The interaction between γ-cyclodextrin (γ-CD) and paeonol (Pae) as well as two of its isomers [4'-hydroxyl-3'-methoxyacetophone (Ace) and 2'-hydroxyl-5'-methoxyacetophone (Hma)] in aqueous solution has been studied with nano-Watt-scale isothermal titration calorimetry (ITC) at 298.15 K. The microcosmic structure of the host-guest combination has been characterized by ¹H NMR spectra at 298 K. The experiments indicate that γ-cyclodextrin binds with each drug molecule in the same 1∶1 stoichiometry. The binding processes of Pae and Hma with γ-cyclodextrin are enthalpy driven while that of Ace with γ-cyclodextrin is predominantly entropy-driven. The ¹H NMR spectra data have provided clear evidence of the inclusion interaction of γ-cyclodextrin with Pae and Ace, which shows that Pae molecule penetrates into the molecular cavity of the γ-CD from the secondary rim whereas Ace does from the primary rim. But Hma binds with γ-cyclodextrin by weak interaction rather than inclusion interaction. Therefore, both thermodynamic parameters and ¹H NMR spectra demonstrate that γ-CD molecule can evidently recognize the three kinds of isomer molecules.

Key words: γ-cyclodextrin, paeonol, molecular recognition, microcalorimetry, ¹H NMR