EXPANDING MOLECULAR-DYNAMICS SIMULATIONS TO THE NMR TIME-SCALE .1. STUDIES OF CONFORMATIONAL INTERCONVERSIONS OF 1,1-DIFLUORO-4,4-DIMETHYLCYCLOHEPTANE USING MM3-MD

A molecular dynamics (MD) simulation of 35,000 picoseconds tps) has be en carried out to study the conformational interconversions of l,l-dif luoro-4,4-dimethylcycloheptane at room temperature using the MM3 force field. The exchange between axial and equatorial fluorine atoms was t he only conformational interconversion that occurred, and it took plac e via the process of pseudorotation. Ring inversions (twist-chair > tw ist-boat > twist-chair) were not observed. The axial-equatorial exchan ge of the two fluorine atoms took place five times during the MD traje ctory of 35,000 ps. The two CH3 groups occupied symmetrical positions (exchangeable by a C-2-like rotations, where C-2-like means it would b e C-2 if the fluorines were not present) in the MM3 structures, and du ring most of the time of the MD trajectory. The methyls occasionally m oved off the C-2-like axis in the simulated process, mostly because th e C-2-like axis was momentarily moved so that it did not pass through the ring atom to which the two CH3 groups are bonded. A C-2-like symme try of the twist-chair conformation was maintained approximately durin g most of the MD simulation. The conformational geometry with the high est energy obtained during the axial-equatorial exchange process was f ound and used to locate the transition state. The energy barrier for t his axial-equatorial exchange was calculated to be 4.7 kcal/mol, and i t compares with the value (5.0 kcal/mol) determined by dynamic nuclear magnetic resonance (NMR). (c) 1994 by John Wiley and Sons, Inc.