Development and Validation of Stability-Indicating UPLC Method for 9-Desmethyl-<Emphasis Type="Italic">α</Emphasis>-dihydrotetrabenazine

A stability-indicating UPLC method was developed for quantitative determination of 9-desmethyl-α-dihydrotetrabenazine (9-DM-α-DTBZ), the precursor for preparing a widely used vesicular monoamine transporter 2 imaging agent ¹¹C-α-DTBZ. Compound 9-DM-α-DTBZ was subjected to various stress conditions consisting of acidic, alkaline, oxidative, thermal and photolytic forced degradation. The decomposition of 9-DM-α-DTBZ was observed under oxidative condition, whereas no obvious degradation was shown under the other stress conditions. For chromatographic separation of 9-DM-α-DTBZ and its degradation products, an Acquity UPLC BEH C18 column (2.1 × 100 mm, 1.7 μm) and a mobile phase of 20:80 (v/v) methanol/ammonium acetate buffer (pH 4.5, 10 mM) were used. Quantitative determination of 9-DM-α-DTBZ was performed using a PDA detector at a flow rate of 0.30 mL min^?1. UPLC–MS analysis was further utilized to characterize the two degradation products. The proposed method was fully validated as per USP guidelines with respect to linearity, accuracy, precision, robustness, limit of detection (LOD) and limit of quantification (LOQ). The linear regression analysis showed a good linear relationship (r ²  = 0.9995) in the concentration range of 0.001–1.00 mg mL^?1 (n = 6). The assay method was found to have good precision (1.14–1.35% RSD) and recovery (98.91–101.23%). Additionally, the LOD and LOQ of 9-DM-α-DTBZ were 0.30 and 1.00 μg mL^?1, respectively. These results indicated that the present method could be used to evaluate the quality of regular production samples and also used in stability assays.     

Structure,bioactivity and theoretical study of 1-cyano-<Emphasis Type="Italic">N</Emphasis>-p-tolylcyclo-propanecarboxamide

A novel cyclopropane derivative, 1-cyano-N-p-tolylcyclopropanecarboxamide (C₁₂H₁₂N₂O, Mr = 200.24) was synthesized and its structure was studied by X-ray diffraction, FTIR, ¹H and ¹³C NMR spectrum and MS. The crystals are monoclinic, space group P2_1/c with a = 7.109 (4), b = 13.758 (7), c = 11.505 (6) Å, α = 90.00, β = 102.731 (8), γ = 90.00 °, V = 1097.6 (9) ų, Z = 4, F(000) = 312, D _c  = 1.212 g/cm³, μ = 0.0800 mm^?1, the final R = 0.0490 and wR = 0.1480 for 1,375 observed reflections with I > 2σ(I). A total of 6,109 reflections were collected, of which 2,290 were independent (R _int = 0.0290). Theoretical calculation of the title compound was carried out with HF/6-31G (d,p), B3LYP/6-31G (d,p), MP2/6-31G (d,p). The full geometry optimization was carried out using 6-31G(d,p) basis set, and the frontier orbital energy. Atomic net charges were discussed, and the structure-activity relationship was also studied. The preliminary biological test showed that the synthesized compound is bioactive against the KARI of Escherichia coli.     

Synthesis,characterization, molecular docking,analgesic, antiplatelet and anticoagulant effects of dibenzylidene ketone derivatives

