Experimental and molecular docking investigations on the inclusion mechanism of the complex of phloridzin and hydroxypropyl-β-cyclodextrin

• The inclusion mechanism between phloridzin and hydroxylpropyl-β-cyclodextrin was studied.
• The inclusion process was investigated by isothermal titration calorimetry.
• Proton nuclear magnetic resonance spectroscopy revealed the binding orientation.
• Autodock clarified the effect of substitution distribution of β-cyclodextrin on the inclusion.

Phloridzin is a nutraceutical. Its use in food, medicine and cosmetics is limited because of its low aqueous solubility and stability limits, but it can be improved by complexing with cyclodextrins. In this study, we investigated the inclusion mechanism between phloridzin and hydroxylpropyl-β-cyclodextrin (HP-β-CD) using isothermal titration calorimetry (ITC), ultraviolet–visible spectrometry (UV), infrared spectrometry (IR), proton nuclear magnetic resonance spectroscopy (1H NMR) and molecular docking simulations. The ITC results found that the equilibrium binding constant of HP-β-CD with phloridzin was higher than that of β-CD. Their inclusion was a spontaneous process with negative ΔG, ΔH and ΔS values. UV spectra showed that the aqueous solubility of phloridzin was enhanced by HP-β-CD. Our IR analysis verified the inclusion complexation of phloridzin into the HP-β-CD cavity. The Autodock determined that the substitution distribution of HP-β-CD influenced not only the orientation and depth degree of phloridzin within the cavity, but also the binding energies.