Divinyl Cross-linker Research Articles

Vinyl and methyl-ester groups in the insoluble polymer drug patiromer identified and quantified by solid-state NMR

Patiromer (Veltassa®) is a crosslinked, insoluble co-polymer drug used as a nonabsorbent potassium binder, approved for treatment of hyperkalemia. Quantitative solid-state 13C nuclear magnetic resonance (NMR) analysis with comprehensive peak assignment, component quantification, and calculation of mole and weight fractions of monomer units was performed on three doses of patiromer. The workflow is documented in detail. Spectrally edited solid-state 13C NMR spectra of patiromer show =CHn peaks of matching intensity at 116 and 141 ppm, characteristic of -CH=CH2 vinyl groups. Similar spectral features can be observed in earlier studies but were previously ignored. In this study, the vinyl signals are well-resolved in a 2-s direct polarization (DP) spectrum without and with dipolar dephasing, which confirms that these sp2-hybridized carbons are bonded to hydrogen and partially mobile, consistent with vinyl side groups from incompletely reacted divinyl crosslinkers. The vinyl groups account for 1.6% of all carbon, 3% of the monomer units, and nearly 1/3 of the crosslinkers. Furthermore, an unexpected OCH3 moiety accounting for ∼1.2% of all carbons was identified by spectral editing; its chemical shift of 54 ppm is more consistent with a methyl ester than with a methyl ether. It can originate from incomplete hydrolysis of ∼6% of methyl-2-fluoroacrylate, the main monomer of patiromer. Characteristic cross peaks in two-dimensional 1H–13C heteronuclear correlation NMR confirm the presence of the vinyl and OCH3 groups. Trace amounts of xanthan gum are also detected. The quantitative 13C NMR spectrum of patiromer has been matched in a simulation using a model with five monomer units.

Exceptionally Fast Temperature-Responsive, Mechanically Strong and Extensible Monolithic Non-Porous Hydrogels: Poly(N-isopropylacrylamide) Intercalated with Hydroxypropyl Methylcellulose.

Exceptionally fast temperature-responsive, mechanically strong, tough and extensible monolithic non-porous hydrogels were synthesized. They are based on divinyl-crosslinked poly(N-isopropyl-acrylamide) (PNIPAm) intercalated by hydroxypropyl methylcellulose (HPMC). HPMC was largely extracted after polymerization, thus yielding a 'template-modified' PNIPAm network intercalated with a modest residue of HPMC. High contents of divinyl crosslinker and of HPMC caused a varying degree of micro-phase-separation in some products, but without detriment to mechanical or tensile properties. After extraction of non-fixed HPMC, the micro-phase-separated products combine superior mechanical properties with ultra-fast T-response (in 30 s). Their PNIPAm network was highly regular and extensible (intercalation effect), toughened by hydrogen bonds to HPMC, and interpenetrated by a network of nano-channels (left behind by extracted HPMC), which ensured the water transport rates needed for ultra-fast deswelling. Moreover, the T-response rate could be widely tuned by the degree of heterogeneity during synthesis. The fastest-responsive among our hydrogels could be of practical interest as soft actuators with very good mechanical properties (soft robotics), while the slower ones offer applications in drug delivery systems (as tested on the example of Theophylline), or in related biomedical engineering applications.

Unusual Stress Upturn in Elastomers Prepared Using Macro Cross-Linkers with Multiple Vinyl Side Groups.

In this study, the unique tensile properties of acrylate elastomers prepared using macro cross-linker polymers with multiple vinyl side groups are analyzed. For the preparation of the macro cross-linker, poly(ethyl acrylate) copolymers bearing hydroxy functional groups are synthesized, followed by the hydroxy-isocyanate reaction with 2-isocyanatoethyl acrylate. Subsequently, the elastomers samples are prepared by UV polymerization of ethyl acrylate in the presence of the macro cross-linkers. The tensile properties of the elastomers in the small elongation region are similar to those of typical elastomers prepared using divinyl cross-linkers, whereas the stress upturn in the large elongation region is considerably different. The stress upturn varies based on the fraction of vinyl side groups in the macro cross-linkers, whereas stress in the small elongation region remains unchanged. These properties are analyzed using various theoretical models. The results reveal that there is artificial inhomogeneity in the cross-link density for samples prepared by the macro cross-linkers, where the short poly(ethyl acrylate) strands inside the macro cross-linker limit the overall chain stretchability. On the whole, this study demonstrates a new method for tuning elastomer properties, especially at large deformation.

