A molecular dynamics simulation study of the association of 1,1′-binaphthyl-2,2′-diyl hydrogenphosphate enantiomers with a chiral molecular micelle

•Molecular micelle-chiral ligand intermolecular interactions were studied.•Ligand enantiomers bound preferentially to one molecular micelle binding pocket.•The ligand (S) enantiomer had a lower micelle binding energy than the (R) enantiomer.•The (S) enantiomer penetrated deeper than the (R) enantiomer into the micelle core.•Molecular dynamics results agreed with NMR and capillary electrophoresis experiments.

Molecular dynamics (MD) simulations were used to investigate the binding of 1,1′-binaphthyl-2,2′-diyl hydrogenphosphate (BNP) enantiomers to the molecular micelle poly-(sodium undecyl-(L,L)-leucine-valine) (poly(SULV)). Poly(SULV) is used as a chiral selector in capillary electrophoresis separations. Four poly(SULV) binding pockets were identified and either (R)-BNP or (S)-BNP were docked into each pocket. MD simulations were then used to identify the preferred BNP binding site. Within the preferred site, both enantiomers formed hydrogen bonds with poly(SULV) and penetrated into the poly(SULV) core. Comparisons of BNP enantiomer binding to the preferred poly(SULV) pocket showed that (S)-BNP formed stronger hydrogen bonds, moved deeper into the binding site, and had a lower poly(SULV) binding free energy than the (R) enantiomer. Finally, MD simulation results were in agreement with capillary electrophoresis and NMR experiments. Each technique showed (S)-BNP interacted more strongly with poly(SULV) than (R)-BNP and that the site of chiral recognition was near the poly(SULV) leucine chiral center.

Graphical abstractDownload full-size image