Physicochemical investigation and molecular modeling of cyclodextrin complexation mechanism with eugenol

The inclusion complexes between a series of cyclodextrins (CDs), which are alpha CD, beta CD, delta CD and hydroxypropyl-beta-CD (HP beta CD), 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 gamma CD. 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 aCD hydrophobic cavity whereas for beta CD and HP beta CD their aromatic parts could completely translocate inside. Moreover, a presence of free eugenol absorbed on CD hydrophilic surface were found as the following order, beta CD < HP beta CD < alpha CD, resulting in varying extents of eugenol release profiles. The intermolecular forces were found primarily due to intermolecular hydrogen bonding, resulting in stable complexes. (C) 2009 Elsevier Ltd. All rights reserved.