European Journal of Chemistry

Four new mixed ligand metal(II) complexes with 1-methylpyrazole-3-aldehyde-4-(2-pyridyl)thiosemicarbazone (MPAPT) and 1,10-phenanthroline are reported. These complexes namely Cu(MPAPT)(1,10-phen)(Cl)] (1), [Ni(MPAPT)(1,10-phen)(Cl)] (2), [Mn(MPAPT)(1,10-phen)(Cl)].H₂O (3) and [Co(MPAPT)(1,10-phen)(Cl)].H₂O (4), were characterized by elemental analysis, spectral (IR, ¹H NMR and UV-Vis) and magnetic moment measurements. The magnetic and spectral data indicates octahedral structure for all complexes. Metal complexes have been modeled using parameterized PM3 semi-empirical method. The free ligand and its M(II) chelates have been screened for their antimicrobial activities. The antimicrobial screening demonstrated that, the Cu(II) complex have the maximum and broad activities among the investigated complexes.

Enantio separation of the local anesthetic drugs; ropivacaine (Rop), bupivacaine (Bup) and potential organic impurities (2,6-Dimethylaniline, 2,6-DMA) were accomplished on HPTLC using mucopolysaccharide selector (Chondroitin) as chiral mobile phase additive (CMPA). The enantioseparation was achieved in acetonitrile:water:methanol (16:3:1, v:v:v) containing 0.25% chondroitin as chiral mobile phase additive. The influence of separation conditions, including type and concentration of chiral selector, organic modifiers and temperatures on enantioseparation were evaluated. The enantioselective HPTLC method was validated to control the enantiomeric purity of the (S)-enantiomers (S-Rop and S-Bup); the active ingredients contained in drug products. In these conditions, linearity over the concentration range, 1.0-10.0 µg/spot for each (R)-enantiomer and 1.0-8.0 µg/spot for 2,6-DMA main organic impurity were obtained. The detection limits are less than 0.6 µg/spot of chiral and organic impurities. The intra and inter-day assay precision was less than 3.0% (RSD%).

Three simple and sensitive methods were developed for the determination of acemetacin (ACM) in presence of its degradation product, indomethacin (DEG). Several methods were evaluated and are presented. Method A was based on measuring the peak amplitude of the first derivative of the ratio spectra ¹DD at 244 nm. In method B, mean centering of ratio spectra method (MCR) was applied, which depends on measuring the mean centered values of ratio spectra of ACM at 234 nm. Method C provided separation of ACM from its DEG on pre-activated silica gel 60F₂₅₄ HPTLC plates using hexane:ethyl acetate:glacial acetic acid (6:4:0.3, v:v:v) as developing system followed by scanning at 254 nm. The suggested methods were validated in compliance with the International Conference on Harmonisation (ICH) guidelines and were successfully applied for quantification of ACM in its commercial capsule. The proposed methods were also statistically compared to a reported HPLC method with no significant difference in performance; indicating the ability of the proposed method to be reliable and suitable for routine analysis of drug product.

One pot synthesis of pyrazolo-1,4-dihydropyridine derivatives from pyranopyrazoles using acidic solvent system is described. The targeted molecules were obtained in good to excellent yield without the use of expensive catalysts, toxic solvents and chromatographic separation. The generality and functional tolerance of this convergent and environmentally benign method is demonstrated.

The starting material azo-benzyloxy acetophenone (2) has been synthesized in three steps; the direct diazotization of p-aminoacetophenone and its coupling reaction with m-cresol gave azo-acetophenone (1), which was benzylated with p-chlorobenzylchloride to give the starting material (2). The later compound was subjected to the one-pot three-component condensation reaction with substituted benzaldehydes and phenylhydrazine in the presence of sodium hydroxide to afford the target molecule azo-pyrazoline derivatives (3a-e) in high yields and short reaction times. The structures of the synthesized compounds were elucidated by using FT-IR, ¹H NMR, ¹³C NMR and ¹³C DEPT 135 spectra.

