Hydrazone Groups Research Articles

Bacterial Hydrazine Biosynthetic Pathways Featuring Cupin/Methionyl tRNA Synthetase-like Enzymes.

Nitrogen-Nitrogen (N-N) bond-containing functional groups in natural products and synthetic drugs play significant roles in exerting biological activities. The mechanisms of N-N bond formation in natural organic molecules have garnered increasing attention over the decades. Recent advances have illuminated various enzymatic and nonenzymatic strategies, and our understanding of natural N-N bond construction is rapidly expanding. A group of didomain proteins with zinc-binding cupin/methionyl-tRNA synthetase (MetRS)-like domains, also known as hydrazine synthetases, generates amino acid-based hydrazines, which serve as key biosynthetic precursors of diverse N-N bond-containing functionalities such as hydrazone, diazo, triazene, pyrazole, and pyridazinone groups. In this review, we summarize the current knowledge on hydrazine synthetase mechanisms and the various pathways employing this unique bond-forming machinery.

Hydrazone-functionalized nanoscale covalent organic frameworks as a nanocarrier for pH-responsive drug delivery enhanced anticancer activity.

Nanoscale covalent organic frameworks (NCOFs) as emerging drug-delivery nanocarriers have received much attention in biomedicine in recent years. However, there are few reports on the application of pH-responsive NCOFs for drug delivery nanosystems. In this work, hydrazone-decorated NCOFs as pH-triggered molecular switches are designed for efficient cancer therapy. These functionalized NCOFs with hydrazone groups on the channel walls (named NCOFs-NHNH2) are obtained via a post-synthetic modification strategy. Subsequently, the anticancer drug doxorubicin (DOX) as the model molecule is loaded through covalent linkage to yield NCOFs-NN-DOX. Finally, soybean phospholipid (SP) is coated on the surface of HNTs-NN-DOX, named NCOFs-NN-DOX@SP, to further enhance the dispersibility, stability and biocompatibility of HNTs in physiological solution. NCOFs-NN-DOX@SP showed an excellent and intelligent sustained-release effect with an almost sixfold increase at pH = 5.2 than at pH = 7.4. In vitro cell toxicity and imaging assays of NCOFs-NN-DOX@SP exhibited an enhanced therapeutic effect on Lewis lung carcinoma (LLC) cells, demonstrating that the fabricated NCOFs have a great potential in cancer therapy. Thus, this work provides a new way toward designing stimulus-responsive functionalized NCOFs and promotes their potential application as an on-demand drug delivery system in the field of cancer treatment.

Lanthanide complexes facilitate wound healing by promoting fibroblast viability, migration and M2 macrophage polarization.

A tridentate ligand LH3 ((2-hydroxy-3-methoxybenzylidene)-2-(hydroxyimino)propanehydrazide) comprising o-vanillin, hydrazone and oxime donor groups has been employed to prepare a series of tetranuclear Ln(III) complexes. The reaction of ligand LH3 with Ln(NO3)3 [Ln = Sm, Eu, Gd, Tb, Dy, Ho, Er] in MeOH yielded Ln4(LH)6(MeOH)2 (Ln = Sm(1), Eu(2), Gd(3), Tb(4), Ho (6) and Er (7))] whereas the corresponding reaction with Dy(NO3)3 afforded Dy4(LH)4(LH2)2(OH)2 (5). All complexes were characterized by various analytical techniques including single crystal X-ray diffraction, IR spectroscopy, UV-Vis spectroscopy, and elemental analysis. To investigate the potential of these lanthanide complexes for wound healing applications, their effects on fibroblast viability, migration, and M2 macrophage polarization were evaluated. The cytotoxicity assessment revealed that complexes 2(Eu), 4(Tb), 5(Dy), and 7(Er) significantly enhanced fibroblast viability compared to the negative control (NC). In vitro wound healing assay demonstrated that complexes 2(Eu) and 7(Eu) substantially promoted fibroblast migration compared to the NC. Moreover, complex 2(Eu) exhibited significant anti-inflammatory effects by reducing the phagocytic ability of lipopolysaccharide (LPS)-stimulated macrophage cells and attenuating nitric oxide (NO) production. In conclusion, among the series of complexes tested, complex 2(Eu) displayed the most potent anti-inflammatory effect on macrophage cells, while simultaneously promoting fibroblast viability and migration. This unique combination of properties renders complex 2 (Eu) highly promising for wound healing applications.

