Foldamer Architectures of Triazine-Based Sequence-Defined Polymers Investigated with Molecular Dynamics Simulations and Enhanced Sampling Methods

Triazine-based sequence-defined
polymers have recently been developed
that are biomimetic and robust. In molecular dynamics (MD) simulations,
the triazine polymers were shown to form linear nanorod foldamers
through hydrogen bonding and π–π interactions.
The nanorod foldamers have motifs resembling those of DNA, α-helices,
and β-sheets and have potential to be useful building blocks
for new macromolecules and materials. To understand the formation
of nanorod foldamers, we investigate how linker structures in the
middle of the triazine polymers lead to folding using MD simulations.
We found that a variety of linkers can participate in folding but
that specific linker structures are more favorable than others, depending
on the polymer length. Folding of hexamers into well-defined nanorod
foldamers was most favorable with pentanediamine and ortho-xylenediamine linkers in the center of the polymers. Foldamers with ortho-xylenediamine linkers in the center were investigated
for longer polymers, i.e., octamers and decamers, using two different
enhanced sampling methods, since regular MD simulations had failed
to show any folding for these longer polymers. In particular, the
recently developed concurrent adaptive sampling (CAS) algorithm and
replica exchange molecular dynamics (REMD) were used. We found that
the two enhanced sampling methods did lead to the observation of foldamers
and that REMD revealed new foldamer architectures where cis–trans isomerizations had occurred. Foldamer
formation, diversity, and the strengths and limitations of simulation
techniques are discussed. These findings provide new insights into
the diversity of foldamer architectures for a new type of biomimetic
synthetic polymer.