Synthesis of novel biaryl 2-benzimidazoles and 2-benzothiazoles

Herein, we describe the synthesis of the novel 4-(1H-benzo[d]imidazol-2-yl)isoxazol-5-amine (7) and 4-(1H-benzo[d]thiazol-2-yl)isoxazol-5-amine scaffolds (8). Initial attempts following literature procedures for the synthesis of similar compounds did not yield the desired product. Instead we obtained the ring-opened adduct 2-(1H-benzo[d]imidazol-2(3H)-ylidene)-2-cyanoacetamide (5). We were able to modify reaction conditions and successfully synthesize the desired product. We also describe a convenient one-pot microwave-assisted relay reaction for the synthesis of novel and reported 2-substituted benzimidazoles and benzothiazoles from inexpensive, commercially available reagents, 2-benzothiazole acetonitrile (2) and 2-benzimidazole acetonitrile (1). In all cases, good yields of products were obtained and reaction times were significantly reduced.     

Synthesis, spectral investigation and thermal aspects of coordination polymeric chain assemblies of some transition metal ions with bis-pyrazolones

A few coordination chain polymeric assemblies of the type [M(SB)(H(2)O)(2)](n).xH(2)O or [VO(SB)(H(2)O)](n).H(2)O [where M=Mn(II), Cu(II) and Zn(II), x=1; Co(II) and Ni(II) x=2, H(2)SB=(4Z,4'Z)-4,4'-(2,2'-(4,4'-methylenebis(4,1-phenylene)bis(azanediyl))bis(1-hydroxy ethan-2-yl-1-ylidene))bis(3-methyl-1-phenyl-1H-pyrazol-5(4H)-one)] have been investigated. Structural and spectroscopic properties have been studied on the basis of elemental analyses, infrared spectra, (1)H and (13)C NMR spectra, electronic spectra, magnetic measurements and thermo gravimetric analyses. FT-IR, (1)H and (13)C NMR studies reveal that the ligand (H(2)SB) exists in the tautomeric enol form in both the states with intramolecular hydrogen bonding. Magnetic moment and reflectance spectral studies reveal that an octahedral geometry has been assigned to all the prepared coordination polymers. The kinetic parameters such as order of reaction (n) and the energy of activation (E(a)) have been reported using Freeman-Carroll method. The pre-exponential factor (A), the activation entropy (DeltaS(#)), the activation enthalpy (DeltaH(#)) and the free energy of activation (DeltaG(#)) have been calculated.     

Assessment of the metabolic profile in Type 2 diabetes mellitus and hypothyroidism through proton MR spectroscopy

The metabolic changes in the brain of patients affected with Type 2 diabetes mellitus (DM) alone, both Type 2 DM and hypothyroidism and hypothyroidism only were investigated using proton magnetic resonance spectroscopy ((1)H MRS). Single-voxel spectroscopy was carried out in right and left frontal lobe white matter, left parietal white matter and left occipital gray matter. Choline (Cho)/creatine (Cr) value was found to be increased in the left occipital gray matter of the subjects affected with Type 2 DM and both Type 2 DM and hypothyroidism as compared to controls. No significant change in the Cho/Cr value in the occipital gray matter was observed in hypothyroid subjects as compared to controls. However, they showed an increased level of Cho/Cr in the frontal white matter. High Cho is associated with altered membrane phospholipid metabolism. The high Cho in frontal white matter in hypothyroids and occipital gray matter in diabetic patients suggests that, though both the diseases are endocrine disorders, they differ from each other in terms of regional brain metabolite changes.     

Green approach for the synthesis of 3‐methyl‐1‐phenyl‐4‐((2‐phenyl‐1H‐indol 3‐yl)methylene)‐1H‐pyrazole‐5(4H)‐ones and their DNA Cleavage,antioxidant, and antimicrobial activities

3‐Methyl‐1‐phenyl‐4‐((2‐phenyl‐1H‐indol‐3‐yl)methylene)‐1H‐pyrazol‐5(4H)‐ones (5a‐i) was prepared by the condensation reaction of different 3‐formyl‐2‐phenylindole derivatives (2a‐i) and 3‐methyl‐1‐phenyl‐2‐pyrazoline‐5‐one in quantitative yield by applying various green synthetic methods as grinding, microwave irradiation using different catalysts under solvent‐free mild reaction conditions with high product yields. The structures of the synthesized compounds were characterized on the basis of elemental analysis, infrared, ¹HNMR, ¹³C NMR, and mass spectral data. The synthesized compounds were screened for free radical scavenging, antimicrobial, and DNA cleavage activities. Most of the tested compounds belonging to the 3‐methyl‐1‐phenyl‐4‐((2‐phenyl‐1H‐indol‐3‐yl)methylene)‐1H‐pyrazol‐5(4H)‐ones series exhibited promising activities.     

