Phase solubility analysis and PMR study of complexing behavior of dinoprostone with beta-cyclodextrin in water.

The mechanism of inclusion compound formation by dinoprostone (prostaglandin E2) with beta-cyclodextrin was studied by phase solubility analysis and PMR spectroscopy. As indicated by the linear increase of aqueous solubility of dinoprostone with beta-cyclodextrin concentration, some types of molecular interactions definitely exist between dinoprostone and the complexing ligands. The temperature dependence of a 1:1 complex formation constant yielded the following thermodynamic data at 20 degrees : deltaG degrees = -4.11 kcal/mole, deltaH degrees = 7.20 kcal/mole, and deltaS degrees = 10.5 e.u. Since water was the solvent system, these parameters appear to be largely determined by solvent reorganization through hydrogen bonding rather than solely by the binding of desolvated free dinoprostone and beta-cyclodextrin entities. PMR data indicate that dinoprostone is included within the cavity and also interacts with protons on the exterior of the beta-cyclodextrin molecule. A model consisting of a 1:1 complex, in which a dinoprostone molecule is partially included within the cavity and the remainder of the molecule extends around the edge of the opening of the cavity to the exterior of the beta-cyclodextrin molecule, is proposed as the most probable structure of this inclusion compound.