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NMR Studies of the Inclusion Complex of Cloprostenol Sodium Salt with β-cyclodextrin in Aqueous Solution

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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 β-cyclodextrin (β-CD) in aqueous solution using NMR and 3D molecular dynamics simulations.

Methods

1D 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.

Results

In 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.

Conclusions

Aromatic 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.

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ACKNOWLEDGEMENTS

This research was supported by USDA Animal Health Formula Funds/State of North Carolina.

Author information

Authors and Affiliations

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

    Hyun Suk Whang & Alan Tonelli

  2. Department of Molecular & Structural Biochemistry, North Carolina State University, Raleigh, North Carolina, 27695-8301, USA

    Franck A. P. Vendeix & Hanna S. Gracz

  3. Department of Molecular Biomedical Sciences, North Carolina State University, Raleigh, North Carolina, 27695-8301, USA

    John Gadsby

Authors
  1. Hyun Suk Whang
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  2. Franck A. P. Vendeix
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  3. Hanna S. Gracz
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  4. John Gadsby
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  5. Alan Tonelli
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Correspondence to Hyun Suk Whang.

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Figure S1-A

Expanded aromatic region of 2D heteronuclear multiple quantum coherence (HMQC) (1H–13C one bond) spectrum of the cloprostenol for assigning the H18, H20, H22 peaks (DOC 558 kb)

Figure S1-B

Expanded region of 2D heteronuclear multiple bond correlation (HMBC) coherence (1H–13C long range) spectrum of cloprostenol for assigning the H5 proton peak (DOC 403 kb)

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Whang, H.S., Vendeix, F.A.P., Gracz, H.S. et al. NMR Studies of the Inclusion Complex of Cloprostenol Sodium Salt with β-cyclodextrin in Aqueous Solution. Pharm Res 25, 1142–1149 (2008). https://doi.org/10.1007/s11095-007-9493-z

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  • DOI: https://doi.org/10.1007/s11095-007-9493-z

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