Crosslinking Units Research Articles

Engineering Supramolecular Hydrogels via Reversible Photoswitching of Cucurbit[8]uril-Spiropyran Complexation Stoichiometry.

The integration of photoswitchable supramolecular units into hydrogels allows for spatiotemporal control over their nanoscale topological network and macroscale properties using light. Nevertheless, the current availability of photoswitchable supramolecular interactions for the development of such materials remains limited. Here, the molecular design of a novel photoswitchable cucurbit[8]uril-spiropyran host-guest complex exhibiting fast and reversible switching of binding ratios between 1:2 and 1:1 is reported. Photoswitchable complexation stoichiometries are rationally exploited as (de)crosslinking units in multiple polymers for the design of supramolecular hydrogels displaying highly dynamic and switchable features that are spatiotemporally controlled by light. The hydrogels exhibit rapid reversible mechanical softening-hardening upon alternating irradiation with blue and UV light, which is used to significantly accelerate and improve the efficiency of self-healing and shape-remolding of hydrogels. Furthermore, spiropyran endows such materials with unique reversible photochromic properties for reproducible patterning/erasing and information storage. Using a dual-light-assisted extrusion process, meter-scale hydrogel fibers with enhanced structural integrity and photoswitchable ionic conductivity are constructed and woven into various slidable knots and fluorescent shapes. This work represents an innovative molecular design strategy for advancing the development of spatiotemporally engineered supramolecular hydrogels using light and opens avenues for their prospective applications in dynamic materials and adaptive systems.

Internal catalysis significantly promotes the bond exchange of covalent adaptable polyurethane networks

Self-healing covalent adaptable networks (CANs) are not only of fundamental interest but also of practical importance for achieving carbon neutrality and sustainable development. However, there is a trade-off between the mobility and cross-linking structure of CANs, making it challenging to develop CANs with excellent mechanical properties and high self-healing efficiency. Here, we report the utilization of a highly dynamic four-arm cross-linking unit with an internally catalyzed oxime-urethane group to obtain CAN-based ionogel with both high self-healing efficiency (>92.1%) at room temperature and superior mechanical properties (tensile strength 4.55 MPa and toughness 13.49 MJ m-3). This work demonstrates the significant potential of utilizing the synergistic electronic, spatial, and topological effects as a design strategy for developing high-performance materials.

Stability Enhancement by Hydrophobic Anchoring and a Cross-Linked Structure of a Phospholipid Copolymer Film for Medical Devices.

Surface modification using zwitterionic 2-methacryloyloxyethylphosphorylcholine (MPC) polymers is one of the most reasonable ways to prepare medical devices that can suppress undesired biological reactions such as blood coagulation. Usable MPC polymers are hydrophilic and water soluble, and their surface modification strategy involves exploiting the copolymer structures by adding physical or chemical bonding moieties. In this study, we developed copolymers composed of MPC, hydrophobic anchoring moiety, and chemical cross-linking unit to clarify the role of hydrophobic interactions in achieving biocompatible and long-term stable coatings. The four kinds of MPC copolymers with cross-linking units, such as 3-methacryloxypropyl trimethoxysilane (MPTMSi), and four different hydrophobic anchoring moieties, such as 3-(methacryloyloxy)propyltris(trimethylsiloxy)silane (MPTSSi) named as PMMMSi, n-butyl methacrylate (BMA) as PMBSi, 2-ethylhexyl methacrylate (EHMA) as PMESi, and lauryl methacrylate as PMLSi, were synthesized and coated on polydimethylsiloxane, polypropylene (PP), and polymethyl pentene. These copolymers were uniformly coated on the substrate materials PP and poly(methyl pentene) (PMP), to achieve hydrophilic and electrically neutral coatings. The results of the antibiofouling test showed that PMBSi repelled the adsorption of fluorescence-labeled bovine serum albumin the most, whereas PMLSi repelled it the least. Notably, all four copolymers suppressed platelet adhesion similarly. The variations in protein adsorption quantities among the four copolymer coatings were attributed to their distinct swelling behaviors in aqueous environments. Further investigations, including 3D scanning force microscopy and neutron reflectivity measurements, revealed that the PMLSi coating exhibited a higher water intake under aqueous conditions in comparison to the other coatings. Consequently, all copolymer coatings effectively prevented the invasion of platelets but the proteins penetrated the PMLSi network. Subsequently, the dynamic stability required to induce shear stress was evaluated using a circulation system. The results demonstrated that the PMMMSi and PMLSi coatings on PMP and PP exhibited exceptional platelet repellency and maintained high stability during circulation. This study highlights the potential of hydrophobic moieties to improve hemocompatibility and stability, offering potential applications in medical devices.

