High-Throughput Synthesis, Purification, and Application of Alkyne-Functionalized Discrete Oligomers.

The development of synthetic oligomers as discrete single molecular entities with accurate control over the number and nature of functional groups along the backbone has enabled a variety of new research opportunities. From fundamental studies of self-assembly in materials science to understanding efficacy and safety profiles in biology and pharmaceuticals, future directions are significantly impacted by the availability of discrete, multifunctional oligomers. However, the preparation of diverse libraries of discrete and stereospecific oligomers remains a significant challenge. We report a novel strategy for accelerating the synthesis and isolation of discrete oligomers in a high-throughput manner based on click chemistry and simplified bead-based purification. The resulting synthetic platform allows libraries of discrete polyether oligomers to be prepared and the impact of variables such as chain length, number, and nature of side chain functionalities and molecular dispersity on antibacterial behavior examined. Significantly, discrete oligomers were shown to exhibit enhanced activity with lower toxicity compared with traditional disperse samples. This work provides a practical and scalable methodology for nonexperts to prepare libraries of multifunctional discrete oligomers and demonstrates the advantages of discrete materials in biological applications.

Crystallization-Induced Flower-like Superstructures via Peptoid Helix Assembly.

We report a unique method to construct hierarchical superstructures based on molecular programming of peptidomimetics. Chiral steric hindrance in the polymer backbone stabilizes peptoid helices that crystallize into nanosheets during solvent evaporation. The stacking of nanosheets results in flower-like superstructures. The helical peptoid, nucleated from chiral monomers, is characterized as locally stiffer and more extended than the unstructured peptoid. Molecular dynamics (MD) simulations further suggest a constraint on the dihedral angles and a preference toward the trans configuration, resulting in an extended chain structure. The nanosheet assemblies at various length scales indicate an extent of intermolecular ordering amplified by chiral steric hindrance. Such molecular programming and processing protocols will benefit the future design and controlled assembly of hierarchical peptidomimetics.

Chromatographic Separation: A Versatile Strategy to Prepare Discrete and Well-Defined Polymer Libraries.

ConspectusThe preparation of discrete and well-defined polymers is an emerging strategy for emulating the remarkable precision achieved by macromolecular synthesis in nature. Although modern controlled polymerization techniques have unlocked access to a cornucopia of materials spanning a broad range of monomers, molecular weights, and architectures, the word "controlled" is not to be confused with "perfect". Indeed, even the highest-fidelity polymerization techniques─yielding molar mass dispersities in the vicinity of D = 1.05─unavoidably create a considerable degree of structural and/or compositional dispersity due to the statistical nature of chain growth. Such dispersity impacts many of the properties that researchers seek to control in the design of soft materials.The development of strategies to minimize or entirely eliminate dispersity and access molecularly precise polymers therefore remains a key contemporary challenge. While significant advances have been made in the realm of iterative synthetic methods that construct oligomers with an exact molecular weight, head-to-tail connectivity, and even stereochemistry via small-molecule organic chemistry, as the word "iterative" suggests, these techniques involve manually propagating monomers one reaction at a time, often with intervening protection and deprotection steps. As a result, these strategies are time-consuming, difficult to scale, and remain limited to lower molecular weights. The focus of this Account is on an alternative strategy that is more accessible to the general scientific community because of its simplicity, versatility, and affordability: chromatography. Researchers unfamiliar with the intricacies of synthesis may recall being exposed to chromatography in an undergraduate chemistry lab. This operationally simple, yet remarkably powerful, technique is most commonly encountered in the purification of small molecules through their selective (differential) adsorption to a column packed with a low-cost stationary phase, usually silica. Because the requisite equipment is readily available and the actual separation takes little time (on the order of 1 h), chromatography is used extensively in small-molecule chemistry throughout industry and academia alike. It is, therefore, perhaps surprising that similar types of chromatography are not more widely leveraged in the field of polymer science as well.Here, we discuss recent advances in using chromatography to control the structure and properties of polymeric materials. Emphasis is placed on the utility of an adsorption-based mechanism that separates polymers based on polarity and composition at tractable (gram) scales for materials science, in contrast to size exclusion, which is extremely common but typically analyzes very small quantities of a sample (∼1 mg) and is limited to separating by molar mass. Key concepts that are highlighted include (1) the separation of low-molecular-weight homopolymers into discrete oligomers (D = 1.0) with precise chain lengths and (2) the efficient fractionation of block copolymers into high-quality and widely varied libraries for accelerating materials discovery. In summary, the authors hope to convey the exciting possibilities in polymer science afforded by chromatography as a scalable, versatile, and even automated technique that unlocks new avenues of exploration into well-defined materials for a diverse assortment of researchers with different training and expertise.

