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Sample records for regioisomeric ring-substituted fluorophenethylamines

  1. Investigating the Activity Spectrum for Ring-Substituted 8-Hydroxyquinolines

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    Aidan Coffey

    2010-01-01

    Full Text Available In this study, a series of fourteen ring-substituted 8-hydroxyquinoline derivatives were prepared. The synthesis procedures are presented. The compounds were analyzed using RP-HPLC to determine lipophilicity. They were tested for their activity related to inhibition of photosynthetic electron transport (PET in spinach (Spinacia oleracea L. chloroplasts. Primary in vitro screening of the synthesized compounds was also performed against four mycobacterial strains and against eight fungal strains. Several compounds showed biological activity comparable with or higher than the standards isoniazid or fluconazole. For all the compounds, the relationships between the lipophilicity and the chemical structure of the studied compounds are discussed.

  2. Differentiation of ring-substituted regioisomers of amphetamine and methamphetamine by supercritical fluid chromatography.

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    Segawa, Hiroki; T Iwata, Yuko; Yamamuro, Tadashi; Kuwayama, Kenji; Tsujikawa, Kenji; Kanamori, Tatsuyuki; Inoue, Hiroyuki

    2017-03-01

    Chromatographic differentiation of the ring-substituted regioisomers of amphetamine (AMP) and methamphetamine (MA) was performed by supercritical fluid chromatography (SFC). The behaviour of the retention against the changes of column temperature and co-solvent proportion was studied. The obtained information facilitated the optimization of the each regioisomer. As a result, 2-, 3-, and 4-ring-substituted analogues of AMP and MA with methyl, methoxy, fluoro, chloro, and bromo groups were separated, generally within 6 min. In addition, we found that the separation pattern of the examined regioisomers was classified into two, which depended on the electron donating/withdrawing effect of the substituent. Our results indicate that SFC could be used in forensic drug analysis for fast, reliable identification of structurally similar drugs of abuse. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  3. Ring-substituted 4-Hydroxy-1H-quinolin-2-ones: Preparation and Biological Activity

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    Jiri Dohnal

    2009-03-01

    Full Text Available In the study, a series of twelve ring-substituted 4-hydroxy-1H-quinolin-2-one derivatives were prepared. The procedures for synthesis of the compounds are presented. The compounds were analyzed using RP-HPLC to determine lipophilicity and tested for their photosynthesis-inhibiting activity using spinach (Spinacia oleracea L. chloroplasts. All the synthesized compounds were also evaluated for antifungal activity using in vitro screening with eight fungal strains. For all the compounds, the relationships between the lipophilicity and the chemical structure of the studied compounds are discussed, as well as their structure-activity relationships (SAR.

  4. Profiling and Quantification of Regioisomeric Caffeoyl Glucoses in Berry Fruits.

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    Patras, Maria A; Jaiswal, Rakesh; McDougall, Gordon J; Kuhnert, Nikolai

    2018-02-07

    On the basis of a recently developed tandem mass spectrometry-based hierarchical scheme for the identification of regioisomeric caffeoyl glucoses, selected berry fruits were profiled for their caffeoyl glucose ester content. Fresh edible berries profiled, including strawberries, raspberries, blueberries, blackberries, red currant, black currant, lingonberries, gooseberries, and juices of elderberries, goji berries, chokeberries, cranberries, açai berries, sea buckthorn berries, Montmorency sour cherries, and pomegranates, were investigated. 1-Caffeoyl glucose was found to be the predominant isomer in the majority of samples, with further profiling revealing the presence of additional hydroxycinnamoyl glucose esters and O-glycosides with p-coumaroyl, feruloyl, and sinapoyl substituents. A quantitative liquid chromatography-mass spectrometry-based method was developed and validated, and all caffeoyl glucose isomers were quantified for the first time in edible berries.

  5. Investigating the Spectrum of Biological Activity of Ring-Substituted Salicylanilides and Carbamoylphenylcarbamates

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    Josef Jampilek

    2010-11-01

    Full Text Available In this study, a series of twelve ring-substituted salicylanilides and carbamoylphenylcarbamates were prepared and characterized. The compounds were analyzed using RP-HPLC to determine lipophilicity. They were tested for their activity related to the inhibition of photosynthetic electron transport (PET in spinach (Spinacia oleracea L. chloroplasts. Moreover, their site of action in the photosynthetic apparatus was determined. Primary in vitro screening of the synthesized compounds was also performed against mycobacterial, bacterial and fungal strains. Several compounds showed biological activity comparable with or higher than the standards 3-(3,4-dichlorophenyl-1,1-dimethylurea, isoniazid, penicillin G, ciprofloxacin or fluconazole. The most active compounds showed minimal anti-proliferative activity against human cells in culture, indicating they would have low cytotoxicity. For all compounds, the relationships between lipophilicity and the chemical structure are discussed.

  6. Antimycobacterial and Photosynthetic Electron Transport Inhibiting Activity of Ring-Substituted 4-Arylamino-7-Chloroquinolinium Chlorides

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    Alois Cizek

    2013-09-01

    Full Text Available In this study, a series of twenty-five ring-substituted 4-arylamino-7-chloroquinolinium chlorides were prepared and characterized. The compounds were tested for their activity related to inhibition of photosynthetic electron transport (PET in spinach (Spinacia oleracea L. chloroplasts and also primary in vitro screening of the synthesized compounds was performed against mycobacterial species. 4-[(2-Bromophenylamino]-7-chloroquinolinium chloride showed high biological activity against M. marinum, M. kansasii, M. smegmatis and 7-chloro-4-[(2-methylphenylamino]quinolinium chloride demonstrated noteworthy biological activity against M. smegmatis and M. avium subsp. paratuberculosis. The most effective compounds demonstrated quite low toxicity (LD50 > 20 μmol/L against the human monocytic leukemia THP-1 cell line within preliminary in vitro cytotoxicity screening. The tested compounds were found to inhibit PET in photosystem II. The PET-inhibiting activity expressed by IC50 value of the most active compound 7-chloro-4-[(3-trifluoromethylphenylamino]quinolinium chloride was 27 μmol/L and PET-inhibiting activity of ortho-substituted compounds was significantly lower than this of meta- and para-substituted ones. The structure-activity relationships are discussed for all compounds.

  7. Preparation and Biological Properties of Ring-Substituted Naphthalene-1-Carboxanilides

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    Tomas Gonec

    2014-07-01

    Full Text Available In this study, a series of twenty-two ring-substituted naphthalene-1-carboxanilides were prepared and characterized. Primary in vitro screening of the synthesized carboxanilides was performed against Mycobacterium avium subsp. paratuberculosis. N-(2-Methoxyphenylnaphthalene-1-carboxamide, N-(3-methoxy-phenylnaphthalene-1-carboxamide, N-(3-methylphenylnaphthalene-1-carboxamide, N-(4-methylphenylnaphthalene-1-carboxamide and N-(3-fluorophenylnaphthalene-1-carboxamide showed against M. avium subsp. paratuberculosis two-fold higher activity than rifampicin and three-fold higher activity than ciprofloxacin. The most effective antimycobacterial compounds demonstrated insignificant toxicity against the human monocytic leukemia THP-1 cell line. The testing of biological activity of the compounds was completed with the study of photosynthetic electron transport (PET inhibition in isolated spinach (Spinacia oleracea L. chloroplasts. The PET-inhibiting activity expressed by IC50 value of the most active compound N-[4-(trifluoromethylphenyl]naphthalene-1-carboxamide was 59 μmol/L. The structure-activity relationships are discussed.

  8. Antibacterial and Herbicidal Activity of Ring-Substituted 2-Hydroxynaphthalene-1-carboxanilides

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    Katarina Kralova

    2013-08-01

    Full Text Available In this study, a series of twenty-two ring-substituted 2-hydroxynaphthalene-1‑carboxanilides were prepared and characterized. Primary in vitro screening of the synthesized compounds was performed against Staphylococcus aureus, three methicillin-resistant S. aureus strains, Mycobacterium marinum, M. kasasii, M. smegmatis. and M. avium paratuberculosis. The compounds were also tested for their activity related to inhibition of photosynthetic electron transport (PET in spinach (Spinacia oleracea L. chloroplasts. 2-Hydroxy-N-phenylnaphthalene-1-carboxanilide and 2-hydroxy-N-(3-trifluoromethylphenylnaphthalene-1-carboxamide (IC50 = 29 µmol/L were the most active PET inhibitors. Some of tested compounds showed the antibacterial and antimycobacterial activity against the tested strains comparable or higher than the standards ampicillin or isoniazid. Thus, for example, 2-hydroxy-N-(3-nitrophenylnaphthalene-1-carboxamide showed MIC = 26.0 µmol/L against methicillin-resistant S. aureus and MIC = 51.9 µmol/L against M. marinum, or 2-hydroxy-N-phenylnaphthalene-1-carboxamide demonstrated MIC = 15.2 µmol/L against M. kansasii. The structure-activity relationships for all compounds are discussed.

  9. Antibacterial and Herbicidal Activity of Ring-Substituted 3-Hydroxynaphthalene-2-carboxanilides

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    Katarina Kralova

    2013-07-01

    Full Text Available In this study, a series of twenty-two ring-substituted 3-hydroxy-N-phenylnaphthalene-2-carboxanilides were prepared and characterized. The compounds were tested for their activity related to inhibition of photosynthetic electron transport (PET in spinach (Spinacia oleracea L. chloroplasts. Primary in vitro screening of the synthesized compounds was also performed against four Staphylococcus strains and against two mycobacterial species. 3-Hydroxy-N-(2-methoxyphenylnaphthalene-2-carboxamide showed high biological activity (MIC = 55.0 µmol/L against S. aureus as well as methicillin-resistant strains. N-(2-Fluorophenyl-3-hydroxynaphthalene-2-carboxamide showed higher activity (MIC = 28.4 µmol/L against M. marinum than the standard isoniazid and 3-hydroxy-N-(4-nitrophenylnaphthalene-2-carboxamide expressed higher activity (MIC = 13.0 µmol/L against M. kansasii than the standard isoniazid. Cytotoxicity assay of effective antimicrobial compounds was performed using the human monocytic leukemia THP-1 cell line. The PET-inhibiting activity expressed by IC50 value of the most active compound 3-hydroxy-N-(3-nitrophenylnaphthalene-2-carboxamide was 16.9 μmol/L. The structure-activity relationships of all compounds are discussed.

  10. Synthesis and reactivity ratios of regioisomeric vinyl-1,2,3-triazoles with styrene

    NARCIS (Netherlands)

    Lartey, M; Gillissen, M.A.J.; Adzima, B.J.; Takizawa, K.; Luebke, D.R.; Nulwala, H.B.

    2013-01-01

    The free radical reactivity ratios between styrene and different vinyl-1,2,3-triazole regioisomeric monomers in 1,4-dioxane at 65 degrees C have been established using nonlinear least square method. The results obtained for the reactivity ratio between regioisomers show exceptionally different

  11. Receptor binding profiles and behavioral pharmacology of ring-substituted N,N-diallyltryptamine analogs.

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    Klein, Landon M; Cozzi, Nicholas V; Daley, Paul F; Brandt, Simon D; Halberstadt, Adam L

    2018-02-27

    Substantial effort has been devoted toward understanding the psychopharmacological effects of tryptamine hallucinogens, which are thought to be mediated by activation of 5-HT 2A and 5-HT 1A receptors. Recently, several psychoactive tryptamines based on the N,N-diallyltryptamine (DALT) scaffold have been encountered as recreational drugs. Despite the apparent widespread use of DALT derivatives in humans, little is known about their pharmacological properties. We compared the binding affinities of DALT and its 2-phenyl-, 4-acetoxy-, 4-hydroxy-, 5-methoxy-, 5-methoxy-2-methyl-, 5-fluoro-, 5-fluoro-2-methyl-, 5-bromo-, and 7-ethyl-derivatives at 45 receptor and transporter binding sites. Additionally, studies in C57BL/6 J mice examined whether these substances induce the head twitch response (HTR), a 5-HT 2A receptor-mediated response that is widely used as a behavioral proxy for hallucinogen effects in humans. Most of the test drugs bound to serotonin receptors, σ sites, α 2 -adrenoceptors, dopaminergic D 3 receptors, histaminergic H 1 receptors, and the serotonin transporter. DALT and several of the ring-substituted derivatives were active in the HTR assay with the following rank order of potency: 4-acetoxy-DALT > 5-fluoro-DALT > 5-methoxy-DALT > 4-hydroxy-DALT > DALT > 5-bromo-DALT. 2-Phenyl-DALT, 5-methoxy-2-methyl-DALT, 5-fluoro-2-methyl-DALT, and 7-ethyl-DALT did not induce the HTR. HTR potency was not correlated with either 5-HT 1A or 5-HT 2A receptor binding affinity, but a multiple regression analysis indicated that 5-HT 2A and 5-HT 1A receptors make positive and negative contributions, respectively, to HTR potency (R 2  = 0.8729). In addition to supporting the established role of 5-HT 2A receptors in the HTR, these findings are consistent with evidence that 5-HT 1A activation by tryptamine hallucinogens buffers their effects on HTR. Published by Elsevier Ltd.

  12. Synthesis of water-soluble, ring-substituted squaraine dyes and their evaluation as fluorescent probes and labels

    Energy Technology Data Exchange (ETDEWEB)

    Tatarets, Anatoliy L. [SSI ' Institute for Single Crystals' of the National Academy of Sciences of Ukraine, 60 Lenin Ave., Kharkov 61001 (Ukraine); Fedyunyayeva, Irina A. [SSI ' Institute for Single Crystals' of the National Academy of Sciences of Ukraine, 60 Lenin Ave., Kharkov 61001 (Ukraine); Dyubko, Tatyana S. [SSI ' Institute for Single Crystals' of the National Academy of Sciences of Ukraine, 60 Lenin Ave., Kharkov 61001 (Ukraine); Povrozin, Yevgeniy A. [SSI ' Institute for Single Crystals' of the National Academy of Sciences of Ukraine, 60 Lenin Ave., Kharkov 61001 (Ukraine); Doroshenko, Andrey O. [Institute of Chemistry, V.N. Karazin National University, 4 Svobody Sq., Kharkov 61077 (Ukraine); Terpetschnig, Ewald A. [SETA BioMedicals, LLC, 2014 Silver Ct East, Urbana, IL 61801 (United States) and ISS, Inc., 1602 Newton Drive, Champaign, IL 61822 (United States)]. E-mail: ewaldte@juno.com; Patsenker, Leonid D. [SSI ' Institute for Single Crystals' of the National Academy of Sciences of Ukraine, 60 Lenin Ave., Kharkov 61001 (Ukraine); SETA BioMedicals, LLC, 2014 Silver Ct East, Urbana, IL 61801 (United States)

    2006-06-16

    A series of ring-substituted squaraines absorbing and emitting in the red and NIR spectral region was synthesized and their spectral and photophysical properties (quantum yields, fluorescence lifetimes) and photostabilities were measured and compared to Cy5, a commonly used fluorescent label. The absorption maxima in aqueous media were found to be between 628 and 667 nm and the emission maxima are between 642 and 685 nm. Squaraine dyes exhibit high extinction coefficients (163,000-265,000 M{sup -1} cm{sup -1}) and lower quantum yields (2-7%) in aqueous buffer but high quantum yields (up to 45%) and long fluorescence lifetimes (up to 3.3 ns) in presence of BSA. Dicyanomethylene- and thio-substituted squaraines exhibit an additional absorption around 400 nm with extinction coefficients between 21,500 and 44,500 M{sup -1} cm{sup -1}. These dyes are excitable not only with red but also with blue diode lasers or light emitting diodes. Due to the favourable spectral and photophysical properties these dyes can be used as fluorescent probes and labels for intensity- and fluorescence lifetime-based biomedical applications.

  13. Synthesis of water-soluble, ring-substituted squaraine dyes and their evaluation as fluorescent probes and labels

    International Nuclear Information System (INIS)

    Tatarets, Anatoliy L.; Fedyunyayeva, Irina A.; Dyubko, Tatyana S.; Povrozin, Yevgeniy A.; Doroshenko, Andrey O.; Terpetschnig, Ewald A.; Patsenker, Leonid D.

    2006-01-01

    A series of ring-substituted squaraines absorbing and emitting in the red and NIR spectral region was synthesized and their spectral and photophysical properties (quantum yields, fluorescence lifetimes) and photostabilities were measured and compared to Cy5, a commonly used fluorescent label. The absorption maxima in aqueous media were found to be between 628 and 667 nm and the emission maxima are between 642 and 685 nm. Squaraine dyes exhibit high extinction coefficients (163,000-265,000 M -1 cm -1 ) and lower quantum yields (2-7%) in aqueous buffer but high quantum yields (up to 45%) and long fluorescence lifetimes (up to 3.3 ns) in presence of BSA. Dicyanomethylene- and thio-substituted squaraines exhibit an additional absorption around 400 nm with extinction coefficients between 21,500 and 44,500 M -1 cm -1 . These dyes are excitable not only with red but also with blue diode lasers or light emitting diodes. Due to the favourable spectral and photophysical properties these dyes can be used as fluorescent probes and labels for intensity- and fluorescence lifetime-based biomedical applications

  14. Impact of Thermal Annealing on Organic Photovoltaic Cells Using Regioisomeric Donor-Acceptor-Acceptor Molecules.

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    Zhang, Tao; Han, Han; Zou, Yunlong; Lee, Ying-Chi; Oshima, Hiroya; Wong, Ken-Tsung; Holmes, Russell J

    2017-08-02

    We report a promising set of donor-acceptor-acceptor (D-A-A) electron-donor materials based on coplanar thieno[3,2-b]/[2,3-b]indole, benzo[c][1,2,5]thiadiazole, and dicyanovinylene, which are found to show broadband absorption with high extinction coefficients. The role of the regioisomeric electron-donating thienoindole moiety on the physical and structural properties is examined. Bulk heterojunction (BHJ) organic photovoltaic cells (OPVs) based on the thieno[2,3-b]indole-based electron donor NTU-2, using C 70 as an electron acceptor, show a champion power conversion efficiency of 5.2% under AM 1.5G solar simulated illumination. This efficiency is limited by a low fill factor (FF), as has previously been the case in D-A-A systems. In order to identify the origin of the limited FF, further insight into donor layer charge-transport behavior is realized by examining planar heterojunction OPVs, with emphasis on the evolution of film morphology with thermal annealing. Compared to as-deposited OPVs that exhibit insufficient donor crystallinity, crystalline OPVs based on annealed thin films show an increase in the short-circuit current density, FF, and power conversion efficiency. These results suggest that that the crystallization of D-A-A molecules might not be realized spontaneously at room temperature and that further processing is needed to realize efficient charge transport in these materials.

