Preparation of O-Glycans from Mucins Using Hydrazine Treatment.

Mucin glycomic analysis is crucial owing to the participation of mucin O-glycans in several biological functions. Liquid chromatographic analysis of fluorescently labeled glycans is an effective tool for glycomic analysis. The first step of this analysis involves the release of O-glycans from mucins. As no enzyme is known to release all glycans, chemical methods are required for the process; therefore, hydrazine treatment is a commonly used chemical method. It enables the release of O-glycans from mucin while preserving the aldehyde group at the reducing end. This ensures that the reducing end can be modified using fluorescent reagents. However, it is also accompanied by the degradation of the glycans through a process called "peeling." Here, we describe a method for releasing glycans from mucins using hydrazine treatment with minimal "peeling."

SAR study of N'-(Salicylidene)heteroarenecarbohydrazides as promising antifungal agents.

Clinically available antifungal drugs have therapeutic limitations due to toxicity, narrow spectrum of activity, and intrinsic or acquired drug resistance. Thus, there is an urgent need for new broad-spectrum antifungal agents with low toxicity and a novel mechanism of action. In this context, we have successfully identified several highly promising lead compounds, i.e., aromatic N'-(salicylidene)carbohydrazides, exhibiting excellent antifungal activities against Cryptococcus neoformans, Candida albicans, Aspergillus fumigatus and several other fungi both in vitro and in vivo. Building upon these highly promising results, 71 novel N'-(salicylidene)heteroarenecarbohydrazides 5 were designed, synthesized and their antifungal activities examined against fungi. Based on the SAR study, four highly promising lead compounds, i.e., 5.6a, 5.6b, 5.7b and 5.13a were identified, which exhibited excellent potency against C. neoformans, C. albicans and A. fumigatus, and displayed impressive time-kill profiles against C. neoformans with exceptionally high selectivity indices (SI ≥ 500). These four lead compounds also showed synergy with clinical antifungal drugs, fluconazole, caspofungin (CS) and amphotericin B against C. neoformans. For the SAR study, we also employed quantitative structure-activity relationship (QSAR) analysis by taking advantage of the accumulated data on a large number of aromatic and heteroaromatic N'-(salicylidene)carbohydrazides, which successfully led to rational design and selection of promising compounds for chemical synthesis and biological evaluation.

Synthesis of Hydrazide Derivative of Betulinic Acid, Its Organometallic Complexes, Characterization and Bioassay.

Betulinic acid and its derivatives comprehend an immense prospective toward the development of cytotoxic, antiviral, antimicrobial and antioxidant agents. Cisplatin (cytotoxic drug) divert the attentions to develop organometallic compounds with pronounced biological activities. The current study was aimed for the first time to synthesize, characterize and evaluate biologically a series of metal (Fe, Cu, Zn, Sn and Sb) complexes of betulinic acid hydrazide. First step involved the formation of hydrazide derivative of betulinic acid (ligand) by modification at C-28 carboxylic acid moiety of betulinic acid with hydrazine followed by the synthesis of its metal complexes using salts of different metals (Fe, Cu, Zn, Sn and Sb). Physical state, melting point, Fourier-transform infrared (FT-IR) and 1 H nuclear magnetic resonance (1 H-NMR) spectral techniques were used to characterized the ligand and its metal complexes. Agar well diffusion method and agar tube dilution assay were performed to evaluate its antibacterial and antifungal activities respectively. DPPH assay was carried out to develop antioxidant properties by the reported methods.

Unique Reaction-Based Polynorbornene Sensing Probes for Ultrasensitive Detection of Hydrazine in Both Environmental and Biological Systems.

Hydrazine-mediated formation of 1,4-phthalazinedione analogues from phthalimide-like components has been utilized to formulate fluorescent probe NorTh. A turn-on fluorescent process has been evaluated to detect hydrazine in a highly selective manner by a small molecular probe NorTh and its homopolymer Poly-NorTh. Both these probes have been evaluated as excellent candidates for nanomolar level detection of hydrazine with a time frame of <15 min, which is rapid in terms of real application. Due to the reaction-based detection process, we have achieved high selectivity for our probes toward the identification of hydrazine in the presence of metal ions, anions, amino acids, and various amines. Limit of detection values are 16 and 35 nM for NorTh and Poly-NorTh, respectively, which are well below the permissible limit given by WHO and EPA. Poly-NorTh has been utilized to detect hydrazine in environmental water samples, soil samples, and biological samples to establish the applicability of our probes in real-field scenarios. We introduce an easy-to-synthesize, cheap, and small molecular probe and its polymer for ultrafast, highly selective, and sensitive detection of hydrazine in all possible mediums to counter the hydrazine toxicity through fluorescence turn-on signal output.

