The reactivity of a molecule is generally tied to molecular structure and energy. In this proposal, the thermochemistry of three reactive functional groups -- epoxides, aziridines and alkyl hydroperoxides -- will be investigated. Epoxides and aziridines are important synthetic intermediates that are often used in the synthesis of complex natural products. These functional groups are also present in a variety of biologically active molecules such as steroid precursor squalene-2,3-epoxide and therapeutic mitomycin. Even simple epoxides and aziridines can react in vivo;many are carcinogenic, reacting with DNA. Alkyl peroxyl radicals are formed via the oxidation of hydrocarbons. They are prevalent in the troposphere where they are involved in smog production. When formed from an unsaturated fatty acid, they can lead to lipid cleavage. As important as these groups are in biological systems, very few thermochemical data are available for these groups. The gas-phase heat of formation, one of the most fundamental properties of a molecule, is known for only eight simple epoxides and one aziridine. Heats of formation for methyl- and ethyl hydroperoxides, the two simplest examples, are unknown. Without a good understanding of the most fundamental of molecules, it is difficult to even begin to understand more complicated systems. In this study, calorimetry will be used to measure heats of reaction for a variety of molecules from each functional group. These reaction enthalpies can ultimately be converted to gas phase heats of formation. These data can be used to gain a better understanding of the influence of structure and substitution patterns on molecular stability, which is often useful in predicting reactivity of molecules. The data obtained in this study will lead to a significant increase in our knowledge of simple yet fundamental biologically-active molecules. In addition, molecular modeling programs are commonly used to design potential drug molecules, as well as understand how molecules work. The data obtained in the proposed work is expected to lead to improved force fields and better modeling results.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Research Continuance Award (SC3)
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Special Emphasis Panel (ZGM1-MBRS-1 (CH))
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Krasnewich, Donna M
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Xavier University of Louisiana
Schools of Arts and Sciences
New Orleans
United States
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Morgan, Kathleen M; Ashline, David J; Morgan, Jessica P et al. (2014) Electrospray ionization (ESI) fragmentations and dimethyldioxirane reactivities of three diverse lactams having full, half, and zero resonance energies. J Org Chem 79:517-28
Morgan, Kathleen M; Ellis, Jamie A; Lee, Joseph et al. (2013) Thermochemical studies of epoxides and related compounds. J Org Chem 78:4303-11
Morgan, Kathleen M; Brown Jr, Garry; Pichon, Monique A et al. (2011) ?-Elimination of an Aziridine to an Allylic Amine: A Mechanistic Study. J Phys Org Chem 24:1144-1150