In this study dibenzylidene ketone derivatives (2E,5E)-2-(4-methoxybenzylidene)-5-(4-nitrobenzylidene) cyclopentanone (AK-1a) and (1E,4E)-4-(4-nitrobenzylidene)-1-(4-nitrophenyl) oct-1-en-3-one (AK-2a) were newly synthesized, inspired from curcuminoids natural origin. Novel scheme was used for synthesis of AK-1a and AK-2a. The synthesized compounds were characterized by spectroscopic techniques. AK-1a and AK-2a showed high computational affinities (E-value >???9.0 kcal/mol) against cyclooxygenase-1, cyclooxygenase-2, proteinase-activated receptor 1 and vitamin K epoxide reductase. AK-1a and AK-2a showed moderate docking affinities (E-value >???8.0 kcal/mol) against mu receptor, kappa receptor, delta receptor, human capsaicin receptor, glycoprotein IIb/IIIa, prostacyclin receptor I₂, antithrombin-III, factor-II and factor-X. AK-1a and AK-2a showed lower affinities (E-value >???7.0 kcal/mol) against purinoceptor-3, glycoprotein-VI and purinergic receptor P₂Y₁₂. In analgesic activity, AK-1a and AK-2a decreased numbers of acetic acid-induced writhes (P?<?0.001 vs. saline group) in mice. AK-1a and AK-2a significantly prolonged the latency time of mice (P?<?0.05, P?<?0.01 and P?<?0.001 vs. saline group) in hotplate assay. AK-1a and AK-2a inhibited arachidonic acid and adenosine diphosphate induced platelet aggregation with IC₅₀ values of 65.2, 37.7, 750.4 and 422 µM respectively. At 30, 100, 300 and 1000 µM concentrations, AK-1a and AK-2a increased plasma recalcification time (P?<?0.001 and P?<?0.001 vs. saline group) respectively. At 100, 300 and 1000 µg/kg doses, AK-1a and AK-2a effectively prolonged bleeding time (P?<?0.001 and P?<?0.01 vs. saline group) respectively. Thus in-silico, in-vitro and in-vivo investigation of AK-1a and AK-2a reports their analgesic, antiplatelet and anticoagulant actions.     

Synthesis,SAR and in vitro therapeutic potentials of thiazolidine-2,4-diones

Background

Thiazolidinedione is a pentacyclic moiety having five membered unsaturated ring system composed with carbon, oxygen, nitrogen and sulfur molecules at 1 and 3 position of the thiazole ring and widely found throughout nature in various form. They favourably alter concentration of the hormones secreted by adipocytes, particularly adiponectin. They also increase total body fat and have mixed effects on circulating lipids. Thiazolidinedione nucleus is present in numerous biological moieties and has different pharmacological activities likes, e.g. antimalarial, antimicrobial, antimycobacterial, anticonvulsant, antiviral, anticancer, anti-inflammatory, antioxidant, anti-HIV (human immunodeficiency virus) and antituberculosis.

Results and discussion

The synthesized compounds were screened for their in vitro antimicrobial potential against Gram (positive and negative) bacterial and fungal strains by tube dilution technique. In this series, compound 10 exhibited significant antimicrobial activity against B. subtilis and S. aureus with MIC?=?4.2?×?10^?2 µM/ml, compound 15 showed significant activity against K. pneumonia with MIC?=?2.60?×?10^?2 µM/ml and compound 4 displayed potent antibacterial activity against E. coli with MIC?=?4.5?×?10^?2 µM/ml. Compound 10 had most potent antifungal activity against C. albicans and A. niger with MIC?=?4.2?×?10^?2 µM/ml. Compounds 12 and 15 were found as most active antidiabetic agents having IC₅₀?=?27.63 μg/ml and 22.35 μg/ml, respectively, using DPPH assay. Antioxidant activity results indicated that compounds 3 and 9 displayed good antioxidant agent with IC₅₀?=?29.04 μg/ml and 27.66 μg/ml respectively, using α amylase assay.

Conclusion

All the synthesized derivatives exhibited good antimicrobial, antidiabetic and antioxidant activities using specific methods then compared with mentioned standard drugs. Especially, compounds 3, 4, 9, 10, 12 and 15 displayed highest activity. Structure activity relationship demonstrated that presence of electron withdrawing group (o-NO₂, p-Cl, p-Br) enhanced the antibacterial activity against E. coli as well as increased the antioxidant activity while the presence of electron releasing group (o/p-OCH₃, 3,4,5-trimethoxy) enhanced the antibacterial activity against S. aureus, B. subtilis, S. typhi, K. pneumonia, C. albicans and A. niger as well as the antidiabetic activity.

