Hydrazide Functional Groups Research Articles

Self-healing hydrogel prepared from gallic acid coupled P(NIPAM-co-AH) and oxidized sodium alginate for diabetic wound repairing

Due to the complex wound microenvironment, diabetic wound repairing remains as an important clinical problem caused by excessive ROS, bacterial infection and persistent inflammation. In this study, gallic acid (GA) was grafted onto the P(NIPAM-co-AH) copolymers to synthesize functional copolymer with hydrazide functional group and GA moiety (PNHG). Then the PNHG was cross-linked by sodium alginate oxide (OSA) to fabricate self-healing hydrogel with multifunctionalility of tissue adhesion, ROS scavenging, biodegradability and antibacterial property. The multifunctional hydrogel showed expected advantages proved the GA enhanced the ROS scavenging property, tissue adhesion and antibacterial activity. Moreover, the hydrogel preserved the biocompatibility and the biodegradability of the precursors. Furthermore, the multifunctional hydrogel showed improved hemostatic property and greatly promoted repairing rate of diabetic wounds on mice model in vivo. In conclusion, this multifunctional PNHG/OSA hydrogel can play a important role as wound dressing in the future.

A Multifunctional Antibacterial Hydrogel with Injectable, Antifouling, and Conductive Properties

Zwitterionic hydrogels have shown promise as effective antifouling materials in wound dressing applications owing to their robust hydrate layer that offers protection against microbial infections. However, the traditional covalently crosslinked zwitterionic hydrogels may not be sufficient to adapt to irregular injury sites and fully address microbial infections within the wound. Herein, we propose an injectable zwitterionic hydrogel that utilizes dynamic hydrazone chemistry via aldehyde and hydrazide functional groups and contains N-halamine antibacterial agents. The dual dynamic exchangeable covalently and physically crosslinked structure resulting from the combination of hydrazone bonds and zwitterion interactions facilitates instantaneous gelation (within a few seconds) and extreme stability without any degradation (for over 2 months). The hydrogels exhibit remarkable fouling resistance against proteins and bacteria while demonstrating excellent antibacterial performance in vitro without compromising cytocompatibility. More importantly, we demonstrate their inherent conductivity properties and sensitivity to external pressure. The combination of the injectability, antifouling, antibacterial, cytocompatibility, and electrical conductivity properties achieved offers the potential to expand the utility of zwitterionic hydrogels in biological applications.

Challenges and Strategies for Synthesizing Glutamyl Hydrazide Containing Peptides

AbstractHerein, we detail several specific challenges that hinder the effective synthesis of glutamyl hydrazide containing peptides, and we describe a synthetic strategy to work around these challenges. Glutamyl hydrazide is an unnatural amino acid residue that bears an acyl hydrazide functional group on its side chain. This family of compounds has the potential to provide potent and selective inhibitor molecules for several families of enzymes. During peptide synthesis, however, these side chains—even in protected form—can derail the synthesis by initiating undesired side reactions. Avoiding these side reactions is critical for enabling effective access to this family of compounds.

Physicochemical Properties of Silicas Modified with Hydrazide Functional Groups

Physicochemical Properties of Silicas Modified with Hydrazide Functional Groups

Facile one pot green synthesis of –NH2 surface functionalized graphene-polymer nanocomposite: Subsequent utilization as stabilizer in pickering emulsions

Simple and cost-effective synthesis of surface functionalized graphene and its nanocomposites with polymers is strongly desirable to further expand their utility. Most of the methods reported till date use separate procedures to reduce the graphene oxide (GO), functionalize the resulting graphene and subsequently prepare the nanocomposite with polymers respectively. In this report, we are utilizing a one-pot hydrothermal synthetic procedure to prepare polymer-graphene nanocomposite through in-situ reduction of GO and amine functionalization of resulting graphene. Polyacryloyl hydrazide (PAHz) possessing hydrazide functional groups is used as the reducing agent to convert the GO to the graphene, subsequently functionalize the resulting graphene with the amino groups and encapsulates the resulting –NH2 functional graphene to prepare the PAHz/rGO nanocomposite. Various characterization techniques including UV-Vis, fluorescence, XPS, HRTEM and DLS is utilized to characterize the nanocomposite. The resulting nanocomposites possessing hydrodynamic size of ~ 40 nm is utilized to stabilize Pickering emulsion based on olive oil/n-decane and water. The resulting Pickering emulsion exhibited excellent stability with proper droplet packing and no sign of creaming till 17 days under ambient conditions suggesting the efficacy of the PAHz/rGO nanocomposite as stabilizing agent, which is superior compared to a number of systems studied in recent literature. Overall, the synthesized nanocomposites with a narrow size distribution can be potentially utilized in a number of useful areas.