  15. Correlation of vapor phase infrared spectra and regioisomeric structure in synthetic cannabinoids

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    Smith, Lewis W.; Thaxton-Weissenfluh, Amber; Abiedalla, Younis; DeRuiter, Jack; Smith, Forrest; Clark, C. Randall

    2018-05-01

    The twelve 1-n-pentyl-2-, 3-, 4-, 5-, 6- and 7-(1- and 2-naphthoyl)-indoles each have the same substituents attached to the indole ring, identical elemental composition (C24H23NO) yielding identical nominal and accurate masses. These twelve isomers cover all possible positions of carbonyl bridge substitution for both indole (positons 2-7) and naphthalene rings (positions 1 and 2). Regioisomeric compounds can represent significant challenges for mass based analytical methods however, infrared spectroscopy is a powerful tool for the identification of positional isomers in organic compounds. The vapor phase infrared spectra of these twelve uniquely similar compounds were evaluated in GC-IR experiments. These spectra show the bridge position on the indole ring is a dominating influence over the carbonyl absorption frequency observed for these compounds. Substitution on the pyrrole moiety of the indole ring yields the lowest Cdbnd O frequency values for position 2 and 3 giving a narrow range from 1656 to 1654 cm-1. Carbonyl absorption frequencies are higher when the naphthoyl group is attached to the benzene portion of the indole ring yielding absorption values from 1674 to 1671 cm-1. The aliphatic stretching bands in the 2900 cm-1 region yield a consistent triplet pattern because the N-alkyl substituent tail group remains unchanged for all twelve regioisomers. The asymmetric CH2 stretch is the most intense of these three bands. Changes in positional bonding for both the indole and naphthalene ring systems results in unique patterns within the 700 wavenumber out-of-plane region and these absorption bands are different for all 12 regioisomers.

  16. Mild one-pot Horner-Wadsworth-Emmons olefination and intramolecular N-arylation for the syntheses of indoles, all regio-isomeric azaindoles, and thienopyrroles.

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    Choi, Ji Hye; Lim, Hwan Jung

    2015-05-14

    The syntheses of various N-protected aromatic-ring fused pyrrole-2-carboxylate derivatives have been accomplished using mild one-pot Horner-Wadsworth-Emmons olefination and Cu-catalyzed intramolecular N-arylation reactions. The optimized mild one-pot reaction conditions of various 2-bromo arylcarboxaldehydes with commercially available N-protected phosphonoglycine trimethylesters gave the desired aromatic-ring fused pyrrole-2-carboxylates, such as substituted indole-, all regio-isomeric azaindole-, and thienopyrrole-2-carboxylates, in good to excellent yields. These conditions showed broad substrate compatibility, without the loss of the protecting group.

  17. Anti-leishmanial and structure-activity relationship of ring substituted 3-phenyl-1-(1,4-di-N-oxide quinoxalin-2-yl-2-propen-1-one derivatives

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    Asunción Burguete

    2008-12-01

    Full Text Available A series of ring substituted 3-phenyl-1-(1,4-di-N-oxide quinoxalin-2-yl-2-propen-1-one derivatives were synthesized and tested for in vitro leishmanicidal activity against amastigotes of Leishmania amazonensis in axenical cultures and murine infected macrophages. Structure-activity relationships demonstrated the importance of a radical methoxy at position R3', R4' and R5'. (2E-3-(3,4,5-trimethoxy-phenyl-1-(3,6,7-trimethyl-1,4-dioxy-quinoxalin-2-yl-propenone was the most active. Cytotoxicity on macrophages revealed that this product was almost six times more active than toxic.

  18. The photochemistry of ring-substituted cinnamyl acetates

    International Nuclear Information System (INIS)

    Fleming, S.A.; Renault, L.; Grundy, E.C.; Pincock, J.A.

    2006-01-01

    The photochemistry of the (E)-cinnamyl acetates ((E)-1-aryl-3-propenyl acetates, 8a-8e) with substituents H, 4-CH 3 O, 3-CH 3 O, 4-CF 3 , and 3-CF 3 , respectively, was examined in both cyclohexane and methanol solvents. Alkene isomerization (E to Z) occurred more efficiently than other reactions and evidence is presented that this process occurs from the excited triplet state. In a slower process, 1,3-migration of the acetoxy group led to the rearranged 3-aryl-3-propenyl acetate isomers (9a-9e) as the major pathway, particularly in cylohexane. In methanol, the isomeric ethers 3-aryl-3-methoxypropene (14) and 1-aryl-3-methoxypropene (15) were formed by reaction of methanol with the photochemically generated cation. The combined yield of 14 and 15 (95% and 5%, respectively) was quantitative for the 4-methoxyphenyl compound (8b). Independent irradiations of the isomers 9a-9c demonstrated that the ethers 14 and 15 were primary photoproducts from 8 and not secondary photoproducts from 9. Fluorescence quantum yields and excited singlet state lifetimes indicated that the reactions, other than the E to Z isomerization, are from the excited singlet state. (author)

  19. Regioisomeric and enantiomeric analysis of triacylglycerols

    Czech Academy of Sciences Publication Activity Database

    Řezanka, Tomáš; Pádrová, K.; Sigler, Karel

    2017-01-01

    Roč. 524, SI (2017), s. 3-12 ISSN 0003-2697 R&D Projects: GA ČR GA14-00227S Institutional support: RVO:61388971 Keywords : Regioisomers * Enantiomers * Triacylglycerols Subject RIV: EE - Microbiology, Virology OBOR OECD: Microbiology Impact factor: 2.334, year: 2016

  20. Ring-substituted 8-hydroxyquinoline-2-carboxanilides as potential antimycobacterial agents

    Czech Academy of Sciences Publication Activity Database

    Kos, J.; Zadražilová, I.; Nevin, E.; Soral, M.; Gonec, T.; Kollár, P.; Oravec, Michal; Coffey, A.; O'Mahony, J.; Liptaj, T.; Kralova, K.; Jampílek, J.

    2015-01-01

    Roč. 23, č. 15 (2015), s. 4188-4196 ISSN 0968-0896 Institutional support: RVO:67179843 Keywords : 8-Hydroxyquinolines * in vitro antimycobacterial activity * in vitro cytotoxicity * MTT assay * Structure–activity relationships Subject RIV: CE - Biochemistry Impact factor: 2.923, year: 2015

  1. Preparation and Biological Properties of Ring-Substituted Naphthalene-1-Carboxanilides

    Czech Academy of Sciences Publication Activity Database

    Goněc, T.; Kos, J.; Nevin, E.; Govender, R.; Peško, M.; Tengler, J.; Kushkevych, I.; Štastná, V.; Oravec, Michal; Kolař, P.; Mahony, J. O.; Králová, K.; Coffey, A.; Jampílek, J.

    2014-01-01

    Roč. 19, č. 7 (2014), s. 10386-10409 ISSN 1420-3049 R&D Projects: GA MŠk(CZ) ED1.1.00/02.0073 Institutional support: RVO:67179843 Keywords : Naphthalene * lipophilicity * in vitro antimycobacterial activity * in vitro cytotoxicity * photosynthetic electron transport inhibition * spinach chloroplasts Subject RIV: EH - Ecology, Behaviour Impact factor: 2.416, year: 2014

  2. Antibacterial and Herbicidal Activity of Ring-Substituted 3-Hydroxynaphthalene-2-carboxanilides

    Czech Academy of Sciences Publication Activity Database

    Kos, J.; Zadražilová, I.; Pesko, M.; Keltosova, S.; Tengler, J.; Goněc, T.; Bobál, P.; Kauerová, T.; Oravec, Michal; Kolař, P.; Čížek, A.; Králová, K.; Jampílek, J.

    2013-01-01

    Roč. 18, č. 7 (2013), s. 7977-7997 ISSN 1420-3049 R&D Projects: GA MŠk(CZ) ED1.1.00/02.0073 Institutional support: RVO:67179843 Keywords : hydroxynaphthalene-2-carboxanilides * lipophilicity * photosynthetic electron transport inhibition * spinach chloroplasts * in vitro antibacterial activity * in vitro antimycobacterial activity * in vitro cytotoxicity * structure-activity relationships Subject RIV: EH - Ecology, Behaviour Impact factor: 2.095, year: 2013

  3. Metabolism and radiosensitization of 4,5-dimethylmisonidazole, a ring-substituted analog of misonidazole

    International Nuclear Information System (INIS)

    Born, J.L.; Smith, B.R.; Harper, N.; Koch, C.J.

    1992-01-01

    In the present study, methyl groups were added to the imidazole ring of misonidazole in order to hinder adduct formation with cellular molecules after reductive-activation of the compound. It was anticipated that this would substantially decrease the hypoxic-cell toxicity of the parent drug. The presence of the two methyl groups reduced the half-wave reduction potential of dimethyl misonidazole (DMM) by about 70 mV, so we expected that its radiosensitizing ability would also decrease. In direct comparison with misonidazole, DMM, at equimolar concentrations, showed dramatically reduced binding to cellular macromolecules under bioreductive conditions, both in vivo, using a liver perfusion system, and in vitro, using tissue culture cells incubated under extreme hypoxia. However, DMM was only moderately less toxic than the parent compound, and showed greatly diminished radiation sensitization capacity. Since the decrease in toxicity was much less than expected, and the decrease in radiosensitization was much more than expected, this compound may be an important drug for continuing studies on the mechanisms of radiation sensitization, binding and cytotoxicity caused by electron affinic drugs. (Author)

  4. Effect of B-ring substitution pattern on binding mode of propionamide selective androgen receptor modulators.

    Science.gov (United States)

    Bohl, Casey E; Wu, Zengru; Chen, Jiyun; Mohler, Michael L; Yang, Jun; Hwang, Dong Jin; Mustafa, Suni; Miller, Duane D; Bell, Charles E; Dalton, James T

    2008-10-15

    Selective androgen receptor modulators (SARMs) are essentially prostate sparing androgens, which provide therapeutic potential in osteoporosis, male hormone replacement, and muscle wasting. Herein we report crystal structures of the androgen receptor (AR) ligand-binding domain (LBD) complexed to a series of potent synthetic nonsteroidal SARMs with a substituted pendant arene referred to as the B-ring. We found that hydrophilic B-ring para-substituted analogs exhibit an additional region of hydrogen bonding not seen with steroidal compounds and that multiple halogen substitutions affect the B-ring conformation and aromatic interactions with Trp741. This information elucidates interactions important for high AR binding affinity and provides new insight for structure-based drug design.

  5. Microbial mineralization of ring-substituted anilines through an ortho-cleavage pathway.

    Science.gov (United States)

    Zeyer, J; Wasserfallen, A; Timmis, K N

    1985-08-01

    Moraxella sp. strain G is able to utilize as sole source of carbon and nitrogen aniline, 4-fluoroaniline, 2-chloroaniline, 3-chloroaniline, 4-chloroaniline (PCA), and 4-bromoaniline but not 4-iodoaniline, 4-methylaniline, 4-methoxyaniline, or 3,4-dichloroaniline. The generation time on PCA was 6 h. The pathway for the degradation of PCA was investigated by analysis of catabolic intermediates and enzyme activities. Mutants of strain G were isolated to enhance the accumulation of specific pathway intermediates. PCA was converted by an aniline oxygenase to 4-chlorocatechol, which in turn was degraded via a modified ortho-cleavage pathway. Synthesis of the aniline oxygenase was inducible by various anilines. This enzyme exhibited a broad substrate specificity. Its specific activity towards substituted anilines seemed to be correlated more with the size than with the electron-withdrawing effect of the substituent and was very low towards anilines having substituents larger than iodine or a methyl group. The initial enzyme of the modified ortho-cleavage pathway, catechol 1,2-dioxygenase, had similar characteristics to those of corresponding enzymes of pathways for the degradation of chlorobenzoic acid and chlorophenol, that is, a broad substrate specificity and high activity towards chlorinated and methylated catechols.

  6. Ring-Substituted Benzohydroxamic Acids: 1H, 13C and 15N NMR Spectra and NHOH Proton Exchange

    Czech Academy of Sciences Publication Activity Database

    Schraml, Jan; Tkadlecová, M.; Pataridis, S.; Soukupová, Ludmila; Blechta, Vratislav; Roithová, Jana; Exner, Otto

    2005-01-01

    Roč. 43, č. 7 (2005), s. 535-542 ISSN 0749-1581 R&D Projects: GA ČR(CZ) GA203/03/1566; GA AV ČR(CZ) IAA4072605; GA AV ČR(CZ) IAA4072005; GA MŠk(CZ) LB98233 Institutional research plan: CEZ:AV0Z40720504 Keywords : proton exchange * substituent effects * chemical shifts Subject RIV: CC - Organic Chemistry Impact factor: 1.553, year: 2005

  7. Phenyl Ring-Substituted Lobelane Analogs: Inhibition of [3H]Dopamine Uptake at the Vesicular Monoamine Transporter-2

    OpenAIRE

    Nickell, Justin R.; Zheng, Guangrong; Deaciuc, Agripina G.; Crooks, Peter A.; Dwoskin, Linda P.

    2011-01-01

    Lobeline attenuates the behavioral effects of methamphetamine via inhibition of the vesicular monoamine transporter (VMAT2). To increase selectivity for VMAT2, chemically defunctionalized lobeline analogs, including lobelane, were designed to eliminate nicotinic acetylcholine receptor affinity. The current study evaluated the ability of lobelane analogs to inhibit [3H]dihydrotetrabenazine (DTBZ) binding to VMAT2 and [3H]dopamine (DA) uptake into isolated synaptic vesicles and determined the m...

  8. Mutagenicity and cytotoxicity of two regioisomeric mercapturic acids and cysteine S-conjugates of trichloroethylene.

    NARCIS (Netherlands)

    Commandeur, J.N.M.; Boogaard, P.J.; Mulder, G.J.; Vermeulen, N.P.E.

    1991-01-01

    The mutagenicity, cytotoxicity and metabolism of two regioisomic l-cysteine- and N-acetyl-l-cysteine-S-conjugates of trichloroethylene were studied. The 1,2-dichlorovinyl(1,2-DCV) isomers of both the cysteine conjugate and the mercapturate were much stronger mutagens in the Ames test with Salmonella

  9. Synthesis and Isolation of New Regioisomeric 4-Thiazolidinones and Their Anticonvulsant Activity

    OpenAIRE

    GÜRSOY, Aysel; TERZİOĞLU, Nalan

    2005-01-01

    Two regioisomer series, 2-(3-ethyl-4(3H)-quinazolinone-2- ylmercaptoacetylhydrazono)-3-alkyl/3-aryl-5-methyl-4-thiazolidinones (12-21) and 2-arylimino-3-(3-ethyl-4(3H)-quinazolinone-2-ylmercaptoacetylamino)- 5-methyl-4-thiazolidinones (22-26), were synthesized by the cyclization of 1-(3-ethyl-4(3H)-quinazolinone-2-ylmercaptoacetyl)-4-alkyl/aryl thiosemicarbazides (1-11) with ethyl 2-bromopropionate in the presence of anhydrous sodium acetate in anhydrous ethanolic medium. The structur...

  10. Synthesis and In Vitro Antiproliferative Activity of Novel Phenyl Ring-Substituted 5-Alkyl-12(H-quino[3,4-b][1,4]benzothiazine Derivatives

    Directory of Open Access Journals (Sweden)

    Andrzej Zięba

    2016-11-01

    Full Text Available A novel series of tetracyclic quinobenzothiazine derivatives was synthetized. Compounds containing a substituent (hydroxyl, methyl, phenyl, piperidyl, or piperazinyl in positions 9 and 11 were obtained by cyclization of suitable 4-aminoquinolinium-3-thiolates. Quinobenzothiazine 10-O-substituted derivatives were obtained by alkylating the hydroxyl group in position 10 of the parent (quinobenzothiazine system. Antiproliferative activity of the synthesized compounds was studied using cultured neoplastic cells (MDA-MB-231, SNB-19, and C-32 cell lines. Four selected compounds were investigated in more detail for cytotoxicity and antiproliferative effect. Transcriptional activity of genes regulating cell cycle (TP53, apoptosis (BAX, BCL-2, as well as proliferation (H3 were assessed. Finally, the ability of the selected compounds to bind DNA was checked in the presence of ethidium bromide.

  11. Synthesis, characterization and biological activity of ring-substituted 6-benzylamino-9-tetrahydropyran-2-yl and 9-tetrahydrofuran-2-ylpurine derivatives

    Czech Academy of Sciences Publication Activity Database

    Szüčová, Lucie; Spíchal, Lukáš; Doležal, Karel; Zatloukal, Marek; Greplová, Jarmila; Galuszka, P.; Kryštof, Vladimír; Voller, Jiří; Popa, Igor; Massino, F.J.; Jorgensen, J.E.; Strnad, Miroslav

    2009-01-01

    Roč. 17, č. 5 (2009), s. 1938-1947 ISSN 0968-0896 R&D Projects: GA MŠk 1M06030; GA ČR GA522/09/1576; GA ČR(CZ) GA522/08/0920 Institutional research plan: CEZ:AV0Z50380511 Keywords : Cytokinins * Antisenescence * Receptor Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.822, year: 2009

  12. Coordination and Bond Activation in Complexes of Regioisomeric Phenylpyridines with the Nickel(II) Chloride Cation in the Gas Phase

    Czech Academy of Sciences Publication Activity Database

    Tsybizova, Alexandra; Rulíšek, Lubomír; Schröder, Detlef; Rokob, Tibor András

    2013-01-01

    Roč. 117, č. 6 (2013), s. 1171-1180 ISSN 1089-5639 Grant - others:European Research Council(XE) AdG HORIZOMS Institutional support: RVO:61388963 Keywords : collision-induced dissociation * ionization mass-spectrometry * donor ligands pyridine * ion mobility measurements Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 2.775, year: 2013

  13. EFSA Panel on Food Contact Materials, Enzymes, Flavourings and Processing Aids (CEF); Scientific Opinion on Flavouring Group Evaluation 22, Revision 1 (FGE.22Rev1): Ring substituted phenolic substances from chemical groups 21 and 25

    DEFF Research Database (Denmark)

    Larsen, John Christian; Nørby, Karin Kristiane; Beltoft, Vibe Meister

    The Panel on Food Contact Materials, Enzymes, Flavourings and Processing Aids of the European Food Safety Authority was requested to evaluate 28 flavouring substances in the Flavouring Group Evaluation 22, Revision 1, using the Procedure in Commission Regulation (EC) No 1565/2000. The substance 3...... through a stepwise approach (the Procedure) that integrates information on structure-activity relationships, intake from current uses, toxicological threshold of concern, and available data on metabolism and toxicity. The Panel concluded that these 27 candidate substances do not give rise to safety...... concerns at their levels of dietary intake, estimated on the basis of the MSDI approach. Adequate specifications for the materials of commerce are available for all 27 flavouring substances evaluated through the Procedure....

  14. Structure activity correlations in the inhibition of brain synaptosomal 3H-norepinephrine uptake by phenethylamine analogs. The role of α-alkyl side chain and methoxyl ring substitutions

    International Nuclear Information System (INIS)

    Makriyannis, A.; Bowerman, D.; Sze, P.Y.; Fournier, D.; Jong, A.P. de

    1982-01-01

    α-Ethylphenethylamine proved to be a weaker inhibitor of rat brain synaptosomal [ 3 H]norepinephrine ([ 3 H]NE) uptake than amphetamine, while 2-amino-tetralin and 2-amino-1,2-dihydronaphtalene, compounds in which the α-side chain ethyl group is tied to the aromatic ring have a similar inhibiting potency as amphetamine. Hallucinogenic polymethoxy substituted phenethylamine analogs have very low inhibitory potencies indicating that inhibition of NE-reuptake in brain noradrenergic neurons is not associated with the drug-induced hallucinogenic syndrome. (Auth.)

