Peptoid polymers are often crystalline in the solid-state as examined by X-ray scattering, but thus far, there has been no attempt to identify a common structural motif among them. In order to probe the relationship between molecular structure and crystal structure, we synthesized and analyzed a series of crystalline peptoid copolymers, systematically varying peptoid side-chain length (S) and main-chain length (N). We also examined X-ray scattering data from 18 previously reported peptoid polymers. In all peptoids, we found that the unit cell dimensions, a, b, and c, are simple functions of S and N: a (Å) = 4.55, b (Å) = [2.98]N + 0.35, and c (Å) = [1.86]S + 5.5. These relationships, which apply to both bulk crystals and self-assembled nanosheets in water, indicate that the molecules adopt extended, planar conformations. Furthermore, we performed molecular dynamics simulations (MD) of peptoid polymer lattices, which indicate that all backbone amides adopt the cis conformation. This is a surprising conclusion, because previous studies on isolated molecules indicated an energetic preference for the trans conformer. This study demonstrates that when packed into supramolecular lattices or crystals, peptoid polymers prefer to adopt a regular, extended, all-cis secondary structure.

Polypeptoid homopolymers and block copolymers undergo thermal transitions in the solid state that can be detected by differential scanning calorimetry (DSC), but so far there is neither consensus on the underpinnings of the observed thermal transitions, nor consensus on the expected number of transitions. We synthesized a series of polypeptoid diblock copolymers containing hydrophobic alkyl sidechains and hydrophilic ethyleneoxide sidechains, systematically varying side-chain length (S), backbone mainchain length (N), block copolymer composition (n/m), and N-terminal group, 1 and studied their thermal transitions by a combination of X-ray scattering and DSC. The thermal transitions are largely unaffected by S, N, and n/m, but strongly affected by the N-terminal group. Block copolymers with an acetylated N-terminus exhibit two thermal transitions. The low temperature thermal transition is due to a transition from a crystalline phase to a sanidic liquid crystalline mesophase. The molecules adopt planar, board-like conformations and are arranged in a rectangular crystal lattice with extended backbones that run parallel to each other. The side-chains extend on either side and are located within the plane of the backbone. The liquid crystalline phase is characterized by conformational disorder in dimensions normal to the molecular plane. The high temperature thermal transition is due to melting of the liquid crystalline phase to give an isotropic phase. Block copolymers with a free N-terminus (non-acetylated) exhibit only one thermal transition, and similar out-of-plane conformational disorder. This disorder appears to be due to a difference in the pendant side chain display angle of the terminal nitrogen atom.