氯前列醇钠与β-环糊精在水溶液中包合物的核磁共振研究

NMR studies of the inclusion complex of cloprostenol sodium salt with beta-cyclodextrin in aqueous solution.

作者信息

Whang Hyun Suk, Vendeix Franck A P, Gracz Hanna S, Gadsby John, Tonelli Alan

机构信息

Fiber & Polymer Science Program, North Carolina State University, Raleigh, NC 27695-8301, USA.

出版信息

Pharm Res. 2008 May;25(5):1142-9. doi: 10.1007/s11095-007-9493-z. Epub 2007 Dec 5.

DOI:10.1007/s11095-007-9493-z

PMID:18064541

Abstract

PURPOSE

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.

摘要