Calorimetry to evaluate inclusion mechanism in the complexation between 2-hydroxypropyl-β-cyclodextrin and barbiturates in aqueous solution

Two different types (structures) of inclusion complexes with a 1:1 stoichiometry between barbiturates and 2-hydroxypropyl-beta -cyclodextrin (HPCyD) were realized in aqueous solution using isothermal titration calorimetry and molecular dynamics simulation. The first type of complex with a higher association constant was entropy driven and the substituent R-2 was inserted into the HPCyD cavity by hydrophobic interaction. The barbituric acid ring contributed to the second type of complex, which was characterized by large negative values of DeltaH and small positive DeltaS reflecting van der Waals interaction and/or hydrogen bonding formation between the hetero atoms in the barbituric acid ring and the secondary hydroxyl groups of HPCyD.