  15. The Effect of Solvent Accessible Surface on Hammett-Type Dependencies of Infinite Dilution 29Si and 13C NMR Shifts in Ring Substituted Silylated Phenols Dissolved in Chloroform and Acetone

    Czech Academy of Sciences Publication Activity Database

    Blechta, Vratislav; Šabata, Stanislav; Sýkora, Jan; Hetflejš, Jiří; Soukupová, Ludmila; Schraml, Jan

    2012-01-01

    Roč. 50, č. 2 (2012), s. 128-134 ISSN 0749-1581 R&D Projects: GA AV ČR IAA400720706; GA ČR GA203/06/0738 Institutional research plan: CEZ:AV0Z40720504 Keywords : 1H NMR * 13C NMR * 29Si NMR Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 1.528, year: 2012

  16. Synthesis, photophysical, structural and electronic properties of novel regioisomerically pure 1,7-disubstituted perylene-3,4,9,10-tetracarboxylic monoimide dibutylester derivatives

    Science.gov (United States)

    Ozser, Mustafa E.; Mohiuddin, Obaidullah

    2018-04-01

    Three new isomerically pure 1,7-disubstituted perylene-3,4,9,10-tetracarboxylic monoimide dibutylester derivatives namely; N-[2-(diethylamino)ethyl]-1,7-dibromoperylene-3,4,9,10-tetracarboxy monoimide dibutylester (PMD-1), N-[2-(diethylamino)ethyl]-1,7-di(4-tert-butylphenoxy)perylene-3,4,9,10-tetracarboxy monoimide dibutylester (PMD-2) and N-[2-(diethylamino)ethyl]-1,7-di(pyrrolidinyl)perylene-3,4,9,10-tetracarboxy monoimide dibutylester (PMD-3), have been synthesized and their electronic absorption spectra, and steady-state fluorescence were investigated experimentally as well as by using density functional theory (DFT) calculations. All three compounds show good solubility in toluene and chloroform. Attachment of two tert-butylphenoxy groups at the 1,7-positions in PMD-2 resulted in a red shifted absorption band with an absorption maximum at 518 nm. UV/Vis absorption spectrum of PMD-3 bearing electron donating pyrrolidinyl groups at the 1,7-positions shows a broad absorption band within the visible region, extending to red region. Absorption maximum of lowest energy transition now shifts to 653 nm. In addition to the S0 → S1 absorption bands, bands belonging to S0 → S2 electronic transitions were observed at 378, 386, and 411 nm for PMD-1, PMD-2, and PMD-3 respectively. Compounds PMD-1, PMD-2 and PMD-3 display low fluorescence quantum yields of 0.027, 0.040 and 0.001, respectively in chloroform. DFT calculations revealed that the attachment of electron donating groups at 1,7-positions of perylene core, results in an increase in frontier orbitals energy levels. Observed energy increase in HOMO level is larger in each case, compared to the energy increase in LUMO levels, due to the higher contribution of side groups to HOMO. DFT calculated band gaps for PMD-1, PMD-2 and PMD-3 are 2.68, 2.63 and 2.29 eV respectively.

  17. Regioisomeric analysis of triacylglycerols using silver-ion liquid chromatography-atmospheric pressure chemical ionization mass spectrometry: Comparison of five different mass analyzers

    Czech Academy of Sciences Publication Activity Database

    Holčapek, M.; Dvořáková, H.; Lísa, M.; Girón, A. J.; Sandra, P.; Cvačka, Josef

    2010-01-01

    Roč. 1217, č. 52 (2010), s. 8186-8194 ISSN 0021-9673 R&D Projects: GA ČR GA203/09/0139 Institutional research plan: CEZ:AV0Z40550506 Keywords : triacylglycerols * silver-ion liquid chromatography * regioisomer * HPLC/MS * APCI Subject RIV: CB - Analytical Chemistry, Separation Impact factor: 4.194, year: 2010

  18. Crystal structures of three anhydrous salts of the Lewis base 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU with the ring-substituted benzoic acid analogues 4-aminobenzoic acid, 3,5-dinitrobenzoic acid and 3,5-dinitrosalicylic acid

    Directory of Open Access Journals (Sweden)

    Graham Smith

    2016-03-01

    Full Text Available The anhydrous salts of the Lewis base 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU with 4-aminobenzoic acid [1-aza-8-azoniabicyclo[5.4.0]undec-7-ene 4-aminobenzoate, C9H17N2+·C7H6NO2− (I], 3,5-dinitrobenzoic acid [1-aza-8-azoniabicyclo[5.4.0]undec-7-ene 3,5-dinitrobenzoate, C9H17N2+·C7H3N2O6−, (II] and 3,5-dinitrosalicylic acid (DNSA [1-aza-8-azoniabicyclo[5.4.0]undec-7-ene 2-hydroxy-3,5-dinitrobenzoate, C9H17N2+·C7H3N2O7−, (III] have been determined and their hydrogen-bonded structures are described. In both (II and (III, the DBU cations have a common disorder in three of the C atoms of the six-membered ring moieties [site-occupancy factors (SOF = 0.735 (3/0.265 (3 and 0.686 (4/0.314 (4, respectively], while in (III, there is additional rotational disorder in the DNSA anion, giving two sites (SOF = 0.72/0.28, values fixed for the phenol group. In the crystals of (I and (III, the cation–anion pairs are linked through a primary N—H...Ocarboxyl hydrogen bond [2.665 (2 and 2.869 (3 Å, respectively]. In (II, the ion pairs are linked through an asymmetric three-centre R12(4, N—H...O,O′ chelate association. In (I, structure extension is through amine N—H...Ocarboxyl hydrogen bonds between the PABA anions, giving a three-dimensional structure. The crystal structures of (II and (III are very similar, the cation–anion pairs being associated only through weak C—H...O hydrogen bonds, giving in both overall two-dimensional layered structures lying parallel to (001. No π–π ring associations are present in any of the structures.

  19. Microwave mediated synthesis of spiro-(indoline-isoxazolidines): mechanistic study and biological activity evaluation

    DEFF Research Database (Denmark)

    Raunak, R.; Kumar, Vineet; Mukherjee, Shubhasish

    2005-01-01

    Regioisomeric spiro-(indoline-isoxazolidines) have been synthesized in moderate yields by the cycloaddition reaction between ethyl (3-indolylidene)acetate and various substituted α,N-diphenylnitrones, using environmentally benign microwave technology. A novel concerted reaction mechanism is descr......Regioisomeric spiro-(indoline-isoxazolidines) have been synthesized in moderate yields by the cycloaddition reaction between ethyl (3-indolylidene)acetate and various substituted α,N-diphenylnitrones, using environmentally benign microwave technology. A novel concerted reaction mechanism...

  20. Effect of Bronsted Acids and Bases, and Lewis Acid (Sn(2+)) on the Regiochemistry of the Reaction of Amines with Trifluoromethyl-β-diketones: Reaction of 3-Aminopyrrole to Selectively Produce Regioisomeric 1H-Pyrrolo[3,2-b]pyridines.

    Science.gov (United States)

    De Rosa, Michael; Arnold, David; Hartline, Douglas; Truong, Linda; Verner, Roman; Wang, Tianwei; Westin, Christian

    2015-12-18

    Reaction of 3-aminopyrrole (as its salt) with trifluoromethyl-β-diketones gave γ-1H-pyrrolo[3,2-b]pyridines via reaction at the less reactive carbonyl group. The trifluoromethyl group increased the electrophilicity of the adjacent carbonyl group and decreased the basicity of the hydroxyl group of the CF3 amino alcohol formed. This amino alcohol was formed faster, but its subsequent dehydration to the β-enaminone was slow resulting in the preferential formation of the γ-regioisomer. Reaction of 4,4,4-trifluoro-1-phenyl-1,3-butadione with 3-aminopyrrole was carried out using a series of 6 amine buffers. Yields of the α-1H-pyrrolo[3,2-b]pyridine increased as the pKa of the amine buffer decreased. Surprisingly the yield went down at higher pKas. There was a change in mechanism as the reaction mixture became more basic. With strong amines trifluoromethyl-β-diketones were present mainly or completely as the enolate. Under reductive conditions (3-nitropyrrole/Sn/AcOH/trifluoromethyl-β-diketone) the α-1H-pyrrolo[3,2-b]pyridine was the major product as a result of Lewis acid catalysis by Sn(2+). Similar α-regiochemistry was observed when the reaction of the 3-aminopyrrole salt with trifluoromethyl-β-diketones was carried out in the presence of base and tin(II) acetate.

  1. Convenient one-step synthesis of 5-carboxy-seminaphthofluoresceins

    DEFF Research Database (Denmark)

    Hammershøj, Peter; Thyhaug, Erling; Harris, Pernille

    2017-01-01

    The one-step synthesis and characterization of a series of regioisomerically pure 5-carboxy-seminaphthofluoresceins (5-carboxy-SNAFLs) is reported. The optical properties were determined in aqueous buffer at around biological pH, and highly pH sensitive, large Stokes-shift fluorophores with emiss......The one-step synthesis and characterization of a series of regioisomerically pure 5-carboxy-seminaphthofluoresceins (5-carboxy-SNAFLs) is reported. The optical properties were determined in aqueous buffer at around biological pH, and highly pH sensitive, large Stokes-shift fluorophores...

  2. Regioisomers of octanoic acid-containing structured triacylglycerols analyzed by tandem mass spectrometry using ammonia negative ion chemical ionization

    DEFF Research Database (Denmark)

    Kurvinen, J.P.; Mu, Huiling; Kallio, H.

    2001-01-01

    Tandem mass spectrometry based on ammonia negative ion chemical ionization and sample introduction via direct exposure probe was applied to analysis of regioisomeric structures of octanoic acid containing structured triacylglycerols (TAG) of type MML, MLM, MLL, and LML (M, medium-chain fatty acid...

  3. Synthesis and radiolabeling of heterocyclic food mutagens

    International Nuclear Information System (INIS)

    Rapoport, H.; Waterhouse, A.L.; Thompson, C.M.; O'Connell, J.F.

    1986-01-01

    The imidazoquinoline and imidazoquinoxaline food mutagens found in cooked meat are being synthesized by unambiguous methods that allow for the preparation of sufficient quantities of material for biological studies. These methods avoid difficult separations of regioisomeric mixtures of products and are designed to allow incorporation of specific high level tritium labeling

  4. Facile Large-Scale Synthesis of 5- and 6-Carboxyfluoresceins

    DEFF Research Database (Denmark)

    Hammershøj, Peter; Ek, Pramod Kumar; Harris, Pernille

    2015-01-01

    A series of fluorescein dyes have been prepared from a common precursor through a very simple synthetic procedure, giving access to important precursors for fluorescent probes. The method has proven an efficient access to regioisomerically pure 5- and 6-carboxyfluoresceins on a large scale, in good...

  5. Ratios of regioisomers of minor acylglycerols less polar than triricinolein in castor oil estimated by mass spectrometry (Abstract)

    Science.gov (United States)

    The ratios of regioisomers of triacylglycerols (TAG) have been estimated by mass spectrometry using the fact that the neutral loss of fatty acid (FA) from the sn-2 position is energetically less favored in comparison with that from sn-1,3 positions. However regioisomeric TAG standards were needed fo...

  6. The redox-Mannich reaction.

    Science.gov (United States)

    Chen, Weijie; Seidel, Daniel

    2014-06-06

    A complement to the classic three-component Mannich reaction, the redox-Mannich reaction, utilizes the same starting materials but incorporates an isomerization step that enables the facile preparation of ring-substituted β-amino ketones. Reactions occur under relatively mild conditions and are facilitated by benzoic acid.

  7. Classroom

    Indian Academy of Sciences (India)

    flipping of the ring carbons. This occurs by twisting (restricted rotation) of the bonds, and results in the interchange of the positions of the axial and equatorial bonds. In monosubstituted cydohexanes, the substituent preferentially occupies the equatorial position, which is on the exterior part of the ring. Substitution on the axial ...

  8. Synthesis and comparing the antibacterial activities of pyrimidine ...

    Indian Academy of Sciences (India)

    heterocyclic ring substituted in pyrimidine derivatives have moderate inhibition against ... moved by boiling in presence of catalyst and hydrazine .... by Biginelli reaction. The structures of the synthesized compounds were confirmed by IR, 1H and 13C NMR,. GC-MS and CHN analysis. Formation of 2a was con- firmed by the ...

  9. [BMIM][PF(6)] promotes the synthesis of halohydrin esters from diols using potassium halides.

    Science.gov (United States)

    Oromí-Farrús, Mireia; Eras, Jordi; Villorbina, Gemma; Torres, Mercè; Llopis-Mestre, Veronica; Welton, Tom; Canela, Ramon

    2008-10-01

    Haloesterification of diverse diols with various carboxylic acids was achieved using potassium halides (KX) as the only halide source in ionic liquids. The best yield was obtained in [BMIM][PF(6)] when 1,2-octanediol, palmitic acid and KBr were used. This yield was 85% and the regioisomer with the bromine in primary position was present in a 75:25 ratio. The regioisomeric ratio could be improved using either KCl or some phenylcarboxylic acids. [BMIM][PF(6)] acts as both reaction media and catalyst of the reaction. To the best of our knowledge, this type of combined reaction using an ionic liquid is unprecedented. The other solvents tested did not lead either to the same yield or to the same regioisomeric ratio.

  10. Analysis and protease-catalysed synthesis of sucrose alkanoate regioisomers

    DEFF Research Database (Denmark)

    Lie, Aleksander

    2014-01-01

    The aims of the presented research were to develop quantifiable methods for reversed-phase high-performance liquid chromatography analysis of sucrose alkanoate regioisomers and to investigate the activity and regioisomeric distribution in the biocatalytic esterification of sucrose with vinyl laur...... in the reaction mixture appeared to be catalysed by the presence of aluminosilicate molecular sieves in the reaction medium. Mass spectrometry analysis of sucrose laurate product confirmed the molecular mass.......The aims of the presented research were to develop quantifiable methods for reversed-phase high-performance liquid chromatography analysis of sucrose alkanoate regioisomers and to investigate the activity and regioisomeric distribution in the biocatalytic esterification of sucrose with vinyl...... laurate in DMF using serine proteases and a metalloprotease. A broad range of elution strategies for the chromatographic analysis of sucrose alkanoate regioisomers was systematically investigated using design of experiments strategies and statistical and multivariate analysis and modelling. Efficiency...

  11. Comparison of the cytotoxic effects of enantiopure PPAPs, including nemorosone and clusianone.

    Science.gov (United States)

    Simpkins, Nigel S; Holtrup, Frank; Rodeschini, Vincent; Taylor, James D; Wolf, Robert

    2012-10-01

    The synthesis of an unnatural polyprenylated acylphloroglucinol (PPAP), regioisomeric with nemorosone and clusianone, has been accomplished. The separated enantiomers of this new PPAP, along with those of nemorosone and clusianone, have been screened for activity against HeLa (cervix carcinoma), MIA-PaCa-2 (pancreatic carcinoma), and MCF7 (mamma carcinoma) cancer cell lines. All of the isomers examined gave surprisingly similar results in the screens. Copyright © 2012 Elsevier Ltd. All rights reserved.

  12. The 2-alkyl-2H-indazole regioisomers of synthetic cannabinoids AB-CHMINACA, AB-FUBINACA, AB-PINACA, and 5F-AB-PINACA are possible manufacturing impurities with cannabimimetic activities

    OpenAIRE

    Longworth, Mitchell; Banister, Samuel D.; Mack, James B. C.; Glass, Michelle; Connor, Mark; Kassiou, Michael

    2016-01-01

    Indazole-derived synthetic cannabinoids (SCs) featuring an alkyl substituent at the 1-position and l-valinamide at the 3-carboxamide position (e.g., AB-CHMINACA) have been identified by forensic chemists around the world, and are associated with serious adverse health effects. Regioisomerism is possible for indazole SCs, with the 2-alkyl-2H-indazole regioisomer of AB-CHMINACA recently identified in SC products in Japan. It is unknown whether this regiosiomer represents a manufacturing impurit...

  13. Synthesis and tritium labeling of the food mutagens IQ and methyl-IQ

    International Nuclear Information System (INIS)

    Waterhouse, A.L.; Rapoport, H.

    1985-01-01

    The mutagens found in cooked meat, 2-amino-3-methylimidazo[4,5-f]-quinoline (IQ) and 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (Methyl-IQ), have been synthesized by unambiguous methods that allow for the preparation of sufficient quantities of material for biological studies. These methods avoid difficult separations of regioisomeric mixtures of products and incorporate specific high level tritium labeling, effected by hydrogenolysis of the appropriately substituted 5-bromo precursors. (author)

  14. Nitrogen containing heterocycles from aldoximes; a one-pot route to isoxazolobenzodiazepinones, N-substituted and N-unsubstituted isoxazoloquinolinones

    OpenAIRE

    Heaney, Frances; Bourke, Sharon

    1998-01-01

    The aldoximes 1 in the presence of electron poor olefins react to form either the 5,6,7-tricyclic isoxazolobenzodiazepinone 3 or the 5,6,6-tricyclic isoxazoloquinolinone 5 ring skeleton. In each case the ring system formed depends on the relative electrophilicity of the added and internal olefin. The oximes 1a,b,c react with N-methylmaleimide, methyl acrylate or phenyl vinyl sulfone to afford the corresponding regioisomeric isoxazolobenzodiazepinones by a tandem intramolecular dipole formatio...

  15. Stereochemistry of substitution at trico-ordinate phosphorus

    DEFF Research Database (Denmark)

    Nielsen, John; Dahl, Otto

    1984-01-01

    A series of reactions of ring-substituted 1,3,2-dioxaphospholanes, 1,3,2-oxazaphospholanes, 1,2-oxaphospholes, and phosphetanes bearing the leaving groups Cl, OR, or NR2 on phosphorus, with the nucleophiles HCl, MeO-, MeOH, PhOH, Me2NH, Et2NH, and [CH 2]5NH have been studied. N.m.r. signals (1H...

  16. N-Boc Amines to Oxazolidinones via Pd(II)/Bis-sulfoxide/Brønsted Acid Co-Catalyzed Allylic C–H Oxidation

    Science.gov (United States)

    2015-01-01

    A Pd(II)/bis-sulfoxide/Brønsted acid catalyzed allylic C–H oxidation reaction for the synthesis of oxazolidinones from simple N-Boc amines is reported. A range of oxazolidinones are furnished in good yields (avg 63%) and excellent diastereoselectivities (avg 15:1) to furnish products regioisomeric from those previously obtained using allylic C–H amination reactions. Mechanistic studies suggest the role of the phosphoric acid is to furnish a Pd(II)bis-sulfoxide phosphate catalyst that promotes allylic C–H cleavage and π-allylPd functionalization with a weak, aprotic oxygen nucleophile and to assist in catalyst regeneration. PMID:24999765

  17. N-Boc amines to oxazolidinones via Pd(II)/bis-sulfoxide/Brønsted acid co-catalyzed allylic C-H oxidation.

    Science.gov (United States)

    Osberger, Thomas J; White, M Christina

    2014-08-06

    A Pd(II)/bis-sulfoxide/Brønsted acid catalyzed allylic C-H oxidation reaction for the synthesis of oxazolidinones from simple N-Boc amines is reported. A range of oxazolidinones are furnished in good yields (avg 63%) and excellent diastereoselectivities (avg 15:1) to furnish products regioisomeric from those previously obtained using allylic C-H amination reactions. Mechanistic studies suggest the role of the phosphoric acid is to furnish a Pd(II)bis-sulfoxide phosphate catalyst that promotes allylic C-H cleavage and π-allylPd functionalization with a weak, aprotic oxygen nucleophile and to assist in catalyst regeneration.

  18. Symmetrically and Unsymmetrically Bridged Methylenebis(allopurinols: Synthesis of Dimeric Potential Anti-Gout Drugs

    Directory of Open Access Journals (Sweden)

    Frank Seela

    2007-03-01

    Full Text Available Liquid-liquid phase transfer alkylation of 4-methoxy-pyrazolo[3,4-d]-pyrimidine (1a with a dichloromethane/dibromomethane mixture (3:1, v/v gave the regioisomeric methylenebis(heterocycles 3a–5a. These were converted by dilute aqueous sodium hydroxide containing dimethylsulfoxide (DMSO at concentrations between 0 and 60 vol-% into the methylenebis(allopurinols 3b–5b by nucleophilic SNAr reactions at C(4. The effect of DMSO on the reaction kinetics was investigated.

