Inclusion complex formation of captopril with alpha- and beta-cyclodextrins in aqueous solution: NMR spectroscopic and molecular dynamic studies.
The inclusion complex formation of alpha-cyclodextrin (alpha-CyD), beta-cyclodextrin (beta-CyD), and 2-hydroxylpropyl-beta-cyclodextrin (HP-beta-CyD) with an angiotensin converting enzyme inhibitor, captopril, in aqueous solution was studied by (1)H- and (13)C-nuclear magnetic resonance spectroscopies, including ROESY and GROESY techniques, by kinetic methods and by molecular dynamic calculations. The oxidative degradation of captopril was markedly suppressed in alpha-CyD solutions, whereas beta-CyD and HP-beta-CyD had negligible stabilizing effects. These NMR and kinetic results suggested that alpha-CyD includes preferably the propyl thioalcohol moiety of captopril, depositing the proline moiety outside the cavity. On the other hand, beta-CyD includes a whole molecule of captopril in the cavity, locating the carboxylic acid within the cavity and the terminal thiol moiety outside the cavity. These inclusion structures were supported by molecular dynamic studies.
Ikeda
Yoichi
Y
Healthcare Research Institute, Wakunaga Pharmaceutical Co., Ltd., 1624 Shimokotachi, Koda-cho, Takata-gun, Hiroshima 739-1195, Japan.
Motoune
Sohko
S
Matsuoka
Toshikazu
T
Arima
Hidetoshi
H
Hirayama
Fumitoshi
F
Uekama
Kaneto
K
D002216:Captopril / Q000737:chemistry* / Q000493:pharmacokinetics; D003505:Cyclodextrins / Q000737:chemistry* / Q000493:pharmacokinetics; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D019999:Pharmaceutical Solutions; D014867:Water / Q000737:chemistry; D047391:alpha-Cyclodextrins; D047392:beta-Cyclodextrins
D003505:Cyclodextrins; D019999:Pharmaceutical Solutions; D047391:alpha-Cyclodextrins; D047392:beta-Cyclodextrins; D014867:Water; D002216:Captopril; C031215:betadex; C032613:alpha-cyclodextrin