Dual Amide Research Articles

A mechanically strong shape-memory organohydrogel based on dual hydrogen bonding and gelator-induced solidification effect

Shape-memory gel materials are widely used in smart drives and biological tissues due to their excellent flexibility and diverse stimuli responsiveness. In particular, shape-memory organohydrogel materials have rose intense interest recently owing to their sophisticated shape memory behavior. However, conventional mechanical enhancement strategies, either by introducing nanoparticles or double-network structure, employed in the preparation of organohydrogels require high energy input, leading to difficulties in emulsification for emulsion precursors of organohydrogels. These strategies are not suitable for large-scale production of high-strength organohydrogels. Herein，a high-strength shape-memory organohydrogel NL-H was prepared based on dual hydrogen bonding and gelator-induced solidification effect. The precursor was easily emulsified, as the aqueous phase involved no nanoparticles or highly viscous polymers. Moreover, the dual hydrogen bonds among the dual amide groups of N-acryloyl glycinamide (NAGA) monomers can endow the organohydrogel with high mechanical properties. Owing to the oil-solidification effect of gelator HSA, the mechanical properties could be greatly enhanced, showing a high Young's modulus of 188.04 kPa. Furthermore, by integrating a high elastic hydrogel matrix and reversible oil domains, the organohydrogel showed a thermo-softening and favorable shape-memory properties. Consequently, this work provides a new enhancement strategy for the preparation of organohydrogel with high mechanical properties and excellent shape memory capabilities. And the simple preparation process can also facilitate the large-scale fabrication.

Poly(N-acryloyl glycinamide-co-N-acryloxysuccinimide) Nanoparticles: Tunable Thermo-Responsiveness and Improved Bio-Interfacial Adhesion for Cell Function Regulation.

Poly(N-acryloyl glycinamide) (PNAGA) can form high-strength hydrogen bonds (H-bonds) through the dual amide motifs in the side chain, allowing the polymer to exhibit gelation behavior and an upper critical solution temperature (UCST) property. These features make PNAGA a candidate platform for biomedical devices. However, most applications focused on PNAGA hydrogels, while few focused on PNAGA nanoparticles. Improving the UCST tunability and bio-interfacial adhesion of the PNAGA nanoparticles may expand their applications in biomedical fields. To address the issues, we established a reactive H-bond-type P(NAGA-co-NAS) copolymer via reversible addition-fragmentation chain transfer polymerization of NAGA and N-acryloxysuccinimide (NAS) monomers. The UCST behaviors and the bio-interfacial adhesion toward the proteins and cells along with the potential application of the copolymer nanoparticles were investigated in detail. Taking advantage of the enhanced H-bonding and reactivity, the copolymer exhibited a tunable UCST in a broad temperature range, showing thermo-reversible transition between nanoparticles (PNPs) and soluble chains; the PNPs efficiently bonded proteins into nano-biohybrids while keeping the secondary structure of the protein, and more importantly, they also exhibited good adhesion ability to the cell membrane and significantly inhibited cell-specific propagation. These features suggest broad prospects for the P(NAGA-co-NAS) nanoparticles in the fields of biosensors, protein delivery, cell surface decoration, and cell-specific function regulation.

Porous boronate imprinted microsphere prepared based on new RAFT functioned cellulose nanocrystalline with multiple H-bonding at the emulsion droplet interface for highly specific separation of Naringin