Phenothiazine-based fluorescent probes for the detection of hydrazine in environment and living cells.

As an important chemical raw material, hydrazine brings convenience to people's lives and provides opportunities for human development. However, the misuse or leakage of hydrazine has brought pollution to the environment, including water, soil and living organisms. At the same time, hydrazine poses a potential threat to human health as a carcinogen. Despite the enormous challenges, it is crucial to develop an effective method to detect hydrazine in environmental samples. In this work, we have synthesized a series of probes based on phenothiazine fluorophore by the introduction of different substituents and developed a novel probe for the detection of hydrazine. The probe is capable of detecting hydrazine in aqueous solutions with high sensitivity and selectivity, and can be easily fabricated into paper test strips for use in in situ samples. In addition, the probe is effective in detecting hydrazine in water, soil, cells, and zebrafish, providing an excellent tool for detecting hydrazine in the environment.

Design, Synthesis, and In Vitro and In Vivo Bioactivity Studies of Hydrazide-Hydrazones of 2,4-Dihydroxybenzoic Acid.

In this research, twenty-four hydrazide-hydrazones of 2,4-dihydroxybenzoic acid were designed, synthesized, and subjected to in vitro and in vivo bioactivity studies. The chemical structure of the obtained compounds was confirmed by spectral methods. Antimicrobial activity screening was performed against a panel of microorganisms for all synthesized hydrazide-hydrazones. The performed assays revealed the interesting antibacterial activity of a few substances against Gram-positive bacterial strains including MRSA-Staphylococcus aureus ATCC 43300 (compound 18: 2,4-dihydroxy-N-[(2-hydroxy-3,5-diiodophenyl)methylidene]benzohydrazide-Minimal Inhibitory Concentration, MIC = 3.91 µg/mL). In addition, we performed the in vitro screening of antiproliferative activity and also assessed the acute toxicity of six hydrazide-hydrazones. The following human cancer cell lines were used: 769-P, HepG2, H1563, and LN-229, and the viability of the cells was assessed using the MTT method. The HEK-293 cell line was used as a reference line. The toxicity was tested in vivo on Danio rerio embryos using the Fish Embryo Acute Toxicity (FET) test procedure according to OECD No. 236. The inhibitory concentration values obtained in the in vitro test showed that N-[(4-nitrophenyl)methylidene]-2,4-dihydroxybenzhydrazide (21) inhibited cancer cell proliferation the most, with an extremely low IC50 (Inhibitory Concentration) value, estimated at 0.77 µM for LN-229. In addition, each of the compounds tested was selective against cancer cell lines. The compounds with a nitrophenyl substituent were the most promising in terms of inhibition cancer cell proliferation. The toxicity against zebrafish embryos and larvae was also very low or moderate.

A Ratiometric Fluorescent Probe for N2H4 Having a Large Detection Range Based upon Coumarin with Multiple Applications.

Although hydrazine (N2H4) is a versatile chemical used in many applications, it is toxic, and its leakage may pose a threat to both human health and environments. Consequently, the monitoring of N2H4 is significant. This study reports a one-step synthesis for coumarin-based ratiometric fluorescent probe (FP) CHAC, with acetyl as the recognition group. Selected deprotection of the acetyl group via N2H4 released the coumarin fluorophore, which recovered the intramolecular charge transfer process, which caused a prominent fluorescent, ratiometric response. CHAC demonstrated the advantages of high selectivity, a strong capacity for anti-interference, a low limit of detection (LOD) (0.16 µM), a large linear detection range (0-500 µM), and a wide effective pH interval (6-12) in N2H4 detection. Furthermore, the probe enabled quantitative N2H4 verifications in environmental water specimens in addition to qualitative detection of N2H4 in various soils and of gaseous N2H4. Finally, the probe ratiometrically monitored N2H4 in living cells having low cytotoxicity.

Fluorescence detection of hydrazine in an aqueous environment by a corrole derivative.

