Synthesis, Crystal Structures, Genotoxicity, and Antifungal and Antibacterial Studies of Ni(II) and Cd(II) Pyrazole Amide Coordination Complexes.

In this study, we synthesized two coordination complexes based on pyrazole-based ligands, namely 1,5-dimethyl-N-phenyl-1H-pyrazole-3-carboxamide (L1) and 1,5-dimethyl-N-propyl-1H-pyrazole-3-carboxamide (L2), with the aim to investigate bio-inorganic properties. Their crystal structures revealed a mononuclear complex [Ni(L1)2](ClO4)2 (C1) and a dinuclear complex [Cd2(L2)2]Cl4 (C2). Very competitive antifungal and anti-Fusarium activities were found compared to the reference standard cycloheximide. Additionally, L1 and L2 present very weak genotoxicity in contrast to the observed increase in genotoxicity for the coordination complexes C1 and C2.

CuII Pyrazolyl-Benzimidazole Dinuclear Complexes with Remarkable Antioxidant Activity.

Three dinuclear coordination complexes generated from 1-n-butyl-2-((5-methyl-1H-pyrazole-3-yl)methyl)-1H-benzimidazole (L), have been synthesized and characterized spectroscopically and structurally by single crystal X-ray diffraction analysis. Reaction with iron(II) chloride and then copper(II) nitrate led to a co-crystal containing 78 % of [Cu(NO3 )(µ-Cl)(L')]2 (C1 ) and 22 % of [Cu(NO3 )(µ-NO3 )(L')]2 (C2 ), where L was oxidized to a new ligand L' . A mechanism is provided. Reaction with copper chloride led to the dinuclear complex [Cu(Cl)(µ-Cl)(L)]2 (C3 ). The presence of N-H⋅⋅⋅O and C-H⋅⋅⋅O intermolecular interactions in the crystal structure of C1 and C2 , and C-H⋅⋅⋅N and C-H⋅⋅⋅Cl hydrogen bonding in the crystal structure of C3 led to supramolecular structures that were confirmed by Hirshfeld surface analysis. The ligands and their complexes were tested for free radical scavenging activity and ferric reducing antioxidant power. The complex C1 /C2 shows remarkable antioxidant activities as compared to the ligand L and reference compounds.

Coordination Complexes Built from a Ditopic Triazole-Pyrazole Ligand with Antibacterial and Antifungal Performances.

Four mononuclear complexes (H3O){[NiL3](ClO4)3} (1), [CoL3](ClO4)2·2H2O (2), [CdL2Cl2] (3) and [CuL3](NO3)2 (4) have been prepared employing a newly synthesized 1,2,4-triazole ligand: 3-(3,5-dimethyl-1H-pyrazol-1-yl)-1H-1,2,4-triazole (L). The structures of the complexes, which crystallized in P63/m (1), P-1 (2), P1 (3), and P21/c (4), are reviewed within the context of the cooperative effect of the hydrogen bonding network and counter anions on the supramolecular formations. Moreover, within the framework of biological activity examination, these compounds showed favorable antibacterial performances compared to those of various species of bacteria, including both Gram-positive and Gram-negative strains. Significant antifungal inhibitory activity towards Fusarium oxysporum f. sp. albedinis fungi was recorded for 3 and 4 over the ligand L.

Mesoporous Silica Modified with 2-Phenylimidazo[1,2-a] pyridine-3-carbaldehyde as an Effective Adsorbent for Cu(II) from Aqueous Solutions: A Combined Experimental and Theoretical Study.

In this study, we will present an efficient and selective adsorbent for the removal of Cu(II) ions from aqueous solutions. The silica-based adsorbent is functionalized by 2-phenylimidazo[1,2-a] pyridine-3-carbaldehyde (SiN-imd-py) and the characterization was carried out by applying various techniques including FT-IR, SEM, TGA and elemental analysis. The SiN-imd-py adsorbent shows a good selectivity and high adsorption capacity towards Cu(II) and reached 100 mg/g at pH = 6 and T = 25 °C. This adsorption capacity is important compared to other similar adsorbents which are currently published. The adsorption mechanism, thermodynamics, reusability and the effect of different experimental conditions, such as contact time, pH and temperature, on the adsorption process, were also investigated. In addition, a theoretical study was carried out to understand the adsorption mechanism and the active sites of the adsorbent, as well as the stability of the complex formed and the nature of the bonds.

