Systematic investigation and molecular modelling of complexation between several groups of flavonoids and HP-β-cyclodextrins

- Changes in flavonoid skeleton and active core affects its HP-β-CDs complexation.
- Conjugation of three elements on the C-ring has a high effect on the complexation.
- Kaempferol shows the highest complexation capacity of all flavonoids studied.

Flavonoids play an important role in the food and pharmaceutical industries and its molecular structure is responsible for their bioavailability and activity. Their very low water-solubility reduces their bioavailability. HP-β-cyclodextrins have been used to improve this parameter. Our results permit a better understanding of the influence of flavonoid molecular skeletons on the cyclodextrin complexation process. Molecular docking analysis showed that the most stable complex with HP-β-CD is that formed by kaempferol, being its stability mainly due to the hydrogen bonds network established between oxygen at positions 3, 4, 5 and 7 and to the hydrophobic stabilization of its aromatic scaffold within the inner cavity of HP-β-CD. The highest relative effect of the different substructures on inclusion efficacy is, primarily, the result of the conjugation between three elements on the flavonoid C-ring: the carbonyl group in C-4 position, the double bond C2C3 and the hydroxyl group in C-3 position.