Stabilized, ROS-sensitive β-cyclodextrin-grafted hyaluronic supramolecular nanocontainers for CD44-targeted anticancer drug delivery

Hyaluronic acid (HA)-based tumor microenvironment-responsive nanocontainers are attractive candidates for anticancer drug delivery due to HA's excellent biocompatibility, biodegradability, and CD44-targeting properties. Nevertheless, the consecutive synthesis of stabilized, stealthy, responsive HA-based multicomponent nanomedicines generally requires multi-step preparation and purification procedures, leading to batch-to-batch variation and scale-up difficulties. To develop a facile yet robust strategy for promoted translations, a silica monomer containing a cross-linkable diethoxysilyl unit was prepared to enable in situ crosslinking without any additives. Further combined with the host-guest inclusion complexation between β-cyclodextrin-grafted HA (HA-CD) and ferrocene-functionalized polymers, ferrocene-terminated poly(oligo(ethylene glycol) methyl ether methacrylate (Fc-POEGMA) and Fc-terminated poly(ε-caprolactone)-b-poly(3-(diethoxymethylsilyl)propyl(2-(methacryloyloxy)ethyl) carbamate) (Fc-PCL-b-PDESPMA), a reactive oxygen species (ROS)-sensitive supramolecular polymer construct, Fc-POEGMA/Fc-PCL-b-PDESPMA@HA-CD was readily fabricated to integrate stealthy POEGMA, tumor active targeting HA, and an in situ cross-linkable PDESPMA sequence. Supramolecular amphiphilic copolymers with two different POEGMA contents of 25 wt% (P1) and 20 wt% (P2) were prepared via a simple physical mixing process, affording two core-crosslinked (CCL) micelles via an in situ sol-gel process of ethoxysilyl groups. The P1-based CCL micelles show not only desired colloidal stability against high dilution, but also an intracellular ROS-mimicking environment-induced particulate aggregation that is beneficial for promoted intracellular release of the loaded cargoes. Most importantly, P1-based nanomedicines exhibited greater cytotoxicity in CD44 receptor-positive HeLa cells than that in CD44 receptor-negative MCF-7 cells. Overall, this work developed HA-based nanomedicines with sufficient extracellular colloidal stability and efficient intracellular destabilization properties for enhanced anticancer drug delivery via smart integration of in situ crosslinking and supramolecular complexation.

Synthesis and study of the structure of copolymers of rarely crosslinked polyacrylic acid

The effect of synthesis conditions on the structure of acrylic acid and N,N-methylene bisacrylamide copolymers has been investigated. Optimal conditions for the synthesis of polymers with linear, tree-like, and crosslinked macromolecular structures have been established. The properties of the synthesized polymers, namely density, degree of swelling, gel fraction, etc., were investigated. It has been shown that copolymers with crosslinked macromolecules form hydrogels, the swelling degree of which considerably depends on the synthesis conditions. For copolymers forming hydrogels, the density of crosslinking units was determined based on the dependence of the density and equilibrium swelling degree.

Cucurbit[8]uril Mediated Supramolecular and Photocrosslinked Interpenetrating Network Hydrogel Matrices for 3D-Bioprinting.

