Bottlebrush Copolymers Research Articles

Enhancing the Biomimetic Mechanics of Bottlebrush Graft-Copolymers through Selective Solvent Annealing.

Self-assembled networks of bottlebrush copolymers are promising materials for biomedical applications due to a unique combination of ultra-softness and strain-adaptive stiffening, characteristic of soft biological tissues. Transitioning from ABA linear-brush-linear triblock copolymers to A-g-B bottlebrush graft copolymer architectures allows significant increasing the mechanical strength of thermoplastic elastomers. Using real-time synchrotron small-angle X-ray scattering, it is shown that annealing of A-g-B elastomers in a selective solvent for the linear A blocks allows for substantial network reconfiguration, resulting in an increase of both the A domain size and the distance between the domains. The corresponding increases in the aggregation number and extension of bottlebrush strands lead to a significant increase of the strain-stiffening parameter up to 0.7, approaching values characteristic of the brain and skin tissues. Network reconfiguration without disassembly is an efficient approach to adjusting the mechanical performance of tissue-mimetic materials to meet the needs of diverse biomedical applications.

Bottlebrush Random Copolymers at Oil‐Oil Interfaces

Comprehensive SummaryOil‐in‐oil nonaqueous emulsions are of great interest for developing emulsion‐templated polymers and encapsulation systems that are incompatible with water‐sensitive substances. Tailor‐made amphiphilic block copolymers are by far the most efficient stabilizers for oil‐in‐oil emulsions while less attention is given to copolymers with more complex architectures. Here, we report the stabilization of DMSO‐silicone oil interface by bottlebrush random copolymers (BRCPs) containing norbornene backbones with densely grafted poly(methyl methacrylate) (PMMA) and polystyrene (PS) side chains. The assembly kinetics of BRCPs at the DMSO‐silicone oil interface can be divided into three processes, including diffusion, reconfiguration and reorganization, and can be varied by tuning the degree of polymerization of the backbone (NB). Due to the high efficiency of BRCPs in reducing the interfacial tension, when using BRCPs as stabilizers, stable silicone oil‐in‐DMSO traditional emulsions and high internal phase emulsions (HIPEs) can be successfully obtained, while no stable emulsions can be achieved with linear PMMA‐b‐PS serving as the stabilizer. This study, for the first time, underscores the great potential of amphiphilic bottlebrush copolymers in preparing oil‐in‐oil emulsions. Given the advances in polymerization strategy, a broad variety of amphiphilic bottlebrush copolymers are expected to be synthesized and applied in the stabilization of nonaqueous biphasic systems.

Ultrastable and Redispersible Zwitterionic Bottlebrush Micelles for Drug Delivery.

Bottlebrush copolymers are increasingly used for drug delivery and biological imaging applications in part due to the enhanced thermodynamic stability of their self-assemblies. Herein, we discuss the effect of hydrophilic block chemistry on the stability of bottlebrush micelles. Amphiphilic bottlebrushes with zwitterionic poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC) and nonionic polyethylene glycol (PEG) hydrophilic blocks were synthesized by "grafting from" polymerization and self-assembled into well-defined spherical micelles. Colloidal stability and stability against disassembly were challenged under high concentrations of NaCl, MgSO4, sodium dodecyl sulfate, fetal bovine serum, and elevated temperature. While both types of micelles appeared to be stable in many of these conditions, those with a PMPC shell consistently surpassed their PEG analogs. Moreover, when repeatedly subjected to lyophilization/resuspension cycles, PMPC micelles redispersed with no apparent variation in size or dispersity even in the absence of a cryoprotectant; PEG micelles readily aggregated. The observed excellent stability of PMPC micelles is attributed to the low critical micelle concentration of the bottlebrushes as well as to the strong hydration shell caused by ionic solvation of the phosphorylcholine moieties. Zwitterionic micelles were loaded with doxorubicin, and higher loading capacity/efficiency, as well as delayed release, was observed with increasing side-chain length. Finally, hemocompatibility studies of PMPC micelles demonstrated no disruption to the red blood cell membranes. The growing concern regarding the immunogenicity of PEG-based systems propels the search for alternative hydrophilic polymers; in this respect and for their outstanding stability, zwitterionic bottlebrush micelles represent excellent candidates for drug delivery and bioimaging applications.

