Water inside β-cyclodextrin cavity: amount, stability and mechanism of binding

Cyclodextrins (CDs) are native host systems with inherent ability to form inclusion complexes with various molecular entities, mostly hydrophobic substances. Host cyclodextrins are accommodative to water molecules as well and contain water in the native state. For beta-cyclodextrin (beta-CD), there is no consensus regarding the number of bound water molecules and the location of their coordination. A number of intriguing questions remain: (1) Which localities of the host's macrocycle are the strongest attractors for the guest water molecules? (2) What are the stabilizing factors for the water clusters in the interior of beta-CD and what type of interactions between water molecules and cavity walls or between the water molecules themselves are dominating the energetics of the beta-CD hydration? (3) What is the maximum number of water molecules inside the cavity of beta-CD? (4) How do the thermodynamic characteristics of beta-CD hydration compare with those of its smaller alpha-cyclodextrin (alpha-CD) counterpart? In this study, we address these questions by employing a combination of experimental (DSC/TG) and theoretical (DFT) approaches.