Carbon dioxide capturing evaluation of polyacryloyl hydrazide solutions via rheological analysis for carbon utilization applications

PAHz is a relatively inexpensive material which has several industrial applications but its interaction and utilization in conjunction with CO2 has not been explored. In this study, carbon dioxide (CO2) capturing potential of a polymeric material viz., polyacryloyl hydrazide (PAHz) with specific hydrazide functional group is reported. Characterization tools i.e., microscopic, absorption rate kinetics and rheological analysis were used to determine optimum composition ensuing CO2 uptake via interaction between functional group and CO2 molecules. A varying concentration i.e., 5–30 wt% of PAHz was used. PAHz solution with ≤10 wt% was entirely saturated by small size CO2 bubbles and absorption increases with increasing equilibrium pressure as shown by molality results. With high PAHz concentration >10 wt%, capturing of CO2 markedly decreased and globules of moderately entrapped gas caused reduction in aqueous phase participating in CO2 absorption. CO2 responsiveness with a functional group to develop gelling in solution depended on PAHz concentration. At low concentration, PAHz chains were lesser in population which developed preliminary gelling in solution while high concentration produced sufficient PAHz chains for CO2 interaction. This resulted in the solution to display premature gelling that restricted further entry of CO2, and several CO2 bubbles aggregated near top of solution. In presence of CO2, a sol-gel transition in PAHz solution was anticipated when concentration ∼15 wt%. Finally, rheological investigations were performed to find out the effect of CO2 capturing on the rheological behaviour of solutions. The rheological properties (viscosity and moduli) for 5 and 10 wt% PAHz solutions did not change much after CO2 capturing and stable Newtonian behaviour was observed. The observations presented in the study present a strong case for application of liquid PAHz sample for use as mobility control agent during CO2 injection for EOR and carbon geo-sequestration.

Investigating Cocrystallization of Carbamazepine with Structurally Compatible Coformers: New Cocrystal and Eutectic Phases with Enhanced Dissolution.

In this work, carbamazepine (CBZ), an anticonvulsant drug was cocrystallized with several structurally complement coformers (coformers with amide, acid and hydrazide functionalgroups) to enhance its dissolution. CBZ formed a cocrystal phase with acetamide (ACE) when mixtures of CBZ and ACE (containing CBZ mole fractions, XCBZ of 0.25, 0.33, 0.5, and 0.67) were subjected to solid-state grinding (SSG), evaporative crystallization (EC), slurry conversion (SC), and slow cooling crystallization (SLC). Upon heating, the CBZ-ACE cocrystal phase formed from CBZ-ACE mixtures containing XCBZ of 0.25, 0.33 and 0.67 underwent solid-state phase transition to CBZ form I and CBZ cocrytsal phase obtained from the CBZ-ACE mixture containing XCBZ of 0.5 converted to CBZ form III. Interestingly, slow cooling cocrystallization experiments resulted in crystallization of a cocrystal as well as the CBZ dihydrate forms. The powder dissolution studies demonstrated that among the different CBZ-ACE-SSG cocrystal phases, CBZ-ACE-SSG-XCBZ-0.33 cocrystal exhibited 7.47 times improved dissolution whereas the CBZ eutectic phase with nicotinic acid hydrazide (NAH) exhibited 4.93 times increased dissolution when compared to raw CBZ.

