Isothermal titration calorimetry (ITC) study of natural cyclodextrins inclusion complexes with tropane alkaloids

Isothermal titration calorimetry (ITC) has been used to characterize inclusion complex formation of natural cyclodextrins (α- and β-cyclodextrin) with three tropane alkaloids (scopolamine, homatropine hydrobromide and atropine sulfate) in aqueous solutions. ITC measurements were taken at 298.15 K on a MicroCal OMEGA ultrasensitive titration calorimeter (MicroCal Inc.). The experimental data were analyzed on the basis of the model of a single set of identical sites (ITC Tutorial Guide). β-CD forms inclusion complexes of stoichiometry 1:2 with homatropine hydrobromide and 1:1 with scopolamine and atropine sulfate. The smaller molecule of α-CD forms very weak inclusion complexes with the tropane alkaloids. So, only one complex of the same stoichiometry 1:2 with homatropine hydrobromide has been detected by the ITC experiment. Based on the experimental values of equilibrium constant (K) and enthalpy of complex formation (ΔH), the Gibbs energy of complex formation (ΔG) and the entropy of complex formation (ΔS) have been calculated, for all the investigated systems. Obtained results showed that complex formation of both α- and β-CD with all the investigated tropane alkaloids is entropy driven. This indicated that the difference in the cavity dimensions is not reflected in different driving forces of complex formation and binding modes which resulted in the same stoichiometry of the obtained inclusion complexes.