Thermochemistry of Strained Organic Heterocycles and Organic Peroxides

描述（由申请人提供）：分子的反应性通常与分子结构和能量有关。在本提案中，将研究三种活性官能团——环氧化物、氮嘧啶和烷基氢过氧化物的热化学。环氧化物和叠氮嘧啶是重要的合成中间体，常用于复杂天然产物的合成。这些官能团也存在于各种生物活性分子中，如类固醇前体角鲨烯-2,3-环氧化物和治疗性丝裂霉素。即使是简单的环氧化物和叠氮嘧啶也能在体内发生反应；许多是致癌物质，与DNA发生反应。烷基过氧自由基是通过碳氢化合物的氧化形成的。它们普遍存在于对流层，在那里它们参与了烟雾的产生。当由不饱和脂肪酸形成时，它们会导致脂质分裂。

DESCRIPTION (provided by applicant): 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.