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Title: Molecular modelling and 1H-NMR: ultimate tools for the investigation of tolbutamide: beta-cyclodextrin and tolbutamide: hydroxypropyl-beta-cyclodextrin complexes
Authors: Veiga, Francisco José Baptista 
Fernandes, Catarina Marques 
Carvalho, Rui Albuquerque 
Geraldes, Carlos Frederico Gusmão Campos 
Keywords: Tolbutamide; Cyclodextrin; 1H-NMR; Molecular modelling
Issue Date: Oct-2001
Publisher: The Pharmaceutical Society of Japan
Citation: Chemical & Pharmaceutical Bulletin. 49:10 (2001) 1251-1256
Abstract: A structural study of the inclusion compound of tolbutamide (TBM) with beta-cyclodextrin (beta-CD) and hydroxypropyl-beta-cyclodextrin (HP-beta-CD) was attempted by means of 1H-nuclear magnetic resonance (1H-NMR) experiments and computer molecular modelling. To establish the stoichiometry and stability constant of the beta-CD:TBM complex, the continuous variation method was used. The presence of true inclusion complexes between TBM and beta-CD or HP-beta-CD in solution was clearly evidenced by the 1H-NMR technique. Changes in chemical shifts of H-3 and H-5 protons, located inside the CD cavity, associated with variations in the chemical shifts of TBM aromatic protons provided clear evidence of inclusion complexation, suggesting that the phenyl moiety of the drug molecule was included in the hydrophobic cavity of CDs. This view was further supported by the observation of intermolecular NOEs between TBM and beta-CD and by the aid of a molecular modelling program, which established the most probable structure of the complex. The molecular graphic computation confirmed that the minimum energy, positioning TBM relative to beta-CD, occurs when the aromatic ring of TBM is included within the beta-CD cavity by its wider side, leaving the aliphatic chain externally, which is in good agreement with the results of 1H-NMR studies
ISSN: 0009-2363
DOI: 10.1248/cpb.49.1251
Rights: openAccess
Appears in Collections:FFUC- Artigos em Revistas Internacionais
FCTUC Ciências da Vida - Artigos em Revistas Internacionais

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