Gelation in Photoinduced ATRP with Tuned Dispersity of the Primary Chains.

We investigated gelation in photoinduced atom transfer radical polymerization (ATRP) as a function of Cu catalyst loading and thus primary chain dispersity. Using parallel polymerizations of methyl acrylate with and without the addition of a divinyl crosslinker (1,6-hexanediol diacrylate), the approximate values of molecular weights and dispersities of the primary chains at incipient gelation were obtained. In accordance with the Flory-Stockmayer theory, experimental gelation occurred at gradually lower conversions when the dispersity of the primary chains increased while maintaining a constant monomer/initiator/crosslinker ratio. Theoretical gel points were then calculated using the measured experimental values of dispersity and initiation efficiency. An empirical modification to the Flory-Stockmayer equation for ATRP was implemented, resulting in more accurate predictions of the gel point. Increasing the dispersity of the primary chains was found not to affect the distance between the theoretical and experimental gel points and hence the extent of intramolecular cyclization. Furthermore, the mechanical properties of the networks, such as equilibrium swelling ratio and shear storage modulus showed little variation with catalyst loading and depended primarily on the crosslinking density.

(Invited) Cross-Linked Radiation-Grafted Anion-Exchange Membranes for Energy Conversion Systems: When to Cross-Link?

Anion-exchange membranes (AEM) are being developed for use in a wide range of electrochemical energy technologies including fuel cells (AEMFC), H2-generating electrolysers (AEM-WE), CO2 reduction cells (CO2ER), and reverse electrodialysis (RED). An interesting class of AEM is radiation-grafted types (RG-AEM), which can exhibit very high conductivities and favourable in situ water transport characteristics. Hence, RG-AEM have shown significant promise in application in AEMFCs, producing high performances and promising durabilities [Energy Environ. Sci., 12, 1575 (2019) and Nature Commun., 11, 3561 (2020)]. An Achilles heel with RG-AEM types is that they can swell excessively in water and have large dimensional changes between the dehydrated and hydrated states. This limits the ion-exchange capacities (IEC) that can be used: excessive IECs in RG-AEM will cause excessive swelling and poorer robustness. This clearly indicates that additional crosslinking is needed. As Kohl et al. have highlighted, optimised crosslinking can lead to production of high-IEC AEMs that are both robust enough to be < 20 µm in thickness and also low swelling [e.g. J. Electrochem. Soc., 166, F637 (2019)], allowing truly world-leading AEMFC performances.RG-AEMs are also being used as a screening platform for down-selecting different (cationic) head-group chemistries for use in RED cells (a salinity gradient power technology) [active UK EPSRC grant EP/R044163/1], where different head-groups may lead to different AEM characteristics such as: in-cell resistance (when in contact with aqueous electrolytes), permselectivity, and fouling characteristics (when real world waters such as industrial brines, seawater and freshwater are used). It was evident very early on in these studies that RG-AEMs (desirably) exhibit extremely low resistances but also (undesirably) very low permselectivities when un-crosslinked (less than the required 90%+). Our work on RG-type cation-exchange membranes [Sustainable Energy Fuels, 3, 1682 (2019)] clearly shows that introduction of crosslinking can improve permselectivity.Crosslinking always involves a compromise, where its introduction can improve a membrane characteristic (e.g. reduced swelling or improved permselectivity) but also leads to lower conductivities or poorer transport of chemical species through the membranes. Hence, crosslinking types and levels need to be carefully controlled. With RG-AEMs (made by electron-beam activation (peroxidation) of inert polymer films, followed by grafting of monomers and post-graft amination), we have a choice of introducing crosslinking at various stages. The figure below summarises the two different approaches to crosslinking that will be discussed in the presentation: adding a divinyl-type crosslinker into the grafting mixture or adding a diamine-type crosslinker into the amination step.This presentation will present the results from an initial investigation of these two crosslinking approaches. As well as crosslinking in the amination stage being practically easier and more repeatable (we used N,N,N',N'-tetramethyl-1,6-hexane diamine (TMHDA) as a model diamine, being readily commercially available) compared to adding divinylbenzene (DVB – a model commercially available divinyl crosslinking agent) in the grafting step, we will show that such diamine crosslinking also enhances desirable properties (such as permselectivity) with less sacrifice of conductivity (less increases in resistance) compared to the use of DVB crosslinking. Figure 1

