Reversible Schiff Base Research Articles

Hofmeister effect driven dynamic-bond cross-linked dialdehyde xylan hydrogels with rapid response and robust mechanical properties for expanding stent

The biomedical field urgently needs for programmable stent materials with nontoxic, autonomous self-healing, injectability, and suitable mechanical strength, especially self-expanding characteristics. However, such materials are still lacking. Herein, based on gelatin and dialdehyde-functionalized xylan, we synthesized 3D-printable, autonomous, self-healing, and mechanically robust hydrogels with a reversible Schiff base crosslink network. The hydrogels exhibited excellent mechanical properties and automatic healing properties at room temperature. The solid mechanical properties originate from the Schiff base, hydrogen bonding interactions, and xylan nanoparticle reinforcement of the polymer networks. As a proof of concept, the Hofmeister effect enabled the hydrogel to contract in highly concentrated salt solutions. In contrast, the same hydrogel expanded and relaxed in dilute salt solutions (quick response within 10 s), showing ionic stimulus-response and excellent shape memory characteristics, which demonstrated that the prepared hydrogel could be used as self-expanding artificial vascular stents. In particular, good biocompatibility was confirmed by cytotoxicity and compatibility tests, and ex vivo arterial experiments further indicated the feasibility of these artificial vascular scaffolds (the expansion force reached 1.51 N). Combined with its ionic stimuli-responsive shape memory ability, the strong mechanical, self-healing, 3D-printable, and biocompatibility properties make this hydrogel a promising material for artificial stents in various biomedical applications.

Exos-Loaded Gox-Modified Smart-Response Self-Healing Hydrogel Improves the Microenvironment and Promotes Wound Healing in Diabetic Wounds.

Wound management has always been a challenge in the clinical treatment of diabetes. In this study, glucose oxidase (GOx) is grafted onto natural pullulan polysaccharides, and oxidization is carried out to form a self-healing hydrogel using carboxymethyl chitosan by means of reversible Schiff base covalent bonding. The smart-response drug release properties of this natural self-healing hydrogel are demonstrated in diabetic wounds by taking advantage of two key factors, namely the pH-responsive nature of Schiff base bonding and the fact that GOx reduces the pH in diabetic wounds. To further enhance the biological functions of the hydrogel dressing, exosomes (Exos) are introduced into the hydrogel system. The GOx present in the hydrogel system improves the high-glucose microenvironment of diabetic wounds, releasing H2O2 to impart antimicrobial effects, and ensuring that the hydrogel realizes a smart-response function. The carboxymethyl chitosan component used to construct the hydrogel plays an effective antibacterial role. Moreover, the Exos loaded into the hydrogel effectively promotes neovascularization of the wound. The Exos also regulates macrophage polarization and reduces the levels of persistent inflammation in diabetic wounds. These results suggest that this smart responsive, multifunctional, and self-healing hydrogel dressing is ideal for the management of diabetic wounds.

Linkage-Mixed Covalent Organic Frameworks Synthesized by a Liquid-Solid Two-Phase Strategy for Photoenhanced Uranium Extraction.

Synthesizing COFs with hybrid linkage coupling with both reversible and irreversible natures remains a challenging issue. Herein, we report the synthesis of two rare COFs constructed by both reversible and irreversible linkages through a liquid-solid two-phase strategy. A systematic study reveals a one-pot, two-step reaction mechanism for the two COFs, the first step being a reversible Schiff base reaction and the second step being an irreversible Knoevenagel reaction. Interestingly, this hybrid linkage COF is found to show an outstanding photoenhanced uranium extraction performance. The results not only provide a general and green approach to develop the linkage chemistry of COFs but also enrich the synthesis toolboxes and application of COFs.

Injectable Nanocomposite Hydrogels Improve Intraperitoneal Co-delivery of Chemotherapeutics and Immune Checkpoint Inhibitors for Enhanced Peritoneal Metastasis Therapy.

