Can the anomalous aqueous solubility of beta-cyclodextrin be explained by its hydration free energy alone?
The well-documented anomalous solubility of beta-cyclodextrin (beta-CD), relative to alpha- and gamma-CD, has been examined by Naidoo et al. (J. Phys. Chem. B, 2004, 108, 4236-4238.) from the perspective of water organization and internal motion of the macrocyclic rings. Whether modulation in the hydration patterns and in the rigidity of the molecular scaffold can be reconciled with the hydration free energy of beta-CD to rationalize its notorious low solubility remains open to further investigation. In this contribution, multi-nanosecond molecular dynamics (MD) simulations have been carried out to investigate the hydration process of alpha-, beta- and gamma-CD. The distribution of water molecules involved in this process and the linearity of intramolecular hydrogen bonds have been analyzed. The results reported here demonstrate that the anomalous solubility for beta-CD can be essentially rationalized by its greater rigidity conferred by the participating intramolecular hydrogen bonds
