The sequence specificity of a class of biologically inspired polymers based on N-substituted glycines (polypeptoids) allows for a degree of tunability in the crystallization and thermal behavior not available in classical polymer systems. It is demonstrated that a series of peptoid homopolymers are stable up to temperatures of 250−300 °C and are crystalline with reversible melting transitions ranging from 150 to 225 °C. Defects inserted at precise locations along the polymer backbone (as monomer substitutions) enable control of the melting temperature. Melting points decrease with increased defect content, and X-ray diffraction (XRD) indicates defect inclusion in the crystal lattice. In addition, it is demonstrated that the distribution of the defects for a given content level affects the thermal properties of the peptoid chain.

The aqueous self-assembly of a sequence-specific bioinspired peptoid diblock copolymer into monodisperse superhelices is demonstrated to be the result of a hierarchical process, strongly dependent on the charging level of the molecule. The partially charged amphiphilic diblock copolypeptoid 30-mer, [N-(2-phenethyl)glycine](15)-[N-(2-carboxyethyl)glycine](15), forms superhelices in high yields, with diameters of 624 ± 69 nm and lengths ranging from 2 to 20 μm. Chemical analogs coupled with X-ray scattering and crystallography of a model compound have been used to develop a hierarchical model of self-assembly. Lamellar stacks roll up to form a supramolecular double helical structure with the internal ordering of the stacks being mediated by crystalline aromatic side chain-side chain interactions within the hydrophobic block. The role of electrostatic and hydrogen bonding interactions in the hydrophilic block is also investigated and found to be important in the self-assembly process.

Control over the shape of a polymer chain is desirable from a materials perspective because polymer stiffness is directly related to chain characteristics such as liquid crystallinity and entanglement, which in turn are related to mechanical properties. However, the relationship between main chain helicity in novel biologically derived and inspired polymers and chain stiffness (persistence length) is relatively poorly understood. Polypeptoids, or poly(N-substituted glycines), constitute a modular, biomimetic system that enables precise tuning of chain sequence and are therefore a good model system for understanding the interrelationship between monomer structure, helicity, and persistence length. The incorporation of bulky chiral monomers is known to cause main chain helicity in polypeptoids. Here, we show that helical polypeptoid chains have a flexibility nearly identical to an analogous random coil polypeptoid as observed via small angle neutron scattering (SANS). Additionally, our findings show that polypeptoids with aromatic phenyl side chains are inherently flexible with persistence lengths ranging from 0.5 to 1 nm. † Electronic supplementary information (ESI) available: Fits of the persistence length using the wormlike chain model over a series of polypeptoid chain lengths. In addition, the persistence length analysis for a 36-mer polypeptoid consisting of a racemic mixture of the a-chiral side chain found in 2 is also available. Finally, the results of the semiflexible cylinder model fit allowing the contour lengths to fluctuate are reported. See

Understanding the driving forces for the collapse of a polymer chain from a random coil to a globule would be invaluable in enabling scientists to predict the folding of polypeptide sequences into defined tertiary structures. The HP model considers hydrophobic collapse to be the major driving force for protein folding. However, due to the inherent presence of chirality and hydrogen bonding in polypeptides, it has been difficult to experimentally test the ability of hydrophobic forces to independently drive structural transitions. In this work, we use polypeptoids, which lack backbone hydrogen bonding and chirality, to probe the exclusive effect of hydrophobicity on the coil-to-globule collapse. Two sequences containing the same composition of only hydrophobic “H” N-methylglycine and polar “P” N-(2-carboxyethyl)glycine monomers are shown to have very different globule collapse behaviors due only to the difference in their monomer sequence. As compared to a repeating sequence with an even distribution of H and P monomers, a designed protein-like sequence collapses into a more compact globule in aqueous solution as evidenced by small-angle X-ray scattering, dynamic light scattering, and probing with environmentally sensitive fluorophores. The free energy change for the coil-to-globule transition was determined by equilibrium denaturant titration with acetonitrile. Using a two-state model, the protein-like sequence is shown to have a much greater driving force for globule formation, as well as a higher m value, indicating increased cooperativity for the collapse transition. This difference in globule collapse behavior validates the ability of the HP model to describe structural transitions based solely on hydrophobic forces.