Theoretical Studies of Chemistry in Solution

耶鲁大学的William Jorgensen在理论和计算化学项目的支持下，继续他在溶液中的有机化学的理论研究。化学体系是用分子量子力学、分子力学、分子动力学和蒙特卡罗统计力学在原子水平上建模的。该项目包括以下努力：(1)开发修订的有机分子势函数，与Jorgensen改进的液态水计算模型一致，并进行测试，强调正确使用纯有机液体和水合自由能的蒙特卡罗模拟；(2)开发改进的半经验量子力学方法，使常规计算研究溶液中的有机和酶反应成为可能；(3)将半经验组态相互作用纳入量子力学框架，初步应用于溶剂分解反应和Bergman环化反应，以及(4)启动对有机氟化合物分子内相互作用的基础研究，以补充目前人们对全氟烷烃作为溶剂和憎氟效应的兴趣。预计结果将使人们能够更好地了解对化学和生物化学至关重要的有机反应、分子性质和分子内相互作用。这项研究将揭示溶液中分子过程的有用信息，以及分子受其溶剂环境影响的方式。这些理论研究与优化有机反应和开发催化剂、包括药物和代谢物在内的有机分子的选择性受体、具有新性能的材料和分子器件的实验研究密切平行和补充。

William Jorgensen of Yale University is supported by the Theoretical and Computational Chemistry Program to continue his theoretical studies of organic chemistry in solution. Chemical systems are modeled at the atomic level using molecular quantum mechanics, molecular mechanics, molecular dynamics, and Monte Carlo statistical mechanics. The project includes the following efforts: (1) developing revised potential functions for organic molecules that are consistent with Jorgensen's improved computational model for liquid water, with testing that emphasizes Monte Carlo simulations for the proper use of pure organic liquids and free energies of hydration, (2) developing improved semiempirical quantum mechanics methods to enable routine computational study of organic and enzymatic reactions in solution, (3) incorporating semiempirical configuration interaction into the quantum mechanics framework, with initial applications to solvolysis reactions and Bergman cyclization, and (4) initiating basic studies of intramolecular interactions with organofluorine compounds to complement current interest in perfluoroalkanes as solvents and in fluorophobic effects. Outcomes are expected to enable an enhanced understanding of organic reactions, molecular properties, and intramolecular interactions that are central to chemistry and biochemistry. This research will reveal useful information on molecular processes in solution, and the ways in which molecules are affected by their solvent environment. The theoretical studies closely parallel and complement experimental research on optimization of organic reactions and on the development of catalysts, selective receptors for organic molecules including drugs and metabolites, materials with novel properties, and molecular devices.