The kinetics of oxidation of 2-(2-methoxyethoxy)-ethanol and 2-(2-ethoxyethoxy)-ethanol by dihydroxydiperiodato nickelate(IV) (DPN) had been studied spectrophotometrically in alkaline medium in the temperature range of 293.2 to 313.2 K. The reaction rate showed first order dependence on DPN, 2-(2-methoxyethoxy)-ethanol and 2-(2-ethoxyethoxy)-ethanol. It was found that the pseudo-first-order rate constant k_obs increased with an increase in concentration of OH^- and a decrease in concentration of IO₄^-. There was a positive salt effect and no free radicals were detected. A plausible mechanism is proposed and the rate equations derived from the mechanism can explain all the experimental observations.

A simple, rapid and sensitive LC-MS/MS method was developed and validated for the quantification of azithromycin (AZI) in human plasma. Sildenafil citrate was used as an internal standard. The analytes were extracted from human plasma samples by liquid-liquid extraction technique. The reconstituted samples were chromatographed on a reversed ‑ phase column C18, 50 × 2.1 mm, 5 µm from Waters, by using a 80:20 (v:v) mixture of acetonitrile and 0.1% formic acid in water as the mobile phase at a flow rate of 0.5 mL/min. The calibration curve was linear (r² > 0.99) over the concentration range of 5.0-1500.0 ng/mL. The results of the intra- and inter-day precision and accuracy studies were within the acceptable limits. A run time of 0.5 min for each sample made it possible to analyze more than 400 plasma samples per day.

Thermal analysis techniques such as thermogravimetric analysis (TGA) have been widely used because they provide rapid quantitative determination of various processes under isothermal or non-isothermal conditions. It allows the estimation of effective kinetic and thermodynamic parameters for various decomposition and thermal reactions. In this article, thermal degradation of sodium carboxymethyl cellulose (SMC) is investigated by means of dynamic thermogravimetric/derivative thermogravimetry (TG/DTG) in helium atmosphere with the flow rate 100 mL/min at the heating rate of 10-30 °C/min until the furnace wall temperature reached 700 °C. The non-isothermal degradation of SMC found to be taking place occurred major one step and minor two steps. Using a non-isothermal kinetic method based on a TGA data, kinetic parameters (Eand ln A) are calculated by Kissinger-Akahira-Sunose (KAS), Flynn-Wall-Ozawa (FWO) and Friedman methods. The results of studied polymer demonstrated that E and ln A is varied with function of conversion (α), which is in good agreement with literature data.

Mixed-ligand bivalent transition metal ion complexes with N-ethyl-2-picolinoyl hydrazinecarbothioamide (EPHC) and 1,10-phenanthroline (1,10-phen) have been synthesized. The complexes namely [Cu(EPHC)(1,10-phen)(Cl)H₂O] (1), [Ni(EPHC)(1,10-phen)(Cl)H₂O] (2), [Mn(EPHC)(1,10-phen)(Cl)H₂O] (3) and [Co(EPHC)(1,10-phen)(Cl)H₂O] (4) were characterized by elemental analysis, spectral (IR, ¹H NMR and UV-Vis) and magnetic moment measurements. The magnetic and spectral data indicates octahedral structure for all complexes. Metal complexes have been modeled using parameterized PM3 semi-empirical method. The free ligand and its M(II)-chelates have been screened for their antimicrobial activities. The antibacterial screening demonstrated that, the Cu(II) complex have the maximum and broad activities among the investigated complexes.

A series of ten new Schiff base ethers were synthesized by etherification of Schiff base-{4-(pyridine-3-methylimino) methyl phenol} with fatty alkyl bromides of different chain lengths (C₄-C₁₈) in the presence of base with 80-85% isolated yields. All the synthesized Schiff base ethers (2a-j) were characterized by FT-IR, ¹H NMR, ¹³C NMR and Mass spectral studies. Presence of a characteristic peak for ether linkage, C-O at 1039 cm^-1 in IR spectra; a triplet around 7.67 ppm in ¹H NMR and a characteristic peak around 69.7 in case of  ¹³C NMR further confirmed the structures of Schiff base ethers. The structure of all the compounds were further confirmed by their characteristic molecular ion peaks in ESI-MS.

