Thermodynamic Driving Forces for the Self-Assembly of Diblock Polypeptoids.

Peptoid polymers with sequence-defined side chains are observed to self-assemble into a variety of structures spanning nanometer and micron scales. We explored a diblock copolypeptoid, poly(N-decylglycine)10-block-poly(N-2-(2-(2-methoxyethoxy)ethoxy)-ethylglycine)10 (abbreviated as Ndc10-Nte10), which forms crystalline nanofibers and nanosheets as evidenced by recent cryo-transmission electron microscopy, atomic force microscopy, X-ray diffraction, and calorimetry. Using all-atom molecular dynamics simulations, we examined the thermodynamic forces driving such self-assembly and how nanoscale morphology is tailored through modification of the N-terminus or via the addition of small molecules (urea). We have found that the hydrophobic Ndc domain alignment is key to the formation of molecular stacks whose growth is limited by electrostatic repulsion between protonated N-termini. These stacks are the building blocks that assemble via cooperative van der Waals attraction between the tips of extended decyl side chains to form nanofibers or nanosheets with a well-converged intermolecular interaction energy. Assemblies are significantly more stable in urea solution due to its strong attraction to the peptoid-solvent interface. Isolated peptoids exhibit curved all-cis backbones, which straighten within molecular stacks to maximize contact and registry between neighboring molecules. We hypothesize that competition between this attractive interaction and a strain cost for straightening the backbone is what leads to finite stack widths that define crystalline nanofibers of protonated Ndc10-Nte10. Growth is proposed to proceed through backbone unfurling via trans defects, which is more prevalent in aqueous solution than in THF, indicating a possible pathway to self-assembly under experimentally defined synthesis conditions (viz., THF evaporation).

Atomic-Scale Corrugations in Crystalline Polypeptoid Nanosheets Revealed by Three-Dimensional Cryogenic Electron Microscopy.

Amphiphilic molecules that can crystallize often form molecularly thin nanosheets in aqueous solutions. The possibility of atomic-scale corrugations in these structures has not yet been recognized. We have studied the self-assembly of amphiphilic polypeptoids, a family of bio-inspired polymers that can self-assemble into various crystalline nanostructures. Atomic-scale structure of the crystals in these systems has been inferred using both X-ray diffraction and electron microscopy. Here we use cryogenic electron microscopy to determine the in-plane and out-of-plane structures of a crystalline nanosheet. Data were collected as a function of tilt angle and analyzed using a hybrid single-particle crystallographic approach. The analysis reveals that adjacent rows of peptoid chains, which are separated by 4.5 Å in the plane of the nanosheet, are offset by 6 Å in the direction perpendicular to the plane of the nanosheet. These atomic-scale corrugations lead to a doubling of the unit cell dimension from 4.5 to 9 Å. Our work provides an alternative interpretation for the observed Å X-ray diffraction peak often reported in polypeptoid crystals.

Structural Elucidation of a Polypeptoid Chain in a Crystalline Lattice Reveals Key Morphology-Directing Role of the N-Terminus.

The ability to engineer synthetic polymers with the same structural precision as biomacromolecules is crucial to enable the de novo design of robust nanomaterials with biomimetic function. Peptoids, poly(N-substituted) glycines, are a highly controllable bio-inspired polymer family that can assemble into a variety of functional, crystalline nanostructures over a wide range of sequences. Extensive investigation on the molecular packing in these lattices has been reported; however, many key atomic-level details of the molecular structure remain underexplored. Here, we use cryo-TEM 3D reconstruction to directly visualize the conformation of an individual polymer chain within a peptoid nanofiber lattice in real space at 3.6 Å resolution. The backbone in the N-decylglycine hydrophobic core is shown to clearly adopt an extended, all-cis-sigma strand conformation, as previously suggested in many peptoid lattice models. We also show that packing interactions (covalent and noncovalent) at the solvent-exposed N-termini have a dominant impact on the local chain ordering and hence the ability of the chains to pack into well-ordered lattices. Peptoids in pure water form fibers with limited growth in the a direction (<14 molecules in width), whereas in the presence of formamide, they grow to over microns in length in the a direction. This dependence points to the significant role of the chain terminus in determining the long-range order in the packing of peptoid lattices and provides an opportunity to modulate lattice stability and nanoscale morphology by the addition of exogenous small molecules. These findings help resolve a major challenge in the de novo structure-based design of sequence-defined biomimetic nanostructures based on crystalline domains and should accelerate the design of functional nanostructures.

Importance of the Positively Charged σ-Hole in Crystal Engineering of Halogenated Polypeptoids.