Coupling Reactions by Highly Efficient Octacalix[4] Pyrrole Wrapped Scrupulous Nano-Palladium Catalyst

Work is focused on OHCP-PdNPs synthesis with the help of meso-modified OHCP derivatives. OHCP-PdNPs utilized for the C-C coupling reactions as an efficient nanocatalyst. This study includes the stability as well as pH studies of fine PdNps. OHCP is an electron-rich ligand that is capable of reducing as well as encapsulate the metal ions because of the availability of electron-rich hydrazide functional group and H-bonding promoter four pyrrole units. In comparison with normal hydrazine, CP-hydrazide has a higher withdrawal ability, so Pd-NPs periphery is surrounded by them and undergoes stronger web-like capping on palladium. Similarly, OHCP-PdNPs are aqueous and air-stable, besides affordable alternatives for the synthesis of stable PdNPs. Moreover, encapsulating the periphery of PdNPs using OHCP enhances its activity and selectivity. Which indicates the perfect association of metal-cage recognition? This recognition may lead to numerous promising applications towards an efficient catalytic activity.

Two-Stage Strategy for Development of Proteolysis Targeting Chimeras and its Application for Estrogen Receptor Degraders.

Proteolysis targeting chimeras (PROTACs) have emerged as useful chemical probes and potential therapeutics by taking advantage of the ubiquitin-proteasome system to degrade intracellular disease-associated proteins. PROTACs are heterobifunctional molecules composed of a target protein ligand, E3 ubiquitin ligase ligand, and a linker between them. The generation of efficient PROTACs requires screening of many parameters, especially the lengths and types of the linkers. We report our proof-of-concept study using a two-stage strategy to facilitate the development of PROTACs against the estrogen receptor (ER). In stage one, a library of close to 100 PROTACs was synthesized by simply mixing a library of ERα ligands containing a hydrazide functional group at different positions with a preassembled library of E3 ligase ligands bearing different types and lengths of linkers with a terminal aldehyde group in a 1:1 ratio. Cell-based screening occurred without further purification, because the formation of the acylhydrazone linkage is highly efficient and produces water as the only byproduct. Compound A3 was the most potent ER degrader in two ER+ cell lines (DC50= ∼ 10 nM, Dmax= ≥ 95%). Stage two involved transformation to a more stable amide linker to generate a more drug-like molecule. The new compound, AM-A3, showed comparable biological activity (DC50 = 1.1 nM, Dmax = 98%) and induced potent antiproliferation (IC50= 13.2 nM, Imax= 69%) in MCF-7. This proof-of -concept study demonstrates that the two-stage strategy can significantly facilitate the development of PROTACs against ER without the tedious process of making large numbers of PROTACs one by one. It has the potential to be expanded to many other targets.

Aromatic Hydrazide Compounds That Inhibit the Growth of Mycobacterium tuberculosis

Aims: To demonstrate the efficacy of aromatic hydrazide compounds to inhibit growth of Mycobacterium tuberculosis.
 Study Design: To synthesize tuberculostats and test their antibacterial activity in-vitro.
 Place and Duration of Study: University of Nebraska, Durham Science Center, 6001 Dodge Street, Omaha NE 68182, and Texas A&M Health Science Center, Department of Microbial Pathogenesis and Immunology, 8447 State Hwy 47, Medical Research and Education Building, Room #3012, Bryan, TX 7780. From March 2019 to October 2019.
 Methodology: Hydrazide functional groups were formed by covalently bonding hydrazine onto a carbonyl carbon that is a substituent of a single aromatic ring. Microwave excitation was utilized for synthesis, followed by evaluation of antibacterial activity. These compounds were placed into tissue culture media at various concentrations and then Mycobacterium tuberculosis bacteria was added, in order to determine the level of growth inhibition. Growth inhibition of the bacteria was measured as a function of compound concentration versus growth inhibition.
 Results: Compounds A, B, C, and D carry hydrazide groups as a substituent to a single aromatic ring. All four compounds show zero violations of Rule of 5, indicating favorable drug-likeness. All four compounds showed greater than 50% growth inhibition of bacteria at concentrations below 50 micrograms per milliliter. Growth inhibition was measured by colony forming units and luminescence. Polar surface area, Log P, molecular volume, and other molecular properties were determined for these four compounds.
 Conclusion: These four hydrazide compounds induced substantial inhibition of bacterial growth. Microwave excitation for the synthesis of hydrazide compounds is effective. These compounds have favorable drug-likeness properties and are highly effective inhibiting the growth of Mycobacterium tuberculosis.