  19. Determination of triacylglycerol regioisomers using electrospray ionization-quadrupole ion trap mass spectrometry with a kinetic method.

    Science.gov (United States)

    Leveque, Nathalie L; Acheampong, Akwasi; Heron, Sylvie; Tchapla, Alain

    2012-04-13

    The kinetic method was applied to differentiate and quantify mixtures of regioisomeric triacylglycerols (TAGs) by generating and mass selecting alkali ion bound metal dimeric clusters with a TAG chosen as reference (ref) and examining their competitive dissociations in a quadrupole ion trap mass spectrometer. This methodology readily distinguished pairs of regioisomers (AAB/ABA) such as LLO/LOL, OOP/OPO and SSP/SPS and consequently distinguished sn-1/sn-3, sn-2 substituents on the glycerol backbone. The dimeric complex ions [ref, Li, TAG((AAB and/or ABA))](+) generated by electrospray ionization mass spectrometry were subjected to collision induced dissociation causing competitive loss of either the neutral TAG reference (ref) leading to [Li(AAB and/or ABA)](+) or the neutral TAG molecule (TAG((AAB and/or ABA))) leading to [ref, Li](+). The ratio of the two competitive dissociation rates, defined by the product ion branching ratio (R(iso)), was related via the kinetic method to the regioisomeric composition of the investigated TAG mixture. In this work, a linear correlation was established between composition of the mixture of each TAG regioisomer and the logarithm of the branching ratio for competitive fragmentation. Depending on the availability of at least one TAG regioisomer as standard, the kinetic method and the standard additions method led to the quantitative analysis of natural TAG mixtures. Copyright © 2012 Elsevier B.V. All rights reserved.

  20. Synthesis and properties of ApA analogues with shortened phosphonate internucleotide linkage.

    Science.gov (United States)

    Králíková, Sárka; Buděšínský, Miloš; Barvík, Ivan; Masojídková, Milena; Točík, Zdeněk; Rosenberg, Ivan

    2011-01-01

    A complete series of the 2 '-5 ' and 3 '-5 ' regioisomeric types of r(ApA) and 2 '-d(ApA) analogues with the α-hydroxy-phosphonate C3 '-O-P-CH(OH)-C4 ″ internucleotide linkage, isopolar but non-isosteric with the phosphodiester one, were synthesized and their hybridization properties with polyU studied. Due to the chirality on the 5 '-carbon atom of the modified internucleotide linkage bearing phosphorus and hydroxy moieties, each regioisomeric type of ApA dimer is split into epimeric pairs. To examine the role of the 5 '-hydroxyl of the α-hydroxy-phosphonate moiety during hybridization, the appropriate r(ApA) analogues with 3 '(2 ')-O-P-CH(2)-C4 ″ linkage lacking the 5 '-hydroxyl were synthesized. Nuclear magnetic resonance (NMR) spectroscopy study on the conformation of the modified sugar-phosphate backbone, along with the hybridization measurements, revealed remarkable differences in the stability of complexes with polyU, depending on the 5 '-carbon atom configuration. Potential usefulness of the α-hydroxy-phosphonate linkage in modified oligoribonucleotides is discussed.

  1. 3,5-Bis[1-acetyl-5-(4-chlorophenyl-4,5-dihydro-1H-pyrazol-3-yl]-2,6-dimethylpyridine tetrahydrofuran solvate

    Directory of Open Access Journals (Sweden)

    Qun Qian

    2008-07-01

    Full Text Available In the title compound, C29H27Cl2N5O2·C4H8O, the polycyclic system is composed of three parts: one central pyridine ring substituted by two functionalized pyrazoline rings. The dihedral angles between the central pyridine plane and pyrazoline planes are 5.11 (1 and 13.99 (1°, whereas the dihedral angles between each chlorophenyl plane and the attached pyrazoline planes are 88.65 (1 and 83.87 (1°. Molecules are linked by intermolecular C—H...O hydrogen bonds, forming a three-dimensional network.

  2. 2,4,8,10,13-Pentamethyl-6-phenyl-13,14-dihydro-12H-6λ5-dibenzo[d,i][1,3,7,2]dioxazaphosphecin-6-thione

    Directory of Open Access Journals (Sweden)

    M. Krishnaiah

    2010-01-01

    Full Text Available In the title compound, C25H28NO2PS, the cyclodecene ring exhibits a crown conformation. The two dimethylbenzene rings which are fused symmetrically on either side of the ten-membered ring, make dihedral angles of 20.2 (1 and 18.0 (1°. The phenyl ring substituted at P is perpendicular to the heterocyclic ring, making a dihedral angle of 88.4 (1°. The crystal structure is stabilized by very weak intramolecular C—H...O hydrogen bonding.

  3. A Novel and Highly Regioselective Synthesis of New Carbamoylcarboxylic Acids from Dianhydrides

    Directory of Open Access Journals (Sweden)

    Adrián Ochoa-Terán

    2014-01-01

    Full Text Available A regioselective synthesis has been developed for the preparation of a series of N,N′-disubstituted 4,4′-carbonylbis(carbamoylbenzoic acids and N,N′-disubstituted bis(carbamoyl terephthalic acids by treatment of 3,3′,4,4′-benzophenonetetracarboxylic dianhydride (1 and 1,2,4,5-benzenetetracarboxylic dianhydride (2 with arylalkyl primary amines (A-N. The carbamoylcarboxylic acid derivatives were synthesized with good yield and high purity. The specific reaction conditions were established to obtain carbamoyl and carboxylic acid functionalities over the thermodynamically most favored imide group. Products derived from both anhydrides 1 and 2 were isolated as pure regioisomeric compounds under innovative experimental conditions. The chemo- and regioselectivity of products derived from dianhydrides were determined by NMR spectroscopy and confirmed by density functional theory (DFT. All products were characterized by NMR, FTIR, and MS.

  4. Recent advances in the ruthenium-catalyzed hydroarylation of alkynes with aromatics: synthesis of trisubstituted alkenes.

    Science.gov (United States)

    Manikandan, Rajendran; Jeganmohan, Masilamani

    2015-11-14

    The hydroarylation of alkynes with substituted aromatics in the presence of a metal catalyst via chelation-assisted C-H bond activation is a powerful method to synthesize trisubstituted alkenes. Chelation-assisted C-H bond activation can be done by two ways: (a) an oxidative addition pathway and (b) a deprotonation pathway. Generally, a mixture of cis and trans stereoisomeric as well as regioisomeric trisubstituted alkenes was observed in an oxidative addition pathway. In the deprotonation pathway, the hydroarylation reaction can be done in a highly regio- and stereoselective manner, and enables preparation of the expected trisubstituted alkenes in a highly selective manner. Generally, ruthenium, rhodium and cobalt complexes are used as catalysts in the reaction. In this review, a ruthenium-catalyzed hydroarylation of alkynes with substituted aromatics is covered completely. The hydroarylation reaction of alkynes with amide, azole, carbamate, phosphine oxide, amine, acetyl, sulfoxide and sulphur directed aromatics is discussed.

  5. Synthesis and Antiplasmodial Evaluation of Analogues Based on the Tricyclic Core of Thiaplakortones A–D

    Directory of Open Access Journals (Sweden)

    Brett D. Schwartz

    2015-09-01

    Full Text Available Six regioisomers associated with the tricyclic core of thiaplakortones A–D have been synthesized. Reaction of 1H-indole-4,7-dione and 1-tosyl-1H-indole-4,7-dione with 2-aminoethanesulfinic acid afforded a regioisomeric series, which was subsequently deprotected and oxidized to yield the tricyclic core scaffolds present in the thiaplakortones. All compounds were fully characterized using NMR and MS data. A single crystal X-ray structure was obtained on one of the N-tosyl derivatives. All compounds were screened for in vitro antiplasmodial activity against chloroquine-sensitive (3D7 and multidrug-resistant (Dd2 Plasmodium falciparum parasite lines. Several analogues displayed potent inhibition of P. falciparum growth (IC50 < 500 nM but only moderate selectivity for P. falciparum versus human neonatal foreskin fibroblast cells.

  6. Synthesis and Antiplasmodial Evaluation of Analogues Based on the Tricyclic Core of Thiaplakortones A-D.

    Science.gov (United States)

    Schwartz, Brett D; Coster, Mark J; Skinner-Adams, Tina S; Andrews, Katherine T; White, Jonathan M; Davis, Rohan A

    2015-09-15

    Six regioisomers associated with the tricyclic core of thiaplakortones A-D have been synthesized. Reaction of 1H-indole-4,7-dione and 1-tosyl-1H-indole-4,7-dione with 2-aminoethanesulfinic acid afforded a regioisomeric series, which was subsequently deprotected and oxidized to yield the tricyclic core scaffolds present in the thiaplakortones. All compounds were fully characterized using NMR and MS data. A single crystal X-ray structure was obtained on one of the N-tosyl derivatives. All compounds were screened for in vitro antiplasmodial activity against chloroquine-sensitive (3D7) and multidrug-resistant (Dd2) Plasmodium falciparum parasite lines. Several analogues displayed potent inhibition of P. falciparum growth (IC50 < 500 nM) but only moderate selectivity for P. falciparum versus human neonatal foreskin fibroblast cells.

  7. Synthesis of Substituted Oxo-Azepines by Regio- and Diastereoselective Hydroxylation

    Directory of Open Access Journals (Sweden)

    Harold Spedding

    2017-10-01

    Full Text Available Substituted seven-membered N-heterocycles are prevalent bioactive epitopes and useful synthons for preparing enzyme inhibitors or molecular recognition systems. To fully exploit the chemical properties of this flexible N-heterocycle scaffold, efficient methods for its diverse functionalization are required. Here we utilize the late-stage oxidation of tetrahydroazepines as an approach to access densely functionalized oxo-azepines in a total of 8 steps and ~30% overall yield from commercially available starting materials. Hydroboration of tetrahydroazepines proceeded with diastereoselectivity in a substrate-dependent manner to yield regioisomeric azepanols before their oxidation to the corresponding oxo-azepines. Regioselectivity of the hydroboration step may be improved moderately by a rhodium catalyst, albeit with loss of conversion to a competing hydrogenation pathway. Overall our method allows efficient access to azepanols and oxo-azepines as versatile epitopes and synthons with a high degree of diastereoselectivity and moderate regioselectivity.

  8. Singlet fission in pentacene dimers

    Science.gov (United States)

    Zirzlmeier, Johannes; Lehnherr, Dan; Coto, Pedro B.; Chernick, Erin T.; Casillas, Rubén; Basel, Bettina S.; Thoss, Michael; Tykwinski, Rik R.; Guldi, Dirk M.

    2015-01-01

    Singlet fission (SF) has the potential to supersede the traditional solar energy conversion scheme by means of boosting the photon-to-current conversion efficiencies beyond the 30% Shockley–Queisser limit. Here, we show unambiguous and compelling evidence for unprecedented intramolecular SF within regioisomeric pentacene dimers in room-temperature solutions, with observed triplet quantum yields reaching as high as 156 ± 5%. Whereas previous studies have shown that the collision of a photoexcited chromophore with a ground-state chromophore can give rise to SF, here we demonstrate that the proximity and sufficient coupling through bond or space in pentacene dimers is enough to induce intramolecular SF where two triplets are generated on one molecule. PMID:25858954

  9. Synthesis of benzo-fused 1-azabicyclo[m.n.0]alkanes via the Schmidt reaction: a formal synthesis of gephyrotoxin.

    Science.gov (United States)

    Pearson, W H; Fang, W

    2000-10-20

    The intramolecular capture of benzocyclobutyl, benzocyclopentyl, and benzocyclohexyl carbocations 7 by azides produces spirocyclic aminodiazonium ions 8, which undergo 1,2-C-to-N rearrangement with loss of dinitrogen to produce benzo-fused iminium ions resulting from either aryl (9) or alkyl (10) migration to the electron-deficient nitrogen atom. Reduction of the iminium ions affords regioisomeric benzo-fused 1-azabicyclo[m.n.0]alkanes, e.g., benzopyrrolizidines, benzoindolizidines, benzoquinolizidines, or perhydrobenzo[f]pyrrolo[1,2-a]azepines in two regioisomeric versions, anilines (e.g., 11-14) and benzylic amines (e.g., 15-18), the result of aryl and alkyl migrations, respectively. Generally, aryl migration is preferred, despite modeling that shows that the lowest energy aminodiazonium ions are those where the departing dinitrogen is preferentially antiperiplanar to the migrating alkyl group rather than the aryl group. The utility of this methodology was illustrated by a formal synthesis of the alkaloid gephyrotoxin 4. A dependence on the efficiency and regioselectivity of the Schmidt reaction upon subtle changes in the structure of the cation precursor was observed, necessitating the exploration of a variety of substrates. Fortunately, these materials were easily made. Ultimately, the azido-alkene 81 bearing a 2-bromoethyl side-chain was useful for the Schmidt reaction, producing the known benzo-fused indolizidine 49, which had been transformed by Ito et al. into gephyrotoxin 4. The synthesis of 49 required nine steps (five purifications) from commercially available 4-methoxy-1-indanone 60 and proceeded in 22% overall yield.

  10. Connecting ring and process to fix heaters in a pressure vessel by means of these rings

    International Nuclear Information System (INIS)

    Bailleul, G.; Caloine, P.; Coville, P.

    1984-01-01

    The invention can applies to the installation of heaters for nuclear reactor pressurizer or to the installation of any kind of reheaters by means of electric resistances when these reheaters have to work under important pressures. The connecting ring is made of a single metallic piece, two coaxial tubes joined each other by a skirt nearly radial; the skirt joins an end of the outer cylindrical tube and an intermediate zone of the inner cylindrical tube. The invention concerns also a heater provided with such a connecting ring, substituted for a part of its metallic envelope, and a process of fastening of these heaters on a pressure vessel. The description given in the frame of a pressurizer applies to the case of a gas reheater or to a reheater for liquid under pressure such as liquid sodium in a tank [fr

  11. 'Smoking' mephedrone: the identification of the pyrolysis products of 4-methylmethcathinone hydrochloride.

    Science.gov (United States)

    Kavanagh, Pierce; O'Brien, John; Power, John D; Talbot, Brian; McDermott, Seán D

    2013-05-01

    The ring-substituted cathinone - mephedrone - has gained popularity among recreational drug users over the past several years. It is generally consumed orally or by snorting but reports indicate that it is also ingested by vaporization/inhalation. This study examines the pyrolysis products produced by heating mephedrone under using simulated 'meth pipe' conditions. Thirteen pyrolysis products were identified, the major ones being iso-mephedrone, 4-methylpropiophenone, 4-methylphenylacetone, two pyrazine derivatives formed by dimerization of mephedrone, N-methylated mephedrone (N,N,4-trimethylcatinone), two hydroxylated oxidation products and a diketone. Other minor products formed were identified as 4-methylacetophenone, two α-chloro ketones and N-methylated iso-mephedrone. Copyright © 2012 John Wiley & Sons, Ltd.

  12. Selectively N-protected enantiopure 2,5-disubstituted piperazines

    DEFF Research Database (Denmark)

    Ottesen, Lars Korsgaard; Olsen, Christian Adam; Witt, Matthias

    2009-01-01

    An efficient solid-phase route to ring-substituted piperazines from O-linked resin-bound (S)-aziridine-2-methanol is described. Regioselective microwave-assisted aminolysis followed by intramolecular Fukuyama-Mitsunobu cyclization constitute the key features of the protocol. Simple piperazines...... and diazepanes were readily obtained without preceding N-protection of the acyclic intermediate, whereas attempts to extend this protocol to chiral 2,5-disubstituted piperazines failed. Modifications encompassing N-carbamoylation prior to ring-closure were therefore investigated. However, standard carbamoylating...... on the bulk of the side chain and type of N-protecting group. This protocol readily provided novel cis- and trans-2,5-disubstituted piperazines displaying a variety of N-protecting group patterns after further on-resin manipulations. Also, unexpected by-products obtained during these optimization studies were...

  13. Synthesis and characterization of phenylethynylcarbonyl terminated novel thermosetting imide compound

    Directory of Open Access Journals (Sweden)

    H. Kimura

    2013-02-01

    Full Text Available Phenylethynyl terminated novel imide compound based on 1,3-bis(3-aminophenoxybenzene (APB and phenylethynyl trimellitic anhydride (PETA were prepared. The curing behavior of phenylethynyl terminated imide compound was investigated by differential scanning calorimetry and Fourier transform infrared spectrometry. The curing reaction of phenylethynylcarbonyl end group completed at 220°C, and proceeded much faster than that of phenylethynyl end group. Glass transition temperature of the thermosetting resin from phenylethynylcarbonyl terminated novel imide compound determined by dynamic mechanical analysis was almost the same as that of o-cresolnovolac type epoxy resin. In addition, the thermosetting resin from phenylethynylcarbonyl terminated novel imide compound exhibited excellent thermal and dimensional stabilities. These excellent properties of these phenylethynyl terminated imide compound might be due to the incorporation of alkene group or aromatic ring substitutes in the backbones, which might enhance the chain interaction (molecular packing and reduce the molecular chain mobility.

  14. Ionic polymerization of p-methoxystyrene and other styrene derivatives by radiation. [Gamma radiation

    Energy Technology Data Exchange (ETDEWEB)

    Hayashi, K; Pepper, D C [Trinity Coll., Dublin (Ireland)

    1976-01-01

    Polymerization of p-methoxystyrene by radiation was studied in bulk. Upon drying the monomer, the rate of polymerization, Rsub(p), became greater, changing its dose rate dependence from 0.5 to 1. The molecular weight distribution of the obtained polymers failed to give a bimodal curve; however, the peak molecular weight increased with higher Rsub(p). These kinetic features can be explained by a coexistence of radical and cationic mechanisms, as has been established in styrene, though there remain ambiguities about the effects of additives. Copolymerizations with styrene and 2-chloroethyl vinyl ether also showed a cationic nature for the reaction. A survey of possibilities of ionic polymerization by radiation was also carried out in ten ring-substituted styrene derivatives.

  15. Investigating Biological Activity Spectrum for Novel Styrylquinazoline Analogues

    Directory of Open Access Journals (Sweden)

    Jaroslaw Polanski

    2009-10-01

    Full Text Available In this study, series of ring-substituted 2-styrylquinazolin-4(3H-one and 4-chloro-2-styrylquinazoline derivatives were prepared. The syntheses of the discussed compounds are presented. The compounds were analyzed by RP-HPLC to determine lipophilicity. They were tested for their inhibitory activity on photosynthetic electron transport (PET in spinach (Spinacia oleracea L. chloroplasts. Primary in vitro screening of the synthesized compounds was also performed against four mycobacterial strains and against eight fungal strains. Several compounds showed biological activity comparable with or higher than that of the standard isoniazid. It was found that the electronic properties of the R substituent, and not the total lipophilicity of the compound, were decisive for the photosynthesis-inhibiting activity of tested compounds.

  16. Radioiodinated iodobenzoyl conjugates of a monoclonal antibody Fab fragment. In vivo comparisons with chloramine-T-labeled Fab

    International Nuclear Information System (INIS)

    Wilbur, D.S.; Hadley, S.W.; Grant, L.M.; Hylarides, M.D.