Effects of Reaction Parameters on Water Absorption of Poly(itaconic acid) Superabsorbent Particles Synthesized by Inverse Suspension Polymerization

Inverse suspension polymerization method was applied to prepare poly(itaconic acid) based superabsorbent particles. The polymerization process was investigated to determine the influence of different parameters on the water absorption properties. It was found that processing parameters, such as oil/aqueous phase ratio, surfactant, stirring speed, as well as concentrations of initiator and crosslinker needed to be optimized to achieve high water absorbency. The hydrolysis sensitivity of the divinyl crosslinker in water affected the crosslinking efficiency to show better performance with hydrolytically stable diacrylamide than diacrylate. The washing solvent to remove surfactant also highly influence the water absorbency of the prepared SAP particles, and solvent with lower polarity induced the collapse of the pores in the SAP particles to give lower value of water absorbency.

Multiarm Star-Crosslinked Hydrogel: Polymer Network with Thermoresponsive Free-End Chains Densely Connected to Crosslinking Points.

Soft tissue in biological system is a hydrogel with elaborate structure exhibiting repeatable dynamic function. In order to approach such sophisticated system, precise construction of a designed network with multi-components is desired. This communication presents a novel hydrogel having highly dense stimuli-responsive free-end chains around crosslinking structure. A key molecule is a core-crosslinked star-shaped polymer with multiple thermoresponsive arms, which can be prepared by reversible addition-fragmentation chain transfer polymerization of divinyl crosslinker with poly(N-isopropylacrylamide) (PNIPAAm) macro-chain transfer agent and have a number of unreacted carbon-carbon double bonds in the core. These unreacted double bonds can be utilized as a crosslinker for poly(acrylamide) (PAAm) gel synthesis by free radical polymerization. The obtained gel contains homogeneously dispersed star PNIPAAms as crosslinking points and exhibits thermoresponsive swelling behavior in water depending on the star contents. In particular, the gel with low content of the star crosslinker shows localized responsive behavior with expansion and shrinkage of the star in one molecule. The mechanical properties of the star-crosslinked gel are significantly high compared to the conventional PAAm gels particularly in compressive strength (≈9MPa). Moreover, the star-crosslinked gel has thermoresponsive mechanical toughening property.

Controlled radical copolymerization of multivinyl crosslinkers: a robust route to functional branched macromolecules

AbstractControlled radical polymerization (CRP) has both revolutionized the synthesis of linear polymers and enabled unprecedented topological complexity. While the synthesis of many polymeric architectures requires careful planning and specialized precursors, branched macromolecules such as segmented hyperbranched polymers (SHPs), knotted polymers, core‐crosslinked stars (CCSs), and more can be synthesized through the copolymerization of vinyl monomers and divinyl crosslinkers in only a few steps. In the nearly two decades since its discovery, this strategy has helped elucidate the fundamental polymerization behavior of crosslinkers and also yielded a variety of functional and stimuli‐responsive materials. The purpose of this mini‐review is to therefore overview critical fundamental aspects of CRP of crosslinkers and materials derived therefrom. The process by which both SHPs and CCS polymers are synthesized, the effect of key reaction parameters and intriguing recent advances are described with the intent of both educating new researchers and inspiring new directions in this area. © 2020 Society of Industrial Chemistry

Crosslinker-Based Regulation of Swelling Behavior of Poly(N-isopropylacrylamide) Gels in a Post-Polymerization Crosslinking System.

