Acryloyl Hydrazide Research Articles

Synthesis, In vitro Antiproliferative and Antibacterial Evaluation and Molecular Docking Studies of 6-Chloro-3,4-Dihydro-4-Oxo-2H-Chromen-3-yl Methylene-2-Cyano-3-Phenyl Acryloyl Hydrazide

Synthesis, In vitro Antiproliferative and Antibacterial Evaluation and Molecular Docking Studies of 6-Chloro-3,4-Dihydro-4-Oxo-2H-Chromen-3-yl Methylene-2-Cyano-3-Phenyl Acryloyl Hydrazide

Discovery of Simple Diacylhydrazine-Functionalized Cinnamic Acid Derivatives as Potential Microtubule Stabilizers.

To develop novel microtubule-binding agents for cancer therapy, an array of N-cinnamoyl-N’-(substituted)acryloyl hydrazide derivatives were facilely synthesized through a two-step process. Initially, the antiproliferative activity of these title compounds was explored against A549, 98 PC-3 and HepG2 cancer cell lines. Notably, compound I23 exhibited the best antiproliferative activity against three cancer lines with IC50 values ranging from 3.36 to 5.99 μM and concurrently afforded a lower cytotoxicity towards the NRK-52E cells. Anticancer mechanism investigations suggested that the highly bioactive compound I23 could potentially promote the protofilament assembly of tubulin, thus eventually leading to the stagnation of the G2/M phase cell cycle of HepG2 cells. Moreover, compound I23 also disrupted cancer cell migration and significantly induced HepG2 cells apoptosis in a dosage-dependent manner. Additionally, the in silico analysis indicated that compound I23 exhibited an acceptable pharmacokinetic profile. Overall, these easily prepared N-cinnamoyl-N’-(substituted)acryloyl hydrazide derivatives could serve as potential microtubule-interacting agents, probably as novel microtubule-stabilizers.

Star polymer-assembled adsorptive membranes for effective Cr(VI) removal

There is a strong demand for materials that can effectively remove highly toxic hexavalent chromium (Cr(VI)) ions from wastewater. Herein, we present a new class of Cr(VI)-adsorptive membranes assembled with a Cr(VI)-adsorptive and cross-linkable star polymer. The poly(acryloyl hydrazide)-branched star polymer (PAH-SP) with numerous amine groups enabled rapid and high-capacity Cr(VI) adsorption and was suitable for assembly into a selective layer via interfacial polymerization (IP). The IP-assembled PAH-SP (PAH-TFC) membrane synergistically rejected Cr(VI) over the entire pH range via a combination of adsorption (under acidic conditions) and membrane filtration (under basic conditions). Furthermore, the PAH-TFC membrane was more resistant to oxidation by acidic Cr(VI) than commercial reverse osmosis (RO) and nanofiltration membranes because of the self-sacrificing effect of its abundant amine groups. Consequently, PAH-TFC exhibited significantly higher Cr(VI) rejection (∼99.5% at pH 3) under acidic conditions than a representative commercial RO membrane (Cr(VI) rejection of ∼55% at pH 3) with similar water permeance, while demonstrating comparable Cr(VI) rejection under basic conditions. Furthermore, PAH-TFC displayed excellent regeneration ability, maintaining its Cr(VI) rejection above the commercial RO level by proper base/acid rinsing.

Star polymer-mediated in-situ synthesis of silver-incorporated reverse osmosis membranes with excellent and durable biofouling resistance

Biofouling mitigation for water purification membranes is critically important for the efficient separation process. Most anti-biofouling thin-film nanocomposite (TFN) membranes have been incorporated with biocidal nanomaterials via ex-situ hybridization, often leading to performance deterioration and ineffective nanomaterial incorporation. Here, we present a new in-situ hybridization strategy for the fabrication of silver-incorporated TFN (CD-Ag-TFN) reverse osmosis (RO) membranes exhibiting excellent anti-biofouling and separation performance by utilizing an amine-functionalized star polymer. CD-Ag-TFN membranes were formed by adding a Ag precursor (AgNO3) to an aqueous solution containing poly(acryloyl hydrazide)-branched star polymers (CD-PAHs) prior to interfacial polymerization with trimesoyl chloride (TMC). Numerous amine groups in CD-PAH strongly adsorbed Ag+ ions via complexation, which were subsequently converted to Ag or AgCl nanoparticles, while simultaneously forming a polyamide (PA) selective layer via the reaction with TMC, consequently creating a uniform PA-Ag hybrid network. Due to its greater hydrophilicity and high crosslinking density, the optimized CD-Ag-TFN membrane exhibited RO performance, which is better than that of the CD-PAH-assembled control (CD-TFC) and comparable to than that of recently reported other lab-made RO membranes. Importantly, the robust and effective incorporation of Ag endowed the CD-Ag-TFN membrane with remarkably long-lasting anti-bacterial activity and greater anti-biofouling performance than control CD-TFC.

