Separation performance and recognition mechanism of mono(6-deoxy-imino)-β-cyclodextrins chiral stationary phases in high-performance liquid chromatography

Different substituent groups were introduced onto the rim of beta-cyclodextrin through rigid C=N bonds to form a series of imino-modified beta-cyclodextrin derivatives: mono(6-deoxy-phenylimino)-beta-cyclodextrin (BCD), mono(6-deoxy-isopropylimino)-beta-cyclodextrin (YBCD), mono(6-deoxy-N-1-phenylethylimino)-beta-cyclodextrin (R-,S-BYCD), mono[6-deoxy-N-1-(2-hydroxyl)-phenylethylimino]-beta-cyclodextrin (R-,S-PGCD), heptakis(2,6-o-diamyl-6-deoxy-phenylimino)-beta-cyclodextrin (WBCD), heptakis(2,6-o-diamyl-6-deoxyisopropylimino)-beta-cyclodextrin (WYBCD) and heptakis[2,6-o-diamyl-6deoxy-R-(-)-N-1-phenylethylimino)-beta-cyclodextrin (WRBYCD). The obtained derivatives were then bonded to silica gel and used in high-performance liquid chromatography (HPLC) as chiral stationary phases (CSPs). The separation performance of these CSPs was examined by separating disubstituted benzenes, amino acids, ferrocene derivatives and chiral aromatic alcohol compounds. Satisfactory separation results were obtained for most of the compounds. The values for selectivity factors can reach up to 8.50 and 8.16 for separating positional isomers and ferrocene derivatives, respectively, and the best resolution was 6.89 for aromatic alcohol derivative separations. Molecular dynamics (MD) simulations were carried out for chiral discrimination of rac-N-benzoyl-phenylglycinol on S-PGCD CSP to study the recognition mechanism. MD simulation results show that the average free-energy of interaction is -1304.83 kcal/mol for the L-enantiomer and S-PGCD and -1324.23 kcal/mol for the D-enantiomer and S-PGCD. In the recognition stage, the L-enantiomer moves along the exterior of the cyclodextrin cavity from the wider edge to the narrower edge of cyclodextrin whereas the D-enantiomer moves slightly towards the cavity. The L-enantiomer thus is separated first due to weaker interaction with S-PGCD. (C) 2010 Elsevier B.V. All rights reserved.