For porous molecular imprinted polymers (MIPs), introduction of special functional groups and integration porous structure support will endow the MIPs with tunable surface properties and specific affinity performance. Herein, by combination of RAFT molecular imprinting, Pickering emulsion, and boronate affinity methods, a new kind of porous imprinted microspheres (BA-HPMIPs) using the low pKa value of APBA (1-allylpyridinium-3-boronic acid, pKa = 7.4) as functional monomer was prepared for specific molecular recognition and separation of NRG. Meanwhile, the novel RAFT functioned surfactants with dual amide multiple H-bonds were designed as stabilized particles was used to promote sustainability, which further confer them multifunctionality and/or by polymerizing the Pickering emulsion itself. Equilibrium adsorption was reached rapidly within 360 min, and the maximum equilibrium binding capacities of BA-HPMIPs were found to be 118.32 µmol g−1 for NRG. Furthermore, they had a stronger selectivity towards NRG than other competitive target (i.e rutin, catechol, ARS, o-nitrophenol). Moreover, BA-HPMIPs have shown outstanding reusability of 8.63 % loss in enrichment performance after five times repeatedly. As a proof of this concept, a commercially avaliable NRG with purity could be effectively extracted and concentrated to 96.75 % purity. These results demonstrated that, a new kind of porous imprinted microsphere with abundant porous structure and boronic acid recognizing sites has great potential for separation and purification of industrial samples under neutral conditions.

An Ultrasoft Self-Fused Supramolecular Polymer Hydrogel for Completely Preventing Postoperative Tissue Adhesion.

The intermolecular H-bonding density heavily influences the gelation and rheological behavior of hydrogen-bonded supramolecular polymer hydrogels, thus offering a delicate pathway to tailor their physicochemical properties for meeting a specific biomedical application. Herein, one methylene spacer between two amides in the side chain of N-acryloyl glycinamide (NAGA) is introduced to generate a variant monomer, N-acryloyl alaninamide (NAAA). Polymerization of NAAA in aqueous solution affords an unprecedented ultrasoft and highly swollen supramolecular polymer hydrogel due to weakened H-bonds caused by an extra methylene spacer, which is verified by variable-temperature Fourier transform infrared (FTIR) spectroscopy and simulation calculation. Intriguingly, poly(N-acryloyl alaninamide) (PNAAA) hydrogel can be tuned to form a transient network with a self-fused and excellent antifouling capability that results from the weakened dual amide H-bonding interactions and enhanced water-amide H-bonding interactions. This self-fused PNAAA hydrogel can completely inhibit postoperative abdominal adhesion and recurrent adhesion after adhesiolysis in vivo. This transient hydrogel network allows for its disintegration and excretion from the body. The molecular mechanism studies reveal the signal pathway of PNAAA hydrogel in inhibiting inflammatory response and regulating fibrinolytic system balance. This self-fused, antifouling ultrasoft supramolecular hydrogel is promising as a barrier biomaterial for completely preventing postoperative tissue adhesion.

T-shaped trifunctional crosslinker-toughening hydrogels

Currently, development of a single network hydrogel with a high fracture toughness in swelling equilibrium remains challenging. In this work, a novel T-shaped trifunctional crosslinker (T-NAGAX) with dual vinyl on the backbone and dual amide group on the side chain is synthesized by Michael addition and acylation. The T-NAGAX is used to prepare chemically crosslinked hydrogel by one-pot photo-initiated polymerization. The resulting single network hydrogels of representative polyacrylamide (PAAm), poly(N-acryloyl 2-glycine) (PACG), and poly(N-isopropyl acrylamide) (PNIPAM) crosslinked with T-NAGAX with additional hydrogen-bonds exhibit much better fracture toughness than that of the corresponding hydrogels crosslinked by N,N′ -methylene bisacrylamide, a conventional crosslinker; higher mechanical strengths are observed in the T-NAGAX crosslinked hydrogels. These hydrogels are promising to be exploited as load-bearing soft tissue substitutes. This T-NAGAX crosslinker can be expanded to toughen various types of hydrogels.

Antifouling Super Water Absorbent Supramolecular Polymer Hydrogel as an Artificial Vitreous Body.