Importance of the Amino Moiety of the Hydrazone Group in the Electrochemical and UV‐Vis Absorption Properties of Simple Isomeric Hydrazones

AbstractThe development of new useful supramolecular systems, as well as the optimization of existing ones, depends on the understanding of the intrinsic properties of each of the components that constitute them. A representative component of supramolecular systems are hydrazones, which can undergo three different, orthogonal dynamic processes (conformational, constitutional, and configurational) thanks to the leading role played by the amino‐like moiety of their hydrazone groups. Herein, we study the electrochemical and UV‐Vis absorption properties of two structurally related pyridylhydrazones in different solvents and analyze them in terms of the chemical environment of the corresponding hydrazone group. In this way, we establish that both the electrochemical and UV‐Vis absorption properties are mainly dominated by the additional polarization of the N−H bond, i. e., by the electron density around the nitrogen atom.

Novel highly sensitive fluorescence probe based on Perylene diimide for formaldehyde in real food samples

A formaldehyde (FA) fluorescence probePDSNwith two hydrazone groups as the recognition site based on the Perylene tetracarboxylic diimide (PDI) skeleton was synthesized, applied in the recognition of FA in food. The probe PDSN presented an obvious color change from purple to bright yellow after the addition of FA. The fluorescent mechanism of PDSN was also confirmed by 1H NMR. Moreover,PDSNexhibited excellent sensitivity, high selectivity, wide pH values, and a low detection limit of 11.2 nM. Satisfactory results were obtained in the water and real food samples in great accordance with an impressed recovery rate and RSD.

Adsorption behaviors of heavy metal ions by different hydrazone-modified sodium alginate in aqueous medium: Experimental and DFT studies

Herein the hydrazone-modified sodium alginate, being prepared with aldimine condensation through dihydrazide and dialdehydes sodium alginate, possessed extremely effective and selective removal of Pb2+, Cd2+, and Cu2+. Equilibrium adsorption data of biphthalate dihydrazidemodified sodium alginate was obeyed the Freundlich isotherm and pseudo-second-order kinetics models, which reflected that the adsorption process was mainly via the chemisorption, and the maximum adsorption capacities for Pb2+, Cd2+, and Cu2+ were found to be 668.42, 472.37, and 200.10 mg g−1, respectively. The thermodynamic parameter for the sorption demonstrated the process was endothermic and spontaneous. Fourier Transform infrared spectroscopy (FT-IR) and X-ray photoelectron spectroscopy (XPS) analyses revealed combination of chelation interactions coordination and ion exchange of nitrogen and oxygen atoms with heavy metal ions, and the density functional theory (DFT) calculations confirmed that heavy metal ions formed a stable five membered ring coordination structure with the nitrogen and oxygen atoms in hydrazone groups. Moreover, the adsorption efficiency was not significantly reduced after 10 adsorption–desorption recycles. To sum up, this study provides a new strategy for the removal of heavy metal ions by hydrazone-modified sodium alginate with great potential for wastewater treatment.

1,4,6,10-Tetraazaadamantanes (TAADs) with N-amino groups: synthesis and formation of boron chelates and host-guest complexes.

A synthetic route to 1,4,6,10-tetraazaadamantanes (TAADs) bearing free and protected amino groups at the bridge N-atoms has been developed via intramolecular cyclotrimerization of C=N units in the corresponding tris(hydrazonoalkyl)amines. In a similar fashion, unsymmetrically substituted TAADs having both amino and hydroxy groups at the bridge N-atoms were prepared via a hitherto unknown co-trimerization of oxime and hydrazone groups. The use of N-TAAD derivatives as potential ligands and receptors was showcased through forming boron chelates and host–guest complexes with water and simple alcohols.

Highly Efficient Adsorption of Heavy Metals and Cationic Dyes by Smart Functionalized Sodium Alginate Hydrogels.

