Thermochemistry of Strained Organic Heterocycles and Organic Peroxides

描述(申请人提供)：分子的反应性通常与分子结构和能量有关。在这项建议中，将研究三个活性官能团--环氧化物、氮杂环丙烷和烷基过氧化氢的热化学。环氧化物和氮杂环丙烷是重要的合成中间体，常用于合成复杂的天然产物。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氮杂环丙烷也可以在体内发生反应；许多都是致癌的，与DNA发生反应。烷基过氧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。当它们由一种不饱和脂肪酸形成时，会导致脂肪分解。 尽管这些基团在生物系统中很重要，但关于这些基团的热化学数据很少。气相生成热是分子最基本的性质之一，已知只有八种简单的环氧化物和一种氮杂环丙烷。最简单的两个例子--甲基和乙基过氧化氢的生成热是未知的。如果不能很好地理解最基本的分子，甚至很难开始理解更复杂的系统。 在这项研究中，量热法将被用来测量来自每个官能团的各种分子的反应热。这些反应热最终可以转化为气相生成热。这些数据可以用来更好地了解结构和取代模式对分子稳定性的影响，这通常有助于预测分子的反应性。 这项研究中获得的数据将大大增加我们对简单但基本的生物活性分子的了解。此外，分子建模程序通常用于设计潜在的药物分子，以及了解分子的工作原理。在拟议的工作中获得的数据有望导致力场的改善和更好的建模结果。

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.