Synthesis and Characterization of New Polymers Bearing Tetrazole and Triazole Moieties with Studying their Corrosion Protection of Stainless Steel Surface in Hydrochloric Acid

A series of polymers containing1,2,4-triazole and tetrazole groups in their main chains were synthesized through several steps. Poly(acryloyl hydrazide) was first prepared and then subjected to a hydrazide reaction with phenyl isothiocyanate to give a 1,2,4-triazole ring (2). This polymer was introduced into a reaction with chloro acetylchloride to yield polymer (3), which was refluxed with sodium azide to give polymer (4). Polymer (5) was synthesized by the reaction of polymer (4) with acrylonitrile in the presence of NH4Cl as a catalyst. Finally, polymer (6) was synthesized by the electrochemical polymerization of polymer (5) using 316L stainless steel as an anti-corrosion coating. Polymer-coated and uncoated stainless steel was tested for corrosion safety in a solution of 0.1 M HCl, followed by Tafel and Potentiostatic procedures at a temperature of 293 K. Nano materials such as ZnO were applied to the monomer solution at different concentrations to enhance the corrosion resistance of the 316L stainless steel surface. The results showed that the performance values of corrosion protection for the polymer coating were increased with the introduction of the nano materials. Furthermore, 13C-NMR, 1H-NMR, and FTIR were recorded to confirm the structures of the poylmers, while their physical properties were tested using atomic force microscope (AFM) and scanning electron microscope (SEM).

Synthesis and Docking Study of N-(Cinnamoyl)-N'-(substituted)acryloyl Hydrazide Derivatives Containing Pyridinium Moieties as a Novel Class of Filamentous Temperature-Sensitive Protein Z Inhibitors against the Intractable Xanthomonas oryzae pv. oryzae Infections in Rice.

Xanthomonas oryzae pv. oryzae (Xoo) is an offensive phytopathogen that can invade a wide range of plant hosts to develop bacterial diseases, including the well-known rice bacterial leaf blight. However, few agrochemicals have been identified to effectively prevent and eliminate Xoo-induced diseases. Thus, designing novel antibacterial compounds on the basis of the potential targets from Xoo may lead to the discovery of highly efficient and innovative anti-Xoo agents. Filamentous temperature-sensitive protein Z (FtsZ), an important functional protein in the progression of cell division, has been widely reported and exploited as a target for creating antibacterial drugs in the field of medicine. Therefore, the fabrication of innovative frameworks targeting XooFtsZ may be an effective method for managing bacterial leaf blight diseases via blocking the binary division and reproduction of Xoo. As such, a series of novel N-(cinnamoyl)-N'-(substituted)acryloyl hydrazide derivatives containing pyridinium moieties were designed, and the anti-Xoo activity was determined. The bioassay results showed that compound A7 had excellent anti-Xoo activity (EC50 = 0.99 mg L-1) in vitro and distinct curative activity (63.2% at 200 mg L-1) in vivo. Further studies revealed that these designed compounds were XooFtsZ inhibitors, validating by the reduced GTPase activity of recombinant XooFtsZ, the nonfilamentous XooFtsZ assembly observed in the TEM images, and the prolonged Xoo cells from the fluorescence patterns. Computational docking studies showed that compound A7 had strong interactions with ASN34, GLN193, and GLN197 residues located in the α helix regions of XooFtsZ. The present study demonstrates the developed FtsZ inhibitors can serve as agents to control Xoo-induced infections.

Fabrication and structural tailoring of reverse osmosis membranes using β-cyclodextrin-cored star polymers

Here, we designed a new chemistry of fouling-resistant reverse osmosis (RO) membranes using a star polymer (CD-PAH) comprising multiple linear polymer (poly(acryloyl hydrazide), PAH) arms grafted onto a β-cyclodextrin (β-CD) core. The well-defined structure of the β-CD-cored star polymer enabled us to systematically synthesize CD-PAHs with different arm lengths, which were assembled into membrane selective layers via a layered interfacial polymerization technique. Increasing the PAH arm length of CD-PAH enhanced the inter-chain entanglement of PAH arms and thus the crosslinking reaction efficiency by providing a higher density of the crosslinkable amine groups of densely-packed PAH arms. Hence, longer PAH arms of CD-PAH resulted in an enhancement in NaCl rejection with a reduction in the water permeance of the CD-PAH-assembled (CD-TFC) membrane. Importantly, the CD-TFC membranes prepared using CD-PAHs with longer PAH arms exhibited RO separation performance comparable to that of a commercial RO membrane, which is not feasible by other reported branch-structured macromolecules. Furthermore, the CD-TFC membrane displayed lower organic fouling with a higher rinsing efficiency than a commercial RO membrane, because of its more negatively charged and hydrophilic surface combined with its smoother surface, overcoming a performance-fouling trade-off.

