Important functions of the Chemistry Core are to furnish critical intermediates and standards and to aid in the development or improvement of techniques in quantitation and characterization of analytes of concern. In general, required synthesis will follow published routes if available. Many of the analytes and standards, particularly metabolites, protein and nucleobase adducts and their isotopomers have not been reported. For these compounds, original synthetic routes will be devised. The Mass Spectrometry Facility is a subunit of the Core, and is charged with an important role in structural characterizations and quantitative analysis by using a variety of mass spectrometric techniques. This role includes development or improvement of derivatization techniques for GCMS determinations in collaboration with a the synthesis laboratory. The Facility will also develop ionization techniques for enhanced acquisition of mass spectral data from refractory samples. The Core will also be a resource for consultation with Research Project Projects on questions concerning matters such as interpretation of spectroscopic data, structural assignments, reactivity. Particular tasks identified at this time include: For Project 1, the Core will synthesize 13C-labelled nucleobases and adducts and 2-chlorooxirane, and will develop electrospray ionization techniques interfaced to liquid chromatography for sample introduction. The Core will provide guidance in selection of suitable compounds for studying the role of secondary effects in generation of cyclic DNA adducts, such as the etheno- and ethano-bridged nucleobases. The Core may also aid in devising strategy for characterizing metabolites and DNA adducts of the dinitrotoluene isomers. For Project 2, the Core will synthesize 2-chlorooxirane, the active intermediate of vinyl chloride. For Project 3, the Core will synthesize stable-isotope-labelled standards of protein adducts, and also active intermediates. The Core may also provide guidance in characterization of cystein e adducts of tetrachlorosemiquinone, if the species anticipated to be present in the analytical protocol (2,3,5,6-tetrachlorophenol) is not observed. For Project 4, the Core will synthesize PAH metabolites, and develop electrospray ionization techniques interfaced to liquid chromatography for sample introduction. The Core will determine the target PAH metabolite structures for synthesis as authentic standards for structural assignments. The Core also anticipates an important role in deduction of metabolites can be collected for direct structural characterization. For Project 5, the Core will synthesize 13C-labelled PAH and metabolites.
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