A Highly Efficient Environmental-Friendly Adsorbent Based on Schiff Base for Removal of Cu(II) from Aqueous Solutions: A Combined Experimental and Theoretical Study.

Removal of heavy metals from drinking water sources and rivers is of strategic health importance and is essential for sustainable ecosystem development, in particular in polluted areas around the globe. In this work, new hybrid inorganic-organic material adsorbents made of ortho- (Si-o-OR) or para-Schiff base silica (Si-p-OR) were synthesized and characterized in depth. These hybrid adsorbents show a high selectivity to Cu(II), even in the presence of competing heavy metals (Zn(II), Cd(II), and Pb(II)), and also demonstrate great reusability after five adsorption-desorption cycles. Maximum sorption capacity for Cu(II) was found for Si-o-OR (79.36 mg g-1) and Si-p-OR (36.20 mg g-1) in no less than 25 min. Energy dispersive X-ray fluorescence and Fourier transform-infrared spectroscopy studies demonstrate that this uptake occurs due to a chelating effect, which allows these adsorbents to trap Cu(II) ions on their surfaces; this result is supported by a theoretical study for Si-o-OR. The new adsorbents were tested against real water samples extracted from two rivers from the Oriental region of Morocco.

Novel ß-keto-enol Pyrazolic Compounds as Potent Antifungal Agents. Design, Synthesis, Crystal Structure, DFT, Homology Modeling, and Docking Studies.

A new family of promising inhibitors bearing ß-keto-enol functionality with greatly improved pharmacophore properties has been prepared. Herein, a series of novel derivatives of ß-keto-enol group embedded with pyrazolic moiety has been designed and synthesized via a one-step procedure using mixed Claisen condensation in the attempt to develop potential antifungal agents. The structures of the synthesized compounds were confirmed by elemental analysis, FT-IR, ESI/LC-MS, and 1H and 13C NMR. In addition, X-ray diffraction analysis (XRD) was used to determine the single crystal structure of compound 10. All of the new compounds have been evaluated for their in vitro antifungal and antibacterial activities. Interestingly, the results indicate that most of the compounds display notable antifungal activity close to that of the benomyl fungicide taken as the standard drug. For the most active compound and for benomyl, a correlation has been evidenced between the experimental antifungal activity and the theoretical predictions by DFT calculations and molecular docking against Fgb1 protein.

Synthesis, Antimicrobial Screening, Homology Modeling, and Molecular Docking Studies of a New Series of Schiff Base Derivatives as Prospective Fungal Inhibitor Candidates.

Twelve new Schiff base derivatives have been prepared by the condensation reaction of different amino substituted compounds (aniline, pyridin-2-amine, o-toluidine, 2-nitrobenzenamine, 4-aminophenol, and 3-aminopropanol) and substituted aldehydes such as nicotinaldehyde, o,m,p-nitrobenzaldehyde, and picolinaldehyde in ethanol using acetic acid as a catalyst. The envisaged structures of the all the synthesized ligands have been confirmed on the basis of their spectral analysis FT-IR, mass spectroscopy, 1H- and 13C-NMR. In vitro screening of their antibacterial and antifungal potential against Escherichia coli bacterium and Fusarium oxysporum f.sp albedinis (F.o.a) fungus, respectively, revealed that all the ligands showed no significant antibacterial activity, whereas most of them displayed good antifungal activity. Homology modeling and docking analysis were performed to explain the antifungal effect of the most and least active compound against two F.o.a fungus proteins.

Supramolecular Hybrid Material Based on Engineering Porphyrin Hosts for an Efficient Elimination of Lead(II) from Aquatic Medium.

