THEORY OF PROTON AND HYDRIDE TRANSFER REACTION RATES

建议构建分析理论，进行模型评价 计算，并进行质子和质子的计算机模拟 氢化物在溶液和酶模型中的转移反应 系统。尽管它们在酸碱化学和 酶催化，这些反应在 分子水平；目前还没有合适的理论 介绍了诸如量子隧道和强 质子和氢化物运动与极性和离子的耦合 环境。这些方面可能导致严重背离 传统的理论框架被广泛应用于 动力学同位素效应的解释。 总的目标是为 解释这些反应，以确定其作用 隧道效应与环境的反应速率，以及 预测探索和揭示它们的实验趋势 分子特征。具体目标是构建 并执行分子内和分子间的计算 质子和氢化物在极性溶剂中的迁移，并计算 反应速率常数对同位素取代度的依赖关系为： 温度和溶剂的极性和动力学。一种相关的理论将 是为这些一般的极性和离子转移而开发的 环境，并应用于临界质子转移模型 在特定的酶催化步骤中，并以氢化物转移 在酶催化氧化还原过程的各个方面的模型中。 这些目标将通过使用和推广 在治疗其他疾病方面取得成功的理论方法 电荷转移反应的类型。其中包括时间相关性 函数方法和分子动力学计算机模拟。 可用的从头算势面信息也将是 使用。

It is proposed to construct analytic theories, perform model rate calculations, and to undertake computer simulations of proton and hydride transfer reactions in solution and in models of enzyme systems. Despite their importance in acid-base chemistry and enzyme catalysis, these reactions are not well understood at the molecular level; no theory currently exists which properly addresses such key features as quantum tunneling and the strong coupling of proton and hydride motion to a polar and ionic environment. These aspects can lead to serious departures from the conventional theoretical framework widely employed in the interpretation of kinetic isotope effects. General goals are to provide the theoretical framework for the interpretation of these reactions, to determine the role of tunneling and the environment in their reaction rates, and to predict the experimental trends which probe and reveal their molecular character. Specific aims are to construct the theory of and perform calculations for intramolecular and intermolecular proton and hydride transfers in polar solvents, and to calculate the dependence of the rate constants on isotopic substitution, tem- perature and solvent polarity and dynamics. A related theory will be developed for these transfers in general polar and ionic environments and applied to a model of a critical proton transfer step in a particular enzyme catalysis, and to a hydride transfer in a model of aspects of an enzymatic redox process. These goals will be accomplished via the use and extension of theoretical methodologies successful in the treatment of other types of charge transfer reactions. These include time correlation function methods and Molecular Dynamics computer simulation. Available ab initio potential surface information will also be used.