Intraperitoneal co-delivery of chemotherapeutic drugs (CDs) and immune checkpoint inhibitors (ICIs) brings hope to improve treatment outcomes in patients with peritoneal metastasis from ovarian cancer (OC). However, current intraperitoneal drug delivery systems face issues such as rapid drug clearance from lymphatic drainage, heterogeneous drug distribution, and uncontrolled release of therapeutic agents into the peritoneal cavity. Herein, we developed an injectable nanohydrogel by combining carboxymethyl chitosan (CMCS) with bioadhesive nanoparticles (BNPs) based on polylactic acid-hyperbranched polyglycerol. This system enables the codelivery of CD and ICI into the intraperitoneal space to extend drug retention. The nanohydrogel is formed by cross-linking of aldehyde groups on BNPs with amine groups on CMCS via reversible Schiff base bonds, with CD and ICI loaded separately into BNPs and CMCS network. BNP/CMCS nanohydrogel maintained the activity of the biomolecules and released drugs in a sustained manner over a 7 day period. The adhesive property, through the formation of Schiff bases with peritoneal tissues, confers BNPs with an extended residence time in the peritoneal cavity after being released from the nanohydrogel. In a mouse model, BNP/CMCS nanohydrogel loaded with paclitaxel (PTX) and anti-PD-1 antibodies (αPD-1) significantly suppressed peritoneal metastasis of OC compared to all other tested groups. In addition, no systemic toxicity of nanohydrogel-loaded PTX and αPD-1 was observed during the treatment, which supports potential translational applications of this delivery system.

Injectable hemostatic hydrogel adhesive with antioxidant, antibacterial and procoagulant properties for hemorrhage wound management

In emergencies, uncontrolled severe bleeding can result in undesired complications and even death of the injured. Designing advanced hemostatic agents is a potential solution for emergency hemostasis, yet it remains challenging to realize the persistent adhesion in a wet wound environment. In this study, based on dynamic reversible Schiff base bond and photo-initiated double-bond polymerization, a novel injectable hemostatic hydrogel (L-COC) consisting of methacrylated carboxymethyl chitosan (CMCSMA), oxidized konjac glucomannan (OKGM) and (+)-catechin hydrate (CH) was synthesized for emergency hemostasis. To our delight, the incorporated CH imparted enhanced blood procoagulantion to the L-COC hydrogel by intensifying the hydrogel-red blood cell interactions. As a result, the hemostatic effect of the engineered L-COC hydrogel was significantly superior to that of fluid gelatin SurgifloTM for liver bleeding wounds in rats (Blood loss: 0.62 ± 0.11 g (L-COC), 0.90 ± 0.08 g (SurgifloTM); hemostasis time: 69.0 ± 2.9 s (L-COC), 84.0 ± 2.2 s (SurgifloTM)). With the favorable antioxidant and antibacterial activities, as well as multifunctional properties, the bio-adhesive L-COC hydrogel and the underlying design principles may facilitate further development of practical hemostatic hydrogels.

Facile synthesis of mechanically robust and injectable tetra-polyethylene glycol/methacrylate chitosan double-network hydrogel cartilage repair

The development of advanced hydrogel scaffolds with good biocompatibility, mechanical strength and bioactive property is highly desirable in cell growth, proliferation, and differentiation for the cartilage tissue regeneration. Herein, we reported a simple, inexpensive, feasible, and environmentally benign strategy to synthesize a biocompatible polyethylene glycol-based methacrylate-modified chitosan (PCSMA) double network (DN) hydrogel via the reversible Schiff base reaction and successive photopolymerization between the tetra-poly (ethylene glycol) aldehyde (Tetra-PEG-CHO) and methacrylate-modified chitosan (CSMA) in mild conditions. The four-terminated CHO groups were hypothesized to not only construct the whole architectural network through the dynamic pH-responsive Schiff base but also contribute to the injectable behavior and good tissue adhesion, which may furnish the surgeon with the availability of injectable and shapeless ability to fill in the gaps. Compared to the single PCS hydrogel with the main similar components of the tetra-PEG-CHO and pure CS moieties, the post-fabrication of PCSMA DN hydrogel possessed slower degradation time, denser network, and stronger mechanical stability, which could facilitate the bone marrow mesenchymal stem cell (BMSCs) activity and promote the chondrogenic differentiation for facilitating cartilage regeneration. Our study highlights the positive effects on chondrogenic performance and supports the PCSMA hydrogel as a promising tissue-engineered scaffold for the cartilage defect repair.