Crystalline nanosheets formed by amphiphilic block copolypeptoids with halogenated phenyl side chains were imaged at the atomic-scale using cryogenic transmission electron microscopy (cryo-TEM). In general, the polypeptoid molecules adopt V-shaped configurations in the crystalline state, and adjacent molecules can pack with one another in either parallel or antiparallel arrangements, depending on the chemical composition. The halogen bond, which can have characteristic energies ranging from 1 to 5 kcal/mol, is commensurate with the parallel configuration. However, cryo-TEM images show that chains in the halogenated crystals were in the antiparallel configuration. Molecular dynamics (MD) simulations show that positively charged σ-holes, which are characteristic of halogen atoms covalently bonded to carbon atoms, play an important role in determining crystal geometry. Parallel and antiparallel configurations exhibited similar stability in simulations when standard force fields that only account for the electronegativity of halogen atoms were used. However, including the σ-hole in the simulations resulted in a destabilization of the parallel configuration. This combination of imaging and simulation, which has played an important role in structural biology, has the potential to improve our understanding of factors that govern noncovalent interactions in synthetic materials.

Coarse-Grained Modeling of Ion-Containing Polymers.

Ion-containing polymers have continued to be an important research focus for several decades due to their use as an electrolyte in energy storage and conversion devices. Elucidation of connections between the mesoscopic structure and multiscale dynamics of the ions and solvent remains incompletely understood. Coarse-grained modeling provides an efficient approach for exploring the structural and dynamical properties of these soft materials. The unique physicochemical properties of such polymers are of broad interest. In this review, we summarize the current development and understanding of the structure-property relationship of ion-containing polymers and provide insights into the design of such materials determined from coarse-grained modeling and simulations accompanying significant advances in experimental strategies. We specifically concentrate on three types of ion-containing polymers: proton exchange membranes (PEMs), anion exchange membranes (AEMs), and polymerized ionic liquids (polyILs). We posit that insight into the similarities and differences in these materials will lead to guidance in the rational design of high-performance novel materials with improved properties for various power source technologies.

Quantitative Evidence of Mobile Ion Hopping in Polymerized Ionic Liquids.

Atomistic molecular dynamics simulations were performed, and an extensive set of analyses were undertaken to understand the ion transport mechanism in the polymerized ionic liquid poly(C2VIm)Tf2N. The ion hopping events were investigated at different time scales. Ion hopping was examined by monitoring the instantaneous cation-anion association and dissociation. Ion diffusion was subsequently evaluated with correlation functions and the calculation of relaxation times at different time scales. Dynamical heterogeneity in the mobility of the ions was observed with only a small portion of the anions classified as fast mobile ions. The mobile ions were characterized as the ones traveling farther than a certain distance during a characteristic period, which was much longer than the time scale of the instant ion pair dissociation. Effective hopping of the mobile ions contributed to the diffusivity which was dominated by interchain hopping and generally facilitated with five associating cations from two different polymer chains. Mobile anions had relatively fewer associating cations from more associating chains than immobile anions. The stringlike cooperative motion was observed in the mobile anions. The string length was determined to decrease with increasing temperature. These findings provided an in-depth understanding of the ion transport in polymerized ionic liquids and important information for the rational design of novel materials.

Proton Transfer in Phosphoric Acid-Based Protic Ionic Liquids: Effects of the Base.

Electronic structure calculations were performed to understand highly decoupled conductivities recently reported in protic ionic liquids (PILs). To develop a molecular-level understanding of the mechanisms of proton conductivity in PILs, minimum-energy structures of trimethylamine, imidazole, lidocaine, and creatinine (CRT) with the addition of one to three phosphoric acid (PA) molecules were determined at the B3LYP/6-311G** level of theory with the inclusion of an implicit solvation model (SMD with ε = 61). The proton affinity of the bases and zero-point energy corrected binding energies were computed at a similar level of theory. Proton dissociation from PA occurs in all systems, resulting in the formation of ion pairs due to the relatively strong basicity of the bases (proton acceptors) and the effect of the high dielectric constant solvent in stabilizing the charge separation. The second and third PA molecules preferentially form "ring-like" hydrogen bonds with one another instead of forming hydrogen bonds at the donor and acceptor sites of the bases. Potential energy scans reveal that the bases with stronger proton affinity exert greater influence on the energetics of proton transfer between the individual PA molecules. However, the effects are minimal when shifted into a single-well from a double-well potential. Barrierless proton transfer was observed to occur in the CRT system with several PA molecules present, implying that the CRT may be a promising PA-based PIL.