Printing of biologically functional constructs is significant for applications in tissue engineering and regenerative medicine. Designing bioinks remains remarkably challenging due to the multifaceted requirements in terms of the physical, chemical, and biochemical properties of the three-dimensional matrix, such as cytocompatibility, printability, and shape fidelity. In order to promote matrix and materials stiffness, while not sacrificing stress relaxation mechanisms which support cell spreading, migration, and differentiation, this work reports an interpenetrating network (IPN) bioink design. The approach makes use of a chemically defined network, combining physical and chemical crosslinking units with a tunable composition and network density, as well as spatiotemporal control over post-assembly material stiffening. To this end, star-shaped poly(ethylene glycol)s functionalized with Phe-Gly-Gly tripeptide or photoactive stilbazolium are synthesized, and used to prepare three-dimensional networks with cucurbit[8]uril (CB[8]) through supramolecular host-guest complexation. The hydrogel obtained shows fast relaxation and thus supports the proliferation and differentiation of cells. Upon irradiation, the mechanical properties of the hydrogel can be rapidly adapted via selective photochemical dimerization of stilbazolium within CB[8], leading to IPNs with increased form stability while retaining the dynamic nature of the hydrogels. This modular approach opens new design opportunities for extrudable and cell-friendly dynamic biomaterials for applications in 3D-bioprinting.

Exploring Cyclodextrin-Based Nanosponges as Drug Delivery Systems: Understanding the Physicochemical Factors Influencing Drug Loading and Release Kinetics.

Cyclodextrin-based nanosponges (CDNSs) are complex macromolecular structures composed of individual cyclodextrins (CDs) and nanochannels created between cross-linked CD units and cross-linkers. Due to their unique structural and physicochemical properties, CDNSs can possess even more beneficial pharmaceutical features than single CDs. In this comprehensive review, various aspects related to CDNSs are summarized. Particular attention was paid to overviewing structural properties, methods of synthesis, and physicochemical analysis of CDNSs using various analytical methods, such as DLS, PXRD, TGA, DSC, FT-IR, NMR, and phase solubility studies. Also, due to the significant role of CDNSs in pharmaceutical research and industry, aspects such as drug loading, drug release studies, and kinetics profile evaluation of drug-CDNS complexes were carefully reviewed. The aim of this paper is to find the relationships between the physicochemical features and to identify crucial characteristics that are influential for using CDNSs as convenient drug delivery systems.

Large-scale preparation of composite membranes for CO2 separation via interfacial polymerization: Monomer selection and processing parameter optimization

The increasingly serious situation of CO2 emissions compels researchers to pay extensive attention to industrial processes for carbon capture. Membrane-based separation technology is widely regarded as a promising reserve method for carbon capture, featuring a wide adjustment range, flexible operation and modular design. In this work, a large-scale interfacial polymerization membrane production process for carbon capture was developed together with the construction of novel interfacial polymerization equipment with an adjustable organic phase bath and surface cross-linking unit. A monomer suitable for efficiently preparing high-performance CO2 separation membranes was selected through a combination of experiments and simulations. The effect of production conditions on the structure and performance of large-scale membranes was investigated. The performance resilience at high pressure and short-term stability in the presence of impurities of the optimized membranes were examined. Techno-economic evaluation targeting carbon capture from post-combustion gas verifies the significant industrial application potential of the membranes.

Biodegradable Dextrin-Based Microgels for Slow Release of Dual Fertilizers for Sustainable Agriculture.

In this research, we report dextrin-based biodegradable microgels (PDXE MGs) having phosphate-based cross-linking units for slow release of urea and a potential P source to improve fertilization. PDXE MGs (∼200 nm) are synthesized by cross-linking the lauroyl-functionalized dextrin chains with sodium tripolyphosphate. The developed PDXE MGs exhibit high loading (∼10%) and encapsulation efficiency (∼88%) for urea. It is observed that functionalization of PDXE MGs with lauroyl chains slows down the release of urea (90% in ∼24 days) as compared to nonfunctionalized microgels (PDX MGs) (99% in ∼17 days) in water. Further studies of the developed formulation display that Urea@PDXE MGs significantly boost maize seed germination and overall plant growth as compared to pure urea fertilizer. Moreover, analysis of maize leaves obtained from plants treated with Urea@PDXE MGs reveals 3.5 ± 0.3% nitrogen content and 90 ± 0.7 mg/g chlorophyll content. These values are significantly higher than 1.4 ± 0.6% nitrogen content and 48 ± 0.05 mg/g chlorophyll content obtained by using bare urea. Further, acid phosphatase activity in roots is reduced upon treatment with PDXE MGs and Urea@PDXE MGs, suggesting the availability of P upon degradation of PDXE MGs by the amylase enzyme in soil. These experimental results present the developed microgel-based biodegradable formulation with a slow release feature as a potential candidate to move toward sustainable agriculture practices.

