An Investigation into Formation Pathway of Peptoid Supramolecular Structures

The functions of nanomaterials assembled from sequence-defined macromolecules are highly determined by their molecular packing and morphologies.^1,2 Peptoids, N-substituted glycines, are a well-developed type of sequence-defined synthetic polymers that mimic the functions of peptides and proteins. Lacking in hydrogen bond donors, peptoids exhibit unique self-assembly characteristics, forming well-defined supramolecular structures such as nanotubes⁴, nanosheets⁴, and nano-helices⁶ through noncovalent interactions. These structures result from the dynamic equilibrium between their intermolecular hydrophobic interactions and amphiphilicity in the surrounding aqueous phase.⁷ Despite extensive efforts in designing peptoid sequences for hierarchical assembly, the formation pathways of many peptoid-based supramolecular structures remain under explored. Macromolecular self-assembly is influenced not only by sequence and composition but also by exposed environmental conditions. Understanding how these conditions affect peptoid assembly structures aids in predicting the assembly of peptoids into designed supramolecular structures. In this presentation, I will report my systematic studies of peptoid self-assembly process by varying factors such as solvent type, solvent ratio, temperature, and ionic strength. Three typical morphologies, nanotubes, nano-helices and nanosheets are formed in a controllable manner from a single peptoid sequence Npm4Nc2-L-Ala with the change of assembly conditions. In acetonitrile and H₂O, this sequence assembles into helices. In acetone with the same ratio, this peptoid forms both tubes and helices. As the percentage of water increases, the pitch distance of peptoid helices becomes longer, and more rod-like structures appear and are easier to observe. Peptoid nanosheets have a much higher energy barrier than tubes and helices. In either acetonitrile or acetone as organic solvents, nanosheets form whenever a 60 ^oC annealing is treated on the dissolved peptoid powder before the self-assembly begins. We also find that the change of solution ionic strength can change the nanohelix formation pathways as this sequence typically undergoes a fiber intermediate structure while an increased ionic strength leads to the formation of a tubular intermediate structure before nanohelix formation. These findings provide evidence for constructing a peptoid self-assembly energy landscape and support the possibility of achieving precise control over formation pathways.<br/><br/>(1) Song, Y.; Cai, X.; Wang, M.; Du, D.; Lin, Y.; Chen, C.-L. Assembly of Highly Efficient Aqueous Light-Harvesting System from Sequence-Defined Peptoids for Cytosolic microRNA Detection. <i>Nano Res.</i> <b>2024</b>, <i>17</i> (2), 788–796.<br/>(2) Song, Y.; Wang, M.; Akkineni, S.; Yang, W.; Hettige, J. J.; Jin, H.; Liao, Z.; Mu, P.; Yan, F.; Baer, M.; De Yoreo, J. J.; Du, D.; Lin, Y.; Chen, -L. Highly Bright and Photostable Two-Dimensional Nanomaterials Assembled from Sequence-Defined Peptoids. <i>ACS Mater. Lett.</i> <b>2021</b>, 3, 420-427<br/>(3) Jin, H.; Ding, Y.-H.; Wang, M.; Song, Y.; Liao, Z.; Newcomb, C. J.; Wu, X.; Tang, X.-Q.; Li, Z.; Lin, Y.; Yan, F.; Jian, T.; Mu, P.; Chen, C.-L. Designable and Dynamic Single-Walled Stiff Nanotubes Assembled from Sequence-Defined Peptoids. <i>Nat Commun</i> <b>2018</b>, <i>9</i> (1), 270.<br/>(4) Jin, H.; Jiao, F.; Daily, M. D.; Chen, Y.; Yan, F.; Ding, Y.-H.; Zhang, X.; Robertson, E. J.; Baer, M. D.; Chen, C.-L. Highly Stable and Self-Repairing Membrane-Mimetic 2D Nanomaterials Assembled from Lipid-like Peptoids. <i>Nat Commun</i> <b>2016</b>, <i>7</i> (1), 12252.<br/>(5) Zheng, R.; Zhao, M.; Du, J. S.; Sudarshan, T. R.; Zhou, Y.; Paravastu, A. K.; De Yoreo, J. J.; Ferguson, A. L.; Chen, C.-L. Assembly of Short Amphiphilic Peptoids into Nanohelices with Controllable Supramolecular Chirality. <i>Nat Commun</i> <b>2024</b>, <i>15</i> (1), 3264.<br/>(6) Li, Z.; Cai, B.; Yang, W.; Chen, C.-L. Hierarchical Nanomaterials Assembled from Peptoids and Other Sequence-Defined Synthetic Polymers. <i>Chem. Rev.</i> <b>2021</b>, <i>121</i> (22), 14031–14087.