Recently, there has been a high expectation that high water absorbent hydrogels can be developed as an artificial vitreous body. However, the drawbacks associated with in vivo instability, biofouling, uncontrollable in situ reaction time, and injection‐induced precrosslinked fragmentation preclude their genuine use as vitreous substitutes. Here, a supramolecular binary copolymer hydrogel termed as PNAGA‐PCBAA by copolymerization of N‐acryloyl glycinamide (NAGA) and carboxybetaine acrylamide (CBAA) is prepared. This PNAGA‐PCBAA hydrogel physically crosslinked by dual amide hydrogen bonds of NAGA exhibits an ultralow solid content (1.6, 98.4 wt% water content), and shear‐thinning behavior, body temperature extrudability/self‐healability, rapid network recoverability, and very close key parameters (modulus, antifouling/antifibrosis, light transmittance, refractive index, ultrastability) to human vitreous body. It is demonstrated that the hydrogel can be readily injected by a 22G needle into the rabbits' eyes where the gelling network is rapidly recovered. After 16 weeks postoperation, the hydrogel acts as a very stable vitreous substitute without affecting the structure of soft tissues in eye, or eliciting adverse effects. This supramolecular binary copolymer hydrogel finds a broad application in ophthalmic fields as not only a self‐recoverable permanent vitreous substitute, but also transient intraocular filling for prevention of inner tissues in postsurgical eyes.

Synergistic Effects of Conjugation and Polarization on Dual Amide Hydrogen-bonding in CCl4: Theory and Experiment

The doubly hydrogen-bonded dimer of pyrrolidinone (γ-lactam) is used as a benchmark for the effect of conjugation on the strength and extent of hydrogen-bonding of the compounds Oxindole and Isoxindole. The experimental portion of this project consists of collecting the FTIR spectrum of γ-lactam, Oxindole and Isoxindole in CCl4. The concentrations and temperatures were varied to determine the thermodynamic properties of ΔHd, ΔSd and Kd. In addition, the spectroscopic parameters of the difference of the monomer and dimer N-H stretching frequencies (Δν) and the ratio of the molar extinction coefficients of the dimer and monomer (ed/em) are experimentally determined. The values of ΔHd, ΔSd, Δν and ed/em are computed using MP2 and B3LYP methods with 6-31G** and 6-31+G** basis sets. The experimental values are best described by B3LYP/6-31G**with the incorporation of the dielectric effect (PCM) of CCl4. The experimental and computational results support the results of increased or decreased hydrogen-bond strength due to conjugation effects on the polarization of the monomers in forming dimers.

Methyl matters: An autonomic rapid self-healing supramolecular poly(N-methacryloyl glycinamide) hydrogel

Poly(N-acryloyl glycinamide) (PNAGA) with a protein-like thermoresponsive gelation behavior in water has been developed as a high strength self-healable supramolecular polymer(SP) hydrogels recently. However, harsh conditions, such as high temperature treatment and long waiting time, were required for achieving the complete healing due to strong dual amide hydrogen bonding interactions. In this study, to create an autonomic rapid self-healing SP hydrogel, we deliberately introduced a methyl into the opposite side to dual amide to synthesize N-methacryloyl glycinamide (MNAGA) monomer. Rheological analysis, dynamic light scattering(DLS), Fourier transform infrared (FTIR) spectroscopy, and Gaussian calculation revealed that one substitution methyl caused a considerable perturbation to the hydrogen bonding interaction, thus leading to the increased starting gelling concentration and pronounced decrease in mechanical properties of PMNAGA hydrogel compared to PNAGA hydrogel. The PMNAGA hydrogel was shown to exhibit rapid autonomic reparability without any external intervention, and dynamic swelling measurement indicated this PMNAGA hydrogel could evolve from permanent to transient network due to the metastable hydrogen bonding crosslinkage, depending on its environmental temperature. This intriguing robust, autonomous healing and autolytic PMNAGA hydrogel holds great potential as a short-term embolic agent for blocking blood vessel and artificial tears for moistening eyes.