Mesenchymal Stem Cell Exosome-Integrated Antibacterial Hydrogels for Nasal Mucosal Injury Treatment.

Hydrogels have emerged as appealing prospects for wound healing due to their superior biocompatible qualities. However, the integration of antibacterial active substances into hydrogels for effective wound repair remains challenging. Here, we present a novel double-network hydrogel for nasal mucosal injury repair with antibacterial and self-healing capabilities. This hydrogel is the result of mixing aldehyde polyethylene glycol (PEG) and a carboxymethyl chitosan (CMCS)-based hydrogel with a photocured methylacrylate gelatin (GelMA) hydrogel to envelop mesenchymal stem cell exosomes (MSC-Exos). CMCS is rich in amino groups and facilitates antibacterial repair. Given the dynamically reversible Schiff base connections between the amino group of chitosan and the aldehyde group of modified PEG, the hydrogel can be easily injected into the lesion site because of its excellent injection and shear thinning properties. GelMA introduces an additional network layer for the hydrogel, which enhances its strength and extends the duration of stem cell exosomes on the wound surface. On the basis of these characteristics, we provide evidence that this compound hydrogel can substantially increase cell proliferation and regeneration, inhibit scar hyperplasia, and stimulate angiogenesis in rabbit nasal septum mucosa trauma models. These results suggest that MSC exosome-loaded hydrogels (ME-Gel) have substantial clinical potential for the repair and regeneration of nasal mucosa after surgery or trauma.

Highly flexible yet strain-insensitive conjugated polymer.

Imparting excellent electrical properties, mechanical robustness, suppleness, conduction stability during deformation, and self-healing to intrinsic conducting polymers is a challenging endeavor. The reversibly interlocked macromolecular networks (RILNs) approach is utilized to tackle this problem. Specifically, poly(3,4-ethylenedioxythiophene) (PEDOT) is mixed with flexible polysulfonic acid networks crosslinked by reversible Diels-Alder bonds, while rigid polyaniline networks crosslinked by reversible Schiff base bonds act as molecular staples. Owing to the joint actions of the doping effect of polyaniline on PEDOT, the specific interlocking architecture and synergy between the component materials, the electrical conductivity (59.3-980.5 S cm-1), tensile strength (8.4-81.6 MPa) and elongation at break (44.5-411.0%) of the resultant PEDOT/RILNs films is significantly tunable according to different usage scenarios by adjusting the PEDOT content from 1.48 to 22.24 wt%. More importantly, the electrical resistance of PEDOT/RILNs remains constant during not only a single large extension and deflection but also repeated stretching (up to 1500 cycles) and bending (up to 106 cycles). The built-in reversible covalent bonds enable the PEDOT/RILNs to autonomously restore damaged mechanical and electrical performance. These record-breaking results and the demonstration of self-powered sensor made of PEDOT/RILNs suggest that the proposed approach successfully satisfies various conflicting requirements of flexible electronics regarding the properties of conducting polymers.