Poly(acryloyl hydrazide)-grafted cellulose nanocrystal adsorbents with an excellent Cr(VI) adsorption capacity

In this study, we prepared poly(acryloyl hydrazide) (PAH)-grafted cellulose nanocrystal (CNC-PAH) particles via the atom transfer radical polymerization method for application to Cr(VI) adsorption. The closely-packed PAH chains grafted on the cellulose nanocrystal (CNC) surface provide a high density of amine groups that can adsorb Cr(VI) through strong electrostatic, hydrogen bonding and chelating interactions. CNC-PAH exhibited the optimum Cr(VI) adsorption capacity at the solution pH = 3, where its electrostatic attraction with Cr(VI) was maximized. Cr(VI) was chemisorbed in CNC-PAH by following the Langmuir isotherm mechanism (homogeneous monolayer adsorption). The Cr(VI) adsorption kinetics of CNC-PAH was controlled predominantly by intra-particle diffusion resistance imparted by the PAH shell layer. Thermodynamic analysis revealed that Cr(VI) adsorption of CNC-PAH is a spontaneous and endothermic process. Importantly, CNC-PAH grafted with the higher Mw (∼50 kg mol−1) PAH exhibited a rapid Cr(VI) adsorption rate and remarkably high Cr(VI) adsorption capacity (∼457.6 mg g-1 at 298.15 K), exceeding those of previously reported adsorbents owing to its numerous Cr(VI)-adsorptive amine groups provided by the closely-packed grafted PAH polymers. Furthermore, CNC-PAH showed excellent reusability to maintain its high adsorption ability during repeated adsorption–desorption cycles owing to the covalently binding nature of the PAH polymers.

Nanocomposite Grafted Stretchable and Conductive Ionic Hydrogels for Use as Soft Electrode in a Wearable Electrocardiogram Monitoring Device

Hydrogels possessing stretchability, toughness, and conductivity together are promising candidates for soft electronics applications. In this report, ionic grafting of poly(acryloyl hydrazide) (PAHz)–silver (Ag) nanocomposites (NC) is used to improve the mechanical properties and conductivity of poly(acrylamidopropanesulfonic acid) (PAMPS) hydrogels. PAHz–Ag NCs possessing different sizes of Ag NPs (3–40 nm) are grafted in the PAMPS hydrogel matrix via −CONHNH3+---–O3S ionic linkage. The resulting PAHz–Ag NC grafted hydrogels at ∼62 wt % water content exhibited ultimate tensile strength (UTS) and fracture energy up to ∼1.14 MPa and ∼1600 J/m2, respectively. The UTS of hydrogels was dependent on the size of Ag NP in PAHz–Ag NCs, and the value increased from 0.70 to 1.14 MPa with the decrease in Ag NP size from ∼40 to 5 nm. The hydrogel samples exhibited adequate skin adhesiveness (tack adhesive strength ≈10.8 kPa), conductivity (50.5 mS/cm), and strain sensing ability (gauge factor ≈0.9), suggesting these samples are potentially useful for various soft electronics applications. As a proof of concept, the hydrogels were employed as soft electrode in an electrocardiogram (ECG) device, and the efficiency was monitored under real-time conditions. The data exhibited noise-free reproducible patterns of ECG with defined P, Q, R, S, and T peaks under different locomotion of the body, suggesting the viability of developed hydrogels for the ECG sensing applications.

Development of anti-virulence polymers targeting mycobacteria

Modern medicine is under the excruciating pressure of drug resistant bacterial strains which are ever advancing with the introduction of every new class of antibiotics. Traditional bactericidal and bacteriostatic drugs, while effective in eliminating the susceptible bacterial strains, also impose a selective pressure on bacteria which often leads to the emergence of antimicrobial resistance. An alternative approach is the development of anti-virulence therapies, which aims reduce bacterial pathogenesis while avoiding the selective pressure of classical antimicrobial inhibitors, thus rendering bacteria harmless and potentiating natural elimination from the host by innate immunity defence mechanisms. We have synthesised a selection of functional polymers of poly(acryloyl hydrazide) using a panel of aldehyde functionalisation groups and evaluated their anti-virulence properties on both Mycobacterium bovis BCG and Mycobacterium smegmatis mc2 155, two surrogate organisms to study Mycobacterium tuberculosis, the etiological agent responsible for tuberculosis. Using a combination of microscopy and in vitro studies, we have shown the effectiveness of anti-virulence polymers in reducing mycobacterial phagocytosis in J774 macrophages with minimal antimicrobial activity.

