Molecular modeling study of beta- and gamma-cyclodextrin complexes with miconazole
| Autor: | S. Henry de Hassonville, Luc Delattre, T. Van Hees, Géraldine Piel, Georges Dive, Brigitte Evrard |
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| Rok vydání: | 2001 |
| Předmět: |
Models
Molecular Antifungal Agents Molecular model Miconazole Stereochemistry Molecular Conformation Pharmaceutical Science Crystallography X-Ray Inclusion compound Excipients chemistry.chemical_compound Computational chemistry medicine Imidazole Molecule chemistry.chemical_classification Cyclodextrins Cyclodextrin Austin Model 1 Ligand beta-Cyclodextrins chemistry Thermodynamics medicine.drug gamma-Cyclodextrins |
| Zdroj: | European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences. 13(3) |
| ISSN: | 0928-0987 |
| Popis: | Different authors have demonstrated the inclusion of miconazole in cyclodextrins (CD). Miconazole can be included in the CD cavity both in the neutral and in the ionized form. The present study tries to understand which fragment of the miconazole molecule is involved in the inclusion. Austin Model 1 approximate molecular orbital calculations have been performed on several complexes between beta-cyclodextrin (betaCD) or gamma-cyclodextrin (gammaCD) and miconazole in the ionized and the non-ionized forms of the two R and S enantiomers in three different orientations. We observed that betaCD is a good vehicle to transport miconazole which can be very easily released. The complexation energy between miconazole and betaCD is not very high but the entropic factor has a great incidence on the stability of the formed complex. The inclusion of the dichlorobenzene-CH(2)-O- and of the imidazole part of the S isomer gives rise to the most probable complex in acidic conditions (ionized miconazole). Nevertheless, the inclusion should be considered as a dynamic process in which different parts of the molecule could be alternatively included in betaCD. The present work demonstrates the high capability of deformation of betaCD which could easily accommodate several types of ligand. By opposite, the cycle extension in gammaCD leads to a more rigid vehicle with regards to miconazole. |
| Databáze: | OpenAIRE |
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