Substituent Effects on the Binding of Phenols to Cyclodextrins in Aqueous Solution

Equilibrium constants and standard enthalpies have been measured calorimetrically for the formation of complexes of α-and β-cyclodextrins with substituted phenols in aqueous solutions at 298.15 K. The study includes variation of the size and shape of the phenol, the size and degree of methylation of the cyclodextrin, and the effects of pH and ionic strength. Substituent effects were measured for p-chloro-, p-bromo-, p-methyl-, p-hydroxy-, p-nitro- and m-nitrophenols. The effects of ionization were studied with m- and p-nitrophenolate ions. The effects of methyl substitutions of β-cyclodextrin were investigated with nitrophenol and nitrophenolate ions complexing with heptakis(2,6-di-O-methyl)-β-cyclodextrin and heptakis(2,3,6-tri-O-methyl)-β-cyclodextrin. All of the effects studied show a substantial amount of entropic-enthalpic compensation, such that free energy effects are relatively small in comparison to enthalpic and/or entropie effects, but there was no simple relationship between the standard enthalpies and entropies of complex formation. However, a linear relationship was observed between the enthalpy and entropy for the transfer of substituted phenols from the complex with α-cyclodextrin to the complex with β-cyclodextrin. This relationship was independent of pH and ionic strength. In general, complex formation of a substituted phenol with α-cyclodextrin is more exothermic than with β-cyclodextrin, but the entropy of complex formation is also more negative. © 1989 American Chemical Society.