Role of tetrahydrofuran in the self-assembly of polypeptoid nanocrystals

Evaporation induced self-assembly is commonly used for the preparation of polypeptoid nanocrystals. This process involves a water-organic solvent mixture with a time-evolving concentration. To precisely control the self-assembly, it is necessary to understand the role of these organic molecules. This work utilized molecular dynamics simulations to study the effects of the commonly used tetrahydrofuran (THF) on the acetylated diblock polypeptoid, poly(N-decylglycine)-b-poly(N-2-(2-(2-methoxyethoxy)ethoxy) ethylglycine) [Ac-Ndc₁₀-Nte₁₀].​​ To probe the stages of self-assembly, isolated molecules and pre-assembled nanofibers/nanosheets were simulated in pure THF, THF/water mixtures and pure water. The assembly energies show that the THF/water mixture has a greater tendency to form nanosheets than pure water, while pure THF does not permit nanofibers or nanosheets to form. Polypeptoids are less compact in the mixed solvent, with more open conformations for both isolated polypeptoids and loose agglomerates, and a reduced requirement for the Nte block to cover hydrophobic Ndc surfaces. Our main conclusion is that mixed solvent is vital to initiate self-assembly. The presence of THF assists the opening of coiled polypeptoid molecules, while water provides the thermodynamic driving forces to aggregate and ultimately form nanocrystals. Near the nanosheet surface, the THF concentration is three to four times higher than that of the 4M bulk solution, due to the strong adsorption of THF at the peptoid surface. This evidence indicates the possibility to control the local solvation environment by managing the evaporation. To obtain wider nanosheets, it is recommended to maintain some THF in the aqueous solvent before it becomes exhausted by evaporation.