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.

Multi Electron Spin Cluster Enabled Dynamic Nuclear Polarization with Sulfonated BDPA.

Dynamic nuclear polarization (DNP) can amplify the solid-state nuclear magnetic resonance (NMR) signal by several orders of magnitude. The mechanism of DNP utilizing α,γ-bisdiphenylene-ß-phenylallyl (BDPA) variants as Polarizing Agents (PA) has been the subject of lively discussions on account of their remarkable DNP efficiency with low demand for microwave power. We propose that electron spin clustering of sulfonated BDPA is responsible for its DNP performance, as revealed by the temperature-dependent shape of the central DNP profile and strong electron-electron (e-e) crosstalk seen by Electron Double Resonance. We demonstrate that a multielectron spin cluster can be modeled with three coupled spins, where electron J (exchange) coupling between one of the e-e pairs matching the NMR Larmor frequency induces the experimentally observed absorptive central DNP profile, and the electron T1e modulated by temperature and magic-angle spinning alters the shape between an absorptive and dispersive feature. Understanding the microscopic origin is key to designing new PAs to harness the microwave-power-efficient DNP effect observed with BDPA variants.

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.

Tailored Polypeptide Star Copolymers for 3D Printing of Bacterial Composites Via Direct Ink Writing.

Hydrogels hold much promise for 3D printing of functional living materials; however, challenges remain in tailoring mechanical robustness as well as biological performance. In addressing this challenge, the modular synthesis of functional hydrogels from 3-arm diblock copolypeptide stars composed of an inner poly(l-glutamate) domain and outer poly(l-tyrosine) or poly(l-valine) blocks is described. Physical crosslinking due to ß-sheet assembly of these star block copolymers gives mechanical stability during extrusion printing and the selective incorporation of methacrylate units allows for subsequent photocrosslinking to occur under biocompatible conditions. This permits direct ink writing (DIW) printing of bacteria-based mixtures leading to 3D objects with high fidelity and excellent bacterial viability. The tunable stiffness of different copolypeptide networks enables control over proliferation and colony formation for embedded Escherichia coli bacteria as demonstrated via isopropyl ß-d-1-thiogalactopyranoside (IPTG) induction of green fluorescent protein (GFP) expression. This translation of molecular structure to network properties highlights the versatility of these polypeptide hydrogel systems with the combination of writable structures and biological activity illustrating the future potential of these 3D-printed biocomposites.

Discrete Libraries of Amphiphilic Poly(ethylene glycol) Graft Copolymers: Synthesis, Assembly, and Bioactivity.

Poly(ethylene glycol) (PEG) is an important and widely used polymer in biological and pharmaceutical applications for minimizing nonspecific binding while improving blood circulation for therapeutic/imaging agents. However, commercial PEG samples are polydisperse, which hampers detailed studies on chain length-dependent properties and potentially increases antibody responses in pharmaceutical applications. Here, we report a practical and scalable method to prepare libraries of discrete PEG analogues with a branched, nonlinear structure. These lipid-PEG derivatives have a monodisperse backbone with side chains containing a discrete number of ethylene glycol units (3 or 4) and unique functionalizable chain ends. Significantly, the branched, nonlinear structure is shown to allow for efficient nanoparticle assembly while reducing anti-PEG antibody recognition when compared to commercial polydisperse linear systems, such as DMG-PEG2000. By enabling the scalable synthesis of a broad library of graft copolymers, fundamental self-assembly properties can be understood and shown to directly correlate with the total number of PEG units, nature of the chain ends, and overall backbone length. These results illustrate the advantages of discrete macromolecules when compared to traditional disperse materials.

Superlubricity of pH-responsive hydrogels in extreme environments.

