# Cooperative Role of Mixed Solvent in the Evaporation-Induced Self-Assembly of Polypeptoid Nanocrystals

## TL;DR

This study explores how mixing solvents helps shape nanocrystals from polypeptoids, which are useful in biotechnology.

## Contribution

The study reveals the molecular-level role of mixed solvents in polypeptoid self-assembly, offering a strategy to improve nanocrystal formation.

## Key findings

- THF/water mixtures promote nanosheet formation more effectively than pure water.
- THF helps uncoil polypeptoids, while water aids aggregation into nanocrystals.
- THF concentration near nanosheet surfaces is 3–4 times higher than in bulk solution.

## Abstract

Peptoids, or polypeptoids, are biomimetic polymers that
can self-assemble
into nanocrystals for biomedical and biotechnological applications.
Polypeptoid nanocrystals can be prepared by evaporation-induced self-assembly,
but the roles of solvent components for this process have long been
overlooked at the molecular level, leaving a tunable parameter for
improving self-assembly protocols. This work utilized molecular dynamics
simulations to study the effects of water and the commonly used tetrahydrofuran
(THF) on the assembly of nanosheets from molecules of acetylated diblock
polypeptoid, poly­(N-decylglycine)-b-poly­(N-2-(2-(2-methoxyethoxy)­ethoxy) ethylglycine),
abbreviated as Ac-Ndc10-Nte10. To probe the
stages of self-assembly, isolated molecules and preassembled nanofibers/nanosheets
were simulated in pure THF, water, and their mixtures, respectively.
The assembly energies show that the THF/water mixture has a greater
tendency to form nanosheets than pure water. In a THF/water mixture,
polypeptoids were found more uncoiled in isolated states, less compact
in disordered agglomerates, and with reduced requirement for the Nte
block to cover hydrophobic Ndc surfaces in the nanocrystals. Mixed
solvent is vital to initiating self-assembly, as THF assists in the
opening of coiled polypeptoid molecules, while water provides the
thermodynamics to aggregate and ultimately form nanocrystals. To obtain
wider nanosheets, it is recommended that some THF be maintained in
the aqueous solvent before it becomes exhausted by evaporation. Near
the nanosheet surface, the THF concentration is higher than that in
bulk solution (3–4 times in 4 M THF/water). The strong adsorption
of THF indicates the self-assembly in a de facto mixed
solvent. These results are expected to guide the refinement of evaporation-induced
self-assembly protocols for polypeptoid nanocrystals.