A Holistic Review of C = C Crosslinkable Conjugated Molecules in Solution-Processed Organic Electronics: Insights into Stability, Processibility, and Mechanical Properties.

Solution-processable organic conjugated molecules (OCMs) consist of a series of aromatic units linked by σ-bonds, which present a relatively freedom intramolecular motion and intermolecular re-arrangement under external stimulation. The cross-linked strategy provides an effective platform to obtain OCMs network, which allows for outstanding optoelectronic, excellent physicochemical properties, and substantial improvement in device fabrication. An unsaturated double carbon-carbon bond (C = C) is universal segment to construct crosslinkable OCMs. In this review, the authors will set C = C cross-linkable units as an example to summarize the development of cross-linkable OCMs for solution-processable optoelectronic applications. First, this review provides a comprehensive overview of the distinctive chemical, physical, and optoelectronic properties arising from the cross-linking strategies employed in OCMs. Second, the methods for probing the C = C cross-linking reaction are also emphasized based on the perturbations of chemical structure and physicochemical property. Third, a series of model C = C cross-linkable units, including styrene, trifluoroethylene, and unsaturated acid ester, are further discussed to design and prepare novel OCMs. Furthermore, a concise overview of the optoelectronic applications associated with this approach is presented, including light-emitting diodes (LEDs), solar cells (SCs), and field-effect transistors (FETs). Lastly, the authors offer a concluding perspective and outlook for the improvement of OCMs and their optoelectronic application via the cross-linking strategy.

Triazine-Based Graphitic Carbon Nitride Thin Film as a Homogeneous Interphase for Lithium Storage.

Triazine-based graphitic carbon nitride is a semiconductor material constituted of cross-linked triazine units, which differs from widely reported heptazine-based carbon nitrides. Its triazine-based structure gives rise to significantly different physical chemical properties from the latter. However, it is still a great challenge to experimentally synthesize this material. Here, we propose a synthesis strategy via vapor-metal interfacial condensation on a planar copper substrate to realize homogeneous growth of triazine-based graphitic carbon nitride films over large surfaces. The triazine-based motifs are clearly shown in transmission electron microscopy with high in-plane crystallinity. An AB-stacking arrangement of the layers is orientationlly parallel to the substrate surface. Eventually, the as-prepared films show dense electrochemical lithium deposition attributed to homogeneous charge transport within this thin film interphase, making it a promising solution for energy storage.

Trimethylsilanol Cleaves Stable Azaylides As Revealed by Unfolding of Robust "Staudinger" Single-Chain Nanoparticles.

Herein, we disclose a unique and selective reagent for the cleavage of stable azaylides prepared by the nonhydrolysis Staudinger reaction, enabling the on-demand unfolding of robust single-chain nanoparticles (SCNPs). SCNPs with promising use in catalysis, nanomedicine, and sensing are obtained through intrachain folding of discrete synthetic polymer chains. The unfolding of SCNPs involving reversible interactions triggered by a variety of external stimuli (e.g., pH, temperature, light, and redox potential) or substances (e.g., competitive reagents, solvents, and anions) is well known. Conversely, methods for the unfolding (i.e., intrachain disassembly) of SCNPs with stronger covalent interactions are scarce. We show that trimethylsilanol (Me3SiOH) triggers the efficient unfolding of robust "Staudinger" SCNPs with stable azaylide (-N=P-) moieties as intrachain cross-linking units showing exceptional stability toward water, air, and CS2, a standard reagent for azaylides. As a consequence, Me3SiOH arises as a rare, exceptional, and valuable reagent for the cleavage of stable azaylides prepared by the nonhydrolysis Staudinger reaction.

Low dielectric polymers at high frequency with bulky adamantane groups as the linker

Two monomers with adamantane and thermo-crosslinkable benzocyclobutene (BCB) groups have been successfully synthesized. These two monomers can be cured to form polymers with low dielectric properties at a high frequency of 10 GHz.