Heterotelechelic Silicones: Facile Synthesis and Functionalization Using Silane-Based Initiators.

The synthetic utility of heterotelechelic polydimethylsiloxane (PDMS) derivatives is limited due to challenges in preparing materials with high chain-end fidelity. In this study, anionic ring-opening polymerization (AROP) of hexamethylcyclotrisiloxane (D3) monomers using a specifically designed silyl hydride (Si-H)-based initiator provides a versatile approach toward a library of heterotelechelic PDMS polymers. A novel initiator, where the Si-H terminal group is connected to a C atom (H-Si-C) and not an O atom (H-Si-O) as in traditional systems, suppresses intermolecular transfer of the Si-H group, leading to heterotelechelic PDMS derivatives with a high degree of control over chain ends. In situ termination of the D3 propagating chain end with commercially available chlorosilanes (alkyl chlorides, methacrylates, and norbornenes) yields an array of chain-end-functionalized PDMS derivatives. This diversity can be further increased by hydrosilylation with functionalized alkenes (alcohols, esters, and epoxides) to generate a library of heterotelechelic PDMS polymers. Due to the living nature of ring-opening polymerization and efficient initiation, narrow-dispersity (D < 1.2) polymers spanning a wide range of molar masses (2-11 kg mol-1) were synthesized. With facile access to α-Si-H and ω-norbornene functionalized PDMS macromonomers (H-PDMS-Nb), the synthesis of well-defined supersoft (G' = 30 kPa) PDMS bottlebrush networks, which are difficult to prepare using established strategies, was demonstrated.

Controlled-Radical Polymerization of α-Lipoic Acid: A General Route to Degradable Vinyl Copolymers.

Here, we present the synthesis and characterization of statistical and block copolymers containing α-lipoic acid (LA) using reversible addition-fragmentation chain-transfer (RAFT) polymerization. LA, a readily available nutritional supplement, undergoes efficient radical ring-opening copolymerization with vinyl monomers in a controlled manner with predictable molecular weights and low molar-mass dispersities. Because lipoic acid diads present in the resulting copolymers include disulfide bonds, these materials efficiently and rapidly degrade when exposed to mild reducing agents such as tris(2-carboxyethyl)phosphine (Mn = 56 → 3.6 kg mol-1). This scalable and versatile polymerization method affords a facile way to synthesize degradable polymers with controlled architectures, molecular weights, and molar-mass dispersities from α-lipoic acid, a commercially available and renewable monomer.

Improved Elastic Recovery from ABC Triblock Terpolymers.

The promise of ABC triblock terpolymers for improving the mechanical properties of thermoplastic elastomers is demonstrated by comparison with symmetric ABA/CBC analogs having similar molecular weights and volume fraction of B and A/C domains. The ABC architecture enhances elasticity (up to 98% recovery over 10 cycles) in part through essentially full chain bridging between discrete hard domains leading to the minimization of mechanically unproductive loops. In addition, the unique phase space of ABC triblocks also enables the fraction of hard-block domains to be higher (fhard ≈ 0.4) while maintaining elasticity, which is traditionally only possible with non-linear architectures or highly asymmetric ABA triblock copolymers. These advantages of ABC triblock terpolymers provide a tunable platform to create materials with practical applications while improving our fundamental understanding of chain conformation and structure-property relationships in block copolymers.

Competition between ß-Sheet and Coacervate Domains Yields Diverse Morphologies in Mixtures of Oppositely Charged Homochiral Polypeptides.