In this paper, functionalized sodium alginate hydrogel (FSAH) was prepared to efficiently adsorb heavy metals and dyes. Hydrazide-functionalized sodium alginate (SA) prepared hydrazone groups to selectively capture heavy metals (Pb2+, Cd2+, and Cu2+), and another functional group (dopamine grafting), serves as sites for adsorption methylene blue (MB), malachite green (MG), crystal violet (CV). Thermodynamic parameters of adsorption indicated that the adsorption process is endothermic and spontaneous. The heavy metals adsorption by FSAH was physical adsorption mainly due to ΔHθ < 40 kJ/mol, and the adsorption of cationic dyes fitted with the Langmuir models, which indicated that the monolayer adsorption is dominated by hydrogen bonds, electrostatic interactions, and π-π interactions. Moreover, the adsorption efficiency maintained above 70% after five adsorption-desorption cycles. To sum up, FSAH has great application prospect.

Hydrazone modified nanoscale metal-organic frameworks as pH responsive nanoplatforms for cancer therapy

Practical clinical applications of chemotherapeutic drug are limited due to inevitable drawbacks such as low water solubility, big side effect and poor therapeutic efficiency. To overcome these drawbacks, we developed a novel nanoscale metal-organic framework (nMOFs)-based pH-responsive drug delivery system designed for efficient cancer therapy. In this work, a zirconium-based nMOFs UiO-66 was synthesized, and its surface was engineered to convert partial amino groups to hydrazone groups through stepwise organic transformations. Subsequently, the anticancer agent doxorubicin (DOX) served as a therapeutic drug and a fluorescent label was loaded through acid-labile hydrazone linkage to yield UiO-66-DOX. Acidic pH conditions (such as those surrounding tumor cells) catalyzed the hydrolysis of the hydrazone linkage and promoted the DOX release. These novel pH-sensitive drug delivery system will help to achieve safe delivery of the very cytotoxic chemotherapeutic drug (such as DOX), allowing to reduce the therapeutic dose and minimizing drug secondary effects.

Non covalent interactions analysis and spectroscopic characterization combined with molecular docking study of N′-(4-Methoxybenzylidene)-5-phenyl-1H-pyrazole-3-carbohydrazide

The structure, spectroscopic features, and pharmaceutical effect of N′-(4-Methoxybenzylidene)-5-phenyl-1H-pyrazole-3-carbohydrazide (MBPPC) has been studied by DFT modeling, X-ray diffraction, FT-IR, 1H and 13C NMR, and molecular docking investigation. Molecular structure analysis was carried out using DFT calculation. Then, the low RMSD value indicates the good agreement between calculated and observed data. In order to understand the electronic charge transition, the electron difference density technical was performed. 1H and 13C NMR spectra were recorded in the region of 0–15 and 5–225 ppm, respectively, and FT-IR spectrum of MBPPC was obtained from 4000 to 500 cm−1. Electronic structure characteristics were achieved at the level of B3LYP/6-311+G(2d,p). Inter and intramolecular interactions are discussed by topological (AIM, RDG) and Hirshfeld surface analyses. TD-DFT calculations were conducted to reveal molecular orbital based reactivity characteristics and nonlinear optical features up to third order. In addition, thanks to the broad biological field of compounds based on pyrazole and hydrazone groups, molecular docking of the title compound was carried out to study their clinical activities. Docking simulation shows the potential of MBPPC against Vibrio cholera, Mycobacterium tuberculosis, and estrogen receptor.

Acid-triggered degradable diblock poly(doxorubicin)-polyethylene glycol polyprodrug with doxorubicin as structural unit for tumor intracellular delivery