Poly(acrylamide-co-acrylic acid) (P(AAm-co-AA)) hydrogels are highly tunable and pH-responsive materials frequently used in biomedical applications. The swelling behavior and mechanical properties of these gels have been extensively characterized and are thought to be controlled by the protonation state of the acrylic acid (AA) through the regulation of solution pH. However, their tribological properties have been underexplored. Here, we hypothesized that electrostatics and the protonation state of AA would drive the tribological properties of these polyelectrolyte gels. P(AAm-co-AA) hydrogels were prepared with constant acrylamide (AAm) concentration (33 wt%) and varying AA concentration to control the amount of ionizable groups in the gel. The monomer:crosslinker molar ratio (200:1) was kept constant. Hydrogel swelling, stiffness, and friction behavior were studied by systematically varying the acrylic acid (AA) concentration from 0-12 wt% and controlling solution pH (0.35, 7, 13.8) and ionic strength (I = 0 or 0.25 M). The stiffness and friction coefficient of bulk hydrogels were evaluated using a microtribometer and borosilicate glass probes as countersurfaces. The swelling behavior and elastic modulus of these polyelectrolyte hydrogels were highly sensitive to solution pH and poorly predicted the friction coefficient (µ), which decreased with increasing AA concentration. P(AAm-co-AA) hydrogels with the greatest AA concentrations (12 wt%) exhibited superlubricity (µ = 0.005 ± 0.001) when swollen in unbuffered, deionized water (pH = 7, I = 0 M) and 0.5 M NaOH (pH = 13.8, I = 0.25 M) (µ = 0.005 ± 0.002). Friction coefficients generally decreased with increasing AA and increasing solution pH. We postulate that tunable lubricity in P(AAm-co-AA) gels arises from changes in the protonation state of acrylic acid and electrostatic interactions between the probe and hydrogel surface.

Ultra-stable all-solid-state sodium metal batteries enabled by perfluoropolyether-based electrolytes.

Rechargeable batteries paired with sodium metal anodes are considered to be one of the most promising high-energy and low-cost energy-storage systems. However, the use of highly reactive sodium metal and the formation of sodium dendrites during battery operation have caused safety concerns, especially when highly flammable liquid electrolytes are used. Here we design and develop solvent-free solid polymer electrolytes (SPEs) based on a perfluoropolyether-terminated polyethylene oxide (PEO)-based block copolymer for safe and stable all-solid-state sodium metal batteries. Compared with traditional PEO SPEs, our results suggest that block copolymer design allows for the formation of self-assembled nanostructures leading to high storage modulus at elevated temperatures with the PEO domains providing transport channels even at high salt concentration (ethylene oxide/sodium = 8/2). Moreover, it is demonstrated that the incorporation of perfluoropolyether segments enhances the Na+ transference number of the electrolyte to 0.46 at 80 °C and enables a stable solid electrolyte interface. The new SPE exhibits highly stable symmetric cell-cycling performance at high current density (0.5 mA cm-2 and 1.0 mAh cm-2, up to 1,000 h). Finally, the assembled all-solid-state sodium metal batteries demonstrate outstanding capacity retention, long-term charge/discharge stability (Coulombic efficiency, 99.91%; >900 cycles with Na3V2(PO4)3 cathode) and good capability with high loading NaFePO4 cathode (>1 mAh cm-2).

A multi-stage single photochrome system for controlled photoswitching responses.

The ability of molecular photoswitches to convert on/off responses into large macroscale property change is fundamental to light-responsive materials. However, moving beyond simple binary responses necessitates the introduction of new elements that control the chemistry of the photoswitching process at the molecular scale. To achieve this goal, we designed, synthesized and developed a single photochrome, based on a modified donor-acceptor Stenhouse adduct (DASA), capable of independently addressing multiple molecular states. The multi-stage photoswitch enables complex switching phenomena. To demonstrate this, we show spatial control of the transformation of a three-stage photoswitch by tuning the population of intermediates along the multi-step reaction pathway of the DASAs without interfering with either the first or final stage. This allows for a photonic three-stage logic gate where the secondary wavelength solely negates the input of the primary wavelength. These results provide a new strategy to move beyond traditional on/off binary photochromic systems and enable the design of future molecular logic systems.

Rational mechanochemical design of Diels-Alder crosslinked biocompatible hydrogels with enhanced properties.