Broadly, the industrial applications of hydrazine cause environmental pollution and damage to living organisms because of the high toxicity of hydrazine. Therefore, monitoring hydrazine in the environmental system is of great significance to human health. Here, a new fluorescent probe PC-N2 H4 based on corrole dye was developed for the detection of hydrazine that had excellent specificity, low limit of detection (LOD: 88 nM), and a wide pH range (6-12). Upon addition of hydrazine into the probe solution, the strong red fluorescence was 'turned on' centred at 653 nm with a 127-fold fluorescence intensity enhancement. The detection mechanism was proved using ESI-MS, 1 H NMR, and density functional theoretical calculations. Importantly, the probe was utilized to fabricate a ready-to-use test strip to realize the visual inspection of hydrazine. Furthermore, PC-N2 H4 was successfully applied for practical detection of hydrazine in water samples with satisfactory recoveries ranging from 96.2% to 105.0%, and indicating that the designed PC-N2 H4 is highly promising for hydrazine detection in an aqueous environment. Considering the diverse toxicological functions of hydrazine, PC-N2 H4 was also successfully used to image exogenous hydrazine in HeLa cells and zebrafish.

Biological Effects and Crystal X-Ray Study of Novel Schiff Base Containing Pentafluorophenyl Hydrazine: In Vitro and in Silico Studies.

A novel Schiff base namely 3,5-di-tert-butyl-6-((2-(perfluorophenyl)hydrazono)methyl)phenol was successfully synthesized and characterized using FT-IR and 1 H-NMR, 13 C-NMR, and 19 F-NMR. The crystal structure analysis of the Schiff base compound was also characterized with single crystal X-ray diffraction studies and supported the spectroscopic results. The cytotoxicity, anti-bacterial properties, and enzyme inhibition of the compound were also investigated. The molecular docking studies were performed in order to explain the interactions of the synthesized compound with target enzymes. The newly synthesized hydrazone derivative Schiff base compound showed high cellular toxicity on MCF-7 and PC-3 cells. Also, this compound caused low antibacterial effect on E. coli and S. aureus. Besides, the compound exhibited the inhibitory effect against pancreatic cholesterol esterase and carbonic anhydrase isoenzyme I, II with IC50 values 63, 99, and 188 µM, respectively. Consequently, it has been determined that the prepared Schiff base is an active compound in terms of cytotoxicity, enzyme inhibition, and anti-bacterial properties. These results provide preliminary information for some biological features of the compound and can play a major role in drug applications of the Schiff base compound.

Injectable, self-healing hydrogel adhesives with firm tissue adhesion and on-demand biodegradation for sutureless wound closure.

Tissue adhesives have garnered extensive interest as alternatives and supplements to sutures, whereas major challenges still remain, including weak tissue adhesion, inadequate biocompatibility, and uncontrolled biodegradation. Here, injectable and biocompatible hydrogel adhesives are developed via catalyst-free o-phthalaldehyde/amine (hydrazide) cross-linking reaction. The hydrogels demonstrate rapid and firm adhesion to various tissues, and an o-phthalaldehyde-mediated tissue adhesion mechanism is established. The hydrogel adhesives show controlled degradation profiles of 6 to 22 weeks in vivo through the incorporation of disulfide bonds into hydrogel network. In liver and blood vessel injury, the hydrogels effectively seal the incisions and rapidly stop bleeding. In rat and rabbit models of full-thickness skin incision, the hydrogel adhesives quickly close the incisions and accelerate wound healing, which exhibit efficacies superior to those of commercially available fibrin glue and cyanoacrylate glue. Thus, the hydrogel adhesives show great potential for sutureless wound closure, hemostasis sealing, and prevention of leakage in surgical applications.

A Comprehensive Investigation of Hydrazide and Its Derived Structures in the Agricultural Fungicidal Field.

Hydrazides are present in many bioactive molecules and exhibit a variety of biological activities, such as insecticidal, herbicidal, antifungal, antitumor, and antiviral effects. In this Review, we review the application of hydrazide and its derived structures in the agricultural fungicidal field, including monohydrazides, diacylhydrazines, hydrazide-hydrazones, and sulfonyl hydrazides. In addition, the antifungal mechanism of action of the hydrazide derivatives was analyzed and summarized, mainly involving succinate dehydrogenase inhibitors, laccase inhibitors, and targeting plasma membranes. Finally, based on the structural analysis of the novel fungicidal lead compounds, the structure-activity relationship of the hydrazide derivatives was constructed and the development trend of hydrazide structures in fungicidal applications was prospected. It is hoped that this Review can provide some significant guidance for the development of new hydrazide fungicides in the future.

A near-infrared ratiometric fluorescent probe for hydrazine and its application for gaseous sensing and cell imaging.

