Peptoids as a Chiral Stationary Phase for Liquid Chromatography: Insights from Molecular Dynamics Simulations

Peptoids
are peptide regioisomers with attractive structural tunability
in terms of sequence and three-dimensional arrangement. Peptoids are
foreseen to have a great potential for many diverse applications,
including their utilization as a chiral stationary phase in chromatography.
To achieve chiral recognition, a chiral side chain is required to
allow specific interactions with a given enantiomer from a racemic
mixture. One of the most studied chiral stationary phases, built with
(S)-N-1-phenylethyl (Nspe) units, was shown to be successful in resolving racemic mixtures
of binaphthyl derivatives. However, there is currently no description
at the atomic scale of the factors favoring its enantioselectivity.
Here, we take advantage of steered molecular dynamics simulations
to mimic the elution process at the atomic scale and present evidence
that the predominantly right-handed helical conformation of Nspe peptoids and their ability to form stronger hydrogen
bonds with the (S) enantiomer are responsible for
the chiral recognition of the popular chiral probe 2,2′-bihydroxy-1,1′-binaphthyl.