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Sample records for mdea methyldiethanolamine piperazine

  1. Effect of chlorides on solution corrosivity of methyldiethanolamine (MDEA) solutions

    SciTech Connect

    Rooney, P.C.; Bacon, T.R.; DuPart, M.S.; Willbanks, K.D.

    1997-08-01

    Solution corrosivity of MDEA/water solutions containing added HCl or NaCl have been measured by weight loss coupons at 250 F and by linear polarization resistance (LPR) at 208 F using carbon steel, 304SS, 316SS and 410SS. General corrosion as well as pitting or crevice corrosion tendencies were recorded for each species. Based on these results, recommendations are made for chlorides in MDEA that minimizes corrosion in gas treating operations.

  2. Aerobic biodegradability of methyldiethanolamine (MDEA) used in natural gas sweetening plants in batch tests and continuous flow experiments.

    PubMed

    Fürhacker, M; Pressl, A; Allabashi, R

    2003-09-01

    Mixtures of different amines including tertiary amines (methyldiethanolamine, MDEA) are commonly used for the removal of CO2 from gas mixtures or in gas sweetening processes for the extraction of CO2 and H2S. The absorber solutions used can be released into the industrial waste water due to continuous substitution of degraded MDEA, periodically cleaning processes or an accidental spill. In this study, the aerobic biodegradability of MDEA was investigated in a standardised batch test and a continuous flow experiment (40 l/d). The results of the batch test indicated that the MDEA-solution was non-biodegradable during the test period of 28 days, whereas the continuous flow experiments showed biodegradation of more than 96% based on TOC-measurements. This was probably due to the adaptation of the microorganisms to this particular waste water contamination during continuous flow experiment. PMID:12871741

  3. Molecular dynamics simulation studies of absorption in piperazine activated MDEA solution.

    PubMed

    Farmahini, Amir Hajiahmadi; Kvamme, Bjørn; Kuznetsova, Tatiana

    2011-07-28

    Development of more efficient solvent solutions for removal of CO(2) from natural gas and flue gases is a major task, which contributes to improved design of process plants and leads to decreased costs for its removal. Understanding the mechanisms of CO(2) absorption as well as analysis of undesired simultaneous processes is crucially important in this regard. In this work, we have applied Molecular Dynamics (MD) to investigate the absorption of CO(2) from a binary mixture of CO(2) and CH(4) into aqueous piperazine activated MDEA solution. The MD simulations were performed at a constant temperature of 298 K for five different systems with a loading factor of 0.07 to provide insight into molecular distribution in the amine solution and to enhance understanding of absorption mechanisms on the molecular scale. Force field parameters that were missing from the OPLS-AA force field, as well as charge distribution of piperazine (PZ), protonated piperazine (PZH(+)), piperazine carbamate (PZCOO(-)) and MDEA were obtained by QM calculations. The results of our simulations emphasize the importance of piperazine and piperazine carbamate in accelerating the absorption process. For the first time, we have shown the undesirable trapping of CH(4) by the amine solution and revealed that amine groups are mainly responsible for both absorption of CO(2) and the undesired trapping of CH(4). PMID:21691636

  4. Modeling CO2 mass transfer in amine mixtures: PZ-AMP and PZ-MDEA.

    PubMed

    Puxty, Graeme; Rowland, Robert

    2011-03-15

    The most common method of carbon dioxide (CO(2)) capture is the absorption of CO(2) into a falling thin film of an aqueous amine solution. Modeling of mass transfer during CO(2) absorption is an important way to gain insight and understanding about the underlying processes that are occurring. In this work a new software tool has been used to model CO(2) absorption into aqueous piperazine (PZ) and binary mixtures of PZ with 2-amino-2-methyl-1-propanol (AMP) or methyldiethanolamine (MDEA). The tool solves partial differential and simultaneous equations describing diffusion and chemical reaction automatically derived from reactions written using chemical notation. It has been demonstrated that by using reactions that are chemically plausible the mass transfer in binary mixtures can be fully described by combining the chemical reactions and their associated parameters determined for single amines. The observed enhanced mass transfer in binary mixtures can be explained through chemical interactions occurring in the mixture without need to resort to using additional reactions or unusual transport phenomena such as the "shuttle mechanism". PMID:21329341

  5. Effect of heat stable salts on MDEA solution corrosivity: Part 2

    SciTech Connect

    Rooney, P.C.; DuPart, M.S.; Bacon, T.R.

    1997-04-01

    A comprehensive coupon corrosion testing program was undertaken to address the effect of various heat stable salts on methyldiethanolamine (MDEA) corrosivity to carbon steel and various stainless steels. Corrosion rates of carbon steel, 304SS, 316SS and 410SS liquid and vapor coupons towards MDEA, and MDEA containing various anions, at 180 F and 250 F, were measured in a reactor. Corrosion results of two refinery plant solutions before and after caustic neutralization were also performed. Based on these results, guidelines were determined for heat stable amine salt (HSAS) levels of oxalates, sulfates, formates, acetates and thiosulfates. In addition, caustic neutralization guidelines for MDEA heat stable salts were determined. Ongoing results include MDEA corrosivity with succinates, and malonates, glycolates, SO{sub 2} and ammonia.

  6. Gas plant converts amine unit to MDEA-based solvent

    SciTech Connect

    Mak, H.Y. )

    1992-10-01

    This paper reports that methyldiethanolamine (MDEA) has successfully replaced monoethanolamine (MEA) solvent at one of Canada's largest gas processing plants. This acid gas treating solvent lowered costs associated with pumping horsepower, reboiler duty, solvent losses, corrosion and other gas processing problems. Not all operating conditions at a gas processing plant favor MDEA or MEA. In the Rimbey plant, originally designed to process sour gas, more sweet gas feed (per volume) called for considering advantages of the lesser-used MDEA. Gulf Canada Resources operates several major sour gas plants in Alberta. The Rimbey Plant was designed in 1960 to process 400 MMscfd of sour gas with 2% H[sub 2]S and 1.32% CO[sub 2]. The amine unit was designed to circulate 2,400 gpm of 20 wt% MEA solution. The single train amine plant has four gas conductors and two amine regenerators. The present raw inlet gas flowrate to the Rimbey Plant is about 312 MMscfd which is made up of three sources: 66 MMscfd of sour gas with 1.5% H[sub 2]S and 1.8% CO[sub 2]; 65 MMscfd of high CO[sub 2] gas with 400 ppmv H[sub 2]S and 3.9% CO[sub 2]; and 181 MMscfd of sweet gas with 2.2% CO[sub 2].

  7. N-methyldiethanolamine: a multifunctional structure-directing agent for the synthesis of SAPO and AlPO molecular sieves.

    PubMed

    Wang, Dehua; Tian, Peng; Fan, Dong; Yang, Miao; Gao, Beibei; Qiao, Yuyan; Wang, Chan; Liu, Zhongmin

    2015-05-01

    In the present study, N-methyldiethanolamine (MDEA) is demonstrated to be a multifunctional structure-directing agent for the synthesis of aluminophosphate-based molecular sieves. Four types of molecular sieves, including SAPO-34, -35, AlPO-9 and -22, are for the first time acquired with MDEA as a novel template. The phase selectivity of the present synthesis is found to be condition-dependent. SAPO-34 (CHA) crystallizes from a conventional hydrothermal system with a higher MDEA concentration. When using MDEA as both the template and solvent, pure SAPO-35 (LEV) is obtained from the synthetic gel with a high P2O5/Al2O3 ratio of (2-3), in which the concentration of MDEA could be varied in a wide range. AlPO-9 and AlPO-22 (AWW) are synthesized under the similar conditions to SAPO-35, except without the addition of Si source. The physicochemical properties of the obtained samples are investigated by XRD, XRF, SEM, N2 physisorption, TG-DSC, and various NMR spectra ((13)C, (29)Si, (27)Al and (31)P). Both SAPO-34 and SAPO-35 show good thermal stability, large surface area, and high pore volume. The catalytic performance of SAPO-34 is evaluated by the methanol-to-olefins (MTO) reaction and a good (C2H4+C3H6) selectivity of 82.7% has been achieved. PMID:25616250

  8. Kinetics of CO{sub 2} desorption from highly concentrated and CO{sub 2}-loaded methyldiethanolamine aqueous solutions in the range 312--383 K

    SciTech Connect

    Cadours, R.; Bouallou, C.; Gaunand, A.; Richon, D.

    1997-12-01

    Absorption by aqueous alkanolamine solutions is the dominant industrial process for acid gases removal, in particular CO{sub 2} and H{sub 2}S, from natural gas. Kinetics of CO{sub 2} desorption from CO{sub 2}-loaded methyldiethanolamine (MDEA) aqueous solutions were measured in the following conditions: 312--383 K, 25--50 wt% MDEA aqueous solutions, CO{sub 2} loadings from 5 to 85%. A thermoregulated constant interfacial area reaction cell was operated by measuring the pressure over the solution. Producing a very slight depression in the cell, the time-dependent equilibrium pressure recovery is accurately recorded during batch desorption. Kinetics are in agreement with a fast reaction regime of desorption according to the film theory. For CO{sub 2} loadings below 0.50 mol of gas/mol of amine, desorption rates are well predicted by using the kinetic constant and orders determined from absorption experiments for the reaction between CO{sub 2} and MDEA. Some discrepancies were pointed out for loadings above 0.50 mol of gas/mol of amine.

  9. Estimation of the CO{sub 2} absorption capacities in aqueous 2-(2-aminoethylamino)ethanol and its blends with MDEA and TEA in the presence of SO{sub 2}

    SciTech Connect

    Bonenfant, D.; Minleault, M.; Hausler, R.

    2007-12-15

    A study of carbon dioxide (CO{sub 2}) and sulfur dioxide (SO{sub 2})/CO{sub 2} mixtures absorption has been carried out in aqueous 2-(2-aminoethylamino)ethanol (AEE) solution and its blends with N-methyldiethanolamine (MDEA) and triethanolamine (TEA) to estimate the influence of SO{sub 2}, MDEA, and TEA on the CO{sub 2} absorption capacity of the AEE. The CO{sub 2} absorption loading has been estimated in 15 wt % AEE alone and in the presence of either 5 and 10 wt % MDEA or 5 and 10 wt % TEA solutions with 100 vol % CO{sub 2} and 5.03 and 15.02 vol % SO{sub 2}/CO{sub 2} mixtures at a starting temperature of 296 K and flow rates of 3.067, 3.229, and 3.605 L/min, respectively. The results revealed that the presence of SO{sub 2} in the gas decreases the CO{sub 2} absorption rate and loading in the AEE solution as a function of the concentration of SO{sub 2}. The additions of 5 and 10 wt % of MDEA and TEA do not seem to influence the CO{sub 2} absorption rate in the AEE solution. Moreover, the addition of MDEA increases slightly the CO{sub 2} absorption capacity of AEE, while TEA decreases the absorption capacity of AEE in the absence and presence Of SO{sub 2}. These effects were enhanced with increases of MDEA and TEA. Altogether, the results indicated that the blend of 15 wt % AEE + 10 wt % MDEA represents an interesting solvent which could be used as absorbent for the removal of CO{sub 2} from emission into the atmosphere by industries.

  10. Improvement of amine-modification with piperazine for the adsorption of CO2

    NASA Astrophysics Data System (ADS)

    Xue, Quanmin; Wu, Di; Zhou, Yaping; Zhou, Li

    2012-02-01

    Both selectivity and capacity of CO2 adsorption were considerably increased when PZ (piperazine) was added in MDEA (methyldiethylamine) that used to modify the surface of silica gels. The adsorbent saturated with CO2 was regenerated at ambient temperature through nitrogen purge. A set of PSA (pressure swing adsorption) operation with 200 cycles was carried out and applicability of the modified adsorbent was thus illustrated. The CO2 content in the column-top stream decreased from 13% to below 0.05% at steady state.

  11. 21 CFR 520.1806 - Piperazine suspension.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Piperazine suspension. 520.1806 Section 520.1806... DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.1806 Piperazine suspension. (a) Specifications. Each milliliter of suspension contains piperazine monohydrochloride equivalent...

  12. 21 CFR 520.1806 - Piperazine suspension.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Piperazine suspension. 520.1806 Section 520.1806... DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.1806 Piperazine suspension. (a) Specifications. Each milliliter of suspension contains piperazine monohydrochloride equivalent...

  13. 21 CFR 520.1806 - Piperazine suspension.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Piperazine suspension. 520.1806 Section 520.1806... DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.1806 Piperazine suspension. (a) Specifications. Each milliliter of suspension contains piperazine monohydrochloride equivalent...

  14. 21 CFR 520.1806 - Piperazine suspension.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Piperazine suspension. 520.1806 Section 520.1806... DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.1806 Piperazine suspension. (a) Specifications. Each milliliter of suspension contains piperazine monohydrochloride equivalent...

  15. 21 CFR 520.1806 - Piperazine suspension.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Piperazine suspension. 520.1806 Section 520.1806... DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.1806 Piperazine suspension. (a) Specifications. Each milliliter of suspension contains piperazine monohydrochloride equivalent...

  16. Piperazine-induced occupational asthma

    SciTech Connect

    Hagmar, L.; Bellander, T.; Bergoeoe, B.; Simonsson, B.G.

    1982-03-01

    Asthmatic reactions were studied among some 130 factory workers who handled amines and other chemicals. Among present employees, we found 15 cases of asthma associated with occupational exposure to chemicals; among former employees there were at least 18. The inducing agent was judged to be piperazine in 29 persons and ethylenediamine (EDA) in three. The asthma was of the late or dual type; immediate reactions alone were to seen. No one had attacks of asthma before employment, and atopic subjects were not preferentially affected. Routine spirometry revealed airway obstruction in fewer than half of the recent cases. Tests of nonspecific bronchial reactivity with methacholine in six subjects with recent asthma showed hyperactivity in five, while tow subjects with earlier asthma did not have hyperactivity. Bronchial provocation tests with piperazine in one subject were positive both in the factory and in the laboratory. The level of piperazine was 1.2 mg/m3 time-weighted average (TWA) in a work place associated with induction of the asthmatic state, and 0.3 mg/m3 in a place connected with attacks in ''sensitized'' subjects.

  17. 21 CFR 520.1807 - Piperazine.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Piperazine. 520.1807 Section 520.1807 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS 520.1807 Piperazine. (a) Specifications. A soluble powder or liquid...

  18. Enantioselective Synthesis of α-Secondary and α-Tertiary Piperazin-2-ones and Piperazines by Catalytic Asymmetric Allylic Alkylation

    PubMed Central

    Korch, Katerina M.; Eidamshaus, Christian; Behenna, Douglas C.; Nam, Sangkil; Horne, David

    2014-01-01

    The asymmetric Pd-catalyzed decarboxylative allylic alkylation of differentially N-protected piperazin-2-ones allows for the synthesis of a variety of highly enantioenriched tertiary piperazine-2-ones. Deprotection and reduction affords the corresponding tertiary piperazines, which can be employed for the synthesis of medicinally important analogs. The introduction of these chiral tertiary piperazines resulted in imatinib analogs that exhibited comparable antiproliferative activity to that of their corresponding imatinib counterparts. PMID:25382664

  19. Piperazine-1,4-diium diacetate

    PubMed Central

    Hou, Shao-Gang

    2011-01-01

    In the title salt, C4H12N2 2+·2C2H3O2 −, the piperazine-1,4-diium cation has 2/m symmetry with the NH2 unit located on a mirror plane and the acetate anion has m symmetry with all non-H atoms and one H atom located on a mirror plane. The piperazine ring adopts a chair conformation. In the crystal, the cations are linked with the anions via N—H⋯O hydrogen bonding into chains parallel to the c axis. PMID:22199795

  20. Piperazine-based nucleic acid analogs

    DOEpatents

    Schmidt, Jurgen; Silks, Louis A.; Michalczyk, Ryszard

    2005-01-11

    A novel nucleoside analog is disclosed which comprises a piperazine ring in the place of the ring ribose or deoxyribose sugar. Monomers utilizing a broad variety of nucleobases are disclosed, as well as oligomers comprising the monomers disclosed herein linked by a variety of linkages, including amide, phosphonamide, and sulfonamide linkages. A method of synthesizing the nucleoside analogs is also disclosed.

  1. An experimental investigation into the atmospheric degradation of piperazine

    NASA Astrophysics Data System (ADS)

    White, Stephen; Angove, Dennys; Azzi, Merched; Tibbett, Anne; Campbell, Ian; Patterson, Michael

    2015-05-01

    The atmospheric degradation of piperazine was investigated using an indoor smog chamber. Experiments were carried out in the presence of nitrogen oxides (NOx), ozone or nitric acid. Piperazine reacted rapidly under all evaluated conditions: irradiated in the presence of NOx and with ozone and nitric acid in the dark. Gas phase products from the oxidation of piperazine were identified by infrared spectroscopy, DNPH cartridges followed by HPLC analysis, and by sampling chamber gas through Tenax sorbent material followed by analysis using thermal desorption GC-ITMS (gas chromatography ion trap mass spectrometry). Eight compounds were positively identified, with a further nine compounds tentatively identified using GC-MS based on molecular weight and mass spectra. Ammonia formation was observed from piperazine oxidation, and its formation was from the subsequent reactions of photooxidation products of piperazine rather than directly from the reaction of piperazine. The nitrosamine and nitramine expected from piperazine, N-nitrosopiperazine, and N-nitropiperazine, were both identified and confirmed using 15NO, with a tentative maximum yield of nitrosamine of less than 5% observed. Aerosol yields, relative to total piperazine reacted not including that which absorbed to the walls, were considerably high but were not able to be quantified absolutely due to unusual behaviour of the scanning mobility particle sizer instrument to aerosol containing amines. The reaction of piperazine with gas phase nitric acid gave rise to immediate formation of aerosol.

  2. Engineering of copper molybdates: Piperazine dictated pseudopolymorphs

    NASA Astrophysics Data System (ADS)

    Pavani, Katikaneani; Singh, Monika; Ramanan, Arunachalam; Lofland, Samuel E.; Ramanujachary, Kandalam V.

    2009-09-01

    The hydrothermal syntheses, crystal structures and magnetic behavior of two compositionally different piperazine pillared copper molybdates, [{Cu( pip) 0.5}MoO 4] ( 1) and a hitherto unknown [Cu( pip)MoO 4] ( pip = piperazine) ( 2), are reported. Both 1 and 2 exhibit three-dimensional covalent frameworks constructed from bimetallic oxide layers pillared by piperazine; however, the {CuMoO 4} networks are quite distinct. The Cu-Mo-O layers in 1 are made of edge-shared {CuO 4N} square pyramidal pairs linked through {MoO 4} tetrahedra, in contrast to the sheets in 2 that are built of corner-sharing {MoO 4} tetrahedra and {CuO 3N 2} square pyramids. Self assembly of the two pseudopolymorphs, 1 and 2, is interpreted in terms of molecular recognition between reasonable soluble molecular species in the supramolecular reaction along the mechanistic approach proposed by Ramanan and Whittingham for rationalizing metal-organic framework structures. Crystal data: 1, Triclinic, space group P-1, a = 5.5765(8) , b = 6.8304(10) , c = 9.2379(14) , ? = 100.688(2), ? = 101.462(2), ? = 112.624(2), Z = 2; 2, Orthorhombic, space group Pbca, a = 11.3899(11) , b = 10.7726(10) , c = 13.2541(12) , Z = 8.

  3. 21 CFR 520.1804 - Piperazine phosphate capsules.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Piperazine phosphate capsules. 520.1804 Section... phosphate capsules. (a) Specifications. Each capsule contains 120, 300, or 600 milligrams of piperazine phosphate monohydrate. (b) Sponsor. See No. 051311 in § 510.600(c) of this chapter. (c) Conditions of...

  4. 21 CFR 520.1804 - Piperazine phosphate capsules.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Piperazine phosphate capsules. 520.1804 Section... phosphate capsules. (a) Specifications. Each capsule contains 120, 300, or 600 milligrams of piperazine phosphate monohydrate. (b) Sponsor. See No. 051311 in § 510.600(c) of this chapter. (c) Conditions of...

  5. 21 CFR 520.1804 - Piperazine phosphate capsules.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Piperazine phosphate capsules. 520.1804 Section... phosphate capsules. (a) Specifications. Each capsule contains 120, 300, or 600 milligrams of piperazine phosphate monohydrate. (b) Sponsor. See No. 051311 in § 510.600(c) of this chapter. (c) Conditions of...

  6. 21 CFR 520.1804 - Piperazine phosphate capsules.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Piperazine phosphate capsules. 520.1804 Section... phosphate capsules. (a) Specifications. Each capsule contains 120, 300, or 600 milligrams of piperazine phosphate monohydrate. (b) Sponsor. See No. 051311 in § 510.600(c) of this chapter. (c) Conditions of...

  7. 21 CFR 520.1804 - Piperazine phosphate capsules.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Piperazine phosphate capsules. 520.1804 Section... phosphate capsules. (a) Specifications. Each capsule contains 120, 300, or 600 milligrams of piperazine phosphate monohydrate. (b) Sponsor. See No. 051311 in § 510.600(c) of this chapter. (c) Conditions of...

  8. Complexation of metals with piperazine-containing azamacrocyclic fluorophores.

    PubMed

    Angelovski, Goran; Costisella, Burkhard; Kolarić, Branko; Engelhard, Martin; Eilbracht, Peter

    2004-08-01

    Azamacrocyclic fluorophores containing piperazine units were synthesized using sequential rhodium-catalyzed regioselective hydroformylation-reductive amination. A piperazine unit is introduced into the macrocycles to act simultaneously as electron donor and binding site. The macrocycles chelate divalent cations, either Zn2+ or Co2+, which considerably enhanced fluorescence. Complexation with Zn2+ was additionally confirmed by NMR. PMID:15287772

  9. 'Eve' and 'Ecstasy'. A report of five deaths associated with the use of MDEA and MDMA.

    PubMed

    Dowling, G P; McDonough, E T; Bost, R O

    1987-03-27

    3,4-Methylenedioxymethamphetamine (MDMA, "Ecstasy"), a synthetic analogue of 3,4-methylenedioxyamphetamine, has been the center of recent debate over its potential for abuse vs its use as a psychotherapeutic agent. Following its emergency classification in Schedule 1 by the Drug Enforcement Administration in 1985, 3,4-methylenedioxyethamphetamine (MDEA, "Eve") has appeared as MDMA's legal replacement. MDMA is thought to be safe by recreational users and by psychotherapists who support its use. The details of five deaths associated with the use of MDMA and MDEA are reported. In three patients, MDMA or MDEA may have contributed to death by the induction of arrhythmias in individuals with underlying natural disease. In another patient, use of MDMA preceded an episode of bizarre and risky behavior that resulted in accidental death. In another patient, MDMA was thought to be the immediate cause of death. Death as a consequence of the use of these drugs appears to be rare, but it does occur; this outcome may be more common in individuals with underlying cardiac disease. PMID:2881002

  10. 21 CFR 520.1802a - Piperazine-carbon disulfide complex suspension.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Piperazine-carbon disulfide complex suspension... § 520.1802a Piperazine-carbon disulfide complex suspension. (a) Specifications. Each fluid ounce of suspension contains 7.5 grams of piperazine-carbon disulfide complex. The piperazine-carbon disulfide...

  11. 21 CFR 520.1805 - Piperazine phosphate with thenium closylate tablets.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Piperazine phosphate with thenium closylate... § 520.1805 Piperazine phosphate with thenium closylate tablets. (a) Specifications. Each scored tablet contains the equivalent of 250 milligrams piperazine hexahydrate (as piperazine phosphate) and...

  12. 21 CFR 520.1805 - Piperazine phosphate with thenium closylate tablets.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Piperazine phosphate with thenium closylate... § 520.1805 Piperazine phosphate with thenium closylate tablets. (a) Specifications. Each scored tablet contains the equivalent of 250 milligrams piperazine hexahydrate (as piperazine phosphate) and...

  13. 21 CFR 520.1805 - Piperazine phosphate with thenium closylate tablets.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Piperazine phosphate with thenium closylate... § 520.1805 Piperazine phosphate with thenium closylate tablets. (a) Specifications. Each scored tablet contains the equivalent of 250 milligrams piperazine hexahydrate (as piperazine phosphate) and...

  14. 21 CFR 520.1805 - Piperazine phosphate with thenium closylate tablets.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Piperazine phosphate with thenium closylate... § 520.1805 Piperazine phosphate with thenium closylate tablets. (a) Specifications. Each scored tablet contains the equivalent of 250 milligrams piperazine hexahydrate (as piperazine phosphate) and...

  15. 21 CFR 520.1805 - Piperazine phosphate with thenium closylate tablets.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Piperazine phosphate with thenium closylate... § 520.1805 Piperazine phosphate with thenium closylate tablets. (a) Specifications. Each scored tablet contains the equivalent of 250 milligrams piperazine hexahydrate (as piperazine phosphate) and...

  16. 21 CFR 520.1802a - Piperazine-carbon disulfide complex suspension.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Piperazine-carbon disulfide complex suspension... § 520.1802a Piperazine-carbon disulfide complex suspension. (a) Specifications. Each fluid ounce of suspension contains 7.5 grams of piperazine-carbon disulfide complex. The piperazine-carbon disulfide...

  17. 21 CFR 520.1802a - Piperazine-carbon disulfide complex suspension.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Piperazine-carbon disulfide complex suspension... § 520.1802a Piperazine-carbon disulfide complex suspension. (a) Specifications. Each fluid ounce of suspension contains 7.5 grams of piperazine-carbon disulfide complex. The piperazine-carbon disulfide...

  18. 21 CFR 520.1802a - Piperazine-carbon disulfide complex suspension.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Piperazine-carbon disulfide complex suspension... § 520.1802a Piperazine-carbon disulfide complex suspension. (a) Specifications. Each fluid ounce of suspension contains 7.5 grams of piperazine-carbon disulfide complex. The piperazine-carbon disulfide...

  19. 21 CFR 520.1802a - Piperazine-carbon disulfide complex suspension.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Piperazine-carbon disulfide complex suspension... § 520.1802a Piperazine-carbon disulfide complex suspension. (a) Specifications. Each fluid ounce of suspension contains 7.5 grams of piperazine-carbon disulfide complex. The piperazine-carbon disulfide...

  20. Gene cloning and characterization of MdeA, a novel multidrug efflux pump in Streptococcus mutans.

    PubMed

    Kim, Do Kyun; Kim, Kyoung Hoon; Cho, Eun Ji; Joo, Seoung-Je; Chung, Jung-Min; Son, Byoung Yil; Yum, Jong Hwa; Kim, Young-Man; Kwon, Hyun-Ju; Kim, Byung-Woo; Kim, Tae Hoon; Lee, Eun-Woo

    2013-03-01

    Multidrug resistance, especially multidrug efflux mechanisms that extrude structurally unrelated cytotoxic compounds from the cell by multidrug transporters, is a serious problem and one of the main reasons for the failure of therapeutic treatment of infections by pathogenic microorganisms as well as of cancer cells. Streptococcus mutans is considered one of the primary causative agents of dental caries and periodontal disease, which comprise the most common oral diseases. A fragment of chromosomal DNA from S. mutans KCTC3065 was cloned using Escherichia coli KAM32 as host cells lacking major multidrug efflux pumps. Although E. coli KAM32 cells were very sensitive to many antimicrobial agents, the transformed cells harboring a recombinant plasmid became resistant to several structurally unrelated antimicrobial agents such as tetracycline, kanamycin, rhodamin 6G, ampicillin, acriflavine, ethidium bromide, and tetraphenylphosphonium chloride. This suggested that the cloned DNA fragment carries a gene encoding a multidrug efflux pump. Among 49 of the multidrug-resistant transformants, we report the functional gene cloning and characterization of the function of one multidrug efflux pump, namely MdeA from S. mutans, which was expressed in E. coli KAM32. Judging from the structural and biochemical properties, we concluded that MdeA is the first cloned and characterized multidrug efflux pump using the proton motive force as the energy for efflux drugs. PMID:23462018

  1. 21 CFR 520.1802c - Piperazine-carbon disulfide complex with phenothiazine suspension.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Piperazine-carbon disulfide complex with... ANIMAL DRUGS § 520.1802c Piperazine-carbon disulfide complex with phenothiazine suspension. (a) Specifications. Each fluid ounce contains 5 grams of piperazine-carbon disulfide complex and 0.83 gram...

  2. 21 CFR 520.1802c - Piperazine-carbon disulfide complex with phenothiazine suspension.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Piperazine-carbon disulfide complex with... ANIMAL DRUGS § 520.1802c Piperazine-carbon disulfide complex with phenothiazine suspension. (a) Specifications. Each fluid ounce contains 5 grams of piperazine-carbon disulfide complex and 0.83 gram...

  3. 21 CFR 520.1802c - Piperazine-carbon disulfide complex with phenothiazine suspension.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Piperazine-carbon disulfide complex with... ANIMAL DRUGS § 520.1802c Piperazine-carbon disulfide complex with phenothiazine suspension. (a) Specifications. Each fluid ounce contains 5 grams of piperazine-carbon disulfide complex and 0.83 gram...

  4. 21 CFR 520.1802c - Piperazine-carbon disulfide complex with phenothiazine suspension.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Piperazine-carbon disulfide complex with... ANIMAL DRUGS § 520.1802c Piperazine-carbon disulfide complex with phenothiazine suspension. (a) Specifications. Each fluid ounce contains 5 grams of piperazine-carbon disulfide complex and 0.83 gram...

  5. 21 CFR 520.1802c - Piperazine-carbon disulfide complex with phenothiazine suspension.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Piperazine-carbon disulfide complex with... ANIMAL DRUGS § 520.1802c Piperazine-carbon disulfide complex with phenothiazine suspension. (a) Specifications. Each fluid ounce contains 5 grams of piperazine-carbon disulfide complex and 0.83 gram...

  6. 21 CFR 520.2520g - Trichlorfon, phenothiazine, and piperazine dihydrochloride powder.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Trichlorfon, phenothiazine, and piperazine... ANIMAL DRUGS § 520.2520g Trichlorfon, phenothiazine, and piperazine dihydrochloride powder. (a....25 grams of phenothiazine, and the equivalent of 20.0 grams of piperazine base (as...

  7. 21 CFR 520.2520g - Trichlorfon, phenothiazine, and piperazine dihydrochloride powder.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Trichlorfon, phenothiazine, and piperazine... ANIMAL DRUGS § 520.2520g Trichlorfon, phenothiazine, and piperazine dihydrochloride powder. (a....25 grams of phenothiazine, and the equivalent of 20.0 grams of piperazine base (as...

  8. 21 CFR 520.2520g - Trichlorfon, phenothiazine, and piperazine dihydrochloride powder.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Trichlorfon, phenothiazine, and piperazine... ANIMAL DRUGS § 520.2520g Trichlorfon, phenothiazine, and piperazine dihydrochloride powder. (a....25 grams of phenothiazine, and the equivalent of 20.0 grams of piperazine base (as...

  9. 21 CFR 520.2520g - Trichlorfon, phenothiazine, and piperazine dihydrochloride powder.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Trichlorfon, phenothiazine, and piperazine... ANIMAL DRUGS § 520.2520g Trichlorfon, phenothiazine, and piperazine dihydrochloride powder. (a....25 grams of phenothiazine, and the equivalent of 20.0 grams of piperazine base (as...

  10. Amiodarone and metabolite MDEA inhibit Ebola virus infection by interfering with the viral entry process.

    PubMed

    Salata, Cristiano; Baritussio, Aldo; Munegato, Denis; Calistri, Arianna; Ha, Huy Riem; Bigler, Laurent; Fabris, Fabrizio; Parolin, Cristina; Palù, Giorgio; Mirazimi, Ali

    2015-07-01

    Ebola virus disease (EVD) is one of the most lethal transmissible infections characterized by a high fatality rate, and a treatment has not been developed yet. Recently, it has been shown that cationic amphiphiles, among them the antiarrhythmic drug amiodarone, inhibit filovirus infection. In the present work, we investigated how amiodarone interferes with Ebola virus infection. Wild-type Sudan ebolavirus and recombinant vesicular stomatitis virus, pseudotyped with the Zaire ebolavirus glycoprotein, were used to gain further insight into the ability of amiodarone to affect Ebola virus infection. We show that amiodarone decreases Ebola virus infection at concentrations close to those found in the sera of patients treated for arrhythmias. The drug acts by interfering with the fusion of the viral envelope with the endosomal membrane. We also show that MDEA, the main amiodarone metabolite, contributes to the antiviral activity. Finally, studies with amiodarone analogues indicate that the antiviral activity is correlated with drug ability to accumulate into and interfere with the endocytic pathway. Considering that it is well tolerated, especially in the acute setting, amiodarone appears to deserve consideration for clinical use in EVD. PMID:25933611

  11. GC-MS studies on side chain regioisomers related to substituted methylenedioxyphenethylamines: MDEA, MDMMA, and MBDB.

    PubMed

    Awad, Tamer; Belal, Tarek; Maher, Hadir M; DeRuiter, Jack; Clark, C Randall

    2010-10-01

    Three regioisomeric 3,4-methylenedioxyphenethylamines having the same molecular weight and major mass spectral fragments of equal mass have been reported as drugs of abuse in forensic studies in recent years. These compounds are 3,4-methylenedioxy-N-ethylamphetamine (MDEA), 3,4-methylenedioxy-N,N-dimethylamphetamine (MDMMA), and N-methyl-1-(3,4-methylenedioxyphenyl)-2-butanamine (MBDB). A series of seven additional side chain regioisomers have mass spectra essentially equivalent to the three controlled drug substances, all have molecular weight of 207 and major fragment ions in their electron ionization mass spectra at m/z 72 and 135/136. The trifluoroacetyl, pentafluoropropionyl, and heptafluorobutryl derivatives of the primary and secondary regioisomeric amines were evaluated in GC-MS studies. The mass spectra for these derivatives were significantly individualized, and the resulting unique fragment ions allowed for specific side chain identification. The trifluoroacetyl and heptafluorobutryl derivatives provided more specific fragment ions for molecular individualization among these regioisomeric substances. These perfluoroacyl derivatives showed reasonable resolution on the polar stationary phase Rtx-200. PMID:20875234

  12. Virtual Screening and Biological Evaluation of Piperazine Derivatives as Human Acetylcholinesterase Inhibitors

    PubMed Central

    Varadaraju, Kavitha Raj; Kumar, Jajur Ramanna; Mallesha, Lingappa; Muruli, Archana; Mohana, Kikkeri Narasimha Shetty; Mukunda, Chethan Kumar; Sharanaiah, Umesha

    2013-01-01

    The piperazine derivatives have been shown to inhibit human acetylcholinesterase. Virtual screening by molecular docking of piperazine derivatives 1-(1,4-benzodioxane-2-carbonyl) piperazine (K), 4-(4-methyl)-benzenesulfonyl-1-(1,4-benzodioxane-2-carbonyl) piperazine (S1), and 4-(4-chloro)-benzenesulfonyl-1-(1,4-benzodioxane-2-carbonyl) piperazine (S3) has been shown to bind at peripheral anionic site and catalytic sites, whereas 4-benzenesulfonyl-1-(1,4-benzodioxane-2-carbonyl) piperazine (S4) and 4-(2,5-dichloro)-benzenesulfonyl-1-(1,4-benzodioxane-2-carbonyl) piperazine (S7) do not bind either to peripheral anionic site or catalytic site with hydrogen bond. All the derivatives have differed in number of H-bonds and hydrophobic interactions. The peripheral anionic site interacting molecules have proven to be potential therapeutics in inhibiting amyloid peptides aggregation in Alzheimer's disease. All the piperazine derivatives follow Lipinski's rule of five. Among all the derivatives 1-(1,4-benzodioxane-2-carbonyl) piperazine (K) was found to have the lowest TPSA value. PMID:24288651

  13. Survey and Down-Selection of Acid Gas Removal Systems for the Thermochemical Conversion of Biomass to Ethanol with a Detailed Analysis of an MDEA System

    SciTech Connect

    Nexant, Inc., San Francisco, California

    2011-05-01

    The first section (Task 1) of this report by Nexant includes a survey and screening of various acid gas removal processes in order to evaluate their capability to meet the specific design requirements for thermochemical ethanol synthesis in NREL's thermochemical ethanol design report (Phillips et al. 2007, NREL/TP-510-41168). MDEA and selexol were short-listed as the most promising acid-gas removal agents based on work described in Task 1. The second report section (Task 2) describes a detailed design of an MDEA (methyl diethanol amine) based acid gas removal system for removing CO2 and H2S from biomass-derived syngas. Only MDEA was chosen for detailed study because of the available resources.

  14. Synthesis and characterization of the novel phosphonates- and phosphonothioate-piperazine as flame retardants for cotton

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Tetraethyl piperazine-1,4-diyldiphosphonate (PDP) and O,O,O',O'-tetramethyl piperazine-1,4-diyldiphosphonothioate (PDSP) were synthesized in one simple step and their structures were confirmed by 1H and 13C nuclear magnetic resonance (NMR) spectroscopy and elemental analysis (EA). Print cloth, twil...

  15. 21 CFR 520.1802 - Piperazine-carbon disulfide complex oral dosage forms.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Piperazine-carbon disulfide complex oral dosage forms. 520.1802 Section 520.1802 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND... § 520.1802 Piperazine-carbon disulfide complex oral dosage forms....

  16. 21 CFR 520.1802 - Piperazine-carbon disulfide complex oral dosage forms.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Piperazine-carbon disulfide complex oral dosage forms. 520.1802 Section 520.1802 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND... § 520.1802 Piperazine-carbon disulfide complex oral dosage forms....

  17. 21 CFR 520.1802 - Piperazine-carbon disulfide complex oral dosage forms.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Piperazine-carbon disulfide complex oral dosage forms. 520.1802 Section 520.1802 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND... § 520.1802 Piperazine-carbon disulfide complex oral dosage forms....

  18. 21 CFR 520.1802 - Piperazine-carbon disulfide complex oral dosage forms.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Piperazine-carbon disulfide complex oral dosage forms. 520.1802 Section 520.1802 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND... § 520.1802 Piperazine-carbon disulfide complex oral dosage forms....

  19. 21 CFR 520.1802 - Piperazine-carbon disulfide complex oral dosage forms.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Piperazine-carbon disulfide complex oral dosage forms. 520.1802 Section 520.1802 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND... § 520.1802 Piperazine-carbon disulfide complex oral dosage forms....

  20. Hepatotoxicity of piperazine designer drugs: Comparison of different in vitro models.

    PubMed

    Dias-da-Silva, D; Arbo, M D; Valente, M J; Bastos, M L; Carmo, H

    2015-08-01

    Piperazine derived drugs emerged on the drug market in the last decade. The aim of this study was to investigate in vitro the potential hepatotoxicity of the designer drugs N-benzylpiperazine (BZP), 1-(3-trifluoromethylphenyl)piperazine (TFMPP), 1-(4-methoxyphenyl)piperazine (MeOPP) and 1-(3,4-methylenedioxybenzyl)piperazine (MDBP) in two human hepatic cell lines (HepaRG and HepG2) and in primary rat hepatocytes. Cell death was evaluated by the MTT assay, after 24 h-incubations. Among the tested drugs, TFMPP was the most cytotoxic. HepaRG cells and primary hepatocytes revealed to be the most and the least resistant cellular models, respectively. To ascertain whether the CYP450 metabolism could explain their higher susceptibility, primary hepatocytes were co-incubated with the piperazines and the CYP450 inhibitors metyrapone and quinidine, showing that CYP450-mediated metabolism contributes to the detoxification of these drugs. Additionally, the intracellular contents of reactive species, ATP, reduced (GSH) and oxidized (GSSG) glutathione, changes in mitochondrial membrane potential (Δψm) and caspase-3 activation were further evaluated in primary cells. Overall, an increase in reactive species formation, followed by intracellular GSH and ATP depletion, loss of Δψm and caspase-3 activation was observed for all piperazines, in a concentration-dependent manner. In conclusion, piperazine designer drugs produce hepatic detrimental effects that can vary in magnitude among the different analogues. PMID:25863214

  1. Theoretical study of differential enthalpy of absorption of CO2 with MEA and MDEA as a function of temperature.

    PubMed

    Gupta, Mayuri; da Silva, Eirik F; Hartono, Ardi; Svendsen, Hallvard F

    2013-08-15

    Temperature dependent correlations for enthalpy of deprotonation, carbamate formation, and heat of absorption of the overall reaction between aqueous MEA and MDEA and gaseous CO2 are calculated on the basis of computational chemistry based ln K values input to the Gibbs-Helmholtz equation. Temperature dependency of reaction equilibrium constants for deprotonation and carbamate formation reactions is calculated with the SM8T continuum solvation model coupled with density functional theoretical calculations at the B3LYP/6-311++G(d,p) level of theory. Calculated reaction equilibrium constants and enthalpies of individual reactions and overall heat of absorption are compared against experimental data in the temperature range 273.15-373 K. Temperature dependent correlations for different reaction equilibrium constants and enthalpies of reactions are given. These correlated results can be used in thermodynamic models such as UNIQUAC and NRTL for better understanding of post-combustion CO2 capture solvent chemistry. PMID:23855311

  2. Differences in binding affinities of MDA, MDMA, MDEA, Amphetamine, Methamphetamine, and their deuterated analogues to solid-phase extraction cartridges.

    PubMed

    Romberg, R W; Ntamack, A G; Blacik, L J; Kazarian, C M; Snyder, J Jacob; Welsh, E R

    2011-01-01

    This study evaluated the potential for partial separation of drugs from their deuterated internal standards using Cerex(®) Polycrom™ CLIN II solid-phase extraction (SPE) cartridges. After elution from the column and derivatization, gas chromatography-mass spectrometry results showed that the target compound eluted from the SPE cartridge prior to its deuterated form. This elution separation effect was greater for 3,4-methylenedioxymethamphetamine (MDMA) and methamphetamine (MAMP) than for the other drugs studied. When the drugs were eluted in 0.5 mL increments from a 50 mg sorbent bed, no drug appeared in the first fraction. The drug to internal standard ratios (expected value 1.00) for subsequent fractions collected were 1.30, 1.07, and 0.83 for MDA/MDA-d(5); 1.65, 1.18, 0.67, and 0.56 for MDMA/MDMAd(5); and 1.37, 1.18, and 0.95 for MDEA/MDEA-d(6). For d-AMP and d-MAMP, the expected ratio was 0.40. The subsequent ratios were 0.63, 0.46, 0.35, and 0.34 for d-AMP/d-AMP-d(11); and 1.00, 0.59, 0.25, and 0.18 for d-MAMP/d-MAMP-d(14). The affinity of d-MAMPd(14) was shown to be greater than that of d-MAMP-d(5), and deuteration at the propyl end of the molecule was shown to increase binding more than deuteration on the phenyl group. PMID:21219698

  3. Synthesis and biological activity of piperazine derivatives of phenothiazine.

    PubMed

    Amani, A M

    2015-01-01

    Some novel piperazine derivatives of phenothiazine were synthesized. The structures of the synthesized compounds were characterized by elemental analysis, FT-IR, (1)H- and (13)C-NMR and Mass Spectroscopy. The compounds were evaluated for antibacterial, antifungal and antitubercular activity by cup plate, disc diffusion and Lowenstein-Jensen medium methods respectively. All the compounds showed good antibacterial activity against Staphylococcus aureus and Bacillus subtilis. Compound V showed equipotent antibacterial activity with streptomycin standard and showed better antibacterial activity against gram positive bacteria profile than gram negative bacteria. Zone of inhibition was not found for the compounds against Escherichia coli and Pseudomonas aeruginosa. All the compounds exhibited good antifungal activity against Aspergillus species and no activity against Candida albicans. All the compounds at a concentration of 100, 10 and 1 µg/L showed inhibition against the growth of Mycobacterium tuberculosis. PMID:24470309

  4. Chrysin-piperazine conjugates as antioxidant and anticancer agents.

    PubMed

    Patel, Rahul V; Mistry, Bhupendra; Syed, Riyaz; Rathi, Anuj K; Lee, Yoo-Jung; Sung, Jung-Suk; Shinf, Han-Seung; Keum, Young-Soo

    2016-06-10

    Synthesis of 7-(4-bromobutoxy)-5-hydroxy-2-phenyl-4H-chromen-4-one intermediate treating chrysin with 1,4-dibromobutane facilitated combination of chrysin with a wide range of piperazine moieties which were equipped via reacting the corresponding amines with bis(2-chloroethyl)amine hydrochloride in diethylene glycol monomethyl ether solvent. Free radical scavenging potential of prepared products was analyzed in vitro adopting DPPH and ABTS bioassay in addition to the evaluation of in vitro anticancer efficacies against cervical cancer cell lines (HeLa and CaSki) and an ovarian cancer cell line SK-OV-3 using SRB assay. Bearable toxicity of 7a-w was examined employing Madin-Darby canine kidney (MDCK) cell line. In addition, cytotoxic nature of the presented compounds was inspected utilizing Human bone marrow derived mesenchymal stem cells (hBM-MSCs). Overall, 7a-w indicated remarkable antioxidant power in scavenging DPPH(·) and ABTS(·+), particularly analogs 7f, 7j, 7k, 7l, 7n, 7q, 7v, 7w have shown promising free radical scavenging activity. Analogs 7j and 7o are identified to be highly active candidates against HeLa and CaSki cell lines, whereas 7h and 7l along with 7j proved to be very sensitive towards ovarian cancer cell line SKOV-3. None of the newly prepared scaffolds showed cytotoxic nature toward hBM-MSCs cells. From the structure-activity point of view, nature and position of the electron withdrawing and electron donating functional groups on the piperazine core may contribute to the anticipated antioxidant and anticancer action. Different spectroscopic techniques (FT-IR, (1)H NMR, (13)C NMR, Mass) and elemental analysis (CHN) were utilized to confirm the desired structure of final compounds. PMID:26924226

  5. Silicon Amine Reagents for the Photocatalytic Synthesis of Piperazines from Aldehydes and Ketones.

    PubMed

    Hsieh, Sheng-Ying; Bode, Jeffrey W

    2016-05-01

    Silicon amine protocol (SLAP) reagents for photocatalytic cross-coupling with aldehydes and ketones to form N-unprotected piperazines have been developed. This blue light promoted process tolerates a wide range of heteroaromatic, aromatic, and aliphatic aldehydes and structurally and stereochemically complex SLAP reagents. It provides a tin-free alternative to SnAP (tin amine protocol) reagents for the synthesis of substituted piperazines. PMID:27101157

  6. Investigations on the stereoselectivity of the phase II metabolism of the 3,4-methylenedioxyethylamphetamine (MDEA) metabolites 3,4-dihydroxyethylamphetamine (DHEA) and 4-hydroxy-3-methoxyethylamphetamine (HMEA).

    PubMed

    Schwaninger, Andrea E; Meyer, Markus R; Zapp, Josef; Maurer, Hans H

    2012-07-01

    Different elimination was reported for the two enantiomers of the designer drug 3,4-methylenedioxyethylamphetamine (MDEA) in vivo. In the present work, the enantioselectivity of glucuronidation and sulfation of the MDEA phase I metabolites 3,4-dihydroxyethylamphetamine (DHEA) and 4-hydroxy-3-methoxyethylamphetamine (HMEA) was investigated. First, glucuronide standards were synthesized using rat liver microsomes. Incubations were performed with recombinant human UDP-glucuronyltransferases (UGT) and pooled human liver microsomes (pHLM) for glucuronidation and using recombinant human sulfotransferases (SULT) and pooled human liver cytosol (pHLC) for sulfation. Product formation experiments were performed by quantification of the phase II metabolites using liquid chromatography-high-resolution mass spectrometry. Additionally, substrate depletion experiments were conducted by gas chromatography-mass spectrometry after chiral derivatization for sulfation. UGT2B7, 2B15, and 2B17 were involved in glucuronidation of HMEA and SULT1A1 and SULT1A3 and SULT1A3 and SULT1E1 in the sulfation of DHEA and HMEA, respectively. SULTs provided much higher affinity, whereas UGTs showed higher capacities. Marked stereoselectivity could be observed for UGT2B15, UGT2B17, and pHLM toward S-HMEA, for SULT1A3 and pHLC toward S-DHEA and for SULT1A3 and pHLC toward R-HMEA. In conclusion, the phase II metabolism might also contribute to the observed different pharmacokinetic properties of MDEA. PMID:22564759

  7. Characterization of tunable piperidine and piperazine carbamates as inhibitors of endocannabinoid hydrolases

    PubMed Central

    Long, Jonathan Z.; Jin, Xin; Adibekian, Alexander; Li, Weiwei; Cravatt, Benjamin F.

    2010-01-01

    Monoacylglycerol lipase (MAGL) and fatty acid amide hydrolase (FAAH) are two enzymes from the serine hydrolase superfamily that degrade the endocannabinoids 2-arachidonoylglycerol and anandamide, respectively. We have recently discovered that MAGL and FAAH are both inhibited by carbamates bearing an N-piperidine/piperazine group. Piperidine/piperazine carbamates show excellent in vivo activity, raising brain endocannabinoid levels and producing CB1-dependent behavioral effects in mice, suggesting that they represent a promising class of inhibitors for studying the endogenous functions of MAGL and FAAH. Herein, we disclose a full account of the syntheses, structure-activity relationships, and inhibitory activities of piperidine/piperazine carbamates against members of the serine hydrolase family. These scaffolds can be tuned for MAGL-selective or dual MAGL-FAAH inhibition by the attachment of an appropriately substituted bisarylcarbinol or aryloxybenzyl moiety, respectively, on the piperidine/piperazine ring. Modifications to the piperidine/piperazine ring ablated inhibitory activity, suggesting a strict requirement for a six-member ring to maintain potency. PMID:20099888

  8. Piperazine-induced airway symptoms: exposure-response relationships and selection in an occupational setting

    SciTech Connect

    Hagmar, L.; Bellander, T.; Ranstam, J.; Skerfving, S.

    1984-01-01

    The heterocyclic secondary amine piperazine is known to cause asthma. In a cohort of 602 workers, employed during the period 1942-1979, at a chemical industry where piperazine is handled, a study conducted by means of a mailed questionnaire showed a strong exposure-response relationship as to frequency of work-related airway symptoms indicating asthma. In the most exposed group about a third of the workers had experienced such symptoms. Age, length of employment, smoking habits, and previous work-related asthmatic symptoms, but not atopy, modified the response. Further, there was an association between piperazine exposure and chronic bronchitis. In the most exposed group every fourth subject had chronic bronchitis. The frequency was modified by smoking habits; atopy was a confounder. Although many subjects, especially high-exposed ones, left work because of airway symptoms, there was no difference in occurrence of airway symptoms between former and present employees.

  9. The mechanism of action of piperazine-phosphonates derivatives in cotton fabric

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Piperazine-phosphonates additives are known to be very effective flame retardants on different polymeric systems, especially cotton cellulose. In order to understand their mechanism of action, we carried out the investigation of their thermal behavior on cotton fabric by, first, employing the attenu...

  10. Synthesis and antitubercular activity of 1,2,4-trisubstitued piperazines.

    PubMed

    Rohde, Kyle H; Michaels, Heather A; Nefzi, Adel

    2016-05-01

    Parallel solid phase synthesis offers a unique opportunity for the synthesis and screening of large numbers of compounds and significantly enhances the prospect of finding new leads. We report the synthesis and antitubercular activity of chiral 1,2,4-trisubstituted piperazines derived from resin bound acylated dipeptides against Mycobacterium tuberculosis strain H37Rv. PMID:27020522

  11. 21 CFR 520.2520g - Trichlorfon, phenothiazine, and piperazine dihydrochloride powder.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Trichlorfon, phenothiazine, and piperazine dihydrochloride powder. 520.2520g Section 520.2520g Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF.... Administer by stomach tube. Do not fast horses before or after treatment. Treatment of mares in...

  12. Thermal decomposition reactions of cotton fabric treated with piperazine-phosphonates derivatives as a flame retardant

    Technology Transfer Automated Retrieval System (TEKTRAN)

    There has been a great scientific interest in exploring the great potential of the piperazine-phosphonates in flame retardant (FR) application on cotton fabric by investigating the thermal decomposition of cotton fabric treated with them. This research tries to understand the mode of action of the t...

  13. Piperazine-phosphonate derivatives: their flame retardant and thermal degradation properties on cotton fibers

    Technology Transfer Automated Retrieval System (TEKTRAN)

    It has been known that phosphorus-nitrogen system shows greater flame resistance in cotton textiles at a lower level than phosphorus used alone. This research aims to compare the effectiveness of Tetraethyl piperazine-1,4-diyldiphosphonate (TEPP) as a flame retardant (FR) for cotton fabric to a prev...

  14. The influences of piperazine-phosphonates derivatives on flame retardancy and thermal behaviors of cotton cellulose

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In an effort to create the environmentally-friendly flame retardants (FRs) for cotton cellulose, two phosphoramidates derivatives, tetraethyl piperazine-1,4-diyldiphosphonate (PDP) and diethyl 4-methylpiperazin-1-ylphosphoramidate (PAP), have been developed. Both were synthesized in high yield and ...

  15. Replacement of cardiotoxic aminopiperidine linker with piperazine moiety reduces cardiotoxicity? Mycobacterium tuberculosis novel bacterial topoisomerase inhibitors.

    PubMed

    Bobesh, Karyakulam Andrews; Renuka, Janupally; Srilakshmi, Rudraraju Reshma; Yellanki, Swapna; Kulkarni, Pushkar; Yogeeswari, Perumal; Sriram, Dharmarajan

    2016-01-01

    Recently numerous non-fluoroquinolone-based bacterial type II topoisomerase inhibitors from both the GyrA and GyrB classes have been reported as antibacterial agents. Inhibitors of the GyrA class include aminopiperidine-based novel bacterial type II topoisomerase inhibitors (NBTIs). However, inhibition of the cardiac ion channel remains a serious liability for the aminopiperidine based NBTIs. In this paper we replaced central aminopiperidine linker with piperazine moiety and tested for its biological activity. We developed a series of twenty four compounds with a piperazine linker 1-(2-(piperazin-1-yl)ethyl)-1,5-naphthyridin-2(1H)-one, by following a multistep protocol. Among them compound 4-(2-(7-methoxy-2-oxo-1,5-naphthyridin-1(2H)-yl)ethyl)-N-(4-nitrophenyl)piperazine-1-carboxamide (11) was the most promising inhibitor with Mycobacterium tuberculosis (MTB) DNA gyrase enzyme supercoiling IC50 of 0.29±0.22μM, with a good MTB MIC of 3.45μM. These kind of compounds retains good potency and showed reduced cardiotoxicity compared to aminopiperidines. PMID:26678175

  16. N-dealkylation of arylpiperazine derivatives: disposition and metabolism of the 1-aryl-piperazines formed.

    PubMed

    Caccia, Silvio

    2007-08-01

    In recent years several arylpiperazine derivatives have reached the stage of clinical application, mainly for the treatment of depression, psychosis or anxiety. Examples are the pyrimidinylpiperazine buspirone, the chlorophenylpiperazine derivatives nefazodone and trazodone, the dichlorophenylpiperazine aripiprazole and the benzisothiazolyl derivatives perospirone and ziprasidone. Most of them undergo extensive pre-systemic and systemic metabolism including CYP3A4-dependent N-dealkylation to 1-aryl-piperazines. These metabolites are best known for the variety of serotonin receptor-related effects they cause in man and animals, although some have affinity for other neurotransmitter receptors; others, however, are still largely unexplored despite uncontrolled use as amphetamine-like designer drugs. Once formed they distribute extensively in tissues, including brain which is the target site of most arylpiperazine derivatives, and are then primarily biotransformed by CYP2D6-dependent oxidation to hydroxylates which are excreted as conjugates; only 1-(2-benzisothiazolyl)-piperazine is more susceptible to sulfur oxidation than to aromatic hydroxylation. In studies analysing animal brain and human blood, 1-aryl-piperazine concentrations were either higher or lower than the parent compound(s), although information is available only for some derivatives. At steady state, the metabolite-to-parent drug ratios varied widely among individuals taking the same dosage of the same arylpiperazine derivative. This is consistent with the known individual variability in the expression and activity of CYP3A4 and CYP2D6. This review also surveys current published information on physiological and pathological factors affecting the 1-aryl-piperazine-to-parent drug ratios and examines the potential role of 1-aryl-piperazine formation in the pharmacological actions of the arylpiperazine derivatives that are already or will shortly be available in major markets. PMID:17691920

  17. GC-MS and GC-IRD analysis of ring and side chain regioisomers of ethoxyphenethylamines related to the controlled substances MDEA, MDMMA and MBDB.

    PubMed

    Al-Hossaini, Abdullah M; Awad, Tamer; DeRuiter, Jack; Clark, C Randall

    2010-07-15

    Three regioisomeric 3, 4-methylenedioxyphenethylamines having the same molecular weight and major mass spectral fragments of equal mass have been reported as drugs of abuse in recent years. These compounds are 3,4-methylenedioxy-N-ethylamphetamine (MDEA), 3,4-methylenedioxy-N,N-dimethylamphetamine (MDMMA), and N-methyl-1-(3,4-methylenedioxyphenyl)-2-butanamine (MBDB). Ring substituted ethoxy phenethylamines having the same side chain are compounds with an isobaric relationship to these controlled drug substances, all have molecular weight of 207 and major fragment ions in their electron ionization mass spectra at m/z 72 and 135/136. The three methylenedioxyphenethylamines were resolved from the ethoxyphenethylamines by capillary gas chromatography using an Rxi-50 stationary phase. The trifluoroacetyl, pentafluoropropionyl and heptafluorobutryl derivatives of the secondary amines were evaluated in GC-MS studies. The mass spectra for these derivatives were significantly individualized and the resulting unique fragment ions allowed for specific side chain identification. The perfluoroacyl derivatives showed reasonable resolution on a non-polar stationary phase such as Rtx-1. GC-IRD studies provided structure-IR spectra relationships used for the discrimination of the three target drugs (MDEA, MDMMA and MBDB) from the other nine ring substituted ethoxyphenethylamine regioisomers. PMID:20427137

  18. Influence of superheated water on the hydrogen bonding and crystallography of piperazine-based (Co)polyamides.

    PubMed

    Vinken, Esther; Terry, Ann E; Spoelstra, Anne B; Koning, Cor E; Rastogi, Sanjay

    2009-05-01

    Here we demonstrate that superheated water is a solvent for polyamide 2,14 and piperazine-based copolyamides up to a piperazine content of 62 mol %. The incorporation of piperazine allows for a variation of the hydrogen bond density without altering the crystal structure (i.e., the piperazine units cocrystallize with the PA2,14 units (Hoffmann, S.; Vanhaecht, B.; Devroede, J.; Bras, W.; Koning, C. E.; Rastogi, S. Macromolecules 2005, 38, 1797-1803). It is shown that the crystallization of PA2,14 from superheated water greatly influences the crystal structure. Water molecules incorporated in the PA2,14 crystal lattice cause a slip on the hydrogen bonded planes, resulting in a coexistence of a triclinic and a monoclinic crystal structure. On heating above the Brill transition, the water molecules exit from the lattice, restoring the triclinic crystal structure. With increasing piperazine content, and hence decreasing hydrogen bond density, the dissolution temperature decreases. It is only possible to grow single crystals from superheated water up to a piperazine content of 62 mol %. For these single crystals, the incorporation of water molecules in the vicinity of the amide group is seen by the presence of COO- stretch vibrations with FTIR spectroscopy. These vibrations disappear on heating above the Brill transition temperature, and the water molecules leave the amide groups. For copolyamides with more than 62 mol % piperazine, no Brill transition is observed, no single crystals can be grown from water, and no water molecules are observed in the vicinity of the amide groups (Vinken, E.; Terry, A. E.; Hoffmann, S.; Vanhaecht, B.; Koning, C. E.; Rastogi, S. Macromolecules 2006, 39, 2546-2552). The high piperazine content (co)polyamides have fewer hydrogen bond donors and are therefore less likely to have interactions with the water molecules. This work demonstrates the relation among the Brill transition, the dissolution of polyamide in superheated water, and its influence on the hydrogen bonds and the amide groups. PMID:19397364

  19. Synthesis and SAR of calcitonin gene-related peptide (CGRP) antagonists containing substituted aryl-piperazines and piperidines.

    PubMed

    Civiello, Rita L; Han, Xiaojun; Beno, Brett R; Chaturvedula, Prasad V; Herbst, John J; Xu, Cen; Conway, Charles M; Macor, John E; Dubowchik, Gene M

    2016-02-15

    Calcitonin gene-related peptide (CGRP) is a potent neuropeptide implicated in the pathophysiology of migraine. In the course of seeking CGRP antagonists with improved oral bioavailability, metabolic stability, and pharmacokinetic properties, lower molecular weight, structurally simpler piperidine and piperazine analogs of BMS-694153 were prepared. Several were found to have nM binding affinity in vitro. The synthesis and SAR of these substituted piperidine and piperazine CGRP antagonists are discussed. PMID:26832218

  20. In vitro neurotoxicity evaluation of piperazine designer drugs in differentiated human neuroblastoma SH-SY5Y cells.

    PubMed

    Arbo, M D; Silva, R; Barbosa, D J; Dias da Silva, D; Silva, S P; Teixeira, J P; Bastos, M L; Carmo, H

    2016-01-01

    Abuse of synthetic drugs is widespread worldwide. Studies indicate that piperazine designer drugs act as substrates at dopaminergic and serotonergic receptors and/or transporters in the brain. This work aimed to investigate the cytotoxicity of N-benzylpiperazine, 1-(3-trifluoromethylphenyl)piperazine, 1-(4-methoxyphenyl)piperazine and 1-(3,4-methylenedioxybenzyl)piperazine in the differentiated human neuroblastoma SH-SY5Y cell line. Cytotoxicity was evaluated after 24 h incubations through the MTT reduction and neutral red uptake assays. Oxidative stress (reactive oxygen and nitrogen species production and glutathione content) and energetic (ATP content) parameters, as well as intracellular Ca(2+), mitochondrial membrane potential, DNA damage (comet assay) and cell death mode were also evaluated. Complete cytotoxicity curves were obtained after 24 h incubations with each drug. A significant decrease in intracellular total glutathione content was noted for all the tested drugs. All drugs caused a significant increase of intracellular free Ca(2+) levels, accompanied by mitochondrial hyperpolarization. However, ATP levels remained unchanged. The investigation of cell death mode revealed a predominance of early apoptotic cells. No genotoxicity was found in the comet assay. Among the tested drugs, 1-(3-trifluoromethylphenyl)piperazine was the most cytotoxic. Overall, piperazine designer drugs are potentially neurotoxic, supporting concerns on risks associated with the abuse of these drugs. PMID:25900438

  1. Syntheses, biological activities and SAR studies of novel carboxamide compounds containing piperazine and arylsulfonyl moieties.

    PubMed

    Wang, Bao-Lei; Shi, Yan-Xia; Zhang, Shu-Jun; Ma, Yi; Wang, Hong-Xue; Zhang, Li-Yuan; Wei, Wei; Liu, Xing-Hai; Li, Yong-Hong; Li, Zheng-Ming; Li, Bao-Ju

    2016-07-19

    A series of novel carboxamide compounds 19a-19j, 20a-20j and 22a-22d containing piperazine and arylsulfonyl moieties have been synthesized. The bioassay results showed that some compounds exhibited favorable herbicidal activities against dicotyledonous plants and many of them possessed excellent antifungal activities. Among 24 novel compounds, some showed superiority over the commercial fungicides Chlorothalonil, Dimethomorph, Thiophanate-methyl, Iprodione, and Zhongshengmycin at 500 mg/L concentration. Some compounds also exhibited high KARI inhibitory activity at 100 μg/mL concentration and could be used as new KARI lead inhibitors for further studies. Moreover, SAR of these new compounds were comprehensively investigated using different computational methods in which 3D-QSAR model obtained provided useful information for further structural optimization for the discovery of new fungicides. The results of this research will contribute to explore comprehensive biological activities of piperazine-containing compounds in different areas of chemistry. PMID:27092414

  2. Scalable Synthesis of Piperazines Enabled by Visible-Light Irradiation and Aluminum Organometallics

    PubMed Central

    Suárez-Pantiga, Samuel; Colas, Kilian; Johansson, Magnus J; Mendoza, Abraham

    2015-01-01

    The development of more active C–H oxidation catalysts has inspired a rapid, scalable, and stereoselective assembly of multifunctional piperazines through a [3+3] coupling of azomethine ylides. A combination of visible-light irradiation and aluminum organometallics is essential to promote this transformation, which introduces visible-light photochemistry of main-group organometallics and sets the basis for new and promising catalysts. PMID:26337253

  3. Screening of Transient Receptor Potential Canonical Channel Activators Identifies Novel Neurotrophic Piperazine Compounds.

    PubMed

    Sawamura, Seishiro; Hatano, Masahiko; Takada, Yoshinori; Hino, Kyosuke; Kawamura, Tetsuya; Tanikawa, Jun; Nakagawa, Hiroshi; Hase, Hideharu; Nakao, Akito; Hirano, Mitsuru; Rotrattanadumrong, Rachapun; Kiyonaka, Shigeki; Mori, Masayuki X; Nishida, Motohiro; Hu, Yaopeng; Inoue, Ryuji; Nagata, Ryu; Mori, Yasuo

    2016-03-01

    Transient receptor potential canonical (TRPC) proteins form Ca(2+)-permeable cation channels activated upon stimulation of metabotropic receptors coupled to phospholipase C. Among the TRPC subfamily, TRPC3 and TRPC6 channels activated directly by diacylglycerol (DAG) play important roles in brain-derived neurotrophic factor (BDNF) signaling, promoting neuronal development and survival. In various disease models, BDNF restores neurologic deficits, but its therapeutic potential is limited by its poor pharmacokinetic profile. Elucidation of a framework for designing small molecules, which elicit BDNF-like activity via TRPC3 and TRPC6, establishes a solid basis to overcome this limitation. We discovered, through library screening, a group of piperazine-derived compounds that activate DAG-activated TRPC3/TRPC6/TRPC7 channels. The compounds [4-(5-chloro-2-methylphenyl)piperazin-1-yl](3-fluorophenyl)methanone (PPZ1) and 2-[4-(2,3-dimethylphenyl)piperazin-1-yl]-N-(2-ethoxyphenyl)acetamide (PPZ2) activated, in a dose-dependent manner, recombinant TRPC3/TRPC6/TRPC7 channels, but not other TRPCs, in human embryonic kidney cells. PPZ2 activated native TRPC6-like channels in smooth muscle cells isolated from rabbit portal vein. Also, PPZ2 evoked cation currents and Ca(2+) influx in rat cultured central neurons. Strikingly, both compounds induced BDNF-like neurite growth and neuroprotection, which were abolished by a knockdown or inhibition of TRPC3/TRPC6/TRPC7 in cultured neurons. Inhibitors of Ca(2+) signaling pathways, except calcineurin, impaired neurite outgrowth promotion induced by PPZ compounds. PPZ2 increased activation of the Ca(2+)-dependent transcription factor, cAMP response element-binding protein. These findings suggest that Ca(2+) signaling mediated by activation of DAG-activated TRPC channels underlies neurotrophic effects of PPZ compounds. Thus, piperazine-derived activators of DAG-activated TRPC channels provide important insights for future development of a new class of synthetic neurotrophic drugs. PMID:26733543

  4. Piperazine sulfonamide BACE1 inhibitors: Design, synthesis, and in vivo characterization

    SciTech Connect

    Cumming, Jared; Babu, Suresh; Huang, Ying; Carrol, Carolyn; Chen, Xia; Favreau, Leonard; Greenlee, William; Guo, Tao; Kennedy, Matthew; Kuvelkar, Reshma; Le, Thuy; Li, Guoqing; McHugh, Nansie; Orth, Peter; Ozgur, Lynne; Parker, Eric; Saionz, Kurt; Stamford, Andrew; Strickland, Corey; Tadesse, Dawit; Voigta, Johannes; Zhang, Lili; Zhang, Qi

    2010-08-17

    With collaboration between chemistry, X-ray crystallography, and molecular modeling, we designed and synthesized a series of novel piperazine sulfonamide BACE1 inhibitors. Iterative exploration of the non-prime side and S2{prime} sub-pocket of the enzyme culminated in identification of an analog that potently lowers peripheral A{beta}{sub 40} in transgenic mice with a single subcutaneous dose.

  5. 4-(2-Azaniumyl-eth-yl)piperazin-1-ium bis(perchlorate).

    PubMed

    Reisi, Mohammad Reza; Saleh Salga, Muhammad; Khaledi, Hamid; Mohd Ali, Hapipah

    2011-09-01

    In the title compound, C(6)H(17)N(3) (2+)·2ClO(4) (-), the piperazine ring adopts a chair conformation with the ethyl-ammonium fragment occupying an equatorial position. In the crystal, the dications and perchlorate anions are linked through N-H⋯O hydrogen bonding and weak C-H⋯O hydrogen bonding into a three-dimensional supra-molecular network. PMID:22064357

  6. trans-2,5-Di­methyl­piperazine-1,4-diium dinitrate

    PubMed Central

    Gatfaoui, Sofian; Roisnel, Thierry; Dhaouadi, Hassouna; Marouani, Houda

    2014-01-01

    In the structure of the title salt, C6H16N2 2+·2NO3 −, the cations are connected to the anions through bifurcated N—H⋯(O,O) and weak C—H⋯O hydrogen bonds, generating corrugated layers parallel to the (100) plane. The organic cation is centrosymmetric and the diprotonated piperazine ring adopts a chair conformation, with the methyl groups occupying equatorial positions. PMID:24940294

  7. Integration of enabling methods for the automated flow preparation of piperazine-2-carboxamide.

    PubMed

    Ingham, Richard J; Battilocchio, Claudio; Hawkins, Joel M; Ley, Steven V

    2014-01-01

    Here we describe the use of a new open-source software package and a Raspberry Pi(®) computer for the simultaneous control of multiple flow chemistry devices and its application to a machine-assisted, multi-step flow preparation of pyrazine-2-carboxamide - a component of Rifater(®), used in the treatment of tuberculosis - and its reduced derivative piperazine-2-carboxamide. PMID:24778715

  8. Integration of enabling methods for the automated flow preparation of piperazine-2-carboxamide

    PubMed Central

    Ingham, Richard J; Battilocchio, Claudio; Hawkins, Joel M

    2014-01-01

    Summary Here we describe the use of a new open-source software package and a Raspberry Pi® computer for the simultaneous control of multiple flow chemistry devices and its application to a machine-assisted, multi-step flow preparation of pyrazine-2-carboxamide – a component of Rifater®, used in the treatment of tuberculosis – and its reduced derivative piperazine-2-carboxamide. PMID:24778715

  9. Substituted dithiazole piperazine benzamides as novel amyloid beta peptide reducing agents

    PubMed Central

    Wang, Hongjie; Wang, Ruizhi; Lakshmana, Madepalli K; Nefzi, Adel

    2014-01-01

    Alzheimer’s disease is a persistent neurodegenerative disorder of elderly characterized clinically by irreversible loss of memory due to accumulation of amyloid beta peptides within the amyloid plaques. We report the parallel synthesis and screening results of diverse substituted di-thiazole piperazine benzamides. A new compound TPI-1917-49 was identified as a promising amyloid reducing agent by lowering the levels of Aβ at least in two cell types and in vivo. PMID:25155386

  10. Substituted dithiazole piperazine benzamides as novel amyloid beta peptide reducing agents.

    PubMed

    Wang, Hongjie; Wang, Ruizhi; Lakshmana, Madepalli K; Nefzi, Adel

    2014-09-15

    Alzheimer's disease is a persistent neurodegenerative disorder of elderly characterized clinically by irreversible loss of memory due to accumulation of amyloid beta peptides within the amyloid plaques. We report the parallel synthesis and screening results of diverse substituted di-thiazole piperazine benzamides. A new compound TPI-1917-49 was identified as a promising amyloid reducing agent by lowering the levels of Aβ at least in two cell types and in vivo. PMID:25155386

  11. Scalable Synthesis of Piperazines Enabled by Visible-Light Irradiation and Aluminum Organometallics.

    PubMed

    Surez-Pantiga, Samuel; Colas, Kilian; Johansson, Magnus J; Mendoza, Abraham

    2015-11-16

    The development of more active C?H oxidation catalysts has inspired a rapid, scalable, and stereoselective assembly of multifunctional piperazines through a [3+3] coupling of azomethine ylides. A combination of visible-light irradiation and aluminum organometallics is essential to promote this transformation, which introduces visible-light photochemistry of main-group organometallics and sets the basis for new and promising catalysts. PMID:26337253

  12. N-(4-Chloro­phen­yl)-4-methyl­piperazine-1-carboxamide

    PubMed Central

    Li, Yu-Feng; Wang, Wen-Mei

    2011-01-01

    In the title compound, C12H16ClN3O, the piperazine ring has a chair conformation. Within this ring, the N-methyl nitro­gen atom has a pyramidal geometry and the N-carboxamide nitro­gen atom is almost planar (bond-angle sum = 359.8°). In the crystal, the mol­ecules are linked by N—H⋯O hydrogen bonds into C(4) chains propagating in [010]. PMID:22059021

  13. A case of levocetirizine-induced fixed drug eruption and cross-reaction with piperazine derivatives

    PubMed Central

    Kim, Mi-Yeong; Jo, Eun-Jung; Chang, Yoon-Seok; Cho, Sang-Heon; Min, Kyung-Up

    2013-01-01

    Fixed drug eruption is an uncommon adverse drug reaction caused by delayed cell-mediated hypersensitivity. Levocetirizine is an active (R)-enatiomer of cetirizine and there have been a few reports of fixed drug eruption related to these antihistamines. We experienced a case of levocetirizine-induced fixed drug eruption and cross-reaction with other piperazine derivatives confirmed by patch test. A 73-year-old female patient presented with recurrent generalized itching, cutaneous bullae formation, rash and multiple pigmentation at fixed sites after taking drugs for common cold. She took bepotastine besilate (Talion®) and levocetirizine (Xyzal®) as antihistamine. She took acetaminophen, pseudoephedrine 60 mg / triprolidine 2.5 mg (Actifed®), dihydrocodeinebitartrate 5 mg / di-methylephedrine hydrochloride 17.5 mg / chlorpheniramine maleate 1.5 mg / guaifenesin 50 mg (Codening®) and aluminium hydroxide 200 mg / magnesium carbonate 120 mg (Antad®) at the same time. Patch test was done with suspected drugs and the result was positive with levocetirizine. We additionally performed patch test for other antihistamines such as cetirizine, hydroxyzine, fexofenadine and loratadine. Piperazine derivatives (cetirizine and hydroxyzine) were positive, but piperidine derivatives (fexofenadine and loratadine) were negative to patch test. There was no adverse drug reaction when she was challenged with fexofenadine. We report a case of levocetirizine-induced fixed drug eruption confirmed by patch test. Cross-reactions were only observed in the piperazine derivatives and piperidine antihistamine was tolerant to the patient. PMID:24260733

  14. A case of levocetirizine-induced fixed drug eruption and cross-reaction with piperazine derivatives.

    PubMed

    Kim, Mi-Yeong; Jo, Eun-Jung; Chang, Yoon-Seok; Cho, Sang-Heon; Min, Kyung-Up; Kim, Sae-Hoon

    2013-10-01

    Fixed drug eruption is an uncommon adverse drug reaction caused by delayed cell-mediated hypersensitivity. Levocetirizine is an active (R)-enatiomer of cetirizine and there have been a few reports of fixed drug eruption related to these antihistamines. We experienced a case of levocetirizine-induced fixed drug eruption and cross-reaction with other piperazine derivatives confirmed by patch test. A 73-year-old female patient presented with recurrent generalized itching, cutaneous bullae formation, rash and multiple pigmentation at fixed sites after taking drugs for common cold. She took bepotastine besilate (Talion®) and levocetirizine (Xyzal®) as antihistamine. She took acetaminophen, pseudoephedrine 60 mg / triprolidine 2.5 mg (Actifed®), dihydrocodeinebitartrate 5 mg / di-methylephedrine hydrochloride 17.5 mg / chlorpheniramine maleate 1.5 mg / guaifenesin 50 mg (Codening®) and aluminium hydroxide 200 mg / magnesium carbonate 120 mg (Antad®) at the same time. Patch test was done with suspected drugs and the result was positive with levocetirizine. We additionally performed patch test for other antihistamines such as cetirizine, hydroxyzine, fexofenadine and loratadine. Piperazine derivatives (cetirizine and hydroxyzine) were positive, but piperidine derivatives (fexofenadine and loratadine) were negative to patch test. There was no adverse drug reaction when she was challenged with fexofenadine. We report a case of levocetirizine-induced fixed drug eruption confirmed by patch test. Cross-reactions were only observed in the piperazine derivatives and piperidine antihistamine was tolerant to the patient. PMID:24260733

  15. Multicomponent Synthesis and Biological Evaluation of a Piperazine-Based Dopamine Receptor Ligand Library.

    PubMed

    Stucchi, Mattia; Gmeiner, Peter; Huebner, Harald; Rainoldi, Giulia; Sacchetti, Alessandro; Silvani, Alessandra; Lesma, Giordano

    2015-08-13

    A series of 1,4-disubstituted piperazine-based compounds were designed, synthesized, and evaluated as dopamine D2/D3 receptor ligands. The synthesis relies on the key multicomponent split-Ugi reaction, assessing its great potential in generating chemical diversity around the piperazine core. With the aim of evaluating the effect of such diversity on the dopamine receptor affinity, a small library of compounds was prepared, applying post-Ugi transformations. Ligand stimulated binding assays indicated that some compounds show a significant affinity, with K i values up to 53 nM for the D2 receptor. Molecular docking studies with the D2 and D3 receptor homology models were also performed on selected compounds. They highlighted key interactions at the indole head and at the piperazine moiety, which resulted in good agreement with the known pharmacophore models, thus helping to explain the observed structure-activity relationship data. Molecular insights from this study could enable a rational improvement of the split-Ugi primary scaffold, toward more selective ligands. PMID:26288260

  16. Enhanced CO2 Adsorption Affinity in a NbO-type MOF Constructed from a Low-Cost Diisophthalate Ligand with a Piperazine-Ring Bridge.