Correction: Poly(acryloyl hydrazide), a versatile scaffold for the preparation of functional polymers: synthesis and post-polymerisation modification

Correction for ‘Poly(acryloyl hydrazide), a versatile scaffold for the preparation of functional polymers: synthesis and post-polymerisation modification’ by Daniel N. Crisan et al., Polym. Chem., 2017, 8, 4576–4584.

Poly(acryloyl hydrazide), a versatile scaffold for the preparation of functional polymers: synthesis and post-polymerisation modification.

Here we present the synthesis and post-polymerisation modification of poly(acryloyl hydrazide), a versatile scaffold for the preparation of functional polymers: poly(acryloyl hydrazide) was prepared from commercially available starting materials in a three step synthesis on a large scale, in good yields and high purity. Our synthetic approach included the synthesis of a Boc-protected acryloyl hydrazide, the preparation of polymers via RAFT polymerisation and the deprotection of the corresponding Boc-protected poly(acryloyl hydrazide). Post-polymerisation modification of poly(acryloyl hydrazide) was then demonstrated using a range of conditions for both hydrophilic and hydrophobic aldehydes. These experiments demonstrate the potential of poly(acryloyl hydrazide) as a scaffold in the synthesis of functional polymers, in particular those applications where in situ screening of the activity of the functionalised polymers may be required (e.g. biological applications).

In Situ Functionalized Polymers for siRNA Delivery.

A new method is reported herein for screening the biological activity of functional polymers across a consistent degree of polymerization and in situ, that is, under aqueous conditions and without purification/isolation of candidate polymers. In brief, the chemical functionality of a poly(acryloyl hydrazide) scaffold was activated under aqueous conditions using readily available aldehydes to obtain amphiphilic polymers. The transport activity of the resulting polymers can be evaluated in situ using model membranes and living cells without the need for tedious isolation and purification steps. This technology allowed the rapid identification of a supramolecular polymeric vector with excellent efficiency and reproducibility for the delivery of siRNA into human cells (HeLa-EGFP). The reported method constitutes a blueprint for the high-throughput screening and future discovery of new polymeric functional materials with important biological applications.

In Situ Functionalized Polymers for siRNA Delivery

AbstractA new method is reported herein for screening the biological activity of functional polymers across a consistent degree of polymerization and in situ, that is, under aqueous conditions and without purification/isolation of candidate polymers. In brief, the chemical functionality of a poly(acryloyl hydrazide) scaffold was activated under aqueous conditions using readily available aldehydes to obtain amphiphilic polymers. The transport activity of the resulting polymers can be evaluated in situ using model membranes and living cells without the need for tedious isolation and purification steps. This technology allowed the rapid identification of a supramolecular polymeric vector with excellent efficiency and reproducibility for the delivery of siRNA into human cells (HeLa‐EGFP). The reported method constitutes a blueprint for the high‐throughput screening and future discovery of new polymeric functional materials with important biological applications.

Synthesis of Glycopolymers for Microarray Applications via Ligation of Reducing Sugars to a Poly(acryloyl hydrazide) Scaffold

In this paper, we report on a general synthetic strategy for the assembly of glycopolymers that capitalizes on the intrinsic reactivity of reducing glycans toward hydrazides to form stable cyclic N-glycosides. We developed a poly(acryloyl hydrazide) (PAH) scaffold to which we conjugated a variety of reducing glycans ranging in structure from simple mono- and disaccharides to considerably more complex human milk and blood oligosaccharides. The conjugation proceeds under mild conditions with excellent ligation efficiencies and in a stereoselective manner, providing glycopolymers with pendant glycans accommodated mostly in their cyclic β-glycosidic form. Utilizing a biotin-terminated PAH scaffold prepared via RAFT polymerization, we quickly assembled a panel of glycopolymers that we microarrayed on streptavidin-coated glass. We then demonstrated that in these microarrays, the glycopolymer ligands bind lectins according to the structures of their pendant glycans. Importantly, glycopolymers containing biologically relevant branched oligosaccharides, such as sialyl Lewisx, as well as sulfated glycosaminoglycan-like epitopes can be readily prepared using our methodology.