The inclusion complexation of daidzein with β-cyclodextrin and 2,6-dimethyl-β-cyclodextrin: a theoretical and experimental study

Daidzein is an isoflavone of the group of phytoestrogens extracted from soybeans and other legumes. As its structure is relatively similar to that of the hormone estrogen, daidzein is able to bind with estrogen receptors leading to a reduced postmenopausal women symptom. A common problem of the compounds of this group is the rather low water solubility with the consequence of limited pharmaceutical applications. Inclusion complexation between daidzein and two beta-CDs (beta-CD and DM-beta-CD) was investigated by theoretical and experimental techniques. Based on multiple MD simulations in combination with different binding-free energy calculations, the most preferential mode of daidzein binding to cyclodextrins is the insertion of the chromone ring fitting well into the hydrophobic cavity. All four methods of binding-free energy calculations (MM/PBSA, MM/GBSA, QM/PBSA, and QM/GBSA) predict the binding affinity of the daidzein/DM-beta-CD complex significantly higher than the daidzein/beta-CD. Following the same trend, the experimental results also indicated the enhancement of solubility and stability of the daidzein/DM-beta-CD complex. Moreover, it was found that the complexation process was favorably enthalpy driven.