MOLECULAR MECHANICS AND STATISTICAL THERMODYNAMICS STUDIES OF COMPLEXES OF A FLEXIBLE HEMICARCERAND WITH NEUTRAL GUESTS

摘要

Computational studies of the structures and conformational properties of hemicarcerand 2, a model for 1, studied experimentally by Cram et al., and the complexation and decomplexation of guest molecules by this host have been carried out with MACROMODEL/MM3*. Energy minimizations, molecular dynamics, and statistical perturbation theory calculations were performed. Conformational processes in the intrahemispheric bridges (OCH2O) of the host molecule have been shown to be important for the passage of guest molecules in and out of the cavity. This transient gate-opening phenomenon has a significant influence on the complexation of bicyclic guests, while smaller aromatic guests can pass in and out without gate-opening. Constrictive binding is crucial for the isolation of hemicarceplexes, since it provides a kinetic barrier which permits isolation of complexes. The 1:1 complexes of hemicarcerand 2 with bicyclic guests and benzene derivatives were found to be energetically favorable by 12-23 kcal/mol in the gas phase. Nevertheless, only the bicyclic guests and some substituted monocyclics form stable complexes. If guests are too large, kinetic barriers prevent complexation. Aromatic guests with disk-like shapes are predicted to farm complexes in solution, but to be unstable because of their low decomplexation energy barriers.