    PubMed

    Mu, Qian; Wang, Haiyan; Li, Liangjun; Wang, Chao; Wang, Ying; Zhao, Xuebo

    2015-09-01

    A metal-organic framework (NPC-6) with an NbO topology based on a piperazine ring-bridged diisophthalate ligand was synthesized and characterized. The incorporated piperazine group leads to an enhanced adsorption affinity for CO2 in NPC-6, in which the CO2 uptake is 4.83?mmol?g(-1) at 293?K and 1?bar, ranking among the top values of CO2 uptake on MOF materials. At 0.15?bar and 293?K, the NPC-6 adsorbs 1.07?mmol?g(-1) of CO2 , which is about 55.1?% higher than that of the analogue MOF NOTT-101 under the same conditions. The enhanced CO2 uptake combined with comparable uptakes for CH4 and N2 leads to much higher selectivities for CO2 /CH4 and CO2 /N2 gas mixtures on NPC-6 than on NOTT-101. Furthermore, an N-alkylation is used in the synthesis of the PDIA ligand, leading to a much lower cost compared with that in the synthesis of ligands in the NOTT series, as the former does not require a palladium-based catalyst and borate esters. Thus, we conclude that NPC-6 is a promising candidate for CO2 capture applications. PMID:26183114

  17. Biochip array technology immunoassay performance and quantitative confirmation of designer piperazines for urine workplace drug testing.

    PubMed

    Castaneto, Marisol S; Barnes, Allan J; Concheiro, Marta; Klette, Kevin L; Martin, Thomas A; Huestis, Marilyn A

    2015-06-01

    Designer piperazines are emerging novel psychoactive substances (NPS) with few high-throughput screening methods for their identification. We evaluated a biochip array technology (BAT) immunoassay for phenylpiperazines (PNP) and benzylpiperazines (BZP) and analyzed 20,017 randomly collected urine workplace specimens. Immunoassay performance at recommended cutoffs was evaluated for PNPI (5 μg/L), PNPII (7.5 μg/L), and BZP (5 μg/L) antibodies. Eight hundred forty positive and 206 randomly selected presumptive negative specimens were confirmed by liquid chromatography high-resolution mass spectrometry (LC-HRMS). Assay limits of detection for PNPI, PNPII, and BZP were 2.9, 6.3, and 2.1 μg/L, respectively. Calibration curves were linear (R (2) > 0.99) with upper limits of 42 μg/L for PNPI/PNII and 100 μg/L for BZP. Quality control samples demonstrated imprecision <19.3 %CV and accuracies 86.0-94.5 % of target. There were no interferences from 106 non-piperazine substances. Seventy-eight of 840 presumptive positive specimens (9.3 %) were LC-HRMS positive, with 72 positive for 1-(3-chlorophenyl)piperazine (mCPP), a designer piperazine and antidepressant trazodone metabolite. Of 206 presumptive negative specimens, one confirmed positive for mCPP (3.3 μg/L) and one for BZP (3.6 μg/L). BAT specificity (21.1 to 91.4 %) and efficiency (27.0 to 91.6 %) increased, and sensitivity slightly decreased (97.5 to 93.8 %) with optimized cutoffs of 25 μg/L PNPI, 42 μg/L PNPI, and 100 μg/L BZP. A high-throughput screening method is needed to identify piperazine NPS. We evaluated performance of the Randox BAT immunoassay to identify urinary piperazines and documented improved performance when antibody cutoffs were raised. In addition, in randomized workplace urine specimens, all but two positive specimens contained mCPP and/or trazodone, most likely from legitimate medical prescriptions. Graphical Abstract Biochip array technology (BAT) immunoassay for designer piperazines detection in urine. In chemiluminescent immunoassay, the labeled-drug (antigen) competes with the drug in the urine. In the absence of drug, the labeled-drug binds to the antibody releasing an enzyme (horseradish peroxidase) to react with the substrate and producing chemiluminescence. The higher the drug concentration in urine, the weaker the chemiluminescent signal is produced. All presumptive positive specimens and randomly selected presumptive negative specimens were analyzed and confirmed by a liquid chromatography high-resolution mass spectrometry with limit of quantification of 2.5 or 5 μg/L. PMID:25903022

  18. Advanced Amine Solvent Formulations and Process Integration for Near-Term CO2 Capture Success

    SciTech Connect

    Fisher, Kevin S.; Searcy, Katherine; Rochelle, Gary T.; Ziaii, Sepideh; Schubert, Craig

    2007-06-28

    This Phase I SBIR project investigated the economic and technical feasibility of advanced amine scrubbing systems for post-combustion CO2 capture at coal-fired power plants. Numerous combinations of advanced solvent formulations and process configurations were screened for energy requirements, and three cases were selected for detailed analysis: a monoethanolamine (MEA) base case and two “advanced” cases: an MEA/Piperazine (PZ) case, and a methyldiethanolamine (MDEA) / PZ case. The MEA/PZ and MDEA/PZ cases employed an advanced “double matrix” stripper configuration. The basis for calculations was a model plant with a gross capacity of 500 MWe. Results indicated that CO2 capture increased the base cost of electricity from 5 cents/kWh to 10.7 c/kWh for the MEA base case, 10.1 c/kWh for the MEA / PZ double matrix, and 9.7 c/kWh for the MDEA / PZ double matrix. The corresponding cost per metric tonne CO2 avoided was 67.20 $/tonne CO2, 60.19 $/tonne CO2, and 55.05 $/tonne CO2, respectively. Derated capacities, including base plant auxiliary load of 29 MWe, were 339 MWe for the base case, 356 MWe for the MEA/PZ double matrix, and 378 MWe for the MDEA / PZ double matrix. When compared to the base case, systems employing advanced solvent formulations and process configurations were estimated to reduce reboiler steam requirements by 20 to 44%, to reduce derating due to CO2 capture by 13 to 30%, and to reduce the cost of CO2 avoided by 10 to 18%. These results demonstrate the potential for significant improvements in the overall economics of CO2 capture via advanced solvent formulations and process configurations.

  19. Ozonation of piperidine, piperazine and morpholine: Kinetics, stoichiometry, product formation and mechanistic considerations.

    PubMed

    Tekle-Röttering, Agnes; Jewell, Kevin S; Reisz, Erika; Lutze, Holger V; Ternes, Thomas A; Schmidt, Winfried; Schmidt, Torsten C

    2016-01-01

    Piperidine, piperazine and morpholine as archetypes for secondary heterocyclic amines, a structural unit that is often present in pharmaceuticals (e.g., ritalin, cetirizine, timolol, ciprofloxacin) were investigated in their reaction with ozone. In principle the investigated compounds can be degraded with ozone in a reasonable time, based on their high reaction rate constants with respect to ozone (1.9 × 10(4)-2.4 × 10(5) M(-1) s(-1)). However, transformation is insufficient (13-16%), most likely due to a chain reaction, which decomposes ozone. This conclusion is based on OH scavenging experiments, leading to increased compound transformation (18-27%). The investigated target compounds are similar in their kinetic and stoichiometric characteristics. However, the mechanistic considerations based on product formation indicate various reaction pathways. Piperidine reacts with ozone via a nonradical addition reaction to N-hydroxypiperidine (yield: 92% with and 94% without scavenging, with respect to compound transformation). However, piperazine degradation with ozone does not lead to N-hydroxypiperazine. In the morpholine/ozone reaction, N-hydroxymorpholine was identified. Additional oxidation pathways in all cases involved the formation of OH with high yields. One important pathway of piperazine and morpholine by ozonation could be the formation of C-centered radicals after ozone or OH radical attack. Subsequently, O2 addition forms unstable peroxyl radicals, which in one pathway loose superoxide radicals by generating a carbon-centered cation. Subsequent hydrolysis of the carbon-centered cation leads to formaldehyde, whereby ozonation of the N-hydroxy products can proceed in the same way and in addition give rise to hydroxylamine. A second pathway of the short-lived peroxyl radicals could be a dimerization to form short-lived tetraoxides, which cleave by forming hydrogen peroxide. All three products have been found. PMID:26624229

  20. Imidazole piperazines: SAR and development of a potent class of cyclin-dependent kinase inhibitors with a novel binding mode.

    PubMed

    Finlay, M Raymond V; Acton, David G; Andrews, David M; Barker, Andrew J; Dennis, Michael; Fisher, Eric; Graham, Mark A; Green, Clive P; Heaton, David W; Karoutchi, Galith; Loddick, Sarah A; Morgentin, Rémy; Roberts, Andrew; Tucker, Julie A; Weir, Hazel M

    2008-08-01

    A piperazine series of cyclin-dependent kinase (CDK) inhibitors have been identified. The compounds exhibit excellent physiochemical properties and a novel binding mode, whereby a bridging interaction via a water molecule with Asp 86 of CDK2, leads to selectivity for the CDK family of enzymes over other kinases. Piperazines 2e and 2i were subsequently shown to inhibit tumour growth when dosed orally in a nude mouse xenograft study. Additional chemical series that exploit this unexpected interaction with Asp 86 are also described. PMID:18617397

  1. Synthesis and antimicrobial evaluation of new chalcones containing piperazine or 2,5-dichlorothiophene moiety.

    PubMed

    Tomar, V; Bhattacharjee, G; Kamaluddin; Kumar, Ashok

    2007-10-01

    Two new series of chalcones have been synthesized by reacting 1-(4-piperazin-1-yl-phenyl)ethanone and 1-(2,5-dichloro-3-thienyl)-1-ethanone with different substituted benzaldehydes in turn by Claisen-Schmidt condensation. The compounds have been characterized by IR, (1)H NMR spectral and microanalysis data. All the synthesized compounds have been evaluated for antimicrobial activity. Some of these derivatives are potentially active against Gram-positive bacteria, Staphylococcus aureus and Escherichia coli while the most potent compound (1) in this study showed MIC(50) value of 2.22 microg/mL against Candida albicans. PMID:17719779

  2. Nitrosamine formation in amine scrubbing at desorber temperatures.

    PubMed

    Fine, Nathan A; Goldman, Mark J; Rochelle, Gary T

    2014-01-01

    Amine scrubbing is a thermodynamically efficient and industrially proven method for carbon capture, but amine solvents can nitrosate in the desorber, forming potentially carcinogenic nitrosamines. The kinetics of reactions involving nitrite and monoethanolamine (MEA), diethanolamine (DEA), methylethanolamine (MMEA), and methyldiethanolamine (MDEA) were determined under desorber conditions. The nitrosations of MEA, DEA, and MMEA are first order in nitrite, carbamate species, and hydronium ion. Nitrosation of MDEA, a tertiary amine, is not catalyzed by the addition of CO2 since it cannot form a stable carbamate. Concentrated and CO2 loaded MEA was blended with low concentrations of N-(2-hydroxyethyl) glycine (HeGly), hydroxyethyl-ethylenediamine (HEEDA), and DEA, secondary amines common in MEA degradation. Nitrosamine yield was proportional to the concentration of secondary amine and was a function of CO2 loading and temperature. Blends of tertiary amines with piperazine (PZ) showed n-nitrosopiperazine (MNPZ) yields close to unity, validating the slow nitrosation rates hypothesized for tertiary amines. These results provide a useful tool for estimating nitrosamine accumulation over a range of amine solvents. PMID:24956458

  3. (4-(Bis(4-Fluorophenyl)Methyl)Piperazin-1-yl)(Cyclohexyl)Methanone Hydrochloride (LDK1229): A New Cannabinoid CB1 Receptor Inverse Agonist from the Class of Benzhydryl Piperazine Analogs

    PubMed Central

    Mahmoud, Mariam M.; Olszewska, Teresa; Liu, Hui; Shore, Derek M.; Hurst, Dow P.; Reggio, Patricia H.; Lu, Dai

    2015-01-01

    Some inverse agonists of cannabinoid receptor type 1 (CB1) have been demonstrated to be anorectic antiobesity drug candidates. However, the first generation of CB1 inverse agonists, represented by rimonabant (SR141716A), otenabant, and taranabant, are centrally active, with a high level of psychiatric side effects. Hence, the discovery of CB1 inverse agonists with a chemical scaffold distinct from these holds promise for developing peripherally active CB1 inverse agonists with fewer side effects. We generated a new CB1 inverse agonist, (4-(bis(4-fluorophenyl)methyl)piperazin-1-yl)(cyclohexyl)methanone hydrochloride (LDK1229), from the class of benzhydryl piperazine analogs. This compound binds to CB1 more selectively than cannabinoid receptor type 2, with a Ki value of 220 nM. Comparable CB1 binding was also observed by analogs 1-[bis(4-fluorophenyl)methyl]-4-cinnamylpiperazine dihydrochloride (LDK1203) and 1-[bis(4-fluorophenyl)methyl]-4-tosylpiperazine hydrochloride (LDK1222), which differed by the substitution on the piperazine ring where the piperazine of LDK1203 and LDK1222 are substituted by an alkyl group and a tosyl group, respectively. LDK1229 exhibits efficacy comparable with SR141716A in antagonizing the basal G protein coupling activity of CB1, as indicated by a reduction in guanosine 5′-O-(3-thio)triphosphate binding. Consistent with inverse agonist behavior, increased cell surface localization of CB1 upon treatment with LDK1229 was also observed. Although docking and mutational analysis showed that LDK1229 forms similar interactions with the receptor as SR141716A does, the benzhydryl piperazine scaffold is structurally distinct from the first-generation CB1 inverse agonists. It offers new opportunities for developing novel CB1 inverse agonists through the optimization of molecular properties, such as the polar surface area and hydrophilicity, to reduce the central activity observed with SR141716A. PMID:25411367

  4. Excretion of N-mononitrosopiperazine after low level exposure to piperazine in air: effects of dietary nitrate and ascorbate

    SciTech Connect

    Bellander, T.; Osterdahl, B.G.; Hagmar, L.

    1988-04-01

    The secondary amine piperazine may be nitrosated in vivo, following oral intake or occupational exposure by inhalation. The suspected carcinogen N-mononitrosopiperazine could be formed in the human stomach, and in part excreted in the urine. In this study, 0.4 microgram N-mononitrosopiperazine, determined by gas chromatography-Thermal Energy Analysis, was observed in the urine in one of four volunteers, at an experimental exposure by inhalation of 0.3 mg piperazine/m3. The intake of spinach and beetroot caused an increased nitrosation of piperazine, and up to 1.7 microgram N-mononitrosopiperazine was excreted in the urine in the four individuals. This excretion indicates that about 5% of the absorbed piperazine dose was converted to N-mononitrosopiperazine. With the same nitrate-rich diet, but with the addition of citrus fruits and fresh vegetables, the highest excretion was 0.6 microgram N-mononitrosopiperazine. The excretion was significantly correlated with the ratio between the maximum level of nitrite in saliva and the ascorbate level in plasma. There was also a significant interindividual variation. N,N'-Dinitrosopiperazine was not found in any sample of urine.

  5. Copper(I) cyanide networks: synthesis, structure, and luminescence behavior. Part 2. Piperazine ligands and hexamethylenetetramine.

    PubMed

    Lim, Mi Jung; Murray, Courtney A; Tronic, Tristan A; deKrafft, Kathryn E; Ley, Amanda N; deButts, Jordan C; Pike, Robert D; Lu, Haiyan; Patterson, Howard H

    2008-08-01

    A variety of photoluminescent, and in some cases thermochromic, metal-organic networks of CuCN were self-assembled in aqueous reactions with amine ligands: (CuCN) 2(Pip) ( 1a), (CuCN) 20(Pip) 7 ( 1b), (CuCN) 7(MePip) 2 ( 2), (CuCN) 2(Me 2Pip) ( 3a), (CuCN) 4(Me 2Pip) ( 3b), (CuCN) 7(EtPip) 2 ( 4), (CuCN) 4(Et 2Pip) ( 5), (CuCN) 3(BzPip) 2 ( 6a), (CuCN) 5(BzPip) 2 ( 6b), (CuCN) 7(BzPip) 2 ( 6c), (CuCN) 4(BzPip) ( 6d), (CuCN) 2(Bz 2Pip) ( 7), (CuCN)(Ph 2CHPip) ( 8a), (CuCN) 2(Ph 2CHPip) ( 8b), (CuCN) 3(HMTA) 2 ( 9a), (CuCN) 5(HMTA) 2 ( 9b), and (CuCN) 5(HMTA) ( 9c) (Pip = piperazine, MePip = N-methylpiperazine, Me 2Pip = N, N'-dimethylpiperazine, EtPip = N-ethylpiperazine, Et 2Pip = N, N'-diethylpiperazine, BzPip = N-benzylpiperazine, Bz 2Pip = N, N'-dibenzylpiperazine, Ph 2CHPip = N-(diphenylmethyl)piperazine, and HMTA = hexamethylenetetramine). New X-ray structures are reported for 1b, 2, 3b, 4, 5, 6a, 6d, 7, 8b, 9b, and 9c. An important structural theme is the formation of (6,3) (CuCN) 2(piperazine) sheets with or without threading of independent CuCN chains. Strong luminescence at ambient temperature is observed for all but complexes 6 and 7. All luminescent compounds show a broad emission band in the blue region at about 450 nm attributable to metal-to-ligand charge transfer behavior based on the large Stokes shift between excitation and emission maxima. 3, 8, and 9 are thermochromic due to an additional lower energy emission band, which is absent at 77 K. PMID:18597424

  6. Design, Synthesis and Biological Evaluation of Novel Piperazine Derivatives as CCR5 Antagonists

    PubMed Central

    Liu, Tao; Weng, Zhiyong; Dong, Xiaowu; Chen, Linjie; Ma, Ling; Cen, Shan; Zhou, Naiming; Hu, Yongzhou

    2013-01-01

    By using a fragment-assembly strategy and bioisosteric-replacement principle, a series of novel piperazine derivatives were designed, synthesized, and evaluated for their cellular target-effector fusion activities and in vitro antiviral activities against HIV-1. Preliminary structure-activity relationships (SARs) of target compounds were concluded in this study, and five compounds were found to exhibited medium to potent CCR5 fusion activities with IC50 values in low micromolar level. Among evaluated compounds, 23 h was found to be a CCR5 antagonist with an IC50 value of 6.29 µM and an anti-HIV-1 inhibitor with an IC50 value of 0.44 µM. PMID:23308267

  7. Solubility of carbon dioxide in an aqueous blend of diethanolamine and piperazine

    SciTech Connect

    Mondal, M.K.

    2009-09-15

    The solubility of CO{sub 2} in aqueous blends of diethanolamine (DEA) and piperazine (PZ), from mixtures of CO{sub 2} and N{sub 2}, was measured for temperatures and CO{sub 2} partial pressures ranging from (303.14 to 353.14) K and (10.133 to 20.265) kPa, respectively. Measurements were made by a saturation method using a laboratory scale bubble column. The results of CO{sub 2} solubility in liquid are expressed as {alpha}(CO{sub 2}) (mol CO{sub 2}/mol amine) for all experimental runs. A solubility model is developed to correlate and predict the solubility data of CO{sub 2} in aqueous blends of DEA and PZ. There is all acceptable degree of agreement between the experimental data of the present study and predictions of the solubility model with an average absolute deviation of less than 4.5%.

  8. Inhibition of adenovirus replication by a trisubstituted piperazin-2-one derivative

    PubMed Central

    Sanchez-Cespedes, Javier; Moyer, Crystal L.; Whitby, Landon R.; Boger, Dale L.; Nemerow, Glen R.

    2014-01-01

    The number of disseminated adenovirus (Ad) infections continues to increase mostly due to the growing use of immunosuppressive treatments. Recipients of solid organ or hematopoietic stem cell transplants, mainly in pediatric units, exhibit a high morbidity and mortality due to these infections. Unfortunately, there are no Ad-specific antiviral drugs currently approved for medical use. To address this situation, we used high-throughput screening (HTS) of synthetic small molecule libraries to identify compounds that restrict Ad infection. Among the more than 25,000 compounds screened, we identified a hit compound that significantly inhibited Ad infection. The compound (15D8) is a trisubstituted piperazin-2-one derivative that showed substantial antiviral activity with little or no cytotoxicity at low micromolar concentrations. Compound 15D8 selectively inhibits Ad DNA replication in the nucleus, providing a potential candidate for the development of a new class of antiviral compounds to treat Ad infections. PMID:24907427

  9. Crystal structure of piperazine-1,4-diium bis-(4-amino-benzene-sulfonate).

    PubMed

    Kumar, K Sathesh; Ranjith, S; Sudhakar, S; Srinivasan, P; Ponnuswamy, M N

    2015-12-01

    The asymmetric unit of the title salt, C4H12N2 (2+)·2C6H6NO3S(-), consists of half a piperazindiium dication, located about an inversion centre, and a 4-amino-benzene-sulfonate anion. The piperazine ring adopts a chair conformation. In the crystal, the cations and anions are linked via N-H⋯O and C-H⋯O hydrogen bonds, forming a three-dimensional framework. Within the framework there are C-H⋯π inter-actions and the N-H⋯O hydrogen bonds result in the formation of R 4 (4)(22) and R 3 (4)(13) ring motifs. PMID:26870510

  10. Synthesis and pharmacological evaluation of piperidine (piperazine)-substituted benzoxazole derivatives as multi-target antipsychotics.

    PubMed

    Huang, Ling; Zhang, Wenjun; Zhang, Xiaohua; Yin, Lei; Chen, Bangyin; Song, Jinchun

    2015-11-15

    The present study describes the optimization of a series of novel benzoxazole-piperidine (piperazine) derivatives combining high dopamine D2 and serotonin 5-HT1A, 5-HT2A receptor affinities. Of these derivatives, the pharmacological features of compound 29 exhibited high affinities for the DA D2, 5-HT1A and 5-HT2A receptors, but low affinities for the 5-HT2C and histamine H1 receptors and human ether-a-go-go-related gene (hERG) channels. Furthermore, compound 29 reduced apomorphine-induced climbing and 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI)-induced head twitching without observable catalepsy, even at the highest dose tested. Thus, compound 29 is a promising candidate as a multi-target antipsychotic treatment. PMID:26483200

  11. Atrazine removal by covalent bonding to piperazine functionalized PolyHIPEs.

    PubMed

    Pulko, Irena; Kolar, Mitja; Krajnc, Peter

    2007-11-01

    The removal of atrazine from water by a solid phase extraction technique using insoluble polymers is described. Porous crosslinked polymers bearing piperazine moieties were prepared in a one step reaction from the precursor 4-nitrophenylacrylate incorporating polymers (PolyHIPE type prepared by the polymerization of the continuous phase of a high internal phase emulsion and polymer beads prepared by suspension polymerization). Polymers were applied to sequester atrazine from aqueous solutions with a concentration of 33 ppb and irreversible covalent bonding to the polymers was achieved. GC/MS/MS was used to monitor the dynamics of atrazine uptake and it was found that almost complete removal of atrazine was accomplished with an excess of polymer after 48 hours at room temperature. For comparison, polymer beads of identical chemistry but lower porosity were also used and showed significantly slower action (near complete removal after 72 hours). PMID:17662371

  12. Piperazine as counter ion for insulin-enhancing anions [VO2(dipic-OH)]-: Synthesis, characterization and X-ray crystal structure

    NASA Astrophysics Data System (ADS)

    Ghasemi, Fatemeh; Ghasemi, Khaled; Rezvani, Ali Reza; Graiff, Claudia

    2016-01-01

    The new complex [H2Pipz][VO2(dipic-OH)]2·2H2O (1), where H2dipic-OH = 4-hydroxypyridine-2,6-dicarboxylic acid and Pipz = piperazine, was synthesized and characterized by elemental analysis, FTIR, 1H NMR, 13C NMR and UV-Vis spectroscopy and single crystal X-ray diffraction. The crystal system is triclinic with space group Pī. In this compound, piperazine is diprotonated and acts as counter ion.

  13. Synthesis and Characterization of New Piperazine-Type Inhibitors for Mitochondrial NADH-Ubiquinone Oxidoreductase (Complex I)†

    PubMed Central

    Ichimaru, Naoya; Murai, Masatoshi; Kakutani, Nobuyuki; Kako, Junko; Ishihara, Atsushi; Nakagawa, Yoshiaki; Nishioka, Takaaki; Yagi, Takao; Miyoshi, Hideto

    2008-01-01

    The mode of action of Δlac-acetogenins, strong inhibitors of bovine heart mitochondrial complex I, is different from that of traditional inhibitors such as rotenone and piericidin A [Murai et al. (2007) Biochemistry 46, 6409−6416]. As further exploration of these unique inhibitors might provide new insights into the terminal electron transfer step of complex I, we drastically modified the structure of Δlac-acetogenins and characterized their inhibitory action. In particular, on the basis of structural similarity between the bis-THF and the piperazine rings, we here synthesized a series of piperazine derivatives. Some of the derivatives exhibited very potent inhibition at nanomolar levels. The hydrophobicity of the side chains and their balance were important structural factors for the inhibition, as is the case for the original Δlac-acetogenins. However, unlike in the case of the original Δlac-acetogenins: (i) the presence of two hydroxy groups is not crucial for the activity, (ii) the level of superoxide production induced by the piperazines is relatively high, (iii) the inhibitory potency for the reverse electron transfer is remarkably weaker than that for the forward event, and (iv) the piperazines efficiently suppressed the specific binding of a photoaffinity probe of natural-type acetogenins ([125I]TDA) to the ND1 subunit. It is therefore concluded that the action mechanism of the piperazine series differs from that of the original Δlac-acetogenins. Photoaffinity labeling study using a newly synthesized photoreactive piperazine ([125I]AFP) revealed that this compound binds to the 49 kDa subunit and an unidentified subunit, not ND1, with a frequency of about 1:3. A variety of traditional complex I inhibitors as well as Δlac-acetogenins suppressed the specific binding of [125I]AFP to the subunits. The apparent competitive behavior of inhibitors that seem to bind to different sites may be due to structural changes at the binding site, rather than occupying the same site. The meaning of the occurrence of diverse inhibitors exhibiting different mechanisms of action is discussed in the light of the functionality of the membrane arm of complex I. PMID:18781777

  14. Synthesis and antioxidant activity of some 1-aryl/aralkyl piperazine derivatives with xanthine moiety at N4

    PubMed Central

    Andonova, Lily; Zheleva-Dimitrova, Dimitrina; Georgieva, Maya; Zlatkov, Alexander

    2014-01-01

    Piperazine nucleus is one of the most important heterocyclic systems exhibiting remarkable pharmacological activities. Thus, in the current study six new aryl/aralkyl substituted piperazine derivatives, containing methylxanthine moiety were synthesized and their structures were confirmed by IR and 1H NMR analysis. All compounds were in vitro screened for their activity as antioxidants using DPPH (2,2′-Diphenyl-1-picrylhydrazyl), ABTS (2,2′-azinobis-(3-ethylbenzo thiazine-6-sulfonic acid)) and FRAP (ferric reducing/antioxidant power) methods. The antioxidant activity of the studied compounds against lipid peroxidation was also measured. The highest antioxidant activity was demonstrated by compound 3c. It is obvious that the presence of a hydroxyl group in the structure is essential for the antioxidant properties and should be taken into consideration in further design of structures with potential antioxidant properties. PMID:26019603

  15. DFT Study of Solvent Effects on Conformational Equilibria and Vibrational Spectra of 4-(1-PYRROLIDINYL)PIPERAZINE

    NASA Astrophysics Data System (ADS)

    Baglayan, O.; Kesan, G.; Parlak, C.; Senyel, M.

    2012-06-01

    The optimized structural parameters (bond lengths, bond and dihedral angles), conformational equilibria and normal mode frequencies and corresponding vibrational assignments of 4-(1-Pyrrolidinyl)piperazine (4-pypp) have been examined by means of B3LYP hybrid density functional theory (DFT) method with 6-31++G(d,p) basis set. Furthermore, reliable vibrational assignments have made on the basis of potential energy distribution (PED) calculated and the thermodynamics functions, highest occupied and lowest unoccupied molecular orbitals (HOMO and LUMO) of 4-pypp (C_8H17N_3) have been predicted. Calculations are employed for different conformations of 4-pypp both in gas phase and in solution. Solvent effects are investigated using chloroform and dimethylsulfoxide. Results from the theoretical values are showed that the structural parameters, mole fractions of stable conformers, vibrational frequencies, IR intensities and Raman activities of 4-pypp are solvent dependent. {Keywords}: 4-(1-Pyrrolidinyl)piperazine, vibrational spectra, solvent effect, DFT.

  16. Substituted piperazines as nootropic agents: 2- or 3-phenyl derivatives structurally related to the cognition-enhancer DM235.

    PubMed

    Guandalini, Luca; Martino, Maria Vittoria; Di Cesare Mannelli, Lorenzo; Bartolucci, Gianluca; Melani, Fabrizio; Malik, Ruchi; Dei, Silvia; Floriddia, Elisa; Manetti, Dina; Orlandi, Francesca; Teodori, Elisabetta; Ghelardini, Carla; Romanelli, Maria Novella

    2015-04-15

    A series of 2-phenyl- or 3-phenyl piperazines, structurally related to DM235 and DM232, two potent nootropic agents, have been prepared and tested in the mouse passive-avoidance test, to assess their ability to revert scopolamine-induced amnesia. Although the newly synthesized molecules were less potent than the parent compounds, some useful information has been obtained from structure-activity relationships. A small but significant enantioselectivity has been found for the most potent compound 5a. PMID:25813160

  17. Mechanism of action of novel piperazine containing a toxicant against human liver cancer cells

    PubMed Central

    Kanthimathi, MS; Haerian, Batoul Sadat

    2016-01-01

    The purpose of this study was to assess the cytotoxic potential of a novel piperazine derivative (PCC) against human liver cancer cells. SNU-475 and 423 human liver cancer cell lines were used to determine the IC50 of PCC using the standard MTT assay. PCC displayed a strong suppressive effect on liver cancer cells with an IC50 value of 6.98 ± 0.11 µM and 7.76 ± 0.45 µM against SNU-475 and SNU-423 respectively after 24 h of treatment. Significant dipping in the mitochondrial membrane potential and elevation in the released of cytochrome c from the mitochondria indicated the induction of the intrinsic apoptosis pathway by PCC. Activation of this pathway was further evidenced by significant activation of caspase 3/7 and 9. PCC was also shown to activate the extrinsic pathways of apoptosis via activation of caspase-8 which is linked to the suppression of NF-κB translocation to the nucleus. Cell cycle arrest in the G1 phase was confirmed by flow cytometry and up-regulation of glutathione reductase expression was quantified by qPCR. Results of this study suggest that PCC is a potent anti-cancer agent inducing both intrinsic and extrinsic pathways of apoptosis in liver cancer cell lines. PMID:27019772

  18. Dimethyl phenyl piperazine iodide (DMPP) induces glioma regression by inhibiting angiogenesis.

    PubMed

    He, Yan-Qing; Li, Yan; Wang, Xiao-Yu; He, Xiao-Dong; Jun, Li; Chuai, Manli; Lee, Kenneth Ka Ho; Wang, Ju; Wang, Li-Jing; Yang, Xuesong

    2014-01-15

    1,1-Dimethyl-4-phenyl piperazine iodide (DMPP) is a synthetic nicotinic acetylcholine receptor (nAChR) agonist that could reduce airway inflammation. In this study, we demonstrated that DMPP could dramatically inhibit glioma size maintained on the chick embryonic chorioallantoic membrane (CAM). We first performed MTT and BrdU incorporation experiments on U87 glioma cells in vitro to understand the mechanism involved. We established that DMPP did not significantly affect U87 cell proliferation and survival. We speculated that DMPP directly caused the tumor to regress by affecting the vasculature in and around the implanted tumor on our chick CAM model. Hence, we conducted detailed analysis of DMPP's inhibitory effects on angiogenesis. Three vasculogenesis and angiogenesis in vivo models were used in the study which included (1) early chick blood islands formation, (2) chick yolk-sac membrane (YSW) and (3) CAM models. The results revealed that DMPP directly suppressed all developmental stages involved in vasculogenesis and angiogenesis - possibly by acting through Ang-1 and HIF-2α signaling. In sum, our results show that DMPP could induce glioma regression grown on CAM by inhibiting vasculogenesis and angiogenesis. PMID:24162003

  19. Novel piperazine core compound induces death in human liver cancer cells: possible pharmacological properties

    PubMed Central

    Samie, Nima; Muniandy, Sekaran; Kanthimathi, M. S.; Haerian, Batoul Sadat; Raja Azudin, Raja Elina

    2016-01-01

    The current study evaluates the cytotoxic mechanism of a novel piperazine derivate designated as PCC against human liver cancer cells. In this context, human liver cancer cell lines, SNU-475 and 243, human monocyte/macrophage cell line, CRL-9855, and human B lymphocyte cell line, CCL-156, were used to determine the IC50 of PCC using the standard MTT assay. PCC displayed a strong suppressive effect on SNU-475 and SNU-423 cells with an IC50 value of 6.98 ± 0.11 μg/ml and 7.76 ± 0.45 μg/ml respectively, after 24 h of treatment. Significant dipping in the mitochondrial membrane potential and elevation in the released of cytochrome c from the mitochondria indicated the induction of the intrinsic apoptosis pathway by PCC. Activation of this pathway was further evidenced by significant activation of caspase 3/7 and 9. PCC was also shown to activate the extrinsic pathways of apoptosis via activation of caspase-8 which is linked to the suppression of NF-ƙB translocation to the nucleus. Cell cycle arrest in the G1 phase was confirmed by flow cytometry and up-regulation of glutathione reductase expression was quantified by qPCR. This study suggests that PCC is a simultaneous inducer of intrinsic and extrinsic pathways of apoptosis in liver cancer cell lines. PMID:27072064

  20. Quantitative determination of some pharmaceutical piperazine derivatives through complexation with iron(III) chloride.

    PubMed

    Abou-Attia, F M; Issa, Y M; Abdel-Gawad, F M; Abdel-Hamid, S M

    2003-08-01

    A simple, accurate and sensitive spectrophotometric method has been developed for the determination of three pharmaceutical piperazine derivatives, namely ketoconazole (KC), trimetazidine hydrochloride (TMH) and piribedil (PD). This method is based on the formation of yellow orange complexes between iron(III) chloride and the investigated drugs. The optimum reaction conditions, spectral characteristics, conditional stability constants and composition of the water soluble complexes have been established. The method permits the determination of KC, TMH and PD over a concentration range 1-15, 1-12 and 1-12 microg ml(-1), respectively. Sandell sensitivity is found to be 0.016, 0.013 and 0.013 microg cm(-2) for KC, TMH and PD, respectively. The method was sensitive, simple, reproducible and accurate within +/-1.5%. The method is applicable to the assay of the three drugs under investigation in different dosage forms and the results are in good agreement with those obtained by the official methods (USP and JP). PMID:12875888

  1. A chemical genetic approach identifies piperazine antipsychotics as promoters of CNS neurite growth on inhibitory substrates

    PubMed Central

    Johnstone, AL; Reierson, GW; Smith, RP; Goldberg, JL; Lemmon, VP; Bixby, JL

    2012-01-01

    Injury to the central nervous system (CNS) can result in lifelong loss of function due in part to the regenerative failure of CNS neurons. Inhibitory proteins derived from myelin and the astroglial scar are major barriers for the successful regeneration of injured CNS neurons. Previously, we described the identification of a novel compound, F05, which promotes neurite growth from neurons challenged with inhibitory substrates in vitro, and promotes axonal regeneration in vivo (Usher et al., 2010). To identify additional regeneration-promoting compounds, we used F05-induced gene expression profiles to query the Broad Institute Connectivity Map, a gene expression database of cells treated with >1,300 compounds. Despite no shared chemical similarity, F05-induced changes in gene expression were remarkably similar to those seen with a group of piperazine phenothiazine antipsychotics (PhAPs). In contrast to antipsychotics of other structural classes, PhAPs promoted neurite growth of CNS neurons challenged with two different glial derived inhibitory substrates. Our pharmacological studies suggest a mechanism whereby PhAPs promote growth through antagonism of calmodulin signaling, independent of dopamine receptor antagonism. These findings shed light on mechanisms underlying neurite-inhibitory signaling, and suggest that clinically approved antipsychotic compounds may be repurposed for use in CNS injured patients. PMID:22561309

  2. Novel piperazine core compound induces death in human liver cancer cells: possible pharmacological properties.

    PubMed

    Samie, Nima; Muniandy, Sekaran; Kanthimathi, M S; Haerian, Batoul Sadat; Raja Azudin, Raja Elina

    2016-01-01

    The current study evaluates the cytotoxic mechanism of a novel piperazine derivate designated as PCC against human liver cancer cells. In this context, human liver cancer cell lines, SNU-475 and 243, human monocyte/macrophage cell line, CRL-9855, and human B lymphocyte cell line, CCL-156, were used to determine the IC50 of PCC using the standard MTT assay. PCC displayed a strong suppressive effect on SNU-475 and SNU-423 cells with an IC50 value of 6.98 ± 0.11 μg/ml and 7.76 ± 0.45 μg/ml respectively, after 24 h of treatment. Significant dipping in the mitochondrial membrane potential and elevation in the released of cytochrome c from the mitochondria indicated the induction of the intrinsic apoptosis pathway by PCC. Activation of this pathway was further evidenced by significant activation of caspase 3/7 and 9. PCC was also shown to activate the extrinsic pathways of apoptosis via activation of caspase-8 which is linked to the suppression of NF-ƙB translocation to the nucleus. Cell cycle arrest in the G1 phase was confirmed by flow cytometry and up-regulation of glutathione reductase expression was quantified by qPCR. This study suggests that PCC is a simultaneous inducer of intrinsic and extrinsic pathways of apoptosis in liver cancer cell lines. PMID:27072064

  3. Quantum chemical studies on solvents for post-combustion carbon dioxide capture: calculation of pKa and carbamate stability of disubstituted piperazines.

    PubMed

    Gangarapu, Satesh; Wierda, Gerben J; Marcelis, Antonius T M; Zuilhof, Han

    2014-06-23

    Piperazine is a widely studied solvent for post-combustion carbon dioxide capture. To investigate the possibilities of further improving this process, the electronic and steric effects of -CH(3), -CH(2)F, -CH(2)OH, -CH(2)NH(2), -COCH3 , and -CN groups of 2,5-disubstituted piperazines on the pKa and carbamate stability towards hydrolysis are investigated by quantum chemical methods. For the calculations, B3LYP, M11L, and spin-component-scaled MP2 (SCS-MP2) methods are used and coupled with the SMD solvation model. The experimental pK(a) values of piperazine, 2-methylpiperazine, and 2,5-dimethylpiperazine agree well with the calculated values. The present study indicates that substitution of -CH(3), -CH(2) NH(2), and -CH(2) OH groups on the 2- and 5-positions of piperazine has a positive impact on the CO(2) absorption capacity by reducing the carbamate stability towards hydrolysis. Furthermore, their higher boiling points, relative to piperazine itself, will lead to a reduction of volatility-related losses. PMID:24782140

  4. Piperazine-derived designer drug 1-(3-chlorophenyl)piperazine (mCPP): GC-MS studies on its metabolism and its toxicological detection in rat urine including analytical differentiation from its precursor drugs trazodone and nefazodone.

    PubMed

    Staack, Roland F; Maurer, Hans H

    2003-01-01

    Studies on the metabolism and the toxicological analysis of the piperazine-derived designer drug 1-(3-chlorophenyl)piperazine (mCPP) in rat urine using gas chromatography-mass spectrometry (GC-MS) are described. mCPP was extensively metabolized, mainly by hydroxylation of the aromatic ring and by degradation of the piperazine moiety to the following metabolites: two hydroxy-mCPP isomers, N-(3-chlorophenyl)ethylenediamine, 3-chloroaniline, and two hydroxy-3-chloroaniline isomers. The hydroxy-mCPP metabolites were partially excreted as the corresponding glucuronides and/or sulfates, and the aniline derivatives were partially acetylated to N-acetyl-hydroxy-3-chloroaniline isomers and N-acetyl-3-chloroaniline. Our systematic toxicological analysis (STA) procedure using full-scan GC-MS after acid hydrolysis, liquid-liquid extraction, and microwave-assisted acetylation allowed the detection of mCPP and its previously mentioned metabolites in rat urine after single administration of a dose calculated from the doses commonly taken by drug users. The hydroxy-mCPP metabolites should be used as target analytes being the major metabolites of mCPP. Assuming similar metabolism, our STA procedure should be suitable for detection of an intake of mCPP in human urine. Furthermore, possibilities for differentiating an intake of mCPP from that of its precursor drugs trazodone or nefazodone, two common antidepressants, are described. Within the context of these studies, N-(3-chlorophenyl)ethylenediamine was identified as a new metabolite of these two antidepressants. PMID:14670134

  5. Determination of piperazine-type stimulants in human urine by means of microextraction in packed sorbent and high performance liquid chromatography-diode array detection.

    PubMed

    Moreno, I E D; da Fonseca, B M; Barroso, M; Costa, S; Queiroz, J A; Gallardo, E

    2012-03-01

    A method using microextraction by packed sorbent (MEPS) and high performance liquid chromatography-diode array detection (HPLC-DAD) is described for the determination of piperazine-type stimulants in human urine. The studied compounds were 1-benzylpiperazine (BZP), 1-(3-trifluoromethylphenyl) piperazine (TFMPP), 1-(3-chlorophenyl) piperazine (mCPP) and 1-(4-methoxyphenyl) piperazine (MeOPP); 1-(2-chlorophenyl)-piperazine (oCPP) was used as internal standard (IS). The factors which might influence the extraction were screened previously using the fractional factorial design approach, and none of them influenced significantly the process. The procedure was linear for concentrations ranging from 0.1 (lower limit of quantitation--LLOQ) to 5 ?g/mL, with determination coefficients (R(2)) higher than 0.99 for all analytes in all runs. The limits of detection were 0.1 ?g/mL for BZP and TFMPP, while for MeOPP and mCPP 0.05 ?g/mL was obtained. Intra- and interday precision ranged from 1 to 14%, and accuracy was within a 15% interval for all analytes, fulfilling the criteria normally accepted in bioanalytical method validation. Under the optimized conditions, extraction efficiency was higher than 80% for all analytes, except BZP (50%). MEPS showed to be a rapid (<2 min) and simple procedure for the determination of piperazine-type stimulants in human urine, allowing reducing the handling time and costs usually associated to this type of analysis. Furthermore, the fact that only 0.1 mL of sample is required make this method a valuable and powerful tool for drug monitoring in human urine in situations where those compounds are involved, for instance in forensic scenarios. PMID:22221903

  6. Control of water molecule aggregations in copper 1,4-cyclohexanedicarboxylate coordination polymers containing pyridyl-piperazine type ligands

    NASA Astrophysics Data System (ADS)

    Qiblawi, Sultan H.; LaDuca, Robert L.

    2014-01-01

    A series of layered divalent copper coordination polymers containing 1,4-cyclohexanedicarboxylate and long-spanning pyridyl-piperazine type ligands exhibits greatly different co-crystallized water molecule aggregations depending on the specific ligands used. Both [Cu(t-14cdc)(4-bpmp)]n (1, t-14cdc = trans-1,4-cyclohexanedicarboxylate, 4-bpmp = bis(4-pyridylmethyl)piperazine) and {[Cu(t-14cdc)(4-bpfp)(H2O)2]·6H2O}n (2, 4-bpfp = bis(4-pyridylformyl)piperazine) possess 2D (4,4) coordination polymer grids. However 1 lacks any co-crystallized water and has pinched grid apertures, while 2 manifests infinite water tapes with T6(2)4(2) classification and rectangular grid apertures. {[Cu2(c-14cdc)2(4-bpmp)]·2H2O}n (3, c-14cdc = cis-1,4-cyclohexanedicarboxylate) has [Cu2(c-14cdc)]2 ribbons with paddlewheel dimeric units linked into 2D slabs by 4-bpmp tethers, along with isolated water molecule pairs. In contrast, {[Cu2(c-14cdc)2(4-bpfp)]·10H2O}n (4) shows a very similar underlying coordination polymer topology but entrains unique decameric water molecule clusters. The minor product {[Cu2(c-14cdcH)2(t-1,4-cdc)(4-bpfp)2(H2O)2]·2H2O}n (5) was isolated along with 4; this compound underwent some in situ cis to trans cyclohexane-dicarboxylate ligand isomerization and exhibits a ladder polymer motif.

  7. Synthesis of New N,N’-Bis(5-arylidene-4-oxo-4,5-dihydrothiazolin-2-yl)piperazine Derivatives Under Microwave Irradiation and Preliminary Biological Evaluation

    PubMed Central

    Coulibaly, Wacothon Karime; Paquin, Ludovic; Bénié, Anoubilé; Bekro, Yves-Alain; Durieux, Emilie; Meijer, Laurent; Le Guével, Rémy; Corlu, Anne; Bazureau, Jean-Pierre

    2012-01-01

    New N,N’-bis(5-arylidene-4-oxo-4,5-dihydrothiazoline-2-yl)diamine derivatives 5 were prepared in two steps from rhodanine and piperazine, or 1,4-bis(3-amino-propyl)piperazine, under microwave reaction conditions with retention of configuration. Some of these compounds were tested for in vitro antiproliferative activities and for their kinase inhibitory potencies towards six kinases (CDK5/p25, GSK3α/β, DYRK1A, DYRK2, CLK1, and CLK2). The compound 5d showed nanomolar activity towards DYRK1A kinase (IC50 = 0.041 μM). PMID:23264934

  8. Synthesis and an angiolytic role of novel piperazine-benzothiazole analogues on neovascularization, a chief tumoral parameter in neoplastic development.

    PubMed

    Al-Ghorbani, Mohammed; Pavankumar, G S; Naveen, P; Thirusangu, Prabhu; Prabhakar, B T; Khanum, Shaukath Ara

    2016-04-01

    A novel series of benzoic acid N'-[2-(4-benzothiazol-2-yl-piperazin-1-yl)-acetyl]-hydrazides 6a-j were synthesized and characterized by IR, (1)H, (13)C NMR, elemental and mass spectral analyses. The in-vitro cytotoxicity and cell viability assay of the synthesized compounds 6a-j were evaluated against Dalton's lymphoma ascites (DLA) cells. Our results showed that compound 6c with a bromo group on phenyl ring has showed promising antiproliferative efficacy. Further investigation of compound 6c on in-vivo treatment model depicts the increased tumor suppression through inhibition of angiogenesis. PMID:26918263

  9. Proton-transfer supramolecular salts of D-/L-tartaric acid and 1-(2-Pyrimidyl)piperazine

    NASA Astrophysics Data System (ADS)

    Ding, Xue-Hua; Li, Yong-Hua; Wang, Shi; Huang, Wei

    2014-03-01

    Ionic supramolecular salts 1 and 2 were prepared by single-proton transfer reactions between 1-(2-pyrimidyl)piperazine and D-/L-tartaric acid. An interesting feature in the tartrate is the head-to-tail arrangement and very wide range of anionic substructures observed through hydrogen-bonding interactions, including ring motifs, infinite double zigzag chain and three-dimensional supramolecular framework. Thermal analysis revealed that salts 1 and 2 undergo an irreversible phase transition at about 158 C, which is ascribed to the loss of water molecule. The temperature- and frequency-dependent dielectric constants in 2 suggested a low-frequency thermal fluctuation above 100 C.

  10. Discovery of 4-(Piperazin-1-yl)-7H-pyrrolo[2,3-d]pyrimidine Derivatives as Akt Inhibitors.

    PubMed

    Liu, Yang; Yin, Yanzhen; Zhang, Jingya; Nomie, Krystle; Zhang, Liang; Yang, Dezhi; Wang, Michael L; Zhao, Guisen

    2016-05-01

    A series of 4-(piperazin-1-yl)-7H-pyrrolo[2,3-d]pyrimidine derivatives was synthesized and evaluated as Akt inhibitors by optimization of a weak screening lead (1). Typically, compounds 5q and 5t significantly improved the Akt1 inhibitory potency with IC50 values of 18.0 and 21.3 nM, respectively, with desirable antiproliferative effect against the cell lines LNCaP and PC-3. The inhibitors 5q and 5t might serve as lead compounds for further exploration of Akt inhibitors as anticancer agents. PMID:26991997

  11. Dimethyl phenyl piperazine iodide (DMPP) induces glioma regression by inhibiting angiogenesis

    SciTech Connect

    He, Yan-qing; Li, Yan; Wang, Xiao-yu; He, Xiao-dong; Jun, Li; Chuai, Manli; Lee, Kenneth Ka Ho; Wang, Ju; Wang, Li-jing; Yang, Xuesong

    2014-01-15

    1,1-Dimethyl-4-phenyl piperazine iodide (DMPP) is a synthetic nicotinic acetylcholine receptor (nAChR) agonist that could reduce airway inflammation. In this study, we demonstrated that DMPP could dramatically inhibit glioma size maintained on the chick embryonic chorioallantoic membrane (CAM). We first performed MTT and BrdU incorporation experiments on U87 glioma cells in vitro to understand the mechanism involved. We established that DMPP did not significantly affect U87 cell proliferation and survival. We speculated that DMPP directly caused the tumor to regress by affecting the vasculature in and around the implanted tumor on our chick CAM model. Hence, we conducted detailed analysis of DMPP's inhibitory effects on angiogenesis. Three vasculogenesis and angiogenesis in vivo models were used in the study which included (1) early chick blood islands formation, (2) chick yolk-sac membrane (YSW) and (3) CAM models. The results revealed that DMPP directly suppressed all developmental stages involved in vasculogenesis and angiogenesis – possibly by acting through Ang-1 and HIF-2α signaling. In sum, our results show that DMPP could induce glioma regression grown on CAM by inhibiting vasculogenesis and angiogenesis. - Highlights: ●We demonstrated that DMPP inhibited the growth of glioma cells on chick CAM. ●DMPP did not significantly affect the proliferation and survival of U87 cells. ●We revealed that DMPP suppressed vasculogenesis and angiogenesis in chick embryo. ●Angiogenesis in chick CAM was inhibited by DMPP via most probably Ang-1 and HIF-2α. ●DMPP could be potentially developed as an anti-tumor drug in the future.

  12. Novel piperazine derivative PMS1339 exhibits tri-functional properties and cognitive improvement in mice.

    PubMed

    Miezan Ezoulin, Jean Marc; Shao, Bi-Yun; Xia, Zheng; Xie, Qiong; Li, Juan; Cui, Yong-Yao; Wang, Hao; Dong, Chang-Zhi; Zhao, Yan-Xing; Massicot, France; Qiu, Zhui-Bai; Heymans, Françoise; Chen, Hong-Zhuan

    2009-11-01

    Amyloid-beta-induced neuroinflammation plays a central role in the extensive loss of cholinergic neurons and cognitive decline in Alzheimer's disease. The acetylcholinesterase (AChE) inhibitors are the first class of drugs used to enhance surviving cholinergic activities. However, their limited effectiveness following long-term treatment raises a need for new multi-target therapies. We report herein a novel piperazine derivative compound PMS1339 possesses multifunctional properties including anti-platelet-activating factor, AChE inhibition, Abeta aggregation inhibition and cognitive improvement. PMS1339 could significantly inhibit both mice brain AChE (IC50=4.41+/-0.63 microM) and sera butyrylcholinesterase (BuChE, IC50=1.09+/-0.20 microM). PMS1339 was also found to inhibit neuronal AChE secreted by SH-SY5Y cell line (IC50=17.95+/-2.31 microM). Enzyme kinetics experiments performed on electric eel AChE indicated that PMS1339 acts as a mixed type competitive AChE inhibitor. Molecular docking studies using the X-ray crystal structure of AChE from Torpedo californica elucidated the interactions between PMS1339 and AChE: PMS1339 is well buried inside the active-site gorge of AChE interacting with Trp84 at the bottom, Tyr121 halfway down and Trp279 at the peripheral anionic site (PAS). Thioflavin T-based fluorimetric assay revealed the ability of PMS1339 to inhibit AChE-induced Abeta aggregation. In-vivo study indicated PMS1339 (1 mg/kg i.p.) reversed scopolamine-induced memory impairment in mice. Overall, these findings indicated that PMS1339 exhibits tri-functional properties in vitro and cognitive improvement in vivo, and revealed the emergence of a multi-target-directed ligand to tackle the determinants of Alzheimer's disease. PMID:19460190

  13. Synthesis of linear piperazine/polyether functional polysiloxane and its modification of surface properties on cotton fabrics.

    PubMed

    Jin, Yufen; Pu, Qun; Fan, Hong

    2015-04-15

    In this work, silicone softener (PTSO-PEG) was synthesized, with piperazine terminated polydimethylsiloxane (PTSO) and epoxy terminated polyethylene glycol (EPEG) as raw materials. Chemical structure of PTSO-PEG was characterized by (1)H NMR, FTIR, GPC, and TGA. Its application on cotton fabrics was studied. Morphologies of silicone modified surfaces on cotton fabrics and silicon wafers were investigated by SEM and AFM, respectively. The morphology images indicated that PTSO-PEG treated surface was macroscopically smooth and microscopically rough. Performance properties of silicone treated cotton fabrics, including hydrophilicity, whiteness, and softness, were tested. The results showed that PTSO-PEG treated cotton fabrics expressed better whiteness and hydrophilicity than traditional amino silicone treated sample. The piperazine and hydrophilic polyether groups on PTSO-PEG molecules disturbed the continuous and orderly arrangement of Si-CH3 groups, giving the cotton a hydrophilic and rough surface. This work provided a cost-effective and environmental method to synthesize and apply high performance silicone softener. PMID:25812599

  14. Preparation, spectral and biological investigation of formaldehyde-based ligand containing piperazine moiety and its various polymer metal complexes

    NASA Astrophysics Data System (ADS)

    Khan, Shamim Ahmad; Nishat, Nahid; Parveen, Shadma; Rasool, Raza

    2011-10-01

    A novel tetradentate salicylic acid-formaldehyde ligand containing piperazine moiety (SFP) was synthesized by condensation of salicylic acid, formaldehyde and piperazine in presence of base catalyst, which was subjected for the preparation of coordination polymers with metal ions like manganese(II), cobalt(II), copper(II), nickel(II) and zinc(II). All the synthesized polymeric compounds were characterized by elemental analysis, IR, 1H NMR and electronic spectral studies. The thermal stability was determined by thermogravimetric analysis and thermal data revealed that all the polymer metal complexes show good thermal stability than their parent ligand. Electronic spectral data and magnetic moment values revealed that polymer metal complexes of Mn(II), Co(II) and Ni(II) show an octahedral geometry while Cu(II) and Zn(II) show distorted octahedral and tetrahedral geometry respectively. The antimicrobial screening of the ligand and coordination polymers was done by using Agar well diffusion method against various bacteria and fungi. It was evident from the data that antibacterial and antifungal activity increased on chelation and all the polymer metal complexes show excellent antimicrobial activity than their parent ligand.

  15. Fire self-extinguishing cotton fabric: development of piperazine derivatives containing phosphorous-sulfur-nitrogen and their flame retardant and thermal behaviors

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Recent studies have shown interest in flame retardants containing phosphorus, nitrogen and sulfur a combination small molecule with a promising new approach in preparing an important class of flame retardant materials. Tetraethyl piperazine-1,4-diyldiphosphonate (TEPP) and O,O,O',O'-tetramethyl pip...

  16. Bis[N-(2-hy-droxy-eth-yl)-N-iso-propyl-dithio-carbamato-?(2) S,S'](piperazine-?N)cadmium: crystal structure and Hirshfeld surface analysis.

    PubMed

    Safbri, Siti Artikah M; Halim, Siti Nadiah Abdul; Jotani, Mukesh M; Tiekink, Edward R T

    2016-02-01

    The title compound, [Cd(C6H12NOS2)2(C4H10N2)], features a distorted square-pyramidal coordination geometry about the central Cd(II) atom. The di-thio-carbamate ligands are chelating, forming similar Cd-S bond lengths and define the approximate basal plane. One of the N atoms of the piperazine mol-ecule, which adopts a chair conformation, occupies the apical site. In the crystal, supra-molecular layers propagating in the ac plane are formed via hy-droxy-O-H?O(hy-droxy), hy-droxy-O-H?N(terminal-piperazine) and coordinated-piperazine-N-H?O(hy-droxy) hydrogen bonds; the layers also feature methine-C-H?S inter-actions and S?S [3.3714?(10)?] short contacts. The layers stack along the b-axis direction with very weak terminal-piperazine-N-H?O(hy-droxy) inter-actions between them. An evaluation of the Hirshfeld surfaces confirms the importance of inter-molecular inter-actions involving oxygen and sulfur atoms. PMID:26958378

  17. Anti-hypertensive property of a nickel-piperazine/NO donor in spontaneously hypertensive rats.

    PubMed

    Monti, Martina; Ciccone, Valerio; Pacini, Aurora; Roggeri, Riccardo; Monzani, Enrico; Casella, Luigi; Morbidelli, Lucia

    2016-05-01

    The nickel-piperazine/NO donor compound, Ni(PipNONO)Cl, belonging to the family of compounds labelled as "metal-nonoates", due to its promising vasodilating activity, has been considered as a potential drug candidate in anti-hypertensive therapy. Drug efficacy has been evaluated in spontaneously hypertensive rats (SHR) in comparison with normotensive animals (C57BL/6 mice and WKY rats). In normotensive animals the metal-nonoate maintained blood pressure at basal level both following acute administration and after 30 days of treatment. In SHR, Ni(PipNONO)Cl reduced blood pressure in the dose range of 3-10mg/kg. When compared with a commercial NONOate, DETA/NO, used at the same doses, Ni(PipNONO)Cl was more active in reducing blood pressure in SHR than DETA/NO in the first two weeks, while the effect of the two molecules was similar in the third and fourth week. The degradation and control compound Ni(Pip)Cl2 had no effect on blood pressure and heart rate in same animal models. Remarkably, the blood pressure reduction induced by the new NO-donor Ni(PipNONO)Cl does not evoke changes in the heart rate and tolerance. Considering the mechanisms of vascular protection, 30 days of administration of Ni(PipNONO)Cl improved endothelial function in SHR by upregulating endothelial NO synthase (eNOS) through increased eNOS protein levels and downregulated Caveolin-1 (Cav-1), and by increasing superoxide dismutase 1 (SOD1) protein level in aortae. In cultured endothelial cells Ni(PipNONO)Cl restored the cell functions (cytoskeletal protein expression, migration and proliferation) altered by the inflammatory mediator interleukin-1β (IL-1β), impairing the endothelial to mesenchimal transition. In conclusion, Ni(PipNONO)Cl maintained unaltered blood pressure in normotensive mice and rats, and it exerted anti-hypertensive effect in SHR through the restoration of vascular endothelial protective functions. PMID:27063892

  18. Temperature-dependence of the influence of the position-2-methyl group on the structure-directing effect of piperazine in the synthesis of open-framework aluminophosphates

    NASA Astrophysics Data System (ADS)

    Huang, Pai; Xu, Jun; Qi, Guodong; Deng, Feng; Xu, Ruren; Yan, Wenfu

    2016-02-01

    The temperature-dependence of the influence of the position-2-methyl group on the structure-directing effect of piperazine in the synthesis of open-framework aluminophosphates was investigated. By heating the initial mixture with the composition of Al2O3:1.5 P2O5:R:125 H2O at 160 °C, where R is the structure-directing agent of 2-methylpiperazine or piperazine, layered aluminophosphates APMeP150 (R = 2-methylpiperazine) and AP2pip (R = piperazine) were obtained. When the same initial reaction mixture was heated at 190 °C, layered aluminophosphates APMeP200 (R = 2-methylpiperazine) and AP2pip (R = piperazine) were crystallized. APMeP200 and AP2pip have the same inorganic sheet topology. We investigated the crystallization processes of the four open-framework aluminophosphates and found that increasing the heating temperature slowed the crystallization of the initial mixtures. The non-bonding interactions between the inorganic layers of the four open-framework aluminophosphates and the experimental or theoretically generated structure-directing agents were calculated. The possible starting points of the crystallization of the four open-framework aluminophosphates were analysed and compared. The temperature-dependence of the influence of the position-2-methyl group on the structure-directing effect of piperazine revealed that the structure-directing effect, the most important factor in the synthesis of zeolites and related open-framework materials, is determined by multiple factors. The structural parameters of the same compound can be affected by the synthesis conditions.

  19. Temperature-dependence of the influence of the position-2-methyl group on the structure-directing effect of piperazine in the synthesis of open-framework aluminophosphates

    PubMed Central

    Huang, Pai; Xu, Jun; Qi, Guodong; Deng, Feng; Xu, Ruren; Yan, Wenfu

    2016-01-01

    The temperature-dependence of the influence of the position-2-methyl group on the structure-directing effect of piperazine in the synthesis of open-framework aluminophosphates was investigated. By heating the initial mixture with the composition of Al2O3:1.5 P2O5:R:125 H2O at 160 °C, where R is the structure-directing agent of 2-methylpiperazine or piperazine, layered aluminophosphates APMeP150 (R = 2-methylpiperazine) and AP2pip (R = piperazine) were obtained. When the same initial reaction mixture was heated at 190 °C, layered aluminophosphates APMeP200 (R = 2-methylpiperazine) and AP2pip (R = piperazine) were crystallized. APMeP200 and AP2pip have the same inorganic sheet topology. We investigated the crystallization processes of the four open-framework aluminophosphates and found that increasing the heating temperature slowed the crystallization of the initial mixtures. The non-bonding interactions between the inorganic layers of the four open-framework aluminophosphates and the experimental or theoretically generated structure-directing agents were calculated. The possible starting points of the crystallization of the four open-framework aluminophosphates were analysed and compared. The temperature-dependence of the influence of the position-2-methyl group on the structure-directing effect of piperazine revealed that the structure-directing effect, the most important factor in the synthesis of zeolites and related open-framework materials, is determined by multiple factors. The structural parameters of the same compound can be affected by the synthesis conditions. PMID:26912387

  20. Influence of silica nanospheres on the separation performance of thin film composite poly(piperazine-amide) nanofiltration membranes

    NASA Astrophysics Data System (ADS)

    Li, Qiang; Wang, Yihua; Song, Jie; Guan, Yipeng; Yu, Hui; Pan, Xianhui; Wu, Feiyang; Zhang, Meng

    2015-01-01

    A novel thin film nanocomposite nanofiltration (TFNN) membrane was fabricated by introducing silica nanospheres (ca. 235 ± 11 nm) in the interfacial polymerization process of trimesoyl chloride (TMC) and piperazine (PIP) over polysulfone (PS) support for investigating the effect of silica nanofiller on the separation performance (i.e., permeability and salt rejection) of conventional thin film composite poly(piperazine-amide) nanofiltration (TFCN) membrane. The physicochemical characterization results show that all of the silica nanospheres are uniformly embedded on the surface of TFNN membrane. The introduction of silica nanospheres improves the hydrophilicity of the TFCN membrane and also causes its isoelectric point shift to a lower pH value. Moreover, the active poly(piperazine-amide) barrier layer of TFNN membrane (60.8 ± 2.3 nm) is thinner than that of the pristine TFCN membrane (72.1 ± 2.5 nm) as a control sample. The separation performance tests reveal that the addition of silica nanospheres can obviously elevate the salt rejection of the pristine TFCN membrane from 87.58 ± 0.15 to 94.81 ± 0.17% under 2000 ppm of MgSO4 solution and 0.5 MPa operating pressure, simultaneously accompanied by the increases of permeate flux from 19.36 ± 0.75 to 22.65 ± 0.68 L/m2 h. Additionally, compared with pristine TFCN membrane, the fabricated TFNN membrane has relatively low salt rejection (43.20 ± 0.27%) in 0.5 MPa operating pressure for 500 ppm of NaCl aqueous solution, which demonstrates that the introduction of silica nanospheres can dramatically promote the divalent-ionic separation selectivity. Furthermore, the experimental results suggest that the nanocomposite TFNN membrane possesses stable filtration performance in the softening process of MgSO4 aqueous solution. The separation performance improvement should be attributed to the optimizations of microstructures and surface features of active barrier layer of TFNN membrane, caused by the addition of silica nanospheres.

  1. Acemetacin cocrystals and salts: structure solution from powder X-ray data and form selection of the piperazine salt.

    PubMed

    Sanphui, Palash; Bolla, Geetha; Nangia, Ashwini; Chernyshev, Vladimir

    2014-03-01

    Acemetacin (ACM) is a non-steroidal anti-inflammatory drug (NSAID), which causes reduced gastric damage compared with indomethacin. However, acemetacin has a tendency to form a less soluble hydrate in the aqueous medium. We noted difficulties in the preparation of cocrystals and salts of acemetacin by mechanochemical methods, because this drug tends to form a hydrate during any kind of solution-based processing. With the objective to discover a solid form of acemetacin that is stable in the aqueous medium, binary adducts were prepared by the melt method to avoid hydration. The coformers/salt formers reported are pyridine carboxamides [nicotinamide (NAM), isonicotinamide (INA), and picolinamide (PAM)], caprolactam (CPR), p-aminobenzoic acid (PABA), and piperazine (PPZ). The structures of an ACM-INA cocrystal and a binary adduct ACM-PABA were solved using single-crystal X-ray diffraction. Other ACM cocrystals, ACM-PAM and ACM-CPR, and the piperazine salt ACM-PPZ were solved from high-resolution powder X-ray diffraction data. The ACM-INA cocrystal is sustained by the acid⋯pyridine heterosynthon and N-H⋯O catemer hydrogen bonds involving the amide group. The acid⋯amide heterosynthon is present in the ACM-PAM cocrystal, while ACM-CPR contains carboxamide dimers of caprolactam along with acid-carbonyl (ACM) hydrogen bonds. The cocrystals ACM-INA, ACM-PAM and ACM-CPR are three-dimensional isostructural. The carboxyl⋯carboxyl synthon in ACM-PABA posed difficulty in assigning the position of the H atom, which may indicate proton disorder. In terms of stability, the salts were found to be relatively stable in pH 7 buffer medium over 24 h, but the cocrystals dissociated to give ACM hydrate during the same time period. The ACM-PPZ salt and ACM-nicotinamide cocrystal dissolve five times faster than the stable hydrate form, whereas the ACM-PABA adduct has 2.5 times faster dissolution rate. The pharmaceutically acceptable piperazine salt of acemetacin exhibits superior stability, faster dissolution rate and is able to overcome the hydration tendency of the reference drug. PMID:25075330

  2. Acemetacin cocrystals and salts: structure solution from powder X-ray data and form selection of the piperazine salt

    PubMed Central

    Sanphui, Palash; Bolla, Geetha; Nangia, Ashwini; Chernyshev, Vladimir

    2014-01-01

    Acemetacin (ACM) is a non-steroidal anti-inflammatory drug (NSAID), which causes reduced gastric damage compared with indomethacin. However, acemetacin has a tendency to form a less soluble hydrate in the aqueous medium. We noted difficulties in the preparation of cocrystals and salts of acemetacin by mechanochemical methods, because this drug tends to form a hydrate during any kind of solution-based processing. With the objective to discover a solid form of acemetacin that is stable in the aqueous medium, binary adducts were prepared by the melt method to avoid hydration. The coformers/salt formers reported are pyridine carboxamides [nicotinamide (NAM), isonicotinamide (INA), and picolinamide (PAM)], caprolactam (CPR), p-aminobenzoic acid (PABA), and piperazine (PPZ). The structures of an ACM–INA cocrystal and a binary adduct ACM–PABA were solved using single-crystal X-ray diffraction. Other ACM cocrystals, ACM–PAM and ACM–CPR, and the piperazine salt ACM–PPZ were solved from high-resolution powder X-ray diffraction data. The ACM–INA cocrystal is sustained by the acid⋯pyridine heterosynthon and N—H⋯O catemer hydrogen bonds involving the amide group. The acid⋯amide heterosynthon is present in the ACM–PAM cocrystal, while ACM–CPR contains carboxamide dimers of caprolactam along with acid–carbonyl (ACM) hydrogen bonds. The cocrystals ACM–INA, ACM–PAM and ACM–CPR are three-dimensional isostructural. The carboxyl⋯carboxyl synthon in ACM–PABA posed difficulty in assigning the position of the H atom, which may indicate proton disorder. In terms of stability, the salts were found to be relatively stable in pH 7 buffer medium over 24 h, but the cocrystals dissociated to give ACM hydrate during the same time period. The ACM–PPZ salt and ACM–nicotinamide cocrystal dissolve five times faster than the stable hydrate form, whereas the ACM–PABA adduct has 2.5 times faster dissolution rate. The pharmaceutically acceptable piperazine salt of acemetacin exhibits superior stability, faster dissolution rate and is able to overcome the hydration tendency of the reference drug. PMID:25075330

  3. HEAT OF DISSOLUTION MEASUREMENTS FOR CO2 IN MIXED ALKANOLAMINE SOLVENTS

    SciTech Connect

    Vinayak N. Kabadi

    2004-04-27

    The main objective of this project is to measure heat of dissolution of CO{sub 2} in carefully selected mixed alkanolamine solvent systems, and provide such directly measured data that might be used for efficient design of CO{sub 2} capture processes, or for better understanding of thermodynamics of CO{sub 2}-alkanolamine systems. Carbon dioxide is one of the major greenhouse gases, and the need for stabilization of its composition in earth's atmosphere is vital for the future of mankind. Although technologies are available for capture and storage of CO{sub 2}, these technologies are far too expensive for economical commercialization. Reduction of cost would require research for refinement of the technology. For more economical CO{sub 2} capture and regeneration, there is a need for development of more efficient solvent systems. In this project we will extend the thermodynamic database by measuring heat of solution data of CO{sub 2} in mixed solvents made of MEA (monoethanolamine), MDEA (methyldiethanolamine), piperazine, and water. Mixed solvents of different compositions will be selected and in each case data will be measured at temperatures 40 and 80 C and various partial pressures of CO{sub 2}. At the end of the project, observations, conclusions, and recommendations will be derived for the choice of mixed solvents for efficient CO{sub 2} capture with potential for commercialization.

  4. HEAT OF DISSOLUTION MEASUREMENTS FOR CO2 IN MIXED ALKANOLAMINE SOLVENTS

    SciTech Connect

    Vinayak N. Kabadi

    2005-05-23

    The main objective of this project is to measure heat of dissolution of CO{sub 2} in carefully selected mixed alkanolamine solvent systems, and provide such directly measured data that might be used for efficient design of CO{sub 2} capture processes, or for better understanding of thermodynamics of CO{sub 2}-alkanolamine systems. Carbon dioxide is one of the major greenhouse gases, and the need for stabilization of its composition in earth's atmosphere is vital for the future of mankind. Although technologies are available for capture and storage of CO{sub 2}, these technologies are far too expensive for economical commercialization. Reduction of cost would require research for refinement of the technology. For more economical CO{sub 2} capture and regeneration, there is a need for development of more efficient solvent systems. In this project we will extend the thermodynamic database by measuring heat of solution data of CO{sub 2} in mixed solvents made of MEA (monoethanolamine), MDEA (methyldiethanolamine), piperazine, and water. Mixed solvents of different compositions will be selected and in each case data will be measured at temperatures 40 and 80C and various partial pressures of CO{sub 2}. At the end of the project, observations, conclusions, and recommendations will be derived for the choice of mixed solvents for efficient CO{sub 2} capture with potential for commercialization.

  5. Heat of Dissolution Measurements for CO2 in Mixed Alkanolamine Solvents

    SciTech Connect

    Vinayak N. Kabadi

    2006-09-30

    The main objective of this project is to measure heat of dissolution of CO{sub 2} in carefully selected mixed alkanolamine solvent systems, and provide such directly measured data that might be used for efficient design of CO{sub 2} capture processes, or for better understanding of thermodynamics of CO{sub 2}-alkanolamine systems. Carbon dioxide is one of the major greenhouse gases, and the need for stabilization of its composition in earth's atmosphere is vital for the future of mankind. Although technologies are available for capture and storage of CO{sub 2}, these technologies are far too expensive for economical commercialization. Reduction of cost would require research for refinement of the technology. For more economical CO{sub 2} capture and regeneration, there is a need for development of more efficient solvent systems. In this project we will extend the thermodynamic database by measuring heat of solution data of CO{sub 2} in mixed solvents made of MEA (monoethanolamine), MDEA (methyldiethanolamine), piperazine, and water. Mixed solvents of different compositions will be selected and in each case data will be measured at temperatures 40 and 80C and various partial pressures of CO{sub 2}. At the end of the project, observations, conclusions, and recommendations will be derived for the choice of mixed solvents for efficient CO{sub 2} capture with potential for commercialization.

  6. HEAT OF DISSOLUTION MEASUREMENTS FOR CO2 IN MIXED ALKANOLAMINE SOLVENTS

    SciTech Connect

    Vinayak N. Kabadi

    2004-11-15

    The main objective of this project is to measure heat of dissolution of CO{sub 2} in carefully selected mixed alkanolamine solvent systems, and provide such directly measured data that might be used for efficient design of CO{sub 2} capture processes, or for better understanding of thermodynamics of CO{sub 2}-alkanolamine systems. Carbon dioxide is one of the major greenhouse gases, and the need for stabilization of its composition in earth's atmosphere is vital for the future of mankind. Although technologies are available for capture and storage of CO{sub 2}, these technologies are far too expensive for economical commercialization. Reduction of cost would require research for refinement of the technology. For more economical CO{sub 2} capture and regeneration, there is a need for development of more efficient solvent systems. In this project we will extend the thermodynamic database by measuring heat of solution data of CO{sub 2} in mixed solvents made of MEA (monoethanolamine), MDEA (methyldiethanolamine), piperazine, and water. Mixed solvents of different compositions will be selected and in each case data will be measured at temperatures 40 and 80 C and various partial pressures of CO{sub 2}. At the end of the project, observations, conclusions, and recommendations will be derived for the choice of mixed solvents for efficient CO{sub 2} capture with potential for commercialization.

  7. Heat of Dissolution Measurements for CO2 in Mixed Alkanolamine Solvents

    SciTech Connect

    Vinayak N. Kabadi

    2005-12-01

    The main objective of this project is to measure heat of dissolution of CO{sub 2} in carefully selected mixed alkanolamine solvent systems, and provide such directly measured data that might be used for efficient design of CO{sub 2} capture processes, or for better understanding of thermodynamics of CO{sub 2}- alkanolamine systems. Carbon dioxide is one of the major greenhouse gases, and the need for stabilization of its composition in earth's atmosphere is vital for the future of mankind. Although technologies are available for capture and storage of CO{sub 2}, these technologies are far too expensive for economical commercialization. Reduction of cost would require research for refinement of the technology. For more economical CO{sub 2} capture and regeneration, there is a need for development of more efficient solvent systems. In this project we will extend the thermodynamic database by measuring heat of solution data of CO{sub 2} in mixed solvents made of MEA (monoethanolamine), MDEA (methyldiethanolamine), piperazine, and water. Mixed solvents of different compositions will be selected and in each case data will be measured at temperatures 40 and 80C and various partial pressures of CO{sub 2}. At the end of the project, observations, conclusions, and recommendations will be derived for the choice of mixed solvents for efficient CO{sub 2} capture with potential for commercialization.

  8. Carbon capture and sequestration: an exploratory inhalation toxicity assessment of amine-trapping solvents and their degradation products.

    PubMed

    McDonald, Jacob D; Kracko, Dean; Doyle-Eisele, Melanie; Garner, C Edwin; Wegerski, Chris; Senft, Al; Knipping, Eladio; Shaw, Stephanie; Rohr, Annette

    2014-09-16

    Carbon dioxide (CO2) absorption with aqueous amine solvents is a method of carbon capture and sequestration (CCS) from flue gases. One concern is the possible release of amine solvents and degradation products into the atmosphere, warranting evaluation of potential pulmonary effects from inhalation. The CCS amines monoethanolamine (MEA), methyldiethanolamine (MDEA), and piperazine (PIP) underwent oxidative and CO2-mediated degradation for 75 days. C57bl/6N mice were exposed for 7 days by inhalation of 25 ppm neat amine or equivalant concentration in the degraded mixture. The aqueous solutions were nebulized to create the inhalation atmospheres. Pulmonary response was measured by changes in inflammatory cells in bronchoalveolar lavage fluid and cytokine expression in lung tissue. Ames mutagenicity and CHO-K1 micronucleus assays were applied to assess genotoxicity. Chemical analysis of the test atmosphere and liquid revealed complex mixtures, including acids, aldehydes, and other compounds. Exposure to oxidatively degraded MEA increased (p < 0.05) total cells, neutrophils, and lymphocytes compared to control mice and caused inflammatory cytokine expression (statistical increase at p < 0.05). MEA and CO2-degraded MEA were the only atmospheres to show statistical (p < 0.05) increase in oxidative stress. CO2 degradation resulted in a different composition, less degradation, and lower observed toxicity (less magnitude and number of effects) with no genotoxicity. Overall, oxidative degradation of the amines studied resulted in enhanced toxicity (increased magnitude and number of effects) compared to the neat chemicals. PMID:25167095

  9. Heat of Dissolution Measurements for CO2 in Mixed Alkanolamine Solvents

    SciTech Connect

    Vinayak N. Kabadi

    2007-03-31

    The main objective of this project is to measure heat of dissolution of CO{sub 2} in carefully selected mixed alkanolamine solvent systems, and provide such directly measured data that might be used for efficient design of CO{sub 2} capture processes, or for better understanding of thermodynamics of CO{sub 2}- alkanolamine systems. Carbon dioxide is one of the major greenhouse gases, and the need for stabilization of its composition in earth's atmosphere is vital for the future of mankind. Although technologies are available for capture and storage of CO{sub 2}, these technologies are far too expensive for economical commercialization. Reduction of cost would require research for refinement of the technology. For more economical CO{sub 2} capture and regeneration, there is a need for development of more efficient solvent systems. In this project we will extend the thermodynamic database by measuring heat of solution data of CO{sub 2} in mixed solvents made of MEA (monoethanolamine), MDEA (methyldiethanolamine), piperazine, and water. Mixed solvents of different compositions will be selected and in each case data will be measured at temperatures 40 and 80C and various partial pressures of CO{sub 2}. At the end of the project, observations, conclusions, and recommendations will be derived for the choice of mixed solvents for efficient CO{sub 2} capture with potential for commercialization.

  10. Heat of Dissolution Measurements for CO2 in Mixed Alkanolamine Solvents

    SciTech Connect

    Vinayak N. Kabadi

    2006-05-29

    The main objective of this project is to measure heat of dissolution of CO{sub 2} in carefully selected mixed alkanolamine solvent systems, and provide such directly measured data that might be used for efficient design of CO{sub 2} capture processes, or for better understanding of thermodynamics of CO{sub 2}-alkanolamine systems. Carbon dioxide is one of the major greenhouse gases, and the need for stabilization of its composition in earth's atmosphere is vital for the future of mankind. Although technologies are available for capture and storage of CO{sub 2}, these technologies are far too expensive for economical commercialization. Reduction of cost would require research for refinement of the technology. For more economical CO{sub 2} capture and regeneration, there is a need for development of more efficient solvent systems. In this project we will extend the thermodynamic database by measuring heat of solution data of CO{sub 2} in mixed solvents made of MEA (monoethanolamine), MDEA (methyldiethanolamine), piperazine, and water. Mixed solvents of different compositions will be selected and in each case data will be measured at temperatures 40 and 80C and various partial pressures of CO{sub 2}. At the end of the project, observations, conclusions, and recommendations will be derived for the choice of mixed solvents for efficient CO{sub 2} capture with potential for commercialization.

