A molecular dynamics study of branched alpha-cyclodextrin.

A branched alpha-cyclodextrin is a derivative of an alpha-cyclodextrin with a branch consisting of an extra glucose unit. Its water solubility is considerably higher than that of the unbranched one. We have studied the high solubility of the molecule in aqueous solution by molecular dynamics simulations. Trajectories of the molecule at 293 K were calculated using GROMOS programs in three different environments, i.e., in vacuo, in the crystalline state, and in aqueous solution. A simulation in vacuo was carried out to explore stable conformations of the molecule in the isolated system. The quality of the simulations were examined by comparing the X-ray and the simulated crystal structures. The results of the simulations show three remarkable structural features of the molecule: self-inclusion with its branched portion, twist-boat conformation of a glucose ring, and wobbling of its macrocycle. Among these, the last feature is closely related to the water solubility of the molecule. The solubility of cyclodextrin appears to be mainly governed by its intramolecular interglucose hydrogen bonds, which inhibit hydration by solvent water molecules. The results of our simulations indicate that the capability to form hydrogen bonds in branched alpha-cyclodextrin decreased as the macrocycle of the molecule lost its regular circular shape. Such wobbling of the macrocycle was observed on a relatively short time scale (several picoseconds). An extra glucose unit introduced to alpha-cyclodextrin may cause the improved water solubility of the molecule through the greater wobbling motion of its macrocycle.