A reversible Schiff base chemosensor for the spectroscopic and colorimetric sensing of Eu3+ ions in solution and solid-state

Herein, the metal sensing properties of a previously reported aluminium sensor (E)-N’-((2-hydroxynapthalene-1-yl)thiophene-2-Carbohydrazide) (L) have been further explored in selective sensing of lanthanide ions. Among many tested lanthanide ions sensor L showed the selective colorimetric response for only Eu3+ ions. The presence of Eu3+ ions caused electronic transitions in the visible region with a color change from colorless to yellow in aqueous acetonitrile media. A red-shift in the absorption band and enhancement in emission intensity is investigated only for the addition of Eu3+ ions to L, without any interference of other existing ions. This chemosensor binds the Eu3+ ions in 1:1 stoichiometric ratio and works upto a detection limits, 2.179 × 10-8 M (LOD for Eu3+ at 415 nm from UV–Visible), 3.443 × 10-8 M (LOD for Eu3+ at 477 nm from fluorescence) with a binding constant of 8.691 × 103 M−1 for the L-Eu3+ binding. However, the developed sensor is used as a paper, cotton-based test kit assay and solid state colorimetric sensing of Eu3+ ions. The reversibility of sensor L is checked by colorimetric observation with the addition of sodium salt ethylenediaminetetraacetic acid (EDTA) and found it reversible up to three cycles.

Schiff Base Reaction in a Living Cell: In Situ Synthesis of a Hollow Covalent Organic Polymer To Regulate Biological Functions

AbstractArtificially performing chemical reactions in living biosystems to attain various physiological aims remains an intriguing but very challenging task. In this study, the Schiff base reaction was conducted in cells using Sc(OTf)3 as a catalyst, enabling the in situ synthesis of a hollow covalent organic polymer (HCOP) without external stimuli. The reversible Schiff base reaction mediated intracellular Oswald ripening endows the HCOP with a spherical, hollow porous structure and a large specific surface area. The intracellularly generated HCOP reduced cellular motility by restraining actin polymerization, which consequently induced mitochondrial deactivation, apoptosis, and necroptosis. The presented intracellular synthesis system inspired by the Schiff base reaction has strong potential to regulate cell fate and biological functions, opening up a new strategic possibility for intervening in cellular behavior.

Schiff Base Reaction in a Living Cell: In Situ Synthesis of a Hollow Covalent Organic Polymer To Regulate Biological Functions.

Artificially performing chemical reactions in living biosystems to attain various physiological aims remains an intriguing but very challenging task. In this work, the Schiff base reaction was conducted in cells using Sc(OTf)3 as a catalyst, based on which the in situ synthesis of hollow covalent organic polymer (HCOP) was readily accomplished without external stimuli. The reversible Schiff base reaction-mediated intracellular Oswald ripening endows the HCOP with a woolen, spherical, hollow porous structure, and a large specific surface area. The intracellularly generated HCOP reduced cellular motility by restraining actin polymerization, which consequently induced mitochondrial deactivation, apoptosis, and necroptosis. The presented Schiff base reaction-inspired intracellular synthesis system has strong potential to regulate cell fate and biological functions, opening up a new strategic possibility for intervening cellular behavior.

Double Cross-Linked Chitosan/Bacterial Cellulose Dressing with Self-Healable Ability.

Self-healing hydrogel products have attracted a great deal of interest in wound healing due to their ability to repair their own structural damage. Herein, an all-natural self-healing hydrogel based on methacrylated chitosan (CSMA) and dialdehyde bacterial cellulose (DABC) is developed. MA is used to modify CS and obtain water-soluble biomaterial-based CSMA with photo crosslinking effects. BC is modified through a simple oxidation method to gain dialdehyde on the polymer chain. The success of the modification is confirmed via FTIR. Hydrogels are formed within 11 min through the establishment of a Schiff base between the amino of CSMA and the aldehyde of DABC. A dynamically reversible Schiff base bond endows hydrogel with good self-healing properties through macroscopic and microscopic observations. We observe the uniform and porous structure in the hydrogel using SEM images, and DABC nanofibers are found to be well distributed in the hydrogel. The compressive strength of the hydrogel is more than 20 kPa and the swelling rate sees over a 10-fold increase. In addition, the CSMA/DABC hydrogel has good cytocompatibility, with cell viability exceeding 90%. These results indicate that the all-natural self-healable CSMA/DABC hydrogel demonstrates strong application potential in wound healing and tissue repair.