Porphyrins show great promise for future purification demands. This is largely due to their unique features as host binding molecules that can be modified at the synthetic level, and largely improved by their incorporation into inorganic based materials. In this study, we assessed the efficacy of a hybrid material obtained from the immobilization of 5,10,15,20-tetrakis(pentafluorophenyl)-porphyrin on silica surface to remove Pb(II), Cu(II), Cd(II), and Zn(II) ions from water. The new organic-inorganic hybrid adsorbent was fully characterized by adequate techniques and the results show that the hybrid exhibits good chemical and thermal stability. From batch assays, it was evaluated how the efficacy of the hybrid was affected by the pH, contact time, initial metal concentration, and temperature. The adsorption kinetic and isotherms showed to fit the recent developed fractal-like pseudo-second-order model and Langmuir⁻Freundlich model respectively. The highest adsorption capacities for Pb(II), Cu(II), Cd(II), and Zn(II) ions were 187.36, 125.17, 82.45, and 56.23 mg g-1, respectively, at pH 6.0 and 25 °C. This study also shows that metal cations from real river water samples can be efficient removed in the presence of the new adsorbent material.

Synthesis and Pharmacological Activities of Pyrazole Derivatives: A Review.

Pyrazole and its derivatives are considered a pharmacologically important active scaffold that possesses almost all types of pharmacological activities. The presence of this nucleus in pharmacological agents of diverse therapeutic categories such as celecoxib, a potent anti-inflammatory, the antipsychotic CDPPB, the anti-obesity drug rimonabant, difenamizole, an analgesic, betazole, a H2-receptor agonist and the antidepressant agent fezolamide have proved the pharmacological potential of the pyrazole moiety. Owing to this diversity in the biological field, this nucleus has attracted the attention of many researchers to study its skeleton chemically and biologically. This review highlights the different synthesis methods and the pharmacological properties of pyrazole derivatives. Studies on the synthesis and biological activity of pyrazole derivatives developed by many scientists around the globe are reported.

New Pyrazole-Hydrazone Derivatives: X-ray Analysis, Molecular Structure Investigation via Density Functional Theory (DFT) and Their High In-Situ Catecholase Activity.

The development of low-cost catalytic systems that mimic the activity of tyrosinase enzymes (Catechol oxidase) is of great promise for future biochemistry technologic demands. Herein, we report the synthesis of new biomolecules systems based on hydrazone derivatives containing a pyrazole moiety (L1-L6) with superior catecholase activity. Crystal structures of L1 and L2 biomolecules were determined by X-ray single crystal diffraction (XRD). Optimized geometrical parameters were calculated by density functional theory (DFT) at B3LYP/6-31G (d, p) level and were found to be in good agreement with single crystal XRD data. Copper (II) complexes of the compounds (L1-L6), generated in-situ, were investigated for their catalytic activities towards the oxidation reaction of catechol to ortho-quinone with the atmospheric dioxygen, in an attempt to model the activity of the copper containing enzyme tyrosinase. The studies showed that the activities depend on four parameters: the nature of the ligand, the nature of counter anion, the nature of solvent and the concentration of ligand. The Cu(II)-ligands, given here, present the highest catalytic activity (72.920 µmol·L-1·min-1) among the catalysts recently reported in the existing literature.

ß-Keto-enol Tethered Pyridine and Thiophene: Synthesis, Crystal Structure Determination and Its Organic Immobilization on Silica for Efficient Solid-Liquid Extraction of Heavy Metals.

Molecules bearing ß-keto-enol functionality are potential candidates for coordination chemistry. Reported herein is the first synthesis and use of a novel designed ligand based on ß-keto-enol group embedded with pyridine and thiophene moieties. The product was prepared in a one-step procedure by mixed Claisen condensation and was characterized by EA, m/z, FT-IR, (¹H, (13)C) NMR and single-crystal X-ray diffraction analysis. The new structure was grafted onto silica particles to afford a chelating matrix which was well-characterized by EA, FT-IR, solid-state (13)C-NMR, BET, BJH, SEM and TGA. The newly prepared organic-inorganic material was used as an adsorbent for efficient solid-phase extraction (SPE) of Cu(II), Zn(II), Cd(II) and Pb(II) from aqueous solutions and showed a capture capacity of 104.12 mg·g(-1), 98.90 mg·g(-1), 72.02 mg·g(-1), and 65.54 mg·g(-1), respectively. The adsorption capacity was investigated, in a batch method, using time of contact, pH, initial concentration, kinetics (Langmuir and Freundlich models), and thermodynamic parameters (ΔG°, ΔH° and ΔS°) of the system effects.

