Ab initio study of chiral recognition of β-butyrolactone by cyclodextrins

Abstract

Separation of stereoisomers of organic compounds is an important and challenge task for chemists. Cyclodextrins and their derivatives have been widely used in chromatography for this application. Experimental results indicated that substituents on the hydroxyl groups of cyclodextrin affect the efficiency of the chiral separation of β-butyrolactone. The understanding of the interactions contributed to the chiral recognition of cyclodextrin would help us predict the separation capability of a specific pair of cyclodextrin and chiral compound. Thus, the cyclodextrin substituent effect on the chiral recognition should be systematically investigated. In this study, Hartree Fock method with 3-21G basis set and density functional theory B3LYP with 6-31G* basis set were applied to determine the chiral recognition of a chiral model, βbutyrolactone, by β-cyclodextrin and its derivatives. Both methods predicted comparable values of chiral recognition of β-cyclodextrin derivatives. We found that methoxyl substitution on the wider rim of cyclodextrin (secondary hydroxyl groups) give the most effective chiral separation (ΔΔE=18.2 kcal/mol in favor of R-isomer) followed by substitution on the narrow rim (ΔΔE=9.5 kcal/mol in favor of S-isomer) while substitution on both side give the worst recognition (ΔΔE=3.2 kcal/mol in favor of S-isomer). This suggests that β-cyclodextrin with substitution only on the wider rim give the best chiral selectivity. By replacing methyl group with chiral hydroxypropyl group, we found that the chiral selectivity is reduced (ΔΔE=6.4 and 8.4 kcal/mol respectively for R- and S-form of hydroxypropyl group). This implies that the bulky group causes the reduction of the chiral selectivity. © Springer-Verlag Berlin Heidelberg 2006.