In the present study, the fatty acid composition of the fixed oil from seeds of Nigella stellaris has been investigated by GC-MS. Linoleic and oleic acids were the major fatty acids. The tocopherols determined by HPLC and α- and δ-tocopherols were detected in the oil. The seeds also were analyzed by ICP-MS to determine mineral content. Ca, P, and K were main elements among seventeen minerals in the seeds. Total phenolic and flavonoid contents of the aqueous methanolic extracts of different plant parts were assessed by Folin-Ciocalteu method and the AlCl₃ assay. The seed extract was also analyzed by RP-HPLC analysis for its thymoquinone content. The present study showed that the seed extract contained low amount of thymoquinone. The seed extract exhibited the significantly higher total phenolic and flavonoid content than the extract of aerial part. DPPH radical scavenging activity was used to evaluate the antioxidant capacity of the extracts. Both of the extracts showed high antioxidant activity.

The present work describes the preparation and characterization of new pyridazine, thiohydrazonate, bis-pyrazole, bis-triazole and polypyrazoles based on tetrazine and hydrazonoyl halides. The structures of the newly synthesized were elucidated on the basis of their spectral data FT-IR, NMR, Mass and elemental analysis.

Three different spectrophotometric methods are developed for the determination of naftidrofuryl oxalate (NAF) in pure form and its pharmaceutical preparation. The methods are based on charge transfer complexation reactions of NAF as n-electron donor with either p-chloranilic acid (PCA) or 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) or tetracyano ethylene (TCNE) as π-receptors to give highly colored anion radicals species. The colored products were quantified spectrophotometrically at 515, 588 and 396 nm in PCA, DDQ and TCNE methods, respectively. Under the optimized experimental conditions, Beer's law is obeyed over the concentration ranges of 75.0-300.0, 25.0-150.0 and 15.0- 50.0 μg/mL NAF for PCA, DDQ and TCNE methods, respectively. The proposed methods were applied successfully to the determination of NAF in pure form and its commercial tablets with good accuracy and precision. Statistical comparison of the results was performed using Student's t-test and F-ratio at 95% confidence level, showing that there is no significant difference between the reference and the proposed methods with regard to accuracy and precision. Further, the validity of the proposed methods was confirmed by standard addition technique.

Expedient and novel alternative synthesis of some fused heteropolycycles containing pyrazole moiety is described. A series of indeno[1,2-c]pyrazoles, 2H-benzo[g]indazoles and benzo[6,7] cyclohepta[1,2-c]pyrazoles were prepared by Friedel-Crafts ring closure of suitable synthesized carboxylic acids and alkanols in the presence of AlCl₃/CH₃NO₂ or P₂O₅ or PPA (polyphosphoric acid) catalysts. The precursor acids were obtained by utilizing KMnO₄ oxidation of the corresponding aldehyde, alkylations of diethyl malonates and Perkin type approaches, whereas starting alkanols were smoothly obtained by reaction of carboxylic acid ester with Grignard reagent. To exemplify, cyclizations of 5-chloro-1,3-diphenyl-1H-pyrazole-4-carboxylic acid (6) were accomplished using the above catalysts afforded 3-chloro-2-phenylindeno[1,2-c]pyrazol-4(2H)-one (1b). Similarly, cyclization of the 2-(5-chloro-1,3-diphenyl-1H-pyrazol-4-yl)propan-2-ol (8) by a Friedel–Crafts-type ring closure afforded the 3-chloro-2,4-dihydro-4,4-dimethyl-2-phenylindeno[1,2-c]pyrazole (1a).

Fourier transform infrared spectroscopy is widely used to analyze protein secondary structures. The common strategy in this field is to analyze the conformation sensitive 1700-1600 cm^-1 amide I region of protein FTIR spectrum. Though the amide III region of protein is also sensitive to secondary structural changes, its potential for protein secondary structural analysis is largely unexplored. In this paper, we performed a detailed investigation on the second structural analysis of bovine serum albumin by monitoring the spectral variation of the amide III band under a variety of pH conditions by FTIR spectroscopy and FTIR second derivative spectroscopy. Our results show that both acidic and basic conditions have pronounced effects on the overall secondary structures of BSA, suggesting denaturation effects. Furthermore, we observe that the amide III band profiles under acidic and basic conditions appear to be quite different. Our results clearly demonstrate that the amide III region is a promising probing region for protein secondary structural analysis.

