Effect of hydroxypropyl-β-cyclodextrin on the aggregation of (E)-resveratrol in different protonation states of the guest molecule

The aggregation state of (E)-resveratrol was studied in the presence and absence of hydroxypropyl-β-cyclodextrin (HP-β-CD) using absorption and steady-state fluorescence at different pH values. The results revealed that this potent antioxidant shows a monomer/aggregate equilibrium which is dependent on the protonation state of (E)-resveratrol. This equilibrium can be modified by the presence of HP-β-CD, which reduces the aggregation of the (E)-resveratrol molecules, producing individual molecules of the solute and preventing side effects due to aggregation phenomena. At pH values higher than the pKa1 of (E)-resveratrol, the coexistence of different protonated/deprotonated forms of this antioxidant does not permit the fluorimetric determination of the complexation constant (KF) of (E)-resveratrol with HP-β-CD. However, when the Hildebrand–Benesi equation was used to calculate this constant at physiological pH, this problem was resolved, with a KF value of 14490 ± 723 M−1 and the stoichiometry of the complexation process 1:1 for all the cases tested. The results obtained in this paper resolve the contradictory data published about the complexation process of (E)-resveratrol by cyclodextrins.