H. Whang, Franck A. P. Vendeix, H. Gracz
May 1, 2008
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Journal
Pharmaceutical Research
Abstract
PurposeCloprostenol sodium salt (referred as cloprostenol) may be used for the synchronization of estrous cycles in farm animal species. Cyclodextrins (CDs) have potential as drug delivery systems through the formation of inclusion complexes between CDs and drugs. This is the first study of the inclusion complex of cloprostenol with β-cyclodextrin (β-CD) in aqueous solution using NMR and 3D molecular dynamics simulations.Methods1D proton NMR spectra of β-CD, a complex of cloprostenol with β-CD, and cloprostenol in D2O were assigned and confirmed. The cross relaxation interactions from ROESY were used as constraints for 3D molecular modeling studies.ResultsIn the 2D ROESY of the complex, cross-peaks were observed between the aromatic protons of cloprostenol and protons of the β-CD as well as between aliphatic protons and protons of the β-CD. The stoichiometry of the complex was found that β-CD forms a 1:1 inclusion complex with cloprostenol. The association constant K was 968 ± 120 M−1 at 298 K.ConclusionsAromatic side and/or aliphatic side chains of the cloprostenol is included in the β-CD while aliphatic side and/or aromatic side chains wraps around β-CD, respectively. The molecular modeling also confirms that β-CD forms a 1:1 inclusion complex with cloprostenol.