An environmentally benign, simple and highly efficient method for the synthesis of 2-thio-substituted benzothiazole derivatives has been achieved in good to excellent yields by reacting a series of aryl halides with 2-mercapto benzothiazole, using recyclable CuFe₂O₄ nanoparticles under ligand free conditions in PEG-400 as solvent. In the present protocol, the copper ferrite nanoparticles can be recovered and reused up to four cycles without significant loss of activity.

The reaction of N,N'-(1,4-phenylene)bis(2-cyanoacetamide) (1) with phenyl isothiocyanate gave thiocarbamoyl derivative 3, which reacted with α-halocarbonyl compounds in a mixture of ethanol:N,N-dimethylformamide in the presence of triethylamineto afford thiazoles 4, 7, 10 and thiophene12 derivatives. While, when the same reaction was refluxed in a mixture of ethanol:N,N-dimethylformamide only afforded the acyclic compounds 5, 6, 8, 9 and 11, which when refluxed in N,N-dimethylformamide in presence of triethylamine gave the corresponding above thiazole and thiophene derivatives. Moreover, the reaction of compound 3 with dihalo compounds afforded cyclic dithio derivatives 13a, 13b and 14. The newly synthesized compounds were characterized by analytical, spectral data and evaluation of their antimicrobial activities of 4, 7, 14 and 15 have a high antimicrobial activity.

IR and Raman spectra of lithium pyruvate monohydrate and its O- and C-deuterated and ¹³C- and ¹⁸O-substituted compounds have been recorded in the solid state, and the observed bands have been assigned by using the isotope effects and the normal coordinate calculations based on the gem-diol structure (lithium 2,2-dihydroxypropionate). The refined force constants have well reproduced the observed frequencies and the ¹³C- and ¹⁸O-shifts. These results support the structures of these compounds discussed by many authors. The potential energy distributions show that many vibrational modes are very complicated except for the well-known group vibrations. The additive property of the isotopic frequency shifts has also been discussed.

Simple, sensitive and precise spectrophotometric and chemometric stability indicating techniques were adopted for Olanzapine (OLA) determination in presence of its degradation products over a concentration range of 0.002-0.02 mg/mL. The spectrophotometric technique involves six methods; first method is first derivative (D1) spectrophotometric one, which allows the determination of OLA in presence of its acidic and alkaline degradation products at 261.2 and 260.6 nm with mean percentage recoveries of 99.90±0.48 and 99.95±0.67, respectively. While second derivative spectrophotometry (D2) was used for determination of drug in presence of alkaline degradation products. Second method is first-derivative of the ratio spectra (DR1) for determination of OLA in presence of its acidic and alkaline degradation products at 267.9 and 251.6 nm, respectively with mean percentage recoveries of 99.81±0.64 and 100.53±1.11, respectively. The third method is pH-induced difference method for determination of OLA in presence of its acidic and alkaline degradation products; with mean percentage recoveries 100.09±0.06 and 99.77±0.78, respectively. Fourth method is the Q-analysis (absorption ratio) method, which involves the formation of absorbance equation at 296.3 nm (isosbestic point) and 271 nm (λ_max of OLA) for the determination of OLA in presence of its acidic degradation products. The mean percentage recovery is 100.07±1.51. Fifth method based on dual wavelength selection was developed for the determination of OLA in presence of its acidic degradation products with mean percentage recovery of 100.36±0.69. Sixth method based on simple mathematic algorithm by the bivariate calibration was also used for the determination of OLA with the mean percentage recovery of 101.72±1.10. The second technique is chemometrics, which includes determination of OLA in presence of its acidic degradation products using multivariate calibration methods (the classical least squares (CLS), principle component regression (PCR) and partial least squares (PLS)) using the information contained in the absorption spectra.

