Capillary Electrophoresis, ROESY NMR and Molecular Modelling Study of the Inclusion Complex Beta-Cyclodextrin/Lipoic acid

The interaction of lipoic acid with b-cyclodextrin (b-CD) has been studied by capillary electrophoresis in aqueous phosphate buffer (20 mM, pH = 9.0) at 20 °C. The results allowed us to detect the formation of an inclusion complex with a 1:1 lipoic acid/ b-CD stoichiometry and an association constant of 1645 M-1. The geometry of the inclusion complex in D2O was investigated by means of 2D-ROESY (Rotating-frame Overhauser Enhancement Spectroscopy) NMR experiments, which showed the occurrence of a bimodal complexation of lipoic acid inside the b-CD cavity. Semi-empirical calculations using the PM3 method show that the orientations of the included lipoic acid are very close in energy, thus confirming the experimental observations.