Calix[4]pyrrole virtuous sensor: a selective and sensitive recognition for Pb(II) ions by spectroscopic and computational study

A novel supramolecular sensor derived from calix[4]pyrrole system i.e. calix[4]pyrrole bearing aminoanthraquinone derivative (CAAQ) have been designed and synthesized. The complexation behavior of metal cations [Ag(I), Ba(II), Ca(II), Ni(II), Co(II), Fe(III), Hg(II), Cu(II), Cr(II), Pb(II), Zn(II), (1 × 10^?4 M)] with CAAQ (1 × 10^?6 M) was studied by spectrophotometry and spectrofluorometry. Metal ion like Pb(II) produces red shift in absorption spectra and quenching in emission spectra likelihood of strong complexation of Pb(II) ions with CAAQ. Fluorescence cell imaging also supports the complexation of Pb(II) ions with CAAQ. The binding constants, quantum yield, stoichiometry of complex, mechanism of quenching by Stern–Volmer equation and Density functional theory calculation have been determined.     

Plasma analysis of celiprolol by HPTLC: a useful technique for pharmacokinetic studies

A rapid and sensitive high performance, thin-layer chromatographic (HPTLC) method has been developed for the measurement of celiprolol in human plasma and its use in pharmacokinetic studies has been evaluated. Detection and quantitation were performed without using an internal standard. A simple extraction procedure was followed for extracting celiprolol from plasma and a known amount of the extract was spotted on precoated silica gel 60 F254 plates using a Camag Linomat IV autosampler. Celiprolol was quantitated using a Camag TLC Scanner 3. The average recovery of authentic analytes (20 to 200 ng/mL) added to plasma was 72.06 +/- 2.8% and the lowest amount of celiprolol that could be detected was 10 ng/mL. The method provides a direct estimate of the amount of celiprolol present in plasma. Pharmacokinetic parameters of 2 marketed preparations have also been determined after oral administration to 12 healthy human volunteers.     

Magnetic behavior of the oxide spinels: Li0.5Fe2.5−2x Al x Cr x O4

In order to study the effect of substitution of Fe³⁺ by Al³⁺ and Cr³⁺ in Li_0.5Fe_2.5O₄ on its structural and magnetic properties, the spinel system Li_0.5Al _x Cr _x Fe_2.5?2x O₄ (x=0.0, 0.2, 0.4, 0.5, 0.6 and 0.8) has been characterized by X-ray diffraction, high field magnetization, low field ac susceptibility and ⁵⁷Fe Mossbauer spectroscopy. Contrary to the earlier reports, about 50% of Al³⁺ is found to occupy the tetrahedral sites. The system exhibits canted spin structure and a central paramagnetic doublet was found superimposed on magnetic sextet in the Mössbauer spectra (x>0.5).     

Estimation of pioglitazone hydrochloride and metformin hydrochloride in tablets by derivative spectrophotometry and liquid chromatographic methods

Two simple and accurate methods of analysis to determine pioglitazone hydrochloride (PIO) and mefformin hydrochloride (MET) in combined dosage forms were developed using second-derivative spectrophotometry and reversed-phase liquid chromatography (LC). PIO and MET in combined preparations (tablets) were quantified using the second-derivative responses at 227.55 nm for PIO and 257.25 nm for MET in spectra of their solutions in a mixture of methanol and acetonitrile (30 + 70). The calibration curves were linear [correlation coefficient (r) = 0.9984 for PIO and 0.9986 for MET] in the concentration range of 8-40 microg/mL for PIO and 4-12 microg/mL for MET. In the LC method, analysis was performed on a Hypersil ODS-C18 column with 5 microm particle size using the mobile phase acetonitrile-water-acetic acid (75 + 25 + 0.3), adjusted to pH 5.5 with liquor ammonia, at a flow rate of 0.5 mL/min. Measurement was made at a wavelength of 230 nm. Both the drugs were well resolved on the stationary phase, and the retention times were 8.5 min for PIO and 16.0 min for MET. The calibration curves were linear (r = 0.9933 for PIO and 0.9958 for MET) in the concentration range of 4-20 microg/mL for PIO and MET. Both methods were validated, and the results were compared statistically. They were found to be accurate, precise, and specific. The methods were successfully applied to the estimation of PIO and MET in combined tablet formulations.     

Solubility and solution thermodynamics of 2, 6-bis (4-hydroybenzylidene) cyclohexanone in pure and binary solvents at various temperatures

Solubility of 2, 6-bis (4-hydroxybenzylidene) cyclohexanone (BHBC) in pure solvents such as 1,4-dioxane, methanol, 1-butanol, 1-propanol, ethyl acetate, acetone, tetrahydrofuran (THF), glacial acetic acid, dimethyl sulphoxide (DMSO) and binary solvents dimethyl formamide (DMF) and (1-Propanol + Tetrahydrofuran) were investigated by gravimetric method at different temperature range. The experiment solubility increases with increase in temperature in both pure and binary solvents. The Maximum solubility is found in DMF at 328.15 K and for binary solvent mixture i.e. 1-propanol and THF (0.9 mol fraction) it was maximum at 318.15 K. Further modified Apelblate and Buchowski-Ksiazczak models were used for the theoretical calculation of solubility of BHBC in pure as well binary solvents. A satisfactory correlation of these models with experimental data was observed. The solution thermodynamics parameters like enthalpies, Gibb's free energy of dissolution and entropy of solutions were calculated using Van't Hoff and Gibb's equation, which reveals the solvation mechanism is non-spontaneous and entropy driven.