Self-assembly of crystalline nanotubes from monodisperse amphiphilic diblock copolypeptoid tiles

Abstract

The folding and assembly of sequence-defined polymers into precisely ordered nanostructures promises a class of well-defined biomimetic architectures with specific function. Amphiphilic diblock copolymers are known to self-assemble in water to form a variety of nanostructured morphologies including spheres, disks, cylinders, and vesicles. In all of these cases, the predominant driving force for assembly is the formation of a hydrophobic core that excludes water, whereas the hydrophilic blocks are solvated and extend into the aqueous phase. However, such polymer systems typically have broad molar mass distributions and lack the purity and sequence-defined structure often associated with biologically derived polymers. Here, we demonstrate that purified, monodisperse amphiphilic diblock copolypeptoids, with chemically distinct domains that are congruent in size and shape, can behave like molecular tile units that spontaneously assemble into hollow, crystalline nanotubes in water. The nanotubes consist of stacked, porous crystalline rings, and are held together primarily by side-chain van der Waals interactions. The peptoid nanotubes form without a central hydrophobic core, chirality, a hydrogen bond network, and electrostatic or π-π interactions. These results demonstrate the remarkable structure-directing influence of n-alkane and ethyleneoxy side chains in polymer self-assembly. More broadly, this work suggests that flexible, low-molecular-weight sequence-defined polymers can serve as molecular tile units that can assemble into precision supramolecular architectures.peptoid polymers | sequence-defined polymers | supramolecular assembly | polymer amphiphiles | peptoid nanostructures S elf-assembly of copolymers comprising hydrophilic and hydrophobic blocks in water is a subject of long-standing interest (1, 2). The hydrophilic blocks can be either charged (e.g., polyacrylic acid) or uncharged (e.g., polyethylene oxide) (3, 4), and the hydrophobic blocks are either amorphous (e.g., polybutadiene) or crystalline (e.g., polyethylene) (5, 6). A variety of morphologies such as spheres, disks, cylinders, and vesicles have been identified in these systems (1, 3, 7-10). These morphologies comprise solid cores of the hydrophobic blocks surrounded by solvated hydrophilic chains that extend into the aqueous phase. In all of these cases, the predominant driving force for assembly is the formation of a hydrophobic core that excludes water. In a few cases, it has been shown that the enthalpic gain from the crystallization of polymer blocks can drive micellar self-assembly in organic solvents (11) and can regulate the micellar morphology or stability in aqueous solutions (12).The recently developed ability to synthesize polymers of precisely controlled monomer sequence (13) opens up the possibility to study the fundamental relationship between polymer sequence and polymer function. Peptoids are one particularly promising class of bioinspired polymer, where the main chain length and monomer sequence can be precisely controlled (1...

Log D versus HPLC derived hydrophobicity: The development of predictive tools to aid in the rational design of bioactive peptoids

“…Natural proteins and peptides explore a variety of conformational states from fully stabilised to unfolded and peptoids are no different. Peptoids have been shown to adopt stable and well defined structures in solution, such as the peptoid helix, threaded loop conformation, peptoid nanosheets, and nanotubes . Unlike peptides where regular backbone hydrogen bonding helps to stabilise the secondary structures adopted, peptoids typically rely upon the local steric or electronic effects of side chains to help stabilise any secondary structures formed.…”

TEM Investigations of Peptoid Structures

“…The structural diversity seen with these materials reflects the range of possibilities for developing peptoid-based membranes with specific properties. [2]. Crystalline sheets are also found in this material, and are the predominant aggregate with the corresponding peptoid having 9 repeats of each sidechain.…”

Assembly and Self‐Assembly of Nanomembrane Materials—From 2D to 3D

“…Man‐made nanomembranes of macroscopic size and nanometric thickness have already found advantageous applications in drug‐delivery vehicles, biomimetic systems, microfluidic valves, platforms for biosensors, wound dressing, and even artificial organs . Especially, many efforts have been made to create nanomembranes assembled from lipids, or synthetic analogues of lipids (e.g., lipid‐like peptides, block copolymers) . Due to their unique properties, peptoids are recently considered as synthetic analogues of lipids .…”