  11. Temperature- and pH-responsive nanoparticles of biocompatible polyurethanes for doxorubicin delivery.

    PubMed

    Wang, Anning; Gao, Hui; Sun, Yanfang; Sun, Yu-long; Yang, Ying-Wei; Wu, Guolin; Wang, Yinong; Fan, Yunge; Ma, Jianbiao

    2013-01-30

    A series of temperature- and pH-responsive polyurethanes based on hexamethylene diisocyanate (HDI) and 4,4'-diphenylmethane diisocyanate (MDI) were synthesized by a coupling reaction with bis-1,4-(hydroxyethyl) piperazine (HEP), N-methyldiethanolamine (MDEA) and N-butyldiethanolamine (BDEA), respectively. The chemical structure, molecular weight, thermal property and crystallization properties were characterized by Fourier transform infrared (FT-IR) spectroscopy, nuclear magnetic resonance (NMR) spectroscopy, gel permeation chromatography (GPC), differential scanning calorimetry (DSC) and X-ray diffraction (XRD) spectroscopy. The resulting polyurethanes were then used to prepare nanoparticles either by direct dispersion method or dialysis method. Their pH and temperature responsibilities were evaluated by optical transmittance and size measurement in aqueous media. Interestingly, HDI-based and MDI-based polyurethanes exhibited different pH and temperature responsive properties. Nanoparticles based on HDI-HEP and HDI-MDEA were temperature-responsive, while MDI-based biomaterials were not. All of them showed pH-sensitive behavior. The possible responsive mechanism was investigated by (1)H NMR spectroscopy. The cytotoxicity of the polyurethanes was evaluated using methylthiazoletetrazolium (MTT) assay in vitro. It was shown that the HDI-based polyurethanes were non-toxic, and could be applied to doxorubicin (DOX) encapsulation. The experimental results indicated that DOX could be efficiently encapsulated into polyurethane nanoparticles and uptaken by Huh-7 cells. The loaded DOX molecules could be released from the drug-loaded polyurethane nanoparticles upon pH and temperature changes, responsively. PMID:23262421

  12. Synthesis, Spectral and Antibacterial Studies of Binuclear Titanium(IV) / Zirconium(IV) Complexes of Piperazine Dithiosemicarbazones

    PubMed Central

    Pandey, O. P.; Sengupta, S. K.; Mishra, M. K.; Tripathi, C. M.

    2003-01-01

    The reactions of mono(cyclopentadienyl)titanium(IV) trichloride and bis(cyclopentadienyl)titanium(IV)/ zirconium(IV) dichloride with a new class of dithiosemicarbazone, derived by condensing piperazine dithiosemicarbazide with benzaldehyde (L1H2), 2-chlorobenzaldehyde (L2H2), 4-nitrobenzaldehyde (L3H2) or salicylaldehyde (L4H4) have been studied and different types of binuclear products, viz. [{CpTiCl2}2L], [{Cp2MCl}2L], ((L=L1, L2 or L3), [{CpTiCI}2L4] and [{Cp2M}2L4] (M=Yi or Zr), have been isolated. Tentative structures are proposed for these complexes based upon elemental analyses, electrical conductance, magnetic moment and spectral (electronic, IR, 1H and 13C NMR) data. Attempts have been made to establish a correlation between antibacterial activity and the structures of the products. PMID:18365041

  13. Synthesis, spectral and antibacterial studies of binuclear titanium(IV) / zirconium(IV) complexes of piperazine dithiosemicarbazones.

    PubMed

    Pandey, O P; Sengupta, S K; Mishra, M K; Tripathi, C M

    2003-01-01

    The reactions of mono(cyclopentadienyl)titanium(IV) trichloride and bis(cyclopentadienyl)titanium(IV)/ zirconium(IV) dichloride with a new class of dithiosemicarbazone, derived by condensing piperazine dithiosemicarbazide with benzaldehyde (L(1)H(2)), 2-chlorobenzaldehyde (L(2)H(2)), 4-nitrobenzaldehyde (L(3)H(2)) or salicylaldehyde (L(4)H(4)) have been studied and different types of binuclear products, viz. [{CpTiCl(2)}(2)L], [{Cp(2)MCl}(2)L], ((L=L(1), L(2) or L(3)), [{CpTiCI}(2)L(4)] and [{Cp(2)M}(2)L(4)] (M=Yi or Zr), have been isolated. Tentative structures are proposed for these complexes based upon elemental analyses, electrical conductance, magnetic moment and spectral (electronic, IR, (1)H and (13)C NMR) data. Attempts have been made to establish a correlation between antibacterial activity and the structures of the products. PMID:18365041

  14. Differentiation of ROMK potency from hERG potency in the phenacetyl piperazine series through heterocycle incorporation.

    PubMed

    Walsh, Shawn P; Shahripour, Aurash; Tang, Haifeng; de Jesus, Reynalda K; Teumelsan, Nardos; Zhu, Yuping; Frie, Jessica; Priest, Birgit T; Swensen, Andrew M; Alonso-Galicia, Magdalena; Felix, John P; Brochu, Richard M; Bailey, Timothy; Thomas-Fowlkes, Brande; Zhou, Xiaoyan; Pai, Lee-Yuh; Hampton, Caryn; Hernandez, Melba; Owens, Karen; Ehrhart, Juliann; Roy, Sophie; Kaczorowski, Gregory J; Yang, Lihu; Garcia, Maria L; Pasternak, Alexander

    2016-05-01

    Following the discovery of small molecule acyl piperazine ROMK inhibitors and their initial preclinical validation as a novel diuretic agent, our group set out to discover new ROMK inhibitors with reduced risk for QT effects, suitable for further pharmacological experiments in additional species. Several strategies for decreasing hERG affinity while maintaining ROMK inhibition were investigated and are described herein. The most promising candidate, derived from the newly discovered 4-N-heteroaryl acetyl series, improved functional hERG/ROMK ratio by >10× over the previous lead. In vivo evaluation demonstrated comparable diuretic effects in rat with no detectable QT effects at the doses evaluated in an in vivo dog model. PMID:27017115

  15. Atypical antipsychotic agents: patterns of activity in a series of 3-substituted 2-pyridinyl-1-piperazine derivatives.

    PubMed

    New, J S; Yevich, J P; Temple, D L; New, K B; Gross, S M; Schlemmer, R F; Eison, M S; Taylor, D P; Riblet, L A

    1988-03-01

    A series of 3-substituted 2-pyridinyl-1-piperazine derivatives have been appended to cyclic imide groups and evaluated for their potential antipsychotic activity. The dopamine receptor affinities of these target molecules, as well as their ability to block apomorphine-induced stereotypy or reverse neuroleptic-induced catalepsy, was dependent on the lipophilic and electronic characteristics of the substituent situated on the pyridine ring. Groups with + omega and - phi values were most consistent with the desired biological profile of the target molecules, the cyano moiety being the optimum choice. Evaluation of compound 12 in a monkey model of amphetamine psychosis, and the regional selectivity it expresses for the A10 dopaminergic cell bodies in electrophysiological experiments, suggest this compound would be an atypical antipsychotic agent with few side effects. PMID:2894466

  16. Crystal structure of piperazine-1,4-diium bis­(4-amino­benzene­sulfonate)

    PubMed Central

    Kumar, K. Sathesh; Ranjith, S.; Sudhakar, S.; Srinivasan, P.; Ponnuswamy, M. N.

    2015-01-01

    The asymmetric unit of the title salt, C4H12N2 2+·2C6H6NO3S−, consists of half a piperazindiium dication, located about an inversion centre, and a 4-amino­benzene­sulfonate anion. The piperazine ring adopts a chair conformation. In the crystal, the cations and anions are linked via N—H⋯O and C—H⋯O hydrogen bonds, forming a three-dimensional framework. Within the framework there are C—H⋯π inter­actions and the N—H⋯O hydrogen bonds result in the formation of R 4 4(22) and R 3 4(13) ring motifs. PMID:26870510

  17. Structural analysis of complexes formed by ethyl 4-phenylthiocarbamoyl piperazine-1-carboxylate with Ni(II), Zn(II) and Cd(II) through spectroscopic and DFT techniques

    NASA Astrophysics Data System (ADS)

    Prakash, Om; Gautam, Priyanka; Dani, R. K.; Nandi, Abhisikta; Singh, N. K.; Singh, Ranjan K.

    2014-04-01

    A piperazine derivative, ethyl 4-phenylthiocarbamoyl piperazine-1-carboxylate and its Ni(II), Zn(II) and Cd(II) complexes have been synthesized and characterized by elemental analyses, magnetic susceptibility measurement, UV-Visible, FTIR, Raman spectroscopic and DFT methods. The Ni(II) and Zn(II) bind through the N and S sites of the two ligand Heptpc and N site of two pyridine molecules. However, the Cd(II) binds through the only N sites of the two ligand Heptpc and N site of two pyridine molecules. On the basis of various techniques used for the characterizations of the complexes, we found that the most possible geometry of the Ni(II) and Zn(II) complexes are distorted octahedral and of the Cd(II) complex is distorted tetrahedral.

  18. 5-(Adamantan-1-yl)-3-[(4-benzyl­piperazin-1-yl)meth­yl]-1,3,4-oxadiazole-2(3H)-thione

    PubMed Central

    El-Emam, Ali A.; El-Brollosy, Nasser R.; Attia, Mohamed I.; Said-Abdelbaky, Mohammed; García-Granda, Santiago

    2012-01-01

    The mol­ecule of the title compound, C24H32N4OS, is a functionalized 1,3,4-oxadiazole-2-thione with substituted piperazine and adamantanyl substituents attached at the 3- and 5-positions, respectively, of the oxadiazole spacer with an approximately C-shaped conformation. In the crystal, mol­ecules form dimers via C—H⋯S inter­action. The piperazine ring has a chair conformation; the substituents S, methyl­ene C and adamantane C of the essentially planar oxadiazole ring are approximately in the same plane, with distances of −0.046 (2), −0.085 (5) and 0.003 (4) Å, respectively. The dihedral angle between the planes of the phenyl and oxadiazole rings is 31.3 (3)°. PMID:22798843

  19. Synthesis, biological evaluation and molecular docking studies of 2-piperazin-1-yl-quinazolines as platelet aggregation inhibitors and ligands of integrin αIIbβ3.

    PubMed

    Krysko, Andrei A; Kornylov, Alexander Yu; Polishchuk, Pavel G; Samoylenko, Georgiy V; Krysko, Olga L; Kabanova, Tatyana A; Kravtsov, Victor Ch; Kabanov, Vladimir M; Wicher, Barbara; Andronati, Sergei A

    2016-04-01

    A series of 2-piperazin-1-yl-quinazolines were synthesized and evaluated for their antiaggregative activity. The synthesized small molecule compounds have potently inhibited platelet aggregation in vitro and blocked FITC-Fg binding to αIIbβ3 integrin in a suspension of washed human platelets. The key αIIbβ3 protein-ligand interactions were determined in docking experiments and some correlations have been observed between values of the affinity and docking scores. PMID:26912112

  20. Inhibitors of HIV-1 attachment: The discovery and structure-activity relationships of tetrahydroisoquinolines as replacements for the piperazine benzamide in the 3-glyoxylyl 6-azaindole pharmacophore.

    PubMed

    Swidorski, Jacob J; Liu, Zheng; Yin, Zhiwei; Wang, Tao; Carini, David J; Rahematpura, Sandhya; Zheng, Ming; Johnson, Kim; Zhang, Sharon; Lin, Pin-Fang; Parker, Dawn D; Li, Wenying; Meanwell, Nicholas A; Hamann, Lawrence G; Regueiro-Ren, Alicia

    2016-01-01

    6,6-Fused ring systems including tetrahydroisoquinolines and tetrahydropyrido[3,4-d]pyrimidines have been explored as possible replacements for the piperazine benzamide portion of the HIV-1 attachment inhibitor BMS-663068. In initial studies, the tetrahydroisoquinoline compounds demonstrate sub-nanomolar activity in a HIV-1 pseudotype viral infection assay used as the initial screen for inhibitory activity. Analysis of SARs and approaches to optimization for an improved drug-like profile are examined herein. PMID:26584882

  1. Click-based synthesis and antitubercular evaluation of novel dibenzo[b,d]thiophene-1,2,3-triazoles with piperidine, piperazine, morpholine and thiomorpholine appendages.

    PubMed

    Pulipati, Lokesh; Yogeeswari, Perumal; Sriram, Dharmarajan; Kantevari, Srinivas

    2016-06-01

    A series of novel piperidine, piperazine, morpholine and thiomorpholine appended dibenzo[b,d]thiophene-1,2,3-triazoles were designed and synthesized utilizing azide-alkyne click chemistry in the penultimate step. The required azide building block 6a-e was synthesized from commercial dibenzo[b,d]thiophene in good yields following five step reaction sequence. All the new analogues 8a-f, 9a-f, 10a-f, 11a-f &12a-f were characterized by their NMR and mass spectral analysis. Screening all thirty new compounds for in vitro antimycobacterial activity against Mycobacterium tuberculosis H37Rv, resulted 8a, 8f and 11e as potent analogues with MIC 0.78μg/mL, 0.78μg/mL & 1.56μg/mL, respectively, and has shown lower cytotoxicity. Interestingly, all six piperazine appended dibenzo[b,d]thiophene-1,2,3-triazoles 11a-f exhibited Mtb inhibition activity with MIC 1.56-12.5μg/mL. To some extent, the data observed here indicated Mycobacterium tuberculosis inhibition among the appendages is in the order, piperazine>thiomorpholine>morpholine. PMID:27101894

  2. Development of a high-performance liquid chromatography with fluorescence detection method for quantification of piperazine in animal products by using precolumn derivatization.

    PubMed

    Park, Jin-A; Zhang, Dan; Kim, Dong-Soon; Kim, Seong-Kwan; Cho, Sang-Hyun; Jeong, Daun; Kim, Jin-Suk; Shim, Jae-Han; Abd El-Aty, A M; Shin, Ho-Chul

    2016-04-01

    A new high-performance liquid chromatography with ​fluorescence detection (HPLC-FLD) method was developed for determination of piperazine residues in food animal products. Samples were extracted with formic acid in water and purified using the PCX cartridge. Following purification, the samples were derivatized using dansyl chloride, and the analyte was separated using water/acetonitrile as a mobile phase. The calibration curves showed good linearity over a concentration range of 20-120 ng/g with coefficient of determination (R(2))⩾0.996. The intra-day accuracy (presented as recovery %) and precision (presented as relative standard deviation, RSD %) were 81-97.3% and 0.83-6.87%, whereas, the inter-day values were 80.5-96.8% and 1.7-6.8%, respectively. The limit of quantification (LOQ) was 20 ng/g, which was considerably lower than the maximum residue limit (MRL). The developed method was used to monitor market samples, and piperazine was not detected in any of the samples. To our knowledge, this is the first study in which the detection of piperazine in various food and animal products by using a sensitive and reliable analytical method has been described. PMID:26593624

  3. Synthesis and bioactivities of novel piperazine-containing 1,5-Diphenyl-2-penten-1-one analogues from natural product lead.

    PubMed

    Xu, Gaofei; Yang, Xinling; Jiang, Biaobiao; Lei, Peng; Liu, Xili; Wang, Qingmin; Zhang, Xuebo; Ling, Yun

    2016-04-01

    A series of novel 1,5-Diphenyl-2-penten-1-one analogues (7a-h, 8a-h) with piperazine moiety have been designed and synthesized on the basis of natural product 1,5-Diphenyl-2-penten-1-one (I). All the synthesized compounds were evaluated in vitro for anti-plant pathogenic fungi activities and insecticidal activities. The results indicated that most of these analogues exhibited moderate antifungal activities and moderate to good insecticidal activities. Amongst them, the most potent 7c, 7e and 7h keep a mortality of 100% against larva of mosquito at the concentration of 1mg/L. Initial structure-activity relationship (SAR) analysis showed that, a methyl group can influence the biological activities of these compounds significantly, the compounds with N'-unsubstituted piperazine showed much better antifungal activities and larvicidal activity against mosquito than the compounds with N'-methylated piperazine. In addition, the larvicidal activity against mosquito had sharply decline when the substituent on benzene ring was changed from 4-position to 2 or 3-position. PMID:26906636

  4. An unknown solvate of 1-(2,4-di-chloro-benz-yl)-4-[(4-methyl-phen-yl)sulfon-yl]piperazine.

    PubMed

    Sreenivasa, S; Manojkumar, K E; Anitha, H C; Suchetan, P A; Palakshamurthy, B S; Jayashree, Yenagi; Tonannavar, J

    2013-05-01

    In the title compound, C18H20Cl2N2O2S, the piperazine ring adopts a chair conformation. The dihedral angle between the sulfonyl-bound benzene ring and the best-fit plane through the six non-H atoms of the piperazine ring is 72.22 (12)°; those between the di-chloro-benzene ring and the sulfonyl and piperazine rings are 2.44 (13) and 74.16 (2)°, respectively. In the crystal, mol-ecules are connected through weak C-H⋯O inter-actions into a hexa-meric unit generating a R 6 (6)(60) motif in the ab plane. The mol-ecules are also connected into C(4) chains through weak C-H⋯N inter-actions. The solvent used to grow the crystal was a mixture of di-chloro-methane and methanol, but the resulting electron density was uninter-pretable. The solvent contribution to the scattering was removed with the SQUEEZE routine in PLATON [Spek (2009 ▶). Acta Cryst. D65, 148-155]. The formula mass and unit-cell characteristics do not take into account the disordered solvent. PMID:23723926

  5. Determination of buspirone and 1-(2-pyrimidinyl)-piperazine (1-PP) in human plasma by capillary gas chromatography.

    PubMed

    Kivistö, K T; Laitila, J; Mårtensson, K; Neuvonen, P J

    1999-06-01

    Two separate gas chromatographic methods for the determination of buspirone and its active metabolite, 1-(2-pyrimidinyl)-piperazine (1-PP) in human plasma are described. Both procedures involve solid-phase extraction (the packing material of the cartridges used was C8 for buspirone and a mixed-mode sorbent for 1-PP), injection of the sample into a gas chromatograph equipped with a fused-silica capillary column and a nitrogen-phosphorus detector, and analysis with temperature programming (from 220 degrees C to 285 degrees C for buspirone and from 138 degrees C to 285 degrees C for 1-PP). The coating material of the analytical column was 5% diphenyl dimethyl silicone for buspirone and 50% diphenyl dimethyl silicone for 1-PP. Zolpidem was used as an internal standard in the buspirone assay and 1-phenylpiperazine in the 1-PP assay. Recovery of buspirone and 1-PP averaged 98% and 89%, respectively, and the limit of quantification was 0.2 ng/mL for both compounds. The between-run coefficients of variation ranged from 3.2% to 9.4% and from 2.9% to 8.6% for samples spiked with three different concentrations of buspirone and 1-PP, respectively. The suitability of these assays for pharmacokinetic studies was shown by analyzing timed plasma samples from volunteers after ingestion of a single therapeutic dose of buspirone (10 mg). PMID:10365644

  6. 2-Benzazolyl-4-Piperazin-1-Ylsulfonylbenzenecarbohydroxamic Acids as Novel Selective Histone Deacetylase-6 Inhibitors with Antiproliferative Activity

    PubMed Central

    Wang, Lei; Kofler, Marina; Brosch, Gerald; Melesina, Jelena; Sippl, Wolfgang; Martinez, Elisabeth D.; Easmon, Johnny

    2015-01-01

    We have screened our compound collection in an established cell based assay that measures the derepression of an epigenetically silenced transgene, the locus derepression assay. The screen led to the identification of 4-[4-(1-methylbenzimidazol-2-yl)piperazin-1-yl]sulfonylbenzenecarbohydroxamic acid (9b) as an active which was found to inhibit HDAC1. In initial structure activity relationships study, the 1-methylbenzimidazole ring was replaced by the isosteric heterocycles benzimidazole, benzoxazole, and benzothiazole and the position of the hydroxamic acid substituent on the phenyl ring was varied. Whereas compounds bearing a para substituted hydroxamic acid (9a-d) were active HDAC inhibitors, the meta substituted analogues (8a-d) were appreciably inactive. Compounds 9a-d selectively inhibited HDAC6 (IC50 = 0.1–1.0μM) over HDAC1 (IC50 = 0.9–6μM) and moreover, also selectively inhibited the growth of lung cancer cells vs. patient matched normal cells. The compounds induce a cell cycle arrest in the S-phase while induction of apoptosis is neglible as compared to controls. Molecular modeling studies uncovered that the MM-GBSA energy for interaction of 9a-d with HDAC6 was higher than for HDAC1 providing structural rationale for the HDAC6 selectivity. PMID:26698121

  7. Pharmacological and pharmacokinetic characterization of 2-piperazine-alpha-isopropyl benzylamine derivatives as melanocortin-4 receptor antagonists.

    TOXLINE Toxicology Bibliographic Information

    Chen C; Tucci FC; Jiang W; Tran JA; Fleck BA; Hoare SR; Wen J; Chen T; Johns M; Markison S; Foster AC; Marinkovic D; Chen CW; Arellano M; Harman J; Saunders J; Bozigian H; Marks D

    2008-05-15

    A series of 2-piperazine-alpha-isopropylbenzylamine derivatives were synthesized and characterized as melanocortin-4 receptor (MC4R) antagonists. Attaching an amino acid to benzylamines 7 significantly increased their binding affinity, and the resulting compounds 8-12 bound selectively to MC4R over other melanocortin receptor subtypes and behaved as functional antagonists. These compounds were also studied for their permeability using Caco-2 cell monolayers and metabolic stability in human liver microsomes. Most compounds exhibited low permeability and high efflux ratio possibly due to their high molecular weights. They also showed moderate metabolic stability which might be associated with their moderate to high lipophilicity. Pharmacokinetic properties of these MC4R antagonists, including brain penetration, were studied in mice after oral and intravenous administrations. Two compounds identified to possess high binding affinity and selectivity, 10d and 11d, were studied in a murine cachexia model. After intraperitoneal (ip) administration of 1mg/kg dose, mice treated with 10d had significantly more food intake and weight gain than the control animals, demonstrating efficacy by blocking the MC4 receptor. Similar in vivo effects were also observed when 11d was dosed orally at 20mg/kg. These results provide further evidence that a potent and selective MC4R antagonist has potential in the treatment of cancer cachexia.

  8. Synthesis and Structure-Activity Relationship Analysis of 5-HT₇ Receptor Antagonists: Piperazin-1-yl Substituted Unfused Heterobiaryls.

    PubMed

    Strekowski, Lucjan; Sączewski, Jarosław; Raux, Elizabeth A; Fernando, Nilmi T; Klenc, Jeff; Paranjpe, Shirish; Raszkiewicz, Aldona; Blake, Ava L; Ehalt, Adam J; Barnes, Samuel; Baranowski, Timothy C; Sullivan, Shannon M; Satała, Grzegorz; Bojarski, Andrzej J

    2016-01-01

    A series of piperazin-1-yl substituted unfused heterobiaryls was synthesized as ligands of the 5-HT₇ receptors. The goal of this project was to elucidate the structural features that affect the 5-HT₇ binding affinity of this class of compounds represented by the model ligand 4-(3-furyl)-2-(4-methylpiperazin-1-yl)pyrimidine (2). The SAR studies included systematical structural changes of the pyrimidine core moiety in 2 to quinazoline, pyridine and benzene, changes of the 3-furyl group to other heteroaryl substituents, the presence of various analogs of the 4-methylpiperazin-1-yl group, as well as additional substitutions at positions 5 and 6 of the pyrimidine. Substitution of position 6 of the pyrimidine in the model ligand with an alkyl group results in a substantial increase of the binding affinity (note a change in position numbers due to the nomenclature rules). It was also demonstrated that 4-(3-furyl) moiety is crucial for the 5-HT₇ binding affinity of the substituted pyrimidines, although, the pyrimidine core can be replaced with a pyridine ring without a dramatic loss of the binding affinity. The selected ethylpyrimidine (12) and butylpyrimidine (13) analogs of high 5-HT₇ binding affinity showed antagonistic properties in cAMP functional test and varied selectivity profile-compound 12 can be regarded as a dual 5-HT₇/5-HT2AR ligand, and 13 as a multi-receptor (5-HT₇, 5-HT2A, 5-HT₆ and D₂) agent. PMID:27043518

  9. Formation of Diastereoisomeric Piperazine-2,5-dione from uc(dl)-Alanine in the Presence of Olivine and Water

    NASA Astrophysics Data System (ADS)

    Fuchida, Shigeshi; Naraoka, Hiroshi; Masuda, Harue

    2016-04-01

    uc(dl)-Alanine (Ala) was heated with/without powdered olivine and water at 120 °C for 8 days to investigate the formation of the diastereoisomers of piperazine-2,5-dione (diketopiperazine, DKP). When only uc(dl)-Ala was heated with a small amount of water, 3.0 % of uc(dl)-Ala changed to cis- and trans-DKP after 8 days. DKPs were not detected after heating when no water was added. The presence of a small amount of water is important factor controlling peptide production rates under thermal conditions. When DL-Ala was heated with olivine powder for 8 days, the yields of cis- and trans-DKP were 6.8 and 4.9 %, respectively. The high yield of cis-DKP compared with trans-DKP was attributed to greater thermal stability of cis-DKP. After heating for 8 days, the diastereoisomeric excess of cis-DKP without olivine was 7.3 %, whereas a much higher value of 16.3 % was obtained in the presence of olivine. Taken together, these results show that olivine is not only an efficient catalyst for the formation of DKPs but that it also play a significant role in determining the diastereoisomer selectivity of these cyclic dipeptides.

  10. Complexation, thermal and catalytic studies of N-substituted piperazine, morpholine and thiomorpholine with some metal ions

    NASA Astrophysics Data System (ADS)

    Kacan, Mesut; Turkyilmaz, Murat; Karabulut, Ferhat; Altun, Ozlen; Baran, Yakup

    2014-01-01

    Several Cu(II), Pt(II) and Ni(II) complexes of N-substituted, piperazine (NN donor), morpholine (NO donor) and thiomorpholine (NS donor) derivatives were synthesized and their thermal behavior and catalytic activity in epoxidation reaction of cis-diphenylethylene were studied using oxygen sources NaOCl. The coordination compounds of Cu(II), Pt(II) and Ni(II) having general formula [MLCl]Cl, [ML2l]Cl2 or [ML]Cl2 with tetra coordinated geometry around metal ions have been isolated as solid. All the ligands and complexes were identified by spectroscopic methods and elemental analysis, magnetic measurements, electrical conductance and thermal analysis. A square planer structures have been proposed for all complexes. The thermal stability of the complexes discussed in terms of ligands donor atoms, geometry and central metal ions. The complexes have a similar thermal behavior for the selected metal ions. The thermogravimetric analyses suggest high thermal stability for most complexes followed by thermal decomposition in different steps. The decomposition processes were observed as water elimination, chloride anion removal and degradation of the organic ligands. Catalytic ability of the complexes were examined and found that all the complexes can effectively catalyze the epoxidation of cis-stilbene with NaOCl.

  11. Thermodynamic Investigation and Mixed Ligand Complex Formation of 1,4-Bis-(3-aminopropyl)-piperazine and Biorelevant Ligands

    PubMed Central

    El-Sherif, Ahmed A.; Shehata, Mohamed R.; Shoukry, Mohamed M.; Barakat, Mohammad H.

    2012-01-01

    Thermodynamic parameters for protonation of 1,4-bis(3-aminopropyl)-piperazine (BAPP) and its metal complexation with some divalent metal ions were determined in aqueous solution at constant ionic strength (0.1 M NaNO3) using a potentiometric technique. The order of –ΔG0 and –ΔH0 was found to obey Co2+ < Ni2+ < Cu2+ > Zn2+, in accordance with the Irving-Williams order. The formation equilibria of zinc (II) complexes and the ternary complexes Zn(BAPP)L, where L = amino acid, amides, or DNA constituents), have been investigated. Ternary complexes are formed by a simultaneous mechanism. The concentration distribution of the complexes in solution was evaluated as a function of pH. Stoichiometry and stability constants for the complexes formed are reported and discussed. The stability of ternary complexes was quantitatively compared with their corresponding binary complexes in terms of the parameter Δlog K. PMID:23226992

  12. A novel piperazine derivative potently induces caspase-dependent apoptosis of cancer cells via inhibition of multiple cancer signaling pathways

    PubMed Central

    She, Edward X; Hao, Zhonglin

    2013-01-01

    Despite rapid progress in anticancer drug development and improvement in clinical outcomes, the survival rate for many types of cancer is still unacceptably low. Therefore, it is crucial to discover novel anticancer drugs to both prevent and treat the disease. In recent years, the advent of combinatorial chemistry allows the design and parallel synthesis of millions of small compounds that have drug-like properties. In vitro high throughput screening of such compound libraries has allowed the identification of many new drug candidates that may be further evaluated for their efficacy and mechanism of action. The overall objective of this study was to identify small molecule compounds as candidates for anti-cancer drug development. We first used cell proliferation and cytotoxicity assays to identify compounds exhibiting anti-cancer activity in vitro in a leukemia cell line (K562). Six top compounds selected from the initial screening of a library of 2,560 compounds were further evaluated in multiple cancer cell lines to rank the drug candidates. The top candidate was further investigated to elucidate the molecular mechanism underlying its anticancer activity. Our studies suggest that this piperazine derivative effectively (GI50 = 0.06-0.16 μM) inhibits cancer cell proliferation and induces caspase-dependent apoptosis via inhibiting multiple cancer signaling pathways including the PI3K/AKT, the Src family kinases and the BCR-ABL pathways. PMID:24093059

  13. Effect of an original piperazine derivative of tetraline on the adrenergically mediated metabolic responses in cats and rats.

    PubMed

    Bogoslovova, T; Staneva-Stoytcheva, D

    1988-01-01

    One piperazine derivative of tetraline (with code P11), possessing hypotensive and anti-hypertensive activity, is studied. Its alpha- and beta-adrenoceptor blocking properties are characterized by using indicators of adrenergically mediated metabolic responses in cats and rats. The parameters studied are: glucose and lactate in the blood, free fatty acids in the plasma and the activity of phosphorylase "a" in rat myocardium. The alpha- and beta-adrenergic properties of P11 are characterized by using adrenergic and dopaminergic agonists and antagonists (adrenaline, isoproterenol, phenylephrine, propranolol, phentolamine, apomorphine and pimozide) in the different experimental setups. Compound P11 studied inhibits the effect of phenylephrine on the glucose level in the blood of rats in a definite dose interval (1-4 mg/kg) which suggests that it possesses alpha-adrenoblocking properties. P11 decreases slightly the effects of isoproterenol or does not change these effects on the levels of glucose, lactate and free fatty acids in cats. There are no changes in the effect of adrenaline on the glucose content in rat blood and the isoproterenol-activated phosphorylase in rat myocardium is not inhibited. This gives grounds to assume that P11 possesses slight beta-adrenoblocking properties. From the analysis of the proper hyperglycaemizing action of P11 in rats in the 1-8 mg/kg dose range it may be assumed that dopamine-agonistic mechanisms are involved. PMID:2907712

  14. 3-(1-Adamant­yl)-1-{[4-(2-meth­oxy­phen­yl)piperazin-1-yl]meth­yl}-4-methyl-1H-1,2,4-triazole-5(4H)-thione

    PubMed Central

    Al-Tamimi, Abdul-Malek S.; Bari, Ahmed; Al-Omar, Mohamed A.; Alrashood, Khalid A.; El-Emam, Ali A.

    2010-01-01

    The title compound, C25H35N5OS, is a functionalized triazoline-3-thione with substituted piperazine and adamantyl substituents attached at the 2- and 5-positions, respectively, of a triazole spacer with an approximately C-shaped conformation of the mol­ecule. The piperazine ring adopts a chair conformation. PMID:21587972

  15. N-Aryl Piperazine Metabotropic Glutamate Receptor 5 Positive Allosteric Modulators Possess Efficacy in Preclinical Models of NMDA Hypofunction and Cognitive Enhancement

    PubMed Central

    Gregory, K.J.; Herman, E.J.; Ramsey, A.J.; Hammond, A.S.; Byun, N.E.; Stauffer, S.R.; Manka, J.T.; Jadhav, S.; Bridges, T.M.; Weaver, C.D.; Niswender, C.M.; Steckler, T.; Drinkenburg, W.H.; Ahnaou, A.; Lavreysen, H.; Macdonald, G.J.; Bartolomé, J.M.; Mackie, C.; Hrupka, B.J.; Caron, M.G.; Daigle, T.L.; Lindsley, C.W.; Conn, P.J.

    2013-01-01

    Impaired transmission through glutamatergic circuits has been postulated to play a role in the underlying pathophysiology of schizophrenia. Furthermore, inhibition of the N-methyl-d-aspartate (NMDA) subtype of ionotropic glutamate receptors (NMDAR) induces a syndrome that recapitulates many of the symptoms observed in patients with schizophrenia. Selective activation of metabotropic glutamate receptor subtype 5 (mGlu5) may provide a novel therapeutic approach for treatment of symptoms associated with schizophrenia through facilitation of transmission through central glutamatergic circuits. Here, we describe the characterization of two novel N-aryl piperazine mGlu5 positive allosteric modulators (PAMs): 2-(4-(2-(benzyloxy)acetyl)piperazin-1-yl)benzonitrile (VU0364289) and 1-(4-(2,4-difluorophenyl)piperazin-1-yl)-2-((4-fluorobenzyl)oxy)ethanone (DPFE). VU0364289 and DPFE induced robust leftward shifts in the glutamate concentration-response curves for Ca2+ mobilization and extracellular signal-regulated kinases 1 and 2 phosphorylation. Both PAMs displayed micromolar affinity for the common mGlu5 allosteric binding site and high selectivity for mGlu5. VU0364289 and DPFE possessed suitable pharmacokinetic properties for dosing in vivo and produced robust dose-related effects in reversing amphetamine-induced hyperlocomotion, a preclinical model predictive of antipsychotic-like activity. In addition, DPFE enhanced acquisition of contextual fear conditioning in rats and reversed behavioral deficits in a mouse model of NMDAR hypofunction. In contrast, DPFE had no effect on reversing apomorphine-induced disruptions of prepulse inhibition of the acoustic startle reflex. These mGlu5 PAMs also increased monoamine levels in the prefrontal cortex, enhanced performance in a hippocampal-mediated memory task, and elicited changes in electroencephalogram dynamics commensurate with procognitive effects. Collectively, these data support and extend the role for the development of novel mGlu5 PAMs for the treatment of psychosis and cognitive deficits observed in individuals with schizophrenia. PMID:23965381

  16. 3-(Adamantan-1-yl)-1-[(4-benzyl­piperazin-1-yl)meth­yl]-4-ethyl-1H-1,2,4-triazole-5(4H)-thione

    PubMed Central

    Al-Abdullah, Ebtehal S.; Al-Tuwaijri, Hanaa M.; El-Emam, Ali A.; Chidan Kumar, C. S.; Fun, Hoong-Kun

    2013-01-01

    In the title compound, C26H37N5S, the piperazine ring adopts a chair conformation with the exocyclic N—C bonds in pseudo-equatorial orientations. The piperazine ring (all atoms) subtends dihedral angles of 79.47 (9) and 73.07 (9)° with the triazole and benzene rings, respectively, resulting in an approximate U-shape for the mol­ecule. No significant inter­molecular inter­actions are observed in the crystal. PMID:24454243

  17. Investigation of the mode of binding of a novel series of N-benzyl-4-heteroaryl-1-(phenylsulfonyl)piperazine-2-carboxamides to the hepatitis C virus polymerase

    SciTech Connect

    Gentles, Robert G.; Sheriff, Steven; Beno, Brett R.; Wan, Changhong; Kish, Kevin; Ding, Min; Zheng, Xiaofan; Chupak, Louis; Poss, Michael A.; Witmer, Mark R.; Morin, Paul; Wang, Ying-Kai; Rigat, Karen; Lemm, Julie; Voss, Stacey; Liu, Mengping; Pelosi, Lenore; Roberts, Susan B.; Gao, Min; Kadow, John F.

    2013-11-20

    Structure based rationales for the activities of potent N-benzyl-4-heteroaryl-1-(phenylsulfonyl)piperazine-2-carboxamide inhibitors of the hepatitis C viral polymerase are described herein. These compounds bind to the hepatitis C virus non-structural protein 5B (NS5B), and co-crystal structures of select examples from this series with NS5B are reported. Comparison of co-crystal structures of a potent analog with both NS5B genotype 1a and genotype 1b provides a possible explanation for the genotype-selectivity observed with this compound class and suggests opportunities for the further optimization of the series.

  18. Design and synthesis of piperazine derivatives as a novel class of γ-secretase modulators that selectively lower Aβ₄₂ production.

    PubMed

    Takai, Takafumi; Koike, Tatsuki; Honda, Eiji; Kajita, Yuichi; Nakamura, Minoru; Morimoto, Sachie; Hoashi, Yasutaka; Kamata, Makoto; Watanabe, Tomomichi; Igari, Tomoko; Terauchi, Jun

    2015-05-01

    Novel piperazine derivatives as γ-secretase modulators (GSMs) were prepared and tested for their ability to selectively lower Aβ₄₂ production. Lead compound 3, with selective Aβ₄₂-lowering activity, was modified by replacing its imidazolylphenyl moiety with an oxazolylphenyl moiety. Optimization of the urea group significantly improved mouse microsomal stability, while retaining both activity and selectivity. These efforts led to the successful identification of an orally available and brain-penetrant GSM, 6j, which selectively reduced brain Aβ₄₂ in mice. PMID:25842363

  19. Mechanism-Based Inactivation of Human Cytochrome P450 3A4 by Two Piperazine-Containing Compounds

    PubMed Central

    Bolles, Amanda K.; Fujiwara, Rina; Briggs, Erran D.; Nomeir, Amin A.

    2014-01-01

    Human cytochrome P450 3A4 (CYP3A4) is responsible for the metabolism of more than half of pharmaceutic drugs, and inactivation of CYP3A4 can lead to adverse drug-drug interactions. The substituted imidazole compounds 5-fluoro-2-[4-[(2-phenyl-1H-imidazol-5-yl)methyl]-1-piperazinyl]pyrimidine (SCH 66712) and 1-[(2-ethyl-4-methyl-1H-imidazol-5-yl)methyl]-4-[4-(trifluoromethyl)-2-pyridinyl]piperazine (EMTPP) have been previously identified as mechanism-based inactivators (MBI) of CYP2D6. The present study shows that both SCH 66712 and EMTPP are also MBIs of CYP3A4. Inhibition of CYP3A4 by SCH 66712 and EMTPP was determined to be concentration, time, and NADPH dependent. In addition, inactivation of CYP3A4 by SCH 66712 was shown to be unaffected by the presence of electrophile scavengers. SCH 66712 displays type I binding to CYP3A4 with a spectral binding constant (Ks) of 42.9 ± 2.9 µM. The partition ratios for SCH 66712 and EMTPP were 11 and 94, respectively. Whole protein mass spectrum analysis revealed 1:1 binding stoichiometry of SCH 66712 and EMTPP to CYP3A4 and a mass increase consistent with adduction by the inactivators without addition of oxygen. Heme adduction was not apparent. Multiple mono-oxygenation products with each inactivator were observed; no other products were apparent. These are the first MBIs to be shown to be potent inactivators of both CYP2D6 and CYP3A4. PMID:25273356

  20. Design, synthesis, biological screening, and molecular docking studies of piperazine-derived constrained inhibitors of DPP-IV for the treatment of type 2 diabetes.

    PubMed

    Kushwaha, Ram N; Srivastava, Rohit; Mishra, Akansha; Rawat, Arun K; Srivastava, Arvind K; Haq, Wahajul; Katti, Seturam B

    2015-04-01

    Novel piperazine-derived conformationally constrained compounds were designed, synthesized, and evaluated for in vitro Dipeptidyl peptidase-IV (DPP-IV) inhibitory activities. From a library of compounds synthesized, 1-(2-(4-(7-Chloro-4-quinolyl)piperazin-1-yl)acetyl)pyrrolidine (2g) was identified as a potential DPP-IV inhibitor exhibiting better inhibitory activity than P32/98, reference inhibitor. The in vivo studies carried out in STZ and db/db mice models indicated that the compound 2g showed moderate antihyperglycemic activity as compared to the marketed drug Sitagliptin. A two-week repeated dose study in db/db mice revealed that compound 2g significantly declined blood glucose levels with no evidence of hypoglycemia risk. Furthermore, it showed improvement in insulin resistance reversal and antidyslipidemic properties. Molecular docking studies established good binding affinity of compound 2g at the DPP-IV active site and are in favor of the observed biological data. These data collectively suggest that compound 2g is a good lead molecule for further optimization studies. PMID:25216392

  1. Benzo[d]thiazol-2-yl(piperazin-1-yl)methanones as new anti-mycobacterial chemotypes: Design, synthesis, biological evaluation and 3D-QSAR studies.

    PubMed

    Pancholia, Sahaj; Dhameliya, Tejas M; Shah, Parth; Jadhavar, Pradeep S; Sridevi, Jonnalagadda Padma; Yogeshwari, Perumal; Sriram, Dharmarajan; Chakraborti, Asit K

    2016-06-30

    The benzo[d]thiazol-2-yl(piperazin-1-yl)methanones scaffold has been identified as new anti-mycobacterial chemotypes. Thirty-six structurally diverse benzo[d]thiazole-2-carboxamides have been prepared and subjected to assessment of their potential anti-tubercular activity through in vitro testing against Mycobacterium tuberculosis H37Rv strain and evaluation of cytotoxicity against RAW 264.7 cell lines. Seventeen compounds showed anti-mycobacterial potential having MICs in the low (1-10) μM range. The 5-trifluoromethyl benzo[d]thiazol-2-yl(piperazin-1-yl)methanones emerged to be the most promising resulting in six positive hits (2.35-7.94 μM) and showed low-cytotoxicity (<50% inhibition at 50 μg/mL). The therapeutic index of these hits is 8-64. The quantitative structure activity relationship has been established adopting a statistically reliable CoMFA model showing high prediction (rpred(2)=0.718,rncv(2)=0.995). PMID:27061982

  2. Cyp2D6 catalyzes 5-hydroxylation of 1-(2-pyrimidinyl)-piperazine, an active metabolite of several psychoactive drugs, in human liver microsomes.

    PubMed

    Raghavan, Nirmala; Zhang, Donglu; Zhu, Mingshe; Zeng, Jianing; Christopher, Lisa

    2005-02-01

    1-(2-Pyrimidinyl)-piperazine (1-PP) is an active metabolite of several psychoactive drugs including buspirone. 1-PP is also the major metabolite in the human circulation and in rat brains following oral administration of buspirone. This study was conducted to identify the enzyme responsible for the metabolic conversion of 1-PP to 5-hydroxy-1-(2-pyrimidinyl)-piperazine (HO-1-PP) in human liver microsomes (HLMs). The product HO-1-PP was quantified by a validated liquid chromatography-tandem mass spectrometry method. In the presence of NADPH, 1-PP (100 microM) was incubated separately with human cDNA-expressed cytochrome P450 isozymes (including CYP2D6, 3A4, 1A2, 2A6, 2C9, 2C19, 2E1, and 2B6) at 37 degrees C. CYP2D6 catalyzed the formation of HO-1-PP from 1-PP. This catalytic activity was >95% inhibited by quinidine, a CYP2D6 inhibitor. HO-1-PP formation rates correlated well with the bufuralol 1-hydroxylase (CYP2D6) activities of individual HLMs. The formation of HO-1-PP followed a Michaelis-Menten kinetics with a K(m) of 171 microM and V(max) of 313 pmol/min x mg protein in HLMs. Collectively, these results indicate that polymorphic CYP2D6 is responsible for the conversion of 1-PP to HO-1-PP. PMID:15507542

  3. Here today, gone tomorrow…and back again? A review of herbal marijuana alternatives (K2, Spice), synthetic cathinones (bath salts), kratom, Salvia divinorum, methoxetamine, and piperazines.

    PubMed

    Rosenbaum, Christopher D; Carreiro, Stephanie P; Babu, Kavita M

    2012-03-01

    Despite their widespread Internet availability and use, many of the new drugs of abuse remain unfamiliar to health care providers. The herbal marijuana alternatives, like K2 or Spice, are a group of herbal blends that contain a mixture of plant matter in addition to chemical grade synthetic cannabinoids. The synthetic cathinones, commonly called "bath salts," have resulted in nationwide emergency department visits for severe agitation, sympathomimetic toxicity, and death. Kratom, a plant product derived from Mitragyna speciosa Korth, has opioid-like effects, and has been used for the treatment of chronic pain and amelioration of opioid-withdrawal symptoms. Salvia divinorum is a hallucinogen with unique pharmacology that has therapeutic potential but has been banned in many states due to concerns regarding its psychiatric effects. Methoxetamine has recently become available via the Internet and is marked as "legal ketamine." Moreover, the piperazine derivatives, a class of amphetamine-like compounds that includes BZP and TMFPP, are making a resurgence as "legal Ecstasy." These psychoactives are available via the Internet, frequently legal, and often perceived as safe by the public. Unfortunately, these drugs often have adverse effects, which range from minimal to life-threatening. Health care providers must be familiar with these important new classes of drugs. This paper discusses the background, pharmacology, clinical effects, detection, and management of synthetic cannabinoid, synthetic cathinone, methoxetamine, and piperazine exposures. PMID:22271566

  4. Synthesis of new 1-phenyl-2-(4-substituted-piperazin-1-yl)-propanol derivatives and evaluation of their antidepressant-like effects.

    PubMed

    Demir Özkay, Ümide; Yurttaş, Leyla; Özkay, Yusuf; Üçel, Umut Irfan; Can, Özgür Devrim; Öztürk, Yusuf

    2013-07-01

    In this study, we synthesized eight novel 1-phenyl-2-(4-substituted-piperazin-1-yl)-propanol derivatives and evaluated their antidepressant-like activities. The chemical structures of the synthesised compounds were elucidated by spectroscopy and elemental analyses. Potential antidepressant-like effects of the test compounds (20 mg kg(-1)) were investigated using the tail-suspension test and modified forced swimming test (MFST) in mice. Additionally, the spontaneous locomotor activity of the mice was assessed using the activity cage apparatus. Both the reference drug fluoxetine (20 mg kg(-1)) and the test compounds 3a-3e and 3g significantly shortened the immobility time of the mice in both the behavioural tests. These test compounds also increased the swimming time in MFST without any change in the climbing duration. Compounds 3c-3e and 3g were significantly more potent in inducing these effects than 3a and 3b. None of the compounds changed the locomotor activities of the animals, thus antidepressant-like effects of test compounds were specific. The findings support those of previous studies that reported antidepressant-like activities of aryl alkanol piperazine derivatives. PMID:23595553

  5. The Reaction of DABCO with 4-Chloro-5H-1,2,3-dithiazoles: Synthesis and Chemistry of 4-[N-(2-Chloroethyl)piperazin-1-yl]-5H-1,2,3-dithiazoles.

    PubMed

    Koyioni, Maria; Manoli, Maria; Koutentis, Panayiotis A

    2016-01-15

    N-(4-Chloro-5H-1,2,3-dithiazol-5-ylidene)anilines react with DABCO in hot PhCl to give N-{4-[N-(2-chloroethyl)piperazin-1-yl]-5H-1,2,3-dithiazol-5-ylidene}anilines in high yields (70-92%). The reaction also works with 4-chloro-5H-1,2,3-dithiazol-5-one and -thione, giving the corresponding products in 85% and 76% yields, respectively. While the reaction of several (4-chloro-5H-1,2,3-dithiazol-5-ylidene)methanes with DABCO failed to give {4-[N-(2-chloroethyl)piperazin-1-yl]-5H-1,2,3-dithiazol-5-ylidene}methanes, these can be prepared in moderate yields via classical cycloaddition-retrocycloaddition strategies from 4-[N-(2-chloroethyl)piperazin-1-yl]-5H-1,2,3-dithiazole-5-thione. The 2-chloroethyl moiety on selected dithiazoles was also modified without cleavage of the 1,2,3-dithiazole by reaction with various nucleophiles, giving access to 4-[N-(2-substituted)piperazin-1-yl]-5H-1,2,3-dithiazoles in moderate to high yields. PMID:26671065

  6. Bis[N-(2-hy­droxy­eth­yl)-N-iso­propyl­dithio­carbamato-κ2 S,S′](piperazine-κN)cadmium: crystal structure and Hirshfeld surface analysis

    PubMed Central

    Safbri, Siti Artikah M.; Halim, Siti Nadiah Abdul; Jotani, Mukesh M.; Tiekink, Edward R. T.

    2016-01-01

    The title compound, [Cd(C6H12NOS2)2(C4H10N2)], features a distorted square-pyramidal coordination geometry about the central CdII atom. The di­thio­carbamate ligands are chelating, forming similar Cd—S bond lengths and define the approximate basal plane. One of the N atoms of the piperazine mol­ecule, which adopts a chair conformation, occupies the apical site. In the crystal, supra­molecular layers propagating in the ac plane are formed via hy­droxy-O—H⋯O(hy­droxy), hy­droxy-O—H⋯N(terminal-piperazine) and coordinated-piperazine-N—H⋯O(hy­droxy) hydrogen bonds; the layers also feature methine-C—H⋯S inter­actions and S⋯S [3.3714 (10) Å] short contacts. The layers stack along the b-axis direction with very weak terminal-piperazine-N—H⋯O(hy­droxy) inter­actions between them. An evaluation of the Hirshfeld surfaces confirms the importance of inter­molecular inter­actions involving oxygen and sulfur atoms. PMID:26958378

  7. Determination of airborne methyl isocyanate as dibutylamine or 1-(2-methoxyphenyl)piperazine derivatives by liquid and gas chromatography.

    PubMed

    Henriks-Eckerman, M L; Välimaa, J; Rosenberg, C

    2000-11-01

    The usefulness of a glass fibre filter method to collect airborne methyl isocyanate (MIC) was studied in laboratory experiments and in a workplace during manufacture of mineral wool insulation material. Filter collection was based on derivatisation in situ with 1-(2-methoxyphenyl)piperazine (2MP). 2MP impinger sampling was also evaluated in the workplace. Impinger sampling with dibutylamine (DBA) was used as an independent method. The samples were analysed by liquid and gas chromatography using various detection techniques: mass spectrometry, ultraviolet and electrochemical detection (LC-MS, LC-UV, LC-EchD and GC-MS). The sampling efficiency of 2MP filters for MIC varied with the origin of the glass fibre filter. Two Whatman filters (diameter 25 mm) with altogether 21 mumol of 2MP collected 100% of 9.8 micrograms of MIC during 30 min at an airflow rate of 1 l min-1. The workplace measurements were performed at two concentration levels, 0.003 and 0.09 mg m-3. The theoretical amounts of derivatisation reagent were 42 mumol (2MP filter), 52 mumol (2MP impinger) and 100 mumol (DBA). MIC concentrations were 20% lower by the 2MP methods compared with the DBA method (statistically significant difference). Breakthrough was 6% for the DBA method and 9% for the 2MP impinger method. To trap both MIC and isocyanic acid, which was also present in the workplace samples, a tenfold molar amount of 2MP reagent was used. The precision of sample preparation, expressed as relative standard deviation, was 3.5% (0.17 microgram ml-1, n = 6). The precision of sampling in the workplace was 15% (0.002 mg m-3, n = 6). The limit of quantification was 0.0006 mg m-3 for 30 l of air by the 2MP impinger method and 0.03-0.05 mg m-3 by the 2MP filter method. Hence, airborne MIC can be determined using 2MP as derivatisation reagent. Impinger sampling is preferable when low concentration levels are expected. PMID:11193080

  8. Lanthanide N,N'-piperazine-bis(methylenephosphonates) (Ln=La, Ce, Nd) that display flexible frameworks, reversible hydration and cation exchange

    SciTech Connect

    Mowat, John P.S.; Groves, John A.; Wharmby, Michael T.; Miller, Stuart R.; Li Yang; Lightfoot, Philip; Wright, Paul A.

    2009-10-15

    Hydrothermal syntheses of lanthanide bisphosphonate metal organic frameworks comprising the light lanthanides lanthanum, cerium and neodymium and N,N'-piperazine bis(methylenephosphonic acid) (H{sub 2}L(1) and its 2-methyl and 2,5-dimethyl derivatives (H{sub 2}L(2) and H{sub 2}L(3)) gives three new structure types. At elevated starting pH (ca. 5 and above) syntheses give 'type I' materials with all metals and acids of the study (MLnLxH{sub 2}O, M=Na, K, Cs; Ln=La, Ce, Nd; x{approx}4: KCeL(1).4H{sub 2}O, C2/c, a=23.5864(2) A, b=12.1186(2) A, c=5.6613(2) A, beta=93.040(2){sup o}). The framework of structure type I shows considerable flexibility as the ligand is changed, due mainly to rotation around the -N-CH{sub 2}- bond of the linker in response to steric considerations. Type I materials demonstrate cation exchange and dehydration and rehydration behaviour. Upon dehydration of KCeL.4H{sub 2}O, the space group changes to P2{sub 1}/n, a=21.8361(12) A, b=9.3519(4) A, c=5.5629(3) A, beta=96.560(4){sup o}, as a result of a change of the piperazine ring from chair to boat configuration. When syntheses are performed at lower pH, two other structure types crystallise. With the 'non-methyl' ligand 1, type II materials result (LnL(1)H{sub 2}L(1).4.5H{sub 2}O: Ln=La, P-1, a=5.7630(13) A, b=10.213(2) A, c=11.649(2) A, alpha=84.242(2){sup o}, beta=89.051(2){sup o}, gamma=82.876(2){sup o}) in which one half of the ligands coordinate via the piperazine nitrogen atoms. With the 2-methyl ligand, structure type III crystallises (LnHL(2).4H{sub 2}O: Ln=Nd, Ce, P2{sub 1}/c, a=5.7540(9) A, b=14.1259(18) A, c=21.156(5) A, beta=90.14(2){sup o}) due to unfavourable steric interactions of the methyl group in structure type II. - Graphical abstract: The lanthanides La, Ce and Nd give a family of metal organic frameworks based on N,N'-piperazinebismethylenephosphonate ligands: these display reversible dehydration, structural flexibility and cation exchange.

  9. Novel 3-nitro-1H-1,2,4-triazole-based piperazines and 2-amino-1,3-benzothiazoles as antichagasic agents.

    PubMed

    Papadopoulou, Maria V; Bloomer, William D; Rosenzweig, Howard S; Kaiser, Marcel; Chatelain, Eric; Ioset, Jean-Robert

    2013-11-01

    We have previously shown that 3-nitro-1H-1,2,4-triazole-based amines demonstrate significant trypanocidal activity, in particular against Trypanosoma cruzi, the causative parasite of Chagas disease. In the present work we further expanded our research by evaluating in vitro the trypanocidal activity of nitrotriazole-based piperazines and nitrotriazole-based 2-amino-1,3-benzothiazoles to establish additional SARs. All nitrotriazole-based derivatives were active or moderately active against T. cruzi; however two of them did not fulfill the selectivity criteria. Five derivatives were active or moderately active against Trypanosoma brucei rhodesiense while one derivative was moderately active against Leishmania donovani. Active compounds against T. cruzi demonstrated selectivity indexes (toxicity to host cells/toxicity to T. cruzi amastigotes) from 117 to 1725 and 12 of 13 compounds were up to 39-fold more potent than the reference compound benznidazole. Detailed SARs are discussed. PMID:24012457

  10. Synthesis and biological evaluation of 1-(1,2-benzisothiazol-3-yl)- and (1,2-benzisoxazol-3-yl)piperazine derivatives as potential antipsychotic agents.

    PubMed

    Yevich, J P; New, J S; Smith, D W; Lobeck, W G; Catt, J D; Minielli, J L; Eison, M S; Taylor, D P; Riblet, L A; Temple, D L

    1986-03-01

    Members of the series of title compounds were tested for potential antipsychotic activity in relevant receptor binding assays and behavioral screens. Structure-activity relationships within the series are discussed. Compound 24 (BMY 13859-1), a (1,2-benzisothiazol-3-yl)piperazine derivative, was selected for further study because of its potent and selective profile in primary CNS tests. It was active in the Sidman avoidance paradigm and blocked amphetamine-induced stereotyped behavior in dogs for up to 7 h. The compound's lack of typical neuroleptic-like effects in the rat catalepsy test and its failure to produce dopamine receptor supersensitivity following chronic administration indicate that it should not cause the movement disorders commonly associated with antipsychotic therapy. Although 24 has potent affinity for dopaminergic binding sites, its even greater affinity for serotonin receptors suggests that a serotonergic component may be relevant to its atypical profile. Compound 24 is currently undergoing clinical evaluation in schizophrenic patients. PMID:2869146

  11. Novel 3-nitro-1H-1,2,4-triazole-based piperazines and 2-amino-1,3-benzothiazoles as antichagasic agents

    PubMed Central

    Papadopoulou, Maria V.; Bloomer, William D.; Rosenzweig, Howard S.; Kaiser, Marcel; Chatelain, Eric; Ioset, Jean-Robert

    2013-01-01

    We have previously shown that 3-nitro-1H-1,2,4-triazole-based amines demonstrate significant trypanocidal activity, in particular against T. cruzi, the causative parasite of Chagas disease. In the present work we further expanded our research by evaluating in vitro the trypanocidal activity of nitrotriazole-based piperazines and nitrotriazole-based 2-amino-1,3-benzothiazoles to establish additional SARs. All nitrotriazole-based derivatives were active or moderately active against T. cruzi; however two of them did not fulfill the selectivity criteria. Five derivatives were active or moderately active against T.b. rhodesiense while one derivative was moderately active against L. donovani. Active compounds against T. cruzi demonstrated selectivity indexes (toxicity to host cells/toxicity to T. cruzi amastigotes) from 117-1725 and 12 of 13 compounds were up to 39-fold more potent than the reference compound benznidazole. Detailed SARs are discussed. PMID:24012457

  12. Synthesis, characterization and biological activities of metal(II) dipicolinate complexes derived from pyridine-2,6-dicarboxylic acid and 2-(piperazin-1-yl)ethanol

    NASA Astrophysics Data System (ADS)

    Büyükkıdan, Nurgün; Yenikaya, Cengiz; İlkimen, Halil; Karahan, Ceyda; Darcan, Cihan; Korkmaz, Tülin; Süzen, Yasemin

    2015-12-01

    The new water-soluble and air stable compounds (H2ppz)[Co(dipic)2]·6H2O (1), (H2ppz)[Ni(dipic)2]·6H2O (2) and (H2ppz)[Zn(dipic)2]·6H2O (3) were prepared by the reaction of corresponding metal(II) acetates and a proton transfer salt, (H2ppz) (Hdipic)2, (4) of pyridine-2,6-dicarboxylic acid (H2dipic) and 2-(piperazin-1-yl)ethanol (ppz). The compounds 1-3 were characterized by elemental, IR, UV-vis. thermal analyses, magnetic measurement and single crystal X-ray diffraction studies. The molecular structures of the title compounds consist of one 1-(2-hydroxyethyl)piperazine-1,4-diium (H2ppz+2) cation, one bis(pyridine-2,6-dicarboxylate)metal(II) [M(dipic)2]2- anion, and six uncoordinated water molecules. In compounds 1-3 the metal ions coordinate to two oxygen and one nitrogen atoms of two pyridine-2,6-dicarboxylate molecules forming an octahedral environment. Antimicrobial activities against Gram (-) wild type (Escherichia coli and Pseudomonas aeruginosa), Gram (+) wild type (Staphylococcus aureus, Staphylococcus epidermidis, Bacillus cereus and Bacillus subtilis) and clinical isolate (Morganella morganii, Proteus vulgaris and Enterobacter aeruginosa) were also studied. The results were reported, discussed and compared with the corresponding starting materials ((H2ppz) (Hdipic)2 (4), H2dipic and ppz). MIC (Minimal Inhibition Concentration) values of the newly synthesized compounds were determined as 4000 μg/ml (except B. subtilis and clinical isolate E. aeruginosa, >4000 μg/ml).

  13. N-(omega-(4-(2-methoxyphenyl)piperazin-1-yl)alkyl)carboxamides as dopamine D2 and D3 receptor ligands.

    PubMed

    Hackling, Anneke; Ghosh, Robin; Perachon, Sylvie; Mann, André; Höltje, Hans-Dieter; Wermuth, Camille G; Schwartz, Jean-Charles; Sippl, Wolfgang; Sokoloff, Pierre; Stark, Holger

    2003-08-28

    The dopamine D(3) receptor is recognized as a potential therapeutic target for the treatment of various neurological and psychiatric disorders. Targetting high affinity and D(3) versus D(2) receptor-preferring ligands, the partial agonist BP 897 was taken as a lead structure. Variations in the spacer and the aryl moiety led to N-alkylated 1-(2-methyoxyphenyl)piperazines with markedly improved affinity and selectivity. Molecular modeling studies supported the structural development. Pharmacophore models for dopamine D(2) and D(3) receptor ligands were developed from their potentially bioactive conformation and were compared in order to get insight into molecular properties of importance for D(2)/D(3) receptor selectivity. For the 72 compounds presented here, an extended and more linear conformation in the aliphatic or aryl spacers turned out to be crucial for dopamine D(3) receptor selectivity. Structural diversity in the aryl moiety (benzamides, heteroarylamides, arylimides) had a major influence on (sub)nanomolar D(3) receptor affinity, which was optimized with more rigid aryl acrylamide derivatives. Compound 38 (ST 280, (E)-4-iodo-N-(4-(4-(2-methoxyphenyl)piperazin-1-yl)butyl)cinnamoylamide) displayed a most promising pharmacological profile (K(i) (hD(3)) = 0.5 nM; K(i) (hD(2L)) = 76.4 nM; selectivity ratio of 153), and above that, compound 38 offered the prospect of a novel radioligand as a pharmacological tool for various D(3) receptor-related in vitro and in vivo investigation. PMID:12930150

  14. Critical tests in equids with fenbendazole alone or combined with piperazine: particular reference to activity on benzimidazole-resistant small strongyles.

    PubMed

    Lyons, E T; Tolliver, S C; Drudge, J H

    1983-02-01

    Seven critical tests in equids were conducted with single doses of fenbendazole (5 mg kg-1) alone (Panacur--American Hoechst, Somerville, NJ); (2 tests with paste and 1 with suspension formulation) or in combination with piperazine (American Hoechst); (40 mg base kg-1); (4 tests with paste formulation). The main purpose of the tests was evaluation of activity against benzimidazole-resistant small strongyles (Cyathostomum catinatum, Cyathostomum coronatum, Cylicocyclus nassatus, Cylicostephanus goldi, and Cylicostephanus longibursatus). Natural infections of 2 populations of benzimidazole-resistant small strongyles were evaluated; 1 was population B in 2 horses and the other was population S in 5 ponies. Removal of the 5 species of population B was 49-91% in the animal treated with fenbendazole paste alone and 100% (4 of these species present) in the animal treated with the combination. For population S, 2 of the 5 resistant species were present in small numbers in 1 animal treated with fenbendazole paste alone and all were removed; the 1 animal receiving fenbendazole suspension alone had removals of 0-70% for the 5 benzimidazole-resistant species. Also for population S, the 5 resistant species were present in 2 animals treated with the paste combination and removal was 98-100% and of 4 of the 5 resistant species in 1 animal, removal was 76-99%. Removal of large strongyles (Strongylus vulgaris and Strongylus edentatus) was 92-100% for fenbendazole paste alone or in combination with piperazine in the 5 infected animals. For Oxyuris equi, present in 1 animal treated with the combination, there was 91% removal of immature and 100% removal of mature specimens. There probHably was no activity by fenbendazole alone or the combination against bots, tapeworms, and parenteral stages of S. vulgaris and S. edentatus. The combination may have had some activity against immature Habronema spp. and mature abronema muscae. PMID:6683041

  15. Toward Understanding Amines and Their Degradation Products from Postcombustion CO2 Capture Processes with Aerosol Mass Spectrometry

    PubMed Central

    2015-01-01

    Amine-based postcombustion CO2 capture (PCCC) is a promising technique for reducing CO2 emissions from fossil fuel burning plants. A concern of the technique, however, is the emission of amines and their degradation byproducts. To assess the environmental risk of this technique, standardized stack sampling and analytical methods are needed. Here we report on the development of an integrated approach that centers on the application of a high-resolution time-of-flight aerosol mass spectrometer (HR-ToF-AMS) for characterizing amines and PCCC-relevant species. Molecular characterization is achieved via ion chromatography (IC) and electrospray ionization high-resolution mass spectrometry (ESI-MS). The method has been optimized, particularly, by decreasing the AMS vaporizer temperature, to gain quantitative information on the elemental composition and major nitrogen-containing species in laboratory-degraded amine solvents commonly tested for PCCC applications, including ethanolamine (MEA), methyldiethanolamine (MDEA), and piperazine (PIP). The AMS-derived nitrogen-to-carbon (N/C) ratios for the degraded solvent and product mixtures agree well with the results from a total organic carbon and total nitrogen (TOC/TN) analyzer. In addition, marker ions identified in the AMS spectra are used to estimate the mass contributions of individual species. Overall, our results indicate that this new approach is suitable for characterizing PCCC-related mixtures as well as organic nitrogen species in other sample types. As an online instrument, AMS can be used for both real-time characterization of emissions from operating PCCC plants and ambient particles in the vicinity of the facilities. PMID:24617831

  16. Measurement of nitrosamine and nitramine formation from NOx reactions with amines during amine-based carbon dioxide capture for postcombustion carbon sequestration.

    PubMed

    Dai, Ning; Shah, Amisha D; Hu, Lanhua; Plewa, Michael J; McKague, Bruce; Mitch, William A

    2012-09-01

    With years of full-scale experience for precombustion CO(2) capture, amine-based technologies are emerging as the prime contender for postcombustion CO(2) capture. However, concerns for postcombustion applications have focused on the possible contamination of air or drinking water supplies downwind by potentially carcinogenic N-nitrosamines and N-nitramines released following their formation by NO(x) reactions with amines within the capture unit. Analytical methods for N-nitrosamines in drinking waters were adapted to measure specific N-nitrosamines and N-nitramines and total N-nitrosamines in solvent and washwater samples. The high levels of amines, aldehydes, and nitrite in these samples presented a risk for the artifactual formation of N-nitrosamines during sample storage or analysis. Application of a 30-fold molar excess of sulfamic acid to nitrite at pH 2 destroyed nitrite with no significant risk of artifactual nitrosation of amines. Analysis of aqueous morpholine solutions purged with different gas-phase NO and NO(2) concentrations indicated that N-nitrosamine formation generally exceeds N-nitramine formation. The total N-nitrosamine formation rate was at least an order of magnitude higher for the secondary amine piperazine (PZ) than for the primary amines 2-amino-2-methyl-1-propanol (AMP) and monoethanolamine (MEA) and the tertiary amine methyldiethanolamine (MDEA). Analysis of pilot washwater samples indicated a 59 μM total N-nitrosamine concentration for a system operated with a 25% AMP/15% PZ solvent, but only 0.73 μM for a 35% MEA solvent. Unfortunately, a greater fraction of the total N-nitrosamine signal was uncharacterized for the MEA-associated washwater. At a 0.73 μM total N-nitrosamine concentration, a ~25000-fold reduction in concentration is needed between washwater units and downwind drinking water supplies to meet proposed permit limits. PMID:22831707

  17. Toward understanding amines and their degradation products from postcombustion CO2 capture processes with aerosol mass spectrometry.

    PubMed

    Ge, Xinlei; Shaw, Stephanie L; Zhang, Qi

    2014-05-01

    Amine-based postcombustion CO2 capture (PCCC) is a promising technique for reducing CO2 emissions from fossil fuel burning plants. A concern of the technique, however, is the emission of amines and their degradation byproducts. To assess the environmental risk of this technique, standardized stack sampling and analytical methods are needed. Here we report on the development of an integrated approach that centers on the application of a high-resolution time-of-flight aerosol mass spectrometer (HR-ToF-AMS) for characterizing amines and PCCC-relevant species. Molecular characterization is achieved via ion chromatography (IC) and electrospray ionization high-resolution mass spectrometry (ESI-MS). The method has been optimized, particularly, by decreasing the AMS vaporizer temperature, to gain quantitative information on the elemental composition and major nitrogen-containing species in laboratory-degraded amine solvents commonly tested for PCCC applications, including ethanolamine (MEA), methyldiethanolamine (MDEA), and piperazine (PIP). The AMS-derived nitrogen-to-carbon (N/C) ratios for the degraded solvent and product mixtures agree well with the results from a total organic carbon and total nitrogen (TOC/TN) analyzer. In addition, marker ions identified in the AMS spectra are used to estimate the mass contributions of individual species. Overall, our results indicate that this new approach is suitable for characterizing PCCC-related mixtures as well as organic nitrogen species in other sample types. As an online instrument, AMS can be used for both real-time characterization of emissions from operating PCCC plants and ambient particles in the vicinity of the facilities. PMID:24617831

  18. Solid-state variable-temperature NMR study of the phase separation of polybutadiene polyurethane zwitterionomers

    NASA Astrophysics Data System (ADS)

    Yang, G.; Chen, Q.; Wang, Y.; Yang, C.; Wu, X.

    1994-07-01

    Polybutadiene polyurethane (PBDPU) zwitterionomers based on 4,4'-diphenylmethane diisocyanate (MDI), methyl-diethanolamine (MDEA), and hydroxy terminated polybutadiene are studied with variable-temperature (VT) wide-line 1H NMR. Spin—spin relaxation times ( T2) and spin—lattice relaxation times ( T1) are measured. It is found that phase separation of PBDPU does not change significantly upon ionization. The initial incorporation of ionization groups destroys the crystallinity of the hard segment while further ionization enhances physical crosslinks in the hard phase. The results are compared with a previous VT NMR study on polyether polyurethane zwitterionomers based on MDI, MDEA and 1000 Da molecular weight polytetramethylene oxide.

  19. Liquid chromatography tandem mass spectrometry determination of selected synthetic cathinones and two piperazines in oral fluid. Cross reactivity study with an on-site immunoassay device.

    PubMed

    de Castro, Ana; Lendoiro, Elena; Fernández-Vega, Hadriana; Steinmeyer, Stefan; López-Rivadulla, Manuel; Cruz, Angelines

    2014-12-29

    Since the past few years, several synthetic cathinones and piperazines have been introduced into the drug market to substitute illegal stimulant drugs such as amphetamine and derivatives or cocaine due to their unregulated situation. These emerging drugs are not usually included in routine toxicological analysis. We developed and validated a LC-MS/MS method for the determination of methedrone, methylone, mephedrone, 3,4-methylenedioxypyrovalerone (MDPV), fluoromethcathinone, fluoromethamphetamine, 1-(3-chlorophenyl)piperazine (mCPP) and 3-trifluoromethylphenylpiperazine (TFMPP) in oral fluid. Sample extraction was performed using Strata X cartridges. Chromatographic separation was achieved in 10min using an Atlantis(®) T3 column (100mm×2.1mm, 3μm), and formic acid 0.1% and acetonitrile as mobile phase. The method was satisfactorily validated, including selectivity, linearity (0.2-0.5 to 200ng/mL), limits of detection (0.025-0.1ng/mL) and quantification (0.2-0.5ng/mL), imprecision and accuracy in neat oral fluid (%CV=0.0-12.7% and 84.8-103.6% of target concentration, respectively) and in oral fluid mixed with Quantisal™ buffer (%CV=7.2-10.3% and 80.2-106.5% of target concentration, respectively), matrix effect in neat oral fluid (-11.6 to 399.7%) and in oral fluid with Quantisal™ buffer (-69.9 to 131.2%), extraction recovery (87.9-134.3%) and recovery from the Quantisal™ (79.6-107.7%), dilution integrity (75-99% of target concentration) and stability at different conditions (-14.8 to 30.8% loss). In addition, cross reactivity produced by the studied synthetic cathinones in oral fluid using the Dräger DrugTest 5000 was assessed. All the analytes produced a methamphetamine positive result at high concentrations (100 or 10μg/mL), and fluoromethamphetamine also at low concentration (0.075μg/mL). PMID:25482853

  20. N-Nitrosopiperazines form at high pH in post-combustion capture solutions containing piperazine: a low-energy collisional behaviour study.

    PubMed

    Jackson, Phil; Attalla, Moetaz I

    2010-12-30

    During the process of exploring aqueous piperazine chemistry under simulated flue-gas scrubbing conditions, positive-ion electrospray ionisation mass spectrometric (ESI-MS) analyses of the resulting reaction mixtures in a triple quadrupole system revealed the presence of peaks at m/z 116 and 145, the putative N-nitroso derivatives of piperazine. Confirmation of the presence of these species in the reaction mixtures was achieved using collision-induced dissociation experiments. A purchased standard, together with in-house synthesised N-nitrosopiperazine standards (including N-nitroso derivatives derived from deuterium-labelled precursor materials), were used for this purpose. Across a small range of collision energies, large fluctuations in the abundance of the two major product ions of protonated N-nitrosopiperazine, m/z 86 and 85, were observed. Using B3LYP/6-311 + +G(d,p) computations, the potential energy surface was determined for loss of NO and [H,N,O]. At an activation energy slightly in excess of 1 eV, intramolecular isomerisation precedes loss of NO (m/z 86) via a 4,1 H-shift, and at activation energies between 2.1-2.3 eV, consecutive loss of NO and atomic hydrogen competes with the direct loss of nitrosyl hydride (m/z 85). It is recommended that any multiple reaction monitoring method for quantifying N-nitrosopiperazines at low collision energies use the sum of both transitions (m/z 116 ← 85, m/z 116 ← 86) to avoid errors that could be introduced by subtle changes in ES source conditions or collision voltages. This approach is adopted in an HPLC/MS/MS method used to monitor the degradation of N-nitrosopiperazine exposed to (i) broad-band UV light and (ii) heat typical of an amine regeneration (stripper) tower. The results reveal that aqueous N-nitrosopiperazine is thermally stable at 150°C but will degrade slowly upon exposure to UV light. PMID:21108305

  1. Single-walled carbon nanotubes functionalized with aptamer and piperazine-polyethylenimine derivative for targeted siRNA delivery into breast cancer cells.

    PubMed

    Mohammadi, Marzieh; Salmasi, Zahra; Hashemi, Maryam; Mosaffa, Fatemeh; Abnous, Khalil; Ramezani, Mohammad

    2015-05-15

    Epithelial cell adhesion molecule (EpCAM) is a glycosylated type 1 membrane protein which is frequently over expressed in most solid tumors and it has recently been identified as a cancer stem cell (CSC) marker. Specific targeting of CSCs using nano-carriers would enhance treatment efficacy of cancer. In this study, we used a RNA aptamer against EpCAM (EpDT3) attached physically to our newly synthesized non-viral vector, based on single-walled carbon nanotube (SWNT) conjugated to piperazine-polyethylenimine derivative. The DNA transfection efficiency and siRNA delivery activity of the synthesized vector was investigated against upregulated BCL9l, which has been associated with breast and colorectal cancers. The complexes of the vector-aptamer/siRNA could specifically induce apoptosis by more than 20% in MCF-7 cell line as a positive EpCAM than MDA-MB-231 cells which are EpCAM negative. The decrease of BCL9l protein level was observed with western blot analysis in MCF-7 cells indicating the targeted silencing activity of the complex. PMID:25712164

  2. Ab initio and density functional theory calculations of molecular structure and vibrational spectra of 4-(2-Hydroxyethyl) piperazine-1-ethanesulfonic acid.

    PubMed

    Kumar, J Sharmi; Devi, T S Renuga; Ramkumaar, G R; Bright, A

    2016-01-01

    The FTIR and FT-Raman spectra of 4-(2-Hydroxyethyl) piperazine-1-ethanesulfonic acid were recorded and the structural and spectroscopic data of the molecule in the ground state were calculated using Hartree-Fock and Density Functional Method (B3LYP). The most stable conformer was optimized and the structural and vibrational parameters were determined. With the observed FTIR and FT-Raman data, a complete vibrational band assignment and analysis of the fundamental modes of the compound were carried out. Thermodynamic properties, Mulliken and natural atomic charge distribution were calculated using both Hartree-Fock and Density Functional Method and compared. UV-Visible and HOMO-LUMO analysis were carried out. (1)H and (13)C NMR chemical shifts of the molecule were calculated using gauge including atomic orbital method and were compared with experimental results. Stability of the molecule arising from hyperconjugative interactions and charge delocalization has been analyzed using natural bond orbital analysis. The first order hyperpolarizability (β) and molecular electrostatic potential of the molecule was computed using DFT calculations. The electron density based local reactivity descriptor such as Fukui functions were calculated to explain the chemically reactive site in the molecule. PMID:26278882

  3. Ab initio and density functional theory calculations of molecular structure and vibrational spectra of 4-(2-Hydroxyethyl) piperazine-1-ethanesulfonic acid

    NASA Astrophysics Data System (ADS)

    Kumar, J. Sharmi; Devi, T. S. Renuga; Ramkumaar, G. R.; Bright, A.

    2016-01-01

    The FTIR and FT-Raman spectra of 4-(2-Hydroxyethyl) piperazine-1-ethanesulfonic acid were recorded and the structural and spectroscopic data of the molecule in the ground state were calculated using Hartree-Fock and Density Functional Method (B3LYP). The most stable conformer was optimized and the structural and vibrational parameters were determined. With the observed FTIR and FT-Raman data, a complete vibrational band assignment and analysis of the fundamental modes of the compound were carried out. Thermodynamic properties, Mulliken and natural atomic charge distribution were calculated using both Hartree-Fock and Density Functional Method and compared. UV-Visible and HOMO-LUMO analysis were carried out. 1H and 13C NMR chemical shifts of the molecule were calculated using gauge including atomic orbital method and were compared with experimental results. Stability of the molecule arising from hyperconjugative interactions and charge delocalization has been analyzed using natural bond orbital analysis. The first order hyperpolarizability (β) and molecular electrostatic potential of the molecule was computed using DFT calculations. The electron density based local reactivity descriptor such as Fukui functions were calculated to explain the chemically reactive site in the molecule.

