Aroyl Hydrazones Research Articles

New hydrophilic mesoporous copper (II) coordination polymers obtained from poly(ethylene terephthalate) (PET) waste for diesel removal in water

Two new hydrophilic mesoporous copper (II) coordination polymers were synthetized from poly(ethylene terephthalate) waste by the coordination reaction under solvothermal conditions in only 60 min with quantitative yields. Both polymers and their aroyl hydrazone derivates were fully characterized by NMR (1H,13C, and 1H-15N HMBC), vibrational analysis, XPS spectroscopy, and high-resolution mass spectrometry. The XPS analysis of the new polymers 3a and 3b evidenced the formation of the N → Cu and O → Cu coordination bonds and the high-resolution mass spectrometry corroborates the presence of copper atoms in their molecular structure. The textural properties of 3a and 3b were analyzed by physisorption revealing that both materials can be classified as mesoporous materials with a pore size distribution of around 14.98 nm. Furthermore, the mesoporous copper (II) coordination polymer 3a exhibits a linear behavior with a maximum adsorption capacity of 743 and 1553 mg g−1 at 0.10 and 0.20 g/L, respectively. The adsorption/desorption cycles of 3a reveal that the novel copper (II) coordination polymers obtained from poly(ethylene terephthalate) (PET) waste had a greater adsorption capacity (1553 mg g−1); showing that structural modification of this type of coordination polymers can be a remarkable tool to increase the adsorption properties through the chemical modification to more hydrophilic, porous and crystalline coordination polymers.

Synthesis, Characterization, and Biological Activity of Di‐2‐pyridyl Ketone Aryl Hydrazone and Its Copper(II) Complex and the Interaction of Di‐2‐pyridyl Ketone Aryl Hydrazone with DNA Bases

AbstractThe development of antibiotic resistance has also increased the interest in hydrazones. In this paper, we describe the new aroyl hydrazone and its Cu(II) complex, which we synthesized. Aroyl hydrazone (HL) was prepared by the condensation reaction of 3‐hydroxy‐2‐naphthoic hydrazide with di‐2‐pyridyl ketone. Ligand (HL) and its transition metal complexes [CuL2] (1), have been characterized by elemental analysis, FT‐IR, UV‐Vis., 1H‐NMR, and LC–MS techniques. The molecular structure of HL, whose crystal structure could not be obtained, was elucidated by the DFT/B3LYP/6‐311+G(d, p) method. The optimized molecular structure, total energy, molecular orbital energy values, molecular electrostatic potential map, reactivity parameters, and interaction with DNA bases were investigated. Theoretical UV‐vis spectra of HL were obtained with TD‐DFT in different solvent environments. In addition, the ligand and its complex were examined for their antimicrobial activity against pathogenic microorganisms by using a minimal inhibitory concentration method (MIC). It was determined that the [CuL2] (1) complex was generally moderately active. It was also observed that the [CuL2] (1) complex was more active than the HL.

Physicochemical and Analytical Studies of Some Monomer and Polymer Complexes Derived from Selected Aroyl Hydrazone

Physicochemical and Analytical Studies of Some Monomer and Polymer Complexes Derived from Selected Aroyl Hydrazone

Tripodal aroyl hydrazone based AIE fluorescent sensor for relay detection Hg2+ and Br− in living cells

The efficient detection of toxic substances is a very important task. Herein, a tripodal receptor TM employing three aroyl hydrazone moieties as binding sites has been designed and used for the selective determination of Hg2+ and Br−. The TM shows AIE properties and could selectively relay fluorescent response for Hg2+ and Br−. The detection limit (LOD) for Hg2+ and Br− is found to be 4.95 × 10−8 M and 1.7 × 10−6 M. More interestingly, the TM could be used for fluorescent sensing Hg2+ and Br− in living cells with high sensitivities.