Hydrazine (N2H4) is a widely used raw material in the chemical industry, but at the same time hydrazine has extremely high toxicity. Therefore, the development of efficient detection methods is crucial for monitoring hydrazine in the environment and evaluating the biological toxicity of hydrazine. This study reports a near-infrared ratiometric fluorescent probe (DCPBCl2-Hz) for the detection of hydrazine by coupling a chlorine-substituted D-π-A fluorophore (DCPBCl2) to the recognition group acetyl. Due to the halogen effect of chlorine substitution, the fluorophore has an elevated fluorescence efficiency and a lowered pKa value and is suitable for physiological pH conditions. Hydrazine can specifically react with the acetyl group of the fluorescent probe to release the fluorophore DCPBCl2, so the fluorescence emission of the probe system significantly shifted from 490 nm to 660 nm. The fluorescent probe has many advantages, such as good selectivity, high sensitivity, large Stokes shift, and wide applicable pH range. The probe-loaded silica plates can realize convenient sensing gaseous hydrazine with content down to 1 ppm (mg/m3). Subsequently, DCPBCl2-Hz was successfully applied to detect hydrazine in soils. In addition, the probe can also penetrate living cells and allow the visualization of intracellular hydrazine. It can be anticipated that probe DCPBCl2-Hz will be a useful tool for sensing hydrazine in biological and environmental applications.

Synthetic Approaches, Biological Activities, and Structure-Activity Relationship of Pyrazolines and Related Derivatives.

It has been established that pyrazolines and their analogs are pharmacologically active scaffolds. The pyrazoline moiety is present in several marketed molecules with a wide range of uses, which has established its importance in pharmaceutical and agricultural sectors, as well as in industry. Due to its broad-spectrum utility, scientists are continuously captivated by pyrazolines and their derivatives to study their chemistry. Pyrazolines or their analogs can be prepared by several synthesis strategies, and the focus will always be on new greener and more economical ways for their synthesis. Among these methods, chalcones, hydrazines, diazo compounds, and hydrazones are most commonly applied under different reaction conditions for the synthesis of pyrazoline and its analogs. However, there is scope for other molecules such as Huisgen zwitterions, different metal catalysts, and nitrile imine to be used as starting reagents. The present article consists of recently reported synthetic protocols, pharmacological activities, and the structure-activity relationship of pyrazoline and its derivatives, which will be very useful to researchers.

A highly sensitive ratiometric fluorescent probe based on fluorescein coumarin for detecting hydrazine in actual water and biological samples.

Hydrazine (N2 H4 ) is a highly toxic and harmful chemical reagent. Fluorescent probes are simple and efficient tools for sensitive monitoring of N2 H4 enrichment in the environment, humans, animals, and plants. In this work, a ratiometric fluorescent probe (FP-1) containing coumarin was used for hydrazine detection. The proposed FP-1 probe had a linear detection range of 0-250 µM and a limit of detection (LOD) of 0.059 µM (1.89 ppb). A large red Stokes shift was observed in fluorescence and UV-vis absorption spectra due to the hydrolysis of ester bonds between FP-1 and hydrazine. The hydrazine detection mechanism of FP-1 was also investigated using density functional theory (DFT) calculations. Finally, FP-1 could sensitively and selectively monitor hydrazine in actual water samples and BEAS-2B cells. Therefore, it has great application potential in environmental monitoring and disease diagnosis.

Naphthalene-based fluorescent probe for on-site detection of hydrazine in the environment.

The widespread occurrence of hydrazine residues in the environment, including in water, soil, and organisms, is a potential health threat to humans. Therefore, the development of an efficient method for the detection of hydrazine in environmental samples is highly desirable although it poses a significant challenge. In this study, we designed and synthesized a series of naphthalene-based fluorescent dyes through structural engineering and developed a novel probe for hydrazine detection. The probe could provide a distinct fluorescence response toward hydrazine in aqueous solution with high sensitivity and selectivity. Moreover, paper-based test strips can be easily fabricated using this probe, enabling the portable on-site detection of hydrazine with the aid of a smartphone. Furthermore, we demonstrated that this probe is capable of recognizing hydrazine in various environmental samples, including water, soil, plants, and zebrafish embryos. This research provides a promising tool for the detection of hydrazine in the environment.

Benzylic C(sp3)-H Bonds Play the Dual Role of Starting Material and Oxidation Inhibitor for Hydrazides in the Electrochemical Synthesis of Hydrazones.

The electrooxidation of benzylic C(sp3)-H bonds to produce hydrazones as an alternate for conventional pathways has an enormous dignity. Under the aegis of electricity, instead of hazardous metal catalysts and external oxidants, we unveil an electrochemical process for electrooxidation of various benzylic C(sp3)-H bonds in aqueous media in all pH ranges that subsequently produce hydrazones with further reactions. This electrooxidative reaction strategy provides an acceptable condition for synthesizing hydrazones with various functional groups in good efficiency and amenable to gram-scale synthesis. The electrochemical oxidation condition proves an excellent level of compatibility with super cheap electrolyte NaCl for the oxidation of benzylic C(sp3)-H position despite the highly oxidizable hydrazide group remaining intact in the reaction.

