Outside Front Cover: Thermodynamics of Water Displacement from Binding Sites and its Contributions to Supramolecular and Biomolecular Affinity (Angew. Chem. 35/2025)

The binding of a hard non-interacting sphere to a macrocyclic cavity has been investigated to expose the importance of cavity water as determinant of supramolecular and biomolecular binding affinity in aqueous solution. The results demonstrate that the thermochemical properties of water molecules present inside different macrocyclic receptors can largely increase or decrease their binding affinities, for example, for the popular host cucurbit[8]uril, as reported by Jeffry Setiadi, Frank Biedermann, Werner M. Nau, and Michael K. Gilson in their Research Article (e202505713).