Quantitative structure activity relationship studies of novel hydrazone derivatives as α-amylase inhibitors with index of ideality of correlation

The present manuscript describes the synthesis, α-amylase inhibition, in silico studies and in-depth quantitative structure–activity relationship (QSAR) of a library of aroyl hydrazones based on benzothiazole skeleton. All the compounds of the developed library are characterized by various spectral techniques. α‐Amylase inhibitory potential of all compounds has been explored, where compound 7n exhibits remarkable α-amylase inhibition of 87.5% at 50 µg/mL. Robust QSAR models are made by using the balance of correlation method in CORAL software. The chemical structures at different concentration with optimal descriptors are represented by SMILES. A data set of 66 SMILES of 22 hydrazones at three distinct concentrations are prepared. The significance of the index of ideality of correlation (IIC) with applicability domain (AD) is also studied at depth. A QSAR model with best = 0.8587 for split 1 is considered as a leading model. The outliers and promoters of increase and decrease of endpoint are also extracted. The binding modes of the most active compound, that is, 7n in the active site of Aspergillus oryzae α-amylase (PDB ID: 7TAA) are also explored by in silico molecular docking studies. Compound 7n displays high resemblance in binding mode and pose with the standard drug acarbose. Molecular dynamics simulations performed on protein–ligand complex for 100 ns, the protein gets stabilised after 20 ns and remained below 2 Å for the remaining simulation. Moreover, the deviation observed in RMSF during simulation for each amino acid residue with respect to Cα carbon atom is insignificant.

Research on Nickel(II) Complexes with Aroyl Hydrazones of 5,5-Dimethyl-2,4-Dioxohexanoic Acid Ethyl Ester

Complex compounds of nickel(II) with aroyl hydrazones of 5,5-dimethyl-2,4-dioxohexanoic acid ethyl ester (H2L1–H2L6) are synthesized and studied. The composition and structure of the obtained complex compounds based on these ligands are established by elemental analysis, infrared spectroscopy, proton nuclear magnetic resonance spectroscopy, and X-ray diffraction analysis. The full set of the X-ray diffraction data of the NiL6 ⋅ 3Py complex is deposited in the Cambridge Structural Database (CCDC deposit no. 1911468), and it is available on request from the following site: www.ccdc.cam.ac.uk/data_request/cif

Design, synthesis and biological evaluation of thieno[3,2-d]pyrimidine derivatives containing aroyl hydrazone or aryl hydrazide moieties for PI3K and mTOR dual inhibition

Recently, PI3K and mTOR have been regarded as promising targets for cancer treatment. Herein, we designed and synthesized four series of novel thieno[3,2-d]pyrimidine derivatives that containing aroyl hydrazone or aryl hydrazide moieties. These derivatives act as PI3K/mTOR dual inhibitors, suggesting that they can be used as cancer therapeutic agents. All compounds were tested for anti-proliferative activity against four cancer cell lines. The structure-activity relationship (SAR) studies were conducted by varying the moieties at the C-6 and C-2 positions of the thieno[3,2-d]pyrimidine core. It indicated that aryl hydrazide at C-6 position and 2-aminopyrimidine at C-2 position are optimal fragments. Compound 18b showed the most potent in vitro activity (PI3Kα IC50 = 0.46 nM, mTOR IC50 = 12 nM), as well as good inhibition against PC-3 (human prostate cancer), HCT-116 (human colorectal cancer), A549 (human lung adenocarcinoma) and MDA-MB-231 (human breast cancer) cell lines. Furthermore, Annexin-V and propidium iodide (PI) double staining confirmed that 18b induces apoptosis in cytotoxic HCT-116 cells. Moreover, the influence of 18b on cell cycle distribution was assessed on the HCT-116 cell line, and a cell cycle arrest was observed at the G1/S phases.

Iron Complexes of an Antiproliferative Aroyl Hydrazone: Characterization of Three Protonation States by Electron Paramagnetic Resonance Methods.

Tridentate aroyl hydrazones are effective metal chelators in biological settings, and their activity has been investigated extensively for medicinal applications in metal overload, cancer, and neurodegenerative diseases. The aroyl hydrazone motif is found in the recently reported prochelator (AH1-S)2, which has shown antiproliferative proapoptotic activity in mammalian cancer cell lines. Intracellular reduction of this disulfide prochelator leads to the formation of mercaptobenzaldehyde benzoylhydrazone chelator AH1 and to iron sequestration, which in turn impacts cell growth. Herein, we investigate the iron coordination chemistry of AH1 to determine the structural and spectroscopic properties of the iron complexes in the solid state and in solution. A neutral iron(III) complex of 2:1 ligand-to-metal stoichiometry was isolated and characterized fully to reveal two different binding modes for the tridentate AH1 ligand. Specifically, one ligand binds in the monoanionic keto form, whereas the other ligand coordinates as a dianionic enolate. Continuous-wave electron paramagnetic resonance experiments in frozen solutions indicated that this neutral complex is one of three low-spin iron(III) complexes observed depending on the pH of the solution. Electron spin echo envelope modulation (ESEEM) experiments allowed assignment of the three species to different protonation states of the coordinated ligands. Our ESEEM analysis provides a method to distinguish the coordination of aroyl hydrazones in the keto and enolate forms, which influences both the ligand field and overall charge of the complex. As such, this type of analysis could provide valuable information in a variety of studies of iron complexes of aroyl hydrazones, ranging from the investigation of spin-crossover behavior to tracking of their distribution in biological samples.

