Enantiodiscrimination by a quinine-based chiral stationary phase: a computational study

A detailed computational study of a derivatized quinine chiral stationary phase (CSP) interacting with enantiomeric 3, 5-dinitrobenzoyl derivatives of leucine was carried out to understand where and how chiral discrimination takes place. The most stable structure of the CSP derived from a conformer search gave a structure whose geometry agrees with an X-ray structure (rmsd 0.6 A). The computed retention order and enantiodiscriminating free energy differences also agree with chromatographic data. The location and characteristics of the analyte binding site were assessed. An evaluation of total energies and intermolecular energies responsible for complex formation and for chiral discrimination was performed. Molecular dynamics trajectories of those intermolecular forces as well as distributions of the stabilizing and destabilizing forces are presented. A partitioning of the CSP into molecular fragments and the role each fragment plays in complexation and chiral recognition is also described.