Synthesis and Thermoresponsive Behaviors of Thermo-, pH-, CO2-, and Oxidation-Responsive Linear and Cyclic Graft Copolymers

Rational macromolecular design allows us to construct multiresponsive architectural polymers with a potential toward multipurpose applications. This study aims at synthesis and LCST-type thermoresponsive behaviors of multisensitive linear and cyclic graft copolymers with polyacrylamide backbone and hydrophilic PEG grafts. The cloud point could be tuned by many factors, and the effect of cyclization was confirmed by the elevated cloud point in H2O up to 12.8 °C under same conditions. The PEG-connecting Y junctions with dual amide, thioether, and tertiary amine groups allowed thermo-, solvent-, pH-, and CO2-switchable inter/intramolecular hydrogen bonding interactions and hence resulted in unusual solvent (H2O or D2O) and pH (about 6.8–8.5) dependent phase transition and irreversible CO2-responsive behavior. Meanwhile, the solution blending could lead to one or two phase transition(s) dependent on types and compositions of the blends. The meticulous introduction of multifunctional Y junctions into graft cop...

A High Strength Self-Healable Antibacterial and Anti-Inflammatory Supramolecular Polymer Hydrogel.

There is a significant cost to mitigate the infection and inflammation associated with the implantable medical devices. The development of effective antibacterial and anti-inflammatory biomaterials with novel mechanism of action has become an urgent task. In this study, a supramolecular polymer hydrogel is synthesized by the copolymerization of N-acryloyl glycinamide and 1-vinyl-1,2,4-triazole in the absence of any chemical crosslinker. The hydrogel network is crosslinked through the hydrogen bond interactions between dual amide motifs in the side chain of N-acryloyl glycinamide. The prepared hydrogels demonstrate excellent mechanical properties-high tensile strength (≈1.2 MPa), large stretchability (≈1300%), and outstanding compressive strength (≈11 MPa) at swelling equilibrium state. A simulation study elaborates the changes of hydrogen bond interactions when 1-vinyl-1,2,4-triazole is introduced into the gel network. It is demonstrated that the introduction of 1-vinyl-1,2,4-triazole endowes the supramolecular hydrogels with self-repairability, thermoplasticity, and reprocessability over a lower temperature range for 3D printing of different shapes and patterns under simplified thermomelting extrusion condition. In addition, these hydrogels exhibit antimicrobial and anti-inflammatory activities, and in vitro cytotoxicity assay and histological staining following in vivo implantation confirm the biocompatibility of the hydrogel. These hydrogels with integrated multifunctions hold promising potential as an injectable biomaterial for treating degenerated soft supporting tissues.

A robust, highly stretchable supramolecular polymer conductive hydrogel with self-healability and thermo-processability

Dual amide hydrogen bond crosslinked and strengthened high strength supramolecular polymer conductive hydrogels were fabricated by simply in situ doping poly (N-acryloyl glycinamide-co-2-acrylamide-2-methylpropanesulfonic) (PNAGA-PAMPS) hydrogels with PEDOT/PSS. The nonswellable conductive hydrogels in PBS demonstrated high mechanical performances—0.22–0.58 MPa tensile strength, 1.02–7.62 MPa compressive strength, and 817–1709% breaking strain. The doping of PEDOT/PSS could significantly improve the specific conductivities of the hydrogels. Cyclic heating and cooling could lead to reversible sol-gel transition and self-healability due to the dynamic breakup and reconstruction of hydrogen bonds. The mending hydrogels recovered not only the mechanical properties, but also conductivities very well. These supramolecular conductive hydrogels could be designed into arbitrary shapes with 3D printing technique, and further, printable electrode can be obtained by blending activated charcoal powder with PNAGA-PAMPS/PEDOT/PSS hydrogel under melting state. The fabricated supercapacitor via the conducting hydrogel electrodes possessed high capacitive performances. These cytocompatible conductive hydrogels have a great potential to be used as electro-active and electrical biomaterials.