  4. Antioxidant, DNA binding and nuclease activities of heteroleptic copper(II) complexes derived from 2-((2-(piperazin-1-yl)ethylimino)methyl)-4-substituted phenols and diimines

    NASA Astrophysics Data System (ADS)

    Ravichandran, J.; Gurumoorthy, P.; Imran Musthafa, M. A.; Kalilur Rahiman, A.

    2014-12-01

    A series of heteroleptic copper(II) complexes of the type [CuL1-4(diimine)](ClO4)2 (1-8) [L1-4 = 2-((2-(piperazin-1-yl)ethylimino)methyl)-4-substituted phenols, and diimine = 2,2‧-bipyridyl (bpy) or 1,10-phenanthroline (phen)], have been synthesized and characterized by spectroscopic methods. The IR spectra of complexes indicate the presence of uncoordinated perchlorate anions and the electronic spectra revealed the square pyramidal geometry with N4O coordination environment around copper(II) nuclei. Electrochemical studies of the mononuclear complexes evidenced one-electron irreversible reduction wave in the cathodic region. The EPR spectra of complexes with g|| (2.206-2.214) and A|| (154-172 × 10-4 cm-1) values support the square-based CuN3O coordination chromophore and the presence of unpaired electron localized in dx-y ground state. Antioxidant studies against DPPH revealed effective radical scavenging properties of the synthesized complexes. Binding studies suggest that the heteroleptic copper(II) complexes interact with calf thymus DNA (CT-DNA) through minor-groove and electrostatic interaction, and all the complexes display pronounced nuclease activity against supercoiled pBR322 DNA.

  5. Mononuclear zinc(II) complexes of 2-((2-(piperazin-1-yl)ethylimino)methyl)-4-substituted phenols: Synthesis, structural characterization, DNA binding and cheminuclease activities

    NASA Astrophysics Data System (ADS)

    Ravichandran, J.; Gurumoorthy, P.; Karthick, C.; Kalilur Rahiman, A.

    2014-03-01

    Four new zinc(II) complexes [Zn(HL1-4)Cl2] (1-4), where HL1-4 = 2-((2-(piperazin-1-yl)ethylimino)methyl)-4-substituted phenols, have been isolated and fully characterized using various spectro-analytical techniques. The X-ray crystal structure of complex 4 shows the distorted trigonal-bipyramidal coordination geometry around zinc(II) ion. The crystal packing is stabilized by intermolecular NH⋯O hydrogen bonding interaction. The complexes display no d-d electronic band in the visible region due to d10 electronic configuration of zinc(II) ion. The electrochemical properties of the synthesized ligands and their complexes exhibit similar voltammogram at reduction potential due to electrochemically innocent Zn(II) ion, which evidenced that the electron transfer is due to the nature of the ligand. Binding interaction of complexes with calf thymus DNA was studied by UV-Vis absorption titration, viscometric titration and cyclic voltammetry. All complexes bind with CT DNA by intercalation, giving the binding affinity in the order of 2 > 1 ≫ 3 > 4. The prominent cheminuclease activity of complexes on plasmid DNA (pBR322 DNA) was observed in the absence and presence of H2O2. Oxidative pathway reveals that the underlying mechanism involves hydroxyl radical.

  6. 4-(2-Meth­oxy­phen­yl)piperazin-1-ium 6-chloro-5-isopropyl-2,4-dioxopyrimidin-1-ide

    PubMed Central

    Al-Omary, Fatmah A. M.; Ghabbour, Hazem A.; El-Emam, Ali A.; Chidan Kumar, C. S.; Fun, Hoong-Kun

    2014-01-01

    In the cation of the title salt, C11H17N2O+·C7H8ClN2O2 −, the piperazine ring adopts a distorted chair conformation and contains a positively charged N atom with quaternary character. Its mean plane makes a dihedral angle of 42.36 (8)° with the phenyl ring of its 2-meth­oxy­phenyl substituent. The 2,4-dioxopyrimidin-1-ide anion is generated by deprotonation of the N atom at the 1-position of the pyrimidine­dione ring. Intra­molecular C—H⋯O hydrogen bonds generate S(6) ring motifs in both the cation and the anion. In the crystal, N—H⋯O, N—H⋯N and C—H⋯O hydrogen bonds are also observed, resulting in a two-dimensional network parallel to the ab plane. The crystal stability is further consolidated by weak C—H⋯π inter­actions. PMID:24764966

  7. 1,4-Disubstituted aromatic piperazines with high 5-HT2A/D2 selectivity: Quantitative structure-selectivity investigations, docking, synthesis and biological evaluation.

    PubMed

    Möller, Dorothee; Salama, Ismail; Kling, Ralf C; Hübner, Harald; Gmeiner, Peter

    2015-09-15

    Simultaneous targeting of dopamine D2 and 5-HT2A receptors for the treatment of schizophrenia is one key feature of typical and atypical antipsychotics. In most of the top-selling antipsychotic drugs like aripiprazole and risperidone, high affinity to both receptors can be attributed to the presence of 1,4-disubstituted aromatic piperazines or piperidines as primary receptor recognition elements. Taking advantage of our in-house library of phenylpiperazine-derived dopamine receptor ligands and experimental data, we established highly significant CoMFA and CoMSIA models for the prediction of 5-HT2A over D2 selectivity. Subsequently, the models were applied to identify the selective candidates 55-57 from our newly synthesized library of GPCR ligands comprising a pyrazolo[1,5-a]pyridine head group and a 1,2,3-triazole based linker unit. The test compound 57 showed subnanomolar a Ki value (0.64 nM) for 5-HT2A and more than 10- and 30-fold selectivity over the dopamine receptor isoforms D2S and D2L, respectively. PMID:26299826

  8. Synthesis of Novel Pyrimidin-4-One Bearing Piperazine Ring-Based Amides as Glycogen Synthase Kinase-3β Inhibitors with Antidepressant Activity.

    PubMed

    Khan, Imran; Tantray, Mushtaq A; Hamid, Hinna; Alam, Mohammad Sarwar; Kalam, Abul; Shaikh, Faraz; Shah, Anamik; Hussain, Firasat

    2016-05-01

    Novel pyrimidin-4-one derivatives have been synthesized using EDC coupling and evaluated as glycogen synthase kinase-3β (GSK-3β) inhibitors. Among all the synthesized compounds, compound 5 (3-methyl-6-phenyl-2-(piperazin-1-yl)-3,4-dihydropyrimidin-4-one) exhibited the most potent inhibitory activity against GSK-3β with IC50 value of 74 nm. The molecular docking studies were performed to elucidate the binding modes of the compounds with the target, and a crucial interaction involving hydrogen bond formation with Val-135 to the active site of GSK-3β was observed. Furthermore, the synthesized compounds were subjected to in vivo evaluation of their antidepressant activity, and compound 5 showing highest inhibition of GSK-3β was also found to significantly reduce the duration of immobility at 50 mg/kg, when compared with fluoxetine, a known antidepressant drug. The results of our study suggest that compound 5 may serve as a valuable template for the design and development of inhibitors of GSK-3β with antidepressant activity. PMID:26714831

  9. Crystal structure of 3-[(4-benzyl-piperazin-1-yl)meth-yl]-5-(thio-phen-2-yl)-2,3-di-hydro-1,3,4-oxa-diazole-2-thione.

    PubMed

    Al-Omary, Fatmah A M; El-Emam, Ali A; Ghabbour, Hazem A; Chidan Kumar, C S; Quah, Ching Kheng; Fun, Hoong-Kun

    2015-03-01

    The title 1,3,4-oxa-diazole-2-thione derivative, C18H20N4OS2, crystallized with two independent mol-ecules (A and B) in the asymmetric unit. The 2-thienyl rings in both mol-ecules are rotationally disordered over two orientations by approximately 180 about the single C-C bond that connects it to the oxa-diazole thione ring; the ratios of site occupancies for the major and minor components were fixed in the structure refinement at 0.8:0.2 and 0.9:0.1 in mol-ecules A and B, respectively. The 1,3,4-oxa-diazole-2-thione ring forms dihedral angles of 7.71?(16), 10.0?(11) and 77.50?(12) (mol-ecule A), and 6.5?(3), 6.0?(9) and 55.30?(12) (mol-ecule B) with the major and minor parts of the disordered thio-phene ring and the mean plane of the adjacent piperazine ring, respectively, resulting in approximately V-shaped conformations for the mol-ecules. The piperazine ring in both mol-ecules adopts a chair conformation. The terminal benzene ring is inclined towards the mean plane of the piperazine ring with N-C-C-C torsion angles of -58.2?(3) and -66.2?(3) in mol-ecules A and B, respectively. In the crystal, no inter-molecular hydrogen bonds are observed. The crystal packing features short S?S contacts [3.4792?(9)?] and ?-? inter-actions [3.661?(3), 3.664?(11) and 3.5727?(10)?], producing a three-dimensional network. PMID:25844234

  10. Microwave-assisted synthesis of 4-chloro-N-(naphthalen-1-ylmethyl)-5-(3-(piperazin-1-yl)phenoxy)thiophene-2-sulfonamide (B-355252): a new potentiator of Nerve Growth Factor (NGF)-induced neurite outgrowth

    PubMed Central

    Williams, Alfred L.; Dandepally, Srinivasa R.; Gilyazova, Nailya; Witherspoon, Sam M; Ibeanu, Gordon

    2010-01-01

    The synthesis of 4-chloro-N-(naphthalen-1-ylmethyl)-5-(3-(piperazin-1-yl)phenoxy)thiophene-2-sulfonamide (B-355252) using a MW-assisted nucleophilic aromatic substitution (SNAr) reaction will be discussed. Utilization of this method allowed for the rapid generation of B-355252 heteroaryl ether core structure in the presence of cesium carbonate in dimethylformamide or tripotassium phosphate in N-methyl-2-pyrrolidone in 94% yield. Evaluation of B-355252 enhancement of nerve growth factors ability to stimulate neurite outgrowths was determined using NS-1 cells. PMID:22973068

  11. (3,3-Difluoro-pyrrolidin-1-yl)-[(2S,4S)-(4-(4-pyrimidin-2-yl-piperazin-1-yl)-pyrrolidin-2-yl]-methanone: A potent, selective, orally active dipeptidyl peptidase IV inhibitor

    SciTech Connect

    Ammirati, Mark J.; Andrews, Kim M.; Boyer, David D.; Brodeur, Anne M.; Danley, Dennis E.; Doran, Shawn D.; Hulin, Bernard; Liu, Shenping; McPherson, R. Kirk; Orena, Stephen J.; Parker, Janice C.; Polivkova, Jana; Qiu, Xiayang; Soglia, Carolyn B.; Treadway, Judith L.; VanVolkenburg, Maria A.; Wilder, Donald C.; Piotrowski, David W.; Pfizer

    2010-10-01

    A series of 4-substituted proline amides was synthesized and evaluated as inhibitors of dipeptidyl pepdidase IV for the treatment of type 2 diabetes. (3,3-Difluoro-pyrrolidin-1-yl)-[(2S,4S)-(4-(4-pyrimidin-2-yl-piperazin-1-yl)-pyrrolidin-2-yl]-methanone (5) emerged as a potent (IC{sub 50} = 13 nM) and selective compound, with high oral bioavailability in preclinical species and low plasma protein binding. Compound 5, PF-00734200, was selected for development as a potential new treatment for type 2 diabetes.

  12. Preparation and biodistribution of 1-((2-methoxyphenyl) piperazine)ferrocenecarboxamide labeled with technetium-99m as a potential brain receptor imaging agent.

    PubMed

    Saied, Nadia Malek; Mejri, Najoua; El Aissi, Radhia; Benoist, Eric; Saidi, Mouldi

    2015-06-01

    The goal of this study is to develop a novel brain receptor imaging agent. This study reports the synthesis, characterization and the biological evaluation of 1-((2-methoxyphenyl) piperazine)ferrocenecarboxamide labeled with technetium-99 m ((99m)Tc-MP). The (99m)Tc-MP was obtained quickly (radiolabelling time < 5 min), in 90% yield. The (99m)Tc-complex, characterized by HPLC (20-50% ACN of 0 at 5 min then 50% ACN of 5 at 17 min to finally with 50 at 20% ACN of 17 at 20 min), is stable, neutral and lipophilic enough to cross the blood-brain barrier which was confirmed by octanol/water partition coefficient (LogP = 1.82). In vivo biodistribution indicated that this complex had exceptional brain uptake (2.47% ID/g at 5 min and 0.75% ID/g at 60 min). The distribution of the activity at 15 min post-injection in various rat brain regions showed a higher accumulation in the hippocampus area. After blocking with 8-hydroxy-2-(dipropylamino) tetralin, the uptake of hippocampus was decreased significantly from 0.87% ID/g to 0.21% ID/g at 15 min p.i., while the cerebellum had no significant decrease. The new (99m)Tc-cyclopentadienyltricarbonyl technetium complex reported here showed promising biological results, making it an interesting starting point for the development of a new (99m)Tc-complex as brain receptor imaging agent. PMID:25993108

  13. Carbon dioxide adsorption by physisorption and chemisorption interactions in piperazine-grafted Ni2(dobdc) (dobdc = 1,4-dioxido-2,5-benzenedicarboxylate).

    PubMed

    Das, Anita; Southon, Peter D; Zhao, Ming; Kepert, Cameron J; Harris, Andrew T; D'Alessandro, Deanna M

    2012-10-14

    The metal-organic framework Ni(2)(dobdc) (CPO-27-Ni, where dobdc = 1,4-dioxido-2,5-benzenedicarboxylate) has been post-synthetically modified with piperazine (pip) - a known 'accelerator' to improve the kinetics of CO(2) uptake in alkanolamine solvents for chemical absorption - and the impact of the modification on the CO(2) uptake and selectivity over N(2) has been probed. While the modified framework, Ni(2)(dobdc)(pip)(0.5) (pip-CPO-27-Ni), exhibits a lower uptake of CO(2) compared with the non-grafted material, the selectivity for CO(2) over N(2) at 25 C and at pressures pertinent to post-combustion flue gas capture (0.1-0.15 bar) is enhanced. Mechanistically, the interaction between the CO(2) molecules and the free amine sites in pip-CPO-27-Ni occurs via physisorption and chemisorption interactions, in which CO(2) binds to the framework with an isosteric heat of adsorption (-Q(st)) of 40.5 kJ mol(-1) at very low coverage (P = 0.033 mbar), followed by binding at a higher heat of adsorption (-Q(st) = 46.2 kJ mol(-1) at P = 3.55 mbar). Pure water adsorption isotherms revealed a two-step mechanism for uptake in CPO-27-Ni, consistent with adsorption into the first and second hydration spheres of Ni(2+) followed by subsequent uptake via physisorption into the pores. Additional steric hindrance in pip-CPO-27-Ni results in a single step only. The working capacity over multiple cycles was also investigated using a temperature swing adsorption process which revealed reversible CO(2) adsorption and desorption of 10 wt% over 10 cycles. PMID:22903310

  14. Synthesis, biological evaluation and molecular docking study of novel piperidine and piperazine derivatives as multi-targeted agents to treat Alzheimer's disease.

    PubMed

    Meena, Poonam; Nemaysh, Vishal; Khatri, Manisha; Manral, Apra; Luthra, Pratibha Mehta; Tiwari, Manisha

    2015-03-01

    Development of Multi-Target Directed Ligands (MTDLs) has emerged as a promising approach for targeting complex etiology of Alzheimer's disease (AD). Following this approach, a new series of N'-(4-benzylpiperidin-/piperazin-/benzhydrylpiperazin-1-yl)alkylamine derivatives were designed, synthesized and biologically evaluated as inhibitors of cholinesterases (ChEs), amyloid-beta (Aβ) self aggregation and also for their radical scavenging activity. The in vitro studies showed that the majority of synthesized derivatives strongly inhibited acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) with IC50 values in the low-nanomolar range, and were clearly more potent than the reference compound donepezil in this regard. Among them, inhibitors 5h and 5k, strongly inhibited AChE, with IC50 value of 6.83nM and 2.13nM, respectively, and particularly, compound 5k was found to be highly selective for AChE (∼38-fold). Moreover, both kinetic analysis of AChE inhibition and the docking study suggested that 5k binds simultaneously to catalytic active site and peripheral anionic site of AChE. Besides, these compounds also exhibited greater ability to inhibit self-induced Aβ1-42 aggregation at 25μM with percentage inhibition from ∼54% to 89% and specially compound 5k provided highest inhibition (88.81%). Also, the derivatives containing methoxy and hydroxy groups showed potent oxygen radical absorbance capacity (ORAC) ranging from 2.2- to 4.4-fold of the Trolox value. Furthermore, results of ADMET studies suggested that all compounds exhibited appropriate drug like properties. Taken together, these results suggest that 5k might be a promising lead compound for further AD drug development. PMID:25624107

  15. 3-(Adamantan-1-yl)-4-methyl-1-[(4-phenyl­piperazin-1-yl)meth­yl]-1H-1,2,4-triazole-5(4H)-thione dichloro­methane hemisolvate

    PubMed Central

    El-Emam, Ali A.; Al-Omar, Mohamed A.; Al-Tamimi, Abdul-Malek S.; Ng, Seik Weng; Tiekink, Edward R. T.

    2012-01-01

    The asymmetric unit of the title dichloro­methane hemisolvate, C24H33N5S·0.5CH2Cl2, comprises an adamantan­yl/triazole derivative and half a CH2Cl2 mol­ecule of crystallization; the latter is disordered about a twofold axis of symmetry. The piperazine ring has a chair conformation and the two N-bound substituents occupy equatorial positions. The piperazine residue is almost normal to the triazole ring [N—N—C—N torsion angle = −79.9 (3)°] so that to a first approximation, the mol­ecule has an L-shape. Linear supra­molecular chains parallel to [001] are formed via C—H⋯S inter­actions. Two such chains are linked into a double chain via C—H⋯Cl inter­actions involving the disordered CH2Cl2 mol­ecules of solvation. PMID:22719551

  16. Crystal structure of catena-poly[[[tetra­aqua­zinc(II)]-μ-1,4-bis­[4-(1H-imidazol-1-yl)benzo­yl]piperazine] dinitrate monohydrate

    PubMed Central

    Hou, Chen; Gan, Hong-Mei; Liu, Jia-Cheng

    2015-01-01

    In the title polymeric complex, {[Zn(C24H22N6O2)(H2O)4](NO3)2·2H2O}n, the ZnII cation, located about a twofold rotation axis, is coordinated by two imidazole groups and four water mol­ecules in a distorted N2O4 octa­hedral geometry; among the four coordinate water mol­ecules, two are located on the same twofold rotation axis. The 1,4-bis­[4-(1H-imidazol-1-yl)benzo­yl]piperazine] ligand is centro-symmetric, with the centroid of the piperazine ring located on an inversion center, and bridges the ZnII cations, forming polymeric chains propagating along [201]. In the crystal, O—H⋯O and weak C—H⋯O hydrogen bonds link the polymeric chains, nitrate anions and solvent water mol­ecules into a three-dimensional supra­molecular architecture. A short O⋯O contact of 2.823 (13) Å is observed between neighboring nitrate anions. PMID:25995894

  17. Crystal structure of catena-poly[[[tetra-aqua-zinc(II)]-μ-1,4-bis-[4-(1H-imidazol-1-yl)benzo-yl]piperazine] dinitrate monohydrate].

    PubMed

    Hou, Chen; Gan, Hong-Mei; Liu, Jia-Cheng

    2015-05-01

    In the title polymeric complex, {[Zn(C24H22N6O2)(H2O)4](NO3)2·2H2O} n , the Zn(II) cation, located about a twofold rotation axis, is coordinated by two imidazole groups and four water mol-ecules in a distorted N2O4 octa-hedral geometry; among the four coordinate water mol-ecules, two are located on the same twofold rotation axis. The 1,4-bis-[4-(1H-imidazol-1-yl)benzo-yl]piperazine] ligand is centro-symmetric, with the centroid of the piperazine ring located on an inversion center, and bridges the Zn(II) cations, forming polymeric chains propagating along [201]. In the crystal, O-H⋯O and weak C-H⋯O hydrogen bonds link the polymeric chains, nitrate anions and solvent water mol-ecules into a three-dimensional supra-molecular architecture. A short O⋯O contact of 2.823 (13) Å is observed between neighboring nitrate anions. PMID:25995894

  18. Seeking potent anti-tubercular agents: Design, synthesis, anti-tubercular activity and docking study of various ((triazoles/indole)-piperazin-1-yl/1,4-diazepan-1-yl)benzo[d]isoxazole derivatives.

    PubMed

    Naidu, Kalaga Mahalakshmi; Srinivasarao, Singireddi; Agnieszka, Napiórkowska; Ewa, Augustynowicz-Kopeć; Kumar, Muthyala Murali Krishna; Chandra Sekhar, Kondapalli Venkata Gowri

    2016-05-01

    A series of thirty eight novel 3-(4-((substituted-1H-1,2,3-triazol-4-yl)methyl)piperazin-1-yl/1,4-diazepan-1-yl)benzo[d]isoxazole and 1-(4-(benzo[d]isoxazol-3-yl)piperazin-1-yl/1,4-diazepan-1-yl)-2-(1H-indol-3-yl)substituted-1-one analogues were synthesised, characterised using various analytical techniques and evaluated for in vitro anti-tubercular activity against Mycobacterium tuberculosis H37Rv strain and two 'wild' strains Spec. 210 and Spec. 192. The titled compounds exhibited minimum inhibitory concentration (MIC) ranging from 6.16 to >200μM. Among the tested compounds, 7i, 7y and 7z exhibited moderate activity (MIC=24.03-29.19μM) and 7j exhibited very good anti-tubercular activity (MIC=6.16μM). Furthermore, 7i, 7j, 7y and 7z were found to be non-toxic against mouse macrophage cell lines when screened for toxicity. All the synthesised compounds were docked to pantothenate synthetase enzyme site to know deferent binding interactions with the receptor. PMID:27020525

  19. Synthesis, structure-activity relationships, and biological properties of 1-heteroaryl-4-[omega-(1H-indol-3-yl)alkyl]piperazines, novel potential antipsychotics combining potent dopamine D2 receptor antagonism with potent serotonin reuptake inhibition.

    PubMed

    Smid, Pieter; Coolen, Hein K A C; Keizer, Hiskias G; van Hes, Rolf; de Moes, Jan-Peter; den Hartog, Arnold P; Stork, Bob; Plekkenpol, Rob H; Niemann, Leonarda C; Stroomer, Cees N J; Tulp, Martin Th M; van Stuivenberg, Herman H; McCreary, Andrew C; Hesselink, Mayke B; Herremans, Arnoud H J; Kruse, Chris G

    2005-11-01

    A series of novel bicyclic 1-heteroaryl-4-[omega-(1H-indol-3-yl)alkyl]piperazines was synthesized and evaluated on binding to dopamine D(2) receptors and serotonin reuptake sites. This class of compounds proved to be potent in vitro dopamine D(2) receptor antagonists and in addition were highly active as serotonin reuptake inhibitors. Some key representatives showed potent pharmacological in vivo activities after oral dosing in both the antagonism of apomorphine-induced climbing and the potentiation of 5-HTP-induced behavior in mice. On the basis of the preclinical data, 8-{4-[3-(5-fluoro-1H-indol-3-yl)propyl]piperazin-1-yl}-4H-benzo[1,4]oxazin-(R)-2-methyl-3-one (45c, SLV314) was selected for clinical development. In vitro and in vivo studies revealed that 45c has favorable pharmacokinetic properties and a high CNS-plasma ratio. Molecular modeling studies showed that the bifunctional activity of 45c can be explained by its ability to adopt two different conformations fitting either the dopamine D(2) receptor pharmacophore or the serotonin transporter pharmacophore. PMID:16250644

  20. Direct Phenotypic Screening in Mice: Identification of Individual, Novel Antinociceptive Compounds from a Library of 734,821 Pyrrolidine Bis-piperazines.

    PubMed

    Houghten, Richard A; Ganno, Michelle L; McLaughlin, Jay P; Dooley, Colette T; Eans, Shainnel O; Santos, Radleigh G; LaVoi, Travis; Nefzi, Adel; Welmaker, Greg; Giulianotti, Marc A; Toll, Lawrence

    2016-01-11

    The hypothesis in the current study is that the simultaneous direct in vivo testing of thousands to millions of systematically arranged mixture-based libraries will facilitate the identification of enhanced individual compounds. Individual compounds identified from such libraries may have increased specificity and decreased side effects early in the discovery phase. Testing began by screening ten diverse scaffolds as single mixtures (ranging from 17,340 to 4,879,681 compounds) for analgesia directly in the mouse tail withdrawal model. The "all X" mixture representing the library TPI-1954 was found to produce significant antinociception and lacked respiratory depression and hyperlocomotor effects using the Comprehensive Laboratory Animal Monitoring System (CLAMS). The TPI-1954 library is a pyrrolidine bis-piperazine and totals 738,192 compounds. This library has 26 functionalities at the first three positions of diversity made up of 28,392 compounds each (26 × 26 × 42) and 42 functionalities at the fourth made up of 19,915 compounds each (26 × 26 × 26). The 120 resulting mixtures representing each of the variable four positions were screened directly in vivo in the mouse 55 °C warm-water tail-withdrawal assay (ip administration). The 120 samples were then ranked in terms of their antinociceptive activity. The synthesis of 54 individual compounds was then carried out. Nine of the individual compounds produced dose-dependent antinociception equivalent to morphine. In practical terms what this means is that one would not expect multiexponential increases in activity as we move from the all-X mixture, to the positional scanning libraries, to the individual compounds. Actually because of the systematic formatting one would typically anticipate steady increases in activity as the complexity of the mixtures is reduced. This is in fact what we see in the current study. One of the final individual compounds identified, TPI 2213-17, lacked significant respiratory depression, locomotor impairment, or sedation. Our results represent an example of this unique approach for screening large mixture-based libraries directly in vivo to rapidly identify individual compounds. PMID:26651386

  1. Direct Phenotypic Screening in Mice: Identification of Individual, Novel Antinociceptive Compounds from a Library of 734 821 Pyrrolidine Bis-piperazines

    PubMed Central

    2015-01-01

    The hypothesis in the current study is that the simultaneous direct in vivo testing of thousands to millions of systematically arranged mixture-based libraries will facilitate the identification of enhanced individual compounds. Individual compounds identified from such libraries may have increased specificity and decreased side effects early in the discovery phase. Testing began by screening ten diverse scaffolds as single mixtures (ranging from 17 340 to 4 879 681 compounds) for analgesia directly in the mouse tail withdrawal model. The “all X” mixture representing the library TPI-1954 was found to produce significant antinociception and lacked respiratory depression and hyperlocomotor effects using the Comprehensive Laboratory Animal Monitoring System (CLAMS). The TPI-1954 library is a pyrrolidine bis-piperazine and totals 738 192 compounds. This library has 26 functionalities at the first three positions of diversity made up of 28 392 compounds each (26 × 26 × 42) and 42 functionalities at the fourth made up of 19 915 compounds each (26 × 26 × 26). The 120 resulting mixtures representing each of the variable four positions were screened directly in vivo in the mouse 55 °C warm-water tail-withdrawal assay (ip administration). The 120 samples were then ranked in terms of their antinociceptive activity. The synthesis of 54 individual compounds was then carried out. Nine of the individual compounds produced dose-dependent antinociception equivalent to morphine. In practical terms what this means is that one would not expect multiexponential increases in activity as we move from the all-X mixture, to the positional scanning libraries, to the individual compounds. Actually because of the systematic formatting one would typically anticipate steady increases in activity as the complexity of the mixtures is reduced. This is in fact what we see in the current study. One of the final individual compounds identified, TPI 2213-17, lacked significant respiratory depression, locomotor impairment, or sedation. Our results represent an example of this unique approach for screening large mixture-based libraries directly in vivo to rapidly identify individual compounds. PMID:26651386

  2. 4-(3-Chloro-5-(trifluoromethyl)pyridin-2-yl)-N-(4-methoxypyridin-2-yl)piperazine-1-carbothioamide (ML267), a Potent Inhibitor of Bacterial Phosphopantetheinyl Transferase That Attenuates Secondary Metabolism and Thwarts Bacterial Growth

    PubMed Central

    2015-01-01

    4′-Phosphopantetheinyl transferases (PPTases) catalyze a post-translational modification essential to bacterial cell viability and virulence. We present the discovery and medicinal chemistry optimization of 2-pyridinyl-N-(4-aryl)piperazine-1-carbothioamides, which exhibit submicromolar inhibition of bacterial Sfp-PPTase with no activity toward the human orthologue. Moreover, compounds within this class possess antibacterial activity in the absence of a rapid cytotoxic response in human cells. An advanced analogue of this series, ML267 (55), was found to attenuate production of an Sfp-PPTase-dependent metabolite when applied to Bacillus subtilis at sublethal doses. Additional testing revealed antibacterial activity against methicillin-resistant Staphylococcus aureus, and chemical genetic studies implicated efflux as a mechanism for resistance in Escherichia coli. Additionally, we highlight the in vitro absorption, distribution, metabolism, and excretion and in vivo pharmacokinetic profiles of compound 55 to further demonstrate the potential utility of this small-molecule inhibitor. PMID:24450337

  3. 1-(2-Hy-droxy-eth-yl)-4-{3-[(E)-2-(trifluoro-meth-yl)-9H-thioxanthen-9-yl-idene]prop-yl}piperazine-1,4-diium bis-(3-carb-oxy-prop-2-enoate).

    PubMed

    Siddegowda, M S; Butcher, Ray J; Akkurt, Mehmet; Yathirajan, H S; Ramesh, A R

    2011-08-01

    In the title salt, C(23)H(27)F(3)N(2)OS(+)·2C(4)H(3)O(4) (-), a non-merohedral twin [ratio of the twin components = 0.402 (1):0.598 (1)], the -CF(3) group is disordered over two sets of sites with occupancy factors in the ratio 0.873 (2):0.127 (2). The dihedral angle between the two outer aromatic rings of the 9H-thioxanthene unit, whose thio-pyran ring has a screw-boat conformation, is 33.01 (9)°. The diprotonated piperazine ring adopts a chair conformation. In the crystal, inter-molecular O-H⋯O, N-H⋯O and C-H⋯O hydrogen bonds between neighboring mol-ecules form zigzag chains along the a axis and contribute to the stabilization of the packing. PMID:22091049

  4. Amine plant troubleshooting and optimization

    SciTech Connect

    Abry, R.G.F.; DuPart, M.S.

    1995-04-01

    A systematic method for troubleshooting and optimization of amine plants, if properly used, will result in fewer plant upsets, quick and correct responses to changing conditions and long-term profitable operations of any amine unit. It is important for amine plants to maintain safe, continuous and optimized operations for short- and long-term success. Effective and fast resolution of maine unit upsets plays a large part in this success. These considerations are as important in plants using generic amines such as monoethanolamine (MEA), diethanolamine (DEA), methyldiethanolamine (MDEA) and specialty amines based on MDEA. The key to troubleshooting and optimization is a systematic approach. Developing and using control charts can also be used to monitor amine plant operations. By using these techniques collectively, a formal method for troubleshooting and optimization can be established. This will ultimately result in a more trouble-free, continuous operation.

  5. Crystal structure of 3-{[4-(2-meth-oxy-phen-yl)piperazin-1-yl]meth-yl}-5-(thio-phen-2-yl)-1,3,4-oxa-diazole-2(3H)-thione.

    PubMed

    Al-Alshaikh, Monirah A; Abuelizz, Hatem A; El-Emam, Ali A; Abdelbaky, Mohammed S M; Garcia-Granda, Santiago

    2016-02-01

    The title compound, C18H20N4O2S2, is a new 1,3,4-oxa-diazole and a key pharmacophore of several biologically active agents. It is composed of a meth-yl(thio-phen-2-yl)-1,3,4-oxa-diazole-2(3H)-thione moiety linked to a 2-meth-oxy-phenyl unit via a piperazine ring that has a chair conformation. The thio-phene ring mean plane lies almost in the plane of the oxa-diazole ring, with a dihedral angle of 4.35 (9)°. The 2-meth-oxy-phenyl ring is almost normal to the oxa-diazole ring, with a dihedral angle of 84.17 (10)°. In the crystal, mol-ecules are linked by weak C-H⋯S hydrogen bonds and C-H⋯π inter-actions, forming layers parallel to the bc plane. The layers are linked via weak C-H⋯O hydrogen bonds and slipped parallel π-π inter-actions [inter-centroid distance = 3.6729 (10) Å], forming a three-dimensional structure. The thio-phene ring has an approximate 180° rotational disorder about the bridging C-C bond. PMID:26958404

  6. Layer silicates modified with 1,4-bis(3-aminopropyl)piperazine for the removal of Th(IV), U(VI) and Eu(III) from aqueous media.

    PubMed

    Guerra, Denis L; Pinto, Alane A; Viana, Rúbia R; Airoldi, Claudio

    2009-11-15

    Natural montmorillonite (M) and synthetic kanemite (K) have been functionalized with 1,4-bis(3-aminopropyl)piperazine reacted with methylacrylate to yield new inorganic-organic chelating materials. The original and modified materials were characterized by X-ray diffractometry, textural analysis, SEM and nuclear magnetic nuclei of carbon-13 and silicon-29. The chemically modified clay samples (M-APPMA and K-APPMA) showed modification of its physical-chemical properties including: specific area 45.0m(2)g(-1) (M) to 978.8 m(2)g(-1) (M-APPMA) and 23.5m(2)g(-1) (K) to 898.9 m(2)g(-1) (K-APPMA). The ability of these materials to remove thorium(IV), uranyl(VI) and europium(III) from aqueous solution was followed by a series of adsorption isotherms, which were fitted to non-linear Sips adsorption isotherm model. To achieve the best adsorption conditions the influence of pH and variation of metal concentration were investigated. The energetic effects (Delta(int)H degrees , Delta(int)G degrees and Delta(int)S degrees ) caused by metal ions adsorption were determined through calorimetric titrations. PMID:19604631

  7. A scanning tunneling microscopy investigation of the phases formed by the sulfur adsorption on Au(100) from an alkaline solution of 1,4-piperazine(bis)-dithiocarbamate of potassium

    NASA Astrophysics Data System (ADS)

    Martínez, Javier A.; Valenzuela B., José; Cao Milán, R.; Herrera, José; Farías, Mario H.; Hernández, Mayra P.

    2014-11-01

    Piperazine-dithiocarbamate of potassium (K2DTC2pz) was used as a new precursor for the spontaneous deposition of sulfur on the Au(100) surface in alkaline solution. Two new sulfur phases were studied by scanning tunneling microscopy (STM). These phases were formed by six sulfur atoms (S6 phase, hexamer) and by four sulfur atoms (S4 phase, tetramer with (√{ 2} ×√{ 2}) structure), and they were observed in coexistence with the well-known quasi-square patterns formed by eight sulfur atoms (S8 phase, octomer). A model was proposed where sulfur multilayers were formed by a (√{ 2} ×√{ 2}) phase adsorbed directly on the gold surface while one of the other structures: hexamers or octomers were deposited on top. Sulfur layers were formed on gold terraces, vacancies and islands produced by lifting reconstructed surface. Sequential high-resolution STM images allowed the direct observation of the dynamic of the octomers, while the (√{ 2} ×√{ 2}) structure remained static. Images also showed the reversible association/dissociation of the octomer.

  8. Fluorescent Derivatives of σ Receptor Ligand 1-Cyclohexyl-4-[3-(5-methoxy-1,2,3,4-tetrahydronaphthalen-1-yl)propyl]piperazine (PB28) as a Tool for Uptake and Cellular Localization Studies in Pancreatic Tumor Cells

    PubMed Central

    Abate, Carmen; Hornick, John R.; Spitzer, Dirk; Hawkins, William G; Niso, Mauro; Perrone, Roberto; Berardi, Francesco

    2011-01-01

    Fluorescent derivatives of σ2 high affinity ligand 1-cyclohexyl-4-[3-(5-methoxy-1,2,3,4-tetrahydronaphthalen-1-yl)propyl]piperazine 1 (PB28) were synthesized. NBD or Dansyl fluorescent tags were connected through a 5- or 6-atoms linker in two diverse positions of 1 structure. Good σ2 affinities were obtained when the fluorescent tag was linked to 5-methoxytetralin nucleus replacing the methyl function. NBD-bearing compound 16 displayed high σ2 affinity (Ki = 10.8 nM) and optimal fluorescent properties. Its uptake in pancreatic tumor cells was evaluated by flow cytometry showing that it partially occurs through endocytosis. In proliferating cells the uptake was higher supporting that σ2 receptors are markers of cell proliferation and that the higher is the proliferation, the stronger is the antiproliferative effect of σ2 agonists. Colocalization of 16 with subcellular organelles was studied by confocal microscopy: the greatest was in endoplasmic reticulum and lysosomes. Fluorescent σ2 ligands show their potential in clarifying the mechanisms of action of σ2 receptors. PMID:21744858

  9. Acute toxicity and primary irritancy of alkylalkanolamines.

    PubMed

    Ballantyne, B; Leung, H W

    1996-12-01

    The acute handling hazards of several alkylalkanolamines were determined by investigating their potential acute toxicity and primary irritancy. Materials studied were N-methylethanolamine (MEA), N, N, -dimethylethanolamine (DMEA), N, N, -dimethylisopropanolamine (DMIPA), N-methyldiethanolamine (MDEA), and tertbutyldiethanolamine (BDEA). All these alkylalkanolamines were of comparable acute peroral toxicity in the rat (LD50 range 1.48-2.83 ml/kg). By 24 h occluded epicutaneous contact in the rabbit, MEA, DMEA and DMIPA were of moderate acute percutaneous toxicity (LD50 range 1.13-2.0 ml/kg), MDEA was of slight acute percutaneous toxicity (LD50 male 9.85 ml/kg, female 10.90 ml/kg), and BDEA of intermediate toxicity (LD50 6.4 ml/kg). Due to differences in vapor pressure the acute vapor exposure toxicity of the alkylalkanolamines to rats varied; MEA, MDEA and BDEA were of a low order of acute toxicity, and DMIPA was moderately toxic with an LT50 of 3.2 h for a saturated vapor atmosphere exposure. A 4 h-LC50 (rat combined sex) of 1461 ppm was determined for DMEA. All alkylalkanolamines studied, except MDEA, were moderately to markedly irritating and caused variable degrees of skin corrosivity; MDEA caused only transient minor skin irritation. In accord with the skin irritancy results, the eye irritancy from 0.005 ml MEA, DMEA, DMIPA and BDEA was severe, and that from MDEA was slight. Exposure to these compounds has implications for occupational health procedures. PMID:8948072

  10. Exploring the Solid State Properties of Enzymatic Poly(amine-co-ester) Terpolymers to Expand their Applications in Gene Transfection.

    PubMed

    Voevodina, Irina; Scandola, Mariastella; Zhang, Junwei; Jiang, Zhaozhong

    2014-01-01

    Polymers bearing amino functional groups are an important class of materials capable of serving as non-viral carriers for DNA delivery to living cells. In this work biodegradable poly(amine-co-ester) terpolymers were synthesized via ring-opening and polycondensation copolymerization of lactone (ε-caprolactone (CL), ω-dodecalactone, ω-pentadecalactone (PDL), and ω-hexadecalactone) with diethyl sebacate (DES) and N-methyldiethanolamine (MDEA) in diphenyl ether, catalyzed by Candida antarctica lipase B (CALB). All lactone-DES-MDEA terpolymers had random distributions of lactone, sebacate, MDEA repeat units in the polymer chains. PDL-DES-MDEA terpolymers were studied in the composition range from 21 mol% to 90 mol% PDL whereas the terpolymers with other lactones were investigated at a single composition (80 mol% lactone). DSC and WAXS analyses showed that all investigated terpolymers crystallize in their respective homopolylactone crystal lattice. Terpolymers with large lactones and a high lactone content melt well above room temperature and are hard solids, whereas terpolymers with small lactones (e.g. CL) or with a low lactone content melt below/around ambient temperature and are waxy/gluey materials. Given the importance of hydrophobicity in influencing gene delivery, water contact angle measurements were carried out on lactone-DES-MDEA terpolymers showing that it is possible to tune the hydrophilic-to-hydrophobic balance by varying polymer composition and size of lactone units. To demonstrate the feasibility of using solid terpolymers as nanocarriers for DNA delivery, PDL-DES-MDEA copolymers with 65-90% PDL were successfully transformed into free-standing nanoparticles with average particle size ranging from 163 to 175 nm. Our preliminary results showed that LucDNA-loaded nanoparticles of the terpolymer with 65% PDL were effective for luciferase gene transfection of HEK293 cells. PMID:24683469

  11. Exploring the Solid State Properties of Enzymatic Poly(amine-co-ester) Terpolymers to Expand their Applications in Gene Transfection

    PubMed Central

    Voevodina, Irina; Scandola, Mariastella; Zhang, Junwei; Jiang, Zhaozhong

    2014-01-01

    Polymers bearing amino functional groups are an important class of materials capable of serving as non-viral carriers for DNA delivery to living cells. In this work biodegradable poly(amine-co-ester) terpolymers were synthesized via ring-opening and polycondensation copolymerization of lactone (ε-caprolactone (CL), ω-dodecalactone, ω-pentadecalactone (PDL), and ω-hexadecalactone) with diethyl sebacate (DES) and N-methyldiethanolamine (MDEA) in diphenyl ether, catalyzed by Candida antarctica lipase B (CALB). All lactone-DES-MDEA terpolymers had random distributions of lactone, sebacate, MDEA repeat units in the polymer chains. PDL-DES-MDEA terpolymers were studied in the composition range from 21 mol% to 90 mol% PDL whereas the terpolymers with other lactones were investigated at a single composition (80 mol% lactone). DSC and WAXS analyses showed that all investigated terpolymers crystallize in their respective homopolylactone crystal lattice. Terpolymers with large lactones and a high lactone content melt well above room temperature and are hard solids, whereas terpolymers with small lactones (e.g. CL) or with a low lactone content melt below/around ambient temperature and are waxy/gluey materials. Given the importance of hydrophobicity in influencing gene delivery, water contact angle measurements were carried out on lactone-DES-MDEA terpolymers showing that it is possible to tune the hydrophilic-to-hydrophobic balance by varying polymer composition and size of lactone units. To demonstrate the feasibility of using solid terpolymers as nanocarriers for DNA delivery, PDL-DES-MDEA copolymers with 65–90% PDL were successfully transformed into free-standing nanoparticles with average particle size ranging from 163 to 175 nm. Our preliminary results showed that LucDNA-loaded nanoparticles of the terpolymer with 65% PDL were effective for luciferase gene transfection of HEK293 cells. PMID:24683469

  12. 3-(Adamantan-1-yl)-1-[(4-ethyl­piperazin-1-yl)meth­yl]-4-[(E)-(4-hy­droxy­benzyl­idene)amino]-1H-1,2,4-triazole-5(4H)-thione

    PubMed Central

    El-Emam, Ali A.; Alrashood, Khalid A.; Al-Tamimi, Abdul-Malek S.; Ng, Seik Weng; Tiekink, Edward R. T.

    2012-01-01

    In the title thione, C26H36N6OS, the 1,2,4-triazole ring is planar (r.m.s. deviation = 0.020 Å) and the benzene ring is twisted out of this plane [dihedral angle = 62.35 (12)°]. Supra­molecular zigzag chains feature in the crystal packing. These are sustained by O—H⋯N(piperazine) hydrogen bonds, and are connected into the three-dimensional crystal structure by C—H⋯S and C—H⋯O inter­actions. The crystal studied was a racemic twin. PMID:22412560

  13. Design, synthesis, and biological evaluation of 3-[4-(2-hydroxyethyl)piperazin-1-yl]-7-(6-methoxypyridin-3-yl)-1-(2-propoxyethyl)pyrido[3,4-b]pyrazin-2(1H)-one, a potent, orally active, brain penetrant inhibitor of phosphodiesterase 5 (PDE5).

    PubMed

    Hughes, Robert O; Rogier, D Joseph; Jacobsen, E Jon; Walker, John K; Macinnes, Alan; Bond, Brian R; Zhang, Lena L; Yu, Ying; Zheng, Yi; Rumsey, Jeanne M; Walgren, Jennie L; Curtiss, Sandra W; Fobian, Yvette M; Heasley, Steven E; Cubbage, Jerry W; Moon, Joseph B; Brown, David L; Acker, Brad A; Maddux, Todd M; Tollefson, Mike B; Mischke, Brent V; Owen, Dafydd R; Freskos, John N; Molyneaux, John M; Benson, Alan G; Blevis-Bal, Rhadika M

    2010-03-25

    We recently described a novel series of aminopyridopyrazinones as PDE5 inhibitors. Efforts toward optimization of this series culminated in the identification of 3-[4-(2-hydroxyethyl)piperazin-1-yl]-7-(6-methoxypyridin-3-yl)-1-(2-propoxyethyl)pyrido[3,4-b]pyrazin-2(1H)-one, which possessed an excellent potency and selectivity profile and demonstrated robust in vivo blood pressure lowering in a spontaneously hypertensive rat (SHR) model. Furthermore, this compound is brain penetrant and will be a useful agent for evaluating the therapeutic potential of central inhibition of PDE5. This compound has recently entered clinical trials. PMID:20196613

  14. The small molecule '1-(4-biphenylylcarbonyl)-4-(5-bromo-2-methoxybenzyl) piperazine oxalate' and its derivatives regulate global protein synthesis by inactivating eukaryotic translation initiation factor 2-alpha.

    PubMed

    Hong, Mi-Na; Nam, Ky-Youb; Kim, Kyung Kon; Kim, So-Young; Kim, InKi

    2016-05-01

    By environmental stresses, cells can initiate a signaling pathway in which eukaryotic translation initiation factor 2-alpha (eIF2-α) is involved to regulate the response. Phosphorylation of eIF2-α results in the reduction of overall protein neogenesis, which allows cells to conserve resources and to reprogram energy usage for effective stress control. To investigate the role of eIF2-α in cell stress responses, we conducted a viability-based compound screen under endoplasmic reticulum (ER) stress condition, and identified 1-(4-biphenylylcarbonyl)-4-(5-bromo-2-methoxybenzyl) piperazine oxalate (AMC-01) and its derivatives as eIF2-α-inactivating chemical. Molecular characterization of this signaling pathway revealed that AMC-01 induced inactivation of eIF2-α by phosphorylating serine residue 51 in a dose- and time-dependent manner, while the negative control compounds did not affect eIF2-α phosphorylation. In contrast with ER stress induction by thapsigargin, phosphorylation of eIF2-α persisted for the duration of incubation with AMC-01. By pathway analysis, AMC-01 clearly induced the activation of protein kinase RNA-activated (PKR) kinase and nuclear factor-κB (NF-κB), whereas it did not modulate the activity of PERK or heme-regulated inhibitor (HRI). Finally, we could detect a lower protein translation rate in cells incubated with AMC-01, establishing AMC-01 as a potent chemical probe that can regulate eIF2-α activity. We suggest from these data that AMC-01 and its derivative compounds can be used as chemical probes in future studies of the role of eIF2-α in protein synthesis-related cell physiology. PMID:26873011

  15. Novel Piperazine Arylideneimidazolones Inhibit the AcrAB-TolC Pump in Escherichia coli and Simultaneously Act as Fluorescent Membrane Probes in a Combined Real-Time Influx and Efflux Assay.

    PubMed

    Bohnert, Jürgen A; Schuster, Sabine; Kern, Winfried V; Karcz, Tadeusz; Olejarz, Agnieszka; Kaczor, Aneta; Handzlik, Jadwiga; Kieć-Kononowicz, Katarzyna

    2016-04-01

    In this study, we tested five compounds belonging to a novel series of piperazine arylideneimidazolones for the ability to inhibit the AcrAB-TolC efflux pump. The biphenylmethylene derivative (BM-19) and the fluorenylmethylene derivative (BM-38) were found to possess the strongest efflux pump inhibitor (EPI) activities in the AcrAB-TolC-overproducingEscherichia colistrain 3-AG100, whereas BM-9, BM-27, and BM-36 had no activity at concentrations of up to 50 μM in a Nile red efflux assay. MIC microdilution assays demonstrated that BM-19 at 1/4 MIC (intrinsic MIC, 200 μM) was able to reduce the MICs of levofloxacin, oxacillin, linezolid, and clarithromycin 8-fold. BM-38 at 1/4 MIC (intrinsic MIC, 100 μM) was able to reduce only the MICs of oxacillin and linezolid (2-fold). Both compounds markedly reduced the MIC of rifampin (BM-19, 32-fold; and BM-38, 4-fold), which is suggestive of permeabilization of the outer membrane as an additional mechanism of action. Nitrocefin hydrolysis assays demonstrated that in addition to their EPI activity, both compounds were in fact weak permeabilizers of the outer membrane. Moreover, it was found that BM-19, BM-27, BM-36, and BM-38 acted as near-infrared-emitting fluorescent membrane probes, which allowed for their use in a combined influx and efflux assay and thus for tracking of the transport of an EPI across the outer membrane by an efflux pump in real time. The EPIs BM-38 and BM-19 displayed the most rapid influx of all compounds, whereas BM-27, which did not act as an EPI, showed the slowest influx. PMID:26824939

  16. The antidepressant-like activity of 6-methoxy-2-[4-(2-methoxyphenyl)piperazin-1-yl]-9H-xanthen-9-one involves serotonergic 5-HT(1A) and 5-HT(2A/C) receptors activation.

    PubMed

    Pytka, Karolina; Walczak, Maria; Kij, Agnieszka; Rapacz, Anna; Siwek, Agata; Kazek, Grzegorz; Olczyk, Adrian; Gałuszka, Adam; Waszkielewicz, Anna; Marona, Henryk; Sapa, Jacek; Filipek, Barbara

    2015-10-01

    Xanthone derivatives have been shown to posses many biological properties. Some of them act within the central nervous system and show neuroprotective or antidepressant-like properties. Taking this into account we investigated antidepressant-like activity in mice and the possible mechanism of action of 6-methoxy-2-[4-(2-methoxyphenyl)piperazin-1-yl]-9H-xanthen-9-one (HBK-11) - a new xanthone derivative. We demonstrated that HBK-11 produced antidepressant-like effects in the forced swim test and tail suspension test, comparable to that of venlafaxine. The combined treatment with sub-effective doses of HBK-11 and fluoxetine (but not reboxetine or bupropion) significantly reduced the immobility in the forced swim test. Moreover, the antidepressant-like activity of HBK-11 in the aforementioned test was blocked by p-chlorophenylalanine, and significantly reduced by serotonergic 5HT1A receptor antagonist - WAY-1006335 and 5HT2A/C receptor antagonist - ritanserin. As none of the above treatments influenced the spontaneous locomotor activity, it can be concluded that HBK-11 mediates its activity through a serotonergic system, and its antidepressant-like effect involves 5HT1A and 5HT2A/C receptor activation. Furthermore, at antidepressant-like doses HBK-11 did not cause the mice to display locomotor deficits in rotarod or chimney tests. Considering the pharmacokinetic profile, HBK-11 demonstrated rapid absorption after i.p. administration, high clearance value, short terminal half-life, very high volume of distribution and incomplete bioavailability. The compound studied had good penetration into the brain tissue of mice. Since studied xanthone derivative seems to present interesting, untypical mechanism of antidepressant-like action i.e. 5HT2A/C receptor activation, it may have a potential in the treatment of depressive disorders, and surely requires further studies. PMID:26210317

  17. Prevalence of efflux-mediated ciprofloxacin and levofloxacin resistance in recent clinical isolates of Pseudomonas aeruginosa and its reversal by the efflux pump inhibitors 1-(1-naphthylmethyl)-piperazine and phenylalanine-arginine-β-naphthylamide.

    PubMed

    Sonnet, Pascal; Izard, Daniel; Mullié, Catherine

    2012-01-01

    To assess the prevalence of efflux-driven fluoroquinolone (FQ) resistance in recent clinical isolates of Pseudomonas aeruginosa, a worrisome and often hospital-acquired pathogen, 115 unique strains were collected over a 5-month period, of which 27 and 33 had decreased susceptibility to ciprofloxacin (CIP) and levofloxacin (LVX), respectively. The MIC(50) (minimum inhibitory concentration for 50% of the organisms) was 16 μg/mL for both FQs. The efflux pump inhibitors (EPIs) phenylalanine-arginine-β-naphthylamide (PAβN) and 1-(1-naphthylmethyl)-piperazine (NMP) were then used to evaluate their efficacy in reducing CIP and LVX MICs. NMP did not significantly modify CIP MICs, whilst PAβN resulted in MIC(50) values of 2 μg/mL and 0.125 μg/mL for CIP and LVX, respectively. With the addition of PAβN, susceptibility to CIP and LVX was recovered in 6 (22.2%) and 31 (93.9%) strains, respectively. The best combination to reverse FQ resistance in this set of strains was LVX with PAβN. The results of this study show that the effect of an EPI is not only dependent on the species on which it is used but also on the molecule associated with it. Therefore, the design of an EPI equally efficient on all resistance-nodulation-cell division (RND) efflux pumps appears to be difficult and, from a practical point of view, if an EPI is developed for clinical use, the efficiency of its combination with a definite molecule should be assessed carefully against a wide range of clinical isolates to evaluate the real benefit of this combination. PMID:21974858

  18. Pharmacological Preconditioning of Mesenchymal Stem Cells with Trimetazidine (1-[2,3,4-Trimethoxybenzyl]piperazine) Protects Hypoxic Cells against Oxidative Stress and Enhances Recovery of Myocardial Function in Infarcted Heart through Bcl-2 Expression

    PubMed Central

    Wisel, Sheik; Khan, Mahmood; Kuppusamy, M. Lakshmi; Mohan, I. Krishna; Chacko, Simi M.; Rivera, Brian K.; Sun, Benjamin C.; Hideg, Kálmán; Kuppusamy, Periannan

    2009-01-01

    Stem cell transplantation is a possible therapeutic option to repair ischemic damage to the heart. However, it is faced with a number of challenges including the survival of the transplanted cells in the ischemic region. The present study was designed to use stem cells preconditioned with trimetazidine (1-[2,3,4-trimethoxybenzyl]piperazine; TMZ), a widely used anti-ischemic drug for treating angina in cardiac patients, to increase the rate of their survival after transplantation. Bone marrow-derived rat mesenchymal stem cells (MSCs) were subjected to a simulated host tissue environment by culturing them under hypoxia (2% O2) and using hydrogen peroxide (H2O2) to induce oxidative stress. MSCs were preconditioned with 10 μM TMZ for 6 h followed by treatment with 100 μM H2O2 for 1 h and characterized for their cellular viability and metabolic activity. The preconditioned cells showed a significant protection against H2O2-induced loss of cellular viability, membrane damage, and oxygen metabolism accompanied by a significant increase in HIF-1α, survivin, phosphorylated Akt (pAkt), and Bcl-2 protein levels and Bcl-2 gene expression. The therapeutic efficacy of the TMZ-preconditioned MSCs was evaluated in an in vivo rat model of myocardial infarction induced by permanent ligation of left anterior descending coronary artery. A significant increase in the recovery of myocardial function and up-regulation of pAkt and Bcl-2 levels were observed in hearts transplanted with TMZ-preconditioned cells. This study clearly demonstrated the potential benefits of pharmacological preconditioning of MSCs with TMZ for stem cell therapy for repairing myocardial ischemic damage. PMID:19218529

  19. N-(3,4-Dimethylisoxazol-5-yl)piperazine-4-[4-(2-fluoro-4-[(11)C]methylphenyl)thiazol-2-yl]-1-carboxamide: A promising positron emission tomography ligand for fatty acid amide hydrolase.

    PubMed

    Shimoda, Yoko; Fujinaga, Masayuki; Hatori, Akiko; Yui, Joji; Zhang, Yiding; Nengaki, Nobuki; Kurihara, Yusuke; Yamasaki, Tomoteru; Xie, Lin; Kumata, Katsushi; Ishii, Hideki; Zhang, Ming-Rong

    2016-02-15

    To visualize fatty acid amide hydrolase (FAAH) in brain in vivo, we developed a novel positron emission tomography (PET) ligand N-(3,4-dimethylisoxazol-5-yl)piperazine-4-[4-(2-fluoro-4-[(11)C]methylphenyl)thiazol-2-yl]-1-carboxamide ([(11)C]DFMC, [(11)C]1). DFMC (1) was shown to have high binding affinity (IC50: 6.1nM) for FAAH. [(11)C]1 was synthesized by C-(11)C coupling reaction of arylboronic ester 2 with [(11)C]methyl iodide in the presence of Pd catalyst. At the end of synthesis, [(11)C]1 was obtained with a radiochemical yield of 20±10% (based on [(11)C]CO2, decay-corrected, n=5) and specific activity of 48-166GBq/μmol. After the injection of [(11)C]1 in mice, high uptake of radioactivity (>2% ID/g) was distributed in the lung, liver, kidney, and brain, organs with high FAAH expression. PET images of rat brains for [(11)C]1 revealed high uptakes in the cerebellar nucleus (SUV=2.4) and frontal cortex (SUV=2.0), two known brain regions with high FAAH expression. Pretreatment with the FAAH-selective inhibitor URB597 reduced the brain uptake. Higher than 90% of the total radioactivity in the rat brain was irreversible at 30min after the radioligand injection. The present results indicate that [(11)C]1 is a promising PET ligand for imaging of FAAH in living brain. PMID:26740152

  20. 3-(Adamantan-1-yl)-1-[(4-benzyl­piperazin-1-yl)meth­yl]-4-[(E)-(2-hy­droxy­benzyl­idene)amino]-1H-1,2,4-triazole-5(4H)-thione

    PubMed Central

    El-Emam, Ali A.; Al-Omar, Mohamed A.; Al-Tamimi, Abdul-Malek S.; Ng, Seik Weng; Tiekink, Edward R. T.

    2012-01-01

    In the title compound, C31H38N6OS, the conformation about the N=C [1.285 (2) Å] imine bond is E. The piperazine ring has a chair conformation and occupies a position almost perpendicular to the plane through the triazole ring; the benzene ring forms a dihedral angle of 31.95 (10)° with the triazole ring. Overall, the mol­ecule has the shape of a flattened bowl. The hy­droxy group is disordered over two positions. The major component has a site-occupancy factor of 0.762 (3) and forms an intra­molecular O—H⋯N(imine) bond to close an S(6) loop. The minor component of the disordered hy­droxy group forms an O—H⋯N(piperazine) hydrogen bond. These, along with C—H⋯S and C—H⋯N inter­actions, link mol­ecules into a three-dimensional architecture. PMID:22719548

  1. Buffer Standards for pH Measurement of N-(2-Hydroxyethyl)piperazine-N’-2-ethanesulfonic Acid (HEPES) for I = 0.16 mol·kg−1 from 5 to 55°C

    PubMed Central

    Roy, Rabindra N.; Roy, Lakshmi N.; Ashkenazi, Shahaf; Wollen, Joshua T.; Dunseth, Craig D.; Fuge, Michael S.; Durden, Jared L.; Roy, Chandra N.; Hughes, Hannah M.; Morris, Brett T.; Cline, Kevin L.

    2009-01-01

    The values of the second dissociation constant, pK2 of N-(2-hydroxyethyl) piperazine-N’-2-ethanesulfonic acid (HEPES) have been reported at 12 temperatures over the temperature range 5 to 55°C, including 37°C. This paper reports the results for the paH of eight isotonic saline buffer solutions with an I = 0.16 mol•kg−1 including compositions: (a) HEPES (0.01 mol•kg−1) + NaHEPES (0.01 mol•kg−1) + NaCl (0.15 mol•kg−1); (b) HEPES (0.02 mol•kg−1) + NaHEPES (0.02 mol•kg−1) + NaCl (0.14 mol•kg−1); (c) HEPES (0.03 mol•kg−1) + NaHEPES (0.03 mol•kg−1) + NaCl (0.13 mol•kg−1); (d) HEPES (0.04 mol•kg−1) + NaHEPES (0.04 mol•kg−1) + NaCl (0.12 mol•kg−1); (e) HEPES (0.05 mol•kg−1) + NaHEPES (0.05 mol•kg−1) + NaCl (0.11 mol•kg−1); (f) HEPES (0.06 mol•kg−1) + NaHEPES (0.06 mol•kg−1) + NaCl (0.10 mol•kg−1); (g) HEPES (0.07 mol•kg−1) + NaHEPES (0.07 mol•kg−1) + NaCl (0.09 mol•kg−1); and (h) HEPES (0.08 mol•kg−1) + NaHEPES (0.08 mol•kg−1) + NaCl (0.08 mol•kg−1). Conventional paH values, for all eight buffer solutions from 5 to 55°C have been calculated. The operational pH values with liquid junction corrections, at 25 and 37°C have been determined based on the NBS/NIST standard between the physiological phosphate standard and four buffer solutions. These are recommended as pH standards for physiological fluids in the range of pH 7.3 to 7.5 at I = 0.16 mol•kg−1. PMID:20161485

  2. Ether modifications to 1-[2-(3,4-dimethoxyphenyl)ethyl]-4-(3-phenylpropyl)piperazine (SA4503): effects on binding affinity and selectivity for sigma receptors and monoamine transporters

    PubMed Central

    Xu, Rong; Lord, Sarah A.; Peterson, Ryan M.; Fergason-Cantrell, Emily A.; Lever, John R.; Lever, Susan Z.

    2014-01-01

    Two series of novel ether analogs of the sigma (σ) receptor ligand 1-[2-(3,4-dimethoxyphenyl)ethyl]-4-(3-phenylpropyl)piperazine (SA4503) have been prepared. In one series, the alkyl portion of the 4-methoxy group was replaced with allyl, propyl, bromoethyl, benzyl, phenethyl, and phenylpropyl moieties. In the second series, the 3,4-dimethoxy was replaced with cyclic methylenedioxy, ethylenedioxy and propylenedioxy groups. These ligands, along with 4-O-des-methyl SA4503, were evaluated for σ1 and σ2 receptor affinity, and compared to SA4503 and several known ether analogs. SA4503 and a subset of ether analogs were also evaluated for dopamine transporter (DAT) and serotonin transporter (SERT) affinity. The highest σ1 receptor affinities, Ki values of 1.75 nM – 4.63 nM, were observed for 4-O-des-methyl SA4503, SA4503 and the methylenedioxy analog. As steric bulk increased, σ1 receptor affinity decreased, but only to a point. Allyl, propyl and bromoethyl substitutions gave σ1 receptor Ki values in the 20 nM – 30 nM range, while bulkier analogs having phenylalkyl, and Z- and E-iodoallyl, ether substitutions showed higher σ1 affinities, with Ki values in the 13 nM – 21 nM range. Most ligands studied exhibited comparable σ1 and σ2 affinities, resulting in little to no subtype selectivity. SA4503, the fluoroethyl analog and the methylenedioxy congener showed modest six- to fourteen-fold selectivity for σ1 sites. DAT and SERT interactions proved much more sensitive than σ receptor interactions to these structural modifications. For example, the benzyl congener (σ1 Ki = 20.8 nM; σ2 Ki = 16.4 nM) showed over 100-fold higher DAT affinity (Ki = 121 nM) and 6-fold higher SERT affinity (Ki = 128 nM) than the parent SA4503 (DAT Ki = 12650 nM; SERT Ki = 760 nM). Thus, ether modifications to the SA4503 scaffold can provide polyfunctional ligands having a broader spectrum of possible pharmacological actions. PMID:25468036

  3. 3-(Adamantan-1-yl)-4-methyl-1-({4-[3-(tri­fluoro­meth­yl)phen­yl]piperazin-1-yl}meth­yl)-4,5-di­hydro-1H-1,2,4-triazole-5-thione

    PubMed Central

    El-Emam, Ali A.; Al-Tamimi, Abdul-Malek S.; Alrashood, Khalid A.; Ng, Seik Weng; Tiekink, Edward R. T.

    2013-01-01

    In the title compound, C25H32F3N5S, two independent mol­ecules comprise the asymmetric unit and are related across a pseudo-centre of inversion. The piperazine rings have chair conformations with each N-bound substituent occupying an equatorial position so that the dihedral angles between the planes of the triazole and benzene ring are 78.20 (19) and 79.10 (19)° for the two independent mol­ecules, indicating that the mol­ecules have an L-shape. In the crystal, a three-dimensional architecture is stabilized by C—H⋯π inter­actions. The crystal studied was an inversion twin with the fractional contribution of the minor component being 0.27 (9). PMID:23723852

  4. 21 CFR 520.1807 - Piperazine.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ...(1) Chickens(i) Amount. 50 milligrams per bird under 6 weeks, 100 milligrams per bird over 6 weeks... in drinking water or feed. Use as sole source of drinking water. Prepare fresh solution daily. Use as... control of parasitism. (2) Turkeys(i) Amount. 100 milligrams per bird up to 12 weeks and 200...

  5. 21 CFR 520.1807 - Piperazine.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ...(1) Chickens(i) Amount. 50 milligrams per bird under 6 weeks, 100 milligrams per bird over 6 weeks... in drinking water or feed. Use as sole source of drinking water. Prepare fresh solution daily. Use as... control of parasitism. (2) Turkeys(i) Amount. 100 milligrams per bird up to 12 weeks and 200...

  6. 21 CFR 520.1807 - Piperazine.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ...(1) Chickens(i) Amount. 50 milligrams per bird under 6 weeks, 100 milligrams per bird over 6 weeks... in drinking water or feed. Use as sole source of drinking water. Prepare fresh solution daily. Use as... control of parasitism. (2) Turkeys(i) Amount. 100 milligrams per bird up to 12 weeks and 200...

  7. 21 CFR 520.1807 - Piperazine.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... for human consumption. Consult your veterinarian for assistance in the diagnosis, treatment, and... veterinarian for assistance in the diagnosis, treatment, and control of parasitism. (3) Swine—(i) Amount. 50... days prior to slaughter. Consult your veterinarian for assistance in the diagnosis, treatment,...

  8. Diethyl piperazine-1,4-diyldioxalate.

    PubMed

    Martínez-Martínez, Francisco J; Rojas-Pérez, Rodrigo E; García-Báez, Efrén V; Höpfl, Herbert; Padilla-Martínez, Itzia I

    2004-09-01

    The ethyl oxamate group, N-C(O)-C(O)-OEt, in the title compound, alternatively called diethyl N,N':N,N'-bis(ethylene)dioxamate, C12H18N2O6, can be considered as being composed of two singly bonded amide and ester functionalities. The ethyl oxamate group is not planar. The two carbonyl groups are almost perpendicular, with an oxalyl O=C-C=O torsion angle of -111.34 (17) degrees. The molecule is located on an inversion centre. Infinite supramolecular tapes, propagating along the b axis, are formed through soft C-H...O interactions which form a centrosymmetric R(2)2(12) motif. PMID:15345861

  9. Polymerization Behavior and Polymer Properties of Eosin-Mediated Surface Modification Reactions

    PubMed Central

    Avens, Heather J.; Randle, Thomas James; Bowman, Christopher N.

    2008-01-01

    Surface modification by surface-mediated polymerization necessitates control of the grafted polymer film thicknesses to achieve the desired property changes. Here, a microarray format is used to assess a range of reaction conditions and formulations rapidly in regards to the film thicknesses achieved and the polymerization behavior. Monomer formulations initiated by eosin conjugates with varying concentrations of poly(ethylene glycol) diacrylate (PEGDA), N-methyldiethanolamine (MDEA), and 1-vinyl-2-pyrrolidone (VP) were evaluated. Acrylamide with MDEA or ascorbic acid as a coinitiator was also investigated. The best formulation was found to be 40 wt% acrylamide with MDEA which yielded four to eight fold thicker films (maximum polymer thickness increased from 180 nm to 1420 nm) and generated visible films from 5-fold lower eosin surface densities (2.8 vs. 14 eosins/m2) compared to a corresponding PEGDA formulation. Using a microarray format to assess multiple initiator surface densities enabled facile identification of a monomer formulation that yields the desired polymer properties and polymerization behavior across the requisite range of initiator surface densities. PMID:19838291

  10. Alternative stripper configurations for CO{sub 2} capture by aqueous amines

    SciTech Connect

    Oyenekan, B.A.; Rochelle, G.T.

    2007-12-15

    Aqueous absorption/stripping is a promising technology for the capture of CO{sub 2} from existing or new coal-fired power plants. Four new stripper configurations (matrix, internal exchange, flashing feed, and multipressure with split feed) have been evaluated with seven model solvents that approximate the thermodynamic and rate properties of 7m (30 wt %) monoethanolamine (MEA), potassium carbonate promoted bypiperazine (PZ), promoted MEA, methyldiethanolamine (MDEA) promoted by PZ, and hindered amines. The results show that solvents with high heats of absorption (MEA, MEA/PZ) favor operation at normal pressure. The relative performance of the alternative configurations is matrix > internal exchange > multipressure with split feed > flashing feed. MEA/PZ and MDEA/PZ are attractive alternatives to 7m MEA. The best solvent and process configuration, matrix with MDEA/PZ, offers 22 and 15% energy savings over the baseline and improved baseline, respectively,with stripping and compression to 10 MPa. The energy requirement for stripping and compression to 10 MPa is about 20% of the power output from a 500 MW power plant with 90% CO{sub 2} removal.

  11. Discovery of 8-Cyclopentyl-2-[4-(4-methyl-piperazin-1-yl)-phenylamino]-7-oxo-7,8-dihydro-pyrido[2,3-d]pyrimidine-6-carbonitrile (7x) as a Potent Inhibitor of Cyclin-Dependent Kinase 4 (CDK4) and AMPK-Related Kinase 5 (ARK5)

    PubMed Central

    2015-01-01

    The success of imatinib, a BCR-ABL inhibitor for the treatment of chronic myelogenous leukemia, has created a great impetus for the development of additional kinase inhibitors as therapeutic agents. However, the complexity of cancer has led to recent interest in polypharmacological approaches for developing multikinase inhibitors with low toxicity profiles. With this goal in mind, we analyzed more than 150 novel cyano pyridopyrimidine compounds and identified structure–activity relationship trends that can be exploited in the design of potent kinase inhibitors. One compound, 8-cyclopentyl-2-[4-(4-methyl-piperazin-1-yl)-phenylamino]-7-oxo-7,8-dihydro-pyrido[2,3-d]pyrimidine-6-carbonitrile (7x), was found to be the most active, inducing apoptosis of tumor cells at a concentration of approximately 30–100 nM. In vitro kinase profiling revealed that 7x is a multikinase inhibitor with potent inhibitory activity against the CDK4/CYCLIN D1 and ARK5 kinases. Here, we report the synthesis, structure–activity relationship, kinase inhibitory profile, in vitro cytotoxicity, and in vivo tumor regression studies by this lead compound. PMID:24417566

  12. Poly[[di­aqua­[μ-1,4-bis(pyridin-4-ylmeth­yl)piperazine-κ2 N:N′]{μ-2,2′-[(1,4-phenyl­ene)bis(­oxy)]di­acetato-κ2 O:O′}cobalt(II)] penta­hydrate

    PubMed Central

    Sample, Alexander D.; LaDuca, Robert L.

    2014-01-01

    In the title compound, {[Co(C10H8O6)(C16H20N4)(H2O)2]·5H2O}n, octa­hedrally coordinated CoII ions on crystallographic inversion centres are bound by trans O atoms belonging to two hydro­quinone-O,O′-di­acetate (hqda) anions {systematic name: 2,2′-[(1,4-phenyl­ene)bis­(­oxy)]di­acetate}, two trans-pyridine N-donor atoms from two bis­(pyridin-4-ylmeth­yl)piperazine (4-bpmp) ligands, and two trans aqua ligands. The exobidentate hqda and 4-bpmp ligands form [Co(hqda)(4-bpmp)(H2O)2]n coordination polymer layers parallel to (110) that are anchored into the full crystal structure by O—H⋯O hydrogen bonding between aqua ligands and ligated hqda O atoms. Disordered water mol­ecules of crystallization occupy incipient channels along [100]. However, these could not modeled reliably and so they were treated with SQUEEZE in PLATON [Spek (2009 ▶). Acta Cryst. D65, 148–155]; the crystal data take the presence of these mol­ecules into account. The crystal under investigation was twinned by non-merohedry, the twin fraction of the components being 53.3% and 46.7%. Only data from the major twin component were used in the refinement. PMID:24940193

  13. Crystal structure of 3-{[4-(2-meth­oxy­phen­yl)piperazin-1-yl]meth­yl}-5-(thio­phen-2-yl)-1,3,4-oxa­diazole-2(3H)-thione

    PubMed Central

    Al-Alshaikh, Monirah A.; Abuelizz, Hatem A.; El-Emam, Ali A.; Abdelbaky, Mohammed S. M.; Garcia-Granda, Santiago

    2016-01-01

    The title compound, C18H20N4O2S2, is a new 1,3,4-oxa­diazole and a key pharmacophore of several biologically active agents. It is composed of a meth­yl(thio­phen-2-yl)-1,3,4-oxa­diazole-2(3H)-thione moiety linked to a 2-meth­oxy­phenyl unit via a piperazine ring that has a chair conformation. The thio­phene ring mean plane lies almost in the plane of the oxa­diazole ring, with a dihedral angle of 4.35 (9)°. The 2-meth­oxy­phenyl ring is almost normal to the oxa­diazole ring, with a dihedral angle of 84.17 (10)°. In the crystal, mol­ecules are linked by weak C—H⋯S hydrogen bonds and C—H⋯π inter­actions, forming layers parallel to the bc plane. The layers are linked via weak C—H⋯O hydrogen bonds and slipped parallel π–π inter­actions [inter­centroid distance = 3.6729 (10) Å], forming a three-dimensional structure. The thio­phene ring has an approximate 180° rotational disorder about the bridging C—C bond. PMID:26958404

  14. In situ hydrothermal syntheses, structures and photoluminescent properties of four novel metal-organic frameworks constructed by lanthanide (Ln=Ce(III), Pr(III), Eu(III)) and Cu(I) metals with flexible dicarboxylate acids and piperazine-based ligands

    NASA Astrophysics Data System (ADS)

    Ay, Burak; Karaca, Serkan; Yildiz, Emel; Lopez, Valerie; Nanao, Max H.; Zubieta, Jon

    2016-01-01

    Four novel metal-organic frameworks,[Cu2Cl2(pyrz)]n (1) and (H2pip)n[Ln2(pydc)4(H2O)2]n (Ln=Ce (2), Pr (3) and Eu (4), H2pzdc=2,3-pyrazinedicarboxylic acid, pyrz=pyrazine, H2pydc=2,6-pyridinedicarboxylic acid, H2pip=piperazine) have been synthesized under hydrothermal conditions and characterized by the elemental analysis, ICP, Far IR (FIR), FT-IR spectra, TGA, single crystal X-ray diffraction analysis and powder X-ray diffraction (PXRD). Compound 1 is two-dimensional containing Cl-Cu-Cl sites, while the lanthanide complexes contain one-dimensional infinite Ln-O-Ln chains. All the complexes show high thermal stability. The complexes 1-3 exhibit luminescence emission bands at 584, 598 and 614 nm at room temperature when excited at 300 nm. Complex 4 exhibits bright red solid-state phosphorescence upon exposure to UV radiation at room temperature.

  15. Development of a Highly Potent D2/D3 Agonist and a Partial Agonist from Structure-Activity Relationship Study of N(6)-(2-(4-(1H-Indol-5-yl)piperazin-1-yl)ethyl)-N(6)-propyl-4,5,6,7-tetrahydrobenzo[d]thiazole-2,6-diamine Analogues: Implication in the Treatment of Parkinson's Disease.

    PubMed

    Das, Banibrata; Vedachalam, Seenuvasan; Luo, Dan; Antonio, Tamara; Reith, Maarten E A; Dutta, Aloke K

    2015-12-10

    Our structure-activity relationship studies with N(6)-(2-(4-(1H-indol-5-yl)piperazin-1-yl)ethyl)-N(6)-propyl-4,5,6,7-tetrahydrobenzo[d]thiazole-2,6-diamine derivatives led to development of a lead compound (-)-21a which exhibited very high affinity (Ki, D2 = 16.4 nM, D3 = 1.15 nM) and full agonist activity (EC50 (GTPγS); D2 = 3.23 and D3 = 1.41 nM) at both D2 and D3 receptors. A partial agonist molecule (-)-34 (EC50 (GTPγS); D2 = 21.6 (Emax = 27%) and D3 = 10.9 nM) was also identified. In a Parkinson's disease (PD) animal model, (-)-21a was highly efficacious in reversing hypolocomotion in reserpinized rats with a long duration of action, indicating its potential as an anti-PD drug. Compound (-)-34 was also able to elevate locomotor activity in the above PD animal model significantly, implying its potential application in PD therapy. Furthermore, (-)-21a was shown to be neuroprotective in protecting neuronal PC12 from toxicity of 6-OHDA. This report, therefore, underpins the notion that a multifunctional drug like (-)-21a might have the potential not only to ameliorate motor dysfunction in PD patients but also to modify disease progression by protecting DA neurons from progressive degeneration. PMID:26555041

  16. Poly[[di-aqua-[μ-1,4-bis(pyridin-4-ylmeth-yl)piperazine-κ(2) N:N']{μ-2,2'-[(1,4-phenyl-ene)bis(-oxy)]di-acetato-κ(2) O:O'}cobalt(II)] penta-hydrate].