Visualization of oxidative stress-induced carbonylation in live mammalian cells.

Oxidative stress (OS) is associated with a wide variety of diseases and disorders. Detection of oxidative stress in living systems typically relies on fluorescent probes for reactive oxygen species (ROS), which is challenging because of their short life span and high reactivity. Oxidative damage caused by OS produces a more stable signal, but these biomarkers are usually detected using techniques that are not compatible with live cells. OS-induced biomolecule carbonylation is a stable modification that also possesses a chemically reactive functional group, and its detection typically employs a chemical reaction with a hydrazine-containing probe within the process. These hydrazone-forming reactions require strong acid catalysis or nucleophilic catalysis with an aromatic amine when performed on isolated biomaterial or on fixed cells. In live cells, however, hydrazone-forming reactions are surprisingly facile. Fluorophores possessing hydrazine or hydrazide functional groups can undergo reaction with carbonylated biomolecules in live cells, and these products can be observed using fluorescence microscopy. In this chapter, standard methods for detection of biomolecule carbonylation in cell lysate and in intact cells are enumerated. Protocols for fluorescently labeling biomolecule carbonylation in live cells are provided for commercially available fluorophores. Also described is a one-step protocol that employs one of the hydrazine-modified fluorophores developed in our lab, which are designed to be live-cell compatible and to undergo a spectral change upon hydrazone formation. Finally, a procedure for observing both biomolecule carbonylation and ROS production simultaneously is provided.

Self-healing PEG-poly(aspartic acid) hydrogel with rapid shape recovery and drug release

Self-healing hydrogels were prepared from hydrazide functionalized poly(aspartic acid) (PAsp). The polymer succinimide (PSI) was reacted with hydrazine and ethanolamine successively to obtain water soluble poly(aspartic acid) derivatives with hydrazide functional groups (PAEH). The hydrogel was prepared by cross-linking PAEH with poly(ethylene glycol) dialdehyde (PEG DA) under mild conditions without addition of catalyst. The rheological property and the self-healing property of the hydrogels were investigated intensively. The in vitro toxicity experiment showed the hydrogels have good bio-compatibility and the doxorubicin (DOX)-loaded hydrogels showed controlled release profile. Importantly, the hydrogel can still be degraded based on poly(aspartic acid) backbone. The bio-degradable poly(amino acid) based on self-healing hydrogel could have great potential application in bioscience including tissue repairing, drug loading and release.

Sorbents based on mesoporous silicas modified with hydrazide functional groups

Sorbents based on mesoporous silicas modified with hydrazide functional groups

Mechanistic Study on the Antibacterial Activity of Self-Assembled Poly(aryl ether)-Based Amphiphilic Dendrimers

The increased threat of bacterial resistance against conventional antibiotics has warranted the need for development of membrane targeting antibacterial agents. Several self-assembled cationic amphiphiles with different supramolecular structures have been reported in recent years for potent antibacterial activity with increased specificity. In this study, we describe the self-assembly and antibacterial activity of four lower generation poly(aryl ether)-based amphiphilic dendrimers (AD-1, AD-2, AD-3, and AD-4) containing terminal amine (PAMAM-based), ester, and hydrazide functional groups with varied hydrophobicity. Among the four dendrimers under study, the amine-terminated dendrimer (AD-1) displayed potent antibacterial activity. The ratio of surface cationic charge to hydrophobicity had a significant effect on the antibacterial activity, where AD-3 dendrimer with increased surface cationic charges exhibited a higher minimum inhibitory concentration (MIC) than AD-1. AD-2 (ester terminated) and AD-4 (hydrazide terminated) dendrimers did not show any bactericidal activity. The amphiphilic dendrimer-bacteria interactions, further validated by binding studies, also showed significant changes in bacterial morphology, effective membrane permeation, and depolarization by AD-1 in comparison with AD-3. Molecular dynamics simulations of AD-1 and AD-3 on bacterial membrane patches further corroborated the experimental findings. The structural conformation of AD-1 dendrimer facilitated increased membrane interaction compared to AD-3 dendrimer. AD-1 also displayed selectivity to bacterial membranes over fibroblast cells (4× MIC), corroborating the significance of an optimal hydrophobicity for potent antibacterial activity with no cytotoxicity. The self-assembled (poly(aryl ether)-PAMAM-based) dendrimer (AD-1) also exhibited potent antibacterial activity in comparison with conventional higher generation dendrimers, establishing the implication of self-assembly for bactericidal activity. Moreover, the detailed mechanistic study reveals that optimal tuning of the hydrophobicity of amphiphilic dendrimers plays a crucial role in membrane disruption of bacteria. We believe that this study will provide valuable insights into the design strategies of amphiphilic dendrimers as antibacterial agents for efficient membrane disruption.

