Molecular dynamics study of the influence of solvents on the chiral discrimination of alanine enantiomers by β-cyclodextrin

The influence of solvents on the separation of alanine enantiomers using beta-cyclodextrin as a chiral selector was studied by means of a molecular dynamics simulation at a constant temperature. The potential energy of the interaction is modelled by the AMBER force field, where different polar and non-polar solvents are represented by the dielectric constant 8 and two configurations for the amino acid derived from its electric charge distribution: the AMBER data base or its zwitterion state. The L enantiomer has more positions inside the cavity of a beta-cyclodextrin where it is more stable than the D-enantiomer in vacuo and solution, except for solvents such as hydrocarbons in which most positions of the D-alanine inside and outside the cavity are more stable. In all cases, the greatest differences are located near the cavity walls. Molecular dynamics simulations show that Ala is able to form inclusion complexes with beta-cyclodextrin in vacuo and in solvents such as hydrocarbons, benzene, acetone, ethanol or water. The chiral discrimination of Ala by beta-cyclodextrin is mainly due to the adaptation of the guest to the host in the presence of non-polar agents, whereas the nonbonded interaction is the driving force for zwitterions. The elution order depends on the type of organic modifiers while a reversal of the enantiomeric elution order can be observed in solvents with higher dielectric constants. (C) 2013 Elsevier Ltd. All rights reserved.