ECM-Inspired Hydrogels with ADSCs Encapsulation for Rheumatoid Arthritis Treatment.

Due to their intrinsic anti-inflammatory and immunomodulatory properties, adipose-derived stem cells (ADSCs) are explored as a promising alternative in treating rheumatoid arthritis (RA). To address the poor survival and function loss of directly injected stem cells, efforts in this area are focus on the generation of efficient cell delivery vehicles. Herein, a novel extracellular matrix (ECM)-inspired injectable hydrogel for ADSCs encapsulation and RA treatment is proposed. The hydrogel with dendritic polylysine and polysaccharide components is formed through the reversible Schiff base crosslinking. It possesses self-healing capability, superior mechanical properties, minimal toxicity, and immunomodulatory ability. When encapsulated with ADSCs, the hydrogel could recover chronic inflammation by directly reversing the dominant macrophage phenotype from M1 to M2 and inhibiting the migration of fibroblast-like synoviocytes. Through a collagen-induced arthritis rat model, the tremendous therapeutic outcomes of this ADSCs-laden hydrogel, including inflammation attenuation, cartilage protection, and bone mineral density promotion are demonstrated. These results make the ECM-inspired hydrogel laden with ADSCs an ideal candidate for treating RA and other autoimmune disorders.

De novo synthesis of enzyme-embedded covalent organic frameworks (COFs) using deep eutectic solvent: Pushing the COF limits

Covalent organic frameworks (COFs), highly stable and porous crystalline materials, are an attractive host for embedding enzymes to protect them from harsh ex vivo conditions. However, because COF pore size must match enzyme size, larger enzyme molecules cannot be absorbed into COF matrices via COF pores. Furthermore, the COF synthesis using high temperatures, acid catalysts, and organic solvents is ineffective for the de novo construction of enzyme-embedded COFs. Herein, enzyme embedding within imine-based COFs regardless of pore dimensions is presented by pre-functionalizing the enzyme with COF aldehyde precursor and facilitating “armor-like” COF exoskeleton formation from the enzyme surface via condensation of COF aldehyde and amine precursors at ambient conditions using choline chloride/urea deep eutectic solvent as both solvent and catalyst. This de novo approach affords glucose oxidase (GOx) embedding within two kinds of COFs with pores smaller than GOx size and activity recovery of 55–62% is achieved, whereas GOx embedding into pre-synthesized COFs was not possible. According to time-dependent TEM analysis, GOx@COF morphology is dependent on enzyme and COF precursor geometry which was governed by reversible Schiff-base and Ostwald ripening. Enzyme confinement within the COF architecture, as well as chemical crosslinking of the enzyme surface with the COF exoskeleton, endows GOx@COF with excellent pH and thermo-stability, tolerance to denaturation by urea, trypsin, and organic solvent, and stable bactericidal activity over 5 recycles. The morphological structure of GOx@COF and extent of GOx cross-linking with COF precursor influence its kinetic performance. This work could open a new avenue for utilizing COFs to create a suite of stable enzyme-COF composites for various applications.

Antifreezing and self-healing organohydrogels regulated by ethylene glycol towards customizable electrochromic displays

Though numerous patterned electrochromic (EC) displays have been developed, a low-cost, eco-friendly and convenient strategy for fabricating customizable EC displays with great low and high temperature adaptability is still desired urgently. Herein, an antifreezing and self-healing EC oganohydrogel with reversible Schiff base linkages was prepared facilely through mixing a chitosan solution based on a water/ethylene glycol (EG) binary solvent and a dibenzaldehyde-modified poly(ethylene oxide) aqueous solution, and its mechanical and electrochromic properties can be regulated by EG content. The optimized gel exhibits a high ionic conductivity of 0.2 mS cm−1 at -60 ℃ and the EC gel-based device shows great cyclic stability with 99%, 98% and 95% optical modulation retention after 1000 cycles at different temperature of -30 ℃, 20 ℃ and 45 ℃, respectively. By extruding the EC gels from syringes onto transparent electrodes to form the specific patterns or characters, a series of customized EC displays for convey information were obtained. Such EC displays are expected to exhibit unique advantages over a wide operating temperature range and become a paradigm for future EC displays manufacturing.