X-ray Single Crystal Structure, DFT Calculations and Biological Activity of 2-(3-Methyl-5-(pyridin-2'-yl)-1H-pyrazol-1-yl) Ethanol.

A pyridylpyrazole bearing a hydroxyethyl substituent group has been synthesized by condensation of (Z)-4-hydroxy-4-(pyridin-2-yl)but-3-en-2-one with 2-hydroxyethylhydrazine. The compound was well characterized and its structure confirmed by single crystal X-ray diffraction. Density functional calculations have been performed using DFT method with 6-31G* basis set. The HOMO-LUMO energy gap, binding energies and electron deformation densities are calculated at the DFT (BLYP, PW91, PWC) level. The electrophilic f(-) and nucleophilic f(+) Fukui functions and also the electrophilic and nucleophilic Parr functions are well adapted to find the electrophile and nucleophile centers in the molecule. The title compound has been tested for its DPPH radical scavenging activity which is involved in aging processes, anti-inflammatory, anticancer and wound healing activity. Compound is also found with a significant antioxidant activity, probably due to the ability to donate a hydrogen atom to the DPPH radical.

Synthesis of Novel ß-Keto-Enol Derivatives Tethered Pyrazole, Pyridine and Furan as New Potential Antifungal and Anti-Breast Cancer Agents.

Recently, a new generation of highly promising inhibitors bearing ß-keto-enol functionality has emerged. Reported herein is the first synthesis and use of novel designed drugs based on the ß-keto-enol group embedded with heterocyclic moieties such as pyrazole, pyridine, and furan, prepared in a one-step procedure by mixed Claisen condensation. All the newly synthesized compounds were characterized by FT-IR, ¹H-NMR, (13)C-NMR, ESI/LC-MS, elemental analysis, and evaluated for their in vitro antiproliferative activity against breast cancer (MDA-MB241) human cell lines and fungal strains (Fusarium oxysporum f.sp albedinis FAO). Three of the synthesized compounds showed potent activity against fungal strains with IC50 values in the range of 0.055-0.092 µM. The results revealed that these compounds showed better IC50 values while compared with positive controls.

Synthesis and biological evaluation of 2-aminobenzamide derivatives as antimicrobial agents: opening/closing pharmacophore site.

A series of new 2-aminobenzamide derivatives (1-10) has been synthesized in good to excellent yields by adopting both conventional and/or a time-efficient microwave assisted methodologies starting from isatoic anhydride (ISA) and characterized on the basis of their physical, spectral and microanalytical data. Selected compounds of this series were then tested against various bacterial (Bacillus subtilis (RCMB 000107) and Staphylococcus aureus (RCMB 000106). Pseudomonas aeruginosa (RCMB 000102) and Escherichia coli (RCMB 000103) and fungal strains (Saccharomyces cerevisiae (RCMB 006002), Aspergillus fumigatus (RCMB 002003) and Candida albicans (RCMB 005002) to explore their potential as antimicrobial agents. Compound 5 was found to be the most active compound among those tested, which showed excellent antifungal activity against Aspergillus fumigatus (RCMB 002003) more potent than standard Clotrimazole, and moderate to good antibacterial and antifungal activity against most of the other strains of bacteria and fungi. Furthermore, potential pharmacophore sites were identified and their activity was related with the structures in the solution.

Design, synthesis, characterization of novel ruthenium(II) catalysts: highly efficient and selective hydrogenation of cinnamaldehyde to (E)-3-phenylprop-2-en-1-ol.

In this contribution, two novel supported and non-supported ruthenium(II) complexes of type [RuCl2(dppme)(NN)] where [dppme is H2C=C(CH2PPh2)2 and NN is N1-(3-(trimethoxysilyl)propyl)ethane-1,2-diamine] were prepared. The NN co-ligand caused release of one of the dppme ligands from [RuCl2(dppme)2] precursor to yield complex 1. The process of substitution of dppme by NN was monitored by 31P{1H}-NMR. Taking advantage of the presence of trimethoxysilane group in the backbone of complex 1, polysiloxane xerogel counterpart, X1, was prepared via sol-gel immobilization using tetraethoxysilane as cross-linker. Both complexes 1 and X1 have been characterized via elemental analysis, CV and a number of spectroscopic techniques including FT-IR, 1H-, 13C-, and 31P-NMR, and mass spectrometry. Importantly, carbonyl selective hydrogenation was successfully accomplished under mild conditions using complex 1 as a homogenous catalyst and X1 as a heterogeneous catalyst, respectively.