Polyprodrugs, in which drug was used as the structural unit by linking with each other via the dynamic covalent bonds in the main chain, are expected to endow excellent drug delivery performance. Here, acid-triggered degradable diblock polyprodrug, poly(doxorubicin)-polyethylene glycol (PDOX-PEG), was designed with DOX as structural unit alternately linked with acid-labile hydrazone and maleic amide groups, by the polycondensation of DOX-based dimers (D-DOXADH or D-DOXMAH) with PEGylated dimer (DOX-ADH-DOX-PEG) as end capping agent. The optimized PDOX-PEG, which was synthesized with D-DOXADH and the PEGylated dimer at a feeding ratio of 10%, possessed a high Mn of 3.1 × 104 g/mol with a high DOX content of 75.42%. It could easily self-assemble into near spherical nanoparticles with average hydrodynamic diameter of 135 nm. They showed excellent pH-triggered sustained drug release owing to the acid-triggered degradation of the polyprodrug block in the tumor intracellular microenvironment, with low premature drug leakage of 4.39 % within 60 h. The MTT results indicated the enhanced antitumor efficacy of the proposed PDOX-PEG nanoparticles than free DOX. The results demonstrated the promising potential of the proposed acid-triggered degradable diblock PDOX-PEG polyprodrug for tumor treatment.

3D Hydrazone-Functionalized Covalent Organic Frameworks as pH-Triggered Rotary Switches.

The property expansion of 3D functionalized covalent organic frameworks (COFs) is important for developing their potential applications. Herein, the first case of 3D hydrazone-decorated COFs as pH-triggered molecular switches is reported, and their application in the stimuli-responsive drug delivery system is explored. These functionalized COFs with hydrazone groups on the channel walls are obtained via a multi-component bottom-up synthesis strategy. They exhibit a reversible E/Z isomerization at various pH values, confirmed by UV-vis absorption spectroscopy and proton conduction. Remarkably, after loading cytarabine (Ara-C) as a model drug molecule, these pH-responsive COFs show an excellent and intelligent sustained-release effect with an almost fourfold increase in the Ara-C release at pH = 4.8 than at pH = 7.4, which will effectively improve drug-targeting. Thus, these results open a way toward designing 3D stimuli-responsive functionalized COF materials and promote their potential application as drug carriers in the field of disease treatment.

Polyamide nanocomposites containing hydrazide–hydrazone group reinforced with functionalized polyethyleneimine modified Mg(OH)2 nanoparticles: Study on thermal properties, combustion resistance, and lead ion adsorption

AbstractPolyamide nanocomposites (PANC) were prepared from an aliphatic–aromatic polyamide (PA) containing hydrazide–hydrazone groups in the side chain, reinforced with functionalized polyethyleneimine (FPEI)/modified Mg(OH)2 nanoparticles (FPMN). For this purpose, a new structure, aromatic diamine (DAHH), containing the hydrazide–hydrazone group, was synthesized, and used to synthesize PA by direct polycondensation. Also, polyethyleneimine (PEI) was structurally modified with salicylaldehyde for the modification of the surface of Mg(OH)2 nanoparticles (MDH). The Field‐Emission Scanning Electron Microscopy and X‐ray diffraction results revealed that MDH were uniformly dispersed in nano‐size in the PA matrix. The thermogravimetric analysis results in both N2 and air environments showed that PANC possesses higher thermal resistance than that of the neat PA. The 5% degradation temperature (T5) of PANC containing 8 wt% of FPMN was obtained 40°C more than that of the pure PA in the N2 environment. The microscale combustion calorimetry (MCC) results exhibited that the loading of FPMN into the PA matrix can efficiently increase the combustion resistance by decreasing the MCC parameters such as the heat release rate values. In addition, the lead ions adsorption efficiency of the prepared nanostructure materials was investigated, and the results exhibited that the adsorption data were obtained following the Langmuir isotherm model. The maximum adsorption efficiency was calculated to be 99.96% for PANC 8.

Fluorescent properties of some polythiophenes synthesized from 2‐(thiophen‐3‐yl)acetohydrazide and acetophenone

AbstractIn this study, new polythiophenes containing hydrazone groups from derivatives of acetophenone were synthesized by chemical oxidative coupling polymerization. Ultraviolet‐visible spectroscopy (UV‐Vis) combined with infrared (IR) analyses proved the supposed structure of novel polythiophenes and proved conformance of the expected synthetic method. Morphology and surface properties of the synthesized polymers were investigated by field‐emission scanning electron microscopy (FE‐SEM). Thermal gravimetry analysis (TGA) has been reported that there was still the presence of small FeCl3 catalyst in polymers and polymers had a stable thermal stability under air atmosphere. The polymers displayed fluorescence emissions at about 590 nm attributed to the π‐conjugated polythiophene. Polymers without doping have a good electrical conductivity (around 4.03×10–7 S/cm at 1 MHz).

