N-Heterocyclic carbene (NHC)-mediated ring-opening polymerization (ROP) of N-substituted N-carboxylanhydride ((N)R-NCA) yields cyclic poly(alpha-peptoid)s with controlled molecular weights (M(n) = 3-30 kg mol(-1)) and narrow molecular weight distributions (PDI = 1.04-1.12). The reactions exhibit characteristics of a living polymerization with minimal chain transfer. This enables the facile synthesis of cyclic diblock copoly(alpha-peptoid)s through sequential monomer addition. The cyclic polymer architectures were verified by MALDI-TOF mass spectrometry and intrinsic viscosity measurements. Mark-Houwink-Sakurada plot analyses revealed that cyclic poly(alpha-peptoid)s prepared from NHC-mediated polymerizations exhibit lower intrinsic viscosities than their linear analogues prepared from primary amine-initiated polymerizations. The ratio of their intrinsic viscosities is consistent with the former being mostly cyclic.

Covalent polymeric networks composed of imine cross-linkages have been prepared by condensation polymerization of poly­(ethylene glycol) bis­(3-aminopropyl) with 1,3,5-triformylbenzene with an equal molar ratio of amine and aldehyde functionalities in organic solvents with varying polarity and in neat condition. The polymer networks exhibit malleability and self-healing characteristics. Rheological measurements revealed that longer reaction time is required to reach the gel point (i.e., crossover of G′ and G″) in polar solvents than in nonpolar solvents. The malleability of the solvent-swelled polymer network is also strongly dependent on the solvent polarity. Polymer gels in polar solvents are more malleable than those in nonpolar solvents, as supported by the dynamic mechanical analysis. These results are consistent with faster dynamic imine bond exchange in the polar solvents relative to the nonpolar solvents, thus requiring higher functionality conversion to form an elastic network in the polar solvent relative to the nonpolar solvent. The imine–imine bond exchange kinetic was also studied by 1H NMR spectroscopy on model compounds in the presence of varying amount of primary amine and water. The exchange reaction was significantly accelerated by the presence of primary amine than water, suggesting that the imine bond exchange is mainly promoted by the residual primary amino functionalities in the polymeric network. This study revealed the molecular and kinetic basis for the macroscopic and dynamical properties of the polymer networks composed of imine cross-linkages. The polymer networks are potentially useful as adhesives.

Random copolymers based on poly(N-ethyl glycine) and poly(N-butyl glycine) have been synthesized by NHC-mediated or primary amine-initiated copolymerization of the corresponding Nsubstituted N-carboxyanhydride monomers (i.e., Et-NCA and Bu-NCA), respectively. The copolymers are thermally responsive and exhibit reversible phase transitions with tunable cloud point temperature (T cp ) in aqueous solution. The T cp can be readily tuned in the temperature range 20−60 °C by controlling the copoly(α-peptoid) composition and the architecture (i.e., cyclic vs linear). The copoly(α-peptoid)s are noncytotoxic (similar to poly(ethylene glycol) (PEG), a benchmark biocompatible polymer), suggesting their potential use in biotechnology and biomedicine.

N-Heterocyclic carbene (NHC)-mediated polymerizations of N-butyl N-carboxyanhydride (Bu-NCA) to produce cyclic poly(N-butyl glycine)s (c-NHC-PNBGs) have been investigated in various solvents with NHCs having differing steric and electronic properties. Control over the polymer molecular weight (MW) and polymerization rate is strongly dependent on the solvent and the NHC structure. Kinetic studies reveal that the propagating intermediates for the polymerization in low dielectric solvents (e.g., THF or toluene) maintain cyclic architectures with two chain ends in close contact through Coulombic interaction. The NHCs not only initiate the polymerization, but also mediate the chain propagation as intramolecular counterions. Side reactions are significantly suppressed in low dielectric solvents due to the reduced basicity and nucleophilicity of the negatively charged chain ends of the zwitterions, resulting in quasi-living polymerization behavior. By contrast, the two charged chain ends of the zwitterionic species are fully dissociated in high dielectric solvents. The chain propagation proceeds as in conventional anionic polymerizations, wherein side reactions (e.g., transamidation) compete with chain propagation, resulting in significantly diminished control over polymer MW. The cyclic zwitterionic propagating species can be converted into their linear polymeric analogues (l-NHC-PNBGs) by end-capping with electrophiles (e.g., acetyl chloride) or the NHC-free cyclic analogues (c-PNBGs) by treatment with NaN(TMS)(2), as evidenced by MALDI-TOF MS, NMR, and SEC analysis.

Polypeptoids have recently emerged as a subject of scientific interest due to their structural resemblance to existing pseudo-peptidic polymers including poly(αpeptide)s, poly(β-peptide)s, poly(2-oxazoline)s, and poly(Nsubstituted acrylamide)s. With demonstrated backbone degradability, biocompatibility, and thermal processability, polypeptoids are potentially useful in a variety of biotechnological applications. Before those applications can be realized, it is important to develop their synthesis and understand their fundamental properties. In this Perspective, we will review recent advances in the synthesis and characterization of polypeptoids and their copolymers as well as the development of polypeptoid-based functional and structured materials. We will conclude by discussing the future prospects for this nascent class of pseudo-peptidic polymers.