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

Abstract

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 γ-CD was observed solely in water. The higher stability of β-CD complexes in this solvent (298 K) was due to the strongly exothermic, entropically opposed inclusion, whereas endothermic hosting of alcohols by γ-CD was observed in all cases except for diamantan-1-ol. The entropically more demanding dehydration of the β-CD cavity hence masks the positive entropy changes accompanying the removal of guest-hydrating water. A strong decrease in Δ_rH°(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.