A fundamental understanding of the effect of a crosslinker on gel properties is important for the design of novel soft materials because a crosslinking is a key component of polymer gels. We focused on post-polymerization crosslinking (PPC) system utilizing activated ester chemistry, which is a powerful tool due to structural diversity of diamine crosslinkers and less susceptibility to solvent effect compared to conventional divinyl crosslinking system, to systematically evaluate the crosslinker effect on the gel properties. A variety of alkyldiamine crosslinkers was employed for the synthesis of poly(N-isopropylacrylamide) (PNIPAAm) gels and it was clarified that the length of alkyl chains of diamine crosslinkers strongly affected the gelation reaction and the swelling behavior. The longer crosslinker induced faster gelation and decreased the swelling degree and the response temperature in water, while the crosslinking density did not significantly change. In addition, we were able to modify the polymer chains in parallel with crosslinking by using a monoamine modifier along with a diamine crosslinker. This simultaneous chain modification during crosslinking (SMC) was demonstrated to be useful for the regulation of the crosslinking density and the swelling behavior of PNIPAAm gels.

Uptake and Release of Species from Carbohydrate Containing Organogels and Hydrogels.

Hydrogels are used for a variety of technical and medical applications capitalizing on their three-dimensional (3D) cross-linked polymeric structures and ability to act as a reservoir for encapsulated species (potentially encapsulating or releasing them in response to environmental stimuli). In this study, carbohydrate-based organogels were synthesized by reversible addition-fragmentation chain transfer (RAFT) polymerization of a β-D-glucose pentaacetate containing methacrylate monomer (Ac-glu-HEMA) in the presence of a di-vinyl cross-linker; these organogels could be converted to hydrogels by treatment with sodium methoxide (NaOMe). These materials were studied using solid state 13C cross-polarization/magic-angle spinning (CP/MAS) NMR, Fourier transform infrared (FTIR) spectroscopy, and field emission scanning electron microscopy (FE-SEM). The swelling of the gels in both organic solvents and water were studied, as was their ability to absorb model bioactive molecules (the cationic dyes methylene blue (MB) and rhodamine B (RhB)) and absorb/release silver nitrate, demonstrating such gels have potential for environmental and biomedical applications.

Colloidal Stabilizer-Assisted Polymerization-Induced Precipitation Method for Colloidally Stable Polyacid Particles.

Near-monodispersed, colloidally stable, submicrometer-sized poly(acid phosphoxy ethyl methacrylate) (PAPEMA) latex particles were synthesized by free-radical dispersion polymerization using poly( N-vinylpyrrolidone) (PNVP) as both a steric colloidal stabilizer and a precipitating agent. Polymerization in the absence of PNVP led to a homogeneous transparent solution of PAPEMA, which indicates that the PNVP is essential for latex formation and the complex of PNVP and PAPEMA was formed during the dispersion polymerization. Dispersion copolymerizations with a divinyl cross-linking comonomer (∼20 wt % based on acid phosphoxy ethyl methacrylate) were also successful in synthesizing near-monodispersed, colloidally stable cross-linked PAPEMA latex particles, and the softness and p Ka values of the resulting PAPEMA latex particles can be controlled by varying the divinyl comonomer concentration. These sterically stabilized latex particles were characterized by electron microscopy, dynamic light scattering, X-ray photoelectron spectroscopy, elemental microanalysis, and Fourier transform infrared spectroscopy. Characterization results indicated that the PNVP colloidal stabilizer was likely to be located homogeneously on the particle surfaces and within the interior of particles. Finally, it was demonstrated that the PAPEMA latex particles worked as an effective surface modifier for metal surfaces.

