Organic Reactions and Interactions in Solution

William Jorgensen获得了理论与计算化学项目的资助，继续他在溶液中有机反应机制的理论模拟研究。这项工作涉及使用从头算MO理论来获得有关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，模拟溶液中的化学反应。这些方法的结合提供了化学反应中溶剂化自由能变化的估计，并提供了关于溶剂化在化学反应中所起作用的重要背景信息。这些方法被应用于各种重要的反应机制，包括（2+2）环加成，氧- cope重排和醇氧烷烷基化。也正在进行主-客体系统的模拟，重点是预测在设计链烷和轮烷方面的重要结合偏好，它们有望成为分子装置的基础。利用过渡态几何图形和从头计算得到的电荷，计算机辅助设计催化宿主也正在进行中。本研究对于阐明溶剂化对溶液中反应速率、分子间相互作用和主-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、具有新性质的材料和分子器件的实验工作密切相关，互为补充。

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.