The cyclotriphosphazene-based covalent organic frameworks constructed entirely by flexible building blocks for adsorping and fluorescence sensing iodine

A series of flexible cyclotriphosphazene-based COFs, we call them fully flexible cyclotriphosphazene-based COFs (HDADE, HBAPB and HBPDA), were prepared by means of reversible Schiff base polycondensation reactions for the first time, which were constructed entirely by flexible building blocks, not only hexa(4-formyl-phenoxy)cyclotriphosphazene (NOP–6–CHO) as a flexible knot but also aromatic ether diamine as flexible linkers. The fully flexible cyclotriphosphazene-based COFs are crystalline porous materials. Their crystallinity and BET specific surface areas increase with the length of the linkers, and are higher than that of the corresponding COFs constructed by the rigid linkers. HDADE, HBAPB and HBPDA can absorb iodine in both gas or liquid phase. The adsorptive capacities are 5.22, 4.55, and 3.86 g g−1, respectively, which are higher than the corresponding COFs formed by rigid linkers. The fully flexible cyclotriphosphazene-based COFs can fluorescently sense iodine with high sensitivity. Their quenching constants (KSV) are 2.22 × 104, 7.07 × 104, and 1.04 × 104 L mol−1. Their LODs are 1.35 × 10−10, 4.24 × 10−11, and 2.88 × 10−10 mol L−1, respectively. The fluorescence quenching of iodine to the fully flexible cyclotriphosphazene-based COFs has both photo-induced charge transfer and resonant energy transfer processes.

Self-healing/pH-responsive/inherently antibacterial polysaccharide-based hydrogel for a photothermal strengthened wound dressing

Hydrogels have been used widely as wound dressings for maintaining a moist environment to rapid wound healing. However, the lack of antibacterial effect limits their further applications. Herein, we developed a polysaccharide-based hydrogel that can achieve photothermal-assisted bacterial inactivation. The hydrogel has inherent antibacterial activity due to introduction of quaternised chitosan (QCS) with a protonated amine group-modified hydrophilic polycationic structure. Under near infrared (NIR) irradiation, the antibacterial effect of the hydrogel was significantly improved because thermal ablation could also combat bacteria. The hydrogel showed self-healing property through reversible Schiff base bonds between QCS and oxidized hyaluronic acid (OHA). The hydrogel is also pH-sensitive to release drugs in acidic wound. The full-thickness skin defect model showed it had a promoting effect on wound healing. Overall, we provide a theoretical basis for a promising wound dressing based on a photothermally improved polysaccharide-based hydrogel with self-healing/pH-responsive/inherently antibacterial capacity.

