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.