Elasticity tuning of a hexameric hemoprotein-based hydrogel by mutation of its protein building block

Abstract Mutants of a hexameric hemoprotein reconstituted with an acryloyl group-tethered heme were prepared and used as cross-linkers to produce polyacrylamide hydrogels to evaluate the effect of mutations on their elastic modulus. The mutations decrease the heme-binding affinities in a solution state, reducing the Young's modulus by 30% relative to that of the wild-type protein-based hydrogel. Furthermore, a stimuli-responsive gel–sol transition occurs upon reduction of the mutant-based gel. This work indicates that the molecular-level heme affinity for the cross-linked protein units has an important influence on macro-level mechanical properties.

Microfluidic fabrication of encapsulated probiotic microspheres using cysteine-modified chitosan with dual functions of bacterial adhesion and intestinal mucosal adhesion

Compared with previous encapsulation methods, the emerging microfluidic approach has the potential of preparing monodispersed particles with considerable advantages, such as controlled size and morphology, stable yield, and enhanced repeatability. In addition to introducing probiotics to the intestine with high-viability, designing a novel carrier matrix to improve the mucoadhesion of probiotics in the intestine is imperative. Thus, in this study, the thiol groups of cysteine were grafted to chitosan to form disulfide bonds with the cysteine residues on the bacterial surface and mucus to achieve the dual function of probiotic adhesion and mucoadhesion. Upon examination, the adhesion rate of Bifidobacterium bifidum FL-276.1 (FL-276.1) to thiolated chitosan film increased by 1.33 times compared with non-modified chitosan film. Thiolated chitosan microspheres prepared by microfluidic method assisted by a crosslinking unit with a crosslinker of genipin had a uniform size distribution, high loading efficiency (80%) to FL-276.1, and improved resistance to simulated gastrointestinal digestion with a survival rate of FL-276.1 up to 92%. Moreover, the results of mucoadhesion test of thiolated chitosan microspheres demonstrated that the amount of thiolated chitosan microspheres adhered to the HT-29 cells was 2.27 times higher than that of chitosan microspheres. The monodispersed cysteine modified chitosan microspheres with dual adhesion function prepared by microfluidic technology has the potential to enhance the viability and function of probiotics after gastrointestinal digestion and intestinal adhesion.

Horizontal to perpendicular transition of lamellar and cylinder phases in block copolymer films induced by interface segregation of single-chain nanoparticles during solvent evaporation.

How to fabricate perpendicularly oriented domains (PODs) of lamellar and cylinder phases in block copolymer thin films remains a major challenge. In this work, via a coarse-grained molecular dynamics simulation study, we report a solvent evaporation strategy starting from a mixed solution of A-b-B-type diblock copolymers (DBCs) and single-chain nanoparticles (SCNPs) with the same composition, which is capable of spontaneously generating PODs in drying DBC films induced by the interface segregation of SCNPs. The latter occurs at both the free surface and substrate and, consequently, neutralizes the interface selectivity of distinct blocks in DBCs, leading to spontaneous formation of PODs at both interfaces. The interface segregation of SCNPs is related to the weak solvophilicity of the internal cross-linker units. A mean-field theory calculation demonstrates that the increase in the chemical potential of SCNPs in the bulk region drives their interface segregation along with solvent evaporation. We believe that such a strategy can be useful in regulating the PODs of DBC films in practical applications.

Improve the Crosslinking Reactivity of Nitrile: Design of Nitrile-Functionalized Pyrazine and its Hydrogen Bond-Assisted Nucleophilic Enhancement Study.

In this study, molecular engineering and biomimetic principles are utilized to prepare highly effective nitrile-functionalized pyrazine crosslinking units by exploiting pyrazine's unique nucleophilic strengthening mechanism and proton bonding ability. The curing behaviors of pyrazine-2,3-dicarbonitrile and phthalonitrile are investigated through model curing systems and molecular simulation. The results indicate that pyrazine-2,3-dicarbonitrile exhibits higher reactivity than phthalonitrile, promoted by amine. The cured products of pyrazine-2,3-dicarbonitrile predominantly comprise thermally stable azaisoindoline and azaphthalocyanine. This novel type of highly effective crosslinking unit, and the comprehended mechanism of action of pyrazine at the molecular level, significantly expand the application of pyrazine in materials science.

