Optimal configurations of "capped" beta-cyclodextrin dimers in water maximise hydrophobic association.

Circular dichroism analysis and proton NMR experiments revealed that solutions of 3-O-(2-methylnaphthyl)-beta-cyclodextrin form different dimer configurations. The exact nature of the dimer configurations were postulated to be of three types in which these capped cyclodextrins (CDs) are orientated in head-to-head and head-to-tail arrangements. Here we show from detailed computer simulations and free-energy calculations on the configurations that the head-to-head configuration in which the naphthyl groups are mutually inserted into each other's CD cavities is the most favoured configuration. This configuration optimises the hydrophobic association of the naphthyl aromatic groups and the ring cavities as well as forming the most inter-CD hydrogen bonds of the three configurations.