β-Cyclodextrin-- rosmarinic acid inclusion complex: A detail molecular modeling, thermodynamic, characterization and antioxidant activity

Polyphenols are a large group of low molecular weight, occurring in big amounts in seeds, fruits and vegetables. Rosmarinic acid (RA) an ester of caffeic acid, is a natural phenolic compound commonly found in rosmary. Despite its low solubility, RA exerts different important biological activities, such as antioxidant, anti-cholinesterase, anti-inflammatory, anti-allergic, anticancer, antimicrobial, and neuroprotective activity .The 1:1 stoichiometry with AL type solubility has been shown for β-cyclodextrin (β-CD): RA inclusion complex that its formation is enthalpy driven, representing the predominant role of hydrophobic interaction. The improvement of solubility and stability accompanying with conservation of antioxidant activity of RA can be taken the advantages of this nanocarrier in food and pharmaceutical applications. Inside 1H-NMR, FTIR, SEM, ICD and XRD spectroscopic methods, molecular dynamics (MD) and molecular docking calculation were applied for the precise determination of molecular structure and interaction of this complex. The entire insertion of RA into the wider site of β-CD and the present of three H-bonds confirmed the formation of a stable complex. The detailed molecular features of the complex formation including the orientation of RA in the nano-cavities of β-CD were determined. The RMSD, RDF, RMSF, distance and H-bonding analyses represent the presence of three hydrogen bonds in β-CD: RA inclusion complex. These results indicated that β-CD as the best choice for encapsulation of RA and this compound can be used in food science, represents the conservation of antioxidant activity and the enhancement of bioavailability, solubility and stability of RA in complexation with β-CD.

Keywords:

β-cyclodextrin , Rosmarinic acid , Molecular modeling , Antioxidant activity