Copper(I)-Catalyzed Three-Component Selenosulfonation of Maleimides with Sulfonyl Hydrazides and Diselenides via Radical Relay.

By employing Cu(CH3CN)4PF6 as the catalyst and tert-butyl hydroperoxide as the oxidant, we realized a three-component radical selenosulfonation of substituted maleimides, sulfonyl hydrazides, and diphenyl diselenides, providing a series of 3,4-selenosulfonylated succinimides in moderate to good yields. This reaction features broad substrate scopes, high functional-group tolerability, and feasibility of gram-scale synthesis, enabling one-step construction of C-SO2 and C-Se bonds under mild reaction conditions. Preliminary mechanistic studies support the free-radical-induced pathway.

Robust ERα-Targeted Near-Infrared Fluorescence Probe for Selective Hydrazine Imaging in Breast Cancer.

Breast cancer is the most common malignancy in women and may become worse when a high concentration of hydrazine is absorbed from the environment or drug metabolite. Therefore, rapid and sensitive detection of hydrazine in vivo is beneficial for people's health. In this work, a novel estrogen receptor α (ERα)-targeted near-infrared fluorescence probe was designed to detect hydrazine levels. The probe showed good ERα affinity and an excellent fluorescence response toward hydrazine. Selectivity experiments demonstrated that the probe had a strong anti-interference ability. Mechanistic studies, including mass spectrometry (MS) and density functional theory (DFT) calculation, indicated that intermolecular charge transfer (ICT) progress was hindered when the probe reacted with hydrazine, resulting in fluorescent quenching. In addition, the probe could selectively bind to MCF-7 breast cancer cells with excellent biocompatibility. The in vivo and ex vivo imaging studies demonstrated that the probe could rapidly visualize hydrazine with high contrast in MCF-7 xenograft tumors. Therefore, this probe can serve as a potential tool to robustly monitor hydrazine levels in vivo.

Decoding the response of complete autotrophic nitrogen removal over nitrite (CANON) performance and microbial succession to hydrazine and hydroxylamine: Linking performance to mechanism.

The influence of hydrazine (N2H4) and hydroxylamine (NH2OH) on performance and microbial community structures of complete autotrophic nitrogen removal over nitrite (CANON) process were assessed in this study. Experimental results demonstrated that CANON process was successfully started up and got total nitrogen removal efficiency (TNRE) of 53.6 % ± 9.8 % and 56.4 % ± 6.5 % under 1.0 and 0.5 mg L-1 N2H4 and NH2OH, respectively. N2H4 and NH2OH promoted activity of ammonia-oxidizing bacteria (AOB) and anaerobic ammonium oxidation bacteria (AnAOB), and inhibited activity of nitrite-oxidizing bacteria (NOB). Meanwhile, the stable operation of CANON process could be maintained without N2H4 auxiliary. While, performance assisted by NH2OH was fluctuated without NH2OH addition, suggesting that both N2H4 and NH2OH had a persistent and reversible inhibition on NOB. This study reveals new insights into influence of N2H4 and NH2OH on CANON performance.

Two Ratiometric Fluorescent Probes Based on the Hydroxyl Coumarin Chalcone Unit with Large Fluorescent Peak Shift for the Detection of Hydrazine in Living Cells.

Hydrazine is widely used in industrial and agricultural production, but excessive hydrazine possesses a serious threat to human health and environment. Here two new ratiometric fluorescence probes, DDP and DDC, with the hydroxyl coumarin chalcone unit as the sensing site are developed, which can achieve colorimetric and ratiometric recognition for hydrazine with good sensitivity, excellent selectivity, and anti-interference. The calculated fluorescence limits of detections are 0.26 µM (DDC) and 0.14 µM (DDP). The ratiometric fluorescence response to hydrazine is realized through the adjustment of donor and receptor units in coumarin conjugate structure terminals, accompanied by fluorescence peak shift about 200 nm (DDC, 188 nm; DDP, 229 nm). Stronger electropositivity in the carbon-carbon double bond is helpful to the first phase addition reaction between the probe and hydrazine. Higher phenol activity in the hydroxyl coumarin moiety will facilitate the following dihydro-pyrazole cyclization reaction. In addition, both of these probes realized the convenient detection of hydrazine vapor. The probes were also successfully applied to detect hydrazine in actual water samples, different soils, and living cells.