Influence of solvent polarity on the separation of leucine enantiomers by β-cyclodextrin: a molecular mechanics and dynamics simulation

The interaction between leucine and beta-cyclodextrin with different solvents was studied by molecular mechanics and dynamics simulations. In order to analyse the influence of the solvent polarity on the inclusion complex formation and separation process of leucine enantiomers by beta-cyclodextrin, the organic modifiers were characterised by the same value of dielectric constant in the electrostatic contribution to the interaction energy, and a different molecular configuration of amino acids (neutral or zwitterion). The complexes formed in polar solvents were more stable than those in non-polar solvents with the same dielectric constant, because the electrostatic contribution is negative for the former and positive for the latter. The optimized structures obtained for leucine enantiomers and beta-cyclodextrin in vacuo are non-inclusion complexes. The solvent polarity contributes to increasing the probability of the presence in an inner position for the guest, whereas the results for non-polar configurations were smaller and distributed in larger areas. The regions where the enantiomers spend more time in the simulation correspond to locations with greater chiral discrimination. D-Leu was the first eluted enantiomer in every case, except for a polar solvent with epsilon = 26. (C) 2017 Elsevier Ltd. All rights reserved.