Chiral Separation of New Triazole Antifungal Active Compounds by Capillary Electrophoresis and Molecular Modeling Study of Chiral Recognition Mechanisms

Chiral separation of seven new triazole antifungal active compounds by capillary electrophoresis and chiral recognition mechanisms by computer-aided molecular modeling techniques was studied. Eight neutral cyclodextrins were used as the chiral selectors. Only the 2, 6-dimethyl-beta-cyclodextrin (DM-beta-CD) exhibited a very high enantioselectivity power to all the seven active compounds compared to the other tested CDs. The influences of concentration of DM-beta-CD, pH and concentration of buffer solution, applied voltage, and temperature were investigated. The enantiomeric separation of seven active compounds were carried out in 30 mmol/L NaH2 PO4 buffer (adjust to pH 2.2 with H3PO4) containing 30 mmol/L DM-beta-CD. The voltage was 20 kV and the temperature was 20 degrees C. The four active compounds were baseline separated on this condition (R-s > 1.5). By means of computer-aided molecular modeling software Discovery Studio 2.5/Sybyl/Gold and binding energy calculations, the inclusion process between DM-beta-CD and enantiomers was investigated and chiral recognition mechanisms were discussed. The results suggested that the enantioseparation result related to the difference of binding energy. And the good separation obtained in the presence of the DM-beta-CD chiral selector was due to the big binding energy difference.