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.