Employing Heterocyclic Hypervalent Iodine Compounds with ICl Bonds as Initiators and Chain Transfer Agents in the Synthesis of Branched Polymers

AbstractHeterocyclic hypervalent (HV) iodine(III) compounds with ICl bonds and various substituents at the N atom are synthesized and found to be very efficient chain transfer agents in the polymerization of styrene with transfer coefficients exceeding that of CCl4 by 2–3 orders of magnitude, depending on the structure. The chain transfer rate coefficients are also determined. Due to the presence of thermally labile HV bonds, the compounds degrade homolytically upon heating and can initiate radical polymerization. For instance, 1‐chloro‐2‐hexyl‐1,2‐benziodazol‐3(2H)‐one, is used in the polymerization of styrene, which yields low molecular weight polymers with alkyl chloride groups at the α‐ (initiation) and the ω‐chain ends (transfer). Chain‐end functionalization reactions with azide and chain extension under low‐catalyst‐concentration atom transfer radical polymerization (ATRP) conditions of the prepared telechelic polymers are carried out. The same initiator/chain transfer agent is successfully employed in the synthesis of highly branched polymers with multiple alkyl chloride‐type chain ends when added to mixtures of styrene and 1,4‐divinylbenzene containing 10–80 mol% of the divinyl crosslinker, or even pure crosslinker. In all cases, soluble hyperbranched polymers are obtained up to moderate monomer conversions. The effects of crosslinker and HV iodine(III) compound concentrations on the polymerization outcome are studied systematically.

Triclosan nanoparticles via emulsion-freeze-drying for enhanced antimicrobial activity

Low water solubility and poor bioavailability of hydrophobic pharmaceuticals are significant problems in drug formulation. This research presents a bottom-up route to prepare nanoparticles of hydrophobic actives which is synthetically straightforward, robust, and can be applied to a range of active molecules. A series of amphiphilic branched diblock copolymers have been prepared via the conventional radical polymerization of a vinyl monomer (styrene, butylmethacrylate, or N-isopropylacrylamide) and a corresponding divinyl cross-linker facilitated by a poly(ethylene glycol)-based macro-initiator. These materials were employed as stabilizers in the emulsion-freeze-drying methodology to prepare nanoparticles of hydrophobic pharmaceuticals. It is demonstrated that these branched diblock copolymers are able to facilitate the formation of Triclosan nanoparticles which display enhanced antimicrobial activity against Candida albicans, when compared to non-processed (used as received) Triclosan. This process requires significantly lower levels of stabilizer compared to previously reported surfactant/polymer systems after optimization of polymer properties and morphology.

Cationic branched polymers for cellular delivery of negatively charged cargo

Receptor-independent cellular uptake of small molecule therapeutics is limited by their physical interaction with the negatively charged surface of cellular membranes. Passive diffusion through the hydrophobic membrane bilayer follows this process. Unless specific carriers exist in the biological membrane, such interactions limit therapeutics to those that are hydrophobic with modest positive charge at physiological pH. Small negatively charged molecules are therefore not efficient as therapeutics. To enable delivery of such molecules into eukaryotic cells, cationic branched polymers with tetraalkylammonium pendant groups were synthesized by copolymerization of a functional monomer (glycidyl methacrylate) with degradable and non-degradable divinyl crosslinkers in the presence of an efficient chain transfer agent, CBr4, followed by reaction of the multiple pendant epoxide groups and most of the alkyl bromide chain ends with amines. Cationic branched polymers with covalently attached fluorescent labels entered human cancerous and non-cancerous cells. The non-labeled analogues were able to carry anionic cargo (carboxyfluorescein) into the cells, while no uptake was observed in the absence of the cationic carriers. Most of the polymers were not significantly toxic at the concentrations used. This pilot study showed that cellular uptake of anionic small molecules can be promoted even in the absence of natural uptake mechanisms.

