The Hydrophobic Effect Revisited—Studies with Supramolecular Complexes Imply High‐Energy Water as a Noncovalent Driving Force

Traditional descriptions of the hydrophobic effect on the basis of entropic arguments or the calculation of solvent-occupied surfaces must be questioned in view of new results obtained with supramolecular complexes. In these studies, it was possible to separate hydrophobic from dispersive interactions, which are strongest in aqueous systems. Even very hydrophobic alkanes associate significantly only in cavities containing water molecules with an insufficient number of possible hydrogen bonds. The replacement of high-energy water in cavities by guest molecules is the essential enthalpic driving force for complexation, as borne out by data for complexes of cyclodextrins, cyclophanes, and cucurbiturils, for which…