Molecular Modeling (MM2 and PM3) and Experimental (NMR and Thermal Analysis) Studies on the Inclusion Complex of Salbutamol and β-Cyclodextrin
| Autor: | Iliana Perdomo-López, Ernesto Estrada, Juan J. Torres-Labandeira |
|---|---|
| Rok vydání: | 2000 |
| Předmět: |
Models
Molecular chemistry.chemical_classification Cyclodextrins Hot Temperature Magnetic Resonance Spectroscopy Aqueous solution Cyclodextrin Molecular model beta-Cyclodextrins Organic Chemistry Crystallography chemistry Proton NMR Physical chemistry Albuterol Thermal analysis Spectroscopy Stoichiometry Alkyl |
| Zdroj: | The Journal of Organic Chemistry. 65:8510-8517 |
| ISSN: | 1520-6904 0022-3263 |
| DOI: | 10.1021/jo0008690 |
| Popis: | The inclusion complex of salbutamol and beta-cyclodextrin (beta-CD) is studied by computational (MM2 and PM3) and experimental techniques. Molecular modeling calculations predict two different orientations of salbutamol in the beta-CD cavity in vacuo and in aqueous solution. In vacuo calculations show that the introduction of the aromatic ring of salbutamol is preferred to the introduction of the tert-butyl group into the beta-CD cavity. However, in aqueous solution both computational methods predict the introduction of the alkyl chain instead of the aromatic ring in the beta-CD cavity contrary to experimental results published previously. These quantitative predictions were experimentally confirmed here by studying the inclusion complex in solution by NMR. A 1:1 stoichiometry was found by (1)H NMR studies for this complex. A 2D ROESY (rotating-frame Overhauser enhancement spectroscopy) experiment shows that there are no cross-peaks between the aromatic protons of salbutamol and any of the protons of beta-CD. Cross-peaks for the protons of the tert-butyl group and protons inside the cavity of beta-CD demonstrate the full involvement of this group in the complexation process and confirm the orientation of the complex predicted by molecular modeling. The solid-state complex was prepared and its stoichiometry (beta-CD.C(13)H(21)NO(3).8H(2)O) and dissociation process studied by thermogravimetric analysis. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
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