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Spironolactone and its Complexes with β-cyclodextrin: Modern NMR Characterization and Structural DFTB-SCC Calculations

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Abstract

In the present work, inclusion complexes of spironolactone (SP) with β-cyclodextrin (β-CD) in solid phase and aqueous solution were studied by solubility methods, NMR spectroscopy and thermal analysis. The results showed different kinds of complexations when freeze-drying and kneading methods were used. The freeze-drying product (1:1, SP:β-CD) showed lower degree of complexation and stability than the (1:2, SP:β-CD) compound obtained by kneading method. The spironolactone molecule was also studied by NMR spectroscopy at 400 MHz. The chemical shifts of all spironolactone atoms and their inclusion compounds were assigned. Extensive use of 1D and 2D NMR techniques, including ROESY experiment, allowed verifying the position of the spironolactone molecule inside the cyclodextrin cavity in both situations. In addition, DFTB-SCC quantum mechanical calculations of the inclusion compounds were performed. The predicted structural properties are in good agreement with ROESY NMR results.

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Abbreviations

2D:

Two-dimensional

β-CD:

β-cyclodextrin

COSY:

Correlation Spectroscopy

DEPT:

Distortionless Enhancement by Polarization Transfer

DFTB-SCC:

Density Functional-Tight Binding- Self-Consistent Charge

HMBC:

Heteronuclear Multiple Bond Correlation

HSQC:

Heteronuclear Single Quantum Coherence

NMR:

Nuclear Magnetic Resonance

ROESY:

Rotating Frame Overhauser Enhancement Spectroscopy

S-Ac:

Thio-acetyl group

SP:

Spironolactone

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Acknowledgements

The authors would like to thank CNPq, CNPq-FAPEMIG-PRONEX for the financial support to develop this work.

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Authors and Affiliations

  1. Departamento de Química – Instituto de Ciências Exatas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, 31270-901, Brazil

    Ivana Lula, Maria F. Gomes, Dorila Piló-Veloso, Antonio L.O. de Noronha, Hélio A. Duarte & Rubén D. Sinisterra

  2. Departamento de Fisiologia e Biofísica – Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil

    Robson A.S. Santos

Authors
  1. Ivana Lula
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  2. Maria F. Gomes
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  3. Dorila Piló-Veloso
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  4. Antonio L.O. de Noronha
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  5. Hélio A. Duarte
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  6. Robson A.S. Santos
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  7. Rubén D. Sinisterra
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Correspondence to Rubén D. Sinisterra.

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Lula, I., Gomes, M.F., Piló-Veloso, D. et al. Spironolactone and its Complexes with β-cyclodextrin: Modern NMR Characterization and Structural DFTB-SCC Calculations. J Incl Phenom Macrocycl Chem 56, 293–302 (2006). https://doi.org/10.1007/s10847-005-9030-9

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  • DOI: https://doi.org/10.1007/s10847-005-9030-9

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