Isothermal Titration Calorimetry and Theoretical Studies on Host-guest Interaction of Ibuprofen with α-, β- and γ -Cyclodextrin

摘要

Thermodynamic parameters for formation of the inclusion complexes of α-, β- and γ -cyclodextrin (α-, β- and γ -CD) with ibuprofen (BF) in Tris-HCl buffer solutions (pH = 7.0) have been determined by isothermal titration calorimetry (ITC) with nanowatt sensitivity, and the inclusion structures have been investigated by using 1H-NMR spectra at 298.15 K. A theoretical study on the inclusion processes between BF and CDs has been performed with the B3LYP/6-31G*//PM3 method in order to investigate the formation mechanism of the inclusion complexes. An analysis of the thermodynamic data indicates that the stoichiometries of α-, β- and γ -CD with BF are all 1:1 and formation of the inclusion complexes α-CD·BF and β-CD·BF are driven by enthalpy and entropy, whereas formation of γ -CD·BF is an entropy driven process. The 1H-NMR spectra provide clear evidence for the inclusion phenomenon, and show that the isobutyl group and aromatic ring of the guest molecule are trapped inside the cavity of the CDs. Theoretical calculations suggest that the complex formed by the BF molecule entering into the cavity of the CD molecule from the wide side is more stable than that from the narrow side.