Doubly Threaded Slide-Ring Polycatenane Networks.

Crosslinking in polymer networks leads to intrinsic structural inhomogeneities that result in brittle materials. Replacing fixed covalent crosslinks with mobile ones in mechanically interlocked polymers (MIPs), such as in slide-ring networks (SRNs) in which interlocked crosslinks are formed when polymer chains are threaded through crosslinked rings, can lead to tougher, more robust networks. An alternative class of MIPs is the polycatenane network (PCN), in which the covalent crosslinks are replaced with interlocked rings that introduce the unusual catenane's mobility elements (elongation, rotation, and twisting) as connections between polymer chains. A slide-ring polycatenane network (SR-PCN), with doubly threaded rings embedded as crosslinks in a covalent network, combines the mobility features of both the SRNs and PCNs, where the catenated ring crosslinks can slide along the polymer backbone between the two limits of network bonding (covalent and interlocked). This work explores using a metal ion-templated doubly threaded pseudo[3]rotaxane (P3R) crosslinker, combined with a covalent crosslinker and a chain extender, to access such networks. A catalyst-free nitrile-oxide/alkyne cycloaddition polymerization was used to vary the ratio of P3R and covalent crosslinker to yield a series of SR-PCNs that vary in the amount of interlocked crosslinking units. Studies on their mechanical properties show that metal ions fix the rings in the network, leading to similar behavior as the covalent PEG gels. Removal of the metal ion frees the rings resulting in a high-frequency transition attributed to the additional relaxation of polymer chains through the catenated rings while also increasing the rate of poroelastic draining at longer timescales.

Heterogeneous Local Dynamics in Mussel-Inspired Elastomers

Materials with increased mechanical strength and toughness bearing mussel-inspired iron–catechol complexes and network architectures exhibit several dynamic features, e.g., high and broad glass-“transition” temperature, not explored so far. By combining differential scanning calorimetry and dielectric spectroscopy, the latter as a function of temperature and pressure, we have explored the increase in the glass temperature, Tg, and the concomitant increase in the breath of Tg in bioinspired networks bearing one (covalent) or two (covalent and coordination) types of cross-links. Cross-linked networks experience heterogeneous segmental dynamics that are responsible for the broad Tg range observed in the thermal measurements. The two distinct dynamics reflect the relaxation of segments in the vicinity versus more distant cross-linked units. The various topologies are shown to have different fragilities and tend to form stronger glasses with increasing network topology. In addition, the ionic conductivity is influenced by the segmental dynamics and the increased Tg in the networks. These features (reduced specific heat step, Δcp, at Tg and “strong” dynamic behavior) are also found in permanently cross-linked polymers with dynamic network topology known as vitrimers. The similarities in the two network systems are discussed.

Study of beyond nearest-neighbor environment and intermediate-range order in a sodium aluminosilicate geopolymer using Reverse Monte Carlo modeling

A large scale three-dimensional structural model of a geopolymer with an approximate composition of NaAlSi2O6.5.5H2O obtained by Reverse Monte Carlo (RMC) modeling based on experimental high-energy x-ray diffraction is presented for the first time in order to obtain information regarding beyond nearest-neighbor environment and intermediate-range order (IRO). RMC model exhibits a three-dimensional network consisting of randomly cross-linked AlO4 and SiO4 tetrahedral units with uniformly distributed Na atoms and H2O molecules. The bond angle distributions, i.e. T-O-T, O-T-O and Na-O-Na angles, are somewhat distorted with lower values compared to analogous crystal systems. The origin of the first peak in the structure factor indicating IRO is investigated using the partial structure factors; Na-Na, Si-Na, Al-Si, O-H, and H-H atom pairs are found to be the main contributors. Ring size distribution analysis demonstrates that the structure mainly involves 6-, 7- and 8-membered rings. The coherence length of these IRO characteristics is ∼10.3 Å.