    PubMed

    Sample, Alexander D; LaDuca, Robert L

    2014-06-01

    In the title compound, {[Co(C10H8O6)(C16H20N4)(H2O)2]·5H2O} n , octa-hedrally coordinated Co(II) ions on crystallographic inversion centres are bound by trans O atoms belonging to two hydro-quinone-O,O'-di-acetate (hqda) anions {systematic name: 2,2'-[(1,4-phenyl-ene)bis-(-oxy)]di-acetate}, two trans-pyridine N-donor atoms from two bis-(pyridin-4-ylmeth-yl)piperazine (4-bpmp) ligands, and two trans aqua ligands. The exobidentate hqda and 4-bpmp ligands form [Co(hqda)(4-bpmp)(H2O)2] n coordination polymer layers parallel to (110) that are anchored into the full crystal structure by O-H⋯O hydrogen bonding between aqua ligands and ligated hqda O atoms. Disordered water mol-ecules of crystallization occupy incipient channels along [100]. However, these could not modeled reliably and so they were treated with SQUEEZE in PLATON [Spek (2009 ▶). Acta Cryst. D65, 148-155]; the crystal data take the presence of these mol-ecules into account. The crystal under investigation was twinned by non-merohedry, the twin fraction of the components being 53.3% and 46.7%. Only data from the major twin component were used in the refinement. PMID:24940193

  17. Highly stretchable nanoalginate based polyurethane elastomers.

    PubMed

    Daemi, Hamed; Barikani, Mehdi; Barmar, Mohammad

    2013-06-20

    Highly stretchable elastomeric samples based on cationic polyurethane dispersions-sodium alginate nanoparticles (CPUD/SA) were prepared by the solution blending of sodium alginate and aqueous polyurethane dispersions. CPUDs were synthesized by step growth polymerization technique using N-methyldiethanolamine (MDEA) as a source of cationic emulsifier. The chemical structure and thermal-mechanical properties of these systems were characterized using FTIR and DMTA, respectively. The presence of nanoalginate particles including nanobead and nanorod particles were proved by SEM and EDX. It was observed that thermal properties of composites increased with increasing SA content. All prepared samples were known as thermoplastic-elastomers with high percentages of elongation. Excellent compatibility of prepared nanocomposites was proved by the DMTA data. PMID:23648022

  18. Piperine as an inhibitor of the MdeA efflux pump of Staphylococcus aureus.

    PubMed

    Mirza, Zahid Mehmood; Kumar, Ashwani; Kalia, Nitin Pal; Zargar, Afzal; Khan, Inshad Ali

    2011-10-01

    Piperine, a trans-trans-isomer of 1-piperoyl-piperidine, was tested in combination with mupirocin for antimicrobial activity against Staphylococcus aureus strains including meticillin-resistant S. aureus. The combination markedly reduced the MIC of mupirocin and also lowered the mutation frequency. Enhanced accumulation and efflux of ethidium bromide from wild-type and mutant (Mup(r)-1) strains in the presence of piperine indicated that inhibition of efflux could be a possible mechanism of potentiation of mupirocin activity by piperine. The combination of piperine with mupirocin in a dermal infection model of mice showed better in vivo efficacy when compared with the commercially available formulation of 2 % mupirocin. PMID:21680766

  19. New MDEA design in gas plant improves sweetening, reduces CO[sub 2

    SciTech Connect

    Law, D. )

    1994-08-29

    Initial tests on a newly installed gas-sweetening unit at a Hungarian gas plant indicate that H[sub 2]S can be removed from inlet feed gas in a high-pressure system to less than 6 mg/cu m (4 ppmv) while rejecting most of the CO[sub 2]. This result was accomplished by use of significantly fewer amine contractor trays than in conventional practice and confirmed earlier computer simulations employed in the design phase. The paper describes the plant, the selective absorption process, the high-pressure stream being processed, the performance tests, and contributions by companies to the process development.

  20. Ditetraalkylammonium amino acid ionic liquids as CO₂ absorbents of high capacity.

    PubMed

    Ma, Jing-Wen; Zhou, Zheng; Zhang, Feng; Fang, Cheng-Gang; Wu, You-Ting; Zhang, Zhi-Bing; Li, Ai-Min

    2011-12-15

    By grafting butyl or ethyl onto tetramethylethylenediamine, quaternary ammonium salts with two positive charge centers were formed at the first step. Metathesis with Ag(2)O followed. Through neutralization with glycine, l-alanine, or valine, a series of new ditetraalkylammonium amino acid ionic liquids (DILs) for CO(2) capture were generated. The structures of DILs, as shown in Figure 1, were verified by using (1)H NMR and EA. These DILs were found to be of quite high viscosity which militated against their industrial application in CO(2) removal. Drawing on the experience of mixed amines' aqueous solutions, these DILs were blended with water or N-methyldiethanolamine (MDEA) aqueous solutions to act as special absorbents of CO(2). Using a Double-Tank Absorption System, the absorption performance of these DIL solutions was investigated in detail. The experimental results indicated that among the three aqueous solutions of DILs (20%, 40%, and 80 wt %), the solution of 40% DIL had a higher absorption rate of CO(2) than the other two, demonstrating the different effects of concentration and viscosity on the absorption. The solution of 40% DIL or the 15% DIL + 15% MDEA had much higher capacity for CO(2) than the corresponding monocation tetraalkylammonium AAILs, due to the special structure of the dication which could influence the solubility of CO(2) in the aqueous solution. PMID:22066493

  1. Micelles of enzymatically synthesized PEG-poly(amine-co-ester) block copolymers as pH-responsive nanocarriers for docetaxel delivery.

    PubMed

    Zhang, Xiaofang; Liu, Bo; Yang, Zhe; Zhang, Chao; Li, Hao; Luo, Xingen; Luo, Huiyan; Gao, Di; Jiang, Qing; Liu, Jie; Jiang, Zhaozhong

    2014-03-01

    A series of PEGylated poly(amine-co-ester) terpolymers were successfully synthesized in one step via lipase-catalyzed copolymerization of ω-pentadecalactone (PDL), diethyl sebacate (DES), and N-methyldiethanolamine (MDEA) comonomers in the presence of poly(ethylene glycol) methyl ether as a chain-terminating agent. The resultant amphiphilic poly(ethylene glycol)-poly(PDL-co-MDEA-co-sebacate) (PEG-PPMS) block copolymers consisted of hydrophilic PEG chain segments and hydrophobic random PPMS chain segments, which self-assembled in aqueous medium to form stable, nanosized micelles at physiological pH of 7.4. Upon decreasing the medium pH from 7.4 to 5.0, the copolymer micelles swell significantly due to protonation of the amino groups in the micelle PPMS cores. Correspondingly, docetaxel (DTX)-encapsulated PEG2K-PPMS copolymer micelles showed gradual sustained drug release at pH of 7.4, but remarkably accelerated DTX release at acidic pH of 5.0. The drug-loaded micelle particles were readily internalized by SK-BR-3 cancer cells and, compared to free DTX drug, DTX-loaded micelles of the copolymers with optimal compositions exhibited enhanced potency against the cells. Biodegradable PEG-PPMS copolymer micelles represent a new type of promising, pH-responsive nanocarriers for anticancer drug delivery, and the drug release rate from the micelles can be systematically controlled by both pH and the copolymer composition. PMID:24398083

  2. Iron(III) carboxylate/aminoalcohol coordination clusters with propeller-shaped Fe8 cores: approaching reasonable exchange energies.

    PubMed

    Botezat, Olga; van Leusen, Jan; Kravtsov, Victor Ch; Ellern, Arkady; Kögerler, Paul; Baca, Svetlana G

    2015-12-21

    A series of new octanuclear propeller-like aminoalcohol-supported Fe(III) oxocarboxylate coordination clusters, [Fe8O3(O2CCHMe2)9(tea)(teaH)3]·MeCN·2(H2O) (1), [Fe8O3(O2CCHMe2)6(N3)3(tea)(teaH)3] (2), [Fe8O3(O2CCMe3)6(N3)3(tea)(teaH)3]·0.5(EtOH) (3), and [Fe8O3(O2CCHMe2)6(N3)3(mdea)3(MeO)3] (4) (where teaH3 = triethanolamine; mdeaH2 = N-methyldiethanolamine) has been isolated and magnetochemically analyzed combining the programs wxJFinder and CONDON in an approach to avoid overparameterization issues that are common to larger spin polytopes. Dominant antiferromagnetic exchange interactions exist in all clusters along the edges of the propellers, while moderate ferromagnetic interactions are found along the propeller axes in their {Fe8O3} metallic cores. PMID:26567887

  3. High-throughput sample preparation and simultaneous column regeneration liquid chromatography-tandem mass spectrometry method for determination of nitrogen mustard metabolites in human urine.

    PubMed

    Reddy, Muntha K; Mills, Grier; Nixon, Christopher; Wyatt, Shane A; Croley, Timothy R

    2011-08-15

    Nitrogen mustards (NMs) are known to have DNA alkylation and strong vesicant properties. Their availability to terrorist organizations makes them a potential choice for chemical attacks on civilian populations. After an exposure, it is difficult to measure NMs directly because of their rapid metabolism in the human body. Therefore to determine an individual's level of exposure to NMs, it is necessary to analyze for NM metabolites being excreted by the body. The metabolites of NMs are generated by a hydrolysis reaction, and are easily detectable by liquid chromatography tandem mass spectrometry (LC-MS/MS). This work is focused on the development of a high-throughput assay for the quantitation of N-ethyldiethanolamine (EDEA) and N-methyldiethanolamine (MDEA) metabolites of bis (2-chloroethyl) ethylethanamine (HN1) and bis (2-chloroethyl) methylethanamine (HN2), respectively. The method uses automated 96-well plate sample preparation of human urine samples and a 2-position 10-port switching valve to allow for simultaneous regeneration of the liquid chromatography (LC) columns. Using this method, over 18 h was saved through the reduction of sample preparation and analysis time when compared to a conventional method for 96 samples. The validated method provided excellent accuracy for both EDEA (100.9%) and MDEA (100.6%) with precision better than 5.27% for each analyte. PMID:21764395

  4. WS-50030 [7-{4-[3-(1H-inden-3-yl)propyl]piperazin-1-yl}-1,3-benzoxazol-2(3H)-one]: a novel dopamine D2 receptor partial agonist/serotonin reuptake inhibitor with preclinical antipsychotic-like and antidepressant-like activity.

    PubMed

    Brennan, Julie A; Graf, Radka; Grauer, Steven M; Navarra, Rachel L; Pulicicchio, Claudine M; Hughes, Zoë A; Lin, Qian; Wantuch, Caitlin; Rosenzweig-Lipson, Sharon; Pruthi, Farhana; Lai, Margaret; Smith, Deborah; Goutier, Wouter; van de Neut, Martina; Robichaud, Albert J; Rotella, David; Feenstra, Rolf W; Kruse, Chris; Broqua, Pierre; Beyer, Chad E; McCreary, Andrew C; Pausch, Mark H; Marquis, Karen L

    2010-01-01

    The preclinical characterization of WS-50030 [7-{4-[3-(1H-inden-3-yl)propyl]piperazin-1-yl}-1,3-benzoxazol-2(3H)-one] is described. In vitro binding and functional studies revealed highest affinity to the D(2) receptor (D(2L) K(i), 4.0 nM) and serotonin transporter (K(i), 7.1 nM), potent D(2) partial agonist activity (EC(50), 0.38 nM; E(max), 30%), and complete block of the serotonin transporter (IC(50), 56.4 nM). Consistent with this in vitro profile, WS-50030 (10 mg/kg/day, 21 days) significantly increased extracellular 5-HT in the rat medial prefrontal cortex, short-term WS-50030 treatment blocked apomorphine-induced climbing (ID(50), 0.51 mg/kg) in a dose range that produced minimal catalepsy in mice and induced low levels of contralateral rotation in rats with unilateral substantia nigra 6-hydroxydopamine lesions (10 mg/kg i.p.), a behavioral profile similar to that of the D(2) partial agonist aripiprazole. In a rat model predictive of antipsychotic-like activity, WS-50030 and aripiprazole reduced conditioned avoidance responding by 42 and 55% at 10 mg/kg, respectively. Despite aripiprazole's reported lack of effect on serotonin transporters, long-term treatment with aripiprazole or WS-50030 reversed olfactory bulbectomy-induced hyperactivity at doses that did not reduce activity in sham-operated rats, indicating antidepressant-like activity for both compounds. Despite possessing serotonin reuptake inhibitory activity in addition to D(2) receptor partial agonism, WS-50030 displays activity in preclinical models predictive of antipsychotic- and antidepressant efficacy similar to aripiprazole, suggesting potential efficacy of WS-50030 versus positive and negative symptoms of schizophrenia, comorbid mood symptoms, bipolar disorder, major depressive disorder, and treatment-resistant depression. Furthermore, WS-50030 provides a tool to further explore how combining these mechanisms might differentiate from other antipsychotics or antidepressants. PMID:19828876

  5. Solubility calculations for acid gases in amine blends

    SciTech Connect

    Chakravarty, T.

    1985-01-01

    Treating with alkanolamines is often used to sweeten gases containing only a few parts per million of CO/sub 2/ and H/sub 2/S. Primary amines such as monoethanolamine (MEA) have great affinity for acid gases and are able to produce high purity sweet gas; on the other hand, tertiary amines like methyldiethanolamine (MDEA) have large capacity and are easy to regenerate but, because they do not bind chemically with CO/sub 2/, they are unable to produce a sweetened gas low in this component. Recently, the use of amine blends has become a subject of potentially great commercial importance. Since, the range of possible amines and blend formulations is large, a method for predicting equilibrium solubility is needed. A rigorous thermodynamic model has been developed which uses the extended Debye-Huckel expression, is very similar to one developed for single-amine solutions, and involves the fitting of binary interaction parameters to experimental data. In this work the interaction parameters found to be important in the activity coefficient expression were fitted to each single-acid-gas single-amine subsystem using all published solubility data. The resulting model was then validated by comparing mixed-acid-gas single-amine solubility predictions with published VLE data. MEA-MDEA and DEA-MDEA blends have been studied in detail in this work. It is found that each amine contributes to the overall acid gas solubility in a nonlinear way and that the solubility curves can exhibit maxima and minima as a function of the relative concentrations of the amines.

  6. 21 CFR 520.2380f - Thiabendazole, piperazine phosphate powder.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... oral dose. Administer as a drench or by stomach tube suspended in 1 pint of warm water; by dose syringe... stomach tube or drench, it shall also bear the statement “Caution: Federal law restricts this drug to use by or on the order of a licensed veterinarian;” if not labeled for use by stomach tube or drench,...

  7. 21 CFR 520.2380f - Thiabendazole, piperazine phosphate powder.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... oral dose. Administer as a drench or by stomach tube suspended in 1 pint of warm water; by dose syringe... stomach tube or drench, it shall also bear the statement “Caution: Federal law restricts this drug to use by or on the order of a licensed veterinarian;” if not labeled for use by stomach tube or drench,...

  8. 21 CFR 520.2380f - Thiabendazole, piperazine phosphate powder.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... oral dose. Administer as a drench or by stomach tube suspended in 1 pint of warm water; by dose syringe... stomach tube or drench, it shall also bear the statement “Caution: Federal law restricts this drug to use by or on the order of a licensed veterinarian;” if not labeled for use by stomach tube or drench,...

  9. 21 CFR 520.2380f - Thiabendazole, piperazine phosphate powder.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... oral dose. Administer as a drench or by stomach tube suspended in 1 pint of warm water; by dose syringe... stomach tube or drench, it shall also bear the statement “Caution: Federal law restricts this drug to use by or on the order of a licensed veterinarian;” if not labeled for use by stomach tube or drench,...

  10. 21 CFR 520.2380f - Thiabendazole, piperazine phosphate powder.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... oral dose. Administer as a drench or by stomach tube suspended in 1 pint of warm water; by dose syringe... stomach tube or drench, it shall also bear the statement “Caution: Federal law restricts this drug to use by or on the order of a licensed veterinarian;” if not labeled for use by stomach tube or drench,...

  11. Scheduling the blended solution as industrial CO2 absorber in separation process by back-propagation artificial neural networks.

    PubMed

    Abdollahi, Yadollah; Sairi, Nor Asrina; Said, Suhana Binti Mohd; Abouzari-lotf, Ebrahim; Zakaria, Azmi; Sabri, Mohd Faizul Bin Mohd; Islam, Aminul; Alias, Yatimah

    2015-11-01

    It is believe that 80% industrial of carbon dioxide can be controlled by separation and storage technologies which use the blended ionic liquids absorber. Among the blended absorbers, the mixture of water, N-methyldiethanolamine (MDEA) and guanidinium trifluoromethane sulfonate (gua) has presented the superior stripping qualities. However, the blended solution has illustrated high viscosity that affects the cost of separation process. In this work, the blended fabrication was scheduled with is the process arranging, controlling and optimizing. Therefore, the blend's components and operating temperature were modeled and optimized as input effective variables to minimize its viscosity as the final output by using back-propagation artificial neural network (ANN). The modeling was carried out by four mathematical algorithms with individual experimental design to obtain the optimum topology using root mean squared error (RMSE), R-squared (R(2)) and absolute average deviation (AAD). As a result, the final model (QP-4-8-1) with minimum RMSE and AAD as well as the highest R(2) was selected to navigate the fabrication of the blended solution. Therefore, the model was applied to obtain the optimum initial level of the input variables which were included temperature 303-323 K, x[gua], 0-0.033, x[MDAE], 0.3-0.4, and x[H2O], 0.7-1.0. Moreover, the model has obtained the relative importance ordered of the variables which included x[gua]>temperature>x[MDEA]>x[H2O]. Therefore, none of the variables was negligible in the fabrication. Furthermore, the model predicted the optimum points of the variables to minimize the viscosity which was validated by further experiments. The validated results confirmed the model schedulability. Accordingly, ANN succeeds to model the initial components of the blended solutions as absorber of CO2 capture in separation technologies that is able to industries scale up. PMID:26119355

  12. Anion exchangers with branched functional ion exchange layers of different hydrophilicity for ion chromatography.

    PubMed

    Shchukina, O I; Zatirakha, A V; Smolenkov, A D; Nesterenko, P N; Shpigun, O A

    2015-08-21

    Novel polystyrene-divinylbenzene (PS-DVB) based anion exchangers differing from each other in the structure of the branched functional ion exchange layer are prepared to investigate the role of linker and functional site on ion exchange selectivity. The proposed method of synthesis includes the obtaining of aminated PS-DVB particles by means of their acylation with following reductive amination with methylamine. Further modification of the obtained secondary aminogroups is provided by the alkylation with either 1,4-butanediol diglycidyl ether (1,4-BDDGE) or resorcinol diglycidyl ether (RDGE), which form the linkers of different hydrophobicity, and amination of terminal epoxide rings with trimethylamine (TMA), dimethylethanolamine (DMEA), methyldiethanolamine (MDEA) or triethanolamine (TEA). The variation of the structure and hydrophobicity of the linker and terminal quaternary ammonium sites in the functional layer allows the alteration of selectivity and separation efficiency of the obtained adsorbents. The ion exchange selectivity and separation efficiency of the anion exchangers are evaluated using the model mixtures of anions (F(-), HCOO(-), Cl(-), NO2(-), Br(-), NO3(-), HPO4(2-) and SO4(2-)) in potassium hydroxide eluents. The adsorbents show the decrease of selectivity with increasing the hydrophilicity of the terminal functional site. The anion exchangers having more flexible and hydrophilic 1,4-BDDGE linker provide smaller separation factors for most of the analytes as compared with RDGE-containing adsorbents with the same terminal ion exchange sites, but are characterized with higher column efficiencies and better peak symmetry for polarizable anions. In case of 1,4-BDDGE-modified anion exchangers of the particle size of 3.3μm functionalized with DMEA and MDEA the calculated values of column efficiencies for polarizable NO3(-) and Br(-) are up to 49,000 and 53,000N/m, respectively, which is almost twice higher than the values obtained for the RDGE-containing analogues. PMID:26159253

  13. Hydrogen-based power generation from bioethanol steam reforming

    NASA Astrophysics Data System (ADS)

    Tasnadi-Asztalos, Zs.; Cormos, C. C.; Agachi, P. S.

    2015-12-01

    This paper is evaluating two power generation concepts based on hydrogen produced from bioethanol steam reforming at industrial scale without and with carbon capture. The power generation from bioethanol conversion is based on two important steps: hydrogen production from bioethanol catalytic steam reforming and electricity generation using a hydrogen-fuelled gas turbine. As carbon capture method to be assessed in hydrogen-based power generation from bioethanol steam reforming, the gas-liquid absorption using methyl-di-ethanol-amine (MDEA) was used. Bioethanol is a renewable energy carrier mainly produced from biomass fermentation. Steam reforming of bioethanol (SRE) provides a promising method for hydrogen and power production from renewable resources. SRE is performed at high temperatures (e.g. 800-900°C) to reduce the reforming by-products (e.g. ethane, ethene). The power generation from hydrogen was done with M701G2 gas turbine (334 MW net power output). Hydrogen was obtained through catalytic steam reforming of bioethanol without and with carbon capture. For the evaluated plant concepts the following key performance indicators were assessed: fuel consumption, gross and net power outputs, net electrical efficiency, ancillary consumptions, carbon capture rate, specific CO2 emission etc. As the results show, the power generation based on bioethanol conversion has high energy efficiency and low carbon footprint.

  14. Rigorous modeling of the acid gas heat of absorption in alkanolamine solutions

    SciTech Connect

    Emilie Blanchon le Bouhelec; Pascal Mougin; Alain Barreau; Roland Solimando

    2007-08-15

    In this work, we are interested in the estimation of CO{sub 2} and H{sub 2}S heats of absorption in aqueous solutions of alkanolamine: monoethanolamine (MEA), diethanolamine (DEA), and methyldiethanolamine (MDEA). Two methods can be used to calculate the heat release during the absorption phenomenon. The easier which consists of applying the integration of the Gibbs-Helmholtz expression remains inaccurate. The second one, more rigorous, evaluates the heat transfer through an internal energy balance for an open system. The balance expression contains partial molar enthalpies of species in the liquid phase which are calculated from the electrolyte nonrandom-two-liquid (NRTL) excess Gibbs energy model. The calculations carried out in this method can be considered as predictive regarding the NRTL model because its interaction parameters were previously and solely fitted on vapor-liquid equilibrium (VLE) data and not on experimental heat of absorption data. The comparison between both methods and experimental data for the three alkanolamines shows the contribution of this rigorous calculation to better estimate both properties (i.e., solubility and heat) and its usefulness to improve processes. Heats of absorption calculated with the second method can be used in addition to VLE data to fit NRTL parameters. This procedure leads to less-correlated parameters and allows extrapolating the model with more confidence. 63 refs., 10 figs., 6 tabs.

  15. Electropolymerized carbonic anhydrase immobilization for carbon dioxide capture.

    PubMed

    Merle, Geraldine; Fradette, Sylvie; Madore, Eric; Barralet, Jake E

    2014-06-17

    Biomimetic carbonation carried out with carbonic anhydrase (CA) in CO2-absorbing solutions, such as methyldiethanolamine (MDEA), is one approach that has been developed to accelerate the capture of CO2. However, there are several practical issues, such as high cost and limited enzyme stability, that need to be overcome. In this study, the capacity of CA immobilization on a porous solid support was studied to improve the instability in the tertiary amine solvent. We have shown that a 63% porosity macroporous carbon foam support makes separation and reuse facile and allows for an efficient supply and presentation of CO2 to an aqueous solvent and the enzyme catalytic center. These enzymatic supports conserved 40% of their initial activity after 42 days at 70 °C in an amine solvent, whereas the free enzyme shows no activity after 1 h in the same conditions. In this work, we have overcome the technical barrier associated with the recovery of the biocatalyst after operation, and most of all, these electropolymerized enzymatic supports have shown a remarkable increase of thermal stability in an amine-based CO2 sequestration solvent. PMID:24856780

  16. A cotton fabric modified with a hydrogel containing ZnO nanoparticles. Preparation and properties study

    NASA Astrophysics Data System (ADS)

    Staneva, Desislava; Atanasova, Daniela; Vasileva-Tonkova, Evgenia; Lukanova, Varbina; Grabchev, Ivo

    2015-08-01

    Two different methods were used to obtain composite materials based on a ZnO nanoparticles-hydrogel-cotton fabric. The hydrogels, synthesized by photopolymerization, were utilized to provide uniform distribution and binding of the nanoparticles to the fiber surface and to prevent their agglomeration. N-methyldiethanolamine (MDEA) was used as a co-initiator in hydrogel photopolymerization and as an alkaline agent in the synthesis of ZnO nanoparticles. Due to the difference in size, shape and morphology of the nanoparticles, examined by a TEM and SEM, it was found that the materials have distinct photoluminescence properties, e.g. in the entire visible or UV range. The composite materials with small size nanoparticles and photoluminescence in near UV range were investigated for antibiotic activity against the bacterial strains Pseudomonas aeruginosa and Acinetobacter johnsonii known as important pathogens in clinical infections. Significantly high antibacterial effect on the bacteria tested was achieved, especially on A. johnsonii. This suggests potential application of the new formulations as effective wound dressings to control the spread of infections.

  17. Synthesis, characterization and antibacterial properties of dihydroxy quaternary ammonium salts with long chain alkyl bromides.

    PubMed

    Liu, Wen-Shuai; Wang, Chun-Hua; Sun, Ju-Feng; Hou, Gui-Ge; Wang, Yu-Peng; Qu, Rong-Jun

    2015-01-01

    Five N-methyl-N-R-N,N-bis(2-hydroxyethyl) ammonium bromides (R = -benzyl (chloride, BNQAS), -dodecyl (C12QAS), -tetradecyl (C14QAS), -hexadecyl (C16QAS), -octadecyl (C18QAS)) were prepared based on N-methyldiethanolamine (MDEA) and halohydrocarbon. Five QAS were characterized by FTIR, NMR, and MS. BNQAS, C12QAS, C14QAS, and C16QAS were confirmed by X-ray single-crystal diffraction. Their antibacterial properties indicated good antibacterial abilities against E. coli, S. aureus, B. subtilis, especially C12QAS with the best antibacterial ability (100% to E. coli, 95.65% to S. aureus, and 91.41% to B. subtilis). In addition, C12QAS also displayed the best antifungal activities than BNQAS and C18QAS against Cytospora mandshurica, Botryosphaeria ribis, Physalospora piricola, and Glomerella cingulata with the ratio of full marks. The strategy provides a facile way to design and develop new types of antibacterial drugs for application in preventing the fruit rot, especially apple. PMID:25215430

  18. The electrochemical and spectroelectrochemical properties of metal free and metallophthalocyanines containing triazole/piperazine units.

    PubMed

    Demirbaş, Ümit; Akyüz, Duygu; Mermer, Arif; Akçay, Hakkı Türker; Demirbaş, Neslihan; Koca, Atıf; Kantekin, Halit

    2016-01-15

    The synthesis and characterization of novel peripherally tetra [1,2,4]-triazole substituted metal-free phthalocyanine and its metal complexes (Zn(II), Ni(II), Pb(II), Cu(II) and Fe(II)) and the investigation of electrochemical and spectroelectrochemical properties of metal-free, Zn(II), Pb(II), Fe(II) phthalocyanines were performed for the first time in this study. Electrochemical characterizations of the complexes were performed with voltammetric and in situ spectroelectrochemical measurements. Voltammetric responses of the complexes supported the proposed structures, since complexes bearing redox inactive Pc ring metal centers just gave Pc based electron transfer reactions, while iron phthalocyanine went to metal based electron transfer reaction in addition to the Pc based ones. Electron withdrawing nature of [1,2,4]-triazole substituents shifted the redox processes toward the positive potentials. All complexes were electropolymerized during the oxidation reactions in dichloromethane (DCM) solvent. Types of the metal center of the complexes altered the electropolymerization reactions of the complexes. Spectra and colors of the electrogenerated redox species of the complexes were also determined with in situ spectroelectrochemical and in situ electrocolorimetric measurements. PMID:26397034

  19. 21 CFR 520.763c - Dithiazanine iodide and piperazine citrate suspension.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... first 500 pounds; 3/4 ounce for each 100 pounds thereafter, up to 1,200 pounds; 101/4 ounces to animals... conditions of use are NAS/NRC reviewed and found effective. Applications for these uses need not...

  20. 21 CFR 520.763c - Dithiazanine iodide and piperazine citrate suspension.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... first 500 pounds; 3/4 ounce for each 100 pounds thereafter, up to 1,200 pounds; 101/4 ounces to animals... conditions of use are NAS/NRC reviewed and found effective. Applications for these uses need not...

  1. 21 CFR 520.763c - Dithiazanine iodide and piperazine citrate suspension.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... first 500 pounds; 3/4 ounce for each 100 pounds thereafter, up to 1,200 pounds; 101/4 ounces to animals... conditions of use are NAS/NRC reviewed and found effective. Applications for these uses need not...

  2. 21 CFR 520.763c - Dithiazanine iodide and piperazine citrate suspension.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... first 500 pounds; 3/4 ounce for each 100 pounds thereafter, up to 1,200 pounds; 101/4 ounces to animals... conditions of use are NAS/NRC reviewed and found effective. Applications for these uses need not...

  3. Design, synthesis and preliminary pharmacological evaluation of new piperidine and piperazine derivatives as cognition-enhancers.

    PubMed

    Martini, Elisabetta; Ghelardini, Carla; Dei, Silvia; Guandalini, Luca; Manetti, Dina; Melchiorre, Michele; Norcini, Monica; Scapecchi, Serena; Teodori, Elisabetta; Romanelli, Maria Novella

    2008-02-01

    A series of 2-oxopiperazine, 4-aminomethyl-, 3-amino- and 3-aminomethylpiperidine analogues of DM235 (sunifiram) and MN19 (sapunifiram), two previously reported potent cognition-enhancers, have been synthesized and tested in the mouse passive-avoidance test. The compounds display minimal effective doses in the range 0.3-10mg/kg. Although the new substances do not show improved activity when compared to the parent compounds, some useful information has been obtained to understand structure-activity relationships. In addition, the 3-aminopiperidine moiety appears to be a promising scaffold to synthesize new drugs endowed with cognition-enhancing activity. PMID:17981042

  4. Tetraaquabis(piperazin-1-ium)cobalt(II) bis(sulfate) dihydrate

    PubMed Central

    Sahbani, Thameur; Smirani Sta, Wajda; Rzaigui, Mohamed

    2013-01-01

    In the centrosymmetric title compound, [Co(C4H11N2)2(H2O)4](SO4)22H2O, the CoII atom is coordinated in a distorted octahedral geometry by four water O atoms and two piperazinium N atoms. These four water O atoms define an equatorial plane with a maximum deviation of 0.0384?(1)? while the two piperazinium N atoms complete the octahedron in the axial positions. Neighboring complex molecules and sulfate anions are connected through an extensive network of NH?O and OH?O hydrogen bonds, which link the different chemical species into layers in the ab plane. Additional OwaterH?O hydrogen bonds involving the non-coordinating water molecules and CH?O interactions connect these layers into a three-dimensional supramolecular structure. PMID:24454163

  5. 21 CFR 520.1242c - Levamisole hydrochloride and piperazine dihydrochloride.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... (Oxyuris equii). (2) Limitations. Aqueous solution: administer by stomach tube or drench 1 fluid ounce per 100 pounds of body weight. Reconstituted soluble powder: administer by stomach tube 1 fluid ounce...

  6. 21 CFR 520.1242c - Levamisole hydrochloride and piperazine dihydrochloride.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... (Oxyuris equii). (2) Limitations. Aqueous solution: administer by stomach tube or drench 1 fluid ounce per 100 pounds of body weight. Reconstituted soluble powder: administer by stomach tube 1 fluid ounce...

  7. 21 CFR 520.1242c - Levamisole hydrochloride and piperazine dihydrochloride.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... (Oxyuris equii). (2) Limitations. Aqueous solution: administer by stomach tube or drench 1 fluid ounce per 100 pounds of body weight. Reconstituted soluble powder: administer by stomach tube 1 fluid ounce...

  8. 21 CFR 520.1242c - Levamisole hydrochloride and piperazine dihydrochloride.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... (Oxyuris equii). (2) Limitations. Aqueous solution: administer by stomach tube or drench 1 fluid ounce per 100 pounds of body weight. Reconstituted soluble powder: administer by stomach tube 1 fluid ounce...

  9. 21 CFR 520.1242c - Levamisole hydrochloride and piperazine dihydrochloride.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... (Oxyuris equii). (2) Limitations. Aqueous solution: administer by stomach tube or drench 1 fluid ounce per 100 pounds of body weight. Reconstituted soluble powder: administer by stomach tube 1 fluid ounce...

  10. Discovery of 1-aryloxyethyl piperazine derivatives as Kv1.5 potassium channel inhibitors (part I).

    PubMed

    Guo, Xiaoke; Ma, Xianglei; Yang, Qian; Xu, Jing; Huang, Lu; Jia, Jianmin; Shan, Jiaojiao; Liu, Li; Chen, Weilin; Chu, Hongxi; Wei, Jinlian; Zhang, Xiaojin; Sun, Haopeng; Tang, Yiqun; You, Qidong

    2014-06-23

    Kv1.5 potassium channel is an efficacious and safe therapeutic target for the treatment of atrial fibrillation (AF), the most common arrhythmia that threatens human. Herein, by modifying the hit compound 7k from an in-house database, 48 derivatives were synthesized for the assay of their Kv1.5 inhibitory effects by whole cell patch clamp technique. Six compounds which showed better potency than the positive compound dronedarone were selected for the next evaluation of their drug-like properties. Compound 8 exhibited balanced solubility and permeability. It also showed acceptable pharmacodynamics profile with very low acute toxicity. Taking all these data into account, compound 8 can serve as a promising lead for the development of novel therapeutic agent for the treatment of AF. PMID:24824064

  11. 21 CFR 520.1802b - Piperazine-carbon disulfide complex boluses.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ...) per 500 pounds body weight; removal of large strongyles, pinworms, and bots, 1 bolus per 250 pounds...), large strongyles (Strongylus spp.) bots (Gastrophilus spp.), small strongyles, and pinworms...

  12. 21 CFR 520.1802b - Piperazine-carbon disulfide complex boluses.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ...) per 500 pounds body weight; removal of large strongyles, pinworms, and bots, 1 bolus per 250 pounds...), large strongyles (Strongylus spp.) bots (Gastrophilus spp.), small strongyles, and pinworms...

  13. 21 CFR 520.1802b - Piperazine-carbon disulfide complex boluses.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ...) per 500 pounds body weight; removal of large strongyles, pinworms, and bots, 1 bolus per 250 pounds...), large strongyles (Strongylus spp.) bots (Gastrophilus spp.), small strongyles, and pinworms...

  14. 21 CFR 520.1802b - Piperazine-carbon disulfide complex boluses.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ...) per 500 pounds body weight; removal of large strongyles, pinworms, and bots, 1 bolus per 250 pounds...), large strongyles (Strongylus spp.) bots (Gastrophilus spp.), small strongyles, and pinworms...

  15. 21 CFR 520.1802b - Piperazine-carbon disulfide complex boluses.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ...), large strongyles (Strongylus spp.) bots (Gastrophilus spp.), small strongyles, and pinworms (Oxyuris equi).1 (3) Limitations. Withhold feed overnight or for 8 to 10 hours. Give water just before...

  16. Synthesis, growth and characterization of a new organic three dimensional framework: Piperazin-1-ium 4-aminobenzenesulfonate

    NASA Astrophysics Data System (ADS)

    Rekha, P.; Peramaiyan, G.; NizamMohideen, M.; Mohan Kumar, R.; Kanagadurai, R.

    2016-05-01

    Piperazinium p-aminobenzenesulfonate (PPABS), a new nonlinear optical material was synthesized and crystals were grown from the methanol solvent by slow evaporation solution growth method. Single crystal X-ray diffraction study elucidated the crystal structure of PPABS. It crystallizes in orthorhombic crystal system with space group of Pbca. UV-vis-NIR spectral study was performed to analyze optical transparency of PPABS crystal and found that the grown crystal has sufficient transparency in the entire visible region with lower cutoff wavelength of 321 nm. The thermal stability and decomposition stages of the sample were studied by TG/DTA analyses. The different environmental carbon and hydrogen atoms of the proposed structure were identified by NMR spectral studies. The electric field response of crystal was determined from the dielectric studies. From the Z-scan measurements, the third order nonlinear optical properties of grown crystal were studied.

  17. The electrochemical and spectroelectrochemical properties of metal free and metallophthalocyanines containing triazole/piperazine units

    NASA Astrophysics Data System (ADS)

    Demirbaş, Ümit; Akyüz, Duygu; Mermer, Arif; Akçay, Hakkı Türker; Demirbaş, Neslihan; Koca, Atıf; Kantekin, Halit

    2016-01-01

    The synthesis and characterization of novel peripherally tetra [1,2,4]-triazole substituted metal-free phthalocyanine and its metal complexes (Zn(II), Ni(II), Pb(II), Cu(II) and Fe(II)) and the investigation of electrochemical and spectroelectrochemical properties of metal-free, Zn(II), Pb(II), Fe(II) phthalocyanines were performed for the first time in this study. Electrochemical characterizations of the complexes were performed with voltammetric and in situ spectroelectrochemical measurements. Voltammetric responses of the complexes supported the proposed structures, since complexes bearing redox inactive Pc ring metal centers just gave Pc based electron transfer reactions, while iron phthalocyanine went to metal based electron transfer reaction in addition to the Pc based ones. Electron withdrawing nature of [1,2,4]-triazole substituents shifted the redox processes toward the positive potentials. All complexes were electropolymerized during the oxidation reactions in dichloromethane (DCM) solvent. Types of the metal center of the complexes altered the electropolymerization reactions of the complexes. Spectra and colors of the electrogenerated redox species of the complexes were also determined with in situ spectroelectrochemical and in situ electrocolorimetric measurements.

  18. Discovery of potent furan piperazine sodium channel blockers for treatment of neuropathic pain.

    PubMed

    Drizin, Irene; Gregg, Robert J; Scanio, Marc J C; Shi, Lei; Gross, Michael F; Atkinson, Robert N; Thomas, James B; Johnson, Matthew S; Carroll, William A; Marron, Brian E; Chapman, Mark L; Liu, Dong; Krambis, Michael J; Shieh, Char-Chang; Zhang, XuFeng; Hernandez, Gricelda; Gauvin, Donna M; Mikusa, Joseph P; Zhu, Chang Z; Joshi, Shailen; Honore, Prisca; Marsh, Kennan C; Roeloffs, Rosemarie; Werness, Stephen; Krafte, Douglas S; Jarvis, Michael F; Faltynek, Connie R; Kort, Michael E

    2008-06-15

    The synthesis and pharmacological characterization of a novel furan-based class of voltage-gated sodium channel blockers is reported. Compounds were evaluated for their ability to block the tetrodotoxin-resistant sodium channel Na(v)1.8 (PN3) as well as the Na(v)1.2 and Na(v)1.5 subtypes. Benchmark compounds from this series possessed enhanced potency, oral bioavailability, and robust efficacy in a rodent model of neuropathic pain, together with improved CNS and cardiovascular safety profiles compared to the clinically used sodium channel blockers mexiletine and lamotrigine. PMID:18501613

  19. Self-assembled 3D heterometallic Cu(II)/Fe(II) coordination polymers with octahedral net skeletons: structural features, molecular magnetism, thermal and oxidation catalytic properties.

    PubMed

    Karabach, Yauhen Y; Guedes da Silva, M Fátima C; Kopylovich, Maximilian N; Gil-Hernández, Beatriz; Sanchiz, Joaquin; Kirillov, Alexander M; Pombeiro, Armando J L

    2010-12-01

    The new three-dimensional (3D) heterometallic Cu(II)/Fe(II) coordination polymers [Cu(6)(H(2)tea)(6)Fe(CN)(6)](n)(NO(3))(2n)·6nH(2)O (1) and [Cu(6)(Hmdea)(6)Fe(CN)(6)](n)(NO(3))(2n)·7nH(2)O (2) have been easily generated by aqueous-medium self-assembly reactions of copper(II) nitrate with triethanolamine or N-methyldiethanolamine (H(3)tea or H(2)mdea, respectively), in the presence of potassium ferricyanide and sodium hydroxide. They have been isolated as air-stable crystalline solids and fully characterized including by single-crystal X-ray diffraction analyses. The latter reveal the formation of 3D metal-organic frameworks that are constructed from the [Cu(2)(μ-H(2)tea)(2)](2+) or [Cu(2)(μ-Hmdea)(2)](2+) nodes and the octahedral [Fe(CN)(6)](4-) linkers, featuring regular (1) or distorted (2) octahedral net skeletons. Upon dehydration, both compounds show reversible escape and binding processes toward water or methanol molecules. Magnetic susceptibility measurements of 1 and 2 reveal strong antiferromagnetic [J = -199(1) cm(-1)] or strong ferromagnetic [J = +153(1) cm(-1)] couplings between the copper(II) ions through the μ-O-alkoxo atoms in 1 or 2, respectively. The differences in magnetic behavior are explained in terms of the dependence of the magnetic coupling constant on the Cu-O-Cu bridging angle. Compounds 1 and 2 also act as efficient catalyst precursors for the mild oxidation of cyclohexane by aqueous hydrogen peroxide to cyclohexanol and cyclohexanone (homogeneous catalytic system), leading to maximum total yields (based on cyclohexane) and turnover numbers (TONs) up to about 22% and 470, respectively. PMID:21028781

  20. Laser direct-write microfabrication and patterning

    NASA Astrophysics Data System (ADS)

    Yuan, Dajun

    The ability to generate small structures is central to modern science and technology. In this work, four laser direct-write microfabrication and micropatterning techniques were studied: (a) Laser micromachining of channels in PMMA using a CO2 laser was investigated experimentally and theoretically. Heat transfer models for the channel depth, channel profile, laser power and scanning speed were developed and applied in this work. These models, are in excellent agreement with experimental results, with a maximum deviation of approximately 5% for the range of experimental parameters (laser power, scanning speed) tested. (b) A sub-micrometer resolution laser direct-write polymerization system for 1 creating two-dimensional and three-dimensional structures was developed using a frequency-doubled Nd:YAG laser. Experimental studies and Monte Carlo simulations were conducted to understand the detailed microscale optical scattering, chemical reaction, polymerization, and their influence on critical fabrication parameters. The experimental data are in good agreement with the theoretical model. (c) Direct laser interference was developed for rapid and large area fabrication of two-dimensional and three dimensional periodic structures on photopolymerizable materials with 10ns pulses from a frequency-tripled Nd:YAG laser emitting at 355 nm. Three different photopolymerizable materials were investigated: pentaerythritol triacrylate (PETIA) with photoinitiator N-methyldiethanolamine (N-MDEA); SU-8 with absorber TINUVIN 384-2; and Shipley 1813. (d) A new approach to fabricating nanometer sized cavity arrays on Poly(3,4-ethylene dioxythiophene)-poly(styrenesulfonate) (PEDOT-PSS) thin films using laser-assisted near-field patterning was investigated. Periodic nano-cavity arrays were patterned by combining direct laser interference technology and laser induced near-field technology. An analytical model based on Mie theory was developed, the predicted intensity distributions on the substrate indicate a strong near-field enhancement confined to a very small area (nanometer scale).

  1. Wipe selection for the analysis of surface materials containing chemical warfare agent nitrogen mustard degradation products by ultra-high pressure liquid chromatography-tandem mass spectrometry.

    PubMed

    Willison, Stuart A

    2012-12-28

    Degradation products arising from nitrogen mustard chemical warfare agent were deposited on common urban surfaces and determined via surface wiping, wipe extraction, and liquid chromatography–tandem mass spectrometry detection. Wipes investigated included cotton gauze, glass fiber filter, non-woven polyester fiber and filter paper, and surfaces included several porous (vinyl tile, painted drywall, wood) and mostly non-porous (laminate, galvanized steel, glass) surfaces. Wipe extracts were analyzed by ultra-high pressure liquid chromatography–tandem mass spectrometry (UPLC–MS/MS) and compared with high performance liquid chromatography–tandem mass spectrometry (HPLC–MS/MS) results. An evaluation of both techniques suggests UPLC–MS/MS provides a quick and sensitive analysis of targeted degradation products in addition to being nearly four times faster than a single HPLC run, allowing for greater throughput during a wide-spread release concerning large-scale contamination and subsequent remediation events. Based on the overall performance of all tested wipes, filter paper wipes were selected over other wipes because they did not contain interferences or native species (TEA and DEA) associated with the target analytes, resulting in high percent recoveries and low background levels during sample analysis. Other wipes, including cotton gauze, would require a pre-cleaning step due to the presence of large quantities of native species or interferences of the targeted analytes. Percent recoveries obtained from a laminate surface were 47–99% for all nitrogen mustard degradation products. The resulting detection limits achieved from wipes were 0.2 ng/cm(2) for triethanolamine (TEA), 0.03 ng/cm(2) for N-ethyldiethanolamine (EDEA), 0.1 ng/cm(2) for N-methyldiethanolamine (MDEA), and 0.1 ng/cm(2) for diethanolamine (DEA). PMID:23218189

  2. CO2 Capture by Absorption with Potassium Carbonate

    SciTech Connect

    Gary T. Rochelle; Andrew Sexton; Jason Davis; Marcus Hilliard; Qing Xu; David Van Wagener; Jorge M. Plaza

    2007-03-31

    The objective of this work is to improve the process for CO{sub 2} capture by alkanolamine absorption/stripping by developing an alternative solvent, aqueous K{sub 2}CO{sub 3} promoted by piperazine. The best K{sup +}/PZ solvent, 4.5 m K{sup +}/4.5 m PZ, requires equivalent work of 31.8 kJ/mole CO{sub 2} when used with a double matrix stripper and an intercooled absorber. The oxidative degradation of piperazine or organic acids is reduced significantly by inhibitor A, but the production of ethylenediamine is unaffected. The oxidative degradation of piperazine in 7 m MEA/2 m PZ is catalyzed by Cu{sup ++}. The thermal degradation of MEA becomes significant at 120 C. The solubility of potassium sulfate in MEA/PZ solvents is increased at greater CO{sub 2} loading. The best solvent and process configuration, matrix with MDEA/PZ, offers 22% and 15% energy savings over the baseline and improved baseline, respectively, with stripping and compression to 10 MPa. The energy requirement for stripping and compression to 10 MPa is about 20% of the power output from a 500 MW power plant with 90% CO{sub 2} removal. The stripper rate model shows that a ''short and fat'' stripper requires 7 to 15% less equivalent work than a ''tall and skinny'' one. The stripper model was validated with data obtained from pilot plant experiments at the University of Texas with 5m K{sup +}/2.5m PZ and 6.4m K{sup +}/1.6m PZ under normal pressure and vacuum conditions using Flexipac AQ Style 20 structured packing. Experiments with oxidative degradation at low gas rates confirm the effects of Cu{sup +2} catalysis; in MEA/PZ solutions more formate and acetate is produced in the presence of Cu{sup +2}. At 150 C, the half life of 30% MEA with 0.4 moles CO{sub 2}/mole amine is about 2 weeks. At 100 C, less than 3% degradation occurred in two weeks. The solubility of potassium sulfate in MEA solution increases significantly with CO{sub 2} loading and decreases with MEA concentration. The base case corrosion rate in 5 M MEA/1.2M PZ is 22 mpy. With 1 wt% heat stable salt, the corrosion rate increases by 50% to 160% in the order: thiosulfate< oxalate

  3. Novel heteroleptic lanthanide organic frameworks containing pyridine-2,5-dicarboxylic acid and in situ generated piperazine-2,5-dicarboxylic acid from piperazine: Hydrothermal synthesis and luminescent properties

    NASA Astrophysics Data System (ADS)

    Ay, Burak; Yildiz, Emel; Kani, İbrahim

    2016-01-01

    Two novel 3D lanthanide metal-organic frameworks [Ln(pydc)(pip)1/2(H2O] (Ln=Ce (1) and Pr (2), H2pydc=2,5-pyridinedicarboxylic acid, H2pip=2,5-piperazinedicarboxylic acid have been synthesized under hydrothermal conditions and characterized by elemental analysis, IR spectroscopy, thermogravimetric analysis (TGA), powder X-ray diffractions (PXRD), and single-crystal X-ray diffractions. Field emission scanning electron microscopy (FESEM) was used for morphological analysis. Complexes are isostructural and feature interesting 3D frameworks. Both compounds crystallize in the monoclinic system, space group P21/c. Structural analyses of 1 and 2 show that Ln3+ ions connect with each other through H2pydc and H2pip. To the best of our knowledge, they are the first heteroleptic lanthanide polymers obtained through in situ 2,5-piperazinedicarboxylic acid syntheses. Moreover, thermal and luminescent properties of the compounds have been investigated.

  4. Head-to-tail assemblies of dipolar, piperazine-linked chromophores: Synthesis, x-ray structure, and dielectric characterization

    SciTech Connect

    Katz, H.E.; Schilling, M.L. )

    1989-09-13

    A dimer and a mixture of oligomers of acceptor-substituted anilines were prepared, either by Knoevenagel condensation of substituted cyanoacetylpiperazines with p-aminobenzaldehydes or by carbonyldiimidazole-promoted coupling of phenylpiperazines with p-aminocyanocinnamic acids. The resulting oligomeric amidopiperazines possess significantly additive molecular moments when in extended conformations and therefore are potentially valuable for the fabrication of polymer films containing electric field oriented chromophores, such as required for second-order nonlinear optics. The dimer is conformationally defined, and x-ray structural analysis of a model compound confirmed the stereochemistry and bond angles at the amide linkage. The enforced extended conformation of the dimer resulted in an enhanced dipole moment relative to the constituent monomers and raises the possibility of further enhancements in extended higher oligomers.

  5. O2-Dependent Efficacy of Novel Piperidine- and Piperazine-Based Chalcones against the Human Parasite Giardia intestinalis

    PubMed Central

    Bahadur, Vijay; Mastronicola, Daniela; Tiwari, Hemandra Kumar; Kumar, Yogesh; Falabella, Micol; Pucillo, Leopoldo Paolo; Sarti, Paolo

    2014-01-01

    Giardia intestinalis is the most frequent protozoan agent of intestinal diseases worldwide. Though commonly regarded as an anaerobic pathogen, it preferentially colonizes the fairly oxygen-rich mucosa of the proximal small intestine. Therefore, when testing new potential antigiardial drugs, O2 should be taken into account, since it also reduces the efficacy of metronidazole, the gold standard drug against giardiasis. In this study, 46 novel chalcones were synthesized by microwave-assisted Claisen-Schmidt condensation, purified, characterized by high-resolution mass spectrometry, 1H and 13C nuclear magnetic resonance, and infrared spectroscopy, and tested for their toxicity against G. intestinalis under standard anaerobic conditions. As a novel approach, compounds showing antigiardial activity under anaerobiosis were also assayed under microaerobic conditions, and their selectivity against parasitic cells was assessed in a counterscreen on human epithelial colorectal adenocarcinoma cells. Among the tested compounds, three [30(a), 31(e), and 33] were more effective in the presence of O2 than under anaerobic conditions and killed the parasite 2 to 4 times more efficiently than metronidazole under anaerobiosis. Two of them [30(a) and 31(e)] proved to be selective against parasitic cells, thus representing potential candidates for the design of novel antigiardial drugs. This study highlights the importance of testing new potential antigiardial agents not only under anaerobic conditions but also at low, more physiological O2 concentrations. PMID:24217695

  6. O(2)-dependent efficacy of novel piperidine- and piperazine-based chalcones against the human parasite Giardia intestinalis.

    PubMed

    Bahadur, Vijay; Mastronicola, Daniela; Tiwari, Hemandra Kumar; Kumar, Yogesh; Falabella, Micol; Pucillo, Leopoldo Paolo; Sarti, Paolo; Giuffrè, Alessandro; Singh, Brajendra Kumar

    2014-01-01

    Giardia intestinalis is the most frequent protozoan agent of intestinal diseases worldwide. Though commonly regarded as an anaerobic pathogen, it preferentially colonizes the fairly oxygen-rich mucosa of the proximal small intestine. Therefore, when testing new potential antigiardial drugs, O2 should be taken into account, since it also reduces the efficacy of metronidazole, the gold standard drug against giardiasis. In this study, 46 novel chalcones were synthesized by microwave-assisted Claisen-Schmidt condensation, purified, characterized by high-resolution mass spectrometry, (1)H and (13)C nuclear magnetic resonance, and infrared spectroscopy, and tested for their toxicity against G. intestinalis under standard anaerobic conditions. As a novel approach, compounds showing antigiardial activity under anaerobiosis were also assayed under microaerobic conditions, and their selectivity against parasitic cells was assessed in a counterscreen on human epithelial colorectal adenocarcinoma cells. Among the tested compounds, three [30(a), 31(e), and 33] were more effective in the presence of O2 than under anaerobic conditions and killed the parasite 2 to 4 times more efficiently than metronidazole under anaerobiosis. Two of them [30(a) and 31(e)] proved to be selective against parasitic cells, thus representing potential candidates for the design of novel antigiardial drugs. This study highlights the importance of testing new potential antigiardial agents not only under anaerobic conditions but also at low, more physiological O2 concentrations. PMID:24217695

  7. Single-molecule magnetism in a family of {Co(III)2Dy(III)2} butterfly complexes: effects of ligand replacement on the dynamics of magnetic relaxation.

    PubMed

    Langley, Stuart K; Ungur, Liviu; Chilton, Nicholas F; Moubaraki, Boujemaa; Chibotaru, Liviu F; Murray, Keith S

    2014-05-01

    The synthesis and structural characterization of four related heterometallic complexes of formulas [Dy(III)2Co(III)2(OMe)2(teaH)2(O2CPh)4(MeOH)4](NO3)2·MeOH·H2O (1a) and [Dy(III)2Co(III)2(OMe)2(teaH)2(O2CPh)4(MeOH)2(NO3)2]·MeOH·H2O (1b), [Dy(III)2Co(III)2(OMe)2(dea)2(O2CPh)4(MeOH)4](NO3)2 (2), [Dy(III)2Co(III)2(OMe)2(mdea)2(O2CPh)4(NO3)2] (3), and [Dy(III)2Co(III)2(OMe)2(bdea)2(O2CPh)4(MeOH)4](NO3)2·0.5MeOH·H2O (4a) and [Dy(III)2Co(III)2(OMe)2(bdea)2(O2CPh)4(MeOH)2(NO3)2]·MeOH·1.5H2O (4b) are reported (teaH3 = triethanolamine, deaH2 = diethanolamine, mdeaH2 = N-methyldiethanolamine, and bdeaH2 = N-n-butyldiethanolamine). Compounds 1 (≡ 1a and 1b) and 4 (≡ 4a and 4b) both display two unique molecules within the same crystal and all compounds display a butterfly type core, with the Dy(III) ions occupying the central body positions and the diamagnetic Co(III) ions the outer wing-tip sites. Compounds 1-4 were investigated via direct current and alternating current magnetic susceptibility measurements, and it was found that each complex displayed single-molecule magnet (SMM) behavior. All four compounds display unique coordination and geometric environments around the Dy(III) ions and it was found that each displays a different anisotropy barrier. Ab initio calculations were performed on 1-4 and these determined the low lying electronic structure of each Dy(III) ion and the magnetic interactions for each cluster. It was found that there was a strong correlation between the calculated energy gap between the ground and first excited states of the single-ion ligand-field split Dy(III) levels and the experimentally observed anisotropy barrier. Furthermore, the transverse g factors found for the Dy(III) ions, defining the tunnelling rates within the ground Kramers doublets, are largest for 1, which agrees with the experimental observation of the shortest relaxation time in the high-temperature domain for this complex. The magnetic exchange between the Dy(III) ions revealed overall antiferromagnetic interactions for each compound, derived from the dominant dipolar exchange resulting in nonmagnetic ground states for 1-4. The diamagnetic ground states coupled with small tunneling gaps resulted in quantum tunneling time scales at zero field of between 0.1 and >1.5 s. PMID:24749511

  8. Rapid and simple LC-MS/MS screening of 64 novel psychoactive substances using dried blood spots.

    PubMed

    Ambach, Lars; Hernández Redondo, Ana; König, Stefan; Weinmann, Wolfgang

    2014-04-01

    The range of novel psychoactive substances (NPS) including phenethylamines, cathinones, piperazines, tryptamines, etc. is continuously growing. Therefore, fast and reliable screening methods for these compounds are essential and needed. The use of dried blood spots (DBS) for a fast straightforward approach helps to simplify and shorten sample preparation significantly. DBS were produced from 10 µl of whole blood and extracted offline with 500 µl methanol followed by evaporation and reconstitution in mobile phase. Reversed-phase chromatographic separation and mass spectrometric detection (RP-LC-MS/MS) was achieved within a run time of 10 min. The screening method was validated by evaluating the following parameters: limit of detection (LOD), matrix effect, selectivity and specificity, extraction efficiency, and short-term and long-term stability. Furthermore, the method was applied to authentic samples and results were compared with those obtained with a validated whole blood method used for routine analysis of NPS. LOD was between 1 and 10 ng/ml. No interference from matrix compounds was observed. The method was proven to be specific and selective for the analytes, although with limitations for 3-FMC/flephedrone and MDDMA/MDEA. Mean extraction efficiency was 84.6 %. All substances were stable in DBS for at least a week when cooled. Cooling was essential for the stability of cathinones. Prepared samples were stable for at least 3 days. Comparison to the validated whole blood method yielded similar results. DBS were shown to be useful in developing a rapid screening method for NPS with simplified sample preparation. PMID:23868723

  9. CO2 Capture by Absorption with Potassium Carbonate

    SciTech Connect

    Gary T. Rochelle; Eric Chen; Babatunde Oyenekan; Andrew Sexton; Jason Davis; Marus Hiilliard; Qing Xu; David Van Wagener; Jorge M. Plaza

    2006-12-31

    The objective of this work is to improve the process for CO{sub 2} capture by alkanolamine absorption/stripping by developing an alternative solvent, aqueous K{sub 2}CO{sub 3} promoted by piperazine. The best solvent and process configuration, matrix with MDEA/PZ, offers 22% and 15% energy savings over the baseline and improved baseline, respectively, with stripping and compression to 10 MPa. The energy requirement for stripping and compression to 10 MPa is about 20% of the power output from a 500 MW power plant with 90% CO{sub 2} removal. The stripper rate model shows that a ''short and fat'' stripper requires 7 to 15% less equivalent work than a ''tall and skinny'' one. The stripper model was validated with data obtained from pilot plant experiments at the University of Texas with 5m K{sup +}/2.5m PZ and 6.4m K{sup +}/1.6m PZ under normal pressure and vacuum conditions using Flexipac AQ Style 20 structured packing. Experiments with oxidative degradation at low gas rates confirm the effects of Cu{sup +2} catalysis; in MEA/PZ solutions more formate and acetate is produced in the presence of Cu{sup +2}. At 150 C, the half life of 30% MEA with 0.4 moles CO{sub 2}/mole amine is about 2 weeks. At 100 C, less than 3% degradation occurred in two weeks. The solubility of potassium sulfate in MEA solution increases significantly with CO{sub 2} loading and decreases with MEA concentration. The base case corrosion rate in 5 M MEA/1,2M PZ is 22 mpy. With 1 wt% heat stable salt, the corrosion rate increases by 50% to 160% in the order: thiosulfate< oxalate

  10. Acute Oral Toxicity Evaluations of Some Zinc(II) Complexes Derived from 1-(2-Salicylaldiminoethyl)piperazine Schiff Bases in Rats

    PubMed Central

    Salga, Muhammad Saleh; Ali, Hapipah Mohd; Abdulla, Mahmood Ameen; Abdelwahab, Siddig Ibrahim

    2012-01-01

    The current study described the synthesis and the in vivo acute oral toxicity evaluations in Sprague Dawley rats. The compounds were characterized by elemental analyses, LC-MS, FTIR, 1H NMR, 13C NMR and UV-visible spectroscopy. In the acute toxicity study, a single administration of the compounds was performed orally to the rats at the single doses of 2000 mg/kg and they were then monitored for possible side effects, mortality or behavioral changes up to 14 days. The serum level of aspartate (AST), alanine aminotransferases (ALT), alkaline phosphate (ALP), triglyceride, high density lipoprotein (HDL), immunoglobulins (GAM) and the C-reactive proteins did not significantly change. The hematological indices white blood cells (WBC), haematocrit (HCT), red blood cells (RBC), mean corpuscular volume (MCV), mean corpuscular haemoglobin concentration (MCHC), and mean corpuscular hemoglobin (MCH) were within the normal range. The renal function indices examined were also within the reference range. Generally, the compounds exhibited low toxic effects as required for further in vivo therapeutic studies. PMID:22408397

  11. Discovery of novel non-peptidic beta-alanine piperazine amide derivatives and their optimization to achiral, easily accessible, potent and selective somatostatin sst1 receptor antagonists.

    PubMed

    Troxler, Thomas; Hurth, Konstanze; Mattes, Henri; Prashad, Mahavir; Schoeffter, Philippe; Langenegger, Daniel; Enz, Albert; Hoyer, Daniel

    2009-03-01

    Structural simplification of the core moieties of obeline and ergoline somatostatin sst(1) receptor antagonists, followed by systematic optimization, led to the identification of novel, highly potent and selective sst(1) receptor antagonists. These achiral, non-peptidic compounds are easily prepared and show promising PK properties in rodents. PMID:19208473

  12. Discovery of spirofused piperazine and diazepane amides as selective histamine-3 antagonists with in vivo efficacy in a mouse model of cognition.

    PubMed

    Brown, Dean G; Bernstein, Peter R; Griffin, Andrew; Wesolowski, Steve; Labrecque, Denis; Tremblay, Maxime C; Sylvester, Mark; Mauger, Russell; Edwards, Phillip D; Throner, Scott R; Folmer, James J; Cacciola, Joseph; Scott, Clay; Lazor, Lois A; Pourashraf, Mehrnaz; Santhakumar, Vijayaratnam; Potts, William M; Sydserff, Simon; Giguère, Pascall; Lévesque, Carine; Dasser, Mohammed; Groblewski, Thierry

    2014-02-13

    A new series of potent and selective histamine-3 receptor (H3R) antagonists was identified on the basis of an azaspiro[2.5]octane carboxamide scaffold. Many scaffold modifications were largely tolerated, resulting in nanomolar-potent compounds in the H3R functional assay. Exemplar compound 6s demonstrated a selective profile against a panel of 144 secondary pharmacological receptors, with activity at only σ2 (62% at 10 μM). Compound 6s demonstrated free-plasma exposures above the IC50 (∼50×) with a brain-to-plasma ratio of ∼3 following intravenous dosing in mice. At three doses tested in the mouse novel object recognition model (1, 3, and 10 mg/kg s.c.), 6s demonstrated a statistically significant response compared with the control group. This series represents a new scaffold of H3 receptor antagonists that demonstrates in vivo exposure and efficacy in an animal model of cognition. PMID:24410637

  13. Dichlorido(4-meth-oxy-2-{[2-(piperazin-4-ium-1-yl)eth-yl]imino-meth-yl}phenol-ate)cadmium.

    PubMed

    Saleh Salga, Muhammad; Khaledi, Hamid; Mohd Ali, Hapipah

    2011-07-01

    In the title compound, [CdCl(2)(C(14)H(21)N(3)O(2))], the Schiff base ligand chelates the Cd(II) ion in an N,N,O-tridentate fashion. Two Cl atoms complete a distorted square-pyramidal coordination environment around the metal atom. In the crystal, adjacent mol-ecules are linked through C-H⋯π inter-actions into infinite chains along the a axis. The mol-ecules are further connected into a three-dimensional network via N-H⋯O, N-H⋯Cl and C-H⋯Cl inter-actions. The ethyl-ene group is disordered over two sets of sites in a 0.520 (10):0.480 (10) ratio. PMID:21836911

  14. Novel push-pull heterocyclic azo disperse dyes containing piperazine moiety: Synthesis, spectral properties, antioxidant activity and dyeing performance on polyester fibers.

    PubMed

    Mohammadi, Asadollah; Khalili, Behzad; Tahavor, Marzieh

    2015-11-01

    Six novel push-pull azo disperse dyes were synthesized via classical azo coupling reaction using 2-amino-thiazolyl derivatives as the diazo components and 1-(4-bromobenzyl)-4-phenylpiperazine as a key coupling intermediate. The structures of the dyes and synthesized intermediate were confirmed by FT-IR, (1)H NMR, (13)C NMR and UV-vis analyses. The solvatochromic behavior of the dyes was studied in a set of 10 solvents of different polarity and considerable results were obtained. The prepared heterocyclic azo dyes were applied for dyeing polyester fibers and their dyeing properties were studied. The fastness properties of the dyed fabrics such as wash, light and rubbing fastness degrees were measured by standard methods. Investigation of antioxidant activity of compounds was carried out by ferric reducing antioxidant power (FRAP) method. The synthesized dyes exhibited significant antioxidant activities. PMID:26112103

  15. Aminoalkoxo-supported heteroleptic hexanuclear gallium(III) wheel as a synthon for group 13 heterometallics: a rare sol-gel precursor for mixed Al-Ga oxide as support for gold catalysts.

    PubMed

    Mishra, Shashank; Jeanneau, Erwann; Daniele, Stéphane; Mendez, Violaine

    2010-08-28

    A new heteroleptic gallium(III) complex, Ga(6)Cl(6)(mdea)(6) (1 x 2 CHCl(3)) (mdeaH(2) = N-methyl diethanolamine) was prepared in good yield by a chloro-aminoalkoxo exchange reaction and used as a synthon for the synthesis of a novel group 13 heterometallic derivative, Ga(2)Al(4)(O)(2)(mdea)(2)(OPr(i))(10) (2 x 2 CHCl(3)), the latter acting as a facile single source precursor for the sol-gel preparation of the mixed Al-Ga oxide as a high surface area support for gold catalysts. PMID:20625595

  16. Evaluation of the genotoxic potential of alkylalkanolamines.

    PubMed

    Leung, H W; Ballantyne, B

    1997-09-18

    Three alkylalkanolamines, N,N-dimethylethanolamine, N-methyldiethanolamine, and tert-butyldiethanolamine, were evaluated for potential genotoxic activity using the Salmonella/microsome reverse gene mutation test, the CHO/HGPRT forward gene mutation test, a sister chromatid exchange test in cultured CHO cells, and an in vivo peripheral blood micronucleus test in Swiss-Webster mice. None of the three alkylalkanolamines produced any significant or dose-related increases in the frequencies of mutations, sister chromatid exchanges or micronuclei. These results indicate that N,N-dimethylethanolamine, N-methyldiethanolamine, and tert-butyldiethanolamine are not genotoxic in the tests conducted. PMID:9357557

  17. Carbonic anhydrase promotes the absorption rate of CO2 in post-combustion processes.

    PubMed

    Vinoba, Mari; Bhagiyalakshmi, Margandan; Grace, Andrews Nirmala; Kim, Dae Hoon; Yoon, Yeoil; Nam, Sung Chan; Baek, Il Hyun; Jeong, Soon Kwan

    2013-05-01

    The rate of carbon dioxide (CO2) absorption by monoethanol amine (MEA), diethanol amine (DEA), N-methyl-2,2'-iminodiethanol (MDEA), and 2-amino-2-methyl 1-propanol (AMP) solutions was found to be enhanced by the addition of bovine carbonic anhydrase (CA), has been investigated using a vapor-liquid equilibrium (VLE) device. The enthalpy (-ΔHabs) of CO2 absorption and the absorption capacities of aqueous amines were measured in the presence and/or absence of CA enzyme via differential reaction calorimeter (DRC). The reaction temperature (ΔT) under adiabatic conditions was determined based on the DRC analysis. Bicarbonate and carbamate species formation mechanisms were elucidated by (1)H and (13)C NMR spectral analysis. The overall CO2 absorption rate (flux) and rate constant (kapp) followed the order MEA > DEA > AMP > MDEA in the absence or presence of CA. Hydration of CO2 by MDEA in the presence of CA directly produced bicarbonate, whereas AMP produced unstable carbamate intermediate, then underwent hydrolytic reaction and converted to bicarbonate. The MDEA > AMP > DEA > MEA reverse ordering of the enhanced CO2 flux and kapp in the presence of CA was due to bicarbonate formation by the tertiary and sterically hindered amines. Thus, CA increased the rate of CO2 absorption by MDEA by a factor of 3 relative to the rate of absorption by MDEA alone. The thermal effects suggested that CA yielded a higher activity at 40 °C. PMID:23621860

  18. Variable dimensionality in the uranium fluoride/2-methyl-piperazine system: Synthesis and structures of UFO-5, -6, and -7; Zero-, one-, and two-dimensional materials with unprecedented topologies

    SciTech Connect

    Francis, R.J.; Halasyamani, P.S.; Bee, J.S.; O'Hare, D.

    1999-02-24

    Recently, low temperature (T < 300 C) hydrothermal reactions of inorganic precursors in the presence of organic cations have proven highly productive for the synthesis of novel solid-state materials. Interest in these materials is driven by the astonishingly diverse range of structures produced, as well as by their many potential materials chemistry applications. This report describes the high yield, phase pure hydrothermal syntheses of three new uranium fluoride phases with unprecedented structure types. Through the systematic control of the synthesis conditions the authors have successfully controlled the architecture and dimensionality of the phase formed and selectively synthesized novel zero-, one-, and two-dimensional materials.

  19. 3-(Adamantan-1-yl)-4-ethyl-1-[(4-phenyl­piperazin-1-yl)meth­yl]-1H-1,2,4-triazole-5(4H)-thione

    PubMed Central

    El-Emam, Ali A.; Al-Abdullah, Ebtehal S.; Al-Tuwaijri, Hanaa M.; Said-Abdelbaky, Mohammed; García-Granda, Santiago

    2012-01-01

    The title compound, C25H35N5S, has an approximately C-shaped conformation. The dihedral angle between the triazole and phenyl planes is 79.5 (2)°. The crystal structure consists of infinite chains parallel to the b axis, constructed by C—H⋯S hydrogen bonds between translation-related mol­ecules. Adjacent chains are linked via weak C—H⋯C inter­actions between the adamantyl and phenyl groups. PMID:22904841

  20. IP66 (1[2-ethoxy-2-(3'-pyridyl)ethyl]-4-(2'-methoxy-phenyl)piperazine) enhances beta-adrenoceptor-induced vasodilatation in rat mesenteric vascular bed.

    PubMed

    Perretti, F; Nediani, C; Manzini, S

    1990-01-01

    The effect of the antihypertensive drug IP66 on dopamine-induced vasodilatation has been investigated in isolated perfused rat mesenteric bed. Experiments were carried out in phenoxybenzamine-pretreated preparations to avoid the involvement of alpha-adrenoceptors. Dopamine (1-100 microM) elicited a concentration-dependent relaxation of high-K(+)-induced vasoconstriction, which was resistant to propranolol (3 microM), but antagonized by the DA1-receptor antagonist SCH 23390 (0.1 microM). However, the dopamine-vasodilating component resistant to SCH 23390 (0.1 microM) could be abolished by simultaneous administration of propranolol. Thus, dopamine-induced vasodilatation is mainly ascribable to stimulation of DA1-receptors, although an action on beta 2-adrenoceptors might contribute as well. In presence of IP66 (10 nM), dopamine-induced vasodilatation was significantly enhanced. This amplifying activity was not observed with prazosin and it was blocked by propranolol (3 microM) but unaffected by SCH 23390 (0.1 microM) or by chemical sympathectomy. Furthermore, IP66 (10 nM) also increased, in a significant manner, the amplitude of vasodilatation elicited by the beta 2-adrenoceptor agonist terbutaline, both in rat mesenteric bed and in rat aortic strips. In rat aortic membranes, IP66 (10 nM) enhanced the stimulatory effect of terbutaline (1 microM) on adenylate cyclase activity. In conclusion, IP66 is able to enhance the vasodilatation of rat mesenteric vasculature induced by dopamine or terbutaline. It is proposed that this action might be consequent to an increase in efficiency of the coupling between beta 2-adrenoceptors and membrane adenylate cyclase. PMID:1963768

  1. Buffer Standards for the Biological pH of the Amino Acid N-[2 hydroxyethyl]piperazine-N’-[3-propanesulfonic acid], HEPPS, From (278.15 to 328.15) K

    PubMed Central

    Roy, Lakshmi N.; Roy, Rabindra N.; Wollen, Joshua T.; Harmon, Meagan A.; Stegner, Jessica M.; Shah, Ankita A.; Henson, Isaac B.

    2011-01-01

    For the HEPPS buffer under investigation, there are seven buffer solutions without NaCl and eight buffer solutions that contain Cl− and have an ionic strength (I = 0.16 mol·kg−1), which is similar to that of blood plasma. These buffer solutions have been evaluated in the temperature range of (278.15 to 328.15) K using the extended Debye- Hückel equation and the Bates-Guggenheim convention. The previously determined Ej values have been used to determine the operational pH values of HEPPS buffer solutions at (298.15 and 310.15) K. These are recommended as secondary standard reference solutions for pH measurements in saline media with an isotonic ionic strength of I = 0.16 mol·kg−1. PMID:22096257

  2. Chemoprevention of Colonic Aberrant Crypt Foci by Novel Schiff Based Dichlorido(4-Methoxy-2-{[2-(Piperazin-4-Ium-1-Yl)Ethyl]Iminomethyl}Phenolate)Cd Complex in Azoxymethane-Induced Colorectal Cancer in Rats

    PubMed Central

    Hajrezaie, Maryam; Shams, Keivan; Moghadamtousi, Soheil Zorofchian; Karimian, Hamed; Hassandarvish, Pouya; Emtyazjoo, Mozhgan; Zahedifard, Maryam; Majid, Nazia Abdul; Ali, Hapipah Mohd; Abdulla, Mahmood Ameen

    2015-01-01

    Schiff-based complexes as a source of cancer chemotherapeutic compounds have been subjected to the variety of anticancer studies. The in-vitro analysis confirmed the CdCl2(C14H21N3O2) complex possess cytotoxicity and apoptosis induction properties in colon cancer cells, so lead to investigate the inhibitory efficiency of the compound on colonic aberrant crypt foci (ACF). Five groups of adult male rats were used in this study: Vehicle, cancer control, positive control groups and the groups treated with 25 and 50 mg/kg of complex for 10 weeks. The rats in vehicle group were injected subcutaneously with 15 mg/kg of sterile normal saline once a week for 2 weeks and orally administered with 5% Tween-20 (5 ml/kg) for 10 weeks, other groups were injected subcutaneously with 15 mg/kg azoxymethane once a week for 2 weeks. The rats in positive groups were injected intra-peritoneally with 35 mg/kg 5-Flourouracil four times in a month. Administration of the complex suppressed total colonic ACF formation up to 73.4% (P < 0.05). The results also showed that treatment with the complex significantly reduced the level of malondialdehyde while increasing superoxide dismutase and catalase activities. Furthermore, the down-regulation of PCNA and Bcl2 and the up-regulation of Bax was confirmed by immunohistochemical staining. PMID:26201720

  3. Design, synthesis, and pharmacological evaluation of novel 2-(4-substituted piperazin-1-yl)1, 8 naphthyridine 3-carboxylic acids as 5-HT3 receptor antagonists for the management of depression.

    PubMed

    Dhar, Arghya K; Mahesh, Radhakrishnan; Jindal, Ankur; Devadoss, Thangaraj; Bhatt, Shvetank

    2014-12-01

    1, 8-naphthyridine-3-carboxylic acid analogs were synthesized and found to possess potential 5-HT3 receptor antagonism as well as antidepressant-like activity. Initially, 5-HT3 receptor antagonism of all the compounds was determined in the form of pA2 value against agonist 2-methyl 5-HT in longitudinal muscle-myenteric plexus preparation from guinea-pig ileum. Among all the compounds tested, compound 7a demonstrated most promising pA2 value of 7.6. Subsequently, all the compounds were evaluated for antidepressant activity using forced swim test and tail suspension test in mice. Compounds 7a, 7d, 7f, 7h, and 7i exhibited significant (p < 0.05) antidepressant-like activity as compound to vehicle-treated group. Importantly, none of the tested compound affected locomotor activity of mice at tested dose levels. PMID:24903617

  4. N-{2-[4-(2-Meth­oxy­phen­yl)piperazin-1-yl]eth­yl}-4-nitro-N-(2-pyrid­yl)benzamide

    PubMed Central

    Lu, Chunxiong; Jiang, Quanfu

    2010-01-01

    In the title compound, C25H27N5O4, the piperizine ring adopts a chair conformation. The dihedral angles between the pyridine ring and the two benzene rings are 65.5 (4) and 70.7 (4)°, while the dihedral angle between the two benzene rings is 17.3 (3)°. An intra­molecular C—H⋯O hydrogen bond occurs. PMID:21587665

  5. 15 CFR Supplement No. 1 to Part 714 - Schedule 3 Chemicals

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 15 Commerce and Foreign Trade 2 2010-01-01 2010-01-01 false Schedule 3 Chemicals No. Supplement No... ACTIVITIES INVOLVING SCHEDULE 3 CHEMICALS Pt. 714, Supp. 1 Supplement No. 1 to Part 714—Schedule 3 Chemicals...) Methyldiethanolamine (105-59-9) (17) Triethanolamine (102-71-6) Note to Supplement No. 1: Refer to Supplement No. 1...

  6. 2-[(4-Benzhydrylpipérazin-1-yl)méthyl]acrylonitrile

    PubMed Central

    Ben Amor, Fatma; Ould M’hamed, Mohamed; Mrabet, Hédi; Driss, Ahmed; Efrit, Mohamed Lotfi

    2008-01-01

    In the title compound, 2-[(4-benz­hydryl­piperazin-1-yl)­methyl]­acrylo­nitrile, C21H23N3, the substituted piperazine ring adopts a chair conformation and the dihedral angle between the mean planes of the aromatic rings is 71.61 (8)°. PMID:21201087

  7. Determination of nitrogen mustard hydrolysis products in rat urine samples using GC-MS.

    PubMed

    Kenar, Levent; Alp, Orkun

    2011-05-01

    A gas chromatographic-mass spectrometric method was developed, validated and demonstrated by measuring the levels of nitrogen mustard hydrolysis products in the urine collected from dosed rats. The recovery values for trimethylsilyl derivatives of EDEA and MDEA are between 82-95% and 88-112%, respectively. In vivo studies performed by using three different doses (0.5 mg/kg, 1.0 mg/kg, and 2.0 mg/kg) of HN2 base of nitrogen mustard. MDEA concentrations were between 43.1-232.2 ng/mL. The limit of detection (S/N = 3) values are 2.5 ng/mL and 1.6 ng/mL for EDEA and MDEA, respectively, and the precision of the method in terms of RSD is between 5-8%. PMID:21549026

  8. Comparison of five derivatizing agents for the determination of amphetamine-type stimulants in human urine by extractive acylation and gas chromatography-mass spectrometry.

    PubMed

    Dobos, Adrienn; Hidvégi, Elod; Somogyi, Gábor Pál

    2012-06-01

    Five acylation reagents have been compared for use as derivatizing agents for the analysis of amphetamine-type stimulants (ATS) in urine by gas chromatography-mass spectrometry (GC-MS). The evaluated reagents were heptafluorobutyric anhydride, pentafluoropropionic anhydride, trifluoroacetic anhydride, acetic anhydride (AA) and N-methyl-bis(trifluoroacetamide). The ATS included amphetamine, methamphetamine (MA), 3,4-methylenedioxyamphetamine (MDA), 3,4-methylenedioxymethamphetamine (MDMA) and 3,4-methylenedioxyethylamphetamine (MDEA). A mixture of the ATS was added to urine (1 mL) followed by KOH solution and saturated NaHCO(3) solution. The sample was then extracted with dichloromethane and the derivatizing agent and 2 µL were injected into the GC-MS instrument. The derivatizing agents were compared with reference to the signal-to-noise (S/N) ratios, peak area values, relative standard deviations (RSDs), linearities, limits of detection (LODs) and selectivities. The acetic anhydride proved to be the best according to the S/N ratio and peak area results for amphetamine, MA, MDMA and MDEA. The best RSD values of peak areas and of S/N ratios at 3 µg/mL were also given by AA in cases of MDA, MDMA and MDEA. At 20 µg/mL, the lowest RSD values of peak areas for MDA and the lowest RSD values of S/N ratios for MA, MDA, MDMA and MDEA were again given by AA. Additionally, the highest correlation coefficients for MA, MDA, MDMA and MDEA and the lowest LOD results for MA, MDMA and MDEA were produced by AA. PMID:22582269

  9. Physiologically based pharmacokinetic modeling to predict drug-drug interactions involving inhibitory metabolite: a case study of amiodarone.

