NMR studies of the inclusion complex of cloprostenol sodium salt with beta-cyclodextrin in aqueous solution.
OBJECTIVE
Cloprostenol 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 beta-cyclodextrin (beta-CD) in aqueous solution using NMR and 3D molecular dynamics simulations.


METHODS
1D proton NMR spectra of beta-CD, a complex of cloprostenol with beta-CD, and cloprostenol in D(2)O were assigned and confirmed. The cross relaxation interactions from ROESY were used as constraints for 3D molecular modeling studies.


RESULTS
In the 2D ROESY of the complex, cross-peaks were observed between the aromatic protons of cloprostenol and protons of the beta-CD as well as between aliphatic protons and protons of the beta-CD. The stoichiometry of the complex was found that beta-CD forms a 1:1 inclusion complex with cloprostenol. The association constant K was 968 +/- 120 M(-1) at 298 K.


CONCLUSIONS
Aromatic side and/or aliphatic side chains of the cloprostenol is included in the beta-CD while aliphatic side and/or aromatic side chains wraps around beta-CD, respectively. The molecular modeling also confirms that beta-CD forms a 1:1 inclusion complex with cloprostenol.
Whang
Hyun Suk
HS
Fiber & Polymer Science Program, North Carolina State University, Raleigh, NC 27695-8301, USA. hswhang@ncsu.edu
Vendeix
Franck A P
FA
Gracz
Hanna S
HS
Gadsby
John
J
Tonelli
Alan
A
D055598:Chemical Phenomena; D002627:Chemistry, Physical; D003008:Cloprostenol / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D012996:Solutions; D047392:beta-Cyclodextrins / Q000737:chemistry*
D012996:Solutions; D047392:beta-Cyclodextrins; D003008:Cloprostenol