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。在这个提议中，三个反应性官能团-环氧化物，氮丙啶和烷基氢过氧化物-的热化学将进行研究。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多种生物活性分子中，例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丙啶也能在体内发生反应;许多都是致癌的，与DNA发生反应。烷基过氧自由基通过烃的氧化形成。它们普遍存在于对流层，参与烟雾的产生。当由不饱和脂肪酸形成时，它们可导致脂质裂解。 尽管这些基团在生物系统中很重要，但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，已知的只有八种简单的环氧化物和一种氮丙啶。甲基和乙基氢过氧化物的生成热，这两个最简单的例子，是未知的。如果不能很好地理解最基本的分子，就很难开始理解更复杂的系统。 在这项研究中，量热法将用于测量反应热的各种分子从每个功能组。这些反应产物最终可转化为气相生成热。这些数据可用于更好地理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。 在这项研究中获得的数据将导致我们对简单但基本的生物活性分子的知识的显着增加。此外，分子建模程序通常用于设计潜在的药物分子，以及了解分子如何工作。在拟议的工作中获得的数据预计将导致改善力场和更好的建模结果。

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.