     

Tetrakis [<Emphasis Type="Italic">N</Emphasis>-(2-pyridyl) sulfonamide] di palladium: synthesize,X-ray diffraction,antibacterial properties and as a novel binuclear Pd-complex for coupling reactions

The N-(2-pyridyl) 4-toluene sulfonamide as a free ligand (PTS) was prepared from the reaction of 2-amino pyridine and 4-toluenesulfonyl chloride in the presence of potassium hydroxide solution 1 M as a base and THF was used as a solvent. The complex tetrakis [N-(2-pyridyl) sulfonamide] di palladium (1) (Pd₂L₄) was also prepared from the reaction of PdCl₂(CH₃CN)₂ using (PTS) in the presence of NaOH 0.5 M and its application in Heck and Suzuki reactions. This complex consists of a binuclear unit consisting of four ligands linked to two palladium atoms via the nitrogen of pyridines ring and the nitrogen of sulfonamides. These compounds were confirmed by FT-IR and ¹H NMR spectroscopy. Moreover, the structure of the complex was studied by single-crystal X-ray diffraction method. The green crystal of Pd₂L₄ [L = N-(2-pyridyl) sulfonamide](1) was found to crystallize in the monoclinic space group C2/c with a = 18.2013(19), b = 19.7544(16), c = 17.2898(19) Å, β = 120.179(8) °; V = 5374.0(9) ų; Z = 4; the final R ₁ = 0.0894, wR ₂ = 0.1754 (or 5867 observed reflections and 318 variables). The Pd–Pd distance is 2.567(2) Å. In addition, PTS and Pd₂L₄ presented different antibacterial behaviors. The free ligand was active against Staphylococcus aureus and Escherichia coli, but the complex was inactive against them.     

One-step preparation of sulfonated carbon and subsequent preparation of hybrid material with polyaniline salt: a promising supercapacitor electrode material

The present trend to increase the energy density of electrochemical supercapacitor is to hybrid the electrochemical double layer capacitance electrode materials of carbon with loading or encapsulation of transition metal oxide or conductive polymeric pseudocapacitor materials as the binary or ternary hybrid electrochemical active materials. In this work, we selected polyaniline salt-sulfonated carbon hybrid (PANI-SA?C _SA ) as a cheaper electrode material for supercapacitor electrode. Sulfonated carbon (C _SA ) was prepared from hydrothermal carbonization of furaldehyde and p-toluenesulfonic acid. Polyaniline-sulfate salt containing sulfonated carbon was prepared by chemical oxidative polymerization of aniline using ammonium persulfate in presence of sulfuric acid and sulfonated carbon via aqueous, emulsion and interfacial polymerization pathways. Formation of hybrid material was confirmed from scanning electron microscopy. Among the hybrid prepared with three different polymerization pathways, hybrid prepared by aqueous polymerization pathway showed better electrochemical performance. The specific capacitance of the hybrid prepared via aqueous polymerization was 600 F g^?1, which is higher than that of the pristine PANI-SA (350 F g^?1) and C _SA (30 F g^?1). Hybrid material was subjected for 8000 charge-discharge cycles and at 8000 cycles; it showed 88% retention of its original specific capacitance value of 485 F g^?1 with coulombic efficiency (97–100%). These results showed that C _SA micro spheres prevent the degradation of PANI-SA chains during charge/discharge cycles. Specific capacitance, cycle life, low solution resistance, low charge transfer resistance and high phase angle value of PANI-SA?C _SA supercapacitor cell indicates a higher performance supercapacitor system.

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Graphical abstract Synthesis of hybrid of sulfonated carbon with polyaniline sulfate salt and its supercapacitor performance Ravi Bolagam, Palaniappan Srinivasan,^* Rajender Boddula

     

Synthesis,characterization, and crystal structure of modified benzophenone UV-absorber containing reactive group

A modified benzophenone UV-absorber containing reactive group (4-(4,6-dichloro-1,3,5-triazin-2-yloxy)-2-hydroxyphenyl)phenyl)methanone (UV-DTHM) has been prepared in good yield from the nucleophilic substitution reaction of 2,4-dihydroxy benzophenone with 2,4,6-trichlorotriazine, catalyzed by 1.3 equiv. NaOH. The most favorable reaction conditions (the catalyst dosage, the mole ratio of the reactants, and reactive time) were selected. The compound was characterized by IR spectroscopy, ¹H NMR, ¹³C NMR, mass spectrometry, elemental analysis, and single crystal X-ray diffraction. The crystal monoclinic, space group C c with the unit cell parameters a = 3.987(2), b = 30.688(16), c = 12.423(6) Å and α = 90.00, β = 92.117(15), γ = 90.00º, Z = 4, R = 0.0620. wR(F ²) = 0.1589. The crystal structure reveals that 2,4,6-trichlorotriazine is boned to 4-seat hydroxyl of 2,4-dihydroxy benzophenone and a intramolecular hydrogen bond is formed with hydrogen of 2-hydroxyl and oxygen of carbonyl group. Moreover, thermogravimetric analysis (TGA) of UV-DTHM was studied, showing two distinct endothermic peaks at temperatures of 281.5 and 358.5 °C. The molar absorption coefficient of UV-DTHM is 1.6 × 10⁴ and 6.3 × 10³ at 268 and 330 nm, respectively, and shows excellent ultraviolet absorption property.     

