temperature capability. Core personnel are trained operators, proficient in all aspects of data acquisition, work-up and interpretation, and will fill the NMR needs of program projects. Additional techniques of physical characterization accessible through the Core are circular dichroism X-ray crystallography, EPR and FTIR. The Mass Spectrometry Facility will provide support for Program Projects when mass spectrometry requirements are beyond the capacity of equipment belonging to Program Projects or when extensive methods development is necessary. The Mass Spectrometry Facility performs characterization and ultra-trace analysis on a routine basis by a variety of mass spectrometric techniques, and is also involved in developmental work. Major objectives of the Mass Spectrometry Facility will be to develop on-line sample clean-up and analyte pre-concentration procedures and to apply HPLC/MS/MS techniques to characterization of DNA adducts, protein adducts and PAH metabolites.
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