Simple Approach to Synthesize Carbohydrate-based Janus-Type Bottlebrush Copolymers and Their Self-Assemblies in Sub-5 nm Features in Thin Films

Simple Approach to Synthesize Carbohydrate-based Janus-Type Bottlebrush Copolymers and Their Self-Assemblies in Sub-5 nm Features in Thin Films

Scaling Behavior of Solution Self-Assembled Micelle of Sequence-Controlled Bottlebrush Copolymer

Scaling Behavior of Solution Self-Assembled Micelle of Sequence-Controlled Bottlebrush Copolymer

Antioxidant activity of bottlebrush copolymers and its self-assembly in mixed monolayers with cholesterol in the presence of cerium nitrate

Antioxidant activity of bottlebrush copolymers and its self-assembly in mixed monolayers with cholesterol in the presence of cerium nitrate

Synthesis of Bottlebrush Polymers with Spontaneous Self-Assembly for Dielectric Generators.

Cross-linked bottlebrush polymers received significant attention as dielectrics in transducers due to their unique softness and strain stiffening caused by their structure. Despite some progress, there is still a great challenge in increasing their dielectric permittivity beyond 3.5 and cross-linking them to defect-free ultrathin films efficiently under ambient conditions. Here, we report the synthesis of bottlebrush copolymers based on ring-opening metathesis polymerization (ROMP) starting from a 5-norbornene-2-carbonitrile and a norbornene modified with a poly(dimethylsiloxane) (PDMS) chain as a macromonomer. The resulting copolymer was subjected to a postpolymerization modification, whereby the double bonds were used both for functionalization with thiopropionitrile and subsequent cross-linking via a thiol-ene reaction. The solutions of both bottlebrush copolymers formed free-standing elastic films by simple casting. DMA and broadband impedance spectroscopy revealed two glass transition temperatures uncommon for a random copolymer. The self-segregation of the nonpolar PDMS chains and the polynorbornane backbone is responsible for this and is supported by the interfacial polarization observed in broadband impedance spectroscopy and the scattering peaks observed in small-angle X-ray scattering (SAXS). Additionally, the modified bottlebrush copolymer was cross-linked to an elastomer that exhibits increased dielectric permittivity and good mechanical properties with significant strain stiffening, an attractive property of dielectric elastomer generators. It has a relative permittivity of 5.24, strain at break of 290%, elastic modulus at 10% strain of 380 kPa, a breakdown field of 62 V μm-1, and a small actuation of 5% at high electric fields of 48.5 V μm-1. All of these characteristics are attractive for dielectric elastomer generator applications. The current work is a milestone in designing functional elastomers based on bottlebrush polymers for transducer applications.

Drug-Polymer Nanodroplet Formation and Morphology Drive Solubility Enhancement of GDC-0810.

Nanodroplet formation is important to achieve supersaturation of active pharmaceutical ingredients (APIs) in an amorphous solid dispersion. The aim of the current study was to explore how polymer composition, architecture, molar mass, and surfactant concentration affect polymer-drug nanodroplet morphology with the breast cancer API, GDC-0810. The impact of nanodroplet size and morphology on dissolution efficacy and drug loading capacity was explored using polarized light microscopy, dynamic light scattering, and cryogenic transmission electron microscopy. Poly(N-isopropylacrylamide-stat-N,N-dimethylacrylamide) (PND) was synthesized as two linear derivatives and two bottlebrush derivatives with carboxylated or PEGylated end-groups. Hydroxypropyl methylcellulose acetate succinate grade MF (HPMCAS-MF) and poly(vinylpyrrolidone-co-vinyl acetate) (PVPVA) were included as commercial polymer controls. We report the first copolymerization synthesis of a PVPVA bottlebrush copolymer, which was the highest performing excipient in this study, maintaining 688 μg/mL GDC-0810 concentration at 60 wt % drug loading. This is likely due to strong polymer-drug noncovalent interactions and the compaction of GDC-0810 along the PVPVA bottlebrush backbone. Overall, it was observed that the most effective formulations had a hydrodynamic radius less than 25 nm with tightly compacted nanodroplet morphologies.

Flow-Driven Translocation of Strung Micelles Formed by Core–Shell Bottle-Brush Copolymers and the Accompanying Morphological Transformation through a Nanochannel

Flow-Driven Translocation of Strung Micelles Formed by Core–Shell Bottle-Brush Copolymers and the Accompanying Morphological Transformation through a Nanochannel

Self‐Assembly of Rod‐Coil Bottlebrush Copolymers into Degradable Nanodiscs with a UV‐Triggered Self‐Immolation Process

AbstractPolymer nanodiscs, especially with stimuli‐responsive features, represent an unexplored frontier in the nanomaterial landscape. Such 2D nanomaterials are considered highly promising for advanced biomedicine applications. Herein, we designed a rod‐coil copolymer architecture based on an amphiphilic, tadpole‐like bottlebrush copolymer, which can directly self‐assemble into core–shell nanodiscs in an aqueous environment. As the bottlebrush side chains are made of amorphous, UV‐responsive poly(ethyl glyoxylate) (PEtG) chains, they can undergo rapid end‐to‐end self‐immolation upon light irradiation. This triggered nanodisc disassembly can be used to boost small molecule release from the nanodisc core, which is further aided by a morphological change from discs to spheres.

