Hosting of diamantane alcohols in water and hydrogen-bonded organic solvents: the (non-)classical hydrophobic effect

Understanding the forces governing hydrophobically driven inclusion provides a path for aimed utilization of non-polar synthons and provides insights into the related hydration thermodynamics. To shed light on the factors that determine the stability of complexes with large, rigid guests, we studied the temperature and the solvent effect on the hosting of diamantane alcohols with heptameric and octameric cyclodextrins and cucurbiturils. The smaller cyclodextrin was a more efficient binder of the explored guests, while inclusion within gamma-CD was observed solely in water. The higher stability of beta-CD complexes in this solvent (298 K) was due to the strongly exothermic, entropically opposed inclusion, whereas endothermic hosting of alcohols by gamma-CD was observed in all cases except for diamantan-1-ol. The entropically more demanding dehydration of the beta-CD cavity hence masks the positive entropy changes accompanying the removal of guest-hydrating water. A strong decrease in Delta rH degrees(T) for all studied systems was noticed in water. In the case of cyclodextrins, the phenomenon shifts the driving force from completely or predominantly classical towards non-classical. Conversely, due to the particularly poor structuring of cucurbituril-confined water, the binding remained essentially non-classical over the explored temperature range. Unlike complexation in water, the complexation in formamide and ethylene glycol was entirely enthalpy-driven and weakly temperature-dependent. Guest hydration sphere melting shifts cyclodextrin inclusion thermodynamics from classical towards non-classical, where with cucurbiturils it is enthalpy-driven despite . Binding with gamma-CD in organic solvents is enthalpy-driven with .