Self-Assembly of Nanocubic Molecular Capsules via Solvent-Guided Formation of Rectangular Blocks

We
investigate the mechanism underlying the self-assembly of gear-shaped
amphiphilic molecules into a highly ordered nanocubic capsule (“nanocube”)
in aqueous methanol. Simulation results show that the solvent molecules
play a significant role in the assembly process by directing the primitive
intermediates to orthogonal/rectangular shapes, thus creating appropriate
building blocks for cubic assembly while avoiding off-pathway stacked
aggregates. Free-energy analyses reveal that the interplay of the
direct intermonomer interaction and the solvent-mediated repulsion
between large aromatic cores (via preferential solvation of methanol
on hydrophobic surfaces) leads to the strong trend for perpendicular
binding of monomers and hence the solvent-guided formation of rectangular
blocks. Furthermore, we report the self-assembly simulation of the
nanocube using replica exchange with solute tempering and demonstrate
that the simulation can predict a highly ordered nanocapsule structure,
assembly intermediates, and encapsulated molecules, which helps promote
computer-aided design of functional molecular self-assemblies in explicit
solvent.