Organic Reactions and Interactions in Solution

William Jorgensen得到了理论和计算化学计划的资助，继续他的研究，涉及溶液中有机反应机理的理论模拟。这项工作涉及到使用从头算分子轨道理论来获得关于有机反应的气相势能面的信息。然后将这些信息与蒙特卡罗模拟技术结合使用，以模拟溶液中的化学反应。这些方法的结合提供了对化学反应中溶剂化自由能变化的估计，并提供了有关溶剂化在化学反应中所起作用的重要背景信息。这些方法正在应用于各种重要的反应机理，包括(2+2)环加成、氧-钴重排和醇烷基化。主客体系统的模拟也在进行中，重点是预测在设计链烷和轮烷时具有重要意义的结合偏好，这显示出作为分子装置基础的前景。使用从从头算获得的过渡态几何构型和电荷的计算机辅助设计催化主体也在进行中。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效应，以及溶剂化对分子结构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 research involving theoretical simulations of organic reaction mechanisms in solution. This work involves the use of ab initio MO theory to obtain information regarding the gas phase potential energy surface for organic reactions. This information is then used in conjunction with Monte Carlo simulation techniques to simulate the chemical reaction in solution. The combination of these methodologies provides estimates of the solvated free energy changes involved in a chemical reaction, and provides important background information on the role which solvation plays in chemical reactions. These methodologies are being applied to various important reaction mechanisms including the (2+2) cycloaddition, oxy-Cope rearrangements, and alkoxide alkylations. Simulations of host-guest systems are also being performed with an emphasis on predicting binding preferences of importance in the design of catenanes and rotaxanes which show promise as the basis for molecular devices. Computer-assisted design of catalytic hosts using transition state geometries and charges obtained from ab initio calculations is also being pursued. 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 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.