Molecular Mechanics and Statistical Thermodynamics Studies of Complexes of a Flexible Hemicarcerand with Neutral Guests

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 (OCH 2 O) 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 form complexes in solution, but to be unstable because of their low decomplexation energy barriers.