Synthesis,spectroscopic characterization,crystal structures,and theoretical studies of (<Emphasis Type="Italic">E</Emphasis>)-2-(2,4-dimethoxybenzylidene)thiosemicarbazone and (<Emphasis Type="Italic">E</Emphasis>)-2-(2,5-dimethoxybenzylidene)thiosemicarbazone

Two thiosemicarbazones, (E)-2-(2,4-dimethoxybenzylidene)thiosemicarbazone (24-MBTSC (1)) and (E)-2-(2,5-dimethoxybenzylidene)thiosemicarbazone (25-MBTSC (2)), derived from 2,4-dimethoxybenzaldehyde and 2,5-dimethoxybenzaldehyde, respectively, with thiosemicarbazide have been synthesized and their structures were characterized by elemental analyses, FT-IR, ¹H NMR spectroscopy, and X-ray single-crystal diffraction analysis. Molecular orbital calculations have been carried out for 1 and 2 by using an ab initio method (HF) and also density functional method (B3LYP) at 6-31G basis set. Compound 1 crystallizes in the monoclinic system, space group P2₁/c, with a = 8.1342(5) Å, b = 18.1406(10) Å, c = 8.2847(6) Å, β = 109.7258(17)°, V = 1150.75(12) Å³, and Z = 4, whereas compound 2 crystallizes in the orthorhombic system, space group Pbca, with a = 11.0868(6) Å, b = 13.1332(6) Å, c = 15.9006(8) Å, V = 2315.2(2) Å³, and Z = 8. The compounds 1 and 2 displays a trans-configuration about the C=N double bond.     

Synthesis,crystal structure,and hydrogen-bonded displacive-type structural phase transition of guanidine dichloroacetate

Guanidine dichloroacetate was synthesized and separated as crystals. Differential scanning calorimetry (DSC) measurement shows that this compound undergoes a reversible phase transition at about 275 K with a heat hysteresis of 28 K. Step-like dielectric anomaly observed at 274 K further confirms the phase transition. The single-crystal X-ray diffraction data suggested that these was a transition from a room-temperature phase with the space group of P2₁/n (a = 8.030(5), b = 12.014(9), c = 8.124(6) Å, β = 96.089(1)°, V = 779.3(1) Å³, and Z = 4) to a low-temperature one with the space group of P2₁/c (a = 7.941(2), b = 11.828(3), c = 10.614(2) Å, β = 130.985(1)°, V = 752.6(3) Å³, and Z = 4). The displacements of hydrogen bonds induce the structure phase transition.     

Determination of mycotoxins,alkaloids, phytochemicals,antioxidants and cytotoxicity in Asiatic ginseng (Ashwagandha,Dong quai, <Emphasis Type="Italic">Panax ginseng</Emphasis>)

Mycotoxins and selected hazardous alkaloids in the medicinal plants (Panax ginseng, Angelica sinensis, and Withania somnifera) and dietary supplements were determined. Purine alkaloids were found in majority of samples; however, isoquinoline alkaloids were less abundant than indole. The predominant alkaloids appear to be caffeine (purine group), harman (indole group) and berberine (isoquinoline). Examined medicinal plants and dietary supplements were contaminated by mycotoxins (especially ochratoxin A 1.72–5.83 µg kg^?1), and many species of mold (e.g. Cladosporium, Eurotium, Aspergillus, Rhizopus, Penicillium). MTT cytotoxicity tests revealed that plant and supplements extracts exhibited medium or high cytotoxicity (only Dong quai—low). Moreover, antioxidant activity, total phenolics content and selected phytochemicals were analyzed by spectrophotometric and chromatographic methods. Quercetin and rutin were predominant flavonols (1.94-9.51 and 2.20–7.28 mg 100 g^?1, respectively). Analysis of phenolic acids revealed—gallic acid, as the most abundant, except Panax ginseng, where ferulic acid was prevailing. The results were analyzed by chemometric methods (cluster analysis, ANOVA).     

