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Chiral recognition of abacavir enantiomers by (2-hydroxy)propyl-β-cyclodextrin: UHPLC, NMR and DFT studies

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Abstract

The diastereomeric complexation of both abacavir (ABA) and its enantiomer (ABAE) with (2-hydroxy)propyl-β-cyclodextrin (2HPβCD) with a degree of substitution of seven was studied. The apparent binding constants of diasteromeric complexes, ABA-2HPβCD and ABAE-2HPβCD were determined by ultra high-pressure liquid chromatography (UHPLC) and found to be 517.0 and 684.4 M−1 respectively. The stoichiometry of the complexes was determined by UHPLC and by the continuous variation method using nuclear magnetic resonance spectroscopy giving 1:1 complexes. The apparent binding constants decrease as the temperatures increases. The observed enantio-differentiation was analyzed theoretically by density functional theory at the PBE/6-31 g** level using a polarizable continuous model (PCM) for solvent effects, the most stable complexes are the ones in which the chiral cyclopentenyl moiety is included in the cavity of CD and the protonated purine ring interact with the hydroxypropyl groups of 2HPβCD. The differences in stability of diasteromeric complexes, due to different intermolecular interactions are consistent with experimental data, providing further insights in the formation of inclusion complexes.

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Acknowledgments

Authors thanks to Secretaría de Investigación y Estudios Avanzados, Universidad Autónoma del Estado de México for the financial support trough the project 3864/2015PIC. Authors are also grateful to Signa S. A. de C. V., for some of the materials and instrumentation used during the development of this work.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Centro Conjunto de Investigación en Química Sustentable UAEM-UNAM, Km 14.5 Carretera Toluca-Atlacomulco, Campus UAEMex “El Rosedal” San Cayetano-Toluca, 50200, Toluca, Mexico State, Mexico

    M. L. Reyes-Reyes, Gabriela Roa-Morales, Nelly Gonzalez-Rivas, Joanatan Bautista-Renedo & Patricia Balderas-Hernández

  2. Departamento de Investigación y Desarrollo, Signa S. A. de C. V., Av. Industria Automotriz No. 301, Zona Industrial Toluca, 50071, Toluca, Mexico State, Mexico

    M. L. Reyes-Reyes & Roberto Melgar-Fernández

  3. Facultad de Química, Universidad Autónoma del Estado de México, Avenida Paseo Tollocan S/N, 50180, Toluca, Mexico State, Mexico

    Horacio Reyes-Pérez & Leobardo M. Gómez-Oliván

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  1. M. L. Reyes-Reyes
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  2. Gabriela Roa-Morales
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  3. Roberto Melgar-Fernández
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  4. Horacio Reyes-Pérez
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  7. Joanatan Bautista-Renedo
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Correspondence to M. L. Reyes-Reyes or Nelly Gonzalez-Rivas.

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Reyes-Reyes, M.L., Roa-Morales, G., Melgar-Fernández, R. et al. Chiral recognition of abacavir enantiomers by (2-hydroxy)propyl-β-cyclodextrin: UHPLC, NMR and DFT studies. J Incl Phenom Macrocycl Chem 82, 373–382 (2015). https://doi.org/10.1007/s10847-015-0499-6

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  • DOI: https://doi.org/10.1007/s10847-015-0499-6

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