Microwave‐assisted Synthesis,Characterization, and Density Functional Theory Study of Biologically Active Ferrocenyl Bis‐pyrazoline and Bis‐pyrimidine as Organometallic Macromolecules

Organometallic macromolecules such as ferrocenyl bis‐pyrazoline ( 2 , 3 ) and bis‐pyrimidine ( 4 , 5 ) derivatives were synthesized by reacting ferrocenyl bis‐chalcone 1 with thiosemicarbazide/phenylhydrazine/guanidine hydrochloride/thiourea, respectively, under microwave irradiation. Ferrocenyl bis‐chalcone 1 was synthesized by reacting acetyl ferrocene with terephthalaldehyde. Synthesized compounds were characterized by using IR, ¹H NMR, ¹³C NMR, EI‐MS, and elemental analysis. In vitro antibacterial activity against two Gram‐negative and two Gram‐positive bacteria was determined by the disc diffusion assay. Moreover, minimum inhibition concentrations were also measured with reference to chloramphenicol. Thioamide functionally containing ferrocenyl bis‐pyrazoline derivative 2 shows the best antibacterial activity on Escherichia coli and Salmonella typhimurium, among all tested compounds including the reference drug chloramphenicol. The structure–activity relationship is also developed by using computational calculations with density functional theory (DFT)/B3LYP method.     

Dicoumarol complexes of Cu(II), Fe(II) and Fe(III): preparation,characterization, in‐vitro antibacterial and DNA binding activity

3‐3′‐Benzylidenebis[4‐hydroxycoumarin] or 4‐nitro,3‐3′‐benzylidenebis[4‐hydroxycoumarin] or 4‐methoxy,3‐3′‐benzylidenebis[4‐hydroxycoumarin] and their complexes with Cu(II), Fe(II) and Fe(III) were synthesized and characterized using ¹H‐NMR, ¹³C‐NMR, IR spectra, electronic spectra, magnetic measurements and elemental analyses. The ligands, metal salts, complexes, control and standard drug were tested for their in‐vitro antibacterial activity against Bacillus cereus, Staphylococcus aureus, Escherichia coli, Bacillus subtilis, Salmonella typhi, and Serratia marcescens. The metal complexes exhibit good activity against bacterial strains compared with parental compounds and moderate compared with the standard drug (ciprofloxacin). In‐vitro DNA‐binding activity was carried out using agarose gel electrophoresis. The synthesized compounds show effective DNA‐binding activity. Copyright © 2007 John Wiley & Sons, Ltd.     

Design,synthesis, characterization and antibacterial properties of copper(II) complexes with chromone‐derived compounds

A new series of six chromone‐derived compounds and their Cu(II) complexes was synthesized and characterized by their physical, spectral and analytical data The elemental analysis data of the complexes agree well with the proposed composition of the compounds, which were found to be dimeric in nature with two hydrazine molecules bridging the two copper atoms through coordination. The ligands and their Cu(II) complexes were screened for their in‐vitro antibacterial activity against four Gram‐negative (Escherichia coli, Pseudomonas aeruginosa, Salmonella typhi, Shigella flexneri) and two Gram‐positive (Bacillus subtilis, Staphylococcus aureus) bacterial strains by the agar‐well diffusion method. The ligands were found to exhibit either no or low to moderate activities against one or more of the bacterial species, whereas all the metal complexes exhibited moderate to high activities against different bacterial species. The ligands which were inactive before complexation turned active and less active ones became more active upon coordination with copper ions. Overall, the complexes 7–12 showed comparatively much higher activities than the ligands. Copyright © 2009 John Wiley & Sons, Ltd.     

Metal‐based sulfonamides: synthesis,characterization, antibacterial,antifungal and cytotoxic properties of pyrrolyl‐ and thienyl‐derived compounds

Pyrrolyl and thienyl derived sulfonamides and their metal [cobalt(II), copper(II), nickel(II) and zinc(II)] complexes were synthesized and characterized by elemental analyses, molar conductances, magnetic moments, IR, ¹H NMR, ¹³C NMR and electronic spectral data. These compounds were screened for in‐vitro antibacterial activity against four Gram‐negative (Escherichia coli, Shigella flexeneri, Pseudomonas aeruginosa and Salmonella typhi) and two Gram‐positive (Bacillus subtilis and Staphylococcus aureus) bacterial strains, and for in‐vitro antifungal activity against Trichophyton longifusus, Candida albicans, Aspergillus flavus, Microsporum canis, Fusarium solani and Candida glaberata. The results of these studies revealed that all compounds showed significant to moderate antibacterial activity; however, the zinc complexes were shown to be the most active against various species. The brine shrimp bioassay was also carried out to study their in vitro cytotoxic properties of all the synthesized ligands and their metal complexes. Only two compounds ( 14 and 19 ) displayed potent cytotoxic activity as LD₅₀ = 5.5637 × 10^?4 and 4.4023 × 10^?4 M ml^?1 respectively, against Artemia salina. Copyright © 2007 John Wiley & Sons, Ltd.     

