Molecular modeling study of beta- and gamma-cyclodextrin complexes with miconazole

Area of Science:

• Computational Chemistry
• Supramolecular Chemistry
• Pharmaceutical Sciences

Background:

• Miconazole is an antifungal agent.
• Cyclodextrins (CDs) are known to form inclusion complexes with various molecules.
• Previous studies have shown miconazole can be included in cyclodextrins.

Purpose of the Study:

• To investigate the specific molecular fragments of miconazole involved in cyclodextrin inclusion.
• To compare the complexation behavior of miconazole with beta-cyclodextrin (betaCD) and gamma-cyclodextrin (gammaCD).
• To understand the role of miconazole's ionization state and enantiomeric form in complex formation.

Main Methods:

• Austin Model 1 (AM1) approximate molecular orbital calculations.
• Simulations of complexes between betaCD/gammaCD and ionized/non-ionized forms of miconazole enantiomers.
• Analysis of complexation energy and entropic contributions.

Main Results:

• Beta-cyclodextrin (betaCD) shows a high capacity for deformation, accommodating miconazole effectively.
• Miconazole can be easily released from betaCD complexes.
• The dichlorobenzene-CH(2)-O- and imidazole moieties of the S-miconazole isomer are most involved in complexation under acidic conditions.
• Complex stability is significantly influenced by entropic factors, despite moderate complexation energy.

Conclusions:

• Beta-cyclodextrin (betaCD) is a suitable vehicle for miconazole delivery, allowing for facile release.
• Miconazole inclusion within cyclodextrins is a dynamic process involving different molecular fragments.
• Gamma-cyclodextrin (gammaCD) presents a more rigid structure compared to betaCD when complexing with miconazole.