Synthesis,biological evaluation,quantitative-SAR and docking studies of novel chalcone derivatives as antibacterial and antioxidant agents

In the present study, a series of chalcone derivatives including 17 new compounds were synthesised; their antibacterial activities against eleven bacteria, and their free radical-scavenging activities using DPPH were evaluated. All compounds showed significant antibacterial activities against both Gram-positive and Gram-negative bacteria. In particular, compound IIIf strongly inhibited Staphylococcus aureus (JMC 2151) and Enterococcus faecalis (CARS 2011-012) with MIC values of 6.25 µg mL^?1 and 12.5 µg mL^?1, respectively, which are comparable to that of the standard antibiotic, nalidixic acid. Compound IIIg also inhibited S. aureus with a MIC value similar to that of nalidixic acid (6.25 µg mL^?1). Furthermore, like nalidixic acid (MIC value of 25 µg mL^?1), compounds IIIa, IIIc and IIId inhibited Listeria monocytogenes (ATCC 43256) with MIC values of 25 µg mL^?1, 12.5 µg mL^?1 and 25 µg mL^?1, respectively. Quantitative structure-activity relationship (Q-SAR) studies using physicochemical calculations indicated that the antibacterial activities of chalcone derivatives correlated well with predicted physicochemical parameters (logP and PSA). Docking simulation by positioning the most active compound IIIf in the active site of the penicillin-binding protein (PBP-1b) of S. aureus was performed to explore the feasible binding mode. Furthermore, most of the compounds synthesised exhibited significant DPPH radical-scavenging activity, although compounds IIc and IIIc exhibited the greatest antioxidant activity with IC₅₀ values of 1.68 µM and 1.44 µM, respectively, comparable to that of the standard antioxidant, ascorbic acid (1.03 µM).     

Growth Parameters,Photosynthetic Performance,and Biochemical Characterization of Newly Isolated Green Microalgae in Response to Culture Condition Variations

This work aimed to characterize two native microalgal strains newly isolated from South Mediterranean areas and identified as Chlorella sorokiniana ES3 and Neochloris sp. AM2. The growth properties and biochemical composition of these microalgae were evaluated in different culture media (Algal, BG-11, f/2, and Conway). Among the tested media, nitrate- and phosphate-rich Algal medium provided the maximum biomass productivities (85.5 and 111.5 mg l^?1 day^?1 for C. sorokiniana and Neochloris sp., respectively), while the nitrate- and phosphate-deficient f/2 medium resulted in the highest lipid productivities (24.1 and 35.8 mg l^?1 day^?1 for C. sorokiniana and Neochloris sp., respectively). The physiological state of both microalgae was investigated under different light and temperature levels using the pulse amplitude-modulated fluorometry. The better photosynthetic efficiency of C. sorokiniana was obtained at 23 °C with a light saturation of 156 μE m^?2 s^?1, while that of Neochloris sp. was achieved at 15 °C with a light saturation of 151 μE m^?2 s^?1. The analysis of fatty acid profile and biodiesel parameters revealed that C. sorokiniana, cultivated in Algal and f/2 media, can be considered as a suitable candidate for high-quality biodiesel production.     

Design,synthesis and therapeutic potential of 3-(2-(1<Emphasis Type="Italic">H</Emphasis>-benzo[<Emphasis Type="Italic">d</Emphasis>]imidazol-2-ylthio)acetamido)-<Emphasis Type="Italic">N</Emphasis>-(substituted phenyl)benzamide analogues

Background

The emergence of bacterial resistance is a major public health problem. It is essential to develop and synthesize new therapeutic agents with better activity. The mode of actions of certain newly developed antimicrobial agents, however, exhibited very limited effect in treating life threatening systemic infections. Therefore, the advancement of multi-potent and efficient antimicrobial agents is crucial to overcome the increased multi-drug resistance of bacteria and fungi. Cancer, which remains as one of the primary causes of deaths and is commonly treated by chemotherapeutic agents, is also in need of novel and efficacious agents to treat resistant cases. As such, a sequence of novel substituted benzamides was designed, synthesized and evaluated for their antimicrobial and anticancer activities.