Novel 7‐Nitro‐1‐(Piperidin‐4‐yl)‐4,5‐Dihydro‐[1,2,4] Triazolo[4,3‐a]Quinoline‐Sulphonamide Derivatives as Antimicrobial Agents: Design,Synthesis, and Bio‐Activity

In attempt to search for more potent antimicrobial agents, a series of 7‐nitro‐1‐(piperidin‐4‐yl)‐4,5‐dihydro‐[1,2,4]triazolo[4,3‐a]quinoline‐derived sulphonamides were synthesized. Their structures were established by elemental analyses, IR, and NMR (¹H and ¹³C) spectral data. The antibacterial activity of the obtained compounds was investigated against different Gram‐negative (Escherichia coli and Pseudomonas aeruginosa) and Gram‐positive (Bacillus subtilis and Staphylococcus aureus) bacteria and antifungal activity against two fungal strains (Aspergillus niger and Aspergillus clavatus) using disk diffusion method at various concentrations (20, 40, 60, and 80 μg/mL). The study reveals that most of the title compounds showed significant antibacterial and fungal activity when compared with their respective standards streptomycin and griseofulvin.     

Synthesis and Biological Evaluation of Novel Bis[1,2,4]triazolo[3,4‐b] [1,3,4]oxadiazoles

A series of novel 6‐2‐methoxy‐5‐[4‐methoxy‐3‐(3‐aryl[1,2,4]triazolo[3,4‐b][1,3,4]oxadiazol‐6‐yl)benzyl]phenyl‐3‐aryl[1,2,4]triazolo[3,4‐b][1,3,4]oxadiazoles 7a , 7b , 7c , 7d , 7e , 7f , 7g , 7h , 7i , 7j has been synthesized and characterized via IR, ¹H NMR, ¹³C NMR, MS, and elemental analyses. Compounds 7a , 7b , 7c , 7d , 7e , 7f , 7g , 7h , 7i , 7j were also screened for their antibacterial activity against Gram‐positive bacteria viz. Bacillus subtilis (MTCC 441), Bacillus sphaericus (MTCC 11), and Staphylococcus aureus (MTCC 96), and Gram‐negative bacteria viz. Pseudomonas aeruginosa (MTCC 741), Klobsinella aerogenes (MTCC 39), and Chromobacterium violaceum (MTCC 2656). The antibacterial screening reveal that the presence of 2,4‐difluorophenyl ( 7e ) or 4‐nitrophenyl ( 7f ) of 2‐pyrazyl ( 7i ), or 2‐furyl ( 7j ) on the triazole moiety exhibited potent inhibitory activity comparable with the standard drug streptomycin, at the tested concentrations, and emerged as potential molecules for further development.     

Silica‐gel‐supported Phosphorus Pentoxide:a Simple and Efficient Solid‐supported Reagent for Esterification of Long‐ Chain Carboxylic Acids and Their Antimicrobial Screening

A silica-gel-supported heterogeneous phosphorus pentoxide reagent has been developed for the esterification of various long-chain carboxylic acids with aromatic alcohols. The reactions occurred under relatively mild conditions and afforded the desired products in good yields. All the compounds 3a—3x were screened for antibacterial and antifungal activity, which showed good activity against Gram positive and Gram negative bacteria and also good results against almost all fungal strains. The structures of the synthesized compounds were elucidated by IR, ¹H NMR, ¹³C NMR, mass spectroscopic techniques and elemental analysis.     