Gated mesoporous carbon nanoparticles as drug delivery system for stimuli-responsive controlled release

Mesoporous carbon nanoparticles (MCNs) show low toxicity suitable for drug delivery carriers but are limited to strong hydrophobic property. Carboxylation and subsequent amination of MCNs were beneficial to drug delivery and release. Gated channel-interconnected MCN vehicles were constructed to realize stimuli-responsive controlled release of drugs. N-(3-Trimethoxysilylpropyl)ethylenediamine triacetate-functionalized ZnO quantum dots (QDs) as gatekeepers were covalently linked with carboxylated MCNs (ca. 115 nm in diameter and 3–3.5 nm in pore size) via dual amide linkages encapsulated drugs within the interconnected channels. The gating of the MCN vehicles not only improved the drug loading capacity but also introduced the stimuli-responsive performance. The controlled release of the drugs could be achieved by lowering pH (acidic microenvironment of tumor cells) to dissolve the ZnO QD gatekeepers and further promoted at elevated temperatures. The ZnO-gated MCN drug delivery system exhibits prospective applications for tumor therapy.

A Concise Access to C2-Symmetric Chiral 4-Pyrrolidinopyridine Catalysts with Dual Functional Side Chains.

A practical method was developed for the preparation of a diastereomeric library of C2-symmetric chiral 4-pyrrolidinopyridine catalysts with dual amide side chains. Use of a racemic precursor is the key to the concise production of catalysts with diverse stereochemisty.

A Mechanically Strong, Highly Stable, Thermoplastic, and Self-Healable Supramolecular Polymer Hydrogel.

Polymerization of glycinamide-conjugated monomer alone in concentrated aqueous solution enables facile formation of a mechanically strong and a highly stable supramolecular polymer (SP) hydrogel because of the cooperatively hydrogen-bonded crosslinking and strengthening effect from dual amide motifs. This SP hydrogel exhibits thermoplastic processability, injectability, and self-reparability because of the dynamic destruction and reconstruction of hydrogen bonds in response to temperature change.

Three-dimensional hydrogen-bonded structures in the hydrated proton-transfer salts of isonipecotamide with the dicarboxylic oxalic and adipic acid homologues

The structures of the 1:1 hydrated proton-transfer compounds of isonipecotamide (piperidine-4-carboxamide) with oxalic acid, 4-carbamoylpiperidinium hydrogen oxalate dihydrate, C6H13N2O(+)·C2HO4(-)·2H2O, (I), and with adipic acid, bis(4-carbamoylpiperidinium) adipate dihydrate, 2C6H13N2O(+)·C6H8O4(2-)·2H2O, (II), are three-dimensional hydrogen-bonded constructs involving several different types of enlarged water-bridged cyclic associations. In the structure of (I), the oxalate monoanions give head-to-tail carboxylic acid O-H···O(carboxyl) hydrogen-bonding interactions, forming C(5) chain substructures which extend along a. The isonipecotamide cations also give parallel chain substructures through amide N-H···O hydrogen bonds, the chains being linked across b and down c by alternating water bridges involving both carboxyl and amide O-atom acceptors and amide and piperidinium N-H···O(carboxyl) hydrogen bonds, generating cyclic R4(3)(10) and R3(2)(11) motifs. In the structure of (II), the asymmetric unit comprises a piperidinium cation, half an adipate dianion, which lies across a crystallographic inversion centre, and a solvent water molecule. In the crystal structure, the two inversion-related cations are interlinked through the two water molecules, which act as acceptors in dual amide N-H···O(water) hydrogen bonds, to give a cyclic R4(2)(8) association which is conjoined with an R4(4)(12) motif. Further N-H···O(water), water O-H···O(amide) and piperidinium N-H···O(carboxyl) hydrogen bonds give the overall three-dimensional structure. The structures reported here further demonstrate the utility of the isonipecotamide cation as a synthon for the generation of stable hydrogen-bonded structures. The presence of solvent water molecules in these structures is largely responsible for the non-occurrence of the common hydrogen-bonded amide-amide dimer, promoting instead various expanded cyclic hydrogen-bonding motifs.