    PubMed

    Chen, Yuan; Mao, Jialin; Hop, Cornelis E C A

    2015-02-01

    Evaluation of drug-drug interaction (DDI) involving circulating inhibitory metabolites of perpetrator drugs has recently drawn more attention from regulatory agencies and pharmaceutical companies. Here, using amiodarone (AMIO) as an example, we demonstrate the use of physiologically based pharmacokinetic (PBPK) modeling to assess how a potential inhibitory metabolite can contribute to clinically significant DDIs. Amiodarone was reported to increase the exposure of simvastatin, dextromethorphan, and warfarin by 1.2- to 2-fold, which was not expected based on its weak inhibition observed in vitro. The major circulating metabolite, mono-desethyl-amiodarone (MDEA), was later identified to have a more potent inhibitory effect. Using a combined "bottom-up" and "top-down" approach, a PBPK model was built to successfully simulate the pharmacokinetic profile of AMIO and MDEA, particularly their accumulation in plasma and liver after a long-term treatment. The clinical AMIO DDIs were predicted using the verified PBPK model with incorporation of cytochrome P450 inhibition from both AMIO and MDEA. The closest prediction was obtained for CYP3A (simvastatin) DDI when the competitive inhibition from both AMIO and MDEA was considered, for CYP2D6 (dextromethorphan) DDI when the competitive inhibition from AMIO and the competitive plus time-dependent inhibition from MDEA were incorporated, and for CYP2C9 (warfarin) DDI when the competitive plus time-dependent inhibition from AMIO and the competitive inhibition from MDEA were considered. The PBPK model with the ability to simulate DDI by considering dynamic change and accumulation of inhibitor (parent and metabolite) concentration in plasma and liver provides advantages in understanding the possible mechanism of clinical DDIs involving inhibitory metabolites. PMID:25324279

  10. Cationic Mn4 single-molecule magnet with a sterically isolated core.

    PubMed

    Heroux, Katie J; Quddusi, Hajrah M; Liu, Junjie; O'Brien, James R; Nakano, Motohiro; del Barco, Enrique; Hill, Stephen; Hendrickson, David N

    2011-08-15

    The synthesis, structure, and magnetic properties of a ligand-modified Mn(4) dicubane single-molecule magnet (SMM), [Mn(4)(Bet)(4)(mdea)(2)(mdeaH)(2)](BPh(4))(4), are presented, where the cationic SMM units are significantly separated from neighboring molecules in the crystal lattice. There are no cocrystallized solvate molecules, making it an ideal candidate for single-crystal magnetization hysteresis and high-frequency electron paramagnetic resonance studies. Increased control over intermolecular interactions in such materials is a crucial factor in the future application of SMMs. PMID:21751785

  11. The skin sensitization potential of four alkylalkanolamines.

    PubMed

    Leung, H W; Blaszcak, D L

    1998-04-01

    The skin sensitization potential of 4 alkylalkanolamines (N-methylethanolamine, N,N-dimethylethanolamine, N-methyldiethanolamine and N,N-diethylethanolamine), was evaluated in a guinea pig maximation procedure by the method of Magnusson and Kligman. While all 4 alkylalkanolamines tested were irritating to the guinea pig skin, only N-methylethanolamine showed potential to induce allergic contact dermatitis. None of the remaining 3 alkylalkanolamines exhibited clear skin responses suggestive of sensitization. PMID:9554055

  12. Acidic gas capture by diamines

    SciTech Connect

    Rochelle, Gary; Hilliard, Marcus

    2011-05-10

    Compositions and methods related to the removal of acidic gas. In particular, the present disclosure relates to a composition and method for the removal of acidic gas from a gas mixture using a solvent comprising a diamine (e.g., piperazine) and carbon dioxide. One example of a method may involve a method for removing acidic gas comprising contacting a gas mixture having an acidic gas with a solvent, wherein the solvent comprises piperazine in an amount of from about 4 to about 20 moles/kg of water, and carbon dioxide in an amount of from about 0.3 to about 0.9 moles per mole of piperazine.

  13. An in situ study of amine and amide molecular interaction on Fe surfaces

    NASA Astrophysics Data System (ADS)

    Taheri, P.; Terryn, H.; Mol, J. M. C.

    2015-11-01

    The interfacial bondings formed between N,N‧-diethylmethylamine, N-methyldiethanolamine and N,N‧-dimethylsuccinamide molecules with iron surfaces have been investigated using Fourier transform infrared spectroscopy (FTIR) and electrochemical spectroscopies. In this case, the interfacial interactions have been evaluated by analyzing ex situ FTIR peaks and probing potential variations upon molecular interactions to Fe surfaces. Moreover, integrated ATR-FTIR and chronovoltammetry analyses in Kretschmann geometry have been employed to probe the interactions between the molecules and Fe surfaces in situ. The results revealed that a charge transfer between molecules and Fe surfaces takes place indicating chemisorption of the molecules on Fe surfaces. In this case, the interaction of N,N‧-diethylmethylamine and Fe surface is negligible. However, N-methyldiethanolamine molecules interact with Fe surfaces through the nitrogen atoms. Interaction of N,N‧-dimethylsuccinamide molecules and Fe surface is promoted by nitrogen and carbonyl functional groups. Moreover, interactions of N-methyldiethanolamine and N,N‧-dimethylsuccinamide molecules to Fe surfaces are encouraged by application of anodic potentials implying that the molecules and Fe surfaces are charged positively and negatively, respectively.

  14. 75 FR 41488 - Agency Information Collection Activities: Submission for OMB Review; Comment Request

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-07-16

    ... HHS Mandatory Guidelines for Federal Workplace Drug Testing Programs (73 FR 71858) dated November 25... section in Step 5(a) on Copy 1. The new drug analytes are methylenedioxymethamphetamine (MDMA), commonly... MDEA are both close chemical analogues of MDMA. The fourth change is to revise the Medical...

  15. Spectral investigations, DFT computations and molecular docking studies of 1,7,8,9-tetrachloro-10,10-dimethoxy-4-{3-[4-(2-methylphenyl)piperazin-1-yl]propyl}-4-azatricyclo[5.2.1.02,6]dec-8-ene-3,5-dione

    NASA Astrophysics Data System (ADS)

    Resmi, K. S.; Mary, Y. Sheena; Varghese, Hema Tresa; Panicker, C. Yohannan; Pakosińska-Parys, Magdalena; Alsenoy, C. Van

    2015-10-01

    The optimized molecular structure, vibrational frequencies, corresponding vibrational assignments of the title compound have been investigated experimentally and theoretically. The HOMO and LUMO analysis is used to determine the charge transfer within the molecule. The stability of the molecule arising from hyper-conjugative interaction and charge delocalization has been analysed using NBO analysis. The hyperpolarisability calculation reveals the present material has a reasonably good propensity for nonlinear optical activity. Due to the different potential biological activity of the title compound, molecular docking study is also reported and the compound might exhibit inhibitory activity against human M2 muscarinic acetylcholine receptor.

  16. 3-(Adamantan-1-yl)-4-[(E)-(2,6-di­fluoro­benzyl­idene)amino]-1-[(4-ethyl­piperazin-1-yl)meth­yl]-4,5-di­hydro-1H-1,2,4-triazole-5-thione

    PubMed Central

    Al-Tamimi, Abdul-Malek S.; Al-Abdullah, Ebtehal S.; El-Emam, Ali A.; Ng, Seik Weng; Tiekink, Edward R. T.

    2013-01-01

    In the title compound, C26H34F2N6S, the triazole ring is linked to a benzene ring via an imine bond [N=C = 1.255 (2) Å; conformation: E], with a dihedral angle of 25.21 (11)° between the rings. The 4-ethyl­piperazinyl residue is folded away from the thione-S atom. In the crystal, helical supra­molecular chains propagating along [010] and sustained by weak C—S⋯π(triazole) inter­actions occur [S⋯centroid distance = 3.2872 (10) Å]. Links between these chains are of the type benzene-C—H⋯N(imine) and π–π [between centrosymmetrically related benzene rings with an inter-centroid distance of 3.9241 (15) Å] and result in a three-dimensional architecture. PMID:23723845

  17. Discovery of 4-(4-(2-((5-hydroxy-1,2,3,4-tetrahydronaphthalen-2-yl)(propyl)amino)-ethyl)piperazin-1-yl)quinolin-8-ol and its analogues as highly potent dopamine D2/D3 agonists and as iron chelator: In vivo activity indicates potential application in symptomatic and neuroprotective therapy for Parkinson’s Disease

    PubMed Central

    Ghosh, Balaram; Antonio, Tamara; Reith, Maarten E. A.; Dutta, Aloke K.

    2010-01-01

    The role of iron in the pathogenesis of Parkinson’s disease (PD) has been implicated strongly due to generation of oxidative stress leading to dopamine cell death. In our overall goal to develop bifunctional/multifunctional drugs, we designed dopamine D2/D3 agonist molecules with a capacity to bind to iron. Binding assays were carried out with HEK-293 cells expressing either D2 or D3 receptors with tritiated spiperone to evaluate inhibition constants (Ki). Functional activity of selected compounds was carried out with GTPγS binding assay. SAR results identified compounds (+)-19a and (−)-19b as two potent agonists for both D2 and D3 receptors (EC50 (GTPγS); D2 = 4.51 and 1.69 nM and D3 = 1.58 and 0.74 nM for (−)-19b and (+)-19a, respectively). In vitro complexation studies with 19b demonstrated efficient chelation with iron. Furthermore, the deoxyribose assay with 19b demonstrated potent antioxidant activity. In PD animal model study, (−)-19b exhibited potent in vivo activity in reversing locomotor activity in reserpinized rats and also in producing potent rotational activity in 6-OHDA lesioned rats. This reports initial development of unique lead molecules which might find potential use in symptomatic and neuroprotective treatment of PD. PMID:20146482

  18. Discovery of 3-(2,6-dichloro-3,5-dimethoxy-phenyl)-1-{6-[4-(4-ethyl-piperazin-1-yl)-phenylamino]-pyrimidin-4-yl}-1-methyl-urea (NVP-BGJ398), a potent and selective inhibitor of the fibroblast growth factor receptor family of receptor tyrosine kinase.

    PubMed

    Guagnano, Vito; Furet, Pascal; Spanka, Carsten; Bordas, Vincent; Le Douget, Mickaël; Stamm, Christelle; Brueggen, Josef; Jensen, Michael R; Schnell, Christian; Schmid, Herbert; Wartmann, Markus; Berghausen, Joerg; Drueckes, Peter; Zimmerlin, Alfred; Bussiere, Dirksen; Murray, Jeremy; Graus Porta, Diana

    2011-10-27

    A novel series of N-aryl-N'-pyrimidin-4-yl ureas has been optimized to afford potent and selective inhibitors of the fibroblast growth factor receptor tyrosine kinases 1, 2, and 3 by rationally designing the substitution pattern of the aryl ring. On the basis of its in vitro profile, compound 1h (NVP-BGJ398) was selected for in vivo evaluation and showed significant antitumor activity in RT112 bladder cancer xenografts models overexpressing wild-type FGFR3. These results support the potential therapeutic use of 1h as a new anticancer agent. PMID:21936542

  19. Discovery of a novel 5-HT(3) antagonist/5-HT(1A) agonist 3-amino-5,6,7,8-tetrahydro-2-{4-[4-(quinolin-2-yl)piperazin-1-yl]butyl}quinazolin-4(3H)-one (TZB-30878) as an orally bioavailable agent for irritable bowel syndrome.

    PubMed

    Asagarasu, Akira; Matsui, Teruaki; Hayashi, Hiroyuki; Tamaoki, Satoru; Yamauchi, Yukinao; Minato, Kouichi; Sato, Michitaka

    2010-11-11

    We have prepared a series of quinazolinone derivatives linked with piperazinylquinoline for the treatment of irritable bowel syndrome (IBS). Using pharmacophore analysis, we designed and synthesized compounds which bind to both serotonin receptor subtype 1A (5-HT(1A)) and subtype 3 (5-HT(3)). Quinazolinone derivatives with a sulfur atom in the linker showed high affinity in in vitro assays, but low in vivo activity. Focusing on the linker to improve the pharmacokinetic profile, the sulfur atom in the linker was replaced with a methylene group. Further optimization led to the discovery of compound 17m (TZB-30878) ( J. Pharmacol. Exp. Ther. 2007 , 322 , 1315 - 1323 , Patent WO2005082887 (A1), 2005 ), a novel 5-HT(1A) agonist/5-HT(3) antagonist in the 3-aminoquinazolinone series. In in vivo functional assays, 17m dose dependently inhibited the Bezold-Jarisch reflex and induced 5-HT(1A)-mediated behaviors, and in an IBS animal model, 17m significantly inhibited stress-induced defecation. Pretreatment by WAY-100635 (5-HT(1A) antagonist) significantly attenuated but did not abolish the inhibitory effects of 17m. These results suggested that 17m exerted inhibitory effects via both 5-HT(1A) agonistic and 5-HT(3) antagonistic activities and that 17m would be useful as a therapeutic agent for IBS. PMID:20931963

  20. Structural analysis of (S)-1-((1H-benzo[d][1,2,3]triazol-1-yl)oxy)-3-(4-(2-methoxyphenyl)piperazin-1-yl)propan-2-ol and binding mechanism with α1A-adrenoceptor: TDDFT calculations, X-ray crystallography and molecular docking

    NASA Astrophysics Data System (ADS)

    Xu, Wei; Shao, Binhao; Xu, Xingjie; Jiang, Renwang; Yuan, Mu

    2016-02-01

    The title compound, (S)-1-((1H-benzo[d][1,2,3]triazol-1-yl)oxy)-3-(4-(2-methoxyphenyl)piperazi-n-1-yl)propan-2-ol (1), belongs to a class of arylpiperazine derivatives that exhibit good bioactivity against α1A-adrenoceptor. The current study describes conformational analysis of five energy-minimized conformers obtained at the B3LYP/6-31G(d) level of theory. The characteristically positive rotatory strengths at an excitation energy of 256 nm were achieved using time-dependent density functional theory (TDDFT) calculations. Molecular orbital studies clearly elucidated the origins of electronic transitions at 256 nm. The absolute configuration of (S)-1 was unambiguously determined by single crystal X-ray diffraction analysis. Molecular docking solved the binding mode of 1-α1A-adrenoceptor complex. This work can serve as a basis for better drug design of highly selective antagonists with chirality.

  1. Synthesis and structure-activity relationship of fluoro analogues of 8-{2-[4-(4-methoxyphenyl)piperazin-1yl]ethyl}-8-azaspiro[4.5]decane-7,9-dione as selective alpha(1d)-adrenergic receptor antagonists.

    PubMed

    Konkel, Michael J; Wetzel, John M; Cahir, Marie; Craig, Douglas A; Noble, Stewart A; Gluchowski, Charles

    2005-04-21

    We have discovered high-affinity antagonists (exemplified by 11 and 12) that are the most selective for alpha(1d)-adrenergic receptors (alpha(1d)-AR) reported to date. In cloned receptor assay systems, 12 displays at least 95-fold selectivity for the alpha(1d)-AR over all other G-protein-coupled receptors tested, and the subtype selectivity of 11 was confirmed in pharmacologically defined isolated tissue preparations. PMID:15828846

  2. Structural Modifications of Neuroprotective Anti-Parkinsonian (−)-N6-(2-(4-(Biphenyl-4-yl)piperazin-1-yl)-ethyl)-N6-propyl-4,5,6,7-tetrahydrobenzo[d]thiazole-2,6-diamine (D-264): An Effort toward the Improvement of in Vivo Efficacy of the Parent Molecule

    PubMed Central

    2015-01-01

    In our overall goal to develop multifunctional dopamine D2/D3 agonist drugs for the treatment of Parkinson’s disease (PD), we previously synthesized potent D3 preferring agonist D-264 (1a), which exhibited neuroprotective properties in two animal models of PD. To enhance the in vivo efficacy of 1a, a structure–activity relationship study was carried out. Competitive binding and [35S]GTPγS functional assays identified compound (−)-9b as one of the lead molecules with preferential D3 agonist activity (EC50(GTPγS); D3 = 0.10 nM; D2/D3 (EC50): 159). Compounds (−)-9b and (−)-8b exhibited high in vivo activity in two PD animal models, reserpinized and 6-hydroxydopamine (OHDA)-induced unilateral lesioned rats. On the other hand, 1a failed to show any in vivo activity in these models unless the compound was dissolved in 5–10% beta-hydroxy propyl cyclodextrin solution. Lead compounds exhibited appreciable radical scavenging activity. In vitro experiments with dopaminergic MN9D cells indicated neuroprotection by both 1a and (−)-9b from toxicity of MPP+. PMID:24471976

  3. Effect of selected anthelmintics on three common helminths in the brown pelican (Pelecanus occidentalis).

    PubMed

    Grimes, J; Suto, B; Greve, J H; Albers, H F

    1989-01-01

    The effect of selected anthelmintics (albendazole, fenbendazole, piperazine dihydrochloride and clorsulon) against three major helminths (Contracaecum multipapillatum, Mesostephanus appendiculatoides, and Phagicola longus) were studied in 29 brown pelicans (Pelecanus occidentalis). Albendazole and fenbendazole were highly effective against all three parasites. Clorsulon had moderate effect against M. appendiculatoides and poor effect against C. multipapillatum and P. longus. Piperazine dihydrochloride had no effect against these helminths. PMID:2915399

  4. A study to investigate the performance of the Benfield-HiPure process of natural gas sweetening using computer simulations

    NASA Astrophysics Data System (ADS)

    Ochieng, Richard

    The removal of CO2 and H2S from natural gas is currently a global issue. Apart from meeting the customer's contract, pipeline, and LNG specifications; it is also a measure for reducing the global environmental emissions. The aim of this study is to investigate the performance of ADGAS' Train#3 plant through process simulations. ADGAS' Train#3 plant uses the Benfield HiPure design commissioned by Universal Oil Product (UOP Honeywell) in 1993. The Benfield HiPure process uses two independent but compatible circulating solutions in series to achieve high product purity in terms of acid gas concentrations that meet the LNG industry specifications. The ability to remove contaminants up to very low levels (1ppm H2S, 50ppm CO2 and 2ppm COS) makes the HiPure process an excellent choice for purifying natural gas for LNG requirement. At Das Island, ADGAS' Train#3 facility receives sour gas containing about 6-7 mole % acid gas content. This gas is first contacted with hot potassium carbonate (30wt% K2CO3) promoted with diethanolamine solution (3wt% DEA) followed by a contact with aqueous amine solution (20wt% DEA) alone as the second solvent. In this thesis, ADGAS Train#3 model was developed using the simulator tool ProMax®. Simulation outputs were found to match reasonably well the design and plant operating data. Based on the model predictions, the carbonate absorber seemed to be over designed with much of the acid gases being absorbed at the bottom of the packing. With the confidence that the model is a reliable replicate of the real plant facility, a parametric sensitivity analysis was carried out to develop a strategy of controlling operational uncertainties and enable plant optimization. The parametric sensitivity analysis showed that the liquid circulation rates, solvent concentrations, trim cooler temperatures, feed gas flow rate, and feed gas H2S/CO2 ratio have a considerable effect on the performance of the plant with respect to acid gas removal, gas production capacity and plant energy efficiency. Due to the complexity and high investment cost of the Benfield HiPure process, potential alternatives are evaluated. The alternatives are basically MDEA based solvents with promoters to enable the simultaneous removal of H 2S and CO2. BASF's MDEA, MDEA/DEA or MDEA/DGA processes seem to be the best alternatives to the Benfield HiPure process. Using MDEA/DEA or MDEA/DGA process will reduce the capital costs of ADGAS by 50% , and up to 48% will be saved on the annual power consumption (0.33 million dollars per years) . BASF's MDEA has slightly higher capital costs due to the additional units required on the high pressure flash and the quenching units used to generate the semi-lean solution. However, BASF's MDEA process still stands as one of the best alternatives with a savings of about 102 million dollars (48%) on the capital costs and up to 36% (3.96 USD per ton of acid gas removed) on the cost stripping.

  5. A single molecule magnet to single molecule magnet transformation via a solvothermal process: Fe4Dy2 → Fe6Dy3.

    PubMed

    Chen, Sihuai; Mereacre, Valeriu; Anson, Christopher E; Powell, Annie K

    2016-01-01

    Two series of heterometallic Fe(III)-Ln(III) compounds, [FeLn(μ3-OH)2(mdea)4(m-NO2C6H4COO)8]·3MeCN where Ln = Y (1) and Dy (2) and [FeLn(μ4-O)3(μ3-O)(mdea)5(m-NO2C6H4COO)9]·3MeCN where Ln = Y (3) and Dy (4), were synthesized. Compounds 1 and 2 were obtained under ambient conditions, whereas 3 and 4 were obtained via a solvothermal transformation process by heating 1 or 2 at 120 °C in MeCN. The magnetic properties of all four compounds have been measured and show that compounds 2 and 4 containing Dy(III) ions exhibit slow relaxation of magnetization characteristic of Single Molecule Magnetic (SMM) behaviour. PMID:26599423

  6. Orally active inhibitors of human leukocyte elastase. III. Identification and characterization of metabolites of L-694,458 by liquid chromatography-tandem mass spectrometry.

    PubMed

    Luffer-Atlas, D; Vincent, S H; Painter, S K; Arison, B H; Stearns, R A; Chiu, S H

    1997-08-01

    The in vitro and in vivo metabolism of N-[1(R)-(1,3-benzodioxol-5-yl)butyl]-3,3-diethyl-2(S)-[4-[(4-methy l-1-piperazinyl)carbonyl]phenoxy]-4-oxo-1-azetidinecarboxamide (L-694,458) was studied in male Sprague-Dawley rats and rhesus monkeys. Analysis by LC-MS/MS and NMR revealed that the major metabolite generated in incubations with rat liver microsomes resulted from N-oxidation of the piperazine group, while the major metabolite generated in monkey liver microsomes was the catechol that resulted from O-dealkylation of the methylenedioxyphenyl group. Other metabolites observed in these incubations include the piperazine N-desmethyl, several monohydroxylated derivatives of the parent compound, and three products that resulted from cleavage of the beta-lactam ring. Incubations of parent compound with rat hepatocytes in culture generated two major metabolites that resulted from cleavage of the piperazine ring with the loss of an ethylene group from one side of the ring; one of these metabolites retained the piperazine N-methyl group, while the other did not. The metabolite profiles in vivo were similar to those observed in vitro, but they were much more complex owing to secondary and, in some cases, tertiary biotransformations of many of the primary metabolites. Bile obtained from orally dosed rats contained more than 40 parent-related components, and many of these metabolites had arisen from piperazine ring cleavage. PMID:9280402

  7. Octanuclear Mn(III)6Mn(II)Ln (Ln = Gd, Dy and Er) clusters with a novel core topology: syntheses, structures, and magnetic properties.

    PubMed

    Chen, Hui; Ma, Cheng-Bing; Hu, Ming-Qiang; Wen, Hui-Min; Cui, Hong-Hua; Liu, Jin-Ying; Song, Xiao-Wei; Chen, Chang-Neng

    2013-04-14

    Reactions of [Mn6O2(piv)10(py)2.5(piv)1.5], Ln(NO3)3·6H2O and N-mdeaH2 in MeCN in the presence of Me3SiCl generated a family of octanuclear Mn/Ln complexes [Mn6(III)Mn(II)Ln(N-mdea)3(N-mdeaH)(piv)8O2(OH)3(NO3)(H2O)]·xCH3CN·xH2O [Ln = Gd (1), Dy (2), Er (3), pivH = pivalic acid, N-mdeaH2 = N-methyl diethanolamine]. Each complex possesses a [Mn6(III)Mn(II)Ln(μ3-O)2(μ3-OH)3](16+) core containing two butterfly-like subunits of [Mn3Ln(μ3-OH)2] and [Mn4(μ3-O)2] sharing a common vertex, and an outer Mn atom ligated to one of the subunits through a μ3-OH(-) ligand. The core topology represents a new Mn/Ln core type. The magnetic susceptibility study of 1-3 indicates the presence of dominant antiferromagnetic interactions within the complexes. For complex 1, which contains an isotropic Gd(III) atom, fitting of the obtained M/(NμB) vs. H/T data gave S = 4, g = 1.90, and D = -0.31 cm(-1). The results were further supported by ac data. Complex exhibits out-of-phase ac susceptibility signals, indicating it may be a SMM. PMID:23377042

  8. The first 4d/4f single-molecule magnet containing a {Ru(III)2Dy(III)2} core.

    PubMed

    Langley, Stuart K; Wielechowski, Daniel P; Vieru, Veacheslav; Chilton, Nicholas F; Moubaraki, Boujemaa; Chibotaru, Liviu F; Murray, Keith S

    2015-02-01

    We report the synthesis, structure and magnetic properties of the first 4d-4f single-molecule magnet. The complex [Ru(III)2Dy(III)2(OMe)2(O2CPh)4(mdea)2(NO3)2] displays a butterfly type core, with an anisotropy barrier of 10.7 cm(-1). Ab initio and DFT calculations provide insight into the observed magnetic behaviour. PMID:25536910

  9. P450-Based Drug-Drug Interactions of Amiodarone and its Metabolites: Diversity of Inhibitory Mechanisms.

    PubMed

    McDonald, Matthew G; Au, Nicholas T; Rettie, Allan E

    2015-11-01

    In this study, IC50 shift and time-dependent inhibition (TDI) experiments were carried out to measure the ability of amiodarone (AMIO), and its circulating human metabolites, to reversibly and irreversibly inhibit CYP1A2, CYP2C9, CYP2D6, and CYP3A4 activities in human liver microsomes. The [I]u/Ki,u values were calculated and used to predict in vivo AMIO drug-drug interactions (DDIs) for pharmaceuticals metabolized by these four enzymes. Based on these values, the minor metabolite N,N-didesethylamiodarone (DDEA) is predicted to be the major cause of DDIs with xenobiotics primarily metabolized by CYP1A2, CYP2C9, or CYP3A4, while AMIO and its N-monodesethylamiodarone (MDEA) derivative are the most likely cause of interactions involving inhibition of CYP2D6 metabolism. AMIO drug interactions predicted from the reversible inhibition of the four P450 activities were found to be in good agreement with the magnitude of reported clinical DDIs with lidocaine, warfarin, metoprolol, and simvastatin. The TDI experiments showed DDEA to be a potent inactivator of CYP1A2 (KI = 0.46 μM, kinact = 0.030 minute(-1)), while MDEA was a moderate inactivator of both CYP2D6 (KI = 2.7 μM, kinact = 0.018 minute(-1)) and CYP3A4 (KI = 2.6 μM, kinact = 0.016 minute(-1)). For DDEA and MDEA, mechanism-based inactivation appears to occur through formation of a metabolic intermediate complex. Additional metabolic studies strongly suggest that CYP3A4 is the primary microsomal enzyme involved in the metabolism of AMIO to both MDEA and DDEA. In summary, these studies demonstrate both the diversity of inhibitory mechanisms with AMIO and the need to consider metabolites as the culprit in inhibitory P450-based DDIs. PMID:26296708

  10. Crystal structure of aqua-1κO-{μ-2-[(2-hydroxy-ethyl)methylamino]ethanolato-2:1κ(4) O (1),N,O (2):O (1)}[μ-2,2'-(methylimino)diethanolato-1:2κ(4) O,N,O':O]dithiocyanato-1κN,2κN-chromium(III)copper(II).

    PubMed

    Rusanova, Julia A; Semenaka, Valentina V; Dyakonenko, Viktoriya V; Shishkin, Oleg V

    2015-09-01

    The title compound, [CrCu(C5H11NO2)(C5H12NO2)(NCS)2(H2O)] or [Cr(μ-mdea)Cu(μ-Hmdea)(NCS)2H2O], (where mdeaH2 is N-methylethanolamine, C5H13NO2) is formed as a neutral heterometal Cu(II)/Cr(III) complex. The mol-ecular structure of the complex is based on a binuclear {CuCr(μ-O)2} core. The coordination environment of each metal atom involves the N,O,O atoms of the tridentate ligand, one bridging O atom of the ligand and the N atom of the thio-cyanato ligands. The Cu(II) ion adopts a distorted square-pyramidal coordination while the Cr(III) ion has a distorted octa-hedral coordination geometry completed by the aqua ligand. In the crystal, the binuclear complexes are linked via two pairs of O-H⋯O hydrogen bonds to form inversion dimers, which are arranged in columns parallel to the a axis. In the μ-mdea ligand two -CH2 groups and the methyl group were refined as disordered over two sets of sites with equal occupancies. The structure was refined as a two-component twin with a twin scale factor of 0.242 (1). PMID:26396853

  11. Crystal structure of aqua-1κO-{μ-2-[(2-hydroxy­ethyl)methylamino]ethanolato-2:1κ4 O 1,N,O 2:O 1}[μ-2,2′-(methylimino)diethanolato-1:2κ4 O,N,O′:O]dithiocyanato-1κN,2κN-chromium(III)copper(II)

    PubMed Central

    Rusanova, Julia A.; Semenaka, Valentina V.; Dyakonenko, Viktoriya V.; Shishkin, Oleg V.

    2015-01-01

    The title compound, [CrCu(C5H11NO2)(C5H12NO2)(NCS)2(H2O)] or [Cr(μ-mdea)Cu(μ-Hmdea)(NCS)2H2O], (where mdeaH2 is N-methylethanolamine, C5H13NO2) is formed as a neutral heterometal CuII/CrIII complex. The mol­ecular structure of the complex is based on a binuclear {CuCr(μ-O)2} core. The coordination environment of each metal atom involves the N,O,O atoms of the tridentate ligand, one bridging O atom of the ligand and the N atom of the thio­cyanato ligands. The CuII ion adopts a distorted square-pyramidal coordination while the CrIII ion has a distorted octa­hedral coordination geometry completed by the aqua ligand. In the crystal, the binuclear complexes are linked via two pairs of O—H⋯O hydrogen bonds to form inversion dimers, which are arranged in columns parallel to the a axis. In the μ-mdea ligand two –CH2 groups and the methyl group were refined as disordered over two sets of sites with equal occupancies. The structure was refined as a two-component twin with a twin scale factor of 0.242 (1). PMID:26396853

  12. In vitro kinetics of amiodarone and its major metabolite in two human liver cell models after acute and repeated treatments.

    PubMed

    Pomponio, Giuliana; Savary, Camille C; Parmentier, Céline; Bois, Frederic; Guillouzo, André; Romanelli, Luca; Richert, Lysiane; Di Consiglio, Emma; Testai, Emanuela

    2015-12-25

    The limited value of in vitro toxicity data for the in vivo extrapolation has been often attributed to the lack of kinetic data. Here the in vitro kinetics of amiodarone (AMI) and its mono-N-desethyl (MDEA) metabolite was determined and modelled in primary human hepatocytes (PHH) and HepaRG cells, after single and repeated administration of clinically relevant concentrations. AMI bioavailability was influenced by adsorption to the plastic and the presence of protein in the medium (e.g. 10% serum protein reduced the uptake by half in HepaRG cells). The cell uptake was quick (within 3h), AMI metabolism was efficient and a dynamic equilibrium was reached in about a week after multiple dosing. In HepaRG cells the metabolic clearance was higher than in PHH and increased over time, as well as CYP3A4. The interindividual variability in MDEA production in PHHs was not proportional to the differences in CYP3A4 activities, suggesting the involvement of other CYPs and/or AMI-related CYP inhibition. After repeated treatment AMI showed a slight potential for bioaccumulation, whereas much higher intracellular MDEA levels accumulated over time, especially in the HepaRG cells, associated with occurrence of phospholipidosis. The knowledge of in vitro biokinetics is important to transform an actual in vitro concentration-effect into an in vivo dose-effect relationship by using appropriate modelling, thus improving the in vitro-to-in vivo extrapolation. PMID:25546373

  13. CO2 Capture by Absorption with Potassium Carbonate

    SciTech Connect

    Gary T. Rochelle; Eric Chen; Babatunde Oyenekan; Andrew Sexton; Jason Davis; Marcus Hilliard; Amornvadee Veawab

    2006-09-30

    The objective of this work is to improve the process for CO{sub 2} capture by alkanolamine absorption/stripping by developing an alternative solvent, aqueous K{sub 2}CO{sub 3} promoted by piperazine. Ethylenediamine was detected in a degraded solution of MEA/PZ solution, suggesting that piperazine is subject to oxidation. Stripper modeling has demonstrated that vacuum strippers will be more energy efficient if constructed short and fat rather than tall and skinny. The matrix stripper has been identified as a configuration that will significantly reduce energy use. Extensive measurements of CO{sub 2} solubility in 7 m MEA at 40 and 60 C have confirmed the work by Jou and Mather. Corrosion of carbon steel without inhibitors increases from 19 to 181 mpy in lean solutions of 6.2 m MEA/PZ as piperazine increases from 0 to 3.1 m.

  14. Mutagenicity of products generated by the reaction between several antiparasitic drugs and nitrite

    SciTech Connect

    Alba, M.A.; Espinose, J.; Cortinas de Nava, C.

    1988-01-01

    Drugs containing secondary aliphatic amines, heterocyclic nitrogen, or secondary aliphatic amido groups (chloroquine, dehydroemetine, mebendazole, and piperazine) and pyrimidine derivatives such as pyrantel pamoate were reacted in vitro with sodium nitrite at pH 3.7 and became mutagenic for Salmonella typhimurium strain TA1535. The products derived from the nitrosation of chloroquine and dehydroemetine required metabolic activation by mammalian hepatic S9 to be mutagenic. The N-nitroso derivatives of mebendazole, piperazine, and pyrantel pamoate were mutagenic with and without S9, although more activity was noted in the presence of S9 with the nitrosated compounds formed from mebendazole and piperazine. Under identical conditions, no mutagenic products were detected from quaternary ammonium salts such as bephenium hydroxynaphthoate or drugs containing tertiary heterocyclic amino groups, such as iodochlorhydroxyquin.

  15. Biosynthesis and identification of an N-oxide/N-glucuronide metabolite and first synthesis of an N-O-glucuronide metabolite of Lu AA21004.

    PubMed

    Uldam, Henriette Kold; Juhl, Martin; Pedersen, Henrik; Dalgaard, Lars

    2011-12-01

    This article describes the biosynthesis and identification of a new class of metabolites, a piperazine N-oxide/N-glucuronide metabolite 4-[2-(2,4-dimethyl-phenylsulfanyl)-phenyl]-1-β-D-glucuronic acid-piperazine 1-oxide (4). The metabolite was found in urine and plasma from humans and animals dosed with 1-[2-(2,4-dimethyl-phenylsulfanyl)-phenyl]-piperazine hydrobromide (Lu AA21004, 1), as a novel multimodal antidepressant under development for treatment of depression. Human liver microsomes in combination with uridine 5'-diphosphoglucuronic acid were used as an in vitro system to generate enough material of 4 to perform one- and two-dimensional (1)H and (13)C NMR experiments for structure elucidation. Based on rotating frame Overhauser enhancement spectroscopy NMR experiments, the distance correlation between a piperazine proton and the anomeric proton of the glucuronic acid moiety is of a magnitude similar to that of the H-3' and H-5' protons and can only be explained by proximity in space and the postulated structure (4). The structural analog, the N-O-glucuronic acid conjugate 6-{4-[2-(2,4-dimethyl-phenylsulfanyl)-phenyl]-piperazin-1-yloxy}-1-β-D-glucuronic acid (3) was also observed in biological samples from humans and animals and the first organic synthesis and structural identification of this metabolite is also reported. Treatment of the glucuronide metabolites 3 and 4 with β-glucuronidase gave mainly the expected hydrolysis product, the hydroxyl amine 4-[2-(2,4-dimethyl-phenylsulfanyl)-phenyl]-piperazin-1-ol (2). PMID:21896789

  16. Synthesis of chiral 2,3-disubstituted 1,4-diazabicyclo[2.2.2]octane derivatives.

    PubMed

    Periasamy, Mariappan; Edukondalu, Athukuri; Reddy, Polimera Obula

    2015-04-01

    Racemic 2,3-diaryl-1,4-diazabicyclo[2.2.2]octane (DABCO) derivatives are synthesized from the readily accessible piperazines in 50-64% yield by cyclization using ethylene bromide, triethylamine, and KI at 80 °C. The enantiomerically enriched 2,3-diphenylpiperazine and the 2,3-bis(1-naphthyl)piperazine derivatives are prepared by a resolution method using commercially available optically active acids, yielding the corresponding DABCO derivatives in 51-64% yield with up to 99% ee. This mild cyclization can also be applied to enantiopure camphanyldiamine derivatives, and the products are obtained in 72-86% yields. PMID:25756201

  17. Microbial models of mammalian metabolism. Fungal metabolism of phenolic and nonphenolic p-cymene-related drugs and prodrugs. II. Metabolites of nonphenolic derivatives.

    PubMed

    Moussa, C; Houziaux, P; Danree, B; Azerad, R

    1997-03-01

    A cymene-derived drug, 3-[4'-(o-ethoxyphenyl)piperazin-1'-yl]-ethyloxy-p-cymene+ ++ (B1178), is not significantly metabolized by fungal microorganisms. On the contrary, one of its metabolites in rat, 3-(piperazin-1'-yl)ethoxy-p-cymene (B1071), is quantitatively converted by Cunninghamella echinulata NRRL 3655 into two hydroxylated products: the corresponding phenol derivative and a benzylic alcohol derivative. Other strains, such as Beauveria bassiana ATCC 7159 and Mortierella isabellina MMP 108, produce exclusively an N-acetyl derivative in high yield. Results obtained are discussed on the grounds of relative hydrophobicity of substrates vs. fungi metabolism and detoxification capabilities. PMID:9172948

  18. Synthesis and functional survey of new Tacrine analogs modified with nitroxides or their precursors

    PubMed Central

    Kálai, Tamás; Altman, Robin; Maezawa, Izumi; Balog, Mária; Morisseau, Christophe; Petrlova, Jitka; Hammock, Bruce D.; Jin, Lee-Way; Trudell, James; Voss, John C.; Hideg, Kálmán

    2014-01-01

    A series of new Tacrine analogs modified with nitroxides or pre-nitroxides on 9-amino group via methylene or piperazine spacers were synthesized; the nitroxide or its precursors were incorporated into the Tacrine scaffold. The new compounds were tested for their hydroxyl radical and peroxyl radical scavenging ability, acetyl cholinesterase inhibitor activity and protection against Aβ-induced cytotoxicity. Based on these assays, we conclude that Tacrine analogs connected to five and six-membered nitroxides via piperazine spacers (9b, 9b/HCl and 12) exhibited the best activity, providing direction for further development of additional candidates with dual functionality (anti Alzheimer’s and antioxidant). PMID:24657571

  19. CO2 CAPTURE BY ABSORPTION WITH POTASSIUM CARBONATE

    SciTech Connect

    Gary T. Rochelle; Eric Chen; J. Tim Cullinane; Marcus Hilliard; Babatunde Oyenekan; Terraun Jones

    2003-07-28

    The objective of this work is to improve the process for CO{sub 2} capture by alkanolamine absorption/stripping by developing an alternative solvent, aqueous K{sub 2}CO{sub 3} promoted by piperazine. A rigorous thermodynamic model has been further developed with a standalone FORTRAN code to represent the CO{sub 2} vapor pressure and speciation of the new solvent. Gas chromatography has been used to measure the oxidative degradation of piperazine. The heat exchangers for the pilot plant have been received. The modifications are on schedule for start-up in November 2003.

  20. 1,1′-Dibenzyl-5,5′′-dichloro-1,1′′,2,2′′-tetra­hydro­dispiro­[indole-3,7′-[6,9]diaza­tricyclo­[7.3.0.02,6]dodecane-8′,3′′-indole]-2,2′′-dione

    PubMed Central

    Al Mamari, Khalil; Ennajih, Hamid; Bouhfid, Rachid; Essassi, El Mokhtar; Ng, Seik Weng

    2012-01-01

    In the title compound, C38H34Cl2N4O2, the piperazine ring adopts a chair conformation. The pyrrolidine rings that are fused to the piperazine ring adopt envelope conformations (in which the C atoms connecting the two rings represent the flap). The indoline ring systems are approximately planar (r.m.s. deviations = 0.026 and 0.034 Å) and are aligned at a dihedral angle of 54.98 (3)°. PMID:22719459

  1. 1,1′′-Bis(prop-2-en-1-yl)-1,1′′,2,2′′-tetra­hydro­dispiro­[indole-3,7′-[6,9]diaza­tricyclo­[7.3.0.02,6]dodecane-8′,3′′-indole]-2,2′′-dione

    PubMed Central

    Al Mamari, Khalil; Ennajih, Hamid; Bouhfid, Rachid; Essassi, El Mokhtar; Ng, Seik Weng

    2012-01-01

    The mol­ecule of the title compound, C30H32N4O2, lies on a twofold rotation axis that passes through the mid-points of the C—C bonds of the piperazine ring, which adopts a chair conformation. The pyrrolidine ring that is fused to the piperazine ring adopts an envelope conformation (in which the N atom represents the flap). The indoline fused-ring system is nearly planar (r.m.s. deviation = 0.044 Å); the two symmetry-related indoline fused-rings systems are aligned at 71.44 (3)°. PMID:22719438

  2. 5,5′′-Dibromo-1,1′′-bis­(prop-2-en-1-yl)-1,1′′,2,2′′-tetra­hydro­dispiro­[indole-3,7′-[6,9]diaza­tricyclo­[7.3.0.02,6]dodecane-8′,3′′-indole]-2,2′′-dione

    PubMed Central

    Al Mamari, Khalil; Ennajih, Hamid; Bouhfid, Rachid; Essassi, El Mokhtar; Ng, Seik Weng

    2012-01-01

    In the mol­ecule of the title compound, C30H30Br2N4O2, the piperazine ring adopts a chair conformation. The pyrrolidine rings that are fused to the piperazine ring adopt envelope conformations (in which the N atom represents the flap). The indoline fused-ring systems are nearly planar (r.m.s. deviations = 0.009 and 0.019 Å); the two fused rings are aligned at 60.63 (6)°. PMID:22719439

  3. CO2 CAPTURE BY ABSORPTION WITH POTASSIUM CARBONATE

    SciTech Connect

    Gary T. Rochelle; A. Frank Seibert; J. Tim Cullinane; Terraun Jones

    2003-01-01

    The objective of this work is to improve the process for CO{sub 2} capture by alkanolamine absorption/stripping by developing an alternative solvent, aqueous K{sub 2}CO{sub 3} promoted by piperazine. Progress has been made in this reporting period on three subtasks. The rigorous Electrolyte Non-Random Two-Liquid (electrolyte-NRTL) model has been regressed to represent CO{sub 2} solubility in potassium carbonate/bicarbonate solutions. An analytical method for piperazine has been developed using a gas chromatograph. Funding has been obtained and equipment has been donated to provide for modifications of the existing pilot plant system with stainless steel materials.

  4. M[superscript 2+]EDTA Binding Affinities: A Modern Experiment in Thermodynamics for the Physical Chemistry Laboratory

    ERIC Educational Resources Information Center

    O'Brien, Leah C.; Root, Hannah B.; Wei, Chin-Chuan; Jensen, Drake; Shabestary, Nahid; De Meo, Cristina; Eder, Douglas J.

    2015-01-01

    Isothermal titration calorimetry was used to experimentally determine thermodynamic values for the ethylenediaminetetraacetic acid (EDTA)(aq) + M[superscript 2+](aq) reactions (M[superscript 2+] = Ca[superscript 2+] and Mg[superscript 2+]). Students showed that for reactions in a N-(2-hydroxyethyl)piperazine-N"-ethanesulfonic acid (HEPES)

  5. The comparison of differences in flammability and thermal degradation between cotton fabrics treated with phosphoramidate derivatives

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The effectiveness of a phosphoramidate Tetraethyl piperazine-1,4-diyldiphosphoramidate (TEPP) as a flame retardant (FR) on cotton twill fabrics was compared with that of a previously studied Diethyl 4-methylpiperazin-1-ylphosphoramidate (DEPP). TEPP was formed in a reaction between two phosphonates...

  6. Synthesis and Characterization of Potential Dimers of Gatifloxacin – an Antibacterial Drug

    PubMed Central

    Garaga, Srinivas; Raghava Reddy, Ambati V.; Prabahar, Koilpillai Joseph; Korupolu, Raghu Babu; Sanasi, Paul Douglas

    2013-01-01

    Gatifloxacin is an antibacterial agent belonging to the fourth-generation fluoroquinolone family. Four piperazine-linked fluoroquinolone dimers of Gatifloxacin were observed during the laboratory process for Gatifloxacin and they were identified. The present work describes the origin, synthesis, characterization, and control of these dimers along with the synthesis of Despropylene Gatifloxacin (metabolite). PMID:24106664

  7. Studies of flammability and thermal degradation for flame retardant cotton fabric with P-N containing derivatives

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The effectiveness of a phosphoramidate Tetraethyl piperazine-1,4- diyldiphosphoramidate (TEPP) as a flame retardant (FR) on cotton twill fabrics was compared with that of a previously studied Diethyl 4- methylpiperazin-1-ylphosphoramidate (DEPP). TEPP was formed in a reaction between two phosphonat...

  8. M[superscript 2+]•EDTA Binding Affinities: A Modern Experiment in Thermodynamics for the Physical Chemistry Laboratory

    ERIC Educational Resources Information Center

    O'Brien, Leah C.; Root, Hannah B.; Wei, Chin-Chuan; Jensen, Drake; Shabestary, Nahid; De Meo, Cristina; Eder, Douglas J.

    2015-01-01

    Isothermal titration calorimetry was used to experimentally determine thermodynamic values for the ethylenediaminetetraacetic acid (EDTA)(aq) + M[superscript 2+](aq) reactions (M[superscript 2+] = Ca[superscript 2+] and Mg[superscript 2+]). Students showed that for reactions in a N-(2-hydroxyethyl)piperazine-N"-ethanesulfonic acid (HEPES)…

  9. A family of novel Mn₃Ln₄ clusters displaying single-molecule magnet behavior.

    PubMed

    Chen, Hui; Ma, Cheng-Bing; Hu, Ming-Qiang; Wen, Hui-Min; Chen, Chang-Neng

    2014-11-28

    Using 3-methyloxysalicylaldoxime (mosaoH2) and N-methyl diethanolamine (N-mdeaH2) as coligands, a family of heptanuclear Mn/Ln heterometallic compounds [Mn(II)Mn(III)2Ln(III)4(mosao)2(mosaoH)4(piv)4(N-mdea)4]·xMeCN [Ln = Dy(1), Tb(2) and Y(3), pivH = pivalic acid] have been prepared. The crystal structures of 1-3 were obtained, and their core consists of two Mn(III)Ln2(μ3-OR)2 (RO(2-) = N-mdea(2-)) triangles linked to a central Mn(II) atom. A dc magnetic susceptibility study reveals that single-ion effects of the Ln ions are dominant in compounds 1 and 2. As for compound 3, which contains diamagnetic Y ions, the magnetic interactions between Mn ions via oximate NO bridges are revealed to be ferromagnetic. Fitting of the χ(m)T vs. T data gives g = 1.96 and J = 1.12 cm(-1), affording a S = 13/2 ground state. All of the three compounds exhibit frequency-dependent out-of-phase ac susceptibility signals indicative of slow magnetization relaxation and potential SMM behavior. Among them, 1 and 3 display the out-of-phase χ"(m) peak maximum above 2.0 K. Fitting of the ac susceptibility data to the Arrhenius law gives an energy barrier U(eff) = 9.27/13.83 K for 1 and 3, respectively. PMID:25273696

  10. Effects of the electrode size and modification protocol on a label-free electrochemical biosensor.

    PubMed

    Arya, Sunil K; Pui, Tze Sian; Wong, Chee Chung; Kumar, Sai; Rahman, Abdur Rub Abdur

    2013-06-01

    In the present work, the effect of a surface modification protocol along with the electrode size has been investigated for developing an efficient, label-free electrochemical biosensing method for diagnosis of traumatic brain injury (TBI) biomarkers. A microdisk electrode array (MDEA) and a macroelectrode with a comb structure (MECS) were modified with an anti-GFAP (GFAP = glial fibrillary acidic protein) antibody using two protocols for optimum and label-free detection of GFAP, a promising acute-phase TBI biomarker. For the MDEA, an array of six microdisks with a 100 μm diameter and, for the MECS, a 3.2 mm × 5.5 mm electrode 5 μm wide with 10 μm spaced comb fingers were modified using an optimized protocol for dithiobis(succinimidyl propionate) (DSP) self-assembled monolayer formation. Anti-GFAP was covalently bound, and the remaining free DSP groups were blocked using ethanolamine (Ea). Sensors were exposed to solutions with different GFAP concentrations, and a label-free electrochemical impedance spectroscopy (EIS) technique was used to determine the concentration. EIS results confirmed that both types of Ea/anti-GFAP/DSP/Au electrodes modified with an optimized DSP-based protocol can accurately detect GFAP in the range of 1 pg mL(-1) to 100 ng mL(-1) with a detection limit of 1 pg mL(-1). However, the cross-use of the MDEA protocol on the MECS and vice versa resulted in very low sensitivity or poor signal resolution, underscoring the importance of proper matching of the electrode size and type and the surface modification protocol. PMID:23651210

  11. Molecular characterization of the mde operon involved in L-methionine catabolism of Pseudomonas putida.

    PubMed Central

    Inoue, H; Inagaki, K; Eriguchi, S I; Tamura, T; Esaki, N; Soda, K; Tanaka, H

    1997-01-01

    A 15-kb region of Pseudomonas putida chromosomal DNA containing the mde operon and an upstream regulatory gene (mdeR) has been cloned and sequenced. The mde operon contains two structural genes involved in L-methionine degradative metabolism: the already-identified mdeA, which encodes L-methionine gamma-lyase (H. Inoue, K. Inagaki, M. Sugimoto, N. Esaki, K. Soda, and H. Tanaka. J. Biochem. (Tokyo) 117:1120-1125, 1995), and mdeB, which encodes a homologous protein to the homodimeric-type E1 component of pyruvate dehydrogenase complex. A rho-independent terminator was present just downstream of mdeB, and open reading frames corresponding to other components of alpha-keto acid dehydrogenase complex were not found. When MdeB was overproduced in Escherichia coli, the cell extract showed the E1 activity with high specificity for alpha-ketobutyrate rather than pyruvate. These results suggest that MdeB plays an important role in the metabolism of alpha-ketobutyrate produced by MdeA from L-methionine. Accordingly, mdeB encodes a novel E1 component, alpha-ketobutyrate dehydrogenase E1 component, of an unknown alpha-keto acid dehydrogenase complex in P. putida. In addition, we found that the mdeR gene was located on the opposite strand and began at 127 bp from the translational start site of mdeA. The mdeR gene product has been identified as a member of the leucine-responsive regulatory protein (Lrp) family and revealed to act as an essential positive regulator allowing the expression of the mdeAB operon. PMID:9190812

  12. Hydrogen sulfide selectivity with carbonyl sulfide removal to less than PPM levels

    SciTech Connect

    Bacon, T.R.; Pearce, R.L.; Foster, W.R. Jr.

    1986-01-01

    Changes in market conditions and plant operating economics require examination of traditional processes and operating practices in gas treating applications for upgrading to more stringent standards of efficiency in order to remain competitive while returning a satisfactory operating profit margin to the company. Anticipated reduction in solvent usage, improvements in Claus sulfur recovery unit performance and lower energy costs induced Ashland's Catlettsburg refinery to convert its entire sulfur removal system from monoethanolamine to methyldiethanolamine. One of the seven product streams being treated required extremely low carbonyl sulfide specifications. When the initial converted operations evidenced a need to improve the carbonyl sulfide removal, GAS/SPEC Tech Service produced an innovative solution which allowed for efficient operation which still achieved these objectives.

  13. Synthesis and characterization of novel polyurethane cationomers with dipeptide sequences and alkylammonium groups.

    PubMed

    Buruiana, Emil C; Buruiana, Tinca

    2004-01-01

    A synthetic approach to polyurethane cationomers containing S-pyroglutamyl-S-glutamic acid dipeptide (S-PyGlu-S-Glu) and alkylammonium groups is presented. Two segmented polycations, based on polycaprolactone diol, isophorone diisocyanate and dipeptide together with N-methyldiethanolamine, subsequently quaternized with dodecylbromide, were synthesized and characterized by IR spectroscopy, GPC, DSC and reduced viscosity measurements. Such polycations exhibited excellent film forming properties and their soft elastomeric nature provides adequate physical properties. Optical rotation varying from +10 (monomer) to -15 (polycation) could be associated with a configuration pertubation through the asymmetric carbon atoms of glutamic residues. Susceptibility of the cationic surface to heparinization and then to blood-polymer interaction suggested an anticoagulant activity of the heparinized polymeric films. PMID:15255526

  14. Screening for illicit drugs on Euro banknotes by LC-MS/MS.

    PubMed

    Wimmer, Kurt; Schneider, Serge

    2011-03-20

    A method for the simultaneous quantification of illicit drugs on Euro banknotes, using an ultra-performance liquid chromatography tandem mass spectrometry, was developed and validated. The method included cocaine, benzoylecgonine, MDMA, MDEA, MDA, methamphetamine, diacetylmorphine, 6-MAM, morphine and Δ(9)-THC. Drug residues were monitored and quantified via positive ESI mode using multiple reaction monitoring. Banknotes were extracted with methanol by vigorous shaking. Recovery rates were in the range of 60-80%. Calibration was performed with spiked banknotes in the range of 10-100 ng/note (R(2) 0.98-0.99). Intra-day analysis showed fair precision and accuracy (≤ 15%). Matrix effects were in the range from 27% to 235%. 7-15 samples of each denomination were analyzed. The calculated median values per note were 106 ng cocaine, 43 ng benzoylecgonine, 41 ng heroin, 15.5 ng 6-MAM, 16.5 ng morphine, 9 ng MDMA and 7 ng methamphetamine. Δ(9)-THC was detected on 4 banknotes. MDEA and MDA were not detected on any note. A widespread background contamination for cocaine and opiates was demonstrated. PMID:20810225

  15. Determination of amphetamine, methamphetamine, 3,4-methylenedioxyamphetamine, 3,4-methylenedioxyethylamphetamine, and 3,4-methylenedioxymethamphetamine in urine by online solid-phase extraction and ion-pairing liquid chromatography with detection by electrospray tandem mass spectrometry.

    PubMed

    Wu, Ti-Yu; Fuh, Ming-Ren

    2005-01-01

    A method using an online solid-phase extraction (SPE) and ion-pairing liquid chromatography with electrospray tandem mass spectrometry (LC/ES-MS/MS) was developed for determination of amphetamine (Amp), methamphetamine (mAmp), 3,4-methylenedioxyamphetamine (MDA), 3,4-methylenedioxyethylamphetamine (MDEA), and 3,4-methylenedioxymethamphetamine (MDMA) in urine samples. A SPE cartridge column with both hydrophilic and lipophilic functions was utilized for online extraction. A reversed-phase C18 LC column was employed for LC separation and MS/MS was used for detection. Trifluoroacetic acid was added to the mobile phase as an ion-pairing reagent. This method was fully automated and the extraction and analysis procedures were controlled by a six-port switch valve. Recoveries ranging from 85-101% were measured. Good linear ranges (10-500 ng/mL) for Amp and mAmp were determined. For MDA, MDMA and MDEA, dual linear ranges were obtained from 5-100 and 100-500 ng/mL, respectively. The detection limit of each analytical compound, based on a signal-to-noise ratio of 3, ranged from 1-3 ng/mL. The applicability of this newly developed method was examined by analyzing several urine samples from drug users. Good agreement was obtained between the results from this method and a literature GC/MS method. PMID:15712289

  16. A rapid method for the extraction, enantiomeric separation and quantification of amphetamines in hair.

    PubMed

    Strano-Rossi, Sabina; Botrè, Francesco; Bermejo, Ana Maria; Tabernero, Maria Jesús

    2009-12-15

    This paper presents a rapid and sensitive method for the determination and chiral separation of amphetamines and related designer drugs in hair samples. The substances are extracted from hair matrix by a 30 min treatment with a saturated carbonate buffer at pH 10 under ultrasonication. A commercial chiral derivatizing agent, trifluoroacetyl-prolyl chloride, is then added to the solution that is directly extracted with hexane and subsequently analyzed by GC/MS in SIM mode. R and S isomers of amphetamine, methamphetamine, MDA, MDMA and MDEA can be separated and detected with a limit of detection of 0.1 ng/mg for amphetamine, methamphetamine and MDA, and of 0.2 ng/mg for MDMA and MDEA. The method was then applied to 12 samples from suspected amphetamines abusers, showing the presence of both isomers of amphetamine and MDMA in one sample (27 and 1.5 ng/mg, respectively) and of MDMA in further eight samples, in concentrations ranging from traces to 2.7 ng/mg. No differences were observed in the disposition of different isomers in hair. PMID:19896309

  17. Differential gene expression in planktonic and biofilm cells of multiple antibiotic-resistant Salmonella Typhimurium and Staphylococcus aureus.

    PubMed

    He, Xinlong; Ahn, Juhee

    2011-12-01

    This study was designed to evaluate gene expression patterns of the planktonic and biofilm cells of Staphylococcus aureus and Salmonella Typhimurium in trypticase soy broth adjusted to pH 5.5 and pH 7.3. The planktonic and biofilm cells of multiple antibiotic-resistant S. aureus (S. aureus(R) ) and S. Typhimurium (S. Typhimurium(R) ) were more resistant to β-lactams than those of antibiotic-susceptible S. aureus (S. aureus(S) ) and S. Typhimurium (S. Typhimurium(S) ) at pH 5.5 and pH 7.3. The relative gene expression levels of norB, norC, and mdeA genes were increased by 7.0-, 4.7-, and 4.6-fold, respectively, in the biofilm cells of S. aureus(S) grown at pH 7.3, while norB, norC, mdeA, sec, seg, sei, sel, sem, sen, and seo genes were stable in the biofilm cells of S. aureus(R) . This study provides useful information for understanding gene expression patterns in the planktonic and biofilm cells of antibiotic-resistance pathogens exposed to acidic stress. PMID:22092573

  18. Simultaneous determination of HFBA-derivatized amphetamines and ketamines in urine by gas chromatography-mass spectrometry.

    PubMed

    Lee, Hei Hwa; Lee, Jong Feng; Lin, Sin Yu; Chen, Ping Ho; Chen, Bai Hsiun

    2011-04-01

    To facilitate the analysis of targeted drugs under high sample volume testing environment, an extraction, derivatization and gas chromatographic-mass spectrometric analysis method was developed for simultaneously determination of amphetamine (AMP), methamphetamine (MAMP), 3,4-methylenedioxyamphetamine (MDA), 3,4-methylenedioxymethamphetamine (MDMA), 3,4-methylenedioxyethylamphetamine (MDEA), ketamine, and norketamine in urine. This method utilized solid-phase extraction in conjunction with derivatization using heptafluorobutyric anhydride (HFBA) as the derivatization reagent. Using a 1-mL sample, the limits of quantitation achieved for the analysis of AMP, MAMP, MDA, MDMA, MDEA, ketamine, and norketamine were 25, 15, 60, 60, 70, 25, and 30 ng/mL, respectively. Upper limits of quantitation were 8000 ng/mL for all amphetamines and 6000 ng/mL for ketamine and norketamine. Except for dehydronorketamine (DHNK), within-day and between-day precisions (as expressed in CV%) for quality control samples were ≤ 3.1% and ≤ 4.95%, respectively. Except DHNK, the within-day accuracy ranged between 96.0% and 110.7% and the between-day accuracy ranged between 96.9% and 108.7%. A group of 107 urine samples previously determined to contain the target analytes were analyzed by this new approach. Quantitative data produced by both methods agreed well. With this new approach, we were able to use a single analytical protocol to conduct the confirmation test for samples that preliminarily tested positive (by immunoassay) for amphetamines, ketamine, or both. PMID:21439152

  19. Aerobic biodegradation of amines in industrial saline wastewaters.

    PubMed

    Campo, Pablo; Platten, William; Suidan, Makram T; Chai, Yunzhou; Davis, John W

    2011-11-01

    The treatment of hypersaline wastewaters represents a challenge since high salt concentrations disrupt bacteria present in normal biological treatments. This study was conducted to determine the fate of amines in two hypersaline wastewaters obtained from an industrial treatment plant processing influents with 3% and 7% of NaCl. The compounds were aniline (ANL), 4,4'-methylenedianiline (4,4'-MDA), cyclohexylamine (CHA), N-(2-aminoethyl)ethanolamine (AEA), N,N-diethylethanolamine (DEA), N,N-bis(2-hydroxyethyl)methylamine (MDEA), and tris(2-hydroxyethyl)amine (TEA). Mixtures of these chemicals with a mixed liquor suspended solids concentration of 1000 mg L(-1) were prepared at two salinities (3% and 7% NaCl). Ethanolamines were readily biodegraded at both salinities, following first-order kinetics with half-lives ranging between 10 and 58 h. Hydroxyl groups present in the ethanolamines had a positive impact on the biodegradation. Salinity did not affect the biodegradation rate of TEA and MDEA, whereas AEA and DEA degraded faster in 3% NaCl. After 48h, CHA was metabolized within a 24-h period in 3% NaCl, while no degradation was observed in 7% NaCl. ANL exhibited lag phases in both salinities and, in the following 24-h period, ANL concentrations dropped 40% and disappeared after 48 h. 4,4'-MDA degraded in 3% NaCl (half-life of 123 h) and remained unaltered after 120 h in 7% NaCl. PMID:21925703

  20. New chlorinated amphetamine-type-stimulants disinfection-by-products formed during drinking water treatment.

    PubMed

    Huerta-Fontela, Maria; Pineda, Oriol; Ventura, Francesc; Galceran, Maria Teresa

    2012-06-15

    Previous studies have demonstrated high removal rates of amphetamine-type-stimulants (ATSs) through conventional drinking water treatments; however the behaviour of these compounds through disinfection steps and their transformation into disinfection-by-products (DBPs) is still unknown. In this work, for the first time, the reactivity of some ATSs such as amphetamine, methamphetamine, 3,4-methylenedioxyamphetamine (MDA), 3,4-methylenedioxymethamphetamine (MDMA) and 3,4-methylenedioxyethylamphetamine (MDEA) with chlorine has been investigated under simulated and real drinking water treatment conditions in order to evaluate their ability to give rise to transformation products. Two new DBPs from these illicit drugs have been found. A common chlorinated-by-product (3-chlorobenzo)-1,3-dioxole, was identified for both MDA and MDEA while for MDMA, 3-chlorocatechol was found. The presence of these DBPs in water samples collected through drinking water treatment was studied in order to evaluate their formation under real conditions. Both compounds were generated through treatment from raw river water samples containing ATSs at concentration levels ranging from 1 to 15 ng/L for MDA and from 2.3 to 78 ng/L for MDMA. One of them, (3-chlorobenzo)-1,3-dioxole, found after the first chlorination step, was eliminated after ozone and GAC treatment while the MDMA DBP mainly generated after the postchlorination step, showed to be recalcitrant and it was found in final treated waters at concentrations ranging from 0.5 to 5.8 ng/L. PMID:22534122

  1. Endogenous generation of hydrogen sulfide and its regulation in Shewanella oneidensis.

    PubMed

    Wu, Genfu; Li, Ning; Mao, Yinting; Zhou, Guangqi; Gao, Haichun

    2015-01-01

    Hydrogen sulfide (H2S) has been recognized as a physiological mediator with a variety of functions across all domains of life. In this study, mechanisms of endogenous H2S generation in Shewanella oneidensis were investigated. As a research model with highly diverse anaerobic respiratory pathways, the microorganism is able to produce H2S by respiring on a variety of sulfur-containing compounds with SirACD and PsrABC enzymatic complexes, as well as through cysteine degradation with three enzymes, MdeA, SO_1095, and SseA. We showed that the SirACD and PsrABC complexes, which are predominantly, if not exclusively, responsible for H2S generation via respiration of sulfur species, do not interplay with each other. Strikingly, a screen for regulators controlling endogenous H2S generation by transposon mutagenesis identified global regulator Crp to be essential to all H2S-generating processes. In contrast, Fnr and Arc, two other global regulators that have a role in respiration, are dispensable in regulating H2S generation via respiration of sulfur species. Interestingly, Arc is involved in the H2S generation through cysteine degradation by repressing expression of the mdeA gene. We further showed that expression of the sirA and psrABC operons is subjected to direct regulation of Crp, but the mechanisms underlying the requirement of Crp for H2S generation through cysteine degradation remain elusive. PMID:25972854

  2. Co-effects of amines molecules and chitosan films on in vitro calcium carbonate mineralization.

    PubMed

    Cui, Jifei; Kennedy, John F; Nie, Jun; Ma, Guiping

    2015-11-20

    Amines monomers, N,N-dimethylaminoethyl methacrylate (DMAEMA), N,N-dimethylethanolamine (DMEA), 2-dimethylaminoethylamine (DMEDA) and N-methiyldiethanolamine (MDEA) were used to induce the formation of calcium carbonate (CaCO3) crystals on chitosan films, by using (NH4)2CO3 diffusion method at ambient temperature. The obtained CaCO3 particles were characterized by scanning electron microscope (SEM), X-ray diffraction (XRD) and Energy dispersive spectroscopy (EDS). The influence of reaction variables, such as the additive concentration and their types were also investigated on the products. The morphologies of CaCO3 crystals, inter-grown in cube-shape, were controlled by DMAEMA and DMEA. It was observed that the morphologies of CaCO3 changed from the cube grown arms to massive calcite with a hole on the face by increasing the concentrations of DMEDA and MDEA. While the precipitation grew on chitosan film without any organic additive, only single cube-shaped crystals were obtained. By these results the possible mechanisms can be proposed that electronic movement of the groups on the monomer effected ions configuration and molecules absorbed on the exposed surface, resulted the change of the surface energy, which caused the change in the morphology of CaCO3. PMID:26344256

  3. Endogenous generation of hydrogen sulfide and its regulation in Shewanella oneidensis

    PubMed Central

    Wu, Genfu; Li, Ning; Mao, Yinting; Zhou, Guangqi; Gao, Haichun

    2015-01-01

    Hydrogen sulfide (H2S) has been recognized as a physiological mediator with a variety of functions across all domains of life. In this study, mechanisms of endogenous H2S generation in Shewanella oneidensis were investigated. As a research model with highly diverse anaerobic respiratory pathways, the microorganism is able to produce H2S by respiring on a variety of sulfur-containing compounds with SirACD and PsrABC enzymatic complexes, as well as through cysteine degradation with three enzymes, MdeA, SO_1095, and SseA. We showed that the SirACD and PsrABC complexes, which are predominantly, if not exclusively, responsible for H2S generation via respiration of sulfur species, do not interplay with each other. Strikingly, a screen for regulators controlling endogenous H2S generation by transposon mutagenesis identified global regulator Crp to be essential to all H2S-generating processes. In contrast, Fnr and Arc, two other global regulators that have a role in respiration, are dispensable in regulating H2S generation via respiration of sulfur species. Interestingly, Arc is involved in the H2S generation through cysteine degradation by repressing expression of the mdeA gene. We further showed that expression of the sirA and psrABC operons is subjected to direct regulation of Crp, but the mechanisms underlying the requirement of Crp for H2S generation through cysteine degradation remain elusive. PMID:25972854

  4. Evaluation of a coated-filter sampling method for the determination of isocyanate concentrations in air

    SciTech Connect

    Seymour, M.J.

    1987-04-01

    An alternative sampling device was evaluated for the determination of isocyanates in air. Diphenylmethane and 1-(2-methoxyphenyl)piperazine were used to coat a glass-fiber filter. The piperazine reacted with aromatic and aliphatic isocyanates, forming ureas. High-pressure liquid chromatography was used to analyze these ureas with electrochemical detection. The mixing of the isocyanate aerosol with the reagent was facilitated by the diphenylmethane. When compared with the results obtained using a reference impinger method in laboratory sampling, the isocyanate air concentrations recorded from the coated-filter method were higher. When tested in the field, air concentrations determined from the impinger samplers for more than 50% of the sample pairs were higher than those obtained by the filter-sample method. The author concludes that this coated-filter method was not reliable enough to be used for determining isocyanate aerosol concentrations in the atmosphere of a work environment.

  5. Synthesis of pyrazinamide Mannich bases and its antitubercular properties.

    PubMed

    Sriram, Dharmarajan; Yogeeswari, Perumal; Reddy, Sushma Pobba

    2006-04-15

    A series of pyrazinamide (PAZ) Mannich bases has been synthesized by reacting PAZ, formaldehyde, and various substituted piperazines using microwave irradiation with the yield ranging from 46% to 86%. The synthesized compounds were evaluated for antimycobacterial activity in vitro and in vivo against Mycobacterium tuberculosis H37Rv (MTB). Among the synthesized compounds, 1-cyclopropyl-6-fluoro-1,4-dihydro-8-methoxy-7-(3-methyl-4-((pyrazine-2-carboxamido)methyl)piperazin-1-yl)-4-oxoquinoline-3-carboxylic acid (17) was found to be the most active compound in vitro with MIC of 0.39 and 0.2 microg/mL against MTB and multidrug-resistant MTB, respectively. In the in vivo animal model 17 decreased the bacterial load in lung and spleen tissues with 1.86 and 1.66-log10 protections, respectively. PMID:16464574

  6. Crystal structure of a new hybrid compound based on an iodido-plumbate(II) anionic motif.

    PubMed

    Mokhnache, Oualid; Boughzala, Habib

    2016-01-01

    Crystals of the one-dimensional organic-inorganic lead iodide-based compound catena-poly[bis-(piperazine-1,4-diium) [[tetra-iodido-plumbate(II)]-μ-iodido] iodide monohydrate], (C4N2H12)2[PbI5]I·H2O, were obtained by slow evaporation at room temperature of a solution containing lead iodide and piperazine in a 1:2 molar ratio. Inorganic lead iodide chains, organic (C4N2H12)(2+) cations, water mol-ecules of crystallization and isolated I(-) anions are connected through N-H⋯·I, N-H⋯OW and OW-H⋯I hydrogen-bond inter-actions. Zigzag chains of corner-sharing [PbI6](4-) octa-hedra with composition [PbI4/1I2/2](3-) running parallel to the a axis are present in the structure packing. PMID:26870585

  7. Synthesis, In silico studies and In vitro evaluation for antioxidant and antibacterial properties of diarylmethylamines: A novel class of structurally simple and highly potent pharmacophore.

    PubMed

    Mahato, Sujit; Singh, Anuma; Rangan, Latha; Jana, Chandan K

    2016-06-10

    A series of novel diarylmethylamines were synthesized via simple three component condensation reaction. In vitro antibacterial activity of the synthesized compounds was assessed against Gram-positive and Gram-negative bacteria. Compound 1f containing phenyl and N-methyl piperazine moiety was found to be potent against both pathogenic bacteria with MIC value of 31μg/mL. Diarylmethylamine 1l containing sesamol and N-methyl piperazine units was found to be the most effective against Gram-positive bacteria with MIC value of 15μg/mL. The compound leads to the damage of the bacterial cell membrane which was demonstrated by flow cytometry (FC) and field emission scanning electron microscopy (FESEM). Radical scavenging activity of compounds 1l and 1m was found out to be comparable with that of standard antioxidant BHT. Further, in silico studies were carried out to calculate the physico-chemical parameter of the synthesized compounds. PMID:26993964

  8. 'Catalysts' for polyacrylamide gel polymerization and detection of proteins by silver staining.

    PubMed

    Hochstrasser, D F; Merril, C R

    1988-01-01

    The crosslinker diacrylyl-piperazine produces polyacrylamide gels which display improved electrophoretic separation of proteins and better physical strength. It also produces gels with improved detection of proteins by ammoniacal silver staining by reducing the background. This reduced background provided us with an opportunity to investigate residual background staining caused by the catalytic reagents utilized in the polymerization of acrylamide gels. The commonly used catalyst system, tetramethyl-ethylenediamine and ammonium persulfate was shown to be responsible for the yellow staining background found after a prolonged development time with silver staining. An alternate catalyst system has been designed to decrease further the formation of this background staining. Dimethyl-piperazine or tetramethylethylenediamine, potassium or ammonium persulfate, and sodium thiosulfate are shown to provide for gels which have excellent mechanical and staining characteristics. These catalytic systems produce little background staining despite prolonged development time with the ammoniacal silver stain, and they reduce background staining with the dichromate silver stain. PMID:2484987

  9. CO2 CAPTURE BY ABSORPTION WITH POTASSIUM CARBONATE

    SciTech Connect

    Gary T. Rochelle; Eric Chen; J.Tim Cullinane; Marcus Hilliard; Jennifer Lu; Babatunde Oyenekan; Ross Dugas

    2004-07-29

    The objective of this work is to improve the process for CO{sub 2} capture by alkanolamine absorption/stripping by developing an alternative solvent, aqueous K{sub 2}CO{sub 3} promoted by piperazine. CO{sub 2} mass transfer rates are second order in piperazine concentration and increase with ionic strength. Modeling of stripper performance suggests that 5 m K{sup +}/2.5 m PZ will require 25 to 46% less heat than 7 m MEA. The first pilot plant campaign was completed on June 24. The CO{sub 2} penetration through the absorber with 20 feet of Flexipac{trademark} 1Y varied from 0.6 to 16% as the inlet CO{sub 2} varied from 3 to 12% CO{sub 2} and the gas rate varied from 0.5 to 3 kg/m{sup 2}-s.

  10. A comparison of the genetic activity of pyrvinium pamoate with that of several other anthelmintic drugs in Saccharomyces cerevisiae.

    PubMed

    Hennig, U G; Galindo-Prince, O C; Cortinas de Nava, C; Savage, E A; von Borstel, R C

    1987-02-01

    Several anthelmintic drugs that are used routinely in oxyuriasis therapy were analyzed for genotoxicity in a diploid mitotic recombination and gene conversion assay (strain D5 of Saccharomyces cerevisiae), and in a haploid yeast reversion assay (strain XV185-14C). Piperazine citrate, piperazine adipate, mebendazole and thiabendazole did not appear to be genotoxic in either yeast strain. Pyrvinium pamoate induced the reversion of the missense, nonsense and frameshift alleles in strain XV185-14C, whereas pyrantel pamoate induced only the reversion of the frameshift allele. Pyrvinium pamoate was recombinogenic in strain D5, and there is an indication that pyrantel pamoate, at the lowest dose that was tested, might induce gene conversion or aneuploidy. PMID:3543669

  11. CO2 Capture by Absorption with Potassium Carbonate

    SciTech Connect

    Gary T. Rochelle; Eric Chen; Babatunde Oyenekan; Andrew Sexton; Amorvadee Veawab

    2006-04-28

    The objective of this work is to improve the process for CO{sub 2} capture by alkanolamine absorption/stripping by developing an alternative solvent, aqueous K{sub 2}CO{sub 3} promoted by piperazine. The final campaign of the pilot plant was completed in February 2006 with 5m K{sup +}/2.5m PZ and 6.4m K{sup +}/1.6m PZ using Flexipac AQ Style 20. The new cross-exchanger reduced the approach temperature to less than 9 C. Stripper modeling has demonstrated that a configuration with a ''Flashing Feed'' requires 6% less work that a simple stripper. The oxidative degradation of piperazine proceeds more slowly than that of monoethanolamine and produces ethylenediamine and other products. Uninhibited 5 m KHCO{sub 3}/2.5 m PZ corrodes 5 to 6 times faster that 30% MEA with 0.2 mol CO{sub 2}/mol MEA.

  12. Synthesis, and Surface-Active Properties of Palm Fatty Acid and 1(2-HYDROXYETHYL - Esteramide Quat

    NASA Astrophysics Data System (ADS)

    Mishra, Shilpi; Tyagi, V. K.

    In this study, an attempt has been made to synthesize esteramide quat by esterification of palm fatty acids with 1(2-hydroxyethyl piperazine) followed by quaternization with dimethyl sulphate (DMS). The optimum reaction conditions for esterification of palm fatty acids and 1(2-hydroxyethyl piperazine) were found to be 170°C reaction temperature and 150 mmHg pressure. The obtained esteramide was subjected to quaternization with different molar ratios of DMS. The consequences revealed that esteramide to DMS ratio of 1 : 0.95 and duration of quaternization for 2 h yielded esteramide quat of maximum cationic content, i.e., 64.9%. The instrumental analysis, viz. FT-IR, 1H NMR, 13C NMR verified the esterification and subsequent quaternization of the obtained esteramide quat. Furthermore, the surface-active and performance properties of synthesized esteramide quat were also evaluated.

  13. CO2 Capture by Absorption with Potassium Carbonate

    SciTech Connect

    Gary T. Rochelle; Eric Chen; Babatunde Oyenekan; Andrew Sexton; Jason Davis; Marcus Hilliard; Amorvadee Veawab

    2006-07-28

    The objective of this work is to improve the process for CO{sub 2} capture by alkanolamine absorption/stripping by developing an alternative solvent, aqueous K{sub 2}CO{sub 3} promoted by piperazine. The pilot plant data have been reconciled using 17% inlet CO{sub 2}. A rate-based model demonstrates that the stripper is primarily controlled by liquid film mast transfer resistance, with kinetics at vacuum and diffusion of reactants and products at normal pressure. An additional major unknown ion, probably glyoxylate, has been observed in MEA degradation. Precipitation of gypsum may be a feasible approach to removing sulphate from amine solutions and providing for simultaneous removal of CO{sub 2} and SO{sub 2}. Corrosion of carbon steel in uninhibited MEA solution is increased by increased amine concentration, by addition of piperazine, and by greater CO{sub 2} loading.