Synthesis and X-ray crystal structures of two different zinc (II) complexes of N,N′-cyclohexane-1,2-diylidene-bis(4-fluorobenzoylhydrazide) based on zinc salt effect

Reaction of zinc chloride or zinc nitrate hexahydrate with N,N′-cyclohexane-1,2-diylidene-bis(4-fluorobenzoylhydrazide) (L) in acetonitrile and under ambient conditions, produced two different zinc(II) complexes 1 and 2 respectively, with different coordination modes and geometrical shapes. A neutral four-coordinate complex with typical tetrahedral geometry was obtained for 1, in which, the zinc atom is sited outside the bis aroyl hydrazone core. While, a cationic eight-coordinate complex with distorted dodecahedral geometry was confirmed for 2, in which, the zinc atom is surrounded by four oxygen and four nitrogen donors from two N,N′-cyclohexane-1,2-diylidene-bis(4-fluorobenzoylhydrazide) molecules. The prepared compounds were identified and their chemical structures determined using various techniques: Nuclear magnetic resonance (NMR), Infrared (IR) and Ultraviolet–visible (UV–Vis) spectroscopy, in addition to single-crystal X-ray crystallography, X-ray powder diffraction (XRD), elemental analysis, atomic absorption and molar conductivity measurements. Furthermore, the in vitro biological activity of L, 1 and 2 was studied against some selected bacterial strains: Bacillus subtilis and Staphylococcus aureus as gram positive bacteria, and Escherichia coli and Salmonella typhimurium as gram negative bacteria. The study revealed that the prepared compound have shown a differentiated biological activity against these bacteria depending on their structural features and lipophilic nature.

Synthesis, characterization, biological, X-ray diffraction analysis and computational chemistry studies of new 2-acetylpyridine derivative hydrazone and its Zn(II) complex

A new aroyl hydrazone ligand ((E)-2-phenyl-N’-(1-(pyridine-2-yl)ethylidene)acetohydrazide) HL and its metal complex [ZnL2] (1) have been synthesized and characterized by using elemental analysis, IR and UV–vis spectroscopy methods. All data indicate that the ligand is coordinated through enolate oxygen, pyridine nitrogen and the imine nitrogen in enolic form towards the metal ions. The single crystal X-ray diffraction analysis and Density Functional Theory (DFT) calculations were carried out for HL and 1 structures. HL and 1 crystallize in the monoclinic and the orthorhombic with P 21/n and P b c n space group with a = 5.2051(4) Å, b = 10.0477(9) Å, c = 25.204(2) Å, with a = 14.1300(18) Å, b = 9.3287(13) Å, c = 21.491(3) Å, respectively. The geometries, molecular orbital energies, and stability of the molecular structures were investigated in different solvent environments by using DFT/B3LYP/6-311G (d, p) method. Theoretical UV–vis spectra of the molecular structures were obtained and the percentage contributions of atomic orbitals of functional groups of the molecular structures to the molecular orbital energy levels were calculated in water media. The global reactivity parameters of the molecular structures were calculated and the interactions between the molecules with DNA bases such as adenine, cytosine, guanine, and thymine were investigated by using the ECT (Electrophilicity-Based Charge Transfer) method and ΔN (charge transfer) parameters. All the compounds were screened for antibacterial activity against Gram-positive, Gram-negative and yeast by using minimal inhibitory concentration method (MIC). [ZnL2] (1) has been found to have more effect than HL in all microorganisms. Moreover, antioxidant activity was determined with the ABTS method. The DNA binding interactions was also determined experimentally by spectrophotometric and electrochemical methods.