Capture and Release of Protein–Nanoparticle Conjugates by Reversible Covalent Molecular Linkers

A hybrid approach to covalently detachable molecules for nanoparticle capture and release from several custom-functionalized surfaces is described. This new surface chemistry capability provides a means for reversible binding of functionalized nanoparticles without relying on costly nucleic acid-based complexation. A new surface linker motif was devised wherein custom molecules were synthesized with components for surface anchoring, cleavage, and target capture through biotin-streptavidin binding. All capture-and-release chemistry is performed using physiological conditions (aqueous, pH 7). Covalent cleavage of linker molecules was achieved through incorporation of a tunable orthogonal reversible covalent (TORC) hydrazone functional group which underwent exchange with a competitive hydrazide aided by an aniline catalyst. The influence of the linker architecture on hydrazone exchange and nanoparticle release was probed by altering the distance between hydrazone and biotin groups using different length PEG spacers. Cleavable linkers were used to functionalize microwells, magnetic separation beads, and gold-coated glass surfaces. Upon functionalization, all surface types bound streptavidin and conjugated nanoparticles regardless of the linker structure. Conversely, the extent of hydrazone exchange as well as release of nanoparticles were influenced both by the hydrazone surface density and the linker molecular structure.

Humidity and Heat Dual Response Cellulose Nanocrystals/Poly(N-Isopropylacrylamide) Composite Films with Cyclic Performance.

It has been widely reported that cellulose nanocrystals (CNCs) demonstrate a special structural color, which stems from chiral nematic domains. Herein, the humidity and heat dual response nanocomposite films with multilayered helical structure were prepared by self-assembling of CNCs and hydrazone groups modified poly(N-isopropylacrylamide) (PNIPAM) copolymers. Furthermore, glutaraldehyde was involved to act as a chemical linker to improve cyclic stability by forming acylhydrazone bonds. The structural color of the films could be easily regulated by humidity, heat, or the content of modified PNIPAM copolymers. The absorption of water in higher humidity led to volume expansion of the resin, resulting in a red shift for up to 145 nm. In contrast, the resin shrank under the temperature above the lower critical solution temperature of PNIPAM, leading to a blue shift for up to 87 nm. It was notable that the change of color can be easily captured by the naked eyes. Moreover, the films exhibited excellent stability and cyclicity in response to either vapor or liquid water due to the chemical linking between CNCs and resins. The as-prepared CNCs/PNIPAM nanocomposite films with humidity or heat responsibilities are promising in stimuli-responsive sensors, printing industry, surface decorations, and so forth.

New Quinoline Based Sulfonamide Derivatives: Cytotoxic and Apoptotic Activity Evaluation Against Pancreatic Cancer Cells

Quinoline is a privileged scaffold especially known with antimalarial and antibacterial drugs before, presently followed anticancer efficiency with a new group of protein kinase inhibitors. In this work, combining quinoline ring, hydrazone and sulphonamide groups, we have synthesized N'-arylidene-2-[4-(quinolin-8-ylsulfonyl)piperazin-1-yl]acetohydrazide derivatives (3a-o) and evaluated their in vitro anticancer activity against cancerous cell lines PANC-1, CAPAN-1, and healthy cell line hTERT-HPNE. Fifteen compounds were synthesized a simple, well-known three-step synthetic procedure starting from 8-quinolinesulfonylchloride. Cytotoxicity studies were performed according to the conventional MTT method. As a second stage, flow cytometric analysis was done to the nine most cytotoxic compounds for determining the mechanism of action which could be apoptosis and/or necrosis. According to anticancer activity evaluation, compound 3b bearing 4-methyl phenyl moiety exhibited significant cytotoxicity which has an IC50 value nearly four-fold lower than cisplatin displayed, whereas compound 3f bearing 4-trifluoromethyl phenyl moiety showed two-fold potency of the standard drug against PANC-1 cell line. Compounds 3h, 3k and 3n against CAPAN-1 also showed significant cytotoxicity, selectively. The most active compounds 3b, 3c, 3d, 3f, 3g, 3h, 3k and 3n against PANC-1 and compounds 3f, 3g, 3h, 3k and 3n against CAPAN-1 were selected to be studied in flow cytometry. Compound 3b induced apoptosis of PANC-1 cells with a percentage of 16.0%, whereas compound 3h induced apoptosis of CAPAN-1 cells with a value of 20.6%.