Methodology

All synthesized compounds were characterized by IR, NMR, Mass and elemental analysis followed by in vitro antimicrobial studies against Gram-positive (Staphylococcus aureus), Gram-negative (Salmonella typhi and Klebsiella pneumoniae) bacterial and fungal (Candida albicans and Aspergillus niger) strains by the tube dilution method. The in vitro anticancer evaluation was carried out against the human colorectal carcinoma cell line (HCT116), using the Sulforhodamine B assay.

Results, discussion and conclusion

Compound W6 (MIC_{sa, st, kp}?=?5.19 µM) emerged as a significant antibacterial agent against all tested bacterial strains i.e. Gram-positive (S. aureus), Gram-negative (S. typhi, K. pneumoniae) while compound W1 (MIC_{ca, an}?=?5.08 µM) was most potent against fungal strains (A. niger and C. albicans) and comparable to fluconazole (MIC?=?8.16 µM). The anticancer screening demonstrated that compound W17 (IC₅₀?=?4.12 µM) was most potent amongst the synthesized  compounds and also more potent than the standard drug 5-FU (IC₅₀?=?7.69 µM).

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Synthesis,characterization, biological evaluation and molecular docking studies of 2-(1H-benzo[d]imidazol-2-ylthio)-<Emphasis Type="Italic">N</Emphasis>-(substituted 4-oxothiazolidin-3-yl) acetamides

Background

A series of 2-(1H-benzo[d]imidazol-2-ylthio)-N-(substituted 4-oxothiazolidin-3-yl) acetamides was synthesized and characterized by physicochemical and spectral means. The synthesized compounds were evaluated for their in vitro antimicrobial activity against Staphylococcus aureus, Bacillus subtilis, Escherichia coli, Candida albicans and Aspergillus niger by tube dilution method. The in vitro cytotoxicity study of the compounds was carried out against human colorectal (HCT116) cell line. The most promising anticancer derivatives (5l, 5k, 5i and 5p) were further docked to study their binding efficacy to the active site of the cyclin-dependent kinase-8.

Results

All the compounds possessed significant antimicrobial activity with MIC in the range of 0.007 and 0.061 µM/ml. The cytotoxicity study revealed that almost all the derivatives were potent in inhibiting the growth of HCT116 cell line in comparison to the standard drug 5-fluorouracil. Compounds 5l and 5k (IC₅₀ = 0.00005 and 0.00012 µM/ml, respectively) were highly cytotoxic towards HCT116 cell line in comparison to 5-fluorouracil (IC₅₀ = 0.00615 µM/ml) taken as standard drug.

Conclusion

The molecular docking studies of potent anticancer compounds 5l, 5k, 5i and 5p showed their putative binding mode and significant interactions with cyclin-dependent kinase-8 as prospective agents for treating colon cancer.

     

Zinc(II), nickel(II) and cadmium(II) coordination polymers based on the ligand oxamide <Emphasis Type="Italic">N,N</Emphasis>-bis(4-phthalic acid): synthesis,structural characterization and magnetic properties

Three coordination polymers based on the new ligand oxamide N,N-bis(4-phthalic acid), namely [Zn(L)_0.5-(2,2′-bpy)] _n (1), [Ni₂(2,2′-bpy)₄(µ ²-Ox)]L·3H₂O (2) and [Cd(L)(1,10-phen)] (3) [L = oxamide N,N-bis(4-phthalic acid)], (2,2′-bpy = 2,2′-bipyridine), (1,10-phen = 1,10-phenanthroline), have been solvothermally synthesized and structurally characterized by single-crystal X-ray diffraction: compound 1 is one-dimensional ladder-like coordination polymer, compound 2 exhibits a three-dimensional structure resulting in extensive hydrogen bonds built with the help of lattice water molecules, compound 3 also exhibits a three-dimensional supramolecular structure. All compounds were also characterized by elemental analysis, IR spectra and thermogravimetric analysis; furthermore, the magnetic measurements for 2 reveal antiferromagnetic coupling between the nickel(II) ions.     