  14. CO{sub 2} CAPTURE BY ABSORPTION WITH POTASSIUM CARBONATE

    SciTech Connect

    Gary T. Rochelle; J.Tim Cullinane; Marcus Hilliard; Eric Chen; Babatunde Oyenekan; Ross Dugas

    2005-01-31

    The objective of this work is to improve the process for CO{sub 2} capture by alkanolamine absorption/stripping by developing an alternative solvent, aqueous K{sub 2}CO{sub 3} promoted by piperazine. Thermodynamic modeling predicts that the heat of desorption of CO{sub 2} from 5m K+/2.5 PZ from 85 kJ/mole at 40 C to 30 kJ/mole at 120 C. Mass transfer modeling of this solvent suggests that carbonate and general salt concentration play a major role in catalyzing the rate of reaction of CO{sub 2} with piperazine. Stripper modeling suggests that with the multipressure stripper, the energy consumption with a generic solvent decreases by 15% as the heat of desorption is decreased from 23.8 to 18.5 kcal/gmol. A second pilot plant campaign with 5m K+/2.5 PZ was successfully completed.

  15. Synthesis and Anti-inflammatory Performance of Newly Cyclizine Derivatives on Adult Male Wistar Rats

    PubMed Central

    Ahmadi, Abbas; Khalili, Mohsen; Chavrogh, Shahnaz; Nahri-Niknafs, Babak

    2012-01-01

    Cyclizine (1-benzhydryl-4-methyl-piperazine, CAS 82-92-8, CYC, I), a piperazine derivative, belongs to H1 antihistamine group of drugs that shows such pharmacological properties as anti-inflammatory, anti-allergic and anti-platelet effects, similar to other H1-receptor antagonists. In this study, two new tolyl and cumene derivatives of I (1-ethyl- 4-[(p-isopropylphenyl) (p-tolyl) methyl]-piperazine, II and 1-[3, 4-dichlorophenyl]-4-[[p-isopropylphenyl] [p-tolyl] methyl]-piperazine, III) were synthesized to investigate their acute and chronic anti-inflammatory activities in formalin and histamine-induced rat paw edema. In addition, the vascular permeability in formalin and histamine-induced paw edema, xylene-induced ear edema, and peritonitis due to acetic acid application into peritoneal cavity were measured. The cotton pellet-induced granuloma model was chosen for inducing chronic inflammation in rats. Findings proved reduction in formalin-induced rat paw edema and vascular permeability (acute inflammation) by I and II at 30 min after the injection. In addition, results in histamine-induced rat paw edema showed anti-inflammatory effects of all drugs started 60 min after the injection as these effects continued for a longer period by II and III comparing to I, as discussed above. In addition, the data on vascular permeability in xylene-induced ear edema and acetic acid-induced to peritoneal cavity confirmed that substitutions on cyclizine molecule were more effective and could decrease the vascular permeability and acute inflammation. However, the results from the cotton pellet-induced granuloma formation in rats revealed that none of the drugs (I-III) were effective to reduce the reactions and intermediates of chronic inflammation. PMID:24250533

  16. Regioselective Green Electrochemical Approach to the Synthesis of Nitroacetaminophen Derivatives.

    PubMed

    Salahifar, Eslam; Nematollahi, Davood; Bayat, Mehdi; Mahyari, Amir; Amiri Rudbari, Hadi

    2015-10-01

    A regioselective green synthesis of nitroacetaminophen derivatives was carried out by electrochemical oxidation of acetaminophen, N-(2-hydroxyphenyl)acetamide, and 1-(4-(4-hydroxyphenyl)piperazin-1-yl)ethanone in the presence of nitrite ion as a nucleophile. The present work has led to the development of a reagentless green and facile electrochemical method for the synthesis of some nitroacetaminophen derivatives. PMID:26381590

  17. Antitussive effects of levodropropizine in the dog.

    PubMed

    Munt, P L; Clavenna, G; Algate, D R; Leach, R M

    1994-02-01

    The antitussive activity of levodropropizine (S(-)3-(4-phenyl-piperazine-1-yl)-propane-1,2-diol, DF 526, CAS 99291-25-5) was evaluated after oral administration to the conscious dog. Levodropropizine had a good antitussive activity, comparable with, but having a longer duration of action than dropropizine, the racemate from which it is derived. The antitussive activity of levodropropizine in the dog was approximately 1/20 of that of codeine phosphate. PMID:8147948

  18. Redox-Neutral α-Sulfenylation of Secondary Amines: Ring-Fused N,S-Acetals

    PubMed Central

    2015-01-01

    Secondary amines react with thiosalicylaldehydes in the presence of catalytic amounts of acetic acid to generate ring-fused N,S-acetals in redox-neutral fashion. A broad range of amines undergo α-sulfenylation, including challenging substrates such morpholine, thiomorpholine, and piperazines. Computational studies employing density functional theory indicate that acetic acid reduces the energy barriers of two separate steps, both of which involve proton transfer. PMID:24927364

  19. Polyamide-polyether copolymers: a new family of impact-resistant thermoplastics

    SciTech Connect

    Rasmussen, J.K.; Smith, H.K. II

    1983-08-01

    A new family of thermoplastic polyamide-polyether copolymers that display outstanding impact resistance and are especially useful as hot melt adhesives are described. These polymers are prepared by copolymerization of polymerized fatty acid derivatives (dimer diamines) and poly(oxyalkylene) diamines with the typical polyamide monomers sebacic acid and piperazine. Impact resistance is apparently achieved through synergistic interaction between the dimer and the polyether portions of the polymers.

  20. Identification of novel GLUT inhibitors.

    PubMed

    Siebeneicher, Holger; Bauser, Marcus; Buchmann, Bernd; Heisler, Iring; Müller, Thomas; Neuhaus, Roland; Rehwinkel, Hartmut; Telser, Joachim; Zorn, Ludwig

    2016-04-01

    The compound class of 1H-pyrazolo[3,4-d]pyrimidines was identified using HTS as very potent inhibitors of facilitated glucose transporter 1 (GLUT1). Extensive structure-activity relationship studies (SAR) of each ring system of the molecular framework was established revealing essential structural motives (i.e., ortho-methoxy substituted benzene, piperazine and pyrimidine). The selectivity against GLUT2 was excellent and initial in vitro and in vivo pharmacokinetic (PK) studies are encouraging. PMID:26949183

  1. Syntheses and antibacterial activity studies of new oxazolidinones from nitroso Diels–Alder chemistry

    PubMed Central

    Yan, Shanshan; Wencewicz, Timothy A.; Möllmann, Ute

    2009-01-01

    A series of novel oxazolidinone antibiotics having [2.2.1] and [2.2.2] bicyclic oxazine moieties at the C-5 side chain of the A ring was synthesized by nitroso Diels–Alder reactions, from three linezolid analogs containing morpholine, piperazine and thiomorpholine, respectively, as the C-ring components. Subsequent N–O bond cleavage generated oxazolidinones with 4-amino cyclo-2- en-1-ol substituents. The in vitro antibacterial activities of these oxazolidinone analogs were evaluated. PMID:20031407

  2. Low resolution and high resolution MS for studies on the metabolism and toxicological detection of the new psychoactive substance methoxypiperamide (MeOP).

    PubMed

    Meyer, Markus R; Holderbaum, Anna; Kavanagh, Pierce; Maurer, Hans H

    2015-10-01

    In 2013, the new psychoactive substance methoxypiperamide (MeOP) was first reported to the European Monitoring Centre for Drug and Drug Addiction. Its structural similarity to already controlled piperazine designer drugs might have contributed to the decision to offer MeOP for online purchase. The aims of this work were to identify the phase I/II metabolites of MeOP in rat urine and the human cytochrome P450 (CYP) isoenzymes responsible for the initial metabolic steps. Finally, the detectability of MeOP in rat urine by gas chromatography-mass spectrometry (GC-MS) and liquid chromatography coupled with multistage mass spectrometry (LC-MS(n)) standard urine screening approaches (SUSAs) was evaluated. After sample preparation by cleavage of conjugates followed by extraction for elucidating phase I metabolites, the analytes were separated and identified by GC-MS as well as liquid chromatography-high resolution-tandem mass spectrometry (LC-HR-MS/MS). For detection of phase II metabolites, the analytes were separated and identified after urine precipitation followed by LC-HR-MS/MS. The following metabolic steps could be postulated: hydrolysis of the amide, N-oxide formation, N- and/or O-demethylation, oxidation of the piperazine ring to the corresponding keto-piperazine, piperazine ring opening followed by oxidation of a methylene group to the corresponding imide, and hydroxylation of the phenyl group. Furthermore, N-acetylation, glucuronidation and sulfation were observed. Using human CYPs, CYP1A2, CYP2C19, CYP2D6, and/or CYP3A4 were found to catalyze N-oxide formation and N-, O-demethylation and/or oxidation. Mostly MeOP and N-oxide-MeOP but to a minor degree also other metabolites could be detected in the GC-MS and LC-MS(n) SUSAs. PMID:26456786

  3. Modification of Marine Natural Product Ningalin B and SAR Study Lead to Potent P-Glycoprotein Inhibitors

    PubMed Central

    Yang, Chao; Wong, Iris L. K.; Jin, Wen Bin; Jiang, Tao; Chow, Larry M. C.; Wan, Sheng Biao

    2014-01-01

    In this study, new marine ningalin B analogues containing a piperazine or a benzoloxy group at ring C have been synthesized and evaluated on their P-gp modulating activity in human breast cancer and leukemia cell lines. Their structure-activity relationship was preliminarily studied. Compounds 19 and 20 are potent P-gp inhibitors. These two synthetic analogues of permethyl ningalin B may be potentially used as effective modulators of P-gp-mediated drug resistance in cancer cells. PMID:25329704

  4. Synthesis and Anti-inflammatory Performance of Newly Cyclizine Derivatives on Adult Male Wistar Rats.

    PubMed

    Ahmadi, Abbas; Khalili, Mohsen; Chavrogh, Shahnaz; Nahri-Niknafs, Babak

    2012-01-01

    Cyclizine (1-benzhydryl-4-methyl-piperazine, CAS 82-92-8, CYC, I), a piperazine derivative, belongs to H1 antihistamine group of drugs that shows such pharmacological properties as anti-inflammatory, anti-allergic and anti-platelet effects, similar to other H1-receptor antagonists. In this study, two new tolyl and cumene derivatives of I (1-ethyl- 4-[(p-isopropylphenyl) (p-tolyl) methyl]-piperazine, II and 1-[3, 4-dichlorophenyl]-4-[[p-isopropylphenyl] [p-tolyl] methyl]-piperazine, III) were synthesized to investigate their acute and chronic anti-inflammatory activities in formalin and histamine-induced rat paw edema. In addition, the vascular permeability in formalin and histamine-induced paw edema, xylene-induced ear edema, and peritonitis due to acetic acid application into peritoneal cavity were measured. The cotton pellet-induced granuloma model was chosen for inducing chronic inflammation in rats. Findings proved reduction in formalin-induced rat paw edema and vascular permeability (acute inflammation) by I and II at 30 min after the injection. In addition, results in histamine-induced rat paw edema showed anti-inflammatory effects of all drugs started 60 min after the injection as these effects continued for a longer period by II and III comparing to I, as discussed above. In addition, the data on vascular permeability in xylene-induced ear edema and acetic acid-induced to peritoneal cavity confirmed that substitutions on cyclizine molecule were more effective and could decrease the vascular permeability and acute inflammation. However, the results from the cotton pellet-induced granuloma formation in rats revealed that none of the drugs (I-III) were effective to reduce the reactions and intermediates of chronic inflammation. PMID:24250533

  5. Process for the reduction of nitrogen oxides in an effluent

    SciTech Connect

    Epperly, W.R.; Sullivan, J.C.; Sprague, B.N.

    1989-09-05

    This patent describes a process for the reduction of the concentration of nitrogen oxides in the effluent from the combustion of a carbonaceous fuel. The process comprises introducing a heterocyclic hydrocarbon selected from the group consisting of piperazine, piperidine, pyrazine, pyrazole, imidazole, oxazolidone, pyrrole and pyrrolidine into the effluent having an effluent temperature of greater than about 1200{sup 0}F. under conditions effective to reduce the concentration of nitrogen oxides in the effluent.

  6. Design, synthesis of new β-carboline derivatives and their selective anti-HIV-2 activity.

    PubMed

    Ashok, Penta; Chander, Subhash; Balzarini, Jan; Pannecouque, Christophe; Murugesan, Sankaranarayanan

    2015-03-15

    In the present study, a new series of β-carboline derivatives were synthesized and evaluated for inhibition activity against both HIV-1 and HIV-2 strains. Among these reported analogues, surprisingly (1-phenyl-9H-pyrido[3,4-b]indol-3-yl)(4-p-tolylpiperazin-1-yl)methanone (7b), (4-(2-methoxyphenyl)piperazin-1-yl)(1-phenyl-9H-pyrido[3,4-b]indol-3-yl)methanone (7f), (4-(4-fluorophenyl)piperazin-1-yl)(1-phenyl-9H-pyrido[3,4-b]indol-3-yl)methanone (7k), (4-(2-fluorophenyl)piperazin-1-yl)(1-phenyl-9H-pyrido[3,4-b]indol-3-yl)methanone (7l) displayed selective inhibition of HIV-2 strain with EC50 values of 3.3, 3.2, 2.6 and 5.4μM, respectively, which are comparable with nucleoside reverse transcriptase inhibitors lamivudine and dideoxyinosine. As these analogues have not shown in vitro HIV-2 reverse transcriptase inhibition, it could be excluded as potential target for their specific anti-HIV-2 activity. PMID:25682562

  7. Targeting tumor hypoxia with 2-nitroimidazole-indocyanine green dye conjugates

    NASA Astrophysics Data System (ADS)

    Xu, Yan; Zanganeh, Saeid; Mohammad, Innus; Aguirre, Andres; Wang, Tianheng; Yang, Yi; Kuhn, Liisa; Smith, Michael B.; Zhu, Quing

    2013-06-01

    Tumor hypoxia is a major indicator of treatment resistance to chemotherapeutic drugs, and fluorescence optical tomography has tremendous potential to provide clinically useful, functional information by identifying tumor hypoxia. The synthesis of a 2-nitroimidazole-indocyanine green conjugate using a piperazine linker (piperazine-2-nitroimidazole-ICG) capable of robust fluorescent imaging of tumor hypoxia is described. In vivo mouse tumor imaging studies were completed and demonstrate an improved imaging capability of the new dye relative to an earlier version of the dye that was synthesized with an ethanolamine linker (ethanolamine-2-nitroimidazole-ICG). Mouse tumors located at imaging depths of 1.5 and 2.0 cm in a turbid medium were imaged at various time points after intravenous injection of the dyes. On average, the reconstructed maximum fluorescence concentration of the tumors injected with piperazine-2-nitroimidazole-ICG was twofold higher than that injected with ethanolamine-2-nitroimidazole-ICG within 3 h postinjection period and 1.6 to 1.7 times higher beyond 3 h postinjection. The untargeted bis-carboxylic acid ICG completely washed out after 3 h postinjection. Thus, the optimal window to assess tumor hypoxia is beyond 3 h postinjection. These findings were supported with fluorescence images of histological sections of tumor samples and an immunohistochemistry technique for identifying tumor hypoxia.

  8. Structural aspects of intermolecular interactions in the solid state of 1,4-dibenzylpiperazines bearing nitrile or amidine groups.

    PubMed

    Rezler, Mateusz; Żołek, Teresa; Wolska, Irena; Maciejewska, Dorota

    2014-10-01

    The crystal structures of the title 1,4-bis(4-cyanobenzyl)piperazine (1) and 1,4-bis(4-amidinobenzyl)piperazine tetrahydrochloride tetrahydrate (2) are reported. Compound (1) crystallizes in the triclinic space group P\\bar 1 and compound (2) in the monoclinic space group P21/n. In both (1) and (2) the asymmetric unit contains one half of the molecule because the central piperazine rings were located across a symmetry center. The packing of both molecules was dominated by hydrogen bonds. The crystal lattice of (1) was formed by weak C-H...N and C-H...π interactions. The crystal structure of (2) was completely different, with cations as well as chloride anions and water molecules taking part in intermolecular interactions. Single-crystal X-ray diffraction studies combined with density functional theory (DFT) calculations allowed the characterization of the intermolecular interactions in those two systems having different types of very strong electrophilic groups: non-ionic nitrile and ionic amidine. Chemical shift data from (13)C CP/MAS (Cross Polarization Magic Angle Spinning) NMR spectra were analyzed using the different procedures for the theoretical computation of shielding constants. PMID:25274515

  9. Substituent Effects on Cytotoxic Activity, Spectroscopic Property, and DNA Binding Property of Naphthalimide Derivatives.

    PubMed

    Wang, Ke-Rang; Qian, Feng; Sun, Qian; Ma, Cui-Lan; Rong, Rui-Xue; Cao, Zhi-Ran; Wang, Xiao-Man; Li, Xiao-Liu

    2016-05-01

    A series of novel naphthalimide derivatives NI1-5 containing piperazine moieties (N-(2-hydroxyethyl)piperazine and 1-piperazinepropanol) and piperidine moieties (4-piperidinemethanol, 4-hydroxypiperidine and 4-piperidineethanol) have been synthesized and evaluated for their cytotoxic activity, spectroscopic property, and DNA binding behaviors. It was found that substituents at the 4-position remarkably influence the various activities of this series of compound. Compounds NI3-5 modified with piperidines exhibited potent cytotoxic activities against Hela, SGC-7901, and A549 cells with the IC50 values from 0.73 μm to 6.80 μm, which are better than NI1-2 functionalized with piperazines. Compounds NI1-2 showed higher binding capacity with Ct-DNA than compounds NI3-5 based on studies of UV-vis, fluorescence and CD spectra. Furthermore, compounds NI3-5, as DNA intercalators, showed fluorescence enhancement upon binding with Ct-DNA. More interestingly, fluorescence imaging studies of compound NI4 with A549 cells showed that the fluorescence predominantly appeared in the cytoplasm. These results provided a potential application of NI3-5 as anticancer therapeutic and cancer cell imaging agents. PMID:26648338

  10. Targeting tumor hypoxia with 2-nitroimidazole-indocyanine green dye conjugates

    PubMed Central

    Xu, Yan; Zanganeh, Saeid; Mohammad, Innus; Aguirre, Andres; Wang, Tianheng; Yang, Yi; Kuhn, Liisa; Smith, Michael B.

    2013-01-01

    Abstract. Tumor hypoxia is a major indicator of treatment resistance to chemotherapeutic drugs, and fluorescence optical tomography has tremendous potential to provide clinically useful, functional information by identifying tumor hypoxia. The synthesis of a 2-nitroimidazole-indocyanine green conjugate using a piperazine linker (piperazine-2-nitroimidazole-ICG) capable of robust fluorescent imaging of tumor hypoxia is described. In vivo mouse tumor imaging studies were completed and demonstrate an improved imaging capability of the new dye relative to an earlier version of the dye that was synthesized with an ethanolamine linker (ethanolamine-2-nitroimidazole-ICG). Mouse tumors located at imaging depths of 1.5 and 2.0 cm in a turbid medium were imaged at various time points after intravenous injection of the dyes. On average, the reconstructed maximum fluorescence concentration of the tumors injected with piperazine-2-nitroimidazole-ICG was twofold higher than that injected with ethanolamine-2-nitroimidazole-ICG within 3 h postinjection period and 1.6 to 1.7 times higher beyond 3 h postinjection. The untargeted bis-carboxylic acid ICG completely washed out after 3 h postinjection. Thus, the optimal window to assess tumor hypoxia is beyond 3 h postinjection. These findings were supported with fluorescence images of histological sections of tumor samples and an immunohistochemistry technique for identifying tumor hypoxia. PMID:23764695

  11. [Prevalence of new designer drugs and their legal status in Japan].

    PubMed

    Kikura-Hanajiri, Ruri; Uchiyama, Nahoko; Kawamura, Maiko; Ogata, Jun; Goda, Yukihiro

    2013-01-01

    In recent years, many analogs of narcotics have been widely distributed as easily available psychotropic substances and have become a serious problem in Japan. To counter the spread of these non-controlled substances, the Pharmaceutical Affairs Law in Japan was amended in 2006 to establish a new category; Designated Substances in order to more strictly control these substances. In April 2007, 31 compounds and 1 plant were first controlled as Designated Substances. Before 2007, the major compounds distributed in the Japanese illegal drug market were tryptamines, phenethylamines and piperazines. Alkyl nitrites, such as isobutyl nitrite and isopentyl nitrite, were also widely distributed. After they were listed as Narcotics or Designated Substances in 2007, these compounds, especially the tryptamines, quickly disappeared from the market. In their place, cathinone derivatives have been widely distributed, as well as different phenethylamines and piperazines. Additionally, in recent years, new herbal products containing synthetic cannabinoids have appeared globally. As at July 2012, 78 substances (including 1 plant; Salvia divinorum) were listed in the category of Designated Substances. They were 13 tryptamines, 17 phenethylamines, 11 cathinones, 4 piperazines, 23 synthetic cannabinoids, 6 alkyl nitrites, 3 other compounds and 1 plant. In this review, we show our survey of the spread of new designer drugs in Japan, focusing especially on synthetic cannabinoids and cathinone derivatives. Also, the prevalence and legal status of these substances in other countries will be presented. PMID:23292017

  12. Synthesis of 9-O-3-(1-piperazinyl/morpholinyl/piperidinyl)pentyl-berberines as Potential Antioxidant and Cytotoxic Agents.

    PubMed

    Mistry, Bhupendra M; Patel, Rahul V; Keum, Young-Soo; Kim, Doo Hwan

    2016-01-01

    A new series of 9-O-3-(1-piperazinyl/morpholinyl/piperidinyl)pentyl-berberines has been efficiently formulated via coupling 1,5-dibromopentane with berberrubine which was obtained by treating berberine in a vacuum oven at optimum temperature and pressure. Nucleophilic substitution of a variety of substituted piperazines, morpholine, carbazole and piperidine furnished analogues 5a-i. Final compounds were evaluated for their in vitro antioxidant activity using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino-bis(3-ethylbenzothiazoline-6- sulphonic acid) (ABTS) bioassays. Also, cancer cell inhibitory potential of titled compounds was screened for cervical cancer, HeLa and CaSki employing SRB assay in terms of cytotoxicity. A minimum inhibitory concentration of 5a-i towards normal cells was studied using Madin-Darby canine kidney (MDCK) cell line. Final compounds with carbazole and 1-(naphthalen-2-yl)piperazine showed excellent free radical scavenging efficacies in DPPH and ABTS bioassays, respectively. The presence of naphthyl, benzhydryl, benzoyl, furoyl and heterocyclic rings on the piperazine system was essential to exert anticipated cytotoxic effects against cancer cell lines. The structure of the final compounds was adequately confirmed via spectroscopic techniques, elemental analysis analysis and characterization of physical properties. PMID:26453450

  13. Synthesis, magnetism, and 57Fe Mössbauer spectroscopic study of a family of [Ln3Fe7] coordination clusters (Ln = Gd, Tb, and Er).

    PubMed

    Abbas, Ghulam; Lan, Yanhua; Mereacre, Valeriu; Buth, Gernot; Sougrati, Moulay T; Grandjean, Fernande; Long, Gary J; Anson, Christopher E; Powell, Annie K

    2013-10-21

    The reaction of N-methydiethanolamine (mdeaH2), benzoic acid, FeCl3, and Ln(NO3)3·6H2O or LnCl3·xH2O yields a series of decanuclear coordination clusters, [Ln3Fe7(μ4-O)2(μ3-OH)2(mdea)7(μ-benzoate)4(N3)6]·4MeCN·H2O, where Ln = Gd(III) (1) or Tb(III) (2), and [Er3Fe7(μ4-O)2(μ3-OH)2(mdea)7(μ-benzoate)4(N3)5(MeOH)]Cl·7.5H2O·11.5MeOH (3). The isostructural compounds 1-3 all crystallize isotypically in the triclinic space group P1̅ with Z = 2, as does the previously reported dysprosium analogue 4. Six of the Fe(III) ions are pseudooctahedrally coordinated, whereas the seventh has a trigonal-bipyramidal coordination geometry. Temperature-dependent direct-current magnetic susceptibility studies indicate that intracluster antiferromagnetic interactions are dominant in 1-3. The frequency-dependent out-of-phase (χ″) alternating-current susceptibility reveals that 2 undergoes a slow relaxation of its magnetization, presumably resulting from anisotropy of the Tb(III) ions. Between 30 and 295 K, the (57)Fe Mössbauer spectra reveal paramagnetic behavior with six partially resolved quadrupole doublets, one for the trigonal-bipyramidal Fe(III) site and five for the six pseudooctahedral Fe(III) sites. The Mössbauer spectra of 2 and 3 obtained between 3 and 30 K are consistent with the presence of Fe(III) intracluster antiferromagnetic coupling with slow magnetic relaxation relative to the Larmor precession time. Further, the observed changes in the effective magnetic field values in the spectra measured at 3 K with increasing applied field are consistent with the effect of the local spin polarization along the applied magnetic field direction, a behavior reminiscent of antiparallel spin-coupled iron molecular paramagnetic systems. PMID:24089701

  14. LC-MS-MS Method for Stimulants in Wastewater During Football Games.

    PubMed

    Gul, Waseem; Stamper, Brandon J; Godfrey, Murrell; ElSohly, Mahmoud A

    2016-03-01

    A method was developed for the analysis of amphetamines and cocaine (Coc) in wastewater samples using liquid chromatography coupled with tandem mass spectrometry (LC-MS-MS). Seven stimulant-type drugs and metabolites were analyzed. These drugs included amphetamine (Amp), methamphetamine (Meth), methylenedioxyamphetamine (MDA), methylenedioxymethamphetamine (MDMA), methylenedioxyethylamphetamine (MDEA), Coc and benzoylecgonine (BE, the major metabolite of Coc). These drugs were chosen because of their widespread use. Wastewater samples were collected at both the Oxford Waste Water Treatment Plant in Oxford, Mississippi (MS) and the University Wastewater Treatment Plant in University, MS. Samples were collected on weekends in which the Ole Miss Rebel football team held home games (Vaught-Hemingway Stadium, University, MS 38677). The collected samples were analyzed using a validated method and found to contain Amp, Meth, MDMA, Coc and BE. The concentrations of Amp and BE significantly rose in the university wastewater during football games. PMID:26538543

  15. Heat of Dissolution Measurements for CO2 in Mixed Alkanolamine Solvents

    SciTech Connect

    Vinayak Kabadi

    2007-03-17

    The main objective of this research was to measure heat of dissolution of CO{sub 2} in carefully mixed alkanolamine solvent systems, and provide such directly measured data that might be used for efficient design of CO{sub 2} capture process, and for better understanding of the thermodynamics of CO{sub 2}-Alkanolamine systems. An experimental set-up has been designed using the Isothermal Micro Calorimeter for measuring the solubilities and enthalpies of CO{sub 2} in mixed solvents made of MEA, MDEA, PZ, KF and water. All the measurements were done at temperatures 15, 40, and 75 C by maintaining a constant pressure of 100 psig. A detailed study has been done on the variation of solubilities and enthalpies over a wide range of temperatures, pressures and concentrations, by extracting the information from the literature.

  16. One-component thioxanthone acetic acid derivative photoinitiator for free radical polymerization.

    PubMed

    Esen, Duygu S; Temel, Gokhan; Balta, Demet K; Allonas, Xavier; Arsu, Nergis

    2014-01-01

    Acetic acid-based thioxanthone (TXCH2 COOH) was synthesized and characterized and used as a photoinitiator for free radical photopolymerization of methyl methacrylate (MMA) in the absence and presence of a tertiary amine (MDEA) in different solvents. Different absorption properties were observed depending on the solvent. Fluorescence and phosphorescence experiments were also carried out successfully. The fluorescence quantum yield was found to be 0.09 and the phosphorescence lifetime was calculated as 138 ms at 77 K. The photoinitiator undergoes efficient intersystem crossing into the triplet state and the lowest triplet state possesses π-π* configuration. Laser flash photolysis experiments show that transient absorption of TXCH2 COOH is similar to the parent thioxanthone and the triplet lifetime was calculated as 2.3 μs at 630 nm. PMID:24372104

  17. Paper spray and extraction spray mass spectrometry for the direct and simultaneous quantification of eight drugs of abuse in whole blood.

    PubMed

    Espy, Ryan D; Teunissen, Sebastiaan Frans; Manicke, Nicholas E; Ren, Yue; Ouyang, Zheng; van Asten, Arian; Cooks, R Graham

    2014-08-01

    Determination of eight drugs of abuse in blood has been performed using paper spray or extraction spray mass spectrometry in under 2 min with minimal sample preparation. A method has been optimized for quantification of amphetamine, methamphetamine, 3,4-methylenedioxyamphetamine (MDA), 3,4-methylenedioxy-N-methylamphetamine (MDMA), 3,4-methylenedioxy-N-ethylamphetamine (MDEA), morphine, cocaine, and Δ9-tetrahydrocannabinol (THC) from a single blood spot. Sample to sample variations of 1-5% relative standard deviation were achieved using stable isotope-labeled internal standards and tandem mass spectrometry. Limits of detection for all drugs were below typical physiological and toxicological levels. Paper spray and extraction spray each used less than 10 μL of whole blood. These methods exhibit the potential for performing rapid and high-throughput assays for selective on-site multicompound quantitative screening of illicit drugs. PMID:24970379

  18. Homoleptic gallium(III) and indium(III) aminoalkoxides as precursors for sol-gel routes to metal oxide nanomaterials.

    PubMed

    Mishra, Shashank; Daniele, Stéphane; Petit, Sarah; Jeanneau, Erwann; Rolland, Marc

    2009-04-14

    New homoleptic aminoalkoxides of gallium(III) and indium(III) of the types M4{(OC2H4)2NMe}6 [M = Ga (1), In (2)] and [Ga{(OC2H4)3N}]n (3), as well as a previously described Ga2(OC2H4NMe2)6 (A) have been prepared by isopropoxo(chloro)-aminoalkoxo exchange reactions and characterised by elemental analyses, FT-IR and 1H NMR spectroscopy. Formation of a star-shaped Ga[Ga{mu-eta3:eta1-(OC2H4)2NMe}2]3 (1.4CHCl3) and a zigzag linear In4{mu-eta3:eta1-(OC2H4)2NMe}6 (2.6CHCl3), as revealed by X-ray single crystal structures, reflects the structural diversity among N-methyldiethanolaminate derivatives. Their hydrolyses in boiling water, either in presence or absence of tetraalkylamonium bromide, have been studied and, for gallium derivatives, compared with similar hydrolytic reactions of Ga(OiPr)3. The hydrolysed products were studied by FT-IR, TG-DTA and XRD techniques. For gallium derivatives, transition from orthorhombic Ga(O)OH phase of as-prepared powder to phase pure rhombohedral- and monoclinic-Ga2O3 occurred at about 500 degrees C and 700 degrees C, respectively, whereas cubic In(OH)3 phase of as-prepared powder of 2 was converted to cubic In2O3 at 250 degrees C. Partial hydrolyses were also performed and evolution of the particle size in solution was recorded by light scattering measurements. Various sol-gel processing parameters such as concentration and hydrolysis ratio (h) were studied in order to stabilise nano-sized colloidal suspensions for access to thin films by spin coating. The N-methyldiethanolamine derivatives 1 and 2 were found to be the most suitable candidates for sol-gel processing. The transparent Ga2O3 and In2O3 films obtained on glass or Si wafers from spin-coating of 1 and 2, respectively, were characterised by SEM, EDX and XRD. PMID:19319402

  19. Enantiomeric analysis of drugs of abuse in wastewater by chiral liquid chromatography coupled with tandem mass spectrometry.

    PubMed

    Kasprzyk-Hordern, Barbara; Kondakal, Vishnu V R; Baker, David R

    2010-07-01

    The manuscript concerns the development and validation of a method for enantiomeric analysis of structurally related amphetamines (amphetamine, methamphetamine, 4-methylenedioxymethamphetamine (MDMA), 3,4-methylenedioxyamphetamine (MDA) and 3,4-methylenedioxy-N-ethylamphetamine (MDEA)), ephedrines (ephedrine, pseudoephedrine and norephedrine) and venlafaxine in wastewater by means of chiral chromatography coupled with tandem mass spectrometry. Solid-phase extraction on Oasis HLB sorbent used for sample clean-up and concentration of analytes resulted in very good recoveries accounting for >70%. Signal suppression during MS analysis was negligible for most studied analytes. Resolution of enantiomers of chiral drugs was found to be higher than 1. Preliminary assay validation was undertaken. The mean correlation coefficients of the calibration curves, which were on average higher than 0.997 for all studied analytes, showed good linearity of the method in the studied range. Intra- and inter-day repeatabilities were on average less than 5%. The method quantification limits in wastewater were at low ppt levels and varied from 2.25 to 11.75ng/L. The method was successfully applied for the analysis of raw and treated wastewater samples collected from four wastewater treatment plants. A common occurrence of 1R,2S (-)-ephedrine, 1S,2S (+)-pseudoephedrine and venlafaxine in both raw and treated wastewater samples was observed. Amphetamine, methamphetamine, MDMA and MDEA were also detected in several wastewater samples. The study of enantiomeric fractions of these chiral drugs proved their variable non-racemic composition. The influence of wastewater treatment processes on the enantiomeric composition of chiral drugs was also noted and might indicate enantioselective processes occurring during treatment, although more comprehensive research has to be undertaken to support this hypothesis. PMID:20537654

  20. Enantioselectivity in the methylation of the catecholic phase I metabolites of methylenedioxy designer drugs and their capability to inhibit catechol-O-methyltransferase-catalyzed dopamine 3-methylation.

    PubMed

    Meyer, Markus R; Maurer, Hans H

    2009-06-01

    The designer drugs R,S-3,4-methylenedioxy-methamphetamine (MDMA, Ecstasy), R,S-3,4-methylenedioxy-ethylamphetamine (MDEA, Eve), and R,S-N-methyl-benzodioxolyl-butanamine (MBDB, Eden) are chiral compounds, and their in vitro and in vivo metabolism is enantioselective with a preference for the S-enantiomer caused in part by P450-mediated demethylenation. As the elimination of the catecholamine metabolites could also be enantioselective, the aim of the present study was to investigate the O-methylation to the corresponding methoxy derivatives catalyzed by the soluble or membrane-bound form of the catechol-O-methyltransferase (COMT). As all three compounds showed substrate inhibition effects during the incubation, their inhibition potential was quantified using the methylation of dopamine as a marker reaction. For investigation of the catechol-O-methylation catalyzed by the soluble form of the COMT (sCOMT), incubations with human liver cytosol (HLC) were performed. Human liver microsomes (HLM) were used for investigation of the membrane-bound form. For inhibition studies, 3-hydroxytyramine (dopamine) was incubated in HLC. The respective catechols were added at various concentrations to check whether they influence the methylation of 3-hydroxytyramine. Our data showed that the S-enantiomers of all studied catecholamines were preferably O-methylated by both types of COMT. Comparing the resulting kinetics of the HLC and HLM assays, the affinity for all substrates was 10-fold higher for the membrane-bound COMT, whereas the turnover rate was 10-fold higher for the soluble COMT. Uncompetitive inhibition of dopamine methylation could be observed for all tested catechols. In conclusion, elimination of the catecholamine metabolites of MDMA, MDEA, and MBDB was shown to be enantioselective and might therefore contribute to the different pharmacokinetic properties observed for both enantiomers. Furthermore, the catecholic metabolites were identified to be uncompetitive inhibitors of the sCOMT localized in HLC. PMID:19462939

  1. Simultaneous determination of psychotropic phenylalkylamine derivatives in human hair by gas chromatography/mass spectrometry.

    PubMed

    Kim, Jin Young; Jung, Kyu Sung; Kim, Min Kyoung; Lee, Jae Il; In, Moon Kyo

    2007-01-01

    A gas chromatography/mass spectrometric (GC/MS) method was developed and validated for the determination of thirteen psychotropic phenylalkylamine derivatives (amphetamine; AP, phentermine; PT, methamphamine; MA, cathinone; Khat, methcathinone; MCAT, fenfluramine; FFA, desmethylselegiline; DSEL, 3,4-methylenedioxyamphetamine; MDA, 3,4-methylenedioxymethamphetamine; MDMA, 3,4-methylenedioxyethylamphetamine; MDEA, norketamine; NKT, mescaline; MES, 4-bromo-2,5-dimethoxyphenethylamine; 2CB) in human hair. Hair samples (20 mg) were washed with distilled water and acetone, cut into small fragments (<1 mm), and incubated in 0.25 M methanolic HCl under ultrasonication at 50 degrees C for 1 h. The resulting solutions were evaporated to dryness, derivatized using trifluoroacetic anhydride (TFAA) at 70 degrees C for 30 min, and analyzed by GC/MS. The linear ranges were 0.02-25.0 ng/mg for AP, PT, Khat, FFA, DSEL, MDMA, and 2CB; 0.05-25.0 ng/mg for MA, MCAT, and MES; 0.05-12.5 ng/mg for MDA; and 0.1-25.0 ng/mg for MDEA and NKT, with good correlation coefficients (r(2) > 0.9985). The intra-day, inter-day, and inter-person precisions were within 12.7%, 14.8%, and 16.8%, respectively. The intra-day, inter-day, and inter-person accuracies were between -10.7 and 13.4%, -12.7 and 11.6%, and -15.3 and 11.9%, respectively. The limits of quantifications (LOQs) for each compound were lower than 0.08 ng/mg. The recoveries were in the range of 76.7-95.6%. The method proved to be suitable for the simultaneous qualification and quantification of phenylalkylamine derivatives in hair specimens. PMID:17474080

  2. Identifying methamphetamine exposure in children

    PubMed Central

    Castaneto, Marisol S.; Barnes, Allan J.; Scheidweiler, Karl B.; Schaffer, Michael; Rogers, Kristen K.; Stewart, Deborah; Huestis, Marilyn A.

    2013-01-01

    Introduction Methamphetamine (MAMP) use, distribution and manufacture remain a serious public health and safety problem in the United States, and children environmentally exposed to MAMP face a myriad of developmental, social and health risks, including severe abuse and neglect necessitating child protection involvement. It is recommended that drug-endangered children receive medical evaluation and care with documentation of overall physical and mental conditions and have urine drug testing.1 The primary aim of this study was to determine the best biological matrix to detect MAMP, amphetamine (AMP), methylenedioxymethamphetamine (MDMA), methylenedioxyamphetamine (MDA) and methylenedioxyethylamphetamine (MDEA) in environmentally exposed children. Method 91 children, environmentally exposed to household MAMP intake, were medically evaluated at the Child and Adolescent Abuse Resource and Evaluation (CAARE) Diagnostic and Treatment Center at the University of California, Davis (UCD) Children's Hospital. MAMP, AMP, MDMA, MDA and MDEA were quantified in urine and oral fluid (OF) by gas chromatography mass spectrometry (GCMS) and in hair by liquid chromatography tandem mass spectrometry (LCMSMS). Results Overall drug detection rates in OF, urine and hair were 6.9%, 22.1% and 77.8%, respectively. Seventy children (79%) tested positive for 1 or more drugs in 1 or more matrices. MAMP was the primary analyte detected in all 3 biological matrices. All positive OF (n=5) and 18 of 19 positive urine specimens also had a positive hair test. Conclusion Hair analysis offered a more sensitive tool for identifying MAMP, AMP and MDMA environmental exposure in children than urine or OF testing. A negative urine, or hair test does not exclude the possibility of drug exposure, but hair testing provided the greatest sensitivity for identifying drug-exposed children. PMID:24263642

  3. Identification of amiodarone metabolites in human bile by ultraperformance liquid chromatography/quadrupole time-of-flight mass spectrometry.

    PubMed

    Deng, Pan; You, Tiangeng; Chen, Xiaoyan; Yuan, Tao; Huang, Haihua; Zhong, Dafang

    2011-06-01

    Amiodarone is recognized as an effective drug in the treatment of arrhythmias. Previous experiments demonstrated that mono-N-desethylamiodarone (MDEA) was the major circulating metabolite in humans. In addition, dealkylation, hydroxylation, and deamination were minor metabolic pathways. The purpose of this study was to identify the metabolites of amiodarone in the bile obtained from patients with T-tube drainage after oral drug administration. Amiodarone metabolism in vitro was also investigated using human liver microsomes (HLMs) and S9 fraction. Ultraperformance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC-Q/TOF MS) revealed 33 metabolites in human bile, including 22 phase I and 11 phase II metabolites. The major metabolites were MDEA (M7) and ω-carboxylate amiodarone (M12). Metabolite M12 was isolated from human bile, and the chemical structure was confirmed using UPLC-Q/TOF MS and ¹H NMR. Moreover, the authentic standards of two hydroxylated metabolites, 2-hydroxylamiodarone and 3'-hydroxylamiodarone, were obtained through microbial transformation. Several novel metabolic pathways of amiodarone in human were proposed, including ω-carboxylation, deiodination, and glucuronidation. The in vitro study demonstrated that incubation of HLMs with amiodarone did not give rise to any carboxyl metabolites. In contrast, M12 and its metabolites were detected in human liver S9 incubation samples, and the production of these metabolites were inhibited almost completely by 4-methylpyrazole, an inhibitor of alcohol dehydrogenase, suggesting the involvement of alcohol dehydrogenase in the ω-carboxylation of amiodarone. Overall, UPLC-Q/TOF MS analysis leads to the discovery of several novel amiodarone metabolites in human bile and underscores the importance of bile as an excretion pathway. PMID:21398391

  4. Exquisite 1D Assemblies Arising from Rationally Designed Asymmetric Donor-Acceptor Architectures Exhibiting Aggregation-Induced Emission as a Function of Auxiliary Acceptor Strength.

    PubMed

    Singh, Roop Shikha; Mukhopadhyay, Sujay; Biswas, Arnab; Pandey, Daya Shankar

    2016-01-11

    One-dimensional nanostructures with aggregation-induced emission (AIE) properties have been fabricated to keep the pace with growing demand from optoelectronics applications. The compounds 2-[4-(4-methylpiperazin-1-yl)benzylidene]malononitrile (PM1), 2-{4-[4-(pyridin-2-yl)piperazin-1-yl]-benzylidene}malononitrile (PM2), and 2-{4-[4-(pyrimidin-2-yl)piperazin-1-yl]benzylidene}malononitrile (PM3) have been designed and synthesized by melding piperazine and dicyanovinylene to investigate AIE in an asymmetric donor-acceptor (D-A) construct of A'-D-π-A- topology. The synthetic route has been simplified by using phenylpiperazine as a weak donor (D), dicyanovinylene as an acceptor (A), and pyridyl/pyrimidyl groups (PM2/PM3) as auxiliary acceptors (A'). It has been established that A' plays a vital role in triggering AIE in these compounds because the same D-A construct led to aggregation-caused quenching upon replacing A' with an electron-donating ethyl group (PM1). Moreover, the effect of restricted intramolecular rotation and twisted intramolecular charge transfer on the mechanism of AIE has also been investigated. Furthermore, it has been clearly shown that the optical disparities of these A'-D-π-A architectures are a direct consequence of comparative A' strength. Single-crystal X-ray analyses provided justification for role of intermolecular interactions in aggregate morphology. Electrochemical and theoretical studies affirmed the effect of the A' strength on the overall properties of the A'-D-π-A system. PMID:26615814

  5. Diketopiperazine Derivatives from the Marine-Derived Actinomycete Streptomyces sp. FXJ7.328

    PubMed Central

    Wang, Pei; Xi, Lijun; Liu, Peipei; Wang, Yi; Wang, Wei; Huang, Ying; Zhu, Weiming

    2013-01-01

    Five new diketopiperazine derivatives, (3Z,6E)-1-N-methyl-3-benzylidene-6-(2S-methyl-3-hydroxypropylidene)piperazine-2,5-dione (1), (3Z,6E)-1-N-methyl-3-benzylidene-6-(2R-methyl-3-hydroxypropylidene)piperazine-2,5-dione (2), (3Z,6Z)-3-(4-hydroxybenzylidene)-6-isobutylidenepiperazine-2,5-dione (3), (3Z,6Z)-3-((1H-imidazol-5-yl)-methylene)-6-isobutylidenepiperazine-2,5-dione (4), and (3Z,6S)-3-benzylidene-6-(2S-but-2-yl)piperazine-2,5-dione (5), were isolated from the marine-derived actinomycete Streptomyces sp. FXJ7.328. The structures of 15 were determined by spectroscopic analysis, CD exciton chirality, the modified Moshers, Marfeys and the C3 Marfeys methods. Compound 3 showed modest antivirus activity against influenza A (H1N1) virus with an IC50 value of 41.5 4.5 ?M. In addition, compound 6 and 7 displayed potent anti-H1N1 activity with IC50 value of 28.9 2.2 and 6.8 1.5 ?M, respectively. Due to the lack of corresponding data in the literature, the 13C NMR data of (3Z,6S)-3-benzylidene-6-isobutylpiperazine-2,5-dione (6) were also reported here for the first time. PMID:23538868

  6. Caenorhabditis elegans Neuromuscular Junction: GABA Receptors and Ivermectin Action

    PubMed Central

    Hernando, Guillermina; Bouzat, Cecilia

    2014-01-01

    The prevalence of human and animal helminth infections remains staggeringly high, thus urging the need for concerted efforts towards this area of research. GABA receptors, encoded by the unc-49 gene, mediate body muscle inhibition in Caenorhabditis elegans and parasitic nematodes and are targets of anthelmintic drugs. Thus, the characterization of nematode GABA receptors provides a foundation for rational anti-parasitic drug design. We therefore explored UNC-49 channels from C. elegans muscle cultured cells of the first larval stage at the electrophysiological and behavioral levels. Whole-cell recordings reveal that GABA, muscimol and the anthelmintic piperazine elicit macroscopic currents from UNC-49 receptors that decay in their sustained presence, indicating full desensitization. Single-channel recordings show that all drugs elicit openings of ∼2.5 pA (+100 mV), which appear either as brief isolated events or in short bursts. The comparison of the lowest concentration required for detectable channel opening, the frequency of openings and the amplitude of macroscopic currents suggest that piperazine is the least efficacious of the three drugs. Macroscopic and single-channel GABA-activated currents are profoundly and apparently irreversibly inhibited by ivermectin. To gain further insight into ivermectin action at C. elegans muscle, we analyzed its effect on single-channel activity of the levamisol-sensitive nicotinic receptor (L-AChR), the excitatory receptor involved in neuromuscular transmission. Ivermectin produces a profound inhibition of the frequency of channel opening without significant changes in channel properties. By revealing that ivermectin inhibits C. elegans muscle GABA and L-AChR receptors, our study adds two receptors to the already known ivermectin targets, thus contributing to the elucidation of its pleiotropic effects. Behavioral assays in worms show that ivermectin potentiates piperazine-induced paralysis, thus suggesting that their combination is a good strategy to overcome the increasing resistance of parasites, an issue of global concern for human and animal health. PMID:24743647

  7. Solvent isotope effects on nucleophilic displacement reactions

    SciTech Connect

    Spiegel, G.W.

    1981-01-01

    The kinetic solvent isotope effect, KSIE, (k/sub H/sub 2/O//k/sub D/sub 2/O/), at 25.0/sup 0/C and ionic strength, I, equal to 0.20 +- 0.02 M was measured for the nucleophilic displacement of iodine ion from iodomethane, iodoacetamide, and iodoacetate ion, thiophene from S-Methylthiophenium ion, and tosylate ion from methyl tosylate by bromide ion, chloride ion, acetate ion, hydroxide ion, water, ammonia, ethylenediamine, n-butylamine, piperazine, piperidine, quinuclidine, and 1,4-Diazabicyclo(2.2.2)octane (DABCO), and the monoprotonated cations of ethylenediamine, piperazine, and DABCO. By means of solvent partition measurements at 25.0/sup 0/C and I = 0.02 M between H/sub 2/O and D/sub 2/O and a common immiscible organic solvent, the ground state activity coefficients in D/sub 2/O, the solution in H/sub 2/O being chosen as the reference state, were determined for the nitrogen-containing nucleophiles (except ammonia) and the substrates methyl tosylate, iodoacetamide, and iodoacetic acid. The solubilities at 25.0/sup 0/C of the picrate and tetraphenylborate salts of the monoprotonated cationic forms of ethylenediamine, piperazine, and DABCO were measured to determine the activity coefficients in D/sub 2/O of these ions relative to an H/sub 2/O reference state. Applying the Eyring equation, the activity coefficients of the transition states in D/sub 2/O, reference state H/sub 2/O, were calculated.

  8. Behavioral approach to nondyskinetic dopamine antagonists: identification of seroquel.

    PubMed

    Warawa, E J; Migler, B M; Ohnmacht, C J; Needles, A L; Gatos, G C; McLaren, F M; Nelson, C L; Kirkland, K M

    2001-02-01

    A great need exists for antipsychotic drugs which will not induce extrapyramidal symptoms (EPS) and tardive dyskinesias (TDs). These side effects are deemed to be a consequence of nonselective blockade of nigrostriatal and mesolimbic dopamine D2 receptors. Nondyskinetic clozapine (1) is a low-potency D2 dopamine receptor antagonist which appears to act selectively in the mesolimbic area. In this work dopamine antagonism was assessed in two mouse behavioral assays: antagonism of apomorphine-induced climbing and antagonism of apomorphine-induced disruption of swimming. The potential for the liability of dyskinesias was determined in haloperidol-sensitized Cebus monkeys. Initial examination of a few close cogeners of 1 enhanced confidence in the Cebus model as a predictor of dyskinetic potential. Considering dibenzazepines, 2 was not dyskinetic whereas 2a was dyskinetic. Among dibenzodiazepines, 1 did not induce dyskinesias whereas its N-2-(2-hydroxyethoxy)ethyl analogue 3 was dyskinetic. The emergence of such distinctions presented an opportunity. Thus, aromatic and N-substituted analogues of 6-(piperazin-1-yl)-11H-dibenz[b,e]azepines and 11-(piperazin-1-yl)dibenzo[b,f][1,4]thiazepines and -oxazepines were prepared and evaluated. 11-(4-[2-(2-Hydroxyethoxy)ethyl]piperazin-1-yl)dibenzo[b,f][1,4]thiazepine (23) was found to be an apomorphine antagonist comparable to clozapine. It was essentially nondyskinetic in the Cebus model. With 23 as a platform, a number of N-substituted analogues were found to be good apomorphine antagonists but all were dyskinetic. PMID:11462978

  9. Morphological Observation Of Enterobius Vermicularis Expelled By Various Anthelmintics.

    PubMed

    Cho, Seung Yull; Hong, Sung Tae; Kang, Shin Yong; Song, Chul Yong

    1981-08-01

    When enterobiasis cases were treated with anthelmintics only for one time, the interval to recurrence was variable by different drugs used. And this phenomenon is supposedly connected with biological or developmental cycle of the worm and the consequent efficacy of the different anthelmintics. This study was undertaken to confirm this fact by studying the expelled worms morphologically to correlate the anthelmintics efficacy and stage of worm development in Enterobius vermicularis. A total of 131 children in 3 orphanages was examined by 4 anal swabs (mean positive rate, 80%). They were randomized into 5 experimental groups. Each group was treated with placebo, mebendazole, pyrantel, pyrvinium, and piperazine (70 mg/kg, single dose) respectively. After treatment, all stool were collected for 3 days to get the expelled Enterobius. A total of 6,165 pinworms was studied under the microscope. The sex was discriminated and the length was individually measured. A number of male pinworms was collected in all groups. Females of 2~11 mm in length were also collected in 5 groups. However, significantly larger number of short females was observed in mebendazole group compared with other groups. Twenty-one days after the first treatment, all children were again treated with mebendazole. Once more stool were examined. A total of 1,853 worms was collected. In mebendazole group, there were no females longer than 8.74 mm in the second treatment. In pyrvinium group, 8.31mm in lenght was the longest for female. However in control, pyrantel and piperazine groups, females of 2~11 mm in length were collected. From above results, one could conclude that the removing ability of mebendazole and pyrvinium was satisfactory for the worms in the early stage of development in Enterobius. Pyrantel and single dose of piperazine showed less effective in worm reduction ability especially on those at the early stages. PMID:12902715

  10. SYNTHESIS AND IN VITRO ANTIPROLIFERATIVE ACTIVITY OF NOVEL 2-ARYLIDENEAMINOBENZIMIDAZOLE DERIVATIVES.

    PubMed

    Nowicka, Anna; Liszkiewicz, Hanna; Nawrocka, Wanda P; Wietrzyk, Joanna; Sadowska, Joanna

    2015-01-01

    A new class of Mannich bases 9-26, derivatives of 2-amino-1H-benzimidazole, were obtained in the condensation of Schiff bases 1-4 or 2-benzylaminobenzimidazoles 5-8 with selected secondary amines: morpholine, piperidine, N-methylpiperazine, N-phenylpiperazine, 1-(2-pyridyl)piperazine, 1(2-methoxyphenyl)piperazine, 1-(2-pyrimidinyl)piperazine and formaldehyde in ethanol. The pyrimido[1,2-albenzimidazole derivatives 27-29 have been synthesized in the reactions of Schiff base 2 with selected compounds containing active methylene group: acetylacetone, benzoylacetone and malononitrile. The structures 1-29 were confirmed by the results of elementary analysis and their IR, 1H- and 13C-NMR spectra. The products 1-29 are of interest for biological studies and can be substrates for further synthesis. All compounds were screened against the cells of MV4-11 human leukemia and then the most active of them 5, 7, 9-16, 24-26, 28, 29 were tested towards human T47D breast and A549 lung cancer cells as well as normal mouse fibroblasts (BALB/3T3). The most active compound against the cancer cell lines was 4-amino-3-cyano-2-(4-hydroxyphenylene)-1,2-dihydropyrimi-do[1,2-a]benzimidazole (29) (IC50 0.23 ± 0.05 µg/mL against MV4-11 cells) showing in parallel very low cytotoxicity towards mouse fibroblasts. Cisplatin was the control drug. PMID:26665403

  11. Identification of new diamine scaffolds with activity against Mycobacterium tuberculosis

    PubMed Central

    Bogatcheva, Elena; Hanrahan, Colleen; Nikonenko, Boris; Samala, Rowena; Chen, Ping; Gearhart, Jacqueline; Barbosa, Francis; Einck, Leo; Nacy, Carol A.; Protopopova, Marina

    2015-01-01

    A diverse 5,000-compound library was synthesized from commercially available diamines and screened for activity against Mycobacterium tuberculosis in vitro, revealing 143 hits with MIC equal to or less than 12.5 µM. New prospective scaffolds with antitubercular activity derived from homopiperazine, phenyl- and benzyl substituted piperazines, 4-aminomethylpiperidine, 4-aminophenylethylamine, 4,4'-methylenebiscyclohexylamine were identified. Compound SQ775 derived from homopiperazine, and compound SQ786 derived from benzylpiperazine had potent antimicrobial activity against M. tuberculosis in experimental animals in vivo. PMID:16722620

  12. CO2 CAPTURE BY ABSORPTION WITH POTASSIUM CARBONATE

    SciTech Connect

    Gary T. Rochelle; A. Frank Seibert

    2002-10-01

    The objective of this work is to improve the process for CO{sub 2} capture by alkanolamine absorption/stripping by developing an alternative solvent, aqueous K{sub 2}CO{sub 3} promoted by piperazine. Progress has been made in this reporting period on three subtasks. A simple thermodynamic model has been developed to represent the CO{sub 2} vapor pressure and speciation of the new solvent. A rate model has been formulated to predict the CO{sub 2} flux with these solutions under absorber conditions. A process and instrumentation diagram and process flow diagram have been prepared for modifications of the existing pilot plant system.

  13. Pharmacophore-based discovery of FXR agonists. Part I: Model development and experimental validation

    PubMed Central

    Schuster, Daniela; Markt, Patrick; Grienke, Ulrike; Mihaly-Bison, Judit; Binder, Markus; Noha, Stefan M.; Rollinger, Judith M.; Stuppner, Hermann; Bochkov, Valery N.; Wolber, Gerhard

    2011-01-01

    The farnesoid X receptor (FXR) is involved in glucose and lipid metabolism regulation, which makes it an attractive target for the metabolic syndrome, dyslipidemia, atherosclerosis, and type 2 diabetes. In order to find novel FXR agonists, a structure-based pharmacophore model collection was developed and theoretically evaluated against virtual databases including the ChEMBL database. The most suitable models were used to screen the National Cancer Institute (NCI) database. Biological evaluation of virtual hits led to the discovery of a novel FXR agonist with a piperazine scaffold (compound 19) that shows comparable activity as the endogenous FXR agonist chenodeoxycholic acid (CDCA, compound 2). PMID:22018919

  14. A new diketopiperazine derivative from a deep sea-derived Streptomyces sp. SCSIO 04496.

    PubMed

    Luo, Minghe; Tang, Guiling; Ju, Jianhua; Lu, Laichun; Huang, Hongbo

    2016-01-01

    A new diketopiperazine (DKP) derivative, (6R,3Z)-3-benzylidene-6-isobutyl-1-methyl piperazine-2,5-dione (1), as well as five known DKPs 2-6 was isolated from a deep sea-derived Streptomyces sp. SCSIO 04496. The structure of 1 was elucidated using a combination of 1D and 2D NMR, HR-ESI-MS and chiral-phase HPLC techniques. Compounds 1-6 did not show cytotoxic activity at a concentration of 100 μM in bioactivity assay. PMID:26197797

  15. Selenium dioxide-mediated synthesis of α-ketoamides from arylglyoxals and secondary amines

    PubMed Central

    Shaw, Arthur Y.; Denning, Christine R.; Hulme, Christopher

    2012-01-01

    A facile and expeditious synthetic approach to α-ketoamides 3 is described. A series of α-ketoamides 3 was synthesized via reaction of selenium dioxide-mediated oxidative amidation between arylglyoxals 1 and secondary amines 2, and accelerated with microwave irradiation. Our findings indicate that constrained amines, such as piperazine and piperidine exhibit higher conversions for this transformation. This reaction was explored by synthesizing a series of α-ketoamides 3 from various arylglyoxals with cyclic and acyclic secondary amines. PMID:23180891

  16. Characterization of two cyclic metabolites of sitagliptin.

    PubMed

    Liu, David Q; Arison, Byron H; Stearns, Ralph A; Kim, Dooseop; Vincent, Stella H

    2007-04-01

    Two novel metabolites of the dipeptidyl peptidase inhibitor sitagliptin (MK-0431, (2R)-4-oxo-4-[3-(trifluoromethyl)-5,6-dihydro[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl]-1-(2,4,5-trifluorophenyl)-butan-2-amine), were identified after purification from dog urine. The metabolites (referred to as M2 and M5) were characterized by hydrogen/deuterium exchange tandem mass spectrometry and NMR spectroscopy nuclear Overhauser effect experiments as the cis and trans stereoisomers formed by cyclization of the primary amino group with the alpha carbon of the piperazine ring, following oxidative desaturation. PMID:17220240

  17. Stereoselective Synthesis of Saturated Heterocycles via Pd-Catalyzed Alkene Carboetherification and Carboamination Reactions

    PubMed Central

    Wolfe, John P.

    2009-01-01

    The development of Pd-catalyzed carboetherification and carboamination reactions between aryl/alkenyl halides and alkenes bearing pendant heteroatoms is described. These transformations effect the stereoselective construction of useful heterocycles such as tetrahydrofurans, pyrrolidines, imidazolidin-2-ones, isoxazolidines, and piperazines. The scope, limitations, and applications of these reactions are presented, and current stereochemical models are described. The mechanism of product formation, which involves an unusual intramolecular syn-insertion of an alkene into a Pd-Heteroatom bond is also discussed in detail. PMID:19183704

  18. Clinical trials with the new antitussive levodropropizine in adult bronchitic patients.

    PubMed

    Allegra, L; Bossi, R

    1988-08-01

    The results of 6 clinical trials involving a total of 174 patients are reported. Levodropropizine (S(-)-3-(4-phenyl-piperazin-1-yl)-propane-1,2-diol, DF 526) was compared in double-blind manner with placebo, morclofone and cloperastine. The antitussive activity and therapeutic efficacy of the drug were shown to be greater than those of placebo and morclofone and similar to those of cloperastine. Levodropropizine was effective in about 80% of patients; in responders, cough frequency was reduced by an average of 33-51%. Levodropropizine was generally well tolerated and mild side-effects were reported for only 3% of patients. PMID:3058135

  19. Antitussive properties of levodropropizine.

    PubMed

    Malandrino, S; Melillo, G; Bestetti, A; Borsa, M; Giuliani, P; Tonon, G C

    1988-08-01

    The antitussive activity of levodropropizine (S(-)-3-(4-phenyl-piperazin-1-yl)-propane-1,2-diol, DF 526), was evaluated in anaesthetized guinea-pigs and rabbits and in unanaesthetized guinea-pigs. Levodropropizine was shown to have good antitussive activity. Intravenously, it was 1/10 to 1/20 as active as codeine and comparable to dropropizine, from which it is derived, on mechanically and electrically induced coughing in rabbits and guinea-pigs. After oral administration to the guinea-pig the antitussive activity of levodropropizine was comparable with those of both dropropizine and codeine against coughing induced by irritant aerosols. PMID:3196407

  20. Beyond the Diketopiperazine Family with Alternatively Bridged Brevianamide F Analogues.

    PubMed

    Wauters, I; Goossens, H; Delbeke, E; Muylaert, K; Roman, B I; Van Hecke, K; Van Speybroeck, V; Stevens, C V

    2015-08-21

    A method for the preparation of 3,5-bridged piperazin-2-ones from a tryptophan-proline-based diketopiperazine is described using diphosgene to induce the ring closure. Density functional theory calculations were conducted to study the mechanism of this C-C bond formation. Several derivatives of the thus obtained α-chloroamine were synthesized by substitution of the chlorine atom using a range of O-, N-, S-, and C-nucleophiles. This novel class of brevianamide F analogues possess interesting breast cancer resistance protein inhibitory activity. PMID:26193166

  1. Synthesis of deuterium-labeled fluphenazine.

    PubMed

    Shetty, H U; Hawes, E M; Midha, K K

    1984-01-01

    The propylpiperazine side chain of fluphenazine has been labeled with two, four, and six deuterium atoms by lithium aluminum deuteride reduction of the appropriate ester or imide. The gamma-carbon of the propyl group was labeled with two deuterium atoms by reduction of 10- (2-methoxycarbonylethyl) -2-trifluoromethyl-10H-phenothiazine, while four deuterium atoms were incorporated into the piperazine ring by reduction of 10-[3-(3,5-dioxo-1-piperazinyl)propyl]-2-trifluoromethyl-10H-pheno thiazine. The latter reduction gave the d4-labeled N-deshydroxyethyl metabolite of fluphenazine. PMID:6694091

  2. Hydrogen bonded structures in organic amine oxalates

    NASA Astrophysics Data System (ADS)

    Vaidhyanathan, R.; Natarajan, S.; Rao, C. N. R.

    2002-05-01

    Oxalates of n-propylamine, n-butylamine, ethylenediamine, 1,4-butanediamine, piperazine, guanidine and 1,4-diazabicyclo[2,2,2]octane (DABCO) have been synthesized and characterized by single crystal X-ray diffraction and other techniques. The amine oxalates show different types of hydrogen bonded networks, linear hydrogen bonded chains characterizing the oxalates of the first five amines. Guanidinium oxalate has a sheet like structure while DABCO oxalate has dimeric hydrogen bonded rings. Hydrogen bonded structures of these oxalates are discussed in detail, besides relating their thermal stability to the strengths of the networks.

  3. Determination of aliphatic and alicyclic amines in water by gas and liquid chromatography after derivatization by chloroformates.

    PubMed

    Pietsch, J; Hampel, S; Schmidt, W; Brauch, H J; Worch, E

    1996-05-01

    Two new methods were developed for the analysis of aliphatic (n-propylamine, pentylamine, hexylamine, heptylamine, octylamine) and alicyclic (pyrrolidine, morpholine, piperidine, piperazine) amines in water samples after derivatization and liquid-liquid-extraction. The carbamate-derivatives formed were determined by GC/MS (trichloroethyl carbamates) as well as by HPLC/fluorescence detection (9-fluorenylmethyl carbamates) in a concentration range between 0.05 and 1.0 microg/l suitable for drinking water analysis. Applications to German rivers and sewage plants show that both new methods produce corresponding results in analysing aliphatic and alicyclic amines in surface waters as well as in waste water samples. PMID:15045442

  4. Bench-Scale Development of a Hybrid Membrane-Absorption CO{sub 2} Capture Process: Preliminary Cost Assessment

    SciTech Connect

    Freeman, Brice; Kniep, Jay; Pingjiao, Hao; Baker, Richard; Rochelle, Gary; Chen, Eric; Frailie, Peter; Ding, Junyuan; Zhang, Yue

    2014-03-31

    This report describes a study of capture costs for a hybrid membrane-absorption capture system based on Membrane Technology and Research, Inc. (MTR)’s low-pressure membrane contactors and the University of Texas at Austin’s 5 m piperazine (PZ) Advanced Flash Stripper (AFS; 5 m PZ AFS) based CO2 capture system. The report is submitted for NETL review, and may be superseded by a final topical report on this topic that will be submitted to satisfy the Task 2 report requirement of the current project (DE-FE0013118).

  5. Evaluation of phenylpiperazines as targeting agents for neuroblastoma.

    PubMed Central

    Babich, J. W.; Graham, W. A.; Fischman, A. J.

    1996-01-01

    The potential of radiolabelled phenylpiperazines as agents for the detection and therapy of tumours of neural crest origin was evaluated by in vitro pharmacological studies with human neuroblastoma cell lines [SK-N-SH and SK-N-BE(2C)], and in vivo by biodistribution measurements. The ability of phenylpiperazines: 4-phenyl-piperazine (PP), 1-carboxamidino-4-phenyl-piperazine (CAPP), [4-(3-chlorophenyl)-piperazine (mCPP), 4-(3-trifluoro methyl phenyl)-piperazine (TFMPP), and (1,1-dimethyl-4-phenyl)-piperazinium hydrochloride (DMPP) and chlorophenyl hydroxypiperidine [CP(OH)P], to inhibit MIBG uptake by neuroblastoma cells was determined by incubation with [125I]MIBG (0.1 microM) for 2 h in the presence of varying concentrations (10(-8)-10(-3) M) of ligand. For measuring uptake, cells were incubated with [125I]IPP (0.1 microM) and cell-associated radioactivity was measured at various times. Retention was studied by incubating cells in the presence of [125I]IPP (0.1 microM) for 2 h, followed by replacement with drug-free medium and determination of cell-bound radioactivity. Selectivity of [125I]IPP uptake was studied by inhibition studies with MIBG, DMI, 5HT and phenylpiperazines. The biodistribution of [125I]IPP was measured in normal rats at 0.083, 0.5, 1, 2 and 24 h (six animals per group). The IC50S (microM) for inhibition of [125I]MIBG uptake were: PP, 1.5; CPP, 2.5; CAPP, 2.5; DMPP, 5; CP(OH)P, 30 and TFMPP, 65. The rate of cellular uptake of [125I]IPP was greatest between 0 and 60 min and decreased after 60 min, similar to MIBG. After an initial rapid washout of approximately 50% of the radioactivity, retention remained constant for 3 h. The IC50S (microM) for inhibition of [125I]IPP uptake were: MIBG, 18-25; DMI, 0.6-1.5; 5HT, > 100; IPP, 1.8-2.5; CPP, 7.0-9.0 and TFMPP, > or = 20. The in vivo studies demonstrated a pattern of distribution similar to MIBG. The results demonstrate that phenylpiperazines display significant affinity for neuroblastoma with uptake and retention characteristics similar to MIBG. PMID:8826858

  6. Separation and determination of chlorophenylpiperazine isomers in confiscated pills by capillary electrophoresis.

    PubMed

    Siroká, Jitka; Polesel, Daniel N; Costa, Jose L; Lanaro, Rafael; Tavares, Marina F M; Polášek, Miroslav

    2013-10-01

    A simple capillary electrophoretic method with spectrophotometric UV detection at 236 nm has been developed for the selective separation and determination of 1-(2-chlorophenyl)piperazine (oCPP), 1-(3-chlorophenyl)piperazine (mCPP) and 1-(4-chlorophenyl)piperazine (pCPP) in confiscated pills. Several cyclodextrin derivatives were tested to compose the background electrolyte (BGE). The optimized BGE contained 20 mmol/L phosphoric acid adjusted to pH 2.5 with triethylamine and 10 mmol/L α-cyclodextrin, which provided acceptable resolution of analytes and candidate interferents in less than 15 min. The analyses were performed at constant voltage of 25 kV in 60 cm (effective length 50 cm; 50 μm i.d.) uncoated fused-silica capillary maintained at 25°C with sample injection at 4,826 Pa for 8s. Procaine at a concentration of 0.1mg/mL was used as internal standard (IS). Possible interference from other drugs such as amphetamine, methamphetamine, 3,4-methylenedioxyamphetamine, 3,4-methylenedioxymethamphetamine, 3,4-methylenedioxy-N-ethylamphetamine, 1-(3-trifluoromethylphenyl)piperazine and cocaine was also examined. The analytical curves were linear (R(2)=0.9994-0.9995) in the range of 10-200 μg/mL (for oCPP and mCPP) and 20-200 μg/mL for pCPP. Limits of detection (LODs) were 2.0 μg/mL (oCPP), 2.5μg/mL (mCPP) and 3.5 μg/mL (pCPP). Intraday precision at three concentration levels and six replicates of each level (10, 100, 200 μg/mL of each analyte; n=18) was evaluated for the corrected peak area ratio of analyte to IS and the migration times giving RSDs ≤ 4.9%. The accuracy was estimated for mCPP by a recovery test at the same three concentration levels and recoveries varied from 101.0 to 101.6%. The method has been successively applied to the analysis of 17 confiscated pills based mostly on mCPP. PMID:23831489

  7. Characterization of potent and selective antagonists at postsynaptic 5-HT1A receptors in a series of N4-substituted arylpiperazines.

    PubMed

    Peglion, J L; Canton, H; Bervoets, K; Audinot, V; Brocco, M; Gobert, A; Le Marouille-Girardon, S; Millan, M J

    1995-09-29

    Benzocycloalkyl and benzocycloalkenyl moities linked, directly or via an alkyl chain, to oxygen-bearing heteroarylpiperazines were synthesized, in an attempt to obtain potent and selective antagonists at postsynaptic 5-HT1A receptors. From the numerous arylpiperazines described in the literature, 1-(2,3-dihydro-1,4-benzodioxin-5-yl)piperazine (3a) was chosen as a model of an arylpiperazine in view of its selectivity for 5-HT1A receptors versus alpha 1-, alpha 2-, and beta-adrenergic receptors, as well as dopamine D1 and D2 receptors. Two other closely-related arylpiperazines, 1-(1,5-benzodioxepin-6-yl)piperazine (3b) and 1-(benzofuran-7-yl)piperazine (3c), were also examined in this study. All compounds showed high affinity at 5-HT1A sites (8.10 < or = pKis < or = 9.35), and the majority behaved as antagonists in vivo in blocking the hypothermia induced by the 5-HT1A agonist 8-OH-DPAT in the absence of a marked effect alone at equivalent doses. An in vivo evaluation of dopamine D2 receptor antagonist properties revealed that the majority of compounds was devoid of activity at this site, in marked contrast to BMY 7378 which displayed virtually no selectivity for 5-HT1A versus dopamine D2 receptors. Moreover, six compounds of the present series, 8, 10, 11, 14, 25, and 37, showed > 10-fold selectivity in vitro for 5-HT1A versus alpha 1-adrenergic receptors. Compound 14 displayed an optimal compromise between potency (pKi = 8.75), marked antagonist activity, and selectivity toward alpha 1-adrenergic (81-fold) and dopamine D2 (195-fold) receptors. These characteristics clearly distinguish 14 from previously-reported ligands such as the postsynaptic 5-HT1A antagonist BMY 7378 and the weak partial agonist NAN 190 which, in contrast to the compounds of this series, belong to the well-exemplified class of imido derivatives of (o-methoxyphenyl)piperazines. The availability of 14 (S 15535) should facilitate the further elucidation of the functional role and potential therapeutic significance of 5-HT1A receptors. PMID:7562940

  8. Discovery, Optimization, and Characterization of Novel Chlorcyclizine Derivatives for the Treatment of Hepatitis C Virus Infection.

    PubMed

    He, Shanshan; Xiao, Jingbo; Dulcey, Andrés E; Lin, Billy; Rolt, Adam; Hu, Zongyi; Hu, Xin; Wang, Amy Q; Xu, Xin; Southall, Noel; Ferrer, Marc; Zheng, Wei; Liang, T Jake; Marugan, Juan J

    2016-02-11

    Recently, we reported that chlorcyclizine (CCZ, Rac-2), an over-the-counter antihistamine piperazine drug, possesses in vitro and in vivo activity against hepatitis C virus. Here, we describe structure-activity relationship (SAR) efforts that resulted in the optimization of novel chlorcyclizine derivatives as anti-HCV agents. Several compounds exhibited EC50 values below 10 nM against HCV infection, cytotoxicity selectivity indices above 2000, and showed improved in vivo pharmacokinetic properties. The optimized molecules can serve as lead preclinical candidates for the treatment of hepatitis C virus infection and as probes to study hepatitis C virus pathogenesis and host-virus interaction. PMID:26599718

  9. CO2 CAPTURE BY ABSORPTION WITH POTASSIUM CARBONATE

    SciTech Connect

    Gary T. Rochelle; Eric Chen; J. Tim Cullinane; Marcus Hillard; Babatunde Oyenekan

    2003-10-31

    The objective of this work is to improve the process for CO{sub 2} capture by alkanolamine absorption/stripping by developing an alternative solvent, aqueous K{sub 2}CO{sub 3} promoted by piperazine. A rigorous thermodynamic model has been further developed with a standalone FORTRAN code to represent the CO{sub 2} vapor pressure and speciation of the new solvent. The welding work has initiated and will be completed for a revised startup of the pilot plant in February 2004.

  10. CO2 CAPTURE BY ABSORPTION WITH POTASSIUM CARBONATE

    SciTech Connect

    Gary T. Rochelle; Eric Chen; J. Tim Cullinane; Marcus Hilliard; Terraun Jones

    2003-04-01

    The objective of this work is to improve the process for CO{sub 2} capture by alkanolamine absorption/stripping by developing an alternative solvent, aqueous K{sub 2}CO{sub 3} promoted by piperazine. A rigorous thermodynamic model has been developed with a stand-alone FORTRAN code to represent the CO{sub 2} vapor pressure and speciation of the new solvent. Parameters have been developed for use of the electrolyte NRTL model in AspenPlus. Analytical methods have been developed using gas chromatography and ion chromatography. The heat exchangers for the pilot plant have been ordered.