    1991-01-01

    A comparative investigation of the biodistributions of radioiodinated p- and m-iodobenzoyl conjugates of a monoclonal antibody Fab fragment, NR-LU-10 Fab, and the same antibody Fab fragment radioiodinated by the chloramine-T (ChT) method has been carried out in mice. Coinjected, dual-isotope studies in athymic mice with tumor xenografts have demonstrated that there are only minor differences in the in vivo distributions of the iodobenzoyl-labeled Fabs, except in the excretory organs, kidneys, and intestines, where major differences were observed. Similarly, coinjection of either the p-iodobenzoyl or m-iodobenzoyl conjugate of NR-LU-10 Fab with the Fab radioiodinated with ChT/radioiodide into BALB/c mice provided additional data that indicated that the two iodobenzoyl conjugates distributed similar in a number of selected tissues. The tissue-distribution differences of the regioisomeric iodobenzoyl conjugates in relation to the ChT-radioiodinated Fab were large for the stomach and neck, consistent with previous studies. The most notable difference between the two iodobenzoyl conjugates was the kidney activity, where the m-iodobenzoyl conjugate was similar to the directly labeled Fab, but the p-iodobenzoyl-conjugated Fab was higher by nearly a factor of 2

  17. Theoretical and conceptual density functional theory (DFT) study on selectivity of 4-hydroxyquinazoline electrophilic aromatic nitration

    Science.gov (United States)

    Makhloufi, A.; Belhadad, O.; Ghemit, R.; Baitiche, M.; Merbah, M.; Benachour, DJ.

    2018-01-01

    In common with other aza-heterocycles, 4-hydroxyquinazoline and their derivatives are important pharmacophores and versatile lead molecule used in several specific biological activities. The potency of these compounds depends on the nature and/or position of their substituents. In this paper, we report a theoretical study of the most probable nitration reaction centers of 4-hydroxyquinazoline for electrophilic attack, the mono and di-nitration was also discussed. In parallel, a computational study has been performed in gas by using the B3LYP/6311 G(d) level. The stability of the four nitro isomers is rationalized by means of the global index and local reactivity indices. Their molecular electrostatic potential (MEP) and Milliken charge were explored. Molecular geometries and NMR H spectra was examined. In addition, stationary points of reactant, transition state and intermediate were optimized in water condensed phase at the same level. The relative energies of the regioisomeric δ-complexes confirm that the substitution at C6 (6-nitro σ-complexes) is favored in these conditions, what was in agreement with our others calculating results (in gas).

  18. A theoretical investigation on the regioselectivity of the intramolecular hetero Diels-Alder and 1,3-dipolar cycloaddition of 2-vinyloxybenzaldehyde derivatives

    Directory of Open Access Journals (Sweden)

    Hamzehloueian Mahshid

    2014-01-01

    Full Text Available The present study reports a systematic computational analysis of the two possible pathways, fused and bridged, for an intramolecular hetero Diels-Alder (IMHDA and an intramolecular 1,3-dipolar cycloaddition (IMDCA of 2-vinyloxybenzaldehyde derivatives. The potential energy surface analysis for both reactions is in agreement with experimental observations. The activation energies associated with the two regioisomeric channels in IMHDA reaction show that the bridged product is favored, although in IMDCA, the most stable TS results the fused product. The global electronic properties of fragments within each molecule were studied to discuss the reactivity patterns and charge transfer direction in the intramolecular processes. The asynchronicity of the bond formation and aromaticity of the optimized TSs in the Diels-Alder reaction as well as cycloaddition reaction were evaluated. Finally, 1H NMR chemical shifts of the possible regioisomers have been calculated using the GIAO method which of the most stable products are in agreement with the experimental data in the both reaction.

  19. Indexing molecules with chemical graph identifiers.

    Science.gov (United States)

    Gregori-Puigjané, Elisabet; Garriga-Sust, Rut; Mestres, Jordi

    2011-09-01

    Fast and robust algorithms for indexing molecules have been historically considered strategic tools for the management and storage of large chemical libraries. This work introduces a modified and further extended version of the molecular equivalence number naming adaptation of the Morgan algorithm (J Chem Inf Comput Sci 2001, 41, 181-185) for the generation of a chemical graph identifier (CGI). This new version corrects for the collisions recognized in the original adaptation and includes the ability to deal with graph canonicalization, ensembles (salts), and isomerism (tautomerism, regioisomerism, optical isomerism, and geometrical isomerism) in a flexible manner. Validation of the current CGI implementation was performed on the open NCI database and the drug-like subset of the ZINC database containing 260,071 and 5,348,089 structures, respectively. The results were compared with those obtained with some of the most widely used indexing codes, such as the CACTVS hash code and the new InChIKey. The analyses emphasize the fact that compound management activities, like duplicate analysis of chemical libraries, are sensitive to the exact definition of compound uniqueness and thus still depend, to a minor extent, on the type and flexibility of the molecular index being used. Copyright © 2011 Wiley Periodicals, Inc.

  20. Baking reduces prostaglandin, resolvin, and hydroxy-fatty acid content of farm-raised Atlantic salmon (Salmo salar).

    Science.gov (United States)

    Raatz, Susan K; Golovko, Mikhail Y; Brose, Stephen A; Rosenberger, Thad A; Burr, Gary S; Wolters, William R; Picklo, Matthew J

    2011-10-26

    The consumption of seafood enriched in n-3 polyunsaturated fatty acids (PUFA) is associated with a decreased risk of cardiovascular disease. Several n-3 oxidation products from eicosapentaenoic acid (EPA; 20:5n-3) and docosahexaenoic acid (22:6n-3) have known protective effects in the vasculature. It is not known whether the consumption of cooked seafood enriched in n-3 PUFA causes appreciable consumption of lipid oxidation products. We tested the hypothesis that baking Atlantic salmon (Salmo salar) increases the level of n-3 and n-6 PUFA oxidation products over raw salmon. We measured the contents of several monohydroxy-fatty acids (MHFA), prostanoids, and resolvins. Our data demonstrate that baking did not change the overall total levels of MHFA. However, baking resulted in selective regioisomeric loss of hydroxy fatty acids from arachidonic acid (20:4n-6) and EPA, while significantly increasing hydroxyl-linoleic acid levels. The contents of prostanoids and resolvins were reduced several-fold with baking. The inclusion of a coating on the salmon prior to baking reduced the loss of some MHFA but had no effect on prostanoid losses incurred by baking. Baking did not decrease n-3 PUFA contents, indicating that baking of salmon is an acceptable means of preparation that does not alter the potential health benefits of high n-3 seafood consumption. The extent to which the levels of MHFA, prostanoids, and resolvins in the raw or baked fish have physiologic consequence for humans needs to be determined.

  1. Synthesis of trans-disubstituted alkenes by cobalt-catalyzed reductive coupling of terminal alkynes with activated alkenes.

    Science.gov (United States)

    Mannathan, Subramaniyan; Cheng, Chien-Hong

    2012-09-10

    A cobalt-catalyzed reductive coupling of terminal alkynes, RC≡CH, with activated alkenes, R'CH=CH(2), in the presence of zinc and water to give functionalized trans-disubstituted alkenes, RCH=CHCH(2)CH(2)R', is described. A variety of aromatic terminal alkynes underwent reductive coupling with activated alkenes including enones, acrylates, acrylonitrile, and vinyl sulfones in the presence of a CoCl(2)/P(OMe)(3)/Zn catalyst system to afford 1,2-trans-disubstituted alkenes with high regio- and stereoselectivity. Similarly, aliphatic terminal alkynes also efficiently participated in the coupling reaction with acrylates, enones, and vinyl sulfone, in the presence of the CoCl(2)/P(OPh)(3)/Zn system providing a mixture of 1,2-trans- and 1,1-disubstituted functionalized terminal alkene products in high yields. The scope of the reaction was also extended by the coupling of 1,3-enynes and acetylene gas with alkenes. Furthermore, a phosphine-free cobalt-catalyzed reductive coupling of terminal alkynes with enones, affording 1,2-trans-disubstituted alkenes as the major products in a high regioisomeric ratio, is demonstrated. In the reactions, less expensive and air-stable cobalt complexes, a mild reducing agent (Zn) and a simple hydrogen source (water) were used. A possible reaction mechanism involving a cobaltacyclopentene as the key intermediate is proposed. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. Structural Analysis of Unsaturated Glycosphingolipids Using Shotgun Ozone-Induced Dissociation Mass Spectrometry

    Science.gov (United States)

    Barrientos, Rodell C.; Vu, Ngoc; Zhang, Qibin

    2017-08-01

    Glycosphingolipids are essential biomolecules widely distributed across biological kingdoms yet remain relatively underexplored owing to both compositional and structural complexity. While the glycan head group has been the subject of most studies, there is paucity of reports on the lipid moiety, particularly the location of unsaturation. In this paper, ozone-induced dissociation mass spectrometry (OzID-MS) implemented in a traveling wave-based quadrupole time-of-flight (Q-ToF) mass spectrometer was applied to study unsaturated glycosphingolipids using shotgun approach. Resulting high resolution mass spectra facilitated the unambiguous identification of diagnostic OzID product ions. Using [M+Na]+ adducts of authentic standards, we observed that the long chain base and fatty acyl unsaturation had distinct reactivity with ozone. The reactivity of unsaturation in the fatty acyl chain was about 8-fold higher than that in the long chain base, which enables their straightforward differentiation. Influence of the head group, fatty acyl hydroxylation, and length of fatty acyl chain on the oxidative cleavage of double bonds was also observed. Application of this technique to bovine brain galactocerebrosides revealed co-isolated isobaric and regioisomeric species, which otherwise would be incompletely identified using contemporary collision-induced dissociation (CID) alone. These results highlight the potential of OzID-MS in glycosphingolipids research, which not only provides complementary structural information to existing CID technique but also facilitates de novo structural determination of these complex biomolecules. [Figure not available: see fulltext.

  3. From pirazoloquinolines to annulated azulene dyes: UV-VIS spectroscopy and quantum chemical study

    International Nuclear Information System (INIS)

    Gasiorski, P.; Danel, K.S.; Matusiewicz, M.; Uchacz, T.; Kityk, A.V.

    2010-01-01

    Paper reports UV-Vis absorption and photoluminescence spectra of 6-R derivatives (R=CH 3 , O-CH 3 , C(C 6 H 5 ) 3 , C 6 H 5 -N-C 10 H 7 ) of 4-(2-chlorophenyl)-1,3-diphenyl-1H-pyrazolo[3,4-b]quinoline, belonging to pyrazoloquinoline (PQ) family, likewise its regioisomeric products 10-R derivatives of 6-phenyl-6H-5,6,7-triazadibenzo[f,h]naphtho[3,2,1-cd]azulene representing cyclized seven-membered annulated azulene (AA) dyes. Cyclization of PQs into AAs is accompanied by a significant red shift of the first optical absorption band. This finding agrees with the results of quantum-chemical calculations performed by means of the semiempirical method PM3. As the solvent polarity rises all the dyes exhibit a blue shift of the first absorption band and a red shift of the fluorescence band. Such opposite trends in solvatochromic behavior have been reproduced within the semiempirical calculations in combination with the Lippert-Mataga dielectric polarization model. Depending on solvent polarity AA dyes emit light in the green, green-yellow or orange range of the visible spectrum what may be of interest for potential luminescent or electroluminescent applications.

  4. Substituted Amides of Pyrazine-2-carboxylic acids: Synthesis and Biological Activity

    Directory of Open Access Journals (Sweden)

    Katarina Kralova

    2002-03-01

    Full Text Available Condensation of 6-chloro-, 5-tert-butyl- or 6-chloro-5-tert-butylpyrazine-2-carboxylic acid chloride with ring substituted anilines yielded a series of amides, which were tested for their in vitro antimycobacterial, antifungal and photosynthesis-inhibiting activities. The highest antituberculotic activity (72% inhibition against Mycobacterium tuberculosis and the highest lipophilicity (log P = 6.85 were shown by the 3,5-bistrifluoromethylphenyl amide of 5-tert-butyl-6-chloropyrazine-2-carboxylic acid (2o. The 3-methylphenyl amides of 6-chloro- and 5-tert-butyl-6-chloro-pyrazine-2-carboxylic acid (2d and 2f exhibited only a poor in vitro antifungal effect (MIC = 31.25-500 μmol·dm-3 against all strains tested, although the latter was the most active antialgal compound (IC50 = 0.063 mmol·dm-3. The most active inhibitor of oxygen evolution rate in spinach chloroplasts was the (3,5-bis-trifluoromethylphenylamide of 6-chloropyrazine-2-carboxylic acid (2m, IC50 = 0.026 mmol·dm-3.

  5. Benzo[1,2-b:4,5-b’]dithiophene-Pyrido[3,4-b]pyrazine Small-Molecule Donors for Bulk Heterojunction Solar Cells

    KAUST Repository

    Wolf, Jannic Sebastian; Babics, Maxime; Wang, Kai; Saleem, Qasim; Liang, Ru-Ze; Hansen, Michael Ryan; Beaujuge, Pierre

    2016-01-01

    We report on the synthesis, material properties and BHJ solar cell characteristics of a set of π-conjugated small-molecule (SM) donors composed of benzo[1,2-b:4,5-b′]dithiophene (BDT) and pyrido[3,4-b]pyrazine (PP) units – examining the perspectives of alkyl-substituted PP acceptor motifs in SM designs. In these systems (SM1-4), both the type of side chains derived from the PP motifs and the presence of ring-substituents on BDT critically impact (i) molecular packing, and (ii) thin-film morphologies and charge transport in BHJ solar cells. With the appropriate side-chain pattern, the ring-substituted analogue SM4 stands out: achieving efficiencies of ca. 6.5% with PC71BM, and fine-scale morphologies comparable to those obtained with some of the best-performing polymer donors in BHJ solar cells. 1H-1H DQ-SQ NMR analyses are used to examine the distinct self-assembly pattern of SM4, expected to factor into the development of the BHJ morphology.

  6. Trypanocidal 1,3-arylene diketone bis(guanylhydrazone)s. Structure-activity relationships among substituted and heterocyclic analogues.

    Science.gov (United States)

    Ulrich, P; Cerami, A

    1984-01-01

    Based on the antitrypanosomal activity of 1,3-diacetylbenzene bis(guanylhydrazone) (4) and 2,6-diacetylpyridine bis(guanylhydrazone) (17), a number of substituted and heterocyclic 1,3-arylene diketone bis(guanylhydrazone)s were prepared and tested against Trypanosoma brucei infections in mice. A wide range of ED50 values was observed among 5-substituted derivatives of 4. The 5-amino analogue 5 and 5-acetamido analogue 6 were about twice as active as 4. 1,3,5-Triacetylbenzene tris(guanylhydrazone) (12) was about 9 times as active as 4 and was approximately one-half as active as the currently used trypanocide diminazene aceturate in this test system. Other 5-derivatives had activity equivalent to or less than that of the parent compound 4. Three new heterocyclic analogues were all less active than 2,6-diacetylpyridine derivative 17 and benzene derivative 4. Ring substitution ortho to the guanylhydrazone side chains was invariably detrimental to activity. Side-chain homologues 1,3-dipentanoylbenzene bis(guanylhydrazone) and 1,3-diacetylbenzene bis(2-imidazolin-2-ylhydrazone) were essentially inactive.

  7. Aromatic products from reaction of lignin model compounds with UV-alkaline peroxide

    International Nuclear Information System (INIS)

    Sun, Y.P.; Wallis, A.F.A.; Nguyen, K.L.

    1997-01-01

    A series of guaiacyl and syringyl lignin model compounds and their methylated analogues were reacted with alkaline hydrogen peroxide while irradiating with UV light at 254 nm. The aromatic products obtained were investigated by gas chromatography-mass spectrometry (GC-MS). Guaiacol, syringol and veratrol gave no detectable aromatic products. However, syringol methyl ether gave small amounts of aromatic products, resulting from ring substitution and methoxyl displacement by hydroxyl radicals. Reaction of vanillin and syringaldehyde gave the Dakin reaction products, methoxy-1,4-hydroquinones, while reaction of their methyl ethers yielded benzoic acids. Acetoguaiacone, acetosyringone and their methyl ethers afforded several hydroxylated aromatic products, but no aromatic products were identified in the reaction mixtures from guaiacylpropane and syringylpropane. In contrast, veratrylpropane gave a mixture from which 17 aromatic hydroxylated compounds were identified. It is concluded that for phenolic lignin model compounds, particularly those possessing electrondonating aromatic ring substituents, ring-cleavage reactions involving superoxide radical anions are dominant, whereas for non-phenolic lignin models, hydroxylation reactions through attack of hydroxyl radicals prevail

  8. Correlation among Singlet-Oxygen Quenching, Free-Radical Scavenging, and Excited-State Intramolecular-Proton-Transfer Activities in Hydroxyflavones, Anthocyanidins, and 1-Hydroxyanthraquinones.

    Science.gov (United States)

    Nagaoka, Shin-Ichi; Bandoh, Yuki; Nagashima, Umpei; Ohara, Keishi

    2017-10-26

    Singlet-oxygen ( 1 O 2 ) quenching, free-radical scavenging, and excited-state intramolecular proton-transfer (ESIPT) activities of hydroxyflavones, anthocyanidins, and 1-hydroxyanthraquinones were studied by means of laser, stopped-flow, and steady-state spectroscopies. In hydroxyflavones and anthocyanidins, the 1 O 2 quenching activity positively correlates to the free-radical scavenging activity. The reason for this correlation can be understood by considering that an early step of each reaction involves electron transfer from the unfused phenyl ring (B-ring), which is singly bonded to the bicyclic chromen or chromenylium moiety (A- and C-rings). Substitution of an electron-donating OH group at B-ring enhances the electron transfer leading to activation of the 1 O 2 quenching and free-radical scavenging. In 3-hydroxyflavones, the OH substitution at B-ring reduces the activity of ESIPT within C-ring, which can be explained in terms of the nodal-plane model. As a result, the 1 O 2 quenching and free-radical scavenging activities negatively correlate to the ESIPT activity. A catechol structure at B-ring is another factor that enhances the free-radical scavenging in hydroxyflavones. In contrast to these hydroxyflavones, 1-hydroxyanthraquinones having an electron-donating OH substituent adjacent to the O-H---O═C moiety susceptible to ESIPT do not show a simple correlation between their 1 O 2 quenching and ESIPT activities, because the OH substitution modulates these reactions.

  9. Solid/liquid extraction equilibria of phenolic compounds with trioctylphosphine oxide impregnated in polymeric membranes.

    Science.gov (United States)

    Praveen, Prashant; Loh, Kai-Chee

    2016-06-01

    Trioctylphosphine oxide based extractant impregnated membranes (EIM) were used for extraction of phenol and its methyl, hydroxyl and chloride substituted derivatives. The distribution coefficients of the phenols varied from 2 to 234, in the order of 1-napthol > p-chlorophenol > m-cresol > p-cresol > o-cresol > phenol > catechol > pyrogallol > hydroquinone, when initial phenols loadings was varied in 100-2000 mg/L. An extraction model, based on the law of mass action, was formulated to predict the equilibrium distribution of the phenols. The model was in excellent agreement (R(2) > 0.97) with the experimental results at low phenols concentrations ( 0.95), which signified high mass transfer resistance in the EIMs. Examination of the effects of ring substitution on equilibrium, and bivariate statistical analysis between the amounts of phenols extracted into the EIMs and factors affecting phenols interaction with TOPO, indicated the dominant role of hydrophobicity in equilibrium determination. These results improve understanding of the solid/liquid equilibrium process between phenols and the EIMs, and these will be useful in designing phenol recovery process from wastewater. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. Abundant and stable char residues in soils: implications for soil fertility and carbon sequestration.