An important but often overlooked feature of Diels-Alder (DA) cycloadditions is the ability for DA adducts to undergo mechanically induced cycloreversion when placed under force. Herein, we demonstrate that the commonly employed DA cycloaddition between furan and maleimide to crosslink hydrogels results in slow gelation kinetics and "mechanolabile" crosslinks that relate to reduced material strength. Through rational computational design, "mechanoresistant" DA adducts were identified by constrained geometries simulate external force models and employed to enhance failure strength of crosslinked hydrogels. Additionally, utilization of a cyclopentadiene derivative, spiro[2.4]hepta-4,6-diene, provided mechanoresistant DA adducts and rapid gelation in minutes at room temperature. This study illustrates that strategic molecular-level design of DA crosslinks can provide biocompatible materials with improved processing, mechanical durability, lifetime, and utility.

Design of Polymeric Zwitterionic Solid Electrolytes with Superionic Lithium Transport.

Progress toward durable and energy-dense lithium-ion batteries has been hindered by instabilities at electrolyte-electrode interfaces, leading to poor cycling stability, and by safety concerns associated with energy-dense lithium metal anodes. Solid polymeric electrolytes (SPEs) can help mitigate these issues; however, the SPE conductivity is limited by sluggish polymer segmental dynamics. We overcome this limitation via zwitterionic SPEs that self-assemble into superionically conductive domains, permitting decoupling of ion motion and polymer segmental rearrangement. Although crystalline domains are conventionally detrimental to ion conduction in SPEs, we demonstrate that semicrystalline polymer electrolytes with labile ion-ion interactions and tailored ion sizes exhibit excellent lithium conductivity (1.6 mS/cm) and selectivity (t + ≈ 0.6-0.8). This new design paradigm for SPEs allows for simultaneous optimization of previously orthogonal properties, including conductivity, Li selectivity, mechanics, and processability.

Carbon Nanotube Composites with Bottlebrush Elastomers for Compliant Electrodes.

Wearable electronics and biointerfacing technology require materials that are both compliant and conductive. The typical design strategy exploits polymer composites containing conductive particles, but the addition of a hard filler generally leads to a substantial increase in modulus that is not well-matched to biological tissue. Here, we report a new class of supersoft, conductive composites comprising carbon nanotubes (CNT) embedded in bottlebrush polymer networks. By virtue of the bottlebrush polymer architecture, these materials are several orders of magnitude softer than comparable composites in the literature involving linear polymer networks. For example, a CNT content of 0.25 wt % yields a shear modulus of 66 kPa while maintaining a typical conductivity for a CNT composite (ca. 10-2 S/m). An added benefit of this bottlebrush matrix chemistry is the presence of dynamic polyester bonds that facilitate thermal (re)processing. This unique strategy of designing soft composites provides new opportunities to tailor the structure and properties of sustainable advanced materials.

Biological Utility of Fluorinated Compounds: from Materials Design to Molecular Imaging, Therapeutics and Environmental Remediation.

The applications of fluorinated molecules in bioengineering and nanotechnology are expanding rapidly with the controlled introduction of fluorine being broadly studied due to the unique properties of C-F bonds. This review will focus on the design and utility of C-F containing materials in imaging, therapeutics, and environmental applications with a central theme being the importance of controlling fluorine-fluorine interactions and understanding how such interactions impact biological behavior. Low natural abundance of fluorine is shown to provide sensitivity and background advantages for imaging and detection of a variety of diseases with 19F magnetic resonance imaging, 18F positron emission tomography and ultrasound discussed as illustrative examples. The presence of C-F bonds can also be used to tailor membrane permeability and pharmacokinetic properties of drugs and delivery agents for enhanced cell uptake and therapeutics. A key message of this review is that while the promise of C-F containing materials is significant, a subset of highly fluorinated compounds such as per- and polyfluoroalkyl substances (PFAS), have been identified as posing a potential risk to human health. The unique properties of the C-F bond and the significant potential for fluorine-fluorine interactions in PFAS structures necessitate the development of new strategies for facile and efficient environmental removal and remediation. Recent progress in the development of fluorine-containing compounds as molecular imaging and therapeutic agents will be reviewed and their design features contrasted with environmental and health risks for PFAS systems. Finally, present challenges and future directions in the exploitation of the biological aspects of fluorinated systems will be described.