Yields of Hydrogen and Hydrogen Peroxide from Argon–Water Vapor in Dielectric Barrier Discharge

Controlled chemical transformation of water vapor in dielectric barrier discharge (DBD) of argon into hydrogen and hydrogen peroxide for its usability as in situ or ex situ H₂ and H₂O₂ source are reported. Online analysis of the product gas mixture by conventional wet-chemical colorimetric method using buffered KI absorber solution revealed typical H₂O₂ G-value = 6.4 × 10^?3 µmol J^?1 (G-value defines as the number of molecules produced/consumed per 100 eV of energy; in SI unit G-value is expressed in µmol J^?1) in the absence of ozone. On the other hand, H₂ in product mixture analyzed in gas chromatograph-thermal conductivity detector (GC-TCD) with argon carrier revealed its G-value = 0.134 µmol J^?1. Enhancements in products’ yields were explored by varying gas residence time inside the plasma zone, and applied voltage and frequency on the dielectric surfaces. Employing a double-DBD reactor, at applied high voltage ~2.5 kV mm^?1 @50 Hz and gas residence time ~20 s resulted in the highest yields of H₂O₂. However, the H₂ yield increased continuously with increase in gas residence time. On the other hand, the single-dielectric barrier surface reactors were more efficient for high and exclusive generation of ex situ H₂ (e.g. maximum 1260 ppm; G-value typically 0.498 µmol J^?1).     

New hybrids of clozapine and haloperidol and their isosteric analogues: synthesis,X-ray crystallography,conformational analysis and preliminary pharmacological evaluation

Schizophrenia is a debilitating mental disorder which affects approximately 1% of the world’s population. Clozapine is an atypical antipsychotic showing unmatched effectiveness in the control of treatment-resistant schizophrenia. Unlike typical antipsychotics, clozapine does not induce extrapyramidal side effects (EPS), tardive dyskinesia or elevate prolactin levels. However, clozapine can induce a potentially fatal blood disorder, agranulocytosis, in 1–2% of patients, severely limiting its clinical use. The model for antipsychotic activity under investigation is based on obtaining a clozapine-like profile with preferential dopamine D₄ and serotonin 5-HT_2A receptor affinity. Profiled herein are three unique members of a series of prospective antipsychotic agents. Compound (I) originated from the structural hybridization of the commercial therapeutics, clozapine and haloperidol, whilst compounds (II) and (III) possess an alternative tricyclic nucleus derived from JL13; a clozapine-like atypical antipsychotic developed by Liégeois et al. These compounds have been synthesized and characterized by means of elemental analysis, IR, ¹H and ¹³C-NMR spectroscopy, MS and X-ray diffraction. Compound (I) crystallizes in space group P(?1) with a = 10.5032(1), b = 10.6261(2), c = 12.6214(3) Å, α = 81.432(1)°, β = 83.292(1)°, γ = 61.604(1)°, Z = 2, V = 1223.62(4) Å³, C₂₈H₂₉ClN₄O, M _r = 473.00, D _c = 1.284 Mg/m³, μ = 0.185 mm^?1, F(000) = 500, R = 0.0506 and wR = 0.1304. Compound (II) crystallizes in the monoclinic space group P2₁/c with a = 10.8212(2), b = 9.3592(2), c = 22.9494(5) Å, β = 106.471(1)°, Z = 4, V = 2228.88(8) Å³, C₂₅H₂₅ClN₄O₂, M _r = 448.94, D _c = 1.338 Mg/m³, μ = 0.202 mm^?1, F(000) = 944, R = 0.0529 and wR = 0.1129. Compound (III) crystallizes in the monoclinic space group P2₁/c with a = 10.5174(2), b = 9.3112(2), c = 24.2949(5) Å, β = 98.666(1)°, Z = 4, V = 2352.03(8) Å³, C₂₅H₂₄Cl₂N₄O₂, M _r = 483.38, D _c = 1.365 Mg/m³, μ = 0.306 mm^?1, F(000) = 1008, R = 0.0478 and wR = 0.1067. The solid state conformations of (I), (II) and (III) exhibit the characteristic V-shaped buckled nature of the respective dibenzodiazepine and pyridobenzoxazepine nuclei with the central seven-membered heterocycle in a boat conformation. The molecules of (I) form a head-to-tail dimeric motif stabilized by hydrogen bonding. The results of a conformational analysis of compounds (I)–(III) investigating the effect of environment (in vacuo and aqueous solution) are presented. These analogues were tested for in vitro affinity for the dopamine D₄ and serotonin 5-HT_2A receptors and their comparative receptor binding profiles to clozapine and JL13 are reported.     

