Physicochemical investigation and molecular modeling of cyclodextrin complexation mechanism with eugenol

The inclusion complexes between a series of cyclodextrins (CDs), which are αCD, βCD, γCD and hydroxypropyl-β-CD (HPβCD), and eugenol was studied by spectroscopy, thermal analysis and in silico molecular modeling. Molecular modeling provided conformation and thermodynamic data, and also confirmed experimental observations that, in aqueous phase, the complex formation was found at 1:1 mole ratio of eugenol and all CDs except those of γCD. Free energy of solvation of CDs and its cavity size are the most crucial factors for complex formation. The aromatic portion of eugenol was partially incorporated in αCD hydrophobic cavity whereas for βCD and HPβCD their aromatic parts could completely translocate inside. Moreover, a presence of free eugenol absorbed on CD hydrophilic surface were found as the following order, βCD < HPβCD < αCD, resulting in varying extents of eugenol release profiles. The intermolecular forces were found primarily due to intermolecular hydrogen bonding, resulting in stable complexes.