Posted by This review summarizes recent findings from both experiments and theory about the degree of hydration in CDs and the mechanism of water encapsulation by the host macrocycle. The data provided demonstrate that the number of trapped water molecules inside the CD internal cavity depends, apart from the cavity size of different CDs, on the varying storage conditions of the powdered substances (as-received vs. stored in desiccators with controlled humidity) and on the configuration of the host CD molecule (“open” vs. “closed” form). The role of hydrogen-bond formation between the water molecules themselves and with CD walls in stabilizing the “water cloud” inside the cavity has been emphasized. Note that, as experiments reveal, the mechanism of dehydration of different CDs may vary—sequential vs. bulk water release. The properties of the confined water cluster appear to be of crucial importance in determining the outcome of the process of the host–guest complexation between CDs and inorganic/organic substances, as well as shaping the crystalline form of the host cavitand.
In this short review, recent findings from both theory and experiment regarding the process of hydration of α-, β-, and γ-cyclodextrins are summarized and critically assessed. Key important questions are addressed, including: What factors govern the number of water molecules entrapped in the internal cavity of the host macrocycle? What is the driving force behind this process? What are the “hot spots” for water entrapment inside the host cavity? What is the underlying mechanism of water hydration and dehydration of cyclodextrins? What is the role of the confined water cluster in determining the outcome of the host–guest complexation between cyclodextrins and molecules of inorganic/organic nature? To what extent does water hydration affect the crystalline structure of the cavitand?
Angelova, S.; Pereva, S.; Dudev, T.; Spassov, T. Cyclodextrins’ Internal Cavity Hydration: Insights from Theory and Experiment. Inorganics 2025, 13, 28. https://doi.org/10.3390/inorganics13010028