Theoretical Studies of Chemistry in Solution

耶鲁大学的William Jorgensen得到了理论与计算化学项目的支持，继续他在溶液中有机化学的理论研究。化学系统在原子水平上使用分子量子力学、分子力学、分子动力学和蒙特卡罗统计力学进行建模。该项目包括以下工作：(1)开发与Jorgensen改进的液态水计算模型相一致的有机分子的修正势函数，并通过强调蒙特卡罗模拟的测试来正确使用纯有机液体和水化自由能；(2)开发改进的半经验量子力学方法，以实现溶液中有机和酶反应的常规计算研究；(3)将半经验构型相互作用纳入量子力学框架，初步应用于溶剂溶解反应和伯格曼环化；(4)启动与有机氟化合物分子内相互作用的基础研究，以补充目前对全氟烷烃作为溶剂和氟效应的兴趣。研究结果有望增强对有机反应、分子性质和分子内相互作用的理解，这些都是化学和生物化学的核心。本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。这些理论研究与有机反应的优化、催化剂的开发、有机分子（包括药物和代谢物）的选择性受体、新性质材料和分子器件的实验研究密切相关，互为补充。

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.