Self-Assembly of Rod-Coil Bottlebrush Copolymers into Degradable Nanodiscs with a UV-Triggered Self-Immolation Process.

Polymer nanodiscs, especially with stimuli-responsive features, represent an unexplored frontier in the nanomaterial landscape. Such 2D nanomaterials are considered highly promising for advanced biomedicine applications. Herein, we designed a rod-coil copolymer architecture based on an amphiphilic, tadpole-like bottlebrush copolymer, which can directly self-assemble into core-shell nanodiscs in an aqueous environment. As the bottlebrush side chains are made of amorphous, UV-responsive poly(ethyl glyoxylate) (PEtG) chains, they can undergo rapid end-to-end self-immolation upon light irradiation. This triggered nanodisc disassembly can be used to boost small molecule release from the nanodisc core, which is further aided by a morphological change from discs to spheres.

Synthesis of Multiblock Bottlebrush Copolymers with Well-Defined Arbitrary Monomer Sequences: Key Factors Influencing Catalytic Stability

Synthesis of Multiblock Bottlebrush Copolymers with Well-Defined Arbitrary Monomer Sequences: Key Factors Influencing Catalytic Stability

Self-assembly prediction of architecture-controlled bottlebrush copolymers in solution using graph convolutional networks.

The investigation of bottlebrush copolymer self-assembly in solution involves a comprehensive approach integrating simulation and experimental research, due to their unique physical characteristics. However, the intricate architecture of bottlebrush copolymers and the diverse solvent conditions introduce a wide range of parameter spaces. In this study, we investigated the solution self-assembly behavior of bottlebrush copolymers by combining dissipative particle dynamics (DPD) simulation results and machine learning (ML) including graph convolutional networks (GCNs). The architecture of bottlebrush copolymers is encoded by graphs including connectivity, side chain length, bead types, and interaction parameters of DPD simulation. Using GCN, we accurately predicted the single chain properties of bottlebrush copolymers with over 95% accuracy. Furthermore, phase behavior was precisely predicted using these single chain properties. Shapley additive explanations (SHAP) values of single chain properties to the various self-assembly morphologies were calculated to investigate the correlation between single chain properties and morphologies. In addition, we analyzed single chain properties and phase behavior as a function of DPD interaction parameters, extracting relevant physical properties for vesicle morphology formation. This work paves the way for tailored design in solution of self-assembled nanostructures of bottlebrush copolymers, offering a GCN framework for precise prediction of self-assembly morphologies under various chain architectures and solvent conditions.

Straightforward synthesis of complex polymeric architectures with ultra-high chain density.

Synthesis of complex polymeric architectures (CPAs) via reversible-deactivation radical polymerization (RDRP) currently relies on the rather inefficient attachment of monofunctional initiation/transfer sites onto CPA precursors. This drawback seriously limits the overall functionality of the resulting (macro)initiators and, consequently, also the total number of installable polymeric chains, which represents a significant bottleneck in the design of new polymeric materials. Here, we show that the (macro)initiator functionality can be substantially amplified by using trichloroacetyl isocyanate as a highly efficient vehicle for the rapid and clean introduction of trichloroacetyl groups (TAGs) into diverse precursors. Through extensive screening of polymerization conditions and comprehensive NMR and triple-detection SEC studies, we demonstrate that TAGs function as universal trifunctional initiators of copper-mediated RDRP of different monomer classes, affording low-dispersity polymers in a wide molecular weight range. We thus unlock access to a whole new group of ultra-high chain density CPAs previously inaccessible via simple RDRP protocols. We highlight new opportunities in CPA synthesis through numerous examples, including the de novo one-pot synthesis of a novel "star-on-star" CPA, the preparation of β-cyclodextrin-based 45-arm star polymers, and facile grafting from otherwise problematic cellulose substrates both in solution and from surface, obtaining effortlessly ultra-dense, ultra-high-molecular weight bottle-brush copolymers and thick spatially-controlled polymeric coatings, respectively.

Janus bottlebrush compatibilizers.