Synthesis and Evaluation of Novel 5‐cyclohexyl‐2‐(4″‐substitutedphenyl)‐3‐(2″‐substitutedphenyl)4H‐2,3,3a,5,6,6a‐hexahydropyrrolo[3,4‐d]isoxazole‐4,6‐dione Derivatives for Their In Vitro Antioxidant and Antibacterial Activities

1,3‐Dipolar cycloaddition reactions of N‐cyclohexyl maleimide ( 1 ) with azomethine N‐oxide ( 2 ) have afforded novel isoxazolidine ( 3 ) in excellent yield. Their structures have been characterized from their IR, ¹H‐NMR, ¹³C‐NMR, ¹H,¹H‐COSY, MS(ESI), and elemental analysis techniques. In vitro antibacterial activity of the synthesized compounds were investigated against a representative panel of pathogenic strains specifically two Gram‐positive bacteria (Staphylococcus aureus and Streptococcus pyogenes ) and two Gram‐negative bacteria (Pseudomonas aeruginosa and Escherichia coli ) using agar‐well diffusion assay. Some of the compounds ( 3a , 3k , 3n , and 3o ) exhibited promising antibacterial activities. All the synthesized compounds have also been screened for their antioxidant activities and were found to be significantly active.     

Synthesis and antimicrobial activity of some 7‐aryl‐5,6‐dihydro‐14‐aza[1]benzopyrano[3,4‐b]phenanthren‐8H‐ones

The title compounds, 7‐aryl‐5,6‐dihydro‐14‐aza[1]benzopyrano[3,4‐b]phenanthren‐8H‐ones 3a , 3b , 3c , 3d , 3e , 3f , 3g , 3h , 3i , 3j , 3k , 3l have been synthesized by reacting various 4‐hydroxy coumarins 1a , 1b , 1c with 2‐arylidene‐1‐tetralones 2a , 2b , 2c , 2d in the presence of ammonium acetate and acetic acid under Krohnke's reaction condition. The structures of all the synthesized compounds were supported by analytical, IR, ¹H‐NMR, and ¹³C‐NMR data. All the synthesized compounds 3a , 3b , 3c , 3d , 3e , 3f , 3g , 3h , 3i , 3j , 3k , 3l have been screened for their antibacterial activities against Escherichia coli (Gram ?ve bacteria), Bacillus subtilis (Gram +ve bacteria), and antifungal activity against Candida albicans (Fungi). J. Heterocyclic Chem., (2011).     

Sulfonamide‐derived compounds and their transition metal complexes: synthesis,biological evaluation and X‐ray structure of 4‐bromo‐2‐[(E)‐{4‐[(3,4‐dimethylisoxazol‐5 yl)sulfamoyl]phenyl} iminiomethyl] phenolate

Sulfonamide‐derived new ligands, 4‐({[(E)‐(5‐bromo‐2‐hydroxyphenyl)methylidene]‐amino}methyl)benzenesulfonamide and 4‐bromo‐2‐((E)‐{4‐[(3,4‐dimethylisoxazol‐5‐yl)sulfamoyl]phenyl}iminiomethyl)phenolate and their transition metal [cobalt(II), copper(II), nickel(II) and zinc(II)] complexes were synthesized and characterized. The nature of bonding and structure of all the synthesized compounds were deduced from physical (magnetic susceptibility and conductivity measurements), spectral (IR, ¹H and ¹³C NMR, electronic, mass spectrometry) and analytical (CHN analysis) data. The structure of the ligand, 4‐bromo‐2‐((E)‐{4‐[(3,4‐dimethylisoxazol‐5‐yl)sulfamoyl]phenyl} iminiomethyl)phenolate was also determined by X‐ray diffraction method. An octahedral geometry was suggested for all the complexes. In order to evaluate the biological activity of the ligands and the effect of metals, the ligands and their metal complexes were screened for in vitro antibacterial, antifungal and cytotoxic activity. The results of these studies revealed that all compounds showed moderate to significant antibacterial activity against one or more bacterial strains and good antifungal activity against various fungal strains. Copyright © 2011 John Wiley & Sons, Ltd.     

N‐Phenyl‐substituted carbene precursors and their silver complexes: synthesis,characterization and antimicrobial activities