  11. Synthesis of new praziquantel analogues: potential candidates for the treatment of schistosomiasis.

    PubMed

    Sadhu, Partha Sarathi; Kumar, Singam Naveen; Chandrasekharam, Malapaka; Pica-Mattoccia, Livia; Cioli, Donato; Rao, Vaidya Jayathirtha

    2012-01-15

    An efficient synthesis of antischistosomal drug praziquantel and analogues was achieved and the synthetic route designed was to afford structurally diverse analogues for better structure-activity relationship understanding. Total of nineteen PZQ analogues with structural variations at amide, piperazine and aromatic moieties have been synthesized and fully characterized. Among all the new analogues tested for antischistosomal activity, one dimethoxy tetrahydroisoquinoline analogue and two tetrahydro-?-carboline analogues exhibited moderate activity against adult Schistosoma mansoni. Tetrahydro-?-carboline analogues showed moderate activity whereas the presence of p-trifluoromethylbenzoyl and p-toluenesulphonyl moieties resulted in complete suppression of antischistosomal activity. PMID:22217873

  12. Discovery, Optimization, and Characterization of Novel Chlorcyclizine Derivatives for the Treatment of Hepatitis C Virus Infection

    PubMed Central

    2015-01-01

    Recently, we reported that chlorcyclizine (CCZ, Rac-2), an over-the-counter antihistamine piperazine drug, possesses in vitro and in vivo activity against hepatitis C virus. Here, we describe structure–activity relationship (SAR) efforts that resulted in the optimization of novel chlorcyclizine derivatives as anti-HCV agents. Several compounds exhibited EC50 values below 10 nM against HCV infection, cytotoxicity selectivity indices above 2000, and showed improved in vivo pharmacokinetic properties. The optimized molecules can serve as lead preclinical candidates for the treatment of hepatitis C virus infection and as probes to study hepatitis C virus pathogenesis and host–virus interaction. PMID:26599718

  13. Novel 5-HT2-like receptor mediates neurogenic relaxation of the guinea-pig proximal colon.

    PubMed

    Briejer, M R; Akkermans, L M; Lefebvre, R A; Schuurkes, J A

    1995-06-12

    The aim of the current investigation was to characterize the 5-HT receptors that mediate neurogenic relaxation of the guinea-pig proximal colon. After blockade of 5-HT2A, 5-HT3 and 5-HT4 receptor-mediated contractions, 5-hydroxytryptamine (5-HT) induced relaxations yielding a biphasic concentration-response curve. Other tryptamines were also agonists with the following rank order of potency: 5-HT > 5-carboxamidotryptamine = 5-methoxytryptamine > or = alpha-methyl-5-HT (partial agonist) > tryptamine (partial agonist). 5-Hydroxytryptophan, 2-methyl-5-HT and N-methyltryptamine were virtually inactive as agonists. The curve to 5-HT was not affected by pargyline, citalopram, phentolamine, or by the 5-HT4 receptor antagonists 2-methoxy-4-amino-5-chloro-benzoic acid 2-(diethylamino)ethyl ester (SDZ 205-557) and (1-butyl-4-piperidinylmethyl)-8-amino-7-chloro-1,4-benzodioxan+ ++-5-carboxylate (SB 204070). 8-Hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT), 5-methoxy-3[1,2,3,6-tetrahydroxypyridin-4-yl]-1H-indole (RU 24969), 2-(2,6-dimethoxyphenoxyethyl)aminomethyl-1,4-benzodioxane (WB 4101), 1-(3-chlorophenyl)piperazine (mCPP), 1-(m-trifluoromethylphenyl)-piperazine (TFMPP), flesinoxan, sumatriptan and 6-chloro-2-(piperazinyl)-pyrazine (MK212) were inactive as 5-HT receptor agonists. The first phase of the curve to 5-HT was inhibited by: metergoline (pA2 = 8.8 +/- 0.3, against 5-methoxytryptamine 9.3 +/- 0.3), methysergide (non-surmountable), methiothepin (non-surmountable), spiroxatrine (non-surmountable), MK212 (non-surmountable), mesulergine (7.8 +/- 0.3), mCPP (7.1 +/- 0.1), mianserin (7.0 +/- 0.4), ritanserin (8.9 +/- 0.2), rauwolscine (7.0 +/- 0.2), yohimbine (6.2 +/- 0.2), 1-(1-naphthyl)-piperazine (7.7 +/- 0.2) and RU 24969 (6.4 +/- 0.1), but not by 1-(2-methoxyphenyl)4-[4-(2-phthalimidobtyl]-piperazine (NAN-190), spiperone, sumatriptan, 8-OH-DPAT and flesinoxan. It is suggested that the 5-HT receptor under study could be considered an unknown 5-HT2-like receptor. PMID:7556392

  14. RGD mimetics containing phthalimidine fragment as novel ligands of fibrinogen receptor.

    PubMed

    Krysko, Andrei A; Samoylenko, Georgiy V; Polishchuk, Pavel G; Andronati, Sergei A; Kabanova, Tatyana A; Khristova, Tetiana M; Kuz'min, Victor E; Kabanov, Vladimir M; Krysko, Olga L; Varnek, Alexandre A; Grygorash, Ruslan Ya

    2011-10-01

    The novel RGD mimetics with phthalimidine central fragment were synthesized with the use of 4-piperidine-4-yl-butyric, 4-piperidine-4-yl-benzoic, 4-piperazine-4-yl-benzoic and 1,2,3,4-tetrahydroisoquinoline-7-carboxylic acids as surrogates of Arg motif. The synthesized compounds potently inhibited platelet aggregation in vitro and blocked FITC-Fg binding to α(IIb)β(3) integrin in a suspension of washed human platelets. The key α(IIb)β(3) protein-ligand interactions were determined in docking experiments. PMID:21852128

  15. N',2-diphenylquinoline-4-carbohydrazide based NK3 receptor antagonists II.

    PubMed

    Elliott, Jason M; Carling, Robert W; Chicchi, Gary G; Crawforth, James; Hutson, Peter H; Jones, A Brian; Kelly, Sarah; Marwood, Rose; Meneses-Lorente, Georgina; Mezzogori, Elena; Murray, Fraser; Rigby, Michael; Royo, Inmaculada; Russell, Michael G N; Shaw, Duncan; Sohal, Bindi; Tsao, Kwei Lan; Williams, Brian

    2006-11-15

    Introduction of selected amine containing side chains into the 3-position of N',2-diphenylquinoline-4-carbohydrazide based NK3 antagonists abolishes unwanted hPXR activation. Introduction of a fluorine at the 8-position is necessary to minimize unwanted hI(Kr) affinity and a piperazine N-tert-butyl group is necessary for metabolic stability. The lead compound (8m) occupies receptors within the CNS following oral dosing (Occ(90) 7 mg/kg po; plasma Occ(90) 0.4 microM) and has good selectivity and excellent PK properties. PMID:16950617

  16. Synthesis of novel 24-amino-25,26,27-trinorlanost-8-enes: cytotoxic and apoptotic potential in U937 cells.

    PubMed

    O'Keeffe, Roisin; Kenny, Olivia; Brunton, Nigel P; Hossain, Mohammad B; Rai, Dilip K; Jones, Peter W; O'Brien, Nora; Maguire, Anita R; Collins, Stuart G

    2015-05-01

    In the present study, the synthesis of a range of novel 24-amino-25,26,27-trinorlanost-8-ene derivatives including 24-piperadino-trinorlanost-8-enes, 24-piperazino-trinorlanost-8-enes, 24-morpholino-trinorlanost-8-enes, and 24-diethylamino-trinorlanost-8-enes is reported and their cytotoxic and apoptotic potential evaluated in U937 cell lines. Excellent IC₅₀ results for piperidine and 1-(2-hydroxyethyl)piperazine derivatives have been observed (IC₅₀ values of 1.9 μM and 2.7 μM in U937 cells, respectively). PMID:25800433

  17. Synthesis of deuterium-labeled fluphenazine

    SciTech Connect

    Shetty, H.U.; Hawes, E.M.; Midha, K.K.

    1984-01-01

    The propylpiperazine side chain of fluphenazine has been labeled with two, four, and six deuterium atoms by lithium aluminum deuteride reduction of the appropriate ester or imide. The gamma-carbon of the propyl group was labeled with two deuterium atoms by reduction of 10- (2-methoxycarbonylethyl) -2-trifluoromethyl-10H-phenothiazine, while four deuterium atoms were incorporated into the piperazine ring by reduction of 10-(3-(3,5-dioxo-1-piperazinyl)propyl)-2-trifluoromethyl-10H-pheno thiazine. The latter reduction gave the d4-labeled N-deshydroxyethyl metabolite of fluphenazine.

  18. Analysis of Ethanolamines: Validation of Semi-Volatile Analysis by HPLC-MS/MS by EPA Method MS888

    SciTech Connect

    Owens, J; Vu, A; Koester, C

    2008-10-08

    The Environmental Protection Agency's (EPA) Region 5 Chicago Regional Laboratory (CRL) developed a method titled 'Analysis of Diethanolamine, Triethanolamine, n-Methyldiethanolamine, and n-Ethyldiethanolamine in Water by Single Reaction Monitoring Liquid Chromatography/Tandem Mass Spectrometry (LC/MS/MS): EPA Method MS888'. This draft standard operating procedure (SOP) was distributed to multiple EPA laboratories and to Lawrence Livermore National Laboratory, which was tasked to serve as a reference laboratory for EPA's Environmental Reference Laboratory Network (ERLN) and to develop and validate analytical procedures. The primary objective of this study was to validate and verify the analytical procedures described in 'EPA Method MS888' for analysis of the listed ethanolamines in aqueous samples. The gathered data from this validation study will be used to: (1) demonstrate analytical method performance; (2) generate quality control acceptance criteria; and (3) revise the SOP to provide a validated method that would be available for use during a homeland security event. The data contained in this report will be compiled, by EPA CRL, with data generated by other EPA Regional laboratories so that performance metrics of 'EPA Method MS888' can be determined.

  19. Natural gas treatment: recent developments in desulphurization process

    SciTech Connect

    Not Available

    1980-03-13

    The discovery and utilization of sour gas requires removal of the sulfur compounds, for environmental reasons, to a rather low level. Removal of CO/sub 2/ is less important; a level of one to 2% is tolerated if the gas is sufficiently dry to prevent corrosion. Since the acidities of H/sub 2/S and CO/sub 2/ are similar, total removal is simpler and less expensive than selective desulfurization. Mercaptans require special treatment since they have no acid properties. The method using diethanolamine (DEA) is discussed in detail: it has been successful in over 30 plants, but improvements are still possible. Construction details depend on the quality of the feed gas, on corrosion and on working conditions. Several variations of the process are in use. The main problem still remaining is how to deal with the content of gas in methyl, ethyl and propyl mercaptan. Selective desulfurization has been tried with a new methyl-diethanolamine process. However, nonselective desulfurization is becoming more attractive if the CO/sub 2/ can be recovered, since there is demand for it in some secondary recovery processes.

  20. Gas separation using ion exchange membranes for producing hydrogen from synthesis gas. Quarterly report 22 covering the period October 1, 1991--December 31, 1991

    SciTech Connect

    Pellegrino, J.J.; Giarratano, P.J.

    1992-01-01

    The main goal of this project is to demonstrate the use of facilitated transport membranes to separate gases resulting from the formation of H{sub 2}, specifically C0{sub 2} and H{sub 2}S from CO and H{sub 2}. As part of this goal a field test is performed at a producing natural gas plant (Carter Creek Chevron Natural Gas Plant, Evanston, WY) to evaluate the performance and long term stability of candidate membranes. Laboratory work at the National Institute of Standard and Technology (NIST) leads and parallels the field tests. Through a series of tests in the WIST laboratory and at the Chevron/Carter Creek test rig, the investigators are establishing the apparent separation and productivity capabilities of polymer membranes imbibed with various solvents and chemical carriers. In some samples the membranes are also subjected to solvent-swelling heat treatment (gel-treatment). The polymer material is polyperfluorosufonic acid (PFSA-Nafion). The chemical carriers, e.g. methyldiethanolamine (EDA) and ethylenediamine (EDA) enhance the transport and selectivity of the membrane. They may be in solution with H{sub 2}0, glycerol, ethylene glycol, and n-methylpyrrolidone (NMP). Nafion 117 (NE117) is a commercial film, 200 microns thick, which is available from DuPont Co. A developmental polymer film, Nafion 111 (NE111) 30--40 microns thick was made available by the DuPont Co.

  1. Gas separation using ion exchange membranes for producing hydrogen from synthesis gas

    SciTech Connect

    Pellegrino, J.J.; Giarratano, P.J.

    1992-01-01

    The main goal of this project is to demonstrate the use of facilitated transport membranes to separate gases resulting from the formation of H{sub 2}, specifically C0{sub 2} and H{sub 2}S from CO and H{sub 2}. As part of this goal a field test is performed at a producing natural gas plant (Carter Creek Chevron Natural Gas Plant, Evanston, WY) to evaluate the performance and long term stability of candidate membranes. Laboratory work at the National Institute of Standard and Technology (NIST) leads and parallels the field tests. Through a series of tests in the WIST laboratory and at the Chevron/Carter Creek test rig, the investigators are establishing the apparent separation and productivity capabilities of polymer membranes imbibed with various solvents and chemical carriers. In some samples the membranes are also subjected to solvent-swelling heat treatment (gel-treatment). The polymer material is polyperfluorosufonic acid (PFSA-Nafion). The chemical carriers, e.g. methyldiethanolamine (EDA) and ethylenediamine (EDA) enhance the transport and selectivity of the membrane. They may be in solution with H{sub 2}0, glycerol, ethylene glycol, and n-methylpyrrolidone (NMP). Nafion 117 (NE117) is a commercial film, 200 microns thick, which is available from DuPont Co. A developmental polymer film, Nafion 111 (NE111) 30--40 microns thick was made available by the DuPont Co.

  2. Synthesis, structure and characterization of a helical seven-coordinated pyridine-2,6-dicarboxylate-bridged cadmium(II) complex.

    PubMed

    Sharif, Mahboubeh A; Najafi, Gholam Reza

    2013-01-01

    [Cd(C7H3NO4)(H2O)1.5]n or [Cd(2,6-pydc)(H2O)1.5]n, (1) (2,6-pydc = pyridine-2,6-dicarboxylate) was obtained from the reaction of pyridine-2,6-dicarboxylic acid and 4-hydroxypyridine-2,6-dicarboxylic acid with cadmium(II) nitrate tetrahydrate in the presence of piperazine and characterized by elemental analysis, IR spectra and X-ray single crystal diffraction. Complex (1) is a novel carboxylate-bridged one-dimensional pincer-shaped helical chain of cadmium(II) polymer. Each Cd atom is seven-coordinate and exhibits an approximately pentagonal-bipyramidal CdNO6 coordination geometry. The metal fragments are linked via the central four-membered Cd2O2 ring and the structural analysis showed that 4-hydroxypyridine-2,6-dicarboxylic acid and piperazine do not appear in the structure. PMID:23841343

  3. Crystal structures of vortioxetine and its methanol monosolvate

    PubMed Central

    Zhou, Xin-Bo; Gu, Jian-Ming; Sun, Meng-ying; Hu, Xiu-Rong; Wu, Su-Xiang

    2015-01-01

    Vortioxetine, C18H22N2S, (1), systematic name 1-{2-[(2,4-di­methyl­phen­yl)sulfan­yl]phen­yl}piperazine, a new drug used to treat patients with major depressive disorder, has been crystallized as the free base and its methanol monosolvate, C18H22N2S·CH3OH, (2). In both structures, the vortioxetine mol­ecules have similar conformations: in (1), the dihedral angle between the aromatic rings is 80.04 (16)° and in (2) it is 84.94 (13)°. The C—S—C bond angle in (1) is 102.76 (14)° and the corresponding angle in (2) is 103.41 (11)°. The piperazine ring adopts a chair conformation with the exocyclic N—C bond in a pseudo-equatorial orientation in both structures. No directional inter­actions beyond normal van der Waals contacts could be identified in the crystal of (1), whereas in (2), the vortioxetine and methanol mol­ecules are linked by N—H⋯O and O—H⋯N hydrogen bonds, generating [001] chains. PMID:26396746

  4. Synthesis of new 3-pyridinecarboxylates of potential vasodilation properties.

    PubMed

    Girgis, Adel S; Mishriky, Nawal; Farag, Ahmad M; El-Eraky, Wafaa I; Farag, Hanaa

    2008-09-01

    2-(alicyclic-amino)-4,6-diaryl-3-pyridinecarboxylates 5a-d were prepared via aromatic nucleophilic substitution reaction of secondary amines (piperidine or morpholine) with 2-bromo-3-pyridinecarboxylate derivatives 3a,b. The latters were obtained through bromination of 3-aryl-4-benzoyl-2-cyanobutyrates 2a and 2b, which were obtained from the base promoted addition of ethyl cyanoacetate to 2-propen-1-ones 1a and 1b, with bromine in glacial acetic acid. Reaction of 3 with piperazine hexahydrate in 2:1 molar ratio afforded 1,4-bis[(ethyl 4,6-diaryl-3-pyridinecarboxylate)-2-yl]piperazines 6a,b. Reaction of 3 with anilines in refluxing pyridine unexpectedly gave 2-(aryl-amino)-3-pyridinecarboxylates 8a-g and 2-amino-3-pyridinecarboxylates 9a and 9b. Vasodilation activity screening for the synthesized pyridinecarboxylates using isolated thoracic aortic rings' standard method of rats shows considerable properties. Compounds 5b, 5c, 6b and 8g reveal remarkable vasodilation potency (IC50, concentrations necessary for 50% reduction of maximal norepinephrine hydrochloride induced contracture) 0.175, 0.146, 0.229 and 0.233 mM, respectively. PMID:18241958

  5. Reinvestigation of hybrid organic-inorganic materials based on molybdate and piperazininum cations: Influence of the synthesis conditions on the chemical composition and characterizations of the photochromic properties

    SciTech Connect

    Coue, Violaine; Dessapt, Remi Bujoli-Doeuff, Martine; Evain, Michel; Jobic, Stephane

    2008-05-15

    The reactivity of the [Mo{sub 7}O{sub 24}]{sup 6-} anion towards the structure directing-reagent piperazine (pipz) has been investigated and new synthetic routes to achieve the known (H{sub 2}pipz){sub 3}[Mo{sub 8}O{sub 27}] 1, (H{sub 2}pipz)[Mo{sub 3}O{sub 10}].H{sub 2}O 2, and (H{sub 2}pipz)[Mo{sub 5}O{sub 16}] 3 molybdenum(VI) containing compounds are proposed. The role of the pH on the stabilization of the different compounds and their interconversion pathways is discussed. Compounds 1 and 2 show photochromic behavior under UV excitation, related to the particular organization of the organic component around the mineral framework. Their optical properties are reported and commented. - Graphical abstract: Three organic-inorganic hybrid materials have been prepared from the investigations of the [Mo{sub 7}O{sub 24}]{sup 6-}/piperazine system in hydrothermal conditions. The role of the pH on the stabilization of the different polyoxomolybdate blocks in the materials i.e. 1/({infinity}) [Mo{sub 3}O{sub 10}]{sup 2-} and 1/({infinity}) [Mo{sub 8}O{sub 27}]{sup 6-} chains and 2/({infinity}) [Mo{sub 5}O{sub 16}]{sup 2-} layer has been investigated.

  6. Cr(III), Fe(III) and Co(III) complexes of tetradentate (ONNO) Schiff base ligands: synthesis, characterization, properties and biological activity.

    PubMed

    Keskioğlu, Eren; Gündüzalp, Ayla Balaban; Cete, Servet; Hamurcu, Fatma; Erk, Birgül

    2008-08-01

    A series of metal complexes were synthesized from equimolar amounts of Schiff bases: 1,4-bis[3-(2-hydroxy-1-naphthaldimine)propyl]piperazine (bappnaf) and 1,8-bis[3-(2-hydroxy-1-naphthaldimine)-p-menthane (damnaf) with metal chlorides. All of synthesized compounds were characterized by elemental analyses, spectral (UV-vis, IR, (1)H-(13)C NMR, LC-MS) and thermal (TGA-DTA) methods, magnetic and conductance measurements. Schiff base complexes supposed in tetragonal geometry have the general formula [M(bappnaf or damnaf)]Cl.nH(2)O, where M=Cr(III), Co(III) and n=2, 3. But also Fe(III) complexes have octahedral geometry by the coordination of two water molecules and the formula is [Fe(bappnaf or damnaf)(H(2)O)(2)]Cl. The changes in the selected vibration bands in FT-IR indicate that Schiff bases behave as (ONNO) tetradentate ligands and coordinate to metal ions from two phenolic oxygen atoms and two azomethine nitrogen atoms. Conductance measurements suggest 1:1 electrolytic nature of the metal complexes. The synthesized compounds except bappnaf ligand have the antimicrobial activity against the bacteria: Escherichia coli (ATCC 11230), Yersinia enterocolitica (ATCC 1501), Bacillus magaterium (RSKK 5117), Bacillus subtilis (RSKK 244), Bacillus cereus (RSKK 863) and the fungi: Candida albicans (ATCC 10239). These results have been considerably interest in piperazine derivatives due to their significant applications in antimicrobial studies. PMID:17904895

  7. Synthesis, in vitro and in vivo pharmacological evaluation of serotoninergic ligands containing an isonicotinic nucleus.

    PubMed

    Fiorino, Ferdinando; Ciano, Antonio; Magli, Elisa; Severino, Beatrice; Corvino, Angela; Perissutti, Elisa; Frecentese, Francesco; Di Vaio, Paola; Izzo, Angelo A; Capasso, Raffaele; Massarelli, Paola; Nencini, Cristina; Rossi, Ilaria; Kędzierska, Ewa; Orzelska-Gòrka, Jolanta; Bielenica, Anna; Santagada, Vincenzo; Caliendo, Giuseppe

    2016-03-01

    Isonicotinamide derivatives, linked to an arylpiperazine moiety, were prepared and their affinity to 5-HT1A, 5-HT2A and 5-HT2C receptors were evaluated. The combination of structural elements (heterocyclic nucleus, alkyl chain and 4-substituted piperazine) known to play critical roles in affinity for serotoninergic receptors and the proper selection of substituents led to compounds with high specificity and affinity towards serotoninergic receptors. In binding studies, several molecules showed high affinity in nanomolar and subnanomolar range at 5-HT1A, 5-HT2A and 5-HT2C receptors and moderate or no affinity for other relevant receptors (D1, D2, α1 and α2). N-(3-(4-(bis(4-fluorophenyl)methyl)piperazin-1-yl)propyl)isonicotinamide (4s) with Ki = 0.130 nM, was the most active and selective derivative for the 5-HT1A receptor compared to other serotoninergic, dopaminergic and adrenergic receptors. Compound 4o, instead, showed 5-HT2A affinity values in subnamolar range. Moreover, the compounds having better affinity and selectivity binding profile towards 5-HT1A and 5-HT2A receptors were selected in order to be tested by in vitro and in vivo assays to determine their functional activity. PMID:26820556

  8. Determination of hexamethylene-based isocyanates in spray-painting operations. Part 1. Evaluation of a polyurethane foam sponge sampler.

    PubMed

    Rudzinski, W E; Yin, J; Norman, S H; Glaska, D A

    1998-10-01

    A polyurethane foam (PUF) sponge was mounted in a cassette sampler and evaluated as a sorbent for the collection of hexamethylene diisocyanate (HDI) monomer and HDI-based oligomers. Recovery studies indicated 112 +/- 34% average recovery of HDI monomer and 92 +/- 9% and 97 +/- 25% average recovery of HDI-based oligomers when using impregnated PUF sponges. The PUF sponge was also evaluated during actual spray-painting operations. In a series of side-by-side sampling events, an impinger filled with 1-(2-methoxyphenyl)piperazine (MOP) in toluene was compared directly with a cassette sampler containing a PUF sponge impregnated with MOP or 1-(9-anthracenylmethyl)piperazine (MAP) in dimethyl sulfoxide (DMSO). For the analysis of HDI-based oligomer, there is no significant difference (p < 0.05, n = 7) in the air concentration when sampling with either the PUF sponge cassette or the impinger. The results are significant because they indicate that a PUF sponge, which is more convenient than an impinger, may be used for the collection of HDI-based oligomer generated during spray-painting operations. PMID:10209893

  9. Quenching of singlet molecular oxygen ( sup 1. Delta. sub g O sub 2 ) in silica gel/cyclohexane heterogeneous systems. A direct time-resolved study

    SciTech Connect

    Iu, Kaikong; Thomas, J.K. )

    1990-04-25

    Direct time-resolved studies of singlet molecular oxygen ({sup 1}{Delta}{sub g}O{sub 2}) phosphorescence ({sup 3}{Sigma}{sub g} {sup {minus}}O{sub 2} ({nu} = 0) {l arrow} {sup 1}{Delta}{sub g}O{sub 2} ({nu} = 0); 1,270 nm) in heterogeneous silica gel/cyclohexane systems are presented. Singlet molecular oxygen ({sup 1}{Delta}{sub g}O{sub 2}) is created through a photosensitization process on silica gel surfaces. The experimental results show that the lifetimes of singlet molecular oxygen ({sup 1}{Delta}{sub g}O{sub 2}) in both porous and compressed fumed silica/gel cyclohexane systems are significantly less than that in liquid cyclohexane. The shortened singlet molecular oxygen lifetime is due mainly to quenching by adsorbed water and silanol groups on the silica gel surface. In addition, monoamines coadsorbed on the silica gel surface do not quench singlet molecular oxygen ({sup 1}{Delta}{sub g}O{sub 2}); however, diamines such as DABCO or piperazine maintain their quenching activity, but the quenching kinetics are not of the Stern-Volmer type. The singlet molecular oxygen lifetime increases on loading the porous silica gel/cyclohexane system with monoamine. Coadsorption of piperazine increases quenching of {sup 1}{Delta}{sub g} O{sub 2} by DABCO.

  10. Preparation of a cyanine-based fluorescent probe for highly selective detection of glutathione and its use in living cells and tissues of mice.

    PubMed

    Yin, Jun; Kwon, Younghee; Kim, Dabin; Lee, Dayoung; Kim, Gyoungmi; Hu, Ying; Ryu, Ji-Hwan; Yoon, Juyoung

    2015-11-01

    Glutathione (GSH) is a major endogenous antioxidant that has a central role in cellular defense against toxins and free radicals. This protocol describes the preparation of CPDSA, a cyanine-based near-infrared (NIR) fluorescent probe for the detection of GSH in cells and in vivo. CPDSA is prepared with high yield through a simple two-step process. The first step is to react commercially available IR-780 iodide with excess anhydrous piperazine in anhydrous N,N-dimethyl formamide at 85 °C to form cyanine-piperazine (CP). The second step is the sulfonylation of CP with dansyl chloride in anhydrous dichloromethane. CPDSA selectively detects GSH in cells, and it has been shown to not react with other biothiols such as cysteine (Cys) and homocysteine (Hcy). This probe can also be used to monitor the GSH level of mouse bone marrow-derived neutrophils (BMDNs). The preparation of probe CPDSA takes 2 d, and experiments in cells and mice take 12-13 d. PMID:26492135

  11. Affinity of An(VI) for N4-Tetradentate Donor Ligands: Complexation of the Actinyl(VI) Ions with N4-Tetradentate Ligands

    SciTech Connect

    Ogden, Mark; Sinkov, Sergey I.; Lumetta, Gregg J.; Nash, Kenneth L.

    2012-05-01

    In this report the affinity of four N4-tetradentate ligands that incorporate the 2- methylpyridyl functionality with hexavalent actinides (AnO2+2 ) has been investigated in methanol solution. The ligands studied include N,N*-bis(2-methylpyridyl)diaminoethane (BPMDAE), N,N-bis(2-methylpyridyl)-1,3-diaminopropane (BPMDAP), N,N*-bis(2-pyridylmethyl) piperazine (BPMPIP), and trans-N,N-bis(2-pyridylmethyl)-1,2-diaminocyclohexane (BPMDAC). Conditional stability constants describing the strength of the interaction were determined by UV-visible spectrophotometry. The log10K101 values for both U(VI) and Pu(VI) are comparable and show the same trend of stability with ligand structure. Dinuclear complexes are also indicated as being important. The log10K201 values for Pu(VI) complexation with the N4-ligands are identical for the four ligands (within experimental error), indicating that the structure of the ligand backbone has little effect on the stability of the (PuO2)2L2+ complex. The exception to this trend is the behavior of N,N*- bis(2-pyridylmethyl)piperazine (BPMPIP) with Pu(VI). This ligand displays a tendency to reduce Pu(VI) within the experimental time frame of 45 minutes. BPMPIP is the only ligand tested that contains tertiary amines in the ligand backbone. The decomposition of BPMPIP by Pu(VI) suggests a susceptibility of tertiary amines to oxidative degradation.

  12. Synthesis of mononuclear copper(II) complexes of acyclic Schiff's base ligands: Spectral, structural, electrochemical, antibacterial, DNA binding and cleavage activity

    NASA Astrophysics Data System (ADS)

    Jayamani, Arumugam; Thamilarasan, Vijayan; Sengottuvelan, Nallathambi; Manisankar, Paramasivam; Kang, Sung Kwon; Kim, Young-Inn; Ganesan, Vengatesan

    2014-03-01

    The mononuclear copper(II) complexes (1&2) of ligands L1 [N,N";-bis(2-hydroxy-5-methylbenzyl)-1,4-bis(3-iminopropyl)piperazine] or L2 [N,N";-bis(2-hydroxy-5-bromobenzyl)-1,4-bis(3-iminopropyl) piperazine] have been synthesized and characterised. The single crystal X-ray study had shown that ligands L1 and L2 crystallize in a monoclinic crystal system with P21/c space group. The mononuclear copper(II) complexes show one quasireversible cyclic voltammetric response near cathodic region (-0.77 to -0.85 V) in DMF assignable to the Cu(II)/Cu(I) couple. Binding interaction of the complexes with calf thymus DNA (CT DNA) investigated by absorption studies and fluorescence spectral studies show good binding affinity to CT DNA, which imply both the copper(II) complexes can strongly interact with DNA efficiently. The copper(II) complexes showed efficient oxidative cleavage of plasmid pBR322 DNA in the presence of 3-mercaptopropionic acid as reducing agent through a mechanistic pathway involving formation of singlet oxygen as the reactive species. The Schiff bases and their Cu(II) complexes have been screened for antibacterial activities which indicates that the complexes exhibited higher antimicrobial activity than the free ligands.

  13. Visualization and characterization of interfacial polymerization layer formation.

    PubMed

    Zhang, Yali; Benes, Nieck E; Lammertink, Rob G H

    2015-01-21

    We present a microfluidic platform to visualize the formation of free-standing films by interfacial polymerization. A microfluidic device is fabricated, with an array of micropillars to stabilize an aqueous-organic interface that allows a direct observation of the films formation process via optical microscopy. Three different amines are selected to react with trimesoyl chloride: piperazine, JEFFAMINE(®)D-230, and an ammonium functionalized polyhedral oligomeric silsesquioxane. Tracking the formation of the free-standing films in time reveals strong effects of the characteristics of the amine precursor on the morphological evolution of the films. Piperazine exhibits a rapid reaction with trimesoyl chloride, forming a film up to 20 μm thick within half a minute. JEFFAMINE(®)D-230 displays much slower film formation kinetics. The location of the polymerization reaction was initially in the aqueous phase and then shifted into the organic phase. Our in situ real-time observations provide information on the kinetics and the changing location of the polymerization. This provides insights with important implications for fine-tuning of interfacial polymerizations for various applications. PMID:25421971

  14. Dissection of N,N-diethyl-N'-phenylpiperazines as α7 nicotinic receptor silent agonists.

    PubMed

    Quadri, Marta; Papke, Roger L; Horenstein, Nicole A

    2016-01-15

    The α7 nicotinic acetylcholine receptor (nAChR) is a target for control of inflammation-related phenomena via compounds that are able to selectively induce desensitized states of the receptor. Compounds that selectively desensitize, without facilitating significant channel activation, are termed 'silent agonists' because they can be discriminated from antagonists by the currents evoked with co-application with type II positive allosteric modulators (PAMs). One example is N,N-diethyl-N'-phenyl-piperazine (diEPP) (J. Pharm. Exp. Ther.2014, 350, 665). We used Ullmann-type aryl amination to synthesize a panel of 27 compounds related to diEPP by substitutions at the aryl ring and in the linkage between the piperazine and phenyl rings. Two-electrode voltage clamping of the human α7 nAChR expressed in Xenopus oocytes revealed that it was possible to tune the behavior of compounds to show enhanced desensitization without corresponding partial agonist activity such that trifluoromethyl and carboxamide aryl substituents showed 33 to 46-fold larger PAM-dependent net-charge responses, indicating selective partitioning of the ligand receptor complexes into the desensitized state. PMID:26707847

  15. Selective naked-eye detection of Hg²⁺ through an efficient turn-on photoinduced electron transfer fluorescent probe and its real applications.

    PubMed

    Srivastava, Priyanka; Razi, Syed S; Ali, Rashid; Gupta, Ramesh C; Yadav, Suresh S; Narayan, Gopeshwar; Misra, Arvind

    2014-09-01

    A simple molecular fluorescent probe 5 has been designed and synthesized by appending anthracene and benzhydryl moieties through a piperazine bridge. The probe upon interaction with different metal ions showed high selectivity and sensitivity (2 ppb) for Hg(2+) through fluorescence "turn-on" response in HEPES buffer. The significant fluorescence enhancement (~10-fold) is attributable to PET arrest due to complexation with nitrogen atoms of the piperazine unit and Hg(2+) in 1:2 stoichiometry, in which a naked-eye sensitive fluorescent blue color of solution changed to a blue-green (switched-on). As a proof of concept, promising prospects for application in environmental and biological sciences 5 have been utilized to detect Hg(2+) sensitively in real samples, on cellulose paper strips, in protein medium (like BSA), and intracellularly in HeLa cells. Moreover, the optical behavior of 5 upon providing different chemical inputs has been utilized to construct individual logic gates and a reusable combinational logic circuit. The combinational circuit (switch ON mode; OR logic gate) is easily resettable to the original position (switch OFF mode; INHIBIT logic gate) by applying reset chemical inputs (OH(-) and PO4(3-)) with great reproducibility. PMID:25098642

  16. Synthesis and characterization of selective dopamine D2 receptor ligands using aripiprazole as the lead compound

    PubMed Central

    Vangveravong, Suwanna; Zhang, Zhanbin; Taylor, Michelle; Bearden, Melissa; Xu, Jinbin; Cui, Jinquan; Wang, Wei; Luedtke, Robert R.; Mach, Robert H.

    2011-01-01

    A series of compounds structurally related to aripiprazole (1), an atypical antipsychotic and antidepressant used clinically for the treatment of schizophrenia, bipolar disorder, and depression, have been prepared and evaluated for affinity at D2-like dopamine receptors. These compounds also share structural elements with the classical D2-like dopamine receptor antagonists, haloperidol, N-methylspiperone, domperidone and benperidol. Two new compounds, 7-(4-(4-(2-methoxyphenyl)piperazin-1-yl)butoxy)-3,4-dihydroquinolin-2(1H)-one oxalate (6) and 7-(4-(4-(2-(2-fluoroethoxy)phenyl)piperazin-1-yl)butoxy)-3,4-dihydroquinolin-2(1H)-one oxalate (7) were found to (a) bind to the D2 receptor subtype with high affinity (Ki values <0.3 nM), (b) exhibit >50-fold D2 versus D3 receptor binding selectivity and (c) be partial agonists at both the D2 and D3 receptor subtype. PMID:21536445

  17. Cr(III), Fe(III) and Co(III) complexes of tetradentate (ONNO) Schiff base ligands: Synthesis, characterization, properties and biological activity

    NASA Astrophysics Data System (ADS)

    Keskioğlu, Eren; Gündüzalp, Ayla Balaban; Çete, Servet; Hamurcu, Fatma; Erk, Birgül

    2008-08-01

    A series of metal complexes were synthesized from equimolar amounts of Schiff bases: 1,4-bis[3-(2-hydroxy-1-naphthaldimine)propyl]piperazine (bappnaf) and 1,8-bis[3-(2-hydroxy-1-naphthaldimine)- p-menthane (damnaf) with metal chlorides. All of synthesized compounds were characterized by elemental analyses, spectral (UV-vis, IR, 1H- 13C NMR, LC-MS) and thermal (TGA-DTA) methods, magnetic and conductance measurements. Schiff base complexes supposed in tetragonal geometry have the general formula [M(bappnaf or damnaf)]Cl· nH 2O, where M = Cr(III), Co(III) and n = 2, 3. But also Fe(III) complexes have octahedral geometry by the coordination of two water molecules and the formula is [Fe(bappnaf or damnaf)(H 2O) 2]Cl. The changes in the selected vibration bands in FT-IR indicate that Schiff bases behave as (ONNO) tetradentate ligands and coordinate to metal ions from two phenolic oxygen atoms and two azomethine nitrogen atoms. Conductance measurements suggest 1:1 electrolytic nature of the metal complexes. The synthesized compounds except bappnaf ligand have the antimicrobial activity against the bacteria: Escherichia coli (ATCC 11230), Yersinia enterocolitica (ATCC 1501), Bacillus magaterium (RSKK 5117), Bacillus subtilis (RSKK 244), Bacillus cereus (RSKK 863) and the fungi: Candida albicans (ATCC 10239). These results have been considerably interest in piperazine derivatives due to their significant applications in antimicrobial studies.

  18. A unique dithiocarbamate chemistry during design & synthesis of novel sperm-immobilizing agents.

    PubMed

    Jangir, Santosh; Bala, Veenu; Lal, Nand; Kumar, Lalit; Sarswat, Amit; Kumar, Lokesh; Kushwaha, Bhavana; Singh, Pratiksha; Shukla, Praveen Kumar; Maikhuri, Jagdamba Prasad; Gupta, Gopal; Sharma, Vishnu Lal

    2014-05-21

    1-Substituted piperazinecarbodithioates were obtained by an unusual removal of CS2 in benzyl substituted dithiocarbamate derivatives under acid and basic conditions during design and synthesis of 1,4-(disubstituted)piperazinedicarbodithioates as double edged spermicides. A plausible mechanism for CS2 removal has been proposed. All synthesized compounds were subjected to spermicidal, antitrichomonal and antifungal activities. Twenty-one compounds irreversibly immobilized 100% sperm (MEC, 0.06-31.6 mM) while seven compounds exhibited multiple activities. Benzyl 4-(2-(piperidin-1-yl)ethyl) piperazine-1-(carbodithioate) (18) and 1-benzyl 4-(2-(piperidin-1-yl)ethyl)piperazine-1,4-bis(carbodithioate) (24) exhibited appreciable spermicidal (MEC, 0.07 and 0.06 mM), antifungal (MIC, 0.069-0.14 and >0.11 mM) and antitrichomonal (MIC, 1.38 and 0.14 mM) activities. The probable mode of action of these compounds seems to be through sulfhydryl binding which was confirmed by fluorescence labeling of sperm thiols. PMID:24705515

  19. Gene delivery efficiency and cytotoxicity of heterocyclic amine-modified PAMAM and PPI dendrimers.

    PubMed

    Hashemi, Maryam; Tabatabai, Seyed Meghdad; Parhiz, Hamideh; Milanizadeh, Soroush; Amel Farzad, Sara; Abnous, Khalil; Ramezani, Mohammad

    2016-04-01

    Poly-(amidoamine) (PAMAM) and poly-(propylenimine) (PPI) are the two most widely investigated dendrimers for drug and gene delivery. In order to enhance DNA transfection activity of these dendrimers, generation 3 and 4 PAMAM and generation 4 and 5 PPI were modified by partial substitution of surface primary amines with histidine, pyridine, and piperazine, which have buffering capacity properties. It was shown that higher dendrimer generations and higher grafting percentages (30% and 50% of primary amines) were associated with higher transfection activity. Pyridine was the most effective substituent for PPI, while piperazine-modified PAMAM dendrimers showed the best transfection efficiency among PAMAM-based vectors in murine neuroblastoma (Neuro-2a) cells. None of the modified carriers showed remarkable cytotoxicity in vitro. Pretreatment of cells with bafilomycin A indicated that endosomal buffering capacity is the main mechanism of endosomal escape. In conclusion, PAMAM and PPI may exhibit different gene delivery efficiency and cytotoxicity profiles with the same chemical modifications. These modified dendrimers could be considered as efficient and safe gene carriers in neuroblastoma cells in vitro. PMID:26838910

  20. Crystal structure of a new hybrid compound based on an iodido­plumbate(II) anionic motif

    PubMed Central

    Mokhnache, Oualid; Boughzala, Habib

    2016-01-01

    Crystals of the one-dimensional organic–inorganic lead iodide-based compound catena-poly[bis­(piperazine-1,4-diium) [[tetra­iodido­plumbate(II)]-μ-iodido] iodide monohydrate], (C4N2H12)2[PbI5]I·H2O, were obtained by slow evaporation at room temperature of a solution containing lead iodide and piperazine in a 1:2 molar ratio. Inorganic lead iodide chains, organic (C4N2H12)2+ cations, water mol­ecules of crystallization and isolated I− anions are connected through N—H⋯·I, N—H⋯OW and OW—H⋯I hydrogen-bond inter­actions. Zigzag chains of corner-sharing [PbI6]4− octa­hedra with composition [PbI4/1I2/2]3− running parallel to the a axis are present in the structure packing. PMID:26870585

  1. Synthesis of ciprofloxacin-conjugated poly (L-lactic acid) polymer for nanofiber fabrication and antibacterial evaluation

    PubMed Central

    Parwe, Sharad P; Chaudhari, Priti N; Mohite, Kavita K; Selukar, Balaji S; Nande, Smita S; Garnaik, Baijayantimala

    2014-01-01

    Ciprofloxacin was conjugated with polylactide (PLA) via the secondary amine group of the piperazine ring using PLA and 7-(4-(2-Chloroacetyl) piperazin-1-yl)-1-cyclopropyl-6-fluoro-1, 4-dihydro-4-oxoquinoline-3-carboxylic acid. Zinc prolinate, a biocompatible catalyst was synthesized, characterized, and used in ring opening polymerization of L-lactide. Five different kinds of OH-terminated poly(L-lactide) (two-, three-, four-, six-arm, star-shaped) homopolymers were synthesized by ring opening polymerization of L-lactide in the presence of dodecanol, glycerol, pentaerythritol, dipentaerythritol as initiator and zinc prolinate as a catalyst. The structures of the polymers and conjugates were thoroughly characterized by means of gel permeation chromatography, matrix-assisted laser desorption/ionization – time of flight mass spectrometry, and nuclear magnetic resonance spectroscopy. PLA (molecular weight =100,000) and ciprofloxacin conjugated PLA were used for fabrication of nonwoven nanofiber mat (diameter ranges; 150–400 nm) having pore size (62–102 nm) using electrospinning. The microbiological assessment shows that the release of ciprofloxacin possesses antimicrobial activity. The drug-release behavior of the mat was studied to reveal potential application as a drug delivery system. The result shows that the ciprofloxacin release rates of the PLA conjugate nonwoven nanofiber mat could be controlled by the drug loading content and the release medium. The development of a biodegradable ciprofloxacin system, based on nonwoven nanofiber mat, should be of great interest in drug delivery systems. PMID:24741303

  2. Chloroquine and chloroquinoline derivatives as models for the design of modulators of amyloid Peptide precursor metabolism.

    PubMed

    Melnyk, Patricia; Vingtdeux, Valrie; Burlet, Stphane; Eddarkaoui, Sabiha; Grosjean, Marie-Eve; Larchanch, Paul-Emmanuel; Hochart, Guillaume; Sergheraert, Christian; Estrella, Cecilia; Barrier, Mathieu; Poix, Virginie; Plancq, Pauline; Lannoo, Ccile; Hamdane, Malika; Delacourte, Andr; Verwaerde, Philippe; Bue, Luc; Sergeant, Nicolas

    2015-04-15

    The amyloid precursor protein (APP) plays a central role in Alzheimer's disease (AD). Preventing deregulated APP processing by inhibiting amyloidogenic processing of carboxy-terminal fragments (APP-CTFs), and reducing the toxic effect of amyloid beta (A?) peptides remain an effective therapeutic strategy. We report the design of piperazine-containing compounds derived from chloroquine structure and evaluation of their effects on APP metabolism and ability to modulate the processing of APP-CTF and the production of A? peptide. Compounds which retained alkaline properties and high affinity for acidic cell compartments were the most effective. The present study demonstrates that (1) the amino side chain of chloroquine can be efficiently substituted by a bis(alkylamino)piperazine chain, (2) the quinoline nucleus can be replaced by a benzyl or a benzimidazole moiety, and (3) pharmacomodulation of the chemical structure allows the redirection of APP metabolism toward a decrease of A? peptide release, and increased stability of APP-CTFs and amyloid intracellular fragment. Moreover, the benzimidazole compound 29 increases APP-CTFs in vivo and shows promising activity by the oral route. Together, this family of compounds retains a lysosomotropic activity which inhibits lysosome-related A? production, and is likely to be beneficial for therapeutic applications in AD. PMID:25611616

  3. Sweat testing in opioid users with a sweat patch.

    PubMed

    Kintz, P; Tracqui, A; Mangin, P; Edel, Y

    1996-10-01

    For many years, toxicologists have detected the presence of drugs of abuse in biological materials using blood or urine. In recent years, remarkable advances in sensitive analytical techniques have enabled the analysis of drugs in unconventional samples such as sweat. In a study conducted in a detoxification center, sweat patches were applied to 20 known heroin abusers. Subjects wore the patch with minimal discomfort for five days. During the same period, two urine specimens were also collected. Target drugs analyzed either by gas chromatography-mass spectrometry (GC-MS) or liquid chromatography-mass spectrometry (LC-MS) included opiates (heroin, 6-monoacetylmorphine, morphine, codeine), cocaine (cocaine, benzoylecgonine, ecgonine methyl ester), delta 9-tetrahydrocannabinol, benzodiazepines (nordiazepam, oxazepam), amphetamines (amphetamine, methamphetamine, methylenedioxyamphetamine [MDA], methylenedioxymethamphetamine [MDMA], methylenedioxyethylamphetamine [MDEA]), and buprenorphine. Patches were positive for opiates in 12 cases. Heroin (37-175 ng/patch) and/or 6-acetylmorphine (60-2386 ng/patch) were identified in eight cases, and codeine exposure (67-4018 ng/patch) was determined in four cases. When detected, heroin was always present in lower concentrations than 6-acetylmorphine, which was the major analyte found in sweat. Cocaine (324 ng/patch) and metabolites were found in only one case. delta 9-Tetrahydrocannabinol (4-38 ng/patch) was identified in nine cases. Benzodiazepine concentrations were very low, ranging from 2 to 44 and from 2 to 15 ng/patch for nordiazepam and oxazepam, respectively. MDEA (121 ng/patch) and its metabolite, MDA (22 ng/patch), were detected in one case. Buprenorphine, which was administered as therapy under close medical supervision, was detected in the range 1.3-153.2 ng/patch with no apparent relationship between the daily dose and amount excreted in sweat. All the urine tests were consistent with the sweat findings, but to identify the same drugs it was necessary to test two urine specimens along with only one sweat specimen. It was concluded that sweat testing appears to offer the advantage of being a relatively noninvasive means of obtaining a cumulative estimate of drug exposure over the period of a week. This new technology may find useful applications in the treatment and monitoring of substance abusers, as the patch provides a long-term continuous monitor of drug exposure or noncompliance. PMID:8889674

  4. Simultaneous determination of methamphetamine, 3,4-methylenedioxy-N-methylamphetamine, 3,4-methylenedioxy-N-ethylamphetamine, N,N-dimethylamphetamine, and their metabolites in urine by liquid chromatography-electrospray ionization-tandem mass spectrometry.

    PubMed

    Kim, Jin Young; Cheong, Jae Chul; Ko, Beom Jun; Lee, Sang Kyu; Yoo, Hye Hyun; Jin, Changbae; In, Moon Kyo

    2008-12-01

    A liquid chromatography-electrospray ionization-tandem mass spectrometric (LC-ESI-MS/MS) method was developed and validated for the simultaneous detection and quantification of seven amphetamine derivatives (amphetamine (AP), methamphetamine (MA), 3,4-methylenedioxy-N-amphetamine (MDA), 3,4-methylenedioxy-N-methamphetamine (MDMA), 3,4-methylenedioxy-N-ethylamphetamine (MDEA), N,N-dimethylamphetamine (DMA), and N,N-dimethylamphetamine-N-oxide (DMANO)) in human urine. Seven deuterium-labeled compounds were prepared for use as internal standards to quantify the analytes. One milliliter of urine was combined with 1 mL of 0.2 M sodium carbonate buffer solution (pH 9.0) before solid phase extraction (SPE). An Oasis HLB SPE column followed by chromatographic separation on a Capcell Pak C18 MG-II column (150 x 2.0 mm I.D., 5 microm) and electrospray mass spectrometry with multiple reaction monitoring were used for selective and sensitive detection. The use of ammonium formate (5 mM, pH adjusted to 4.0 with formic acid, Solvent A) and acetonitrile (Solvent B) as the mobile phase at a flow rate of 230 microL/min was found to be the most effective for the separation. The linear ranges were 5.0-1000 ng/mL for AP, MDA, MDMA, MDEA, DMA, and DMANO and 10.0-1000 ng/mL for MA, with good correlation coefficients (r2 > 0.996). The intra-day, inter-day, and interperson precisions were within 14.6%, 12.1% and 15.5%, respectively. The intra-day, inter-day, and interperson accuracies were between -11.6 and 9.0%, -7.9 and 2.3%, and -13.2 and 4.3%, respectively. The limits of detection (LODs) for each analytical compound were lower than 1.95 ng/mL. The recovery ranged from 72.3 to 103.3%. The applicability of the developed method was examined by analyzing several urine samples from confirmed drug abusers. PMID:19099236

  5. The role of CYP3A4 in amiodarone-associated toxicity on HepG2 cells.

    PubMed

    Zahno, Anja; Brecht, Karin; Morand, Réjane; Maseneni, Swarna; Török, Michael; Lindinger, Peter W; Krähenbühl, Stephan

    2011-02-01

    Amiodarone is a class III antiarrhythmic drug with potentially life-threatening hepatotoxicity. Recent in vitro investigations suggested that the mono-N-desethyl (MDEA) and di-N-desethyl (DDEA) metabolites may cause amiodarone's hepatotoxicity. Since cytochrome P450 (CYP) 3A4 is responsible for amiodarone N-deethylation, CYP3A4 induction may represent a risk factor. Our aim was therefore to investigate the role of CYP3A4 in amiodarone-associated hepatotoxicity. First, we showed that 50μM amiodarone is more toxic to primary human hepatocytes after CYP induction with rifampicin. Second, we overexpressed human CYP3A4 in HepG2 cells (HepG2 cells/CYP3A4) for studying the interaction between CYP3A4 and amiodarone in more detail. We also used HepG2 wild type cells (HepG2 cells/wt) co-incubated with human CYP3A4 supersomes for amiodarone activation (HepG2 cells/CYP3A4 supersomes). Amiodarone (10-50μM) was cytotoxic for HepG2 cells/CYP3A4 or HepG2 cells/CYP3A4 supersomes, but not for HepG2 cells/wt or less toxic for HepG2 cells/wt incubated with control supersomes without CYP3A4. Co-incubation with ketoconazole, attenuated cytotoxicity of amiodarone incubated with HepG2 cells/CYP3A4 or HepG2 cells/CYP3A4 supersomes. MDEA and DDEA were formed only in incubations containing HepG2 cells/CYP3A4 or HepG2 cells/CYP3A4 supersomes but not by HepG2 cells/wt or HepG2 cells/wt with control supersomes. Metabolized amiodarone triggered the production of reactive oxygen species, induced mitochondrial damage and cytochrome c release, and promoted apoptosis/necrosis in HepG2 cells/CYP3A4, but not HepG2 cells/wt. This study supports the hypothesis that a high CYP3A4 activity is a risk factor for amiodarone's hepatotoxicity. Since CYP3A4 inducers are used frequently and amiodarone-associated hepatotoxicity can be fatal, our observations may be clinically relevant. PMID:21070748

  6. Development of Fluorescent Polymerization-based Signal Amplification for Sensitive and Non-enzymatic Biodetection in Antibody Microarrays

    PubMed Central

    Avens, Heather J.; Bowman, Christopher N.

    2009-01-01

    Antibody microarrays are a critical tool for proteomics, requiring broad, highly sensitive detection of numerous low abundance biomarkers. Fluorescent polymerization-based amplification (FPBA) is presented as a novel, non-enzymatic signal amplification method that takes advantage of the chain-reaction nature of radical polymerization to achieve a highly amplified fluorescent response. A streptavidin-eosin conjugate localizes eosin photoinitiators for polymerization on the chip where biotinylated target protein is bound. The chip is contacted with acrylamide as a monomer, N-methyldiethanolamine as a coinitiator and yellow/green fluorescent nanoparticles (NPs) which, upon initiation, combine to form a macroscopically visible and highly fluorescent film. The rapid polymerization kinetics and the presence of cross-linker favor entrapment of the fluorescent NPs in the polymer, enabling highly sensitive fluorescent biodetection. This method is demonstrated as being appropriate for antibody microarrays and is compared to detection approaches which utilize streptavidin-FITC (SA-FITC) and streptavidin-labeled yellow/green NPs (SA-NPs). It is found that FPBA is able to detect 0.16 (+/− 0.01) biotin-antibody/µm2 (or 40 zeptomole surface-bound target molecules), while SA-FITC has a limit of detection of 31 (+/− 1) biotin-antibody/µm2 and SA-NPs fail to achieve any significant signal under the conditions evaluated here. Further, FPBA in conjunction with fluorescent stereomicroscopy yields equal or better sensitivity compared to fluorescent detection of SA-eosin using a much more costly microarray scanner. By facilitating highly sensitive detection, FPBA is expected to enable detection of low abundance antigens and also make possible a transition towards less expensive fluorescence detection instrumentation. PMID:19508906

  7. High throughput screening of CO2 solubility in aqueous monoamine solutions.

    PubMed

    Porcheron, Fabien; Gibert, Alexandre; Mougin, Pascal; Wender, Aurlie

    2011-03-15

    Post-combustion Carbon Capture and Storage technology (CCS) is viewed as an efficient solution to reduce CO(2) emissions of coal-fired power stations. In CCS, an aqueous amine solution is commonly used as a solvent to selectively capture CO(2) from the flue gas. However, this process generates additional costs, mostly from the reboiler heat duty required to release the carbon dioxide from the loaded solvent solution. In this work, we present thermodynamic results of CO(2) solubility in aqueous amine solutions from a 6-reactor High Throughput Screening (HTS) experimental device. This device is fully automated and designed to perform sequential injections of CO(2) within stirred-cell reactors containing the solvent solutions. The gas pressure within each reactor is monitored as a function of time, and the resulting transient pressure curves are transformed into CO(2) absorption isotherms. Solubility measurements are first performed on monoethanolamine, diethanolamine, and methyldiethanolamine aqueous solutions at T = 313.15 K. Experimental results are compared with existing data in the literature to validate the HTS device. In addition, a comprehensive thermodynamic model is used to represent CO(2) solubility variations in different classes of amine structures upon a wide range of thermodynamic conditions. This model is used to fit the experimental data and to calculate the cyclic capacity, which is a key parameter for CO(2) process design. Solubility measurements are then performed on a set of 50 monoamines and cyclic capacities are extracted using the thermodynamic model, to asses the potential of these molecules for CO(2) capture. PMID:21341690

  8. HPLC and MS/MS study of polar contaminants in a wetland adjoining a sour-gas plant

    SciTech Connect

    Dickson, L.C.; Headley, J.V.; Peru, K.; Spiegel, K.; Gandrass, J.

    1995-12-31

    An analytical methodology was developed for target analyses and broad spectrum characterization of polar contaminants such as nitrogenous and organosulfur compounds in wetlands using the complementary techniques of HPLC with electrochemical (EC) detection and tandem MS with probe and electrospray ionization. Tandem MS was well suited for the identification and quantification of mixtures of polar compounds in water samples and soil extracts, while HPLC-EC provided sensitive detection of compounds transparent to MS detection and conventional methods. The usefulness of the methodology is demonstrated by studying the removal of polar contaminants from a wetland in western Canada affected by releases of hydrocarbon-rich condensate and free product from an adjoining sour-gas plant. The concern is that the mobile water-soluble polar contaminants may not be as efficiently attenuated by volatilization or adsorption processes as the more hydrophobic hydrocarbons and that some of the polar toxic compounds may break through to contaminate groundwater and surface waters. Samples of groundwater, surface water, and aqueous soil extracts were analyzed to quantify levels of polar contaminants in the presence of high concentrations of hydrocarbons. The use of water extracts reduced the background interference from hydrocarbons and other non-polar compounds that were present in the soil samples. HPLC-EC was used to quantify the target compounds that included monoethanolamine, diethanolamine and methyldiethanolamine and sulfolane-derived compounds while tandem MS was used to identify related compounds and degradation products. Influent concentrations were in the ppm range and discharge concentrations were in the ppb range.

  9. Synthesis, structure and characterization of two new open-framework gallium phosphite-oxalates of varying dimensionality

    SciTech Connect

    Li, Caixia; Huang, Liangliang; Zhou, Mingdong; Xia, Jing; Ma, Hongwei; Zang, Shuliang; Wang, Li

    2013-12-15

    Using N, N-dimethyl-piperazine as structure directing agent, two new gallium phosphite-oxalates [Ga{sub 2}(HPO{sub 3}){sub 2}(H{sub 2}PO{sub 3}){sub 2}(C{sub 2}O{sub 4})](C{sub 6}N{sub 2}H{sub 16}) (I) and [Ga{sub 2}(HPO{sub 3}){sub 2}(H{sub 2}PO{sub 3})(C{sub 2}O{sub 4})](C{sub 6}N{sub 2}H{sub 16}){sub 0.5} (II) have been synthesized under solvothermal and hydrothermal conditions, respectively and further characterized by powder X-ray diffraction, IR spectroscopy, TGA, ICP-AES and elemental analyses. Single crystal X-ray diffraction reveals that the striking feature of I and II is that they possess the same second building unit (SBU) Ga{sub 2}P{sub 2} constructed from two GaO{sub 6} octahedra and two [HPO{sub 3}{sup 2−}] pseudo-pyramids sharing oxygen atoms. However, due to the different connecting fashions of SBUs, [C{sub 2}O{sub 4}{sup 2−}] groups and [H{sub 2}PO{sub 3}{sup −}] pseudo-pyramids, the final frameworks of them are distinctly different. Compound I shows 2D layered structures with 8-membered ring (8-MR) windows in the ab plane while compound II presents a 3D open-framework with 8-MR channels along the b axis. - Graphical abstract: Using N, N-dimethyl-piperazine as structure directing agent, two new gallium phosphite-oxalates I showing 2D layered structure and II presenting 3D open-framework have been synthesized under solvothermal and hydrothermal conditions, respectively. - Highlights: • Using N, N-dimethyl-piperazine as structure directing agent, two new gallium phosphite-oxalates have been synthesized under solvothermal and hydrothermal conditions, respectively. • The same second building unit (SBU) is displayed in both compounds. • Compound I shows 2D layered structure with 8-MR windows while compound II presents 3D open-framework with 8-MR channels. • The solvent plays an important role on the formation of microporous compounds.

  10. Photoaffinity labeling of the. cap alpha. /sub 1/-adrenergic receptor using an /sup 125/I-labeled aryl azide analogue of prazosin. [Rats

    SciTech Connect

    Seidman, C.E.; Hess, H.J.; Homcy, C.J.; Graham, R.M.

    1984-07-31

    ..cap alpha../sub 1/-Adrenergic receptor probes, which can be radioiodinated to yield high specific activity radioligands, have been synthesized and characterized. 2-(4-(4-Amino-benzoyl)piperazin-1-yl)-4-amino-6,7-dimethoxyquinazoline (CP63,155), an arylamine analogue of the selective ..cap alpha../sub 1/-adrenergic antagonist prazosin, and its iodinated derivative, 2-(4-(4-amino-3-(/sup 125/I)iodobenzoyl)piperazin-1-yl)-4-amino-6,7-dimethoxyquinazoline ((/sup 125/I)CP63,789), bind reversibly and with high affinity (K/sub D/ = 1 nM and 0.6 nM, respectively) to rat hepatic membrane ..cap alpha../sub 1/-adrenergic receptors. Conversion of (/sup 125/I)CP63,789 to the aryl azide yields a photolabile derivative, 2-(4-(4-azido-3-(/sup 125/I)iodobenzoyl)piperazin-1-yl)-4-amino-6,7-dimethoxyquinazoline ((/sup 125/I)CP65,526), which prior to photolysis binds competitively and with high affinity (K/sub D/ = 0.3 nM). Binding of (/sup 125/I)CP63,789 and (/sup 125/I)CP65,526 (prior to photolysis) is rapid and saturable. Both ligands identify similar ..cap alpha../sub 1/-adrenergic receptor binding site concentrations as the parent probe, (/sup 3/H)prazosin. Specific binding by these iodinated ligands is stereoselective and inhibited by a variety of adrenergic agents with a specificity typical of the ..cap alpha../sub 1/-adrenergic receptor. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and autoradiography of (/sup 125/I)CP65,526-labeled rat hepatic membranes reveal major protein species with molecular weights of 77K, 68K and 59K. Each protein binds adrenergic ligands with stereoselectivity and with a specificity typical of the ..cap alpha../sub 1/-adrenergic receptor. Smaller peptides with molecular weights of 42K and 31K display prazosin-inhibitable (/sup 125/I)CP65,526 binding. Labeling of these protein species with (/sup 125/I)CP65,526 is not inhibitable by other adrenergic agonists or antagonists. They are thus unlikely to represent subunits of the receptor.

  11. Molar heat capacity and molar excess enthalpy measurements in aqueous amine solutions

    NASA Astrophysics Data System (ADS)

    Poozesh, Saeed

    Experimental measurements of molar heat capacity and molar excess enthalpy for 1, 4-dimethyl piperazine (1, 4-DMPZ), 1-(2-hydroxyethyl) piperazine (1, 2-HEPZ), I-methyl piperazine (1-MPZ), 3-morpholinopropyl amine (3-MOPA), and 4-(2-hydroxy ethyl) morpholine (4, 2-HEMO) aqueous solutions were carried out in a C80 heat flow calorimeter over a range of temperatures from (298.15 to 353.15) K and for the entire range of the mole fractions. The estimated uncertainty in the measured values of the molar heat capacity and molar excess enthalpy was found to be +/- 2%. Among the five amines studied, 3-MOPA had the highest values of the molar heat capacity and 1-MPZ the lowest. Values of molar heat capacities of amines were dominated by --CH 2, --N, --OH, --O, --NH2 groups and increased with increasing temperature, and contributions of --NH and --CH 3 groups decreased with increasing temperature for these cyclic amines. Molar excess heat capacities were calculated from the measured molar heat capacities and were correlated as a function of the mole fractions employing the Redlich-Kister equation. The molar excess enthalpy values were also correlated as a function of the mole fractions employing the Redlich-Kister equation. Molar enthalpies at infinite dilution were derived. Molar excess enthalpy values were modeled using the solution theory models: NRTL (Non Random Two Liquid) and UNIQUAC (UNIversal QUAsi Chemical) and the modified UNIFAC (UNIversal quasi chemical Functional group Activity Coefficients - Dortmund). The modified UNIFAC was found to be the most accurate and reliable model for the representation and prediction of the molar excess enthalpy values. Among the five amines, the 1-MPZ + water system exhibited the highest values of molar excess enthalpy on the negative side. This study confirmed the conclusion made by Maham et al. (71) that -CH3 group contributed to higher molar excess enthalpies. The negative excess enthalpies were reduced due to the contribution of --O and --OH groups in 3-MOPA; 1, 2-HEPZ and 4, 2-HEMO. Conclusions made by Maham et al. (71 ) stating that the interaction between water (--OH group) and diethylamine (--NH group) was more dominant than the interactions between --OH groups from water and alcohol molecules were supported by this study for cyclic amines.

  12. Carbon dioxide but not bicarbonate inhibits N-nitrosation of secondary amines. Evidence for amine carbamates as protecting entities.

    PubMed

    Kirsch, M; Korth, H G; Sustmann, R; de Groot, H

    2000-06-01

    Hydrogen carbonate (bicarbonate, HCO(3)(-)) has been proposed to accelerate the decomposition of N(2)O(3) because N-nitrosation of morpholine via a nitric oxide/oxygen mixture ((*)NO/O(2)) was inhibited by the addition of HCO(3)(-) at pH 8.9 [Caulfield, J. L., Singh, S. P., Wishnok, J. S., Deen, W. M., and Tannenbaum, S. R. (1996) J. Biol. Chem. 271, 25859-25863]. In the study presented here, it is shown that carbon dioxide (CO(2)) is responsible for this kind of protective effect because of formation of amine carbamates, whereas an inhibitory function of HCO(3)(-) is excluded. N-Nitrosation of morpholine (1-10 mM) at pH 7.4-7.5 by the (*)NO-donor compounds PAPA NONOate and MAMA NONOate (0.5 mM each) was not affected by the presence of large amounts of HCO(3)(-) (up to 100 mM) in aerated aqueous solution. Similar results were obtained by replacing the (*)NO-donor compounds with authentic (*)NO (900 microM). In agreement with data from the study cited above, (*)NO/O(2)-mediated formation of N-nitrosomorpholine (NO-Mor) was indeed inhibited by about 45% in the presence of 50 mM HCO(3)(-) at pH 8.9. However, 500 MHz (13)C NMR analysis with (13)C-enriched bicarbonate revealed that significant amounts of morpholine carbamate are formed from reaction of equilibrated CO(2) with morpholine (1-100 mM) at pH 8.9, but only to a minor extent at pH 7. 5. The protective effect of morpholine carbamate formation is explained by a significantly reduced charge density at nitrogen. This view is supported by the results of density functional theory/natural population analysis, i.e., quantumchemical calculations for morpholine and morpholine carbamate. In agreement with its lower pK(a), another secondary amine, piperazine, had already produced significant amounts of piperazine carbamate at pH 7. 4 as shown by (13)C NMR spectrometry. Consequently, and in contrast to morpholine, N-nitrosation of piperazine (2 mM) by both (*)NO/O(2) (PAPA NONOate, 0.5 mM) and the (*)NO/O(2)(-)(*)-releasing compound SIN-1 (1 mM) was inhibited by about 66% in the presence of 200 mM HCO(3)(-). PMID:10858318

  13. The effects of non-medically used psychoactive drugs on monoamine neurotransmission in rat brain.

    PubMed

    Nagai, Fumiko; Nonaka, Ryouichi; Satoh Hisashi Kamimura, Kanako

    2007-03-22

    We developed a reproducible, simple, and small-scale method for determining the re-uptake and release of monoamines (dopamine, serotonin (5-HT) and norepinephrine) using rat brain synaptosomes. These assays were then applied to study the effects of different kinds of non-medically used psychoactive drugs on monoamine re-uptake and release. The phenethylamine derivatives, 4-fluoroamphetamine, 2-methylamino-3,4-methylene-dioxy-propiophenone (methylone), 1-(1,3-benzodioxol-5-yl)-2-butanamine (BDB), and N-methyl-1-(1,3-benzodioxol-5-yl)-2-butanamine (MBDB), had strong inhibitory effects on the re-uptake of dopamine, 5-HT and norepinephrine. 4-Fluoroamphetamine, methylone and BDB also strongly increased the release of the three monoamines, but MBDB increased 5-HT and norepinephrine release, but had little effect on dopamine release. However, 2,5-dimethoxy-4-iodophenethylamine (2C-I), 2,5-dimethoxy-4-ethylphenethylamine (2C-E), 2,5-dimethoxy-4-chlorophenethylamine (2C-C), 2,4,5-trimethoxyamphetamine (TMA-2) and 2,4,6-trimethoxyamphetamine (TMA-6), which are methoxylated phenethylamine derivatives, slightly influenced the re-uptake and release of monoamines. Alpha-metyltryptamine (AMT), a tryptamine derivative, was one of the strongest re-uptake inhibitors and releasers of the three monoamines. The tryptamine derivative, 5-methoxy-alpha-methyltryptamine (5-MeO-AMT), also strongly inhibited re-uptake and increased the release of the three monoamines. N,N-dipropyltryptamine (DPT), 5-methoxy-N,N-diisopropyltryptamine (5-MeO-DIPT), 5-methoxy-N,N-methylisopropyltryptamine (5-MeO-MIPT), and 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) inhibited monoamine re-uptake, but had a few effects on monoamine release. 1-(3-Chlorophenyl)piperazine (3CPP) and 1-(methoxyphenyl)piperazine (4MPP), which are piperazine derivatives, inhibited monoamine re-uptake and accelerated their release. The results suggest that some designer drugs strongly act on the central nerve system to the same extent as restricted drugs. PMID:17223101

  14. Detection of p-chloroamphetamine in urine samples with mass spectrometry.

    PubMed

    Lin, Tsz C; Lin, Dong-Liang; Lua, Ahai C

    2011-05-01

    Designer drugs are introduced periodically to avoid detection and to provide new drugs with different pharmacological activities. During our routine analysis of amphetamine in urine samples, we observed one sample that reacted with immunoassay with high activity. There is one prominent peak in the gas chromatography- mass spectrometry (GC-MS) chromatogram. However, no amphetamine, methamphetamine, MDA, MDMA, MDEA, or ephedrine was detected with GC-MS. Careful examination of the mass spectrum indicated the presence of one fragment ion (m/z 140), which is similar to the base peak of trifluoroacetic anhydride derivative of amphetamine. The characteristic ion cluster representing the presence of one chlorine atom was observed. Investigation with liquid chromatography (LC)-MS detected an unknown compound with molecular ion of m/z 170. This compound was tentatively identified as chloroamphetamine. Pure standard material of p-chloroamphetamine (PCA) was purchased and analyzed with both GC-MS and LC-MS. Identical GC-MS spectra and LC-MS-MS fragmentation patterns were obtained. A GC-MS procedure was developed for the quantitation of PCA. The limits of detection and quantification were 10 μg/L. Precision was between 1.26% and 4.26%, and bias was between -0.91% and 4.27%. The prevalence PCA positive rate is 0.35% of the samples screened positive for amphetamine. PMID:21513613

  15. Development of a method for the analysis of drugs of abuse in vitreous humor by capillary electrophoresis with diode array detection (CE-DAD).

    PubMed

    Costa, Jose Luiz; Morrone, Andre Ribeiro; Resende, Rodrigo Ribeiro; Chasin, Alice Aparecida da Matta; Tavares, Marina Franco Maggi

    2014-01-15

    This work presents the development of an analytical method based on capillary electrophoresis with diode array detection for the analysis of drugs of abuse and biotransformation products in vitreous humor. Composition of the background electrolyte, implementation of an online pre-concentration strategy and sample preparation procedures were objects of study. The complete electrophoretic separation of 12 analytes (amphetamine, methamphetamine, 3,4-methylenedioxyamphetamine (MDA), 3,4-methylenedioxymethamphetamine (MDMA), 3,4-methylenedioxyethylamphetamine (MDEA), ketamine, cocaine, cocaethylene, lidocaine, morphine, 6-monoacetylmorphine and heroin) and the internal standard N-methyl-1-(3,4-methylenedioxyphenyl)-2-butamine (MBDB) was obtained within 13min of run. The method was validated presenting good linearity (r(2)>0.99), recovery ≥90%, precision better than 12% RSD and acceptable accuracy in the range of 86-118% at three concentration levels (50, 100 and 500ng/mL). LODs and LOQs in the order of 1-5ng/mL and 5-10ng/mL, respectively, were obtained. After validation, the method was applied to eighty-seven vitreous humor samples and the results were compared to those obtained by a liquid chromatography tandem mass spectrometry (LC-MS/MS) screening method, routinely used by the forensic toxicology laboratory of the Sao Paulo State Police, Brazil. Cocaine was detected in 7.1%, cocaethylene in 3.6%, lidocaine in 2.4% and ketamine in 1.2% of the total number of analyzed samples. PMID:24325829

  16. Development and validation of a single LC-MS/MS assay following SPE for simultaneous hair analysis of amphetamines, opiates, cocaine and metabolites.

    PubMed

    Imbert, L; Dulaurent, S; Mercerolle, M; Morichon, J; Lachâtre, G; Gaulier, J-M

    2014-01-01

    The two major challenges in hair analysis are the limited amount of samples usually available and the low targeted concentrations. To overcome these limitations, a liquid chromatography-electrospray-tandem mass spectrometry method (LC-ESI-MS/MS) allowing the simultaneous analysis of 17 amphetamines (amphetamine, BDB, m-CPP, dexfenfluramine, DOB, DOM, ephedrine, MBDB, MDA, MDEA, MDMA, methamphetamine, methylphenidate, 4-MTA, norephedrine, norfenfluramine and PMA), 5 opiates (morphine, codeine, heroin, ethylmorphine, and 6AM), cocaine and 5 metabolites [ecgonine methyl ester (EME), benzoylecgonine (BZE), anhydroecgonine methyl ester (AME), cocaethylene, and norcocaine] has been developed. The validation procedure included linearity, intra-day and inter-day variability and accuracy for 5 days (5 replicates at 3 concentration levels). Proficiency studies were used to check the accuracy of the method. As a result, all amphetamines, opiates and cocaine derivatives were satisfactory identified by 2 MRM transitions in 15 min. Calibration curves were performed by a quadratic 1/X weighted regression. The calibration model fits from 0.05 to 10 ng/mg. The limits of detection (LODs) range between 0.005 and 0.030 ng/mg. Precision has been checked by intra-day and inter-day RSD, and associated relative bias, which were lower than 25% for the limits of quantifications (LOQs) and lower than 20% for the other levels tested. This method was routinely applied to hair samples: two positive results of adult drug addicts are presented. PMID:24378313

  17. Hybrid Membrane/Absorption Process for Post-combustion CO2 Capture

    SciTech Connect

    Li, Shiguang; Shou, S.; Pyrzynski, Travis; Makkuni, Ajay; Meyer, Howard

    2013-12-31

    This report summarizes scientific/technical progress made for bench-scale membrane contactor technology for post-combustion CO2 capture from DOE Contract No. DE-FE-0004787. Budget Period 1 (BP1) membrane absorber, Budget Period 2 (BP2) membrane desorber and Budget Period 3 (BP3) integrated system and field testing studies have been completed successfully and met or exceeded the technical targets (≥ 90% CO2 removal and CO2 purity of 97% in one membrane stage). Significant breakthroughs are summarized below: BP1 research: The feasibility of utilizing the poly (ether ether ketone), PEEK, based hollow fiber contractor (HFC) in combination with chemical solvents to separate and capture at least 90% of the CO2 from simulated flue gases has been successfully established. Excellent progress has been made as we have achieved the BP1 goal: ≥ 1,000 membrane intrinsic CO2 permeance, ≥ 90% CO2 removal in one stage, ≤ 2 psi gas side pressure drop, and ≥ 1 (sec)-1 mass transfer coefficient. Initial test results also show that the CO2 capture performance, using activated Methyl Diethanol Amine (aMDEA) solvent, was not affected by flue gas contaminants O2 (~3%), NO2 (66 ppmv), and SO2 (145 ppmv). BP2 research: The feasibility of utilizing the PEEK HFC for CO2-loaded solvent regeneration has been successfully established High CO2 stripping flux, one order of magnitude higher than CO2 absorption flux, have been achieved. Refined economic evaluation based on BP1 membrane absorber and BP2 membrane desorber laboratory test data indicate that the CO2 capture costs are 36% lower than DOE’s benchmark amine absorption technology. BP3 research: A bench-scale system utilizing a membrane absorber and desorber was integrated into a continuous CO2 capture process using contactors containing 10 to 20 ft2 of membrane area. The integrated process operation was stable through a 100-hour laboratory test, utilizing a simulated flue gas stream. Greater than 90% CO2 capture combined with 97% CO2 product purity was achieved throughout the test. Membrane contactor modules have been scaled from bench scale 2-inch diameter by 12-inch long (20 ft2 membrane surface area) modules to 4-inch diameter by 60-inch long pilot scale modules (165 ft2 membrane surface area). Pilot scale modules were tested in an integrated absorption/regeneration system for CO2 capture field tests at a coal-fired power plant (Midwest Generation’s Will County Station located in Romeoville, IL). Absorption and regeneration contactors were constructed utilizing high performance super-hydrophobic, nano-porous PEEK membranes with CO2 gas permeance of 2,000 GPU and a 1,000 GPU, respectively. Field tests using aMDEA solvent achieved greater than 90% CO2 removal in a single stage. The absorption mass transfer coefficient was 1.2 (sec)-1, exceeding the initial target of 1.0 (sec)-1. This mass transfer coefficient is over one order of magnitude greater than that of conventional gas/liquid contacting equipment. The economic evaluation based on field tests data indicates that the CO2 capture cost associated with membrane contactor technology is $54.69 (Yr 2011$)/tonne of CO2 captured when using aMDEA as a solvent. It is projected that the DOE’s 2025 cost goal of $40 (Yr 2011$)/tonne of CO2 captured can be met by decreasing membrane module cost and by utilizing advanced CO2 capture solvents. In the second stage of the field test, an advanced solvent, Hitachi’s H3-1 was utilized. The use of H3-1 solvent increased mass transfer coefficient by 17% as compared to aMDEA solvent. The high mass transfer coefficient of H3-1 solvent combined with much more favorable solvent regeneration requirements, indicate that the projected savings achievable with membrane contactor process can be further improved. H3-1 solvent will be used in the next pilot-scale development phase. The integrated absorption/regeneration process design and high performance membrane contactors developed in the current bench-scale program will be used as the base technology for future pilot-scale development.

  18. Screening determination of four amphetamine-type drugs in street-grade illegal tablets and urine samples by portable capillary electrophoresis with contactless conductivity detection.

    PubMed

    Nguyen, Thi Anh Huong; Pham, Thi Ngoc Mai; Ta, Thi Thao; Nguyen, Xuan Truong; Nguyen, Thi Lien; Le, Thi Hong Hao; Koenka, Israel Joel; Sáiz, Jorge; Hauser, Peter C; Mai, Thanh Duc

    2015-12-01

    A simple and inexpensive method for the identification of four substituted amphetamines, namely, 3,4-methylenedioxy methamphetamine (MDMA), methamphetamine (MA), 3,4-methylenedioxy amphetamine (MDA) and 3,4-methylenedioxy-N-ethylamphetamine (MDEA) was developed using an in-house constructed semi-automated portable capillary electrophoresis instrument (CE) with capacitively coupled contactless conductivity detection (C(4)D). Arginine 10mM adjusted to pH4.5 with acetic acid was found to be the optimal background electrolyte for the CE-C(4)D determination of these compounds. The best detection limits achieved with and without a sample preconcentration process were 10ppb and 500ppb, respectively. Substituted amphetamines were found in different seized illicit club drug tablets and urine samples collected from different suspected users. Good agreement between results from CE-C(4)D and those with the confirmation method (GC-MS) was achieved, with correlation coefficients for the two pairs of data of more than 0.99. PMID:26654084

  19. [Application of hair analysis of selected psychoactive substances for medico-legal purposes. Part I. Segmental hair analysis in cases of fatal opioids and amphetamines poisoning].

    PubMed

    Rojek, Sebastian; Kłys, Małgorzata; Konopka, Tomasz

    2009-01-01

    The present experimental investigations were inspired by the necessity of standardizing the procedures and analytical methods employed in hair analysis aiming at a retrospective evaluation of ingestion of various xenobiotics. Thus, in keeping with the principal premises, the main objective of the study was development of unique, novel chemico-toxicological procedures for analyzing hair content of psychoactive substances in two basic groups of substances of abuse: opioids (morphine, 6-monoacetylmorphine, codeine) and amphetamines (amphetamine, methamphetamine, MDA, MDMA, MDEA) by HPLC-APCI-MS-MS, followed by verification of the thus worked out procedures in medico-legal practice through opinionating in selected group of patients deceased due to fatal psychoactive substance poisoning (cause of death determination). Determinations of opioids and amphetamines in the hair biological matrix were performed using high performance liquid chromatography - atmospheric pressure chemical ionization - tandem mass spectrometry (HPLC-APCI-MS-MS). In the group of fatal poisonings by ,,Polish heroine", hair segmental analysis confirmed the abuse profile of the opiate or mixed (opiate-amphetamine) type, which to some measure is characteristic of Polish drug addiction, indicating the presence of these xenobiotics in the investigating hair samples in the premortem period. PMID:20860298

  20. Silver nanoflower-reduced graphene oxide composite based micro-disk electrode for insulin detection in serum.

    PubMed

    Yagati, Ajay Kumar; Choi, Yonghyun; Park, Jinsoo; Choi, Jeong-Woo; Jun, Hee-Sook; Cho, Sungbo

    2016-06-15

    Sensitive and selective determination of protein biomarkers remains a significant challenge due to the existence of various biomarkers in human body at a low concentration level. Therefore, new technologies were incessantly steered to detect tiny biomarkers at a low concentration level, yet, it is difficult to develop reliable, stable and sensitive detection methods for disease diagnostics. Therefore, the present study demonstrates a methodology to detect insulin in serum at low levels based on Ag nanoflower (AgNF) decorated reduced graphene oxide (rGO) modified micro-disk electrode arrays (MDEAs). The morphology of AgNF-rGO composite was characterized by scanning electron microscopy, the structure was analyzed using X-ray diffraction patterns and Raman spectra. The hybrid interface exhibited enhanced electrical conductivity when compared with its individual elements and had improved capturing ability for antibody-antigen binding towards insulin detection. In order to measure quantitatively the insulin concentration in PBS and human serum, the change in impedance (ΔZ) from electrochemical impedance spectroscopy was analyzed for various concentrations of insulin in [Fe(CN)6](3-/4-) redox couple. The electrode with adsorbed antibodies showed an increase in ΔZ for the addition of antigen concentrations over a working range of 1-1000ngmL(-1). The detection limits were 50 and 70pgmL(-1) in PBS and human serum, respectively. PMID:26852199