Biomolecular assembly processes involving competition between specific intermolecular interactions and thermodynamic phase instability have been implicated in a number of pathological states and technological applications of biomaterials. As a model for such processes, aqueous mixtures of oppositely charged homochiral polypeptides such as poly-l-lysine and poly-l-glutamic acid have been reported to form either ß-sheet-rich solid-like precipitates or liquid-like coacervate droplets depending on competing hydrogen bonding interactions. Herein, we report studies of polypeptide mixtures that reveal unexpectedly diverse morphologies ranging from partially coalescing and aggregated droplets to bulk precipitates, as well as a previously unreported re-entrant liquid-liquid phase separation at high polypeptide concentration and ionic strength. Combining our experimental results with all-atom molecular dynamics simulations of folded polypeptide complexes reveals a concentration dependence of ß-sheet-rich secondary structure, whose relative composition correlates with the observed macroscale morphologies of the mixtures. These results elucidate a crucial balance of interactions that are important for controlling morphology during coacervation in these and potentially similar biologically relevant systems.

Tailoring Writability and Performance of Star Block Copolypeptides Hydrogels through Side-Chain Design.

Shear-recoverable hydrogels based on block copolypeptides with rapid self-recovery hold potential in extrudable and injectable 3D-printing applications. In this work, a series of 3-arm star-shaped block copolypeptides composed of an inner hydrophilic poly(l-glutamate) domain and an outer ß-sheet forming domain is synthesized with varying side chains and block lengths. By changing the ß-sheet forming domains, hydrogels with diverse microstructures and mechanical properties are prepared and structure-function relationships are determined using scattering and rheological techniques. Differences in the properties of these materials are amplified during direct-ink writing with a strong correlation observed between printability and material chemistry. Significantly, it is observed that non-canonical ß-sheet blocks based on phenyl glycine form more stable networks with superior mechanical properties and writability compared to widely used natural amino acid counterparts. The versatile design available through block copolypeptide materials provides a robust platform to access tunable material properties based solely on molecular design. These systems can be exploited in extrusion-based applications such as 3D-printing without the need for additives.

Building Tunable Degradation into High-Performance Poly(acrylate) Pressure-Sensitive Adhesives.

Pressure-sensitive adhesives (PSAs) based on poly(acrylate) chemistry are common in a wide variety of applications, but the absence of backbone degradability causes issues with recycling and sustainability. Here, we report a strategy to create degradable poly(acrylate) PSAs using simple, scalable, and functional 1,2-dithiolanes as drop-in replacements for traditional acrylate comonomers. Our key building block is α-lipoic acid, a natural, biocompatible, and commercially available antioxidant found in various consumer supplements. α-Lipoic acid and its derivative ethyl lipoate efficiently copolymerize with n-butyl acrylate under conventional free-radical conditions leading to high-molecular-weight copolymers (Mn > 100 kg mol-1) containing a tunable concentration of degradable disulfide bonds along the backbone. The thermal and viscoelastic properties of these materials are practically indistinguishable from nondegradable poly(acrylate) analogues, but a significant reduction in molecular weight is realized upon exposure to reducing agents such as tris (2-carboxyethyl) phosphine (e.g., Mn = 198 kg mol-1 → 2.6 kg mol-1). By virtue of the thiol chain ends produced after disulfide cleavage, degraded oligomers can be further cycled between high and low molecular weights through oxidative repolymerization and reductive degradation. Transforming otherwise persistent poly(acrylates) into recyclable materials using simple and versatile chemistry could play a pivotal role in improving the sustainability of contemporary adhesives.

Modular Synthesis and Patterning of High-Stiffness Networks by Postpolymerization Functionalization with Iron-Catechol Complexes.

Bioinspired iron-catechol cross-links have shown remarkable success in increasing the mechanical properties of polymer networks, in part due to clustering of Fe3+-catechol domains which act as secondary network reinforcing sites. We report a versatile synthetic procedure to prepare modular PEG-acrylate networks with independently tunable covalent bis(acrylate) and supramolecular Fe3+-catechol cross-linking. Initial control of network structure is achieved through radical polymerization and cross-linking, followed by postpolymerization incorporation of catechol units via quantitative active ester chemistry and subsequent complexation with iron salts. By tuning the ratio of each building block, dual cross-linked networks reinforced by clustered iron-catechol domains are prepared and exhibit a wide range of properties (Young's moduli up to ∼245 MPa), well beyond the values achieved through purely covalent cross-linking. This stepwise approach to mixed covalent and metal-ligand cross-linked networks also permits local patterning of PEG-based films through masking techniques forming distinct hard, soft, and gradient regions.