A series of unsymmetrically substituted N‐heterocyclic carbene (NHC) precursors ( 1a , 1b , 1c , 1d , 1e ) were synthesized from the reaction of N‐phenylbenzimidazole with various alkyl halides. These compounds were used to synthesize NHC–silver(I) complexes ( 2a , 2b , 2c , 2d , 2e ). The five new 1‐phenyl‐3‐alkylbenzimidazolium salts ( 1a , 1b , 1c , 1d , 1e ) and their NHC–silver complexes ( 2a , 2b , 2c , 2d , 2e ) were characterized by the ¹H NMR, ¹³C NMR and FT‐IR spectroscopic methods and elemental analysis techniques. Also, the two NHC–silver complexes 2b and 2c were characterized by single‐crystal X‐ray crystallography, which confirmed the linear C―Ag―Cl arrangements. The antibacterial activities of the NHC precursor and NHC–silver complexes were tested against three Gram‐positive bacterial strains (Bacillus subtilis, Listeria monocytogenes and Staphylococcus aureus) and three Gram‐negative bacterial strains (Escherichia coli, Klebsiella pneumoniae and Pseudomonas aeruginosa) using the microdilution broth method. The NHC–silver complexes showed higher antibacterial activity than the NHC precursors. In addition, silver complexes 2a , 2b , 2c , 2d showed high antibacterial activity against the Gram‐positive bacteria L. monocytogenes and S. aureus compared to the standard, tetracycline. Copyright © 2014 John Wiley & Sons, Ltd.     

Synthesis and in vitro Antimicrobial Activity of New Ethyl 2-(Ethoxyphosphono)-1-cyano-2-(substituted tetrazolo-[1,5-a]quinolin-4-yl)ethanoate Derivatives

A series of new ethyl 2‐(ethoxyphosphono)‐1‐cyano‐2‐(substituted tetrazolo[1,5‐a]quinolin‐4‐yl)ethanoate derivatives have been synthesized for the first time of tetrazolo[1,5‐a]quinoline derivatives. Elemental analysis, IR, ¹H NMR, ¹³C NMR, ³¹P NMR and mass spectral data elucidated the structures of the all newly synthesized compounds. In vitro antimicrobial activities of synthesized compounds have been investigated against Gram‐positive Bacillus subtilis, Gram‐negative Escherichia coli and two fungi Candida albicans and Aspergillus niger in comparison with standard drugs. Significantly microbiological behavior of these newly synthesized derivatives possesses significant antibacterial and antifungal activity.     

Synthesis,Characterization, and In Vitro Antibacterial Activities of Macromolecules Derived from Bis‐Chalcone

We investigated the antibacterial activity of some new macromolecules such as bis‐pyrazoline, bis‐pyrazole, bis‐pyrimidines prepared from the reaction of bis‐chalcone with thiosemicarbazide/phenyl hydrazine/guanidine hydrochloride/thiourea. All the macromolecules have been characterized by IR, ¹H NMR, ¹³C NMR, mass and elemental analyses. The antibacterial activity of these compounds was first tested in vitro by the disc diffusion assay against two Gram‐positive and two Gram‐negative bacteria, and then the minimum inhibitory concentration was determined with the reference to standard drug chloramphenicol. The results showed that pyrazoline derivative showed better antibacterial activity on S. typhimurium and E. coli than the reference drug chloramphenicol.     

Synthesis and In Vitro Antibacterial Activity of Novel Steroidal (6R)‐Spiro‐1,3,4‐thiadiazoline Derivatives

Novel steroidal (6R)‐spiro‐1,3,4‐thiadiazoline derivatives were synthesized by the cyclization of steroidal thiosemicarbazones with acetic anhydride, screened in vitro against antibacterial activity using disc‐diffusion method and the minimum inhibitory concentration. The results showed that steroidal thiadiazoline derivatives exhibited better antibacterial activity than the steroidal thiosemicarbazone derivatives. Chloro and acetoxy substituents on the 3β‐position of the steroidal thiadiazoline ring increased the antibacterial activity. Among all the compounds, compound 7 and 8 were found better inhibitors of both types of bacteria (Gram‐positive and Gram‐negative) as compared to the respective drug amoxicillin. All the synthesized compounds were well characterized by spectroscopic methods such as IR, ¹H‐NMR, ¹³C‐NMR mass, and elemental analysis and their stereochemistry was also discussed.     

Microwave‐Assisted Synthesis and Spectral Characterization of Biological Activity Heterocyclic Thiosemicarbazone and Its Organometallic Derivatives

The thiosemicarbazone coordinates to metal through the thionic sulfur and the azomethine nitrogen. The thiosemicarbazone was obtained by the thiosemicarbazide with 3‐acetyl‐2,5‐dimethylfuran by microwave irradiation. Metal complexes were prepared by the reaction of thiosemicarbazone with metal salts. IR, ¹H, ¹³C NMR, FAB‐mass spectroscopic methods, and elemental analysis elucidated the structure of these compounds. The antibacterial activity of these compounds were first tested in vitro by the disk diffusion assay against two Gram‐positive and two Gram‐negative bacteria, and then minimum inhibitory concentration was determined, chloramphenicol as reference drug. The results showed that copper ( II ) metal complex of the thiosemicarbazone ( 1.1 ) is a better inhibitor as compared with chloramphenicol.     