Synthesis, structural characterizations, in vitro biological evaluation and computational investigations of pyrazole derivatives as potential antidiabetic and antioxidant agents.

In this study, a two pyrazole derivatives; 2-(5-methyl-1H-pyrazole-3-carbonyl)-N-phenylhydrazine-1-carboxamide (Pyz-1) and 4-amino-5-(5-methyl-1H-pyrazol-3-yl)-4H-1,2,4-triazole-3-thiol (Pyz-2) were synthesized and characterized by 13C-NMR, 1H-NMR, FT-IR, and mass spectrometry. A complete molecular structures optimization, electronic and thermodynamic properties of Pyz-1 and Pyz-2 in gas phase and aqueous solution were predicted by using hybrid B3LYP method with the 6-311++G** basis sets. Pyz-1 and Pyz-2 were evaluated in vitro for their anti-diabetic, antioxidant and xanthine oxidase inhibition activities. For anti-diabetic activity, Pyz-1 and Pyz-2 showed a potent α-glucosidase and α-amylase inhibition with IC50 values of 75.62 ± 0.56, 95.85 ± 0.92 and 119.3 ± 0.75, 120.2 ± 0.68 µM, respectively, compared to Acarbose (IC50(α-glucosidase) = 72.58 ± 0.68 µM, IC50(α-amylase) = 115.6 ± 0.574 µM). In xanthine oxidase assay, Pyz-1 and Pyz-2 exhibited remarkable inhibitory ability with IC50 values 24.32 ± 0.78 and 10.75 ± 0.54 µM, respectively. The result of antioxidant activities showed that the title compounds have considerable antioxidant and radical scavenger abilities. In addition, molecular docking simulation was used to determine the binding modes and energies between the title compounds and α-glucosidase and α-amylase enzymes.

Organically modified silica with pyrazole-3-carbaldehyde as a new sorbent for solid-liquid extraction of heavy metals.

A new chelating matrix, SiNP, has been prepared by immobilizing 1.5-dimethyl-1H-pyrazole-3-carbaldehyde on silica gel modified with 3-aminopropyl-trimethoxysilane. This new chelating material was well characterized by elemental analysis, FT-IR spectroscopy, cross polarization magic angle spinning solid state 13C-NMR, nitrogen adsorption-desorption isotherm, BET surface area, BJH pore size, and scanning electron microscopy (SEM). The new product exhibits good chemical and thermal stability as determined by thermogravimetry curves (TGA). The new prepared material was used as an adsorbent for the solid-phase extraction (SPE) of Pb(II), Cd(II), Cu(II) and Zn(II) from aqueous solutions using a batch method, prior to their determination by flame atomic adsorption spectrometry. The adsorption capacity was investigated using kinetics and pH effects. Common coexisting ions did not interfere with separation and determination.

New triazole-based coordination complexes as antitumor agents against triple negative breast cancer MDA-MB-468 cell line.

The present work describes the synthesis of a new triazole based ligand 3-(3,5-dimethyl-1H-pyrazol-1-yl)-1-methyl-1H-1,2,4-triazole (LM) and demonstration of its coordination diversity giving rise to a family of seven new coordination complexes, namely: [Ni(LM)3](ClO4)2·C2H6OS (5), [Co2(LM)6](ClO4)4·(C2H5)O (6), [Cd(LM)2Cl2] (7), [Cu(LM)2NO3]NO3 (8), [Fe(LM)3](BF4)2 (9), [Zn(LM)3](BF4)2 (10) and [Zn(LM)2NO3]NO3 (11), whose crystal structure was determined by single-crystal X-ray diffraction. Cytotoxic activity was evaluated against the MDA-MB-468 cancer cell line, which serves as a model for triple-negative breast cancer, and compared to the precursor molecule (L), as well as their coordination complexes (H3O){[NiL3](ClO4)3} (1), [CoL3](ClO4)2·2H2O (2), [CdL2Cl2] (3) and [CuL3](NO3)2 (4), for which the crystal structure was earlier determined. Notably, cadmium complexes 3 and 7 exhibit remarkable cytotoxicity and demonstrated a high selectivity index towards cancer cells when compared to peripheral blood mononuclear cells. Such activity highlights their potential function as anticancer agents.

