Chiral Recognition of Dansyl Derivatives with an Amino Acid-Based Molecular Micelle: A Molecular Dynamics Investigation

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.

Update on chiral recognition mechanisms in separation science

“…Instead, polymeric micelles have been studied and the interaction between analytes and the micelles could be concluded from modeling data as summarized in [18,19]. Garcia and colleagues investigated the chiral separation mechanisms of the dansyl (Dns) amino acids Dns-Leu, Dns-Nle, Dns-Trp, and Dns-Phe by the polymeric micelle system poly-sodium N-undecanoyl-(l)leucylvalinate (poly-SULV) using MD simulations [183]. The calculated binding free energy values for the interaction of the Dns amino acids with poly-SULV indicated a stronger interaction with the l-enantiomers, which was in agreement with the enantiomer migration order d-> lamino acids.…”

“…An exception was Dns‐ l ‐Phe, which established a single major hydrogen bond in pocket 3 as compared to three in the case of the d ‐enantiomer. However, the lifetime of this hydrogen bond as well as its occupancy was much longer than the three hydrogen bonds formed by the d ‐enantiomer indicating also preferential binding of Dns‐ l ‐Phe by poly‐SULV [183].…”

“…(A) Spatial orientation of the three binding pockets in the poly‐sodium N ‐undecanoyl‐(L)‐leucylvalinate (poly‐SULV) micelle and (B) highest scoring docked positions of Dns‐ l ‐Leu (blue, top) and Dns‐ d ‐Leu (red, bottom) in binding pockets 1–3. (Reproduced with permission [183], © Scientific Research Publishing 2021).…”

Interface Chirality: From Biological Effects to Biomedical Applications

“…The interactions between biological systems and chiral surfaces typically exhibit a diastereomeric nature between enantiomeric guest molecules and homochiral biological receptors. This characteristic leads to potential diastereomeric energy differences between homochiral vs. heterochiral interactions, L-L vs. L-D for instance [21][22][23]. Such research not only helps us understand chiral response mechanisms but also promotes the applications of the chiral effects in biological systems.…”