Synthesis,characterization, density functional theory calculations,and in vitro antibacterial activity of novel transition metal complexes containing an O3-tridentate amoxicillin-based Schiff base: A silver(II) complex as alternative against Pseudomonas aeruginosa resistant to amoxicillin

Transition metal complexes containing an amoxicillin-based Schiff base (H₂L, 3 ) obtained from the condensation of amoxicillin 1 with salicylaldehyde 2 were prepared. Spectroscopic and physicochemical techniques, namely, UV–visible, Fourier-transform infrared spectroscopy, ¹H NMR, electron paramagnetic resonance, transmission electron microscopy, mass spectrometry, magnetic susceptibility, molar conductance, density functional theory (DFT) calculations, together with elemental and thermal analyses were used to characterize the synthesized complexes. Based on these studies, the general formulae [ML(H₂O)₃], where M = Mn 4 , Ni 5 , Zn 6 , and [ML(H₂O)], where M = Cu 7 , Ag 8 , were proposed for the complexes. The amoxicillin-based Schiff base ligand behaved as a dianionic O₃-tridentate chelating agent. DFT studies and magnetic and spectral data revealed octahedral geometries for Mn, Ni, and Zn atoms and distorted tetrahedral geometries for Cu(II) and Ag(II) complexes. Synthesized compounds were tested for antibacterial activity by both agar disk diffusion method and the minimum inhibitory concentration. in vitro bacterial viability revealed that complex 5 had similar antibacterial activity as 1 against Staphylococcus aureus and Staphylococcus epidermidis, whereas Pseudomonas aeruginosa, resistant to amoxicillin, was sensitive to complex 8 . The antibacterial activity of complex 8 could be attributed to its greater catalytic activity as shown by DFT calculations. Toxicity bioassay of the tested compounds showed LC₅₀ values > 1000 ppm, indicating their nontoxicity against brine shrimp nauplii (Artemia salina).     

Derivational,Structural, and Biological Studies of Some New Pyrazolyl,Isoxazolyl, Pyrimidinyl,Pyridazinyl, and Pyridopyridazinyl from 4‐Substituted Antipyrine

(1,5‐Dimethyl‐3‐oxo‐2‐phenyl‐2,3‐dihydro‐1H‐pyrazol‐4‐yl)carbono‐hydrazonoyl dicyanide was used as a key intermediate for the synthesis of novel pyrazole, isoxazole, pyrimidine, and pyridazine derivatives. The newly synthesized compounds were characterized by elemental analyses and spectral data (IR, ¹H‐NMR, ¹³C‐NMR, and mass spectra). The compounds were tested for their in vitro antibacterial activity against Gram‐positive bacteria as (Staphylococcus aureus and Bacillus subtilis ) and Gram‐negative bacteria (Pseudomonas aeruginosa and Escherichia coli ). The investigated compounds were tested against two strains of fungi Botrytis fabae and Fusarium oxysporum using diffusion agar technique. The biological results showed clearly that most of the synthesized compounds revealed mild to moderate activity against the used microorganisms.     

Structural,spectroscopic, molecular docking,thermal and DFT studies on metal complexes of bidentate orthoquinone ligand

4‐Triphenylmethyl‐1,2‐benzoquinone (TPMBQ) reacted with some metal ions and the structure of the new compounds had been identified. The metal to ligand ratio was 1:2 which was revealed by elemental analysis. The complexes were found to have octahedral geometry and their thermal stability was studied using thermogravimetric analysis technique. The molar conductance measurements revealed the electrolytic nature of the synthesized chelates. The IR spectra concluded the bidentate nature of the TPMBQ ligand while the ¹H NMR revealed the presence of water molecules. The XRD spectra of Mn (II) and Fe (III) complexes concluded their crystalline structure while Co (II) and Cu (II) chelates refer to amorphous structures. The geometries of the TPMBQ ligand were optimized using Gaussian 09 W; density functional theory B3LYP method. (DFT)/basis set 6–311++G (d, p). HOMO and LUMO energy values for chelates, chemical hardness and electro‐negativity had been calculated. The ligand and its metal complexes had been examined against different kinds of bacteria such as Proteus vulgaris, Escherichia coli, Staphylococcus aurous and Bacillus subtitles to examine their antimicrobial activity. Molecular docking using Auto Dock tools were utilized.