Novel family of bis-pyrazole coordination complexes as potent antibacterial and antifungal agents.

A new pyrazole ligand, N,N-bis(2(1',5,5'-trimethyl-1H,1'H-[3,3'-bipyrazol]-1-yl)ethyl)propan-1-amine (L) was synthesized and characterized by 1H-NMR, 13C-NMR, FT-IR and HRMS. The coordination ability of the ligand has been employed for the construction of a new family of coordination complexes, namely: [Cu2LCl4] (1), [ML(CH3OH)(H2O)](ClO4)2 (MII = Ni (2), Co (3)) and [FeL(NCS)2] (4). The series of complexes were characterized using single-crystal X-ray diffraction, HRMS, FT-IR and UV-visible spectroscopy. Moreover, the iron(ii) analogue was investigated by 57Fe Mössbauer spectroscopy and SQUID magnetometry. Single-crystal X-ray structures of the prepared complexes are debated within the framework of the cooperative effect of the hydrogen bonding network and counter anions on the supramolecular formations observed. Furthermore, within the context of biological activity surveys, these compounds were reviewed against different types of bacteria to validate their efficiency, including both Gram-positive as well as Gram-negative bacteria. Enhanced behaviour towards Fusarium oxysporum f. sp. albedinis fungi, were detected for 1 and 4.

Experimental and theoretical study for removal of trimethoprim from wastewater using organically modified silica with pyrazole-3-carbaldehyde bridged to copper ions.

BACKGROUND: Human and veterinary antibiotics are typically discharged as parent chemicals in urine or feces and are known to be released into the environment via wastewater treatment plants (WWTPs). Several research investigations have recently been conducted on the removal and bioremediation of pharmaceutical and personal care products (PPCPs) disposed of in wastewater. RESULTS: SiNP-Cu, a chelating matrix, was produced by delaying and slowing 1.5-dimethyl-1H-pyrazole-3-carbaldehyde on silica gel from functionalized with 3-aminopropyltrimethoxysilane. The prepared sorbent material was characterized using several techniques including BET surface area, FT-IR spectroscopy, Scanning electron microscopy (SEM), thermogravimetric analysis (TGA), and nitrogen adsorption-desorption isotherm. The pseudo-second-order model provided the best correlation due to the big match between the experimental and theoretical of different adsorption coefficients. The Langmuir and Freundlich adsorption models were used and the study showed a better match with the Freundlich model with a capacity of removal reached up to 420 mg g-1. The removal capacity was dependent on pH and increased by increasing pH. The removal percentage reached 91;5% at pH = 8. The adsorbent demonstrated a high percentage removal of TMP, reaching more than 94% when increased pH. The sample was simply regenerated by soaking it for a few minutes in 1 N HCl and drying it. The sorbent was repeated five times with no discernible decrease in removal capacity. The thermodynamic study also showed endothermic, increasing randomness and not spontaneous. The free energy was 2.71 kJ/mol at 320 K. The findings of the DFT B3LYP/6-31 + g (d, p) local reactivity descriptors revealed that nitrogen atoms and π-electrons of the benzene and pyrimidine rings in the TMP are responsible for the adsorption process with the SiNP surface. The negative values of the adsorption energies obtained by molecular dynamic simulation indicated the spontaneity of the adsorption process. CONCLUSION: The global reactivity indices prove that TMP is stable and it can be removed from wastewater using SiNP surface. The results of the local reactivity indices concluded that the active centers for the adsorption process are the nitrogen atoms and the π-electrons of the pyrimidine and benzene rings. Furthermore, the positive value of the maximum charge transfer number (ΔN) proves that TMP has a great tendency to donate electrons to SiNP surface during the process of adsorption.