Structure-antioxidant activity relationship of β-cyclodextrin inclusion complexes with olive tyrosol, hydroxytyrosol and oleuropein: Deep insights from X-ray analysis, DFT calculation and DPPH assay

Olives and olive oil, a key food type of the Mediterranean diets, are packed with various important polyphenols including oleuropein (OLE), hydroxytyrosol (HTY) and tyrosol (TYR). OLE and HTY are highly powerful antioxidants and play a prime role in the therapeutics of free radical-related diseases. Their molecular stabilities and antioxidant properties can be improved by cyclodextrin (CD) encapsulation. Here, we present a systematic investigation on the inclusion complexes of beta-CD-TYR (1), beta-CD-HTY (2) and beta-CD-OLE (3) by combined single-crystal structure determination, DFT complete-geometry optimization and DPPH antioxidant assay. X-ray analysis and DFT calculation reveal the preference of inclusion geometry with deep protrusion of the aromatic ring moieties of TYR, HTY and OLE from the beta-CD O6-H-side, and the common host-guest stabilization scheme via intermolecular O-H center dot center dot center dot O hydrogen bonding interactions. No polyphenol OH group is shielded in the beta-CD cavity, in contrast to the structures of beta-CD-tea catechins complexes. The established host-guest O-H center dot center dot center dot O hydrogen bonds help to elevate antioxidant capacities of the olive polyphenols upon beta-CD encapsulation. The order of antioxidant activity 2 > 3 >> 1 based on the DPPH measurement is in fair agreement with their relative thermodynamic stabilities derived from DFT calculation.