Vitamin A aldehyde-taurine adducts function in photoreceptor cells

To facilitate the movement of retinoids through the visual cycle and to limit nonspecific chemical reaction, multiple mechanisms are utilized to handle these molecules when not contained within the binding pocket of opsin. Vitamin A aldehyde is sequestered by reversible Schiff base formation with phosphatidylethanolamine (PE) and subsequently undergoes NADPH-dependent reduction. Otherwise inefficient handling of retinaldehyde can lead to the formation of fluorescent di-retinal compounds within the outer segments of photoreceptor cells. These bisretinoid fluorophores initiate photooxidative processes having adverse consequences for retina. Various carrier proteins confer water solubility and maintain the 11-cis-retinoid configuration. Mechanisms for sequestration of retinoid include the formation of a reversible Schiff base between retinaldehyde and taurine (A1-taurine, A1T), the most abundant amino acid in photoreceptor cells. Here we have undertaken to examine the effects of taurine depletion using the transport inhibitors guanidinoethyl sulfonate (GES) and β-alanine. Oral treatment of BALB/cJ mice with β-alanine reduced ocular A1T and the mice exhibited significantly lower scotopic and photopic a-wave amplitudes. As a secondary effect of retinal degeneration, A1T was not detected and taurine was significantly reduced in mice carrying a P23H opsin mutation. The thinning of ONL that is indicative of reduced photoreceptor cell viability in albino Abca4−/− mice was more pronounced in β-alanine treated mice. Treatment of agouti and albino Abca4−/− mice with β-alanine and GES was associated with reduced bisretinoid measured chromatographically. Consistent with a reduction in carbonyl scavenging activity by taurine, methylglyoxal-adducts were also increased in the presence of β-alanine. Taken together these findings support the postulate that A1T serves as a reservoir of vitamin A aldehyde, with diminished A1T explaining reduced photoreceptor light-sensitivity, accentuated ONL thinning in Abca4−/− mice and attenuated bisretinoid formation.

Mechanical enhancement mechanism of interlocked polymer networks

To understand the molecular origin of the significantly improved mechanical properties of the newly emerged reversibly interlocked polymer networks (ILNs), which are composed of two dynamically crosslinked polymers regardless of their miscibility, the present work employs small angle neutron scattering (SANS) technique to study the microstructural evolution of the materials during stretching. Accordingly, polyacrylate networks containing reversible Diels-Alder (DA) bonds and polyether networks containing reversible Schiff base bonds are synthesized and then interlocked together through topological rearrangement of the two single networks. By using deuterated acrylate monomers, furthermore, the single networks with DA bonds are labeled, providing the model ILNs with necessary contrast for the SANS measurements. The strain-dependent SANS profiles and 2D SANS patterns of the ILNs reveal that the latter maintain the homogeneity after extension. It means that the two parent single networks are simultaneously deformed because the interlocking sites act as movable crosslinkages, so that the chains conformation can be modulated and the applied stress can be effectively transferred. When relative movement of the neighboring molecular chains occurs, a great number of molecular chains in the interlocked polymer networks are able to be tightened at the same time, and more mechanical energy can be dissipated by internal friction in the process. The findings reveal that the mechanical enhancement results from the unique interlocked structure, and provide guidance for the rational design of high-performance multi-component polymer materials.

Synthesis of Core@Brush microspheres by atom transfer radical polymerization for capturing phosphoprotein β-casein utilizing iron ion chelation and Schiff base bio-conjugation

This paper aims to design a highly efficient adsorbent to capture phosphoprotein in a facile way. One of the applications would be removing the allergenic β-casein from vaccines. To avoid the use of organic reagents and improve the capacity of immobilized metal ion affinity chromatography applied for bio-products at neutral pH, synergistic functional Core@Brush microspheres were designed utilizing iron ion chelation and Schiff base bio-conjugation. Surface-initiated atom transfer radical polymerization (ATRP) was used to grow polymer brushes, composed of one carbonyl-containing functional monomer diacetone acrylamide (DAAM) and the other monomer glycidyl methacrylate (GMA), on active microspheres as the cores. Then the material was chemically modified with iminodiacetic acid and chelated with Fe(III). Adsorption studies show that the Core@Brush microspheres can selectively distinguish phosphoproteins with non-phosphoproteins, and has an excellent adsorption capacity over 2000 μg/mg towards β-casein owing to a large number of adsorption sites. The adsorption was well fitted to a pseudo-second-order kinetic model, indicating multi-valent chemisorption. The assumption is that β-casein was selectively captured by the synergistic function of stable iron ion chelation and reversible Schiff base bio-conjugation, and the particle-protein-particle aggregates formed.