Abstract
In this study, the chiral separation mechanisms of Dansyl amino acids, including Dansyl-Leucine (Dans-Leu), Dansyl-Norleucine (Dans-Nor), Dansyl-Tryptophan (Dans-Trp) and Dansyl-Phenylalanine (Dans-Phe) binding to poly-sodium N-undecanoyl-(L)-Leucylvalinate, poly(SULV), were investigated using molecular dynamics simulations. Micellar electrokinetic chromatography (MEKC) has previously shown that when separating the enantiomers of these aforementioned Dansyl amino acids, the L- enantiomers bind stronger to poly(SULV) than the D- enantiomers. This study aims to investigate the molecular interactions that govern chiral recognition in these systems using computational methods. This study reveals that the computationally-calculated binding free energy values for Dansyl enantiomers binding to poly(SULV) are in agreement with the enantiomeric order produced in experimental MEKC studies. The L- enantiomers of Dans-Leu, Dans-Nor, Dans-Trp, and Dans-Phe binding to their preferred binding pockets in poly(SULV) yielded binding free energy values of -21.8938, -22.1763, -21.3329 and -13.3349 kJ·mol-1, respectively. The D- enantiomers of Dans-Leu, Dans-Nor, Dans-Trp, and Dans-Phe binding to their preferred binding pockets in poly(SULV) yielded binding free energy values of -14.5811, -15.9457, -13.6408, and -12.0959 kJ·mol-1, respectively. Furthermore, hydrogen bonding analyses were used to investigate and elucidate the molecular interactions that govern chiral recognition in these molecular systems.
Highlights
More than half of all pharmaceutical drugs currently in use are chiral, and the synthesis of these drugs often yields a racemic mixture, containing both enantiomers of the compound [1]
This study reveals that the computationally-calculated binding free energy values for Dansyl enantiomers binding to poly (SULV) are in agreement with the enantiomeric order produced in experimental Micellar electrokinetic chromatography (MEKC) studies
The binding free energy values for the Dansyl amino acids examined in this study to poly (SULV) were all in agreement with the enantiomeric order determined by MEKC, in which the L-enantiomer of each Dansyl amino acid interacted stronger with poly (SULV) than the D-enantiomer
Summary
More than half of all pharmaceutical drugs currently in use are chiral, and the synthesis of these drugs often yields a racemic mixture, containing both enantiomers of the compound [1]. While the physical and chemical properties of the enantiomers are similar, they often produce very different pharmacological effects [1] [2] [3]. One enantiomer may produce the desired medicinal effect, whereas the other may cause adverse health effects. (+)-Ethambutol is primarily used to treat Tuberculosis, whereas its enantiomer, (−)-Ethambutol, causes blindness [4]. Due to the enantiomers of chiral drugs often producing vastly different effects, the United States Food and Drug Administration has mandated that each enantiomer of a chiral drug be tested for enantiomeric purity prior to being marketed [5]. The enantiomers differ in stereoconfiguration, which allows them to interact differently with chiral separation mediums, allowing for enantioseparation [5]
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