    Science.gov (United States)

    Mao, J-D; Johnson, R L; Lehmann, J; Olk, D C; Neves, E G; Thompson, M L; Schmidt-Rohr, K

    2012-09-04

    Large-scale soil application of biochar may enhance soil fertility, increasing crop production for the growing human population, while also sequestering atmospheric carbon. But reaching these beneficial outcomes requires an understanding of the relationships among biochar's structure, stability, and contribution to soil fertility. Using quantitative (13)C nuclear magnetic resonance (NMR) spectroscopy, we show that Terra Preta soils (fertile anthropogenic dark earths in Amazonia that were enriched with char >800 years ago) consist predominantly of char residues composed of ~6 fused aromatic rings substituted by COO(-) groups that significantly increase the soils' cation-exchange capacity and thus the retention of plant nutrients. We also show that highly productive, grassland-derived soils in the U.S. (Mollisols) contain char (generated by presettlement fires) that is structurally comparable to char in the Terra Preta soils and much more abundant than previously thought (~40-50% of organic C). Our findings indicate that these oxidized char residues represent a particularly stable, abundant, and fertility-enhancing form of soil organic matter.

  11. Antiproliferative and Pro-Apoptotic Effect of Novel Nitro-Substituted Hydroxynaphthanilides on Human Cancer Cell Lines

    Directory of Open Access Journals (Sweden)

    Tereza Kauerova

    2016-07-01

    Full Text Available Ring-substituted hydroxynaphthanilides are considered as cyclic analogues of salicylanilides, compounds possessing a wide range of pharmacological activities, including promising anticancer properties. The aim of this study was to evaluate the potential anticancer effect of novel nitro-substituted hydroxynaphthanilides with a special focus on structure-activity relationships. The antiproliferative effect was assessed by Water Soluble Tetrazolium Salts-1 (WST-1 assay, and cytotoxicity was evaluated via dye exclusion test. Flow cytometry was used for cell cycle analysis and detection of apoptosis using Annexin V-FITC/PI assay. Protein expression was estimated by Western blotting. Our data indicate that the potential to cause the antiproliferative effect increases with the shift of the nitro substituent from the ortho- to the para-position. The most potent compounds, 3-hydroxy-N-(3-nitrophenylnaphthalene-2-carboxamide (2, and 2-hydroxy-N-(4-nitrophenyl-naphthalene-1-carboxamide (6 showed antiproliferative activity against THP-1 and MCF-7 cancer cells without affecting the proliferation of 3T3-L1 non-tumour cells. Compounds 2 and 6 induced the accumulation of THP-1 and MCF-7 cells in G1 phase associated with the downregulation of cyclin E1 protein levels, while the levels of cyclin B1 were not affected. Moreover, compound 2 was found to exert the pro-apoptotic effect on the THP-1 cells. These results suggest that hydroxynaphthanilides might represent a potential model structure for the development of novel anticancer agents.

  12. Measurement of 3,4-MDMA and related amines in diagnostic and forensic laboratories.

    Science.gov (United States)

    Skrinska, Victor A; Gock, Susan B

    2005-01-01

    The phenylalkylamine derivatives, 3,4-methylenedioxymethamphetamine (MDMA, ecstasy, XTC, Adam), 3,4-methylenedioxyethamphetamine (MDEA, MDE, Eve), and 3,4-methylenedioxyamphetamine (MDA), are psychostimulants with hallucinogenic properties. MDA is also a metabolite of both MDMA and MDEA. These drugs are ring-substituted amphetamine derivatives that produce hallucinogenic, entactogenic ('love drug'), and stimulating effects. MDMA was initially developed as an appetite suppressant, however, its use as a therapeutic drug has been very limited. Because of its effects as a hallucinogenic psychostimulant with relatively low toxicity, it has emerged over the last two decades as a common recreational psychostimulant or 'club drug' at 'raves'. MDMA, MDEA, and MDA are often referred to as 'rave' or 'designer' drugs. They are produced in clandestine laboratories and have an increasing presence on the illicit drug market worldwide. Significant adverse health effects have been reported that include: serotonin neurotoxicity, severe psychiatric disorders, renal failure, malignant hyperthermia, hepatitis, rhabdomyolysis, and disseminated intravascular coagulation. A number of fatal outcomes associated with severe MDMA intoxication have been reported.

  13. Imidazole Alkaloids from the South China Sea Sponge Pericharax heteroraphis and Their Cytotoxic and Antiviral Activities

    Directory of Open Access Journals (Sweden)

    Kai-Kai Gong

    2016-01-01

    Full Text Available Marine sponges continue to serve as a rich source of alkaloids possessing interesting biological activities and often exhibiting unique structural frameworks. In the current study, chemical investigation on the marine sponge Pericharax heteroraphis collected from the South China Sea yielded one new imidazole alkaloid named naamidine J (1 along with four known ones (2–5. Their structures were established by extensive spectroscopic methods and comparison of their data with those of the related known compounds. All the isolates possessed a central 2-aminoimidazole ring, substituted by one or two functionalized benzyl groups in some combination of the C4 and C5 positions. The cytotoxicities against selected HL-60, HeLa, A549 and K562 tumor cell lines and anti-H1N1 (Influenza a virus (IAV activity for the isolates were evaluated. Compounds 1 and 2 exhibited cytotoxicities against the K562 cell line with IC50 values of 11.3 and 9.4 μM, respectively. Compound 5 exhibited weak anti-H1N1 (influenza a virus, IAV activity with an inhibition ratio of 33%.

  14. Substituted N-Phenylpyrazine-2-carboxamides, Their Synthesis and Evaluation as Herbicides and Abiotic Elicitors

    Directory of Open Access Journals (Sweden)

    Katarína Kráľová

    2007-12-01

    Full Text Available The condensation of substituted pyrazine-2-carboxylic acid chlorides with ring-substituted anilines yielded five substituted pyrazine-2-carboxylic acid amides. Thesynthesis, and analytical, lipophilicity and biological data of the newly synthesizedcompounds are presented in this paper. The photosynthesis inhibition, antialgal activityand the effect of a series of pyrazine derivatives as abiotic elicitors on the accumulation offlavonoids in a callus culture of Ononis arvensis (L. were investigated. The most activeinhibitor of the oxygen evolution rate in spinach chloroplasts was 6-chloro-pyrazine-2-carboxylic acid (3-iodo-4-methylphenyl-amide (2, IC50 = 51.0 μmol·L-1. The highestreduction of chlorophyll content in Chlorella vulgaris was found for 5-tert-butyl-N-(4-chloro-3-methylphenyl-pyrazine-2-carboxamide (3, IC50 = 44.0 μmol·L-1. The maximalflavonoid production (about 900% was reached after a twelve-hour elicitation processwith 6-chloropyrazine-2-carboxylic acid (3-iodo-4-methylphenyl-amide (2.

  15. Benzo[1,2-b:4,5-b’]dithiophene-Pyrido[3,4-b]pyrazine Small-Molecule Donors for Bulk Heterojunction Solar Cells

    KAUST Repository

    Wolf, Jannic Sebastian

    2016-01-22

    We report on the synthesis, material properties and BHJ solar cell characteristics of a set of π-conjugated small-molecule (SM) donors composed of benzo[1,2-b:4,5-b′]dithiophene (BDT) and pyrido[3,4-b]pyrazine (PP) units – examining the perspectives of alkyl-substituted PP acceptor motifs in SM designs. In these systems (SM1-4), both the type of side chains derived from the PP motifs and the presence of ring-substituents on BDT critically impact (i) molecular packing, and (ii) thin-film morphologies and charge transport in BHJ solar cells. With the appropriate side-chain pattern, the ring-substituted analogue SM4 stands out: achieving efficiencies of ca. 6.5% with PC71BM, and fine-scale morphologies comparable to those obtained with some of the best-performing polymer donors in BHJ solar cells. 1H-1H DQ-SQ NMR analyses are used to examine the distinct self-assembly pattern of SM4, expected to factor into the development of the BHJ morphology.

  16. Synthesis, Antimycobacterial, Antifungal and Photosynthesis-Inhibiting Activity of Chlorinated N-phenylpyrazine-2-carboxamides †

    Directory of Open Access Journals (Sweden)

    Katarina Kralova

    2010-11-01

    Full Text Available A series of sixteen pyrazinamide analogues with the -CONH- linker connecting the pyrazine and benzene rings was synthesized by the condensation of chlorides of substituted pyrazinecarboxylic acids with ring-substituted (chlorine anilines. The prepared compounds were characterized and evaluated for their antimycobacterial and antifungal activity, and for their ability to inhibit photosynthetic electron transport (PET. 6-Chloro-N-(4-chlorophenylpyrazine-2-carboxamide manifested the highest activity against Mycobacterium tuberculosis strain H37Rv (65% inhibition at 6.25 μg/mL. The highest antifungal effect against Trichophyton mentagrophytes, the most susceptible fungal strain tested, was found for 6-chloro-5-tert-butyl-N-(3,4-dichlorophenylpyrazine-2-carboxamide (MIC = 62.5 μmol/L. 6-Chloro-5-tert-butyl-N-(4-chlorophenylpyrazine-2-carboxamide showed the highest PET inhibition in spinach chloroplasts (Spinacia oleracea L. chloroplasts (IC50 = 43.0 μmol/L. For all the compounds, the relationships between the lipophilicity and the chemical structure of the studied compounds as well as their structure-activity relationships are discussed.

  17. Revised mechanism of Boyland-Sims oxidation.

    Science.gov (United States)

    Marjanović, Budimir; Juranić, Ivan; Cirić-Marjanović, Gordana

    2011-04-21

    New computational insights into the mechanism of the Boyland-Sims oxidation of arylamines with peroxydisulfate (S(2)O(8)(2-)) in an alkaline aqueous solution are presented. The key role of arylnitrenium cations, in the case of primary and secondary arylamines, and arylamine dications and immonium cations, in the case of tertiary arylamines, in the formation of corresponding o-aminoaryl sulfates, as prevalent soluble products, and oligoarylamines, as prevalent insoluble products, is proposed on the basis of the AM1 and RM1 computational study of the Boyland-Sims oxidation of aniline, ring-substituted (2-methylaniline, 3-methylaniline, 4-methylaniline, 2,6-dimethylaniline, anthranilic acid, 4-aminobenzoic acid, sulfanilic acid, sulfanilamide, 4-phenylaniline, 4-bromoaniline, 3-chloroaniline, and 2-nitroaniline) and N-substituted anilines (N-methylaniline, diphenylamine, and N,N-dimethylaniline). Arylnitrenium cations and sulfate anions (SO(4)(2-)) are generated by rate-determining two-electron oxidation of primary and secondary arylamines with S(2)O(8)(2-), while arylamine dications/immonium cations and SO(4)(2-) are initially formed by two-electron oxidation of tertiary arylamines with S(2)O(8)(2-). The subsequent regioselectivity-determining reaction of arylnitrenium cations/arylamine dications/immonium cations and SO(4)(2-), within the solvent cage, is computationally found to lead to the prevalent formation of o-aminoaryl sulfates. The formation of insoluble precipitates during the Boyland-Sims oxidation of arylamines was also computationally studied.

  18. Structure-Activity Relationships of 1,2-Disubstituted Benzimidazoles: Selective Inhibition of Heme Oxygenase-2 Activity.

    Science.gov (United States)

    Kong, Xianqi; Vukomanovic, Dragic; Nakatsu, Kanji; Szarek, Walter A

    2015-08-01

    Devising ways to up- or down-regulate heme oxygenase activity is attracting much interest as a strategy for the treatment of a variety of disorders. With a view of obtaining compounds that exhibit high potency and selectivity as inhibitors of the heme oxygenase-2 (HO-2) isozyme (constitutive) relative to the heme oxygenase-1 (HO-1) isozyme (inducible), several 1,2-disubstituted 1H-benzimidazoles were designed and synthesized. Specifically, analogues were synthesized in which the C2 substituent was the following: (1H-imidazol-1-yl)methyl, (N-morpholinyl)methyl, cyclopentylmethyl, cyclohexylmethyl, or (norborn-2-yl)methyl. Compounds with the cyclic system in the C2 substituent being a carbocyclic ring, especially cyclohexyl or norborn-2-yl, and the N1 substituent being a ring-substituted benzyl group, especially 4-chlorobenzyl or 4-bromobenzyl, best exhibited the target criteria of high potency and selectivity toward inhibition of HO-2. The new candidates should be useful pharmacological tools and may have therapeutic applications. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  19. Kinetic investigation of the catalytic mechanism for bovine liver mitochondrial monoamine oxidase

    International Nuclear Information System (INIS)

    Walker, M.C.

    1988-01-01

    The kinetic behavior of the oxidative deamination reaction catalyzed by bovine liver mitochondrial monoamine oxidase was investigated with a series of ring-substituted benzylamines. Oxidation rates were fastest with the meta isomers. Dalziel coefficients were consistent with a mechanism involving a ternary complex for all substrates tested. Alterations in the Michaelis constant for oxygen were similar in magnitude to those for the rate of catalysis. Deuterium and tritium isotope effects were determined to obtain more detailed information on the mechanism of catalysis. Large deuterium isotope effects expressed on k cat were obtained for all substrates. Determination of the tritium isotope effect for benzylamine allowed the calculation of an intrinsic isotope effect of 6.5 and a secondary isotope effect of 1.17. Steady-state experiments were supplemented with pre-steady-state kinetic techniques. Rates of flavin reduction were faster than that of turnover. The deuterium isotope effect obtained for the rate of flavin reduction was 7-15 for the various substrates. The observed isotope effect was found to be an appropriate estimate for the intrinsic isotope effect

  20. Diallyl 5-[(4-hexyloxyphenyliminomethyl]-m-phenylene dicarbonate

    Directory of Open Access Journals (Sweden)

    Ana María Herrera-González

    2009-11-01

    Full Text Available The title molecule, C27H31NO7, an imine derivative bearing both carbonate and allyl functionalities, was synthesized in the hope of obtaining a mesogenic polymerizable material. The allylcarbonate arms are fully disordered over two sets of sites, reflecting a large degree of rotational freedom about σ bonds [occupancies: 0.665 (9/0.335 (9 for one substituent, 0.564 (9/0.436 (9 for the other]. In contrast, the hexyl chain is ordered, and presents the common all-trans extended conformation. The benzene rings connected via the imine group make a dihedral angle of 9.64 (11°. In the crystal, the Y-shaped molecules are weakly associated into centrosymmetric dimers through pairs of C—H...O(hexyl contacts. The resulting layers of dimers, approximately parallel to (2overline{2}5, are closely packed in the crystal, allowing π...π interactions between benzene rings of neighboring layers: the separation between the centroid of the benzene ring substituted by allylcarbonate and the centroid of the benzene ring bearing the hexyloxy group in the adjacent layer is 3.895 (1 Å.

  1. Diallyl 5-[(4-hexyl-oxyphen-yl)imino-meth-yl]-m-phenyl-ene dicarbonate.

    Science.gov (United States)

    Herrera-González, Ana María; López-Velázquez, Delia; Bernès, Sylvain

    2009-10-23

    The title mol-ecule, C(27)H(31)NO(7), an imine derivative bearing both carbonate and allyl functionalities, was synthesized in the hope of obtaining a mesogenic polymerizable material. The allyl-carbonate arms are fully disordered over two sets of sites, reflecting a large degree of rotational freedom about σ bonds [occupancies: 0.665 (9)/0.335 (9) for one substituent, 0.564 (9)/0.436 (9) for the other]. In contrast, the hexyl chain is ordered, and presents the common all-trans extended conformation. The benzene rings connected via the imine group make a dihedral angle of 9.64 (11)°. In the crystal, the Y-shaped mol-ecules are weakly associated into centrosymmetric dimers through pairs of C-H⋯O(hex-yl) contacts. The resulting layers of dimers, approximately parallel to (25), are closely packed in the crystal, allowing π⋯π inter-actions between benzene rings of neighboring layers: the separation between the centroid of the benzene ring substituted by allyl-carbonate and the centroid of the benzene ring bearing the hex-yloxy group in the adjacent layer is 3.895 (1) Å.

  2. Identification of regioisomers of methylated kaempferol and quercetin by ultra high performance liquid chromatography quadrupole time-of-flight (UHPLC–QTOF) tandem mass spectrometry combined with diagnostic fragmentation pattern analysis

    International Nuclear Information System (INIS)

    Ma, Chengying; Lv, Haipeng; Zhang, Xinzhong; Chen, Zongmao; Shi, Jiang; Lu, Meiling; Lin, Zhi

    2013-01-01

    Highlights: •Found methane elimination is position-specific for methylated flavonols. •Found retro Diels–Alder fragments retained methoxy at original ring of flavonols. •Proposed a diagnostic pattern for discriminating regioisomers of flavonols. •Identified the specificity of three novel flavonol O-methyltransferases. •Identified six biologically active compounds and four new compounds. -- Abstract: The O-methylation of active flavonoids can enhance their antiallergic, anticancerous, and cardioprotective effects depending on the methylation position. Thus, it is biologically and pharmacologically important to differentiate methylated flavonoid regioisomers. In this study, we examined the regioisomers of methylated kaempferol and quercetin using ultra high performance liquid chromatography quadrupole time-of-flight tandem mass spectrometry. The methyl groups on the flavonoids can generally be cleaved as methyl radicals in a position-independent manner. We found that methyl groups can be cleaved as methane. If there are protons adjacent the methoxy on the flavonol rings, intra-molecule proton transfer can occur via collision-induced dissociation, and one molecule of methane can then be eliminated. The remaining charged fragment ([M+H−CH 4 ] + ) reflects the adjacent structure and is specific to the methoxy position. Furthermore, the retro Diels–Alder (RDA) fragmentation of methylated flavonols can generate fragments with the methoxy at the original methylated ring. Combining the position-specific [M+H−CH 4 ] + fragment with the RDA fragments provides a diagnostic pattern for rapidly identifying methylated regioisomeric flavonols. Along with their retention behaviour, we have successfully identified ten regioisomers of methylated kaempferol and quercetin, which include six compounds previously reported in plants and shown to be biologically active. The developed approach is sensitive, rapid, reliable, and requires few standard compounds. It is highly

  3. Liquid-chromatography mass spectrometry (LC-MS) of steroid hormone metabolites and its applications

    Science.gov (United States)

    Penning, Trevor M.; Lee, Seon-Hwa; Jin, Yi; Gutierrez, Alejandro; Blair, Ian A.

    2010-01-01

    Advances in liquid chromatography-mass spectrometry (LC-MS) can be used to measure steroid hormone metabolites in vitro and in vivo. We find that LC-Electrospray Ionization (ESI)-MS using a LCQ ion trap mass spectrometer in the negative ion mode can be used to monitor the product profile that results from 5α–dihydrotestosterone(DHT)-17β-glucuronide, DHT-17β-sulfate, and tibolone-17β-sulfate reduction catalyzed by human members of the aldo-keto reductase (AKR) 1C subfamily and assign kinetic constants to these reactions. We also developed a stable-isotope dilution LC-electron capture atmospheric pressure chemical ionization (ECAPCI)-MS method for the quantitative analysis of estrone (E1) and its metabolites as pentafluorobenzyl (PFB) derivatives in human plasma in the attomole range. The limit of detection for E1-PFB was 740 attomole on column. Separations can be performed using normal-phase LC because ionization takes place in the gas phase rather than in solution. This permits efficient separation of the regioisomeric 2- and 4-methoxy-E1. The method was validated for the simultaneous analysis of plasma E2 and its metabolites: 2-methoxy-E2, 4-methoxy-E2, 16α-hydroxy-E2, estrone (E1), 2-methoxy-E1, 4-methoxy-EI, and 16α-hydroxy-E1 from 5 pg/mL to 2,000 pg/mL. Our LC-MS methods have sufficient sensitivity to detect steroid hormone levels in prostate and breast tumors and should aid their molecular diagnosis and treatment. PMID:20083198

  4. Analysis of epoxyeicosatrienoic acids by chiral liquid chromatography/electron capture atmospheric pressure chemical ionization mass spectrometry using [13C]-analog internal standards

    Science.gov (United States)

    Mesaros, Clementina; Lee, Seon Hwa; Blair, Ian A.

    2012-01-01

    The metabolism of arachidonic acid (AA) to epoxyeicosatrienoic acids (EETs) is thought to be mediated primarily by the cytochromes P450 (P450s) from the 2 family (2C9, 2C19, 2D6, and 2J2). In contrast, P450s of the 4 family are primarily involved in omega oxidation of AA (4A11 and 4A22). The ability to determine enantioselective formation of the regioisomeric EETs is important in order to establish their potential biological activities and to asses which P450 isoforms are involved in their formation. It has been extremely difficult to analyze individual EET enantiomers in biological fluids because they are present in only trace amounts and they are extremely difficult to separate from each other. In addition, the deuterium-labeled internal standards that are commonly used for stable isotope dilution liquid chromatography/mass spectrometry (LC/MS) analyses have different LC retention times when compared with the corresponding protium forms. Therefore, quantification by LC/MS-based methodology can be compromised by differential suppression of ionization of the closely eluting isomers. We report the preparation of [13C20]-EET analog internal standards and the use of a validated high-sensitivity chiral LC/electron capture atmospheric pressure chemical ionization (ECAPCI)-MS method for the trace analysis of endogenous EETs as their pentafluorobenzyl (PFB) ester derivatives. The assay was then used to show the exquisite enantioselectivity of P4502C19-, P4502D6-, P4501A1-, and P4501B1-mediated conversion of AA into EETs and to quantify the enantioselective formation of EETs produced by AA metabolism in a mouse epithelial hepatoma (Hepa) cell line. PMID:20972997

  5. Effects of alkyl chain length and substituent pattern of fullerene bis-adducts on film structures and photovoltaic properties of bulk heterojunction solar cells.

    Science.gov (United States)

    Tao, Ran; Umeyama, Tomokazu; Kurotobi, Kei; Imahori, Hiroshi

    2014-10-08

    A series of alkoxycarbonyl-substituted dihydronaphthyl-based [60]fullerene bis-adduct derivatives (denoted as C2BA, C4BA, and C6BA with the alkyl chain of ethyl, n-butyl, and n-hexyl, respectively) have been synthesized to investigate the effects of alkyl chain length and substituent pattern of fullerene bis-adducts on the film structures and photovoltaic properties of bulk heterojunction polymer solar cells. The shorter alkyl chain length caused lower solubility of the fullerene bis-adducts (C6BA > C4BA > C2BA), thereby resulting in the increased separation difficulty of respective bis-adduct isomers. The device performance based on poly(3-hexylthiophene) (P3HT) and the fullerene bis-adduct regioisomer mixtures was enhanced by shortening the alkyl chain length. When using the regioisomerically separated fullerene bis-adducts, the devices based on trans-2 and a mixture of trans-4 and e of C4BA exhibited the highest power conversion efficiencies of ca. 2.4%, which are considerably higher than those of the C6BA counterparts (ca. 1.4%) and the C4BA regioisomer mixture (1.10%). The film morphologies as well as electron mobilities of the P3HT:bis-adduct blend films were found to affect the photovoltaic properties considerably. These results reveal that the alkyl chain length and substituent pattern of fullerene bis-adducts significantly influence the photovoltaic properties as well as the film structures of bulk heterojunction solar cells.

  6. Polymer Main-Chain Substitution Effects on the Efficiency of Nonfullerene BHJ Solar Cells

    KAUST Repository

    Firdaus, Yuliar; Maffei, Luna Pratali; Cruciani, Federico; Mü ller, Michael A.; Liu, Shengjian; Lopatin, Sergei; Wehbe, Nimer; Ngongang Ndjawa, Guy Olivier; Amassian, Aram; Laquai, Fré dé ric; Beaujuge, Pierre

    2017-01-01

    “Nonfullerene” acceptors are proving effective in bulk heterojunction (BHJ) solar cells when paired with selected polymer donors. However, the principles that guide the selection of adequate polymer donors for high-efficiency BHJ solar cells with nonfullerene acceptors remain a matter of some debate and, while polymer main-chain substitutions may have a direct influence on the donor–acceptor interplay, those effects should be examined and correlated with BHJ device performance patterns. This report examines a set of wide-bandgap polymer donor analogues composed of benzo[1,2-b:4,5-b′]dithiophene (BDT), and thienyl ([2H]T) or 3,4-difluorothiophene ([2F]T) motifs, and their BHJ device performance pattern with the nonfullerene acceptor “ITIC”. Studies show that the fluorine- and ring-substituted derivative PBDT(T)[2F]T largely outperforms its other two polymer donor counterparts, reaching power conversion efficiencies as high as 9.8%. Combining several characterization techniques, the gradual device performance improvements observed on swapping PBDT[2H]T for PBDT[2F]T, and then for PBDT(T)[2F]T, are found to result from (i) notably improved charge generation and collection efficiencies (estimated as ≈60%, 80%, and 90%, respectively), and (ii) reduced geminate recombination (being suppressed from ≈30%, 25% to 10%) and bimolecular recombination (inferred from recombination rate constant comparisons). These examinations will have broader implications for further studies on the optimization of BHJ solar cell efficiencies with polymer donors and a wider range of nonfullerene acceptors.

  7. Synthesis, characterization, and monoamine transporter activity of the new psychoactive substance 3',4'-methylenedioxy-4-methylaminorex (MDMAR).

    Science.gov (United States)

    McLaughlin, Gavin; Morris, Noreen; Kavanagh, Pierce V; Power, John D; Twamley, Brendan; O'Brien, John; Talbot, Brian; Dowling, Geraldine; Mahony, Olivia; Brandt, Simon D; Patrick, Julian; Archer, Roland P; Partilla, John S; Baumann, Michael H

    2015-07-01

    The recent occurrence of deaths associated with the psychostimulant cis-4,4'-dimethylaminorex (4,4'-DMAR) in Europe indicated the presence of a newly emerged psychoactive substance on the market. Subsequently, the existence of 3,4-methylenedioxy-4-methylaminorex (MDMAR) has come to the authors' attention and this study describes the synthesis of cis- and trans-MDMAR followed by extensive characterization by chromatographic, spectroscopic, mass spectrometric platforms and crystal structure analysis. MDMAR obtained from an online vendor was subsequently identified as predominantly the cis-isomer (90%). Exposure of the cis-isomer to the mobile phase conditions (acetonitrile/water 1:1 with 0.1% formic acid) employed for high performance liquid chromatography analysis showed an artificially induced conversion to the trans-isomer, which was not observed when characterized by gas chromatography. Monoamine release activities of both MDMAR isomers were compared with the non-selective monoamine releasing agent (+)-3,4-methylenedioxymethamphetamine (MDMA) as a standard reference compound. For additional comparison, both cis- and trans-4,4'-DMAR, were assessed under identical conditions. cis-MDMAR, trans-MDMAR, cis-4,4'-DMAR and trans-4,4'-DMAR were more potent than MDMA in their ability to function as efficacious substrate-type releasers at the dopamine (DAT) and norepinephrine (NET) transporters in rat brain tissue. While cis-4,4'-DMAR, cis-MDMAR and trans-MDMAR were fully efficacious releasing agents at the serotonin transporter (SERT), trans-4,4'-DMAR acted as a fully efficacious uptake blocker. Currently, little information is available about the presence of MDMAR on the market but the high potency of ring-substituted methylaminorex analogues at all three monoamine transporters investigated here might be relevant when assessing the potential for serious side-effects after high dose exposure. Copyright © 2014 John Wiley & Sons, Ltd.

  8. Polymer Main-Chain Substitution Effects on the Efficiency of Nonfullerene BHJ Solar Cells

    KAUST Repository

    Firdaus, Yuliar

    2017-07-21

    “Nonfullerene” acceptors are proving effective in bulk heterojunction (BHJ) solar cells when paired with selected polymer donors. However, the principles that guide the selection of adequate polymer donors for high-efficiency BHJ solar cells with nonfullerene acceptors remain a matter of some debate and, while polymer main-chain substitutions may have a direct influence on the donor–acceptor interplay, those effects should be examined and correlated with BHJ device performance patterns. This report examines a set of wide-bandgap polymer donor analogues composed of benzo[1,2-b:4,5-b′]dithiophene (BDT), and thienyl ([2H]T) or 3,4-difluorothiophene ([2F]T) motifs, and their BHJ device performance pattern with the nonfullerene acceptor “ITIC”. Studies show that the fluorine- and ring-substituted derivative PBDT(T)[2F]T largely outperforms its other two polymer donor counterparts, reaching power conversion efficiencies as high as 9.8%. Combining several characterization techniques, the gradual device performance improvements observed on swapping PBDT[2H]T for PBDT[2F]T, and then for PBDT(T)[2F]T, are found to result from (i) notably improved charge generation and collection efficiencies (estimated as ≈60%, 80%, and 90%, respectively), and (ii) reduced geminate recombination (being suppressed from ≈30%, 25% to 10%) and bimolecular recombination (inferred from recombination rate constant comparisons). These examinations will have broader implications for further studies on the optimization of BHJ solar cell efficiencies with polymer donors and a wider range of nonfullerene acceptors.

  9. Structural and functional characterization of solute binding proteins for aromatic compounds derived from lignin: p-coumaric acid and related aromatic acids.

    Science.gov (United States)

    Tan, Kemin; Chang, Changsoo; Cuff, Marianne; Osipiuk, Jerzy; Landorf, Elizabeth; Mack, Jamey C; Zerbs, Sarah; Joachimiak, Andrzej; Collart, Frank R

    2013-10-01

    Lignin comprises 15-25% of plant biomass and represents a major environmental carbon source for utilization by soil microorganisms. Access to this energy resource requires the action of fungal and bacterial enzymes to break down the lignin polymer into a complex assortment of aromatic compounds that can be transported into the cells. To improve our understanding of the utilization of lignin by microorganisms, we characterized the molecular properties of solute binding proteins of ATP-binding cassette transporter proteins that interact with these compounds. A combination of functional screens and structural studies characterized the binding specificity of the solute binding proteins for aromatic compounds derived from lignin such as p-coumarate, 3-phenylpropionic acid and compounds with more complex ring substitutions. A ligand screen based on thermal stabilization identified several binding protein clusters that exhibit preferences based on the size or number of aromatic ring substituents. Multiple X-ray crystal structures of protein-ligand complexes for these clusters identified the molecular basis of the binding specificity for the lignin-derived aromatic compounds. The screens and structural data provide new functional assignments for these solute-binding proteins which can be used to infer their transport specificity. This knowledge of the functional roles and molecular binding specificity of these proteins will support the identification of the specific enzymes and regulatory proteins of peripheral pathways that funnel these compounds to central metabolic pathways and will improve the predictive power of sequence-based functional annotation methods for this family of proteins. Copyright © 2013 Wiley Periodicals, Inc.

  10. UV-vis spectroscopy and colorimetric models for detecting anthocyanin-metal complexes in plants: An overview of in vitro and in vivo techniques.

    Science.gov (United States)

    Fedenko, Volodymyr S; Shemet, Sergiy A; Landi, Marco

    2017-05-01

    Although anthocyanin (ACN) biosynthesis is one of the best studied pathways of secondary metabolism in plants, the possible physiological and ecological role(s) of these pigments continue to intrigue scientists. Like other dihydroxy B-ring substituted flavonoids, ACNs have an ability to bind metal and metalloid ions, a property that has been exploited for a variety of purposes. For example, the metal binding ability may be used to stabilize ACNs from plant food sources, or to modify their colors for using them as food colorants. The complexation of metals with cyanidin derivatives can also be used as a simple, sensitive, cheap, and rapid method for determination concentrations of several metals in biological and environmental samples using UV-vis spectroscopy. Far less information is available on the ecological significance of ACN-metal complexes in plant-environment interactions. Metalloanthocyanins (protocyanin, nemophilin, commelinin, protodelphin, cyanosalvianin) are involved in the copigmentation phenomenon that leads to blue-pigmented petals, which may facilitate specific plant-pollinator interactions. ACN-metal formation and compartmentation into the vacuole has also been proposed to be part of an orchestrated detoxification mechanism in plants which experience metal/metalloid excess. However, investigations into ACN-metal interactions in plant biology may be limited because of the complexity of the analytical techniques required. To address this concern, here we describe simple methods for the detection of ACN-metal both in vitro and in vivo using UV-vis spectroscopy and colorimetric models. In particular, the use of UV-vis spectra, difference absorption spectra, and colorimetry techniques will be described for in vitro determination of ACN-metal features, whereas reflectance spectroscopy and colorimetric parameters related to CIE L * a * b * and CIE XYZ systems will be detailed for in vivo analyses. In this way, we hope to make this high-informative tool

  11. Tamaractam, a New Bioactive Lactam from Tamarix ramosissima, Induces Apoptosis in Rheumatoid Arthritis Fibroblast-Like Synoviocytes.

    Science.gov (United States)

    Yao, Yao; Jiang, Cheng-Shuai; Sun, Na; Li, Wei-Qi; Niu, Yang; Han, Huai-Qin; Miao, Zhen-Hua; Zhao, Xun-Xia; Zhao, Jing; Li, Juan

    2017-01-10

    Chemical investigation of Tamarix ramosissima Ledeb, a traditional herbal medicine used for rheumatoid arthritis (RA) treatment in northwest China, led to the discovery of a new phenolic aromatic rings substituted lactam, tamaractam ( 1 ), together with the previously reported compounds cis - N -feruloyl-3- O -methyldopamine ( 2 ) and trans - N -feruloyl-3- O -methyldopamine ( 3 ). The structures of the compounds were determined by high resolution electrospray ionization mass spectroscopy (HRESIMS) and 1D and 2D-NMR experiments, as well as comparison with the literature data. The effects of the three compounds on the viability of RA fibroblast-like synoviocytes (RA-FLS) were assessed by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2- H -tetrazolium bromide (MTT) assay. Pro-apoptosis effect of compound 1 in RA-FLS was further investigated by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay, activated caspase-3/7 level assessment using luminescence assay, and sub-G₁ fraction measurement using flow cytometry. It was found that these three compounds displayed variable proliferation inhibitory activity in RA-FLS, and compound 1 exhibited the strongest effect. Compound 1 could remarkably induce cellular apoptosis of RA-FLS, increase activated caspase-3/7 levels, and significantly increase sub-G₁ fraction in the cell cycle. The results suggested that compound 1 may inhibit the proliferation of RA-FLS through apoptosis-inducing effect, and these compounds may contribute to the anti-RA effect of T. ramosissima .

  12. Tamaractam, a New Bioactive Lactam from Tamarix ramosissima, Induces Apoptosis in Rheumatoid Arthritis Fibroblast-Like Synoviocytes

    Directory of Open Access Journals (Sweden)

    Yao Yao

    2017-01-01

    Full Text Available Chemical investigation of Tamarix ramosissima Ledeb, a traditional herbal medicine used for rheumatoid arthritis (RA treatment in northwest China, led to the discovery of a new phenolic aromatic rings substituted lactam, tamaractam (1, together with the previously reported compounds cis-N-feruloyl-3-O-methyldopamine (2 and trans-N-feruloyl-3-O-methyldopamine (3. The structures of the compounds were determined by high resolution electrospray ionization mass spectroscopy (HRESIMS and 1D and 2D-NMR experiments, as well as comparison with the literature data. The effects of the three compounds on the viability of RA fibroblast-like synoviocytes (RA-FLS were assessed by 3-(4,5-dimethyl-2-thiazolyl-2,5-diphenyl-2-H-tetrazolium bromide (MTT assay. Pro-apoptosis effect of compound 1 in RA-FLS was further investigated by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL assay, activated caspase-3/7 level assessment using luminescence assay, and sub-G1 fraction measurement using flow cytometry. It was found that these three compounds displayed variable proliferation inhibitory activity in RA-FLS, and compound 1 exhibited the strongest effect. Compound 1 could remarkably induce cellular apoptosis of RA-FLS, increase activated caspase-3/7 levels, and significantly increase sub-G1 fraction in the cell cycle. The results suggested that compound 1 may inhibit the proliferation of RA-FLS through apoptosis-inducing effect, and these compounds may contribute to the anti-RA effect of T. ramosissima.

  13. Photoinduced electron transfer interaction of anthraquinones with aniline quenchers: Influence of methyl substitution in aniline donors

    Science.gov (United States)

    Sivakumar, V.; Ponnamma, Deepalekshmi; Hussein, Yasser H. A.

    2017-02-01

    Photoinduced electron transfer between triplet state of 9,10-anthraquinone (AQ) and its two derivatives: 2-chloro-9,10-anthraquinone (CAQ) and sodium anthraquinone-2-sulfonate (AQS) and ground state aniline (AN) and its dimethyl substitutions: 2,3-dimethylaniline (2,3-DMA), 2,6-dimethylaniline (2,6-DMA), 3,5-dimethylaniline (3,5-DMA) and N,N-dimethylaniline (N,N-DMA) is studied using nanosecond laser flash photolysis at room temperature. Detection of radical bands of quinone anions and aniline cations along with their formation and/or decay kinetics are used to confirm the electron transfer (ET) process. In MeCN medium, AN quenches the triplet state of CAQ (CAQT) but not the triplets AQT or AQST. However in aqueous medium, AN quenches AQST and forms radical ion pair. All the DMAs can react through ET with all the triplet quinones at different degrees of efficiency in MeCN medium. Noticeably, the ring substituted DMAs are less efficient in electron donation to AQT or AQST while the N,N-DMA shows high efficiency in donating electron to all triplet quinones in MeCN medium. Charge distribution of donor molecules, in MeCN medium is calculated using density functional theory (DFT), and shows an enhancement of electron density of the ring of N,N-DMA, making it an ideal electron donor for ET studies compared to other DMAs. This systematic selection and usage of anilines with electrochemically tunable quinones can be viewed as a working model of donor-acceptor system that can be utilized in photoinduced ET applications.

  14. Nonsteroidal selective androgen receptor modulators enhance female sexual motivation.

    Science.gov (United States)

    Jones, Amanda; Hwang, Dong Jin; Duke, Charles B; He, Yali; Siddam, Anjaiah; Miller, Duane D; Dalton, James T

    2010-08-01

    Women experience a decline in estrogen and androgen levels after natural or surgically induced menopause, effects that are associated with a loss of sexual desire and bone mineral density. Studies in our laboratories have shown the beneficial effects of selective androgen receptor modulators (SARMs) in the treatment of osteoporosis and muscle wasting in animal models. A series of S-3-(phenoxy)-2-hydroxy-2-methyl-N-(4-cyano-3-trifluoromethyl-phenyl)-propionamide analogs was synthesized to evaluate the effects of B-ring substitutions on in vitro and in vivo pharmacologic activity, especially female sexual motivation. The androgen receptor (AR) relative binding affinities ranged from 0.1 to 26.5% (relative to dihydrotestosterone) and demonstrated a range of agonist activity at 100 nM. In vivo pharmacologic activity was first assessed by using male rats. Structural modifications to the B-ring significantly affected the selectivity of the SARMs, demonstrating that single-atom substitutions can dramatically and unexpectedly influence activity in androgenic (i.e., prostate) and anabolic (i.e., muscle) tissues. (S)-N-(4-cyano-3-trifluoromethyl-phenyl)-3-(3-fluoro,4-chlorophenoxy)-2-hydroxy-2-methyl-propanamide (S-23) displayed full agonist activity in androgenic and anabolic tissues; however, the remaining SARMs were more prostate-sparing, selectively maintaining the size of the levator ani muscle in castrated rats. The partner-preference paradigm was used to evaluate the effects of SARMs on female sexual motivation. With the exception of two four-halo substituted analogs, the SARMs increased sexual motivation in ovariectomized rats, with potency and efficacy comparable with testosterone propionate. These results indicate that the AR is important in regulating female libido given the nonaromatizable nature of SARMs and it could be a superior alternative to steroidal testosterone preparations in the treatment of hypoactive sexual desire disorder.

  15. Substituted Pyrazinecarboxamides: Synthesis and Biological Evaluation

    Directory of Open Access Journals (Sweden)

    Katarina Kralova

    2006-03-01

    Full Text Available Condensation of the corresponding chlorides of some substituted pyrazine-2-carboxylic acids (pyrazine-2-carboxylic acid, 6-chloropyrazine-2-carboxylic acid, 5-tert-butylpyrazine-2-carboxylic acid or 5-tert-butyl-6-chloropyrazine-2-carboxylic acid withvarious ring-substituted aminothiazoles or anilines yielded a series of amides. Thesyntheses, analytical and spectroscopic data of thirty newly prepared compounds arepresented. Structure-activity relationships between the chemical structures and the anti-mycobacterial, antifungal and photosynthesis-inhibiting activity of the evaluatedcompounds are discussed. 3,5-Bromo-4-hydroxyphenyl derivatives of substitutedpyrazinecarboxylic acid, 16-18, have shown the highest activity against Mycobacteriumtuberculosis H37Rv (54-72% inhibition. The highest antifungal effect againstTrichophyton mentagrophytes, the most susceptible fungal strain tested, was found for5-tert-butyl-6-chloro-N-(4-methyl-1,3-thiazol-2-ylpyrazine-2-carboxamide (8, MIC =31.25 μmol·mL-1. The most active inhibitors of oxygen evolution rate in spinachMolecules 2006, 11 243 chloroplasts were the compounds 5-tert-butyl-6-chloro-N-(5-bromo-2-hydroxyphenyl- pyrazine-2-carboxamide (27, IC50 = 41.9 μmol·L-1 and 5-tert-butyl-6-chloro-N-(1,3- thiazol-2-yl-pyrazine-2-carboxamide (4, IC50 = 49.5 μmol·L-1.

  16. Chemical interactions in complex matrices: Determination of polar impurities in biofuels and fuel contaminants in building materials

    Science.gov (United States)

    Baglayeva, Ganna

    monoacylglycerols was developed. The identification and quantification of analytes were performed using a 15-m high temperature capillary column (DB-1HT) with a GC coupled to both flame ionization and mass spectrometric detectors. To eliminate discrimination of low or high molecular weight species, programmed temperature vaporization (PTV) injection parameters were optimized using design of experiments methodology. Evaluation of the column temperature program and MS parameters allowed achieving separation of majority of target compounds based on their total number of carbon atoms, regioisomerization and, to some extent, degree of unsaturation.

  17. Synthesis of chlorophyll-c derivatives by modifying natural chlorophyll-a.

    Science.gov (United States)

    Xu, Meiyun; Kinoshita, Yusuke; Matsubara, Shogo; Tamiaki, Hitoshi

    2016-03-01

    Chlorophyll-a (Chl-a) was extracted from cyanobacterial cells and modified to methyl pyropheophorbide-a. The 3-vinyl-chlorin was transformed to zinc complex of the corresponding 3-acetyl-porphyrin. The zinc porphyrin was oxidized to give cis-7,8- and 17,18-dihydroxy-chlorins as well cis-7,8-cis-17,18-tetrahydroxybacteriochlorin. After zinc-demetallation, the isolated cis-7,8- and 17,18-diols were reduced at the 3-acetyl group and triply dehydrated under acidic conditions to afford two regioisomeric 3-vinyl-porphyrins, methyl divinyl-pyroprotopheophorbide-a possessing the 8-vinyl group and 17-propionate residue (one of the divinyl-protoChl-a derivatives) and methyl pyropheophorbide-c 1 possessing the 8-ethyl group and 17-acrylate residue (one of the Chl-c 1 derivatives), respectively. The resulting 7,8,17,18-tetrol was reduced and then acidically treated, giving five-fold dehydrated free base porphyrin, methyl pyropheophorbide-c 2 possessing the 3,8-divinyl groups and 17-acrylate residue (one of the Chl-c 2 derivatives). The visible absorption and fluorescence emission spectra of the three semi-synthetic 3-vinyl-porphyrins in dichloromethane were compared with those of the corresponding 8-ethyl-porphyrin bearing the 17-propionate residue, methyl pyroprotopheophorbide-a (one of the protoChl-a derivatives). The Soret and Qy absorption maxima were shifted to longer wavelengths with an increase of π-conjugation in a molecule: protoChl-a (8-CH2CH3/17-CH2CH2COOCH3) < divinyl-protoChl-a (8-CH=CH2/17-CH2CH2COOCH3) < Chl-c 1 (8-CH2CH3/17-CH=CHCOOCH3) < Chl-c 2 derivatives (8-CH=CH2/17-CH=CHCOOCH3). The 17(1),17(2)-dehydrogenation broadened the absorption bands. The emission maxima were bathochromically shifted in the same order. The reaction mechanism of the present dehydration indicates that the biosynthetic pathway of Chls-c would include the hydroxylation of the 17-propionate reside at the 17(1)-position and successive dehydration to the 17-acrylate residue.

  18. Mechanistic Basis for Regioselection and Regiodivergence in Nickel-Catalyzed Reductive Couplings

    Science.gov (United States)

    Jackson, Evan P.; Malik, Hasnain A.; Sormunen, Grant J.; Baxter, Ryan D.; Liu, Peng; Wang, Hengbin; Shareef, Abdur-Rafay; Montgomery, John

    2015-01-01

    CONSPECTUS The control of regiochemistry is a considerable challenge in the development of a wide array of catalytic processes. Simple π-components such as alkenes, alkynes, 1,3-dienes, and allenes are among the many classes of substrates that present complexities in regioselective catalysis. Considering an internal alkyne as a representative example, when steric and electronic differences between the two substituents are minimal, differentiating among the two termini of the alkyne presents a great challenge. In cases where the differences between the alkyne substituents are substantial, overcoming those biases to access the regioisomer opposite that favored by substrate biases often presents an even greater challenge. Nickel-catalyzed reductive couplings of unsymmetrical π-components make up a group of reactions where control of regiochemistry presents a challenging but important objective. In the course of our studies of aldehyde-alkyne reductive couplings, complementary solutions to challenges in regiocontrol have been developed. Through careful selection of the ligand and reductant, as well as the more subtle reaction variables such as temperature and concentration, effective protocols have been established that allow highly selective access to either regiosiomer of the the allylic alcohol products using a wide range of unsymmetrical alkynes. Computational studies and an evaluation of reaction kinetics have provided an understanding of the origin of the regioselectivity control. Throughout the various procedures described, the development of ligand-substrate interactions play a key role, and the overall kinetic descriptions were found to differ between protocols. Rational alteration of the rate-determining step plays a key role in the regiochemistry reversal strategy, and in one instance, the two possible regioisomeric outcomes in a single reaction were found to operate by different kinetic descriptions. With this mechanistic information in hand, the

  19. Identification of regioisomers of methylated kaempferol and quercetin by ultra high performance liquid chromatography quadrupole time-of-flight (UHPLC–QTOF) tandem mass spectrometry combined with diagnostic fragmentation pattern analysis

    Energy Technology Data Exchange (ETDEWEB)

    Ma, Chengying; Lv, Haipeng; Zhang, Xinzhong; Chen, Zongmao; Shi, Jiang [Tea Research Institute, Chinese Academy of Agricultural Sciences, 9 Meiling South Road, Hangzhou, Zhejiang 310008 (China); Lu, Meiling, E-mail: meilinglu@hotmail.com [Chemical Analysis Group, Agilent Technologies, No. 3 Wangjing North Road, Chaoyang Distr., Beijing 100102 (China); Lin, Zhi, E-mail: linz@mail.tricaas.com [Tea Research Institute, Chinese Academy of Agricultural Sciences, 9 Meiling South Road, Hangzhou, Zhejiang 310008 (China)

    2013-09-17

    Highlights: •Found methane elimination is position-specific for methylated flavonols. •Found retro Diels–Alder fragments retained methoxy at original ring of flavonols. •Proposed a diagnostic pattern for discriminating regioisomers of flavonols. •Identified the specificity of three novel flavonol O-methyltransferases. •Identified six biologically active compounds and four new compounds. -- Abstract: The O-methylation of active flavonoids can enhance their antiallergic, anticancerous, and cardioprotective effects depending on the methylation position. Thus, it is biologically and pharmacologically important to differentiate methylated flavonoid regioisomers. In this study, we examined the regioisomers of methylated kaempferol and quercetin using ultra high performance liquid chromatography quadrupole time-of-flight tandem mass spectrometry. The methyl groups on the flavonoids can generally be cleaved as methyl radicals in a position-independent manner. We found that methyl groups can be cleaved as methane. If there are protons adjacent the methoxy on the flavonol rings, intra-molecule proton transfer can occur via collision-induced dissociation, and one molecule of methane can then be eliminated. The remaining charged fragment ([M+H−CH{sub 4}]{sup +}) reflects the adjacent structure and is specific to the methoxy position. Furthermore, the retro Diels–Alder (RDA) fragmentation of methylated flavonols can generate fragments with the methoxy at the original methylated ring. Combining the position-specific [M+H−CH{sub 4}]{sup +} fragment with the RDA fragments provides a diagnostic pattern for rapidly identifying methylated regioisomeric flavonols. Along with their retention behaviour, we have successfully identified ten regioisomers of methylated kaempferol and quercetin, which include six compounds previously reported in plants and shown to be biologically active. The developed approach is sensitive, rapid, reliable, and requires few standard

  20. Stability of Synthetic Cathinones in Urine.

    Science.gov (United States)

    Glicksberg, Lindsay; Kerrigan, Sarah

    2018-03-01

    In this report, we evaluate the concentration, pH, temperature and analyte-dependent effects on cathinone stability in preserved human urine. A total of 22 synthetic cathinones were evaluated at 100 ng/mL and 1,000 ng/mL in pH 4 and pH 8 urine over 6 months. Specimens were stored at -20°C, 4°C, 20°C and 32°C. The stability of synthetic cathinones was highly dependent on urine pH and storage temperature. Cathinones were considerably more stable in acidic urine (pH 4) at low temperature. In alkaline urine (pH 8) at 32°C, significant losses (>20%) were observed within hours for the majority of drugs. In contrast, all drugs were stable in frozen and refrigerated urine at pH 4 for the duration of the study. These results highlight the importance of sample storage and the potential for pre-analytical changes in concentration during routine shipping and handling of specimens. Significant structural influence was also observed. Cathinones bearing a tertiary amine (pyrrolidine group) were significantly more stable than their secondary amine counterparts. The methylenedioxy group also exerted a significant stabilizing effect on both the tertiary and secondary amines. In the absence of the methylenedioxy group, no significant differences in stability were observed between the unsubstituted and ring substituted secondary amines. Half-lives at ambient temperature in pH 8 urine ranged from 9 h (3-fluoromethcathinone) to 4.3 months (methylenedioxypyrovalerone and 3,4-methylenedioxy-α-pyrrolidinobutiophenone), demonstrating the importance of analyte dependence, and the dual stabilizing effect of both the pyrollidine and methylenedioxy groups. Biological evidence may be subjected to a variety of environmental conditions prior to, and during transport to the forensic laboratory. These findings demonstrate the inherent instability of certain cathinone species in biological evidence under some conditions. Moreover, this study highlights the need for quantitative drug findings in

  1. Structure-based prediction of subtype selectivity of histamine H3 receptor selective antagonists in clinical trials.

    Science.gov (United States)

    Kim, Soo-Kyung; Fristrup, Peter; Abrol, Ravinder; Goddard, William A

    2011-12-27

    interacting with D114(3.32), the spacer, the aromatic ring substituted with the hydrophilic or lipophilic groups interacting with lipophilic pockets in transmembranes (TMs) 3-5-6 and the aliphatic ring located in TMs 2-3-7. These 3D structures for all four HRs should help guide the rational design of novel drugs for the subtype selective antagonists and agonists with reduced side effects.

  2. Clinical toxicology of newer recreational drugs.

    Science.gov (United States)

    Hill, Simon L; Thomas, Simon H L

    2011-10-01

    Novel synthetic 'designer' drugs with stimulant, ecstasy-like (entactogenic) and/or hallucinogenic properties have become increasingly popular among recreational drug users in recent years. The substances used change frequently in response to market trends and legislative controls and it is an important challenge for poisons centres and clinical toxicologists to remain updated on the pharmacological and toxicological effects of these emerging agents. To review the available information on newer synthetic stimulant, entactogenic and hallucinogenic drugs, provide a framework for classification of these drugs based on chemical structure and describe their pharmacology and clinical toxicology. A comprehensive review of the published literature was performed using PUBMED and Medline databases, together with additional non-peer reviewed information sources, including books, media reports, government publications and internet resources, including drug user web forums. Novel synthetic stimulant, entactogenic or hallucinogenic designer drugs are increasingly available to users as demonstrated by user surveys, poisons centre calls, activity on internet drug forums, hospital attendance data and mortality data. Some population sub groups such as younger adults who attend dance music clubs are more likely to use these substances. The internet plays an important role in determining the awareness of and availability of these newer drugs of abuse. Most novel synthetic stimulant, entactogenic or hallucinogenic drugs of abuse can be classified according to chemical structure as piperazines (e.g. benzylpiperazine (BZP), trifluoromethylphenylpiperazine), phenethylamines (e.g. 2C or D-series of ring-substituted amfetamines, benzodifurans, cathinones, aminoindans), tryptamines (e.g. dimethyltryptamine, alpha-methyltryptamine, ethyltryptamine, 5-methoxy-alphamethyltryptamine) or piperidines and related substances (e.g. desoxypipradrol, diphenylprolinol). Alternatively classification may

  3. Novel method for determining DDT in vapour and particulate phases within contaminated indoor air in a malaria area of South Africa

    International Nuclear Information System (INIS)

    Naudé, Yvette; Rohwer, Egmont R.

    2012-01-01

    Highlights: ► We present a novel denuder for the determination of DDT in contaminated indoor air. ► Single step concentration of vapour phase on PDMS, particulate phase on filter. ► Solvent-free green technique, sample extraction not required. ► Ratios of airborne p,p′-DDD/p,p′-DDT and of o,p′-DDT/p,p′-DDT are unusual. ► Insecticidal efficacy of technical DDT may be compromised. - Abstract: The organochlorine insecticide DDT (1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane) is still used for malaria vector control in certain areas of South Africa. The strict Stockholm Convention on Persistent Organic Pollutants (POPs) allows spraying on the inside of traditional dwellings with DDT. In rural villages contaminated dust presents an additional pathway for exposure to DDT. We present a new method for the determination of DDT in indoor air where separate vapour and particulate samples are collected in a single step with a denuder configuration of a multi-channel open tubular silicone rubber (polydimethylsiloxane (PDMS)) trap combined with a micro quartz fibre filter. The multi-channel PDMS trap section of the denuder concentrates vapour phase insecticide whereas particle associated insecticide is transferred downstream where it is collected on a micro-fibre filter followed by a second multi-channel PDMS trap to capture the blow-off from the filter. The multi-channel PDMS trap and filter combination are designed to fit a commercial thermal desorber for direct introduction of samples into a GC–MS. The technique is solvent-free. Analyte extraction and sample clean-up is not required. Two fractions, vapour phase and particulate phase p,p′-DDT, o,p′-DDT; p,p′-DDD, o,p′-DDD; p,p′-DDE and o,p′-DDE in 4 L contaminated indoor air, were each quantitatively analysed by GC–MS using isotopically labelled ring substituted 13 C 12 –p,p′-DDT as an internal standard. Limits of detection were 0.07–0.35 ng m −3 for p,p′-DDT, o,p′-DDT, p

  4. Synthesis and complexation of acyclic dithiolate ligands

    International Nuclear Information System (INIS)

    Ashford, L.

    1999-11-01

    Four approaches to ring substituted and unsubstituted N,N'-bis(o-mercaptobenzyliden)propylenediaminate ligands are described using N,N-dimethylcarbamate as a thiolate protecting group. Of the four basic methods, substitution, reduction, rearrangement and oxidation, the latter two successfully synthesise the aldehyde precursor. Rearrangement of the thiocarbamoyl group to the protected thiophenol is shown to be facilitated by a para-nitro substiuent. Ni(II) and Cu(II) complexes of N,N'-bis(p-nitro-o-mercaptobenzyliden)-propylenediaminate are synthesised by reaction of 2-formyl-4-nitro-N,N-dimethylcarbamoyI thiophenol, [Ni(OAc) 2 ].4(H 2 O) and 1,3-diaminopropane. The para-unsubstituted Ni(II) complex, Nickel-[N,N'-bis(o-mercaptobenzyliden) propylenediaminate] is prepared via reaction of the aldehyde, 2-formyl-N,N-dimethylcarbamoyl thiophenol with [Ni(OAc) 2 ].4(H 2 O) and 1,3-diaminopropane. The analogous carbamoyl-protected amine ligands, N,N'-dimethyl-N.N'-di[2-(N'',N''-dimethylcarbamyl)mercapto] benzyl-1,3-propane-diamine and N,N'-dimethyl-N,N'-di[2-(N'',N''-dimethylcarbamyl)mercapto] benzyl-1,2-ethane-diamine are also studied. The tertiary-butyl-protected diimine ligand, N,N'-bis-(o-mercaptobenzylidene)-propylenediaminate is prepared from 2-(tert-butylsulfanyl)benzaldehyde and 1,3-diaminopropane. Reaction with [Ni(H 2 O) 6 ]Cl 2 gives Nickel-[N,N'-bis(o-mercaptobenzyliden)-propylenediaminate], the crystal structure showing a distorted square-planar Ni(II) centre. Reaction with ZnCl 2 gives Zinc-[N,N'-bis(o-mercaptobenzyliden)propylenediaminate]dichloride. The crystal structure shows the thiolate donors remain protected and uncoordinated. The Zn(II) ion is coordinated by two imine donors and two chloride ions in a tetrahedral environment. In reactions with Ag(I) and Hg(II), N,N'-bis-(o-mercaptobenzylidene)-propylenediaminate acts as a reductant giving the free metals. Structural data and NMR and IR spectroscopic data for Nickel

  5. Novel method for determining DDT in vapour and particulate phases within contaminated indoor air in a malaria area of South Africa

    Energy Technology Data Exchange (ETDEWEB)

    Naude, Yvette, E-mail: yvette.naude@up.ac.za [Department of Chemistry, University of Pretoria, Private Bag X20, Hatfield 0028, Pretoria (South Africa); Rohwer, Egmont R., E-mail: egmont.rohwer@up.ac.za [Department of Chemistry, University of Pretoria, Private Bag X20