Theoretical Studies of Chemistry in Solution

William Jorgensen得到了理论和计算化学计划的资助，继续他对溶液中有机反应的理论研究。Jorgensen将向三个新方向扩展他之前在这一领域的工作：1)他将寻求改进的液态水计算模型，能够在大范围的温度和压力下再现实验密度；2)他将开发使用线性响应理论的蒙特卡罗模拟方法，以快速预测分子性质，包括水合自由能和辛醇/水分配系数；3)他将寻求改进组合量子力学和分子力学计算的方法，包括将目前的半经验分子轨道技术扩展到包含d电子的第二排原子。这些技术将应用于几个有机反应，包括：1)羊毛甾醇的生物合成；2)硫醇酸盐的Michael加成；3)杯芳基吡咯的卤化物选择性。这一研究对于阐明溶剂化对反应速率、分子间相互作用和溶液中主客体结合的分子水平的影响以及溶剂化对分子结构和反应活性的影响具有重要意义。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、具有新性质的材料和分子器件的实验工作密切平行和补充。

William Jorgensen is supported by a grant from the Theoretical and Computational Chemistry Program to continue his theoretical studies of organic reactions in solution. Jorgensen will extend his previous work in this area in three new directions: 1) he will seek an improved computational model for liquid water that can reproduce experimental densities over large ranges of temperature and pressure; 2) he will develop Monte Carlo simulation approaches using linear response theory to perform rapid prediction of molecular properties including free energies of hydration and octanol / water partition coefficients; 3) he will seek to improve the methodology for combined quantum and molecular mechanics calculations including the extension of current semi-empirical molecular orbital techniques to second row atoms containing d electrons. These techniques will be applied to several organic reactions including: 1) biosynthesis of lanosterol; 2) Michael additions of thiolates; and 3) halide selectivity for calixpyrroles.This research is important for the elucidation of molecular-level effects of solvation on reaction rates, intermolecular interactions and host-guest binding in solution, and the influence of solvation on the structures and reactivity of molecules. The theoretical studies closely parallel and complement experimental work on the 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.