Three components; ethyl cyanoacetate, ethyl amines, and methyl propionylacetate were condensed using solid supports in microwave to give 1,4-diethyl-2,6-dioxo-1,2,5,6-tetrahydropyridine-3-carbonitrile (9) that was then coupled with aromatic diazonium salts to give the corresponding arylhydrazono-1,4-diethyl-2,6-dioxo-1,2,5,6-tetrahydropyridine-3-carbonitrile disperse dyes, 10a-g. Structures of the afforded compounds were confirmed by (IR, NMR, EI/MS) and one of them was further confirmed by X-ray crystallography (10g). Fastness properties of the reported dyes were intensively examined against light, perspiration and washing fastness, exhibiting moderate, very good and excellent fastness levels, respectively. The antimicrobial activity of the dyes were tested against different bacterial strains of Gram positive and Gram negative characteristics, and yeast, at where most of them showed promising activities against such test organisms.

The mixed-ligand complexes of Co(II), Ni(II), Mn(II) and Zn(II) with 2-aminomethyl thiophenyl-4-bromosalicylaldehyde Schiff base (ATS) and glycine as a representative example of amino acids have been achieved. These complexes namely [Ni(ATS)(Gly)] (1), [Co(ATS)(Gly)].H₂O (2) [Mn(ATS)(Gly)].2H₂O (3), and [Zn(ATS)(Gly)] (4) were characterized by elemental, molar conductance, infrared, magnetic moment, and electronic spectra. ATS behaves as mononegatively charged bidentate ligand with coordination through azomethine nitrogen and phenolate oxygen groups while glycine acts as monobasic bidentate ligand is coordinated via amino and ionized carboxylate group after deprotonation. The low molar conductance values suggest the non-electrolytic nature of these complexes. The magnetic and spectral data indicates a square planar geometry for Ni(II) complex, tetrahedral geometry for Zn(II) and octahedral geometry for both Mn(II) and Co(II) complexes. The isolated chelates have been screened for their antimicrobial activity.

Condensation of 1H-1,2,4-triazol-5-amine with the appropriate sodium (E)-(2-oxocycloalkylidene)methanolate gave 7,8-dihydro-6H-cyclopenta[e][1,2,4]triazolo [1,5-a]pyrimidine, 6,7,8,9-tetrahydro-[1,2,4]triazolo[1,5-a]quinazoline, 7,8,9,10-tetra hydro-6H-cyclohepta[e][1,2,4]triazolo[1,5-a]pyrimidine and 6,7,8,9,10,11-hexahydro cycloocta[e][1,2,4]triazolo[1,5-a]pyrimidine. Structures of the newly synthesized compounds were elucidated via elemental analyses, spectral (IR, ¹H NMR, ¹³C NMR, 2D NMR), and X-ray single crystal diffraction data. These derivatives showed potent anti-tumor cytotoxic activity in vitro using different human cancer cell lines.

The binding properties of a cyanopyranopyridothiazole (L1), aminothiazole (L2), iminothiazole (L3) and phenyliminothiazole (L4) derivatives toward some transition metal and heavy metal cations, have been investigated in methanol, followed by UV spectrophotometry absorption and conductivity determination. The stoichiometries of the formed complexes and their stability constants were determined by a digital data processing. The study of extraction properties from water into dichloromethane shows a lower extraction affinity for the metal picrates with L1, unlike L2-L4 which are better extracted and specially Fe(III) with L4.