Highly selective extraction of peptides with an N‐terminal 2‐amino alcohol structure using a hydrazide functionalized magnetic chitosan nanostructure

AbstractA novel hydrazide functionalized magnetic chitosan nanostructure was developed as a sorbent for the selective extraction of peptides with N‐terminal serine and threonine. Iron oxide nanoparticles were synthesized by the co‐precipitation method. Chitosan was covalently bonded onto the surface of magnetic Fe3O4 nanoparticles. Magnetic chitosan was modified by glutaraldehyde as a linking agent. Hydrazide functional groups were created on the sorbent surface by immobilization of adipic dihydrazide. The sorbent characterization was performed by scanning electron microscopy and Fourier transform infrared spectroscopy. The studied peptides were labeled by oxidation of the hydroxyl group in 1,2‐amino alcohol structure under controlled conditions. The aldehyde‐form peptides were immobilized on the surface of the sorbent through the hydrazide group. The formed hydrazone compounds were eluted by hydroxylamine reagent. The release oximated peptides were determined by high‐performance liquid chromatography. The effect of extraction time, elution time and elution volume on extraction performance were studied. Extraction and desorption processes were performed in 6 h. The adsorption efficiency of the sorbent was 68 and 61% for peptides with N‐terminal serine and threonine, respectively. The sorbent showed excellent specificity in extracting peptides with N‐terminal serine and threonine in the presence of a peptide with non‐N‐terminal serine and threonine.

Evaluation of Colorimetric BCA-Based Quantification of Hydrazide Groups on Magnetic Particles

Magnetic micro- and nanoparticles (MPs) are considered to provide excellent solid support for many immunoanalytical and bioaffinity applications, particularly when they contain hydrazide groups available for site-specific immobilization of various glycoproteins, such as immunoglobulin G and enzymes. To prepare a highly active bioaffinity carrier with sufficient binding capacity, knowledge as to the type and concentration of functional groups used for ligand binding is crucial. Described here is a simple, nontoxic method for rapid estimation of hydrazide functional groups bound to MPs using bicinchoninic acid (BCA). BCA kits are routinely used for colorimetric detection and quantification of total protein in liquid samples. In this study, the BCA reagent was applied for quantification of hydrazide groups on MPs. The approach was carried out using an adipic acid dihydrazide (ADH) solution and subsequently using various hydrazide-containing magnetic and nonmagnetic carriers differing in the density of hydrazide groups. The BCA test’s results obtained on the MPs were compared with those from conventional amino and hydrazide group quantification by the 2,4,6-trinitrobenzenesulfonic acid (TNBS) test.

New crosslinked hydrazide–based polymers as Cr(VI) ions adsorbents

Cr(VI) salts are abundantly used in the industrial processes, but they have become serious water pollutants and their removal from the wastewaters is a huge challenge. In the present study, two new crosslinked polymers having hydrazide functional group, differing in the nature of crosslinking agents ethyleneglycol dimethacrylate or divinyl benzene, were synthesized for use as Cr(VI) ion adsorbents. These were analysed by FTIR, SEM, EDS, TEM, AFM and XRD to confirm their structure. The adsorption parameters such as contact time, temperature, pH and Cr(VI) ions concentration were investigated. Adsorption of Cr(VI) ions was rapid, pH dependent, and up to 100% adsorption from 100ppm solution was observed within 1min at pH=2.0 and 25°C. Langmuir isotherm best fitted the experimental values. These adsorbents, synthesized by a simple green protocol, show 100% adsorption efficiency even at a very low concentration of 1.0ppm. Adsorption kinetics, mechanism and thermodynamics of the adsorption process were also investigated.

