Hydrophobic hydration in cyclodextrin complexation.

We report temperature-dependent acoustic and densimetric data on changes in volume, expansibility, and adiabatic compressibility accompanying the binding of 1-adamantanecarboxylic acid (AD) to beta-cyclodextrin (beta-CD). We interpret our volumetric results in terms of hydration. Based on our compressibility and expansibility data, we estimate that, at 25 degrees C, the binding of AD to beta-CD is accompanied by displacement of 20 to 25 water molecules from the hydration shells of the two interacting species. Comparison of the temperature-dependent compressibility changes accompanying the binding of AD to beta-CD with the compressibility contribution of aliphatic groups suggests that displaced water molecules predominantly come from the hydrophobic loci of AD and beta-CD. Thus, we conclude that hydrophobic interactions play a major role in stabilizing the AD-beta-CD complex. Our estimate of the number of water molecules released to the bulk is consistent with structural considerations. There is also good agreement between our volumetric data and osmotic stress results reported by Harries et al. (Harries, D.; Rau, D. C.; Parsegian, V. A. J. Am. Chem. Soc. 2005, 127, 2184). This observation is consistent with the picture in which the two techniques probe the same population of water molecules solvating AD and beta-CD.