Self-healing hydrogels with stimuli responsiveness based on acylhydrazone bonds

Thermo-responsive hydrogels consist of natural and synthetic macromolecules were presented based on dynamic acylhydrazone formation, which is self-healable and pH-sensitive. Hydrazone groups modified poly(N-isopropylacrylamide) (PNIPAM) copolymers and aldehyde groups exposed oxidized sodium alginate (OSA) were adopted to prepare the functional hydrogels without any catalyst. Specifically, acylhydrazone bonds, which were served as cross-linking points, endowed the hydrogels with self-healing property confirmed by rheological recovery test. Meanwhile, the hydrogels displayed obvious reversible sol-gel transition under different conditions, leading to that the hydrogels were able to be reshaped repeatedly exposed to pH trigger. Besides, due to the PNIPAM segments were served as the frameworks, the hydrogels were testified to exhibit tunable phase transition temperature between 30 °C and 40 °C around body temperature, which was regulated by variation in aldehyde and hydrazone ratio. The as-prepared hydrogels with self-healing and dual stimuli-responsive properties are beneficial to their bioapplications as drug delivery system, biosensors and soft tissue filling agents, etc.

Codelivery of Hydrophobic and Hydrophilic Drugs by Graphene-Decorated Magnetic Dendrimers.

In this study, a nanocarrier was prepared for the codelivery of a hydrophilic drug (doxorubicin) and a hydrophobic drug (curcumin) to cancer cells. In this nanocarrier, the edges of graphene oxide sheets were decorated with a magnetic-functionalized polyamidoamine dendrimer with hydrazone groups at the end of the polymer. The edge functionalization of graphene sheets not only improved the solubility and dispersibility of graphene sheets but also imparted the magnetic properties to the nanocarrier. The resulting nanocarrier was loaded with doxorubicin through the covalent linkage and curcumin through π-π stacking. The nanocarrier showed a pH-sensitive release for both drugs, and the drug release behavior was also improved by the coimmobilization of both drugs. The cytotoxicity assay of nanocarrier showed low toxicity toward MCF-7 cell compared to unmodified graphene oxide, which was attributed to the presence of a magnetic dendrimer. Besides, the drug-loaded nanocarrier was highly toxic for cells even more than for free drugs. The cellular uptake images revealed higher drug internalization for coloaded nanocarrier than for the nanocarrier loaded with one drug alone. All of the results showed that the codelivery of curcumin and doxorubicin in the presence of the nanocarrier was more effective in chemotherapy than the nanocarrier loaded with one drug.

Supramolecular assembly of hydrogen bonding, ESR studies and theoretical calculations of Cu(II) complexes

A series of copper(II) complexes were synthesized by the reaction of copper(II) chlorid with 1‐phenyl‐3methyl‐(3‐dervitives phenylhydrazo)‐5‐pyrazolone (HLn) yields 1:1 and 1:2 (M:L) complexes depending on the reaction conditions. The elemental analysis, spectral (IR, 1H NMR, UV‐Vis and ESR), conductance and magnetic measurements were used to characterize the isolated complexes. The IR spectral data indicate that the metal ions are coordinated through the oxygen of the keto and nitrogen of hydrazone groups. The UV‐Vis spectra, magnetic moments and ESR studies indicate square planar geometry for Cu(II) complexes (1–3) by NO monobasic bidentate and the two monobasic trans bidentate in octahedral geometry for Cu(II) complexes (4–6). It is found that the change of substituent affects the theoretical calculations of Cu(II) complexes. Molecular docking was used to predict the binding between the ligands (HLn) and the receptors of prostate cancer mutant (2Q7K), breast cancer mutant (3HB5), crystal structure of E. coli (3T88) and crystal structure of S. aureus (3Q8U). The molecular and electronic structures of Cu(II) complexes and quantum chemical calculations were studied. According to intramolecular hydrogen bond leads to increasing of the complexes stability.