Aroyl hydrazone with large Stokes shift as a fluorescent probe for detection of Cu2+ in pure aqueous medium and in vivo studies

An aroyl hydrazone based fluorescent probe, hpsh, has been developed for the selective detection of Cu2+ ions in pure aqueous medium by static fluorescence quenching. The fluorescence quenching of hpsh in the presence of Cu2+ takes place as a result of ground state complex formation through intramolecular charge transfer (ICT). Addition of Cu2+ ions changes the color of the solution from colorless to yellow-green which is clearly visible by naked eye. Large Stokes shift of hpsh prevents the self-quenching of the probe in absence of metal ions. The observed stoichiometry between Cu2+ and probe has been found as 1:2 (M: L). MTT assay of hpsh on fruit flies confirms that the probe is non-toxic and biocompatible. The plausible in vivo bioimaging application of the probe to detect Cu2+ in Drosophila gut tissues as well as in adult fruit fly has been investigated with excellent results.

Synthesis and Crystal Structure of the Nickel(II) Complex with Aroyl Hydrazone of Ethyl Ether of 5,5-Dimethyl-2,4-Dioxohexane Acid

Coordination complexes of nickel(II) with aroyl hydrazones of ethyl ether of 5,5-dimethyl-2,4-dioxohexane acid (H2L1–H2L6) are prepared and studied. The composition and structure of complexes obtained on the basis of these ligands are established by elemental analysis, IR, 1H NMR spectroscopy, and XRD methods. IR and 1H NMR parameters correlate with each other under the variation of the substituents in the p-position of the benzene ring located in the hydrazide part of ligand molecules. The ring-chain equilibrium in the complexes is established.

Synthesis, Structural Characterization, Thermal and Biological Studies of Some Metal Complexes with Aroyl Hydrazone Based Ligand

The metal complexes of Ti(III), Cr(III), Fe(III), VO(IV), MoO2(VI), WO2(VI), Th(IV) have been synthesized with hydrazone ligand. The mononucleating hydrazone ligand has been synthesized via condensation reaction between pyrazine-2-carbohydrazide and 2,4-dihydroxy benzophenone in 1:1 ratio. The ligand and its complexes were studied on the basis of elemental analysis, magnetic susceptibility measurements, IR and electronic spectra, TGA, XRD, 1H NMR, mass spectroscopy and SEM analysis. Spectroscopic and magnetic studies suggest coordination of most of the metal complexes in a regular octahedral around the central metal ions except vanadium which is square pyramidal. Free ligand as well as its metal complexes were screened against the growth of pathogenic bacteria. The inhibition data revealed that metal complexes exhibit higher inhibition potential against growth of bacteria and fungi than free ligand.

Structural investigation of discrete solvent protonated vanadium and other transition metal complexes of N'-[(E)-(3-ethoxy-2-hydroxyphenyl)methylidene]benzohydrazide, synthetic, spectroscopic and cytotoxicity studies

A new ligand 3-ethoxysalicylaldehyde benzoic hydrazone (H2ESB) and its copper(II), nickel(II), cobalt(II), zinc(II), and dioxidovanadium(V) complexes have been synthesized and characterized by elemental analysis, IR, UV–Vis and EPR studies. Copper(II) complex (2) contains 2,2′-bipyridine as a coligand. Aroyl hydrazone and its copper and vanadium complexes were characterised by single crystal XRD. The vanadium compound crystallized in triclinic space group P1- and copper compound in orthorhombic space group P212121. The solvent molecule DMF protonates to form ammonium ion in vanadium complex which neutralises the charge on the vanadium ion. Both complexes copper and vanadium show distorted square pyramidal geometry. From EPR results, spin Hamiltonian and bonding parameters were calculated. The g values in copper complexes indicate the presence of the unpaired electron in the dx2−y2 orbital. In vitro cytotoxicity studies of aroylhydrazone and its complexes showed that copper, cobalt and vanadium complexes are more cytotoxic than hydrazone and other complexes against Dalton’s lymphoma ascites cells (DLA).

Preparation, Characterization and Study of Ethyl Pyruvate Aroyl Hydrazone Metal Complexes

Preparation, Characterization and Study of Ethyl Pyruvate Aroyl Hydrazone Metal Complexes

Design, synthesis, in vivo and in silico evaluation of phenacyl triazole hydrazones as new anticonvulsant agents

A series of phenacyl triazole hydrazones 3 have been designed based on the hybridization of (arylalkly)triazole and aroyl hydrazone scaffolds as new anticonvulsant agents. The target compounds 3 were easily synthesized from appropriate phenacyl triazoles and aryl acid hydrazides and characterized by IR, NMR and Mass spectroscopy. The in vivo anticonvulsant evaluation of synthesized compounds by using MES and PTZ tests revealed that they are more effective in MES model respect to PTZ test. All compounds showed 33–100% protection against MES-induced seizures at the dose of 100 mg/kg. However, the isonicotinic acid hydrazide derivative 3h showed the best profile of activity in both models. Molecular docking studies of compound 3h with different targets (NMDA, AMPA, GABAA and sodium channel), postulated that the compound acts mainly via GABAA receptors. In silico molecular properties predictions indicated that all compounds have favourable oral bioavailability and BBB permeability.