The calculation of ¹³C isotropic shielding constants by means of GIAO and CSGT methods of eight Schiff base ligands containing piperazine moiety at the Hartree-Fock and B3LYP levels of theory are presented. Good linear correlations between the calculated chemical shielding at gas-phase and experimental shift values in CDCl₃ solution were obtained. Density functional theory (DFT) calculations at the B3LYP/6-31G(2d,p) level of theory is used to optimize the geometry of ligands. Calculated nuclear magnetic resonance (NMR) chemical shifts ¹³C are reported for the some N₄O₂, N₄S₂ and N₆ Schiff base ligands containing piperazine moiety. In order to establish a convenient and consistent protocol to be employed for confirming the experimental ¹³C NMR spectra of Schiff base ligands, different combinations of models and basis sets were considered. The most reliable results were obtained at B3LYP/6-311G++ (d,p) level and CSGT method which can be used to predict ¹³C NMR chemical shifts with a very high accuracy for latter compounds. These results show the agreement between theoretical and experimental ¹³C NMR chemical shielding of mentioned ligands.

Condensation of 4,4-diaminodiphenyl sulfone (Dapsone) with aliphatic and aromatic aldehydes yielded a few Schiff base derivatives in good yields. The optimized structural parameters (bond lengths and bond angles) of three azomethine compounds have been obtained by using the GAUSSIAN 09 program package. Conformer of compound 1 has the highest energy, which has less stability than compounds 2 and 3 at the same model. The synthesized compounds were screened for antibacterial activity against Staphylococcus aureus, Escherichia coli, Bacillus subtilis and fungicidal activity against Aspergillus niger and Candida albicans. All compounds exhibited potent antibacterial and antifungal activity with the reference standard ciprofloxacin and Amphotericin B, respectively.

Coupling of 5-acetyl-2-amino-4-methylthaizole diazonium sulphate (1) with 3-chloro-pentane-2,4-dione (2) afforded the thiazolo[2,3-c]-1,2,4-triazole derivative, (5). Bormination of compound (5) followed by reaction with potassium cyanide afforded bis-3-oxo-propanenitrile derivative (7) which, reacts with CS₂/NaH/CH₃I to afford the ketene S,S-dithioacetal, (8). Synthesis of 1,3-dithiolane (11) and thiophene (15) derivatives have been reported.

X-ray tube has been used for selective M sub-shell excitations in a single reflection set-up for Pt, Au, Pb, Th and U required for M sub-shell fluorescence cross-sections measurements. Weighted photon energy and total intensity of the incident flux between E_M5 edge and tube anode voltage were evaluated following a specific procedure. Comparison of measured cross-sections with the calculated ones from existing DHS/DF model based theoretical data on atomic parameters lend support to the present findings.

A new receptor named, 2-(2-(2,4-dinitrophenyl)hydrazono)2H-indene-1,3-dione, used as a colorimetric sensor based on 2,4-dinitrophenylhydrazone derivative of ninhydrin was synthesized by simple step with good yields and characterized by IR and ¹H, ¹³C NMR and MS spectroscopic techniques. The anion recognition properties were studied by UV-Vis spectroscopic technique. The results showed that the receptor had a higher affinity to F^-, CN^-, H₂PO₄^-, CH₃COO^- and OH^-, but showed no evident binding with Cl^-, Br^- and I^-. Binding of the reseptor to anions such as CN^-, AcO^-, F^-, H₂PO₄^- and OH^-exhibited an obvious color change from greenish yellow to purplish blue, which was possible to observe by the naked eye.

A series of 1,3,5-triazine-bis-azomethinehybrid molecules (4a-p and 5a-p) were synthesized and tested against Mycobacterium tuberculosis H37Rv strain. Preparation of the titled compounds was achieved by reaction of N-(4-aminobenzylidene)-4-methoxy-6-methyl-1,3,5-triazin-2-amine (3) with aromatic/heteroaromatic aldehydes (4a-p)and ketones (5a-p). Among the compounds tested, (4d) was identified as the most active in vitro with MIC value 3.125 µg/mL against Mycobacterium tuberculosis H37Rv.

Simple and precise spectrofluorometric method has been developed and validated for the determination of linagliptin (LNG) in the range of 10-110 μg/mL. The results obtained were of good precision and statistically compared to the reference method using one-way analysis of variance (ANOVA). The method developed was satisfactorily applied to the analysis of the pharmaceutical formulation and proved to be specific and accurate for the quality control of linagliptin in its pharmaceutical dosage form. The development of spectrofluorometric method for the determination of LNG was of interest as no such methods have been reported.