Synthesis,structural phase transition,and characterization of potassium hydrogen bis-dichloroacetate

Potassium hydrogen bis-dichloroacetate (1) was synthesized and separated as crystals. Differential scanning calorimetry (DSC) measurement reveals that this compound undergoes a reversible phase transition at about 259 K with a heat hysteresis of 23.5 K. Dielectric anomaly observed at 260 K in the heating process further confirms the phase transition. The room temperature X-ray single-crystal structure determination indicates that 1 crystallizes in the monoclinic crystal system with a centrosymmetric space group P2₁/c, and cell parameters are a =?6.240(1), b =?23.177(4), c =?7.335(1) Å, β =?106.938(1)°, V =?1014.8(3) ų, and Z =?4. In the low temperature phase, 1 also crystallizes in monolinic with space group P2₁/c, and cell parameters are a =?6.180(1), b =?22.988(2), c =?7.200(1) Å, β =?108.098(1)°, V =?972.4(1) ų, and Z =?4. The structural phase transition is dominating caused by the torsion of bond angles.     

Synthesis,crystal structure and fungicidal activity of 1-(4-chlorophenyl)-2-(5-((3,5-dimethyl-1H-pyrazol-1-yl)methyl)-4-phenyl-4H-1,2,4-triazol-3-ylthio)ethanone

A novel bis-heterocyclic compound was synthesized and characterized. The crystal structure of the title compound (C₂₂H₂₀ClN₅OS, Mr = 437.94) has been determined by single-crystal X-ray diffraction. The crystal is of triclinic, space group P-1 with a = 8.646 (2), b = 9.148 (3), c = 14.540 (4) Å, α = 94.422 (4), β = 98.500 (4), γ = 102.823 (4)°, V = 1101.8 (5) Å³, Z = 2, F(000) = 312, Dc = 1.320 g/cm³, μ = 0.2900 mm^?1, the final R ₁ = 0.041000 and wR ₂ = 0.1160 for 2675 observed reflections with I > 2σ(I). A total of 5623 reflections were collected, of which 3866 were independent (R _int = 0.019000). The fungicidal activity of title compound was determined, the results showed the title compound displayed moderate fungicidal activity against G. zeae Petch, Phytophthora infestans (Mont.) de Bary, Botryosphaeria berengeriana f. sp. piricola (Nose) koganezawa et Sakuma, Fusarium oxysporum f.sp. cucumerinum, and Cercospora arachidicola.     

Synthesis,characterization, antimicrobial activity and ultrastructure of the affected bacteria of new quinoline compounds

The reaction on 8-hydroxy quinoline-7-aldehyde azo compounds (HL _n ) (where n = 1–5) with 4-amino-1,2-dihydro-2,3-dimethyl-1-phenylpyrazol-5-one to obtain HL _n (where n = 6–10) have been characterized by means of TLC, melting point and spectral data, such as IR, ¹H NMR, mass spectra and thermal studies. The X-ray diffraction patterns of two starting materials 8-hydroxy quinoline-7-aldehyde (start 1), 4-amino-1,2-dihydro-2,3-dimethyl-1-phenylpyrazol-5-one (start 2) and the ligands (HL_5,10) are investigated in powder form. All the ligands have been screened for their antimicrobial activity against four local bacterial species, two Gram-positive bacteria (Bacillus cereus and Staphylococcus aureus) and two Gram-negative bacteria (Escherichia coli and Klebsiella pneumoniae) as well as against four local fungi; Aspergillus niger, Alternaria alternata, Penicillium italicum and Fusarium oxysporium. The results show that the azo ligands (HL _n ) (where n = 1–5) have no antimicrobial activity against bacteria and fungi while most azomethine ligands (HL _n ) (where n = 6–10) are good antibacterial agents against E. coli and K. pneumoniae as well as antifungal agents against P. italicum and A. alternata. The results were compared to standard substances (start 1) and (start 2). Among the azomethine ligands, HL₁₀ was the most effective against the most microorganisms tested. The size of clear zone was ordered as p-(OCH₃ < CH₃ < H < Cl < NO₂) as expected from Hammett’s constant (σ ^R ). Also, the ultrastructure study of the affected bacteria confirmed that HL₈ is good antibacterial agent against E. coli and S. aureus.