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Tunable pH and redox-responsive drug release from curcumin conjugated γ-polyglutamic acid nanoparticles in cancer microenvironment

Tunable pH and redox responsive polymer was prepared using γ-polyglutamic acid (γ-PGA) with linker 3-mercaptopropionic acid (3-MPA) (γ-PGA_SH) via oxidation to obtain redox responsive disulfide (γ-PGA_SS) backbone and adipic acid dihydrazide (ADH) (γ-PGA_SS_ADH) with hydrazide functional group for pH responsiveness. Further curcumin (Cur) was conjugated through hydrazone bond of the γ-PGA_SS_ADH via Schiff base reaction to obtain (γ-PGA_SS_ADH_Cur). The prepared systems were characterized by Fourier transform infrared spectroscopy (FTIR), Raman spectroscopy, Electrospray ionization quadrupole time-of-flight mass spectrometry (ESI-Qq-TOF-MS/MS) and Solid state nuclear magnetic resonance (SS NMR) techniques. γ-PGA_SS_ADH_Cur formed self-assembled core shell nanoparticles (NPs) in existence of stabilized aqueous medium. γ-PGA_SS_ADH_Cur NPs maintained its stability in physiological condition. NPs tunable Cur release and cytotoxicity were observed for γ-PGA_SS_ADH_Cur NPs in both acidic and redox conditions mimicking the cancer microenvironment. γ-PGA_SS_ADH_Cur NPs uptake study showed via endocytosis mechanism resulted in the lysosomal entrapment of these NPs within the cell. γ-PGA_SS_ADH_Cur NPs exhibited a dual stimuli responsive drug delivery and can be used as a smart and potential drug delivery system in cancer microenvironment.

COMPARATIVE CHARACTERISTICS OF Co(II), Ni (II), Cu(II) COORDINATION COMPOUNDS WITH SOME HYDRAZONES OF PYRUVIC ACID

Сonducted comparative analysis of the coordination compounds of Co2+, Ni2+, Cu2+ with condensation products of 2-(7-bromo-2-oxo-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepin-1-yl) acetohydrazide – Hydazepam (Hydr), nicotinoyl- and isonicotinoyl hydrazones (H2N, H2I) with pyruvic acid (HPv): [Co(HydrHPv)Cl2]·2H2O (I), [Ni(HydrPv)2] (II), [Cu(HydrHPv) (H2O)Cl2] (III), [CoCl(HNPv)(H2O)2] (IV), [CoCl(HIPv)(H2O)2] (V), [NiCl(HNPv)(H2O)2] (VI), [NiCl(HIPv)(H2O)2] (VII), [CuCl(HNPv)]·H2O (VIII), [CuCl(HIPv)]·H2O (IX). Complexes characterized by elemental analysis, IR spectroscopy, electrical conductivity, and magnetic susceptibility. Thermal stability of the complexes has been characterized. Structure of the coordination node of the complexes has been determined by EXAFS-spectroscopy. Regardless of composition, structure by heterocyclic nitrogen-containing moiety of the molecules HydrHPv, H2NРv, H2IРv formation of I-IX complexes is due to binding of complexing with a hydrazide functional group ketone form of the ligands. Ni2+ complexes II, VI, VII are different by composition (Ni2+:HydrHPv в II = 1:2, Ni2+:H2NРv(H2IРv) в VI, VII = 1:1). Co2+, Cu2+ complexes with the same composition (M2+:ligand = 1:1). H2NPv, H2IPv in all complexes IV-IX – tridentate, occurs deprotonation and bonding carboxylate group НPv. HydrHPv coordinated to the Co2+, Cu2+ bidentate (I, III), without participation of the carboxylic group, and to the Ni2+ – tridentate (II).