Crystal structure and Hirshfeld surface analysis of (E)-4-{[2-(4-hy-droxy-benzo-yl)hydrazin-1-yl-idene]meth-yl}pyridin-1-ium nitrate.

The asymmetric unit of the title aroyl hydrazone Schiff base salt, C13H12N3O2+·N O3-, consists of one mol-ecular cation in the keto tautomeric form, adopting an E configuration with respect to the azomethine bond, and one nitrate anion. The two units are linked via an N-H⋯O hydrogen bond. The mol-ecule overall is non-planar, with the pyridinium and benzene rings being inclined to each other by 4.21 (4)°. In the crystal, cations and anions are linked via inter-molecular O-H⋯O and bifurcated N-H⋯O hydrogen bonds, forming a two-dimensional network parallel to (101). These networks are further linked by C-H⋯O hydrogen bonds, forming slabs parallel to (101). The slabs are linked by offset π-π inter-actions, involving the benzene and pyridinium rings of adjacent slabs [inter-centroid distance = 3.610 (2) Å], forming a three-dimensional structure. The Hirshfeld surface analysis of the crystal structure indicates that the most important contributions for the crystal packing are from H⋯O/O⋯H (45.1%), H⋯H (19.3%), H⋯C/C⋯H (14.5%), H⋯N/N⋯H (7.9%) and C⋯C (6.0%) inter-actions.

Cd(II) and Ni(II) complexes from aroyl hydrazones: Unravelling the intermolecular interactions and electronic, crystal structures through experimental and theoretical studies

Three complexes of Cd(II) 1, 2 and Ni(II), 3 were prepared from two different aroyl hydrozone ligands (HL1 (C15H13N3O4) & HL2 (C20H17N3O2)) using their respective metal bromides. Crystal structures of all the three complexes have been established and the anionic/neutral nature of the coordinating ligand is mainly dictated by the nature of the metal center used. Quantification of intermolecular interactions is done using Hirshfeld surface and 2D finger print analysis. The Electrostatic Potential (ESP) analysis reveals that 2 has a collective concentration of negative electrostatic potentials to one side of the molecule giving a perfect separation of charges. DFT/semiempirical calculations revealed the same, giving a very high dipole moment for the optimized geometry of 2. Analysis of frontier orbitals is done through DFT calculations at the B3LYP/def2-TZVP level of theory and atomic charge distributions are predicted using AIM method.

In vitro and in silico evaluation of chromene based aroyl hydrazones as anticonvulsant agents

Series of aroyl hydrazones of 2H-chromene and coumarin carbaldehydes were synthesized and evaluated for their anticonvulsant activity and neurotoxicity. Further docking study on gamma-aminobutyric acid receptor was performed to elucidate their mechanisms of action. The highest protection was demonstrated by 2-furyl substituted 2H-chromene 8b in the maximal electroshock test (ED50 = 12.51 mg kg−1, PI MES > 23.98) and the subcutaneous pentylenetetrazole tests (ED50 = 127.10 mg kg−1). Furyl-substituted derivative 4b (ED50 = 68.66 mg kg−1) was the most active in the maximal electroshock test while methoxyphenyl-substituted derivate 4c was the most active in the 6-Hz test (ED50 = 94.34 mg kg−1). None of the compounds displayed neurotoxicity in the rota-rod test. In silico assessment of their blood-brain barrier permeability indicated them as central nervous system active agents. The results suggest that coumarin/2H-chromene aroyl hydrazones scaffold deserve further evaluation in models of epilepsy and derivatization.

Iron(III)/TEMPO-Catalyzed Synthesis of 2,5-Disubstituted 1,3,4-Oxadiazoles by Oxidative Cyclization under Mild Conditions

A simple and efficient cationic Fe(III)/TEMPO-catalyzed oxidative cyclization of aroyl hydrazones has been developed for the synthesis of 2,5-disubstituted 1,3,4-oxadiazole derivatives. The reaction offers a broad scope, good functional-group tolerance, and high yields under mild conditions in the presence of O2.