Effect of reaction conditions on poly(N-isopropylacrylamide) gels synthesized by post-polymerization crosslinking system

In this paper, the effect of gelation solvent and temperature on poly(N-isopropylacrylamide) (PNIPAAm) gels synthesized by post-polymerization crosslinking (PPC) was discussed in detail. PPC was two-step synthesis performed by (1) radical copolymerization of NIPAAm and activated ester monomer (NHSA) and (2) crosslinking reaction of the obtained prepolymer and diamine crosslinker. In PPC, various solvents could afford gels, while the gelation time was strongly dependent on solvent polarity. The obtained gels showed similar swelling curves in water, indicating that the network structure of PPC gels was dominantly determined by the prepolymer structure. It was quite contrasting to conventional divinyl crosslinking (DVC), by which gelation could be observed only in water and not in organic solvents under the same concentration condition as PPC gelation system. We also examined the effect of gelation temperature in PPC synthesis in water. The PPC-PNIPAAm gel prepared in water at high temperature was consistently white turbid as same as DVC-PNIPAAm gel, suggesting that this turbidity was derived from polymer aggregation and entanglement fixed by chemical crosslinking.

Employing a Sugar-Derived Dimethacrylate to Evaluate Controlled Branch Growth during Polymerization with Multiolefinic Compounds

Radical copolymerization of divinyl monomers in the presence of chain transfer agents leads to soluble hyperbranched polymers. In this work, hyperbranched poly(poly(ethylene glycol) methyl ether methacrylate) (PPEGMA) with degradable cross-linker branch points derived from glucarodilactone methacrylate was prepared via reversible addition–fragmentation chain transfer (RAFT) polymerization to provide insight into hyperbranch formation during copolymerizations of multiolefinic compounds. The number-average molecular weight of the polymers increased nonlinearly with monomer conversion, implying that the incorporation of the divinyl cross-linker led to chain branching and a rapid increase in molecular weight at high conversion. The degree of branching was varied by controlling the feed ratio of monomer to cross-linker to chain transfer agent. Hydrolytic degradation of the sugar-derived dilactone branch points was examined under acidic, neutral, and basic aqueous conditions. To provide fundamental insight into...

Direct one-pot synthesis of poly(ionic liquid) nanogels by cobalt-mediated radical cross-linking copolymerization in organic or aqueous media

Nanogels of controlled kinetic chain length were synthesized by cobalt-mediated radical cross-linking copolymerization (CMRccP) involving a vinyl monomer and a divinyl cross-linker.

Influence of intramolecular crosslinking on gelation in living copolymerization of monomer and divinyl cross-linker. Monte Carlo simulation studies

The effect of intramolecular crosslinking (IC) (cyclization) on gelation was studied using Monte Carlo simulations. The consumption of crosslinker in the IC process is proposed as one of the main reasons of significant overestimation of the gel point by Flory-Stockmayer theory. The system under study is atom transfer radical polymerization (ATRP) of a monomer and bifunctional (e.g. divinyl) crosslinker. The simulation method is based on dynamic lattice liquid algorithm (DLL) and reproduces changes of the system dynamics during polymerization. The effect of cyclization on gel point for various reagents ratios and dilutions was investigated. It is shown that intramolecular crosslinking does not change significantly the gel point in condensed systems (no solvent or below 10%). By contrast, it significantly increases gel points in diluted systems (40–90% of the solvent).

成長する架橋剤&amp;mdash;RAFT重合によりビニル基間の鎖長を変化させる架橋剤の合成とそれを用いたゲル化

成長する架橋剤&amp;mdash;RAFT重合によりビニル基間の鎖長を変化させる架橋剤の合成とそれを用いたゲル化

Monte Carlo Simulations of Free Radical Polymerizations with Divinyl Cross-Linker: Pre- and Postgel Simulations of Reaction Kinetics and Molecular Structure

A computationally efficient Monte Carlo method was used to simulate the reaction kinetics and molecular structure development during free-radical copolymerizations with divinyl monomers. A single parameter was used to describe the reduced reactivity of the pendent vinyl groups incorporated within the polymer backbone. The simulation results were compared with published experimental data for the bulk copolymerization of methyl methacrylate with different levels of ethylene glycol dimethacrylate. The model was able to effectively predict the reaction kinetics, the gel point, and sol–gel fractions in both the pre- and postgel regimes, including the swelling index of the gel. In the postgel regime the cross-linked molecule becomes the primary locus of reactions, and all chains eventually become part of this massive cross-linked polymer network. The Monte Carlo method allows the determination of the complete molecular structure as it evolves with time, including properties like cross-linking density, number of...