Bottlebrush random copolymers (BRCPs), consisting of a random distribution of two homopolymer chains along a backbone, can segregate to the interface between two immiscible homopolymers. BRCPs undergo a reconfiguration, where each block segregates to one of the homopolymer phases, adopting a Janus-type structure, reducing the interfacial tension and promoting adhesion between the two homopolymers, thereby serving as a Janus bottlebrush copolymer (JBCP) compatibilizer. We synthesized a series of JBCPs by copolymerizing deuterated or hydrogenated polystyrene (DPS/PS) and poly(tert-butyl acrylate) (PtBA) macromonomers using ruthenium benzylidene-initiated ring-opening metathesis polymerization (ROMP). Subsequent acid-catalyzed hydrolysis converted the PtBA brushes to poly(acrylic acid) (PAA). The JBCPs were then placed at the interface between DPS/PS homopolymers and poly(2-vinyl pyridine) (P2VP) homopolymers, where the degree of polymerization of the backbone (NBB) and the grafting density (GD) of the JBCPs were varied. Neutron reflectivity (NR) was used to determine the interfacial width and segmental density distributions (including PS homopolymer, PS block, PAA block and P2VP homopolymer) across the polymer-polymer interface. Our findings indicate that the star-like JBCP with NBB = 6 produces the largest interfacial broadening. Increasing NBB to 100 (rod-like shape) and 250 (worm-like shape) reduced the interfacial broadening due to a decrease in the interactions between blocks and homopolymers by stretching of blocks. Decreasing the GD from 100% to 80% at NBB = 100 caused an increase the interfacial width, yet further decreasing the GD to 50% and 20% reduced the interfacial width, as 80% of GD may efficiently increase the flexibility of blocks and promote interactions between homopolymers, while maintaining relatively high number of blocks attached to one molecule. The interfacial conformation of JBCPs was further translated into compatibilization efficiency. Thin film morphology studies showed that only the lower NBB values (NBB = 6 and NBB = 24) and the 80% GD of NBB = 100 had bicontinuous morphologies, due to a sufficient binding energy that arrested phase separation, supported by mechanical testing using asymmetric double cantilever beam (ADCB) tests. These provide fundamental insights into the assembly behavior of JBCPs compatibilizers at homopolymer interfaces, opening strategies for the design of new BCP compatibilizers.

Saltwater-Induced Rapid Gelation of Photoredox-Responsive Mucomimetic Hydrogels.

Shear-thinning hydrogels represent an important class of injectable soft materials that are often used in a wide range of biomedical applications. Creation of new shear-thinning materials often requires that factors such as viscosity, injection rate/force, and needle gauge be evaluated to achieve efficient delivery, while simultaneously protecting potentially sensitive cargo. Here, a new approach to establishing shear-thinning hydrogels is reported where a host-guest cross-linked network initially remains soluble in deionized water but is kinetically trapped as a viscous hydrogel once exposed to saltwater. The shear-thinning properties of the hydrogel is then "switched on" in response to heating or exposure to visible light. These hydrogels consist of polynorbornene-based bottlebrush copolymers with porphyrin- and oligoviologen-containing side chains that are cross-linked through the reversible formation of β-cyclodextrin-adamantane inclusion complexes. The resultant viscous hydrogels display broad adhesive properties across polar and nonpolar substrates, mimicking that of natural mucous and thus making it easier to distribute onto a wide range of surfaces. Additional control over the hydrogel's mechanical properties (storage/loss moduli) and performance (adhesion) is achieved post-injection using a low-energy (blue light) photoinduced electron-transfer process. This work envisions these injectable copolymers and multimodal hydrogels can serve as versatile next-generation biomaterials capable of light-based mechanical manipulation post-injection.

Diblock bottlebrush polymer in a non-polar medium: Self-assembly, surface forces, and superlubricity

Whilst bottlebrush polymers have been studied in aqueous media for their conjectured role in biolubrication, surface forces and friction mediated by bottlebrush polymers in non-polar media have not been previously reported. Here, small-angle neutron scattering (SANS) showed that a diblock bottlebrush copolymer (oligoethyleneglycol acrylate/ethylhexyl acrylate; OEGA/EHA) formed spherical core–shell aggregates in n-dodecane (a model oil) in the polymer concentration range 0.1–2.0 wt%, with a radius of gyration Rg ∼ 7 nm, comprising 40–65 polymer molecules per aggregate. The surface force apparatus (SFA) measurements revealed purely repulsive forces between surfaces bearing inhomogeneous polymer layers of thickness L ∼ 13–23 nm, attributed to adsorption of a mixture of polymer chains and surface-deformed micelles. Despite the surface inhomogeneity, the polymer layers could mediate effective lubrication, demonstrating superlubricity with the friction coefficient as low as µ ∼ 0.003. The analysis of velocity-dependence of friction using the Eyring model shed light on the mechanism of the frictional process. That is, the friction mediation was consistent with the presence of nanoscopic surface aggregates, with possible contributions from a gel-like network formed by the polymer chains on the surface. These unprecedented results, correlating self-assembled polymer micelle structure with the surface forces and friction the polymer layers mediate, highlight the potential of polymers with the diblock bottlebrush architecture widespread in biological living systems, in tailoring desired surface interactions in non-polar media.

Anisotropy in Antimicrobial Bottle Brush Copolymers and Its Influence on Biological Activity

AbstractAntimicrobial polymers are a promising alternative to conventional antibiotics in the fight against antimicrobial resistance. Cationic bottle brush copolymers have shown to be superior to linear topologies in previous studies. Herein, the aspect ratio of such polymers is varied creating differently shaped confined unimolecular structures with varying degrees of side chain mobility. Using reversible addition‐fragmentation chain‐transfer (RAFT) polymerization, bottle brushes are produced in a one‐pot procedure. The morphology is confirmed by atomic force microscopy. The hydrophobicity, as determined via high performance‐liquid chromatography (HPLC) analysis, is drastically influenced by the topology. Using Fourier‐transform infrared (FTIR) spectroscopy, it is found that polymers with a high side chain mobility and increased global hydrophilicity, are less hydrated, and have stronger intramolecular hydrogen bonds. A phase segregated morphology leading to unimolecular micellization is assumed. Biological tests reveal increased antimicrobial activity for such segregated polymers. Their excellent hemocompatibility results in highly selective antimicrobial polymers whose adaptability seems to be a key feature in their excellent performance. This study highlights the tremendous importance of structural control in antimicrobial polymers.

Synthetic Evolution of a Supramolecular Harpooning Mechanism to Immobilize Vesicles at Antifouling Interfaces

AbstractThe immobilization of vesicles has been conceptualized as a method to functionalize biointerfaces. However, the preservation of their integrity post immobilization remains a considerable challenge. Interfacial interactions can cause vesicle rupture upon close surface contact and non‐specific protein adsorption impairing surface functions. To date, immobilization of vesicles has relied solely on either entrapment or prior modification of vesicles, both of which require laborious preparation and limit their applications. This work develops a bioinspired strategy to pin vesicles without prior modification while preserving their intact shape. This work introduces antifouling diblock copolymers and ultrathin surface‐attached hydrogels containing a brush‐like interface consisting of a bottle brush copolymer of N‐(2‐hydroxypropyl) methacrylamide (HPMA) and N‐(3‐methacrylamidopropyl)‐N,N‐dimethyldodecan‐1‐aminiumiodide (C12+). The presence of positive charges generates an attractive force that pulls vesicles toward the surface. At the surface, the amphiphilic properties of the combs facilitate their insertion into the membrane, mimicking the harpooning mechanism observed in antimicrobial peptides. Importantly, the antifouling poly(HPMA) backdrop serves to safeguard the vesicles by preventing deformation and breakage. Using a combination of thermodynamic analysis, surface plasmon resonance, and confocal laser scanning microscopy, this work demonstrates the efficiency of this biomimetic system to capture vesicles while maintaining an antifouling interface necessary for bioapplications.

Quantitative X‐ray scattering and reflectivity measurements of polymer thin films with 2D detectors

AbstractWe describe a fully open‐sourced Python package to process raw X‐ray scattering data using a GANESHA SAXSLAB facility, and review in this manuscript the connection of X‐ray scattering theories with the open‐sourced package. This package affords researchers more flexibility in analyzing and visualizing X‐ray scattering and reflectivity data from what is now a commonplace facility at many universities and research laboratories engaged in polymer research. We briefly review the applications of X‐ray scattering and diffraction, followed by the scattering theories. A pedagogical introduction to processing X‐ray scattering data is provided using the modules in the Python package. We compare conventions to visualize and interpret transmission and grazing‐incidence scattering data using self‐assembled lamellar morphology of bottlebrush copolymers as an example, then describe how area detectors measure specular and off‐specular reflectivity. Examples of in‐house reflectivity and grazing incidence scattering for the metrological examination of a grating are provided, where the full pitch and pitch height of a line pattern is measured easily without needing to simulate the full scattering intensity profile.