Thermodynamic Driving Forces for the Self-Assembly of Diblock Polypeptoids

Peptoid polymers
with sequence-defined side chains are observed
to self-assemble into a variety of structures spanning nanometer and
micron scales. We explored a diblock copolypeptoid, poly(N-decylglycine)10-block-poly(N-2-(2-(2-methoxyethoxy)ethoxy)-ethylglycine)10 (abbreviated
as Ndc10-Nte10), which forms crystalline nanofibers
and nanosheets as evidenced by recent cryo-transmission electron microscopy,
atomic force microscopy, X-ray diffraction, and calorimetry. Using
all-atom molecular dynamics simulations, we examined the thermodynamic
forces driving such self-assembly and how nanoscale morphology is
tailored through modification of the N-terminus or via the addition
of small molecules (urea). We have found that the hydrophobic Ndc
domain alignment is key to the formation of molecular stacks whose
growth is limited by electrostatic repulsion between protonated N-termini.
These stacks are the building blocks that assemble via cooperative
van der Waals attraction between the tips of extended decyl side chains
to form nanofibers or nanosheets with a well-converged intermolecular
interaction energy. Assemblies are significantly more stable in urea
solution due to its strong attraction to the peptoid–solvent
interface. Isolated peptoids exhibit curved all-cis backbones, which straighten within molecular stacks to maximize
contact and registry between neighboring molecules. We hypothesize
that competition between this attractive interaction and a strain
cost for straightening the backbone is what leads to finite stack
widths that define crystalline nanofibers of protonated Ndc10-Nte10. Growth is proposed to proceed through backbone
unfurling via trans defects, which is more prevalent
in aqueous solution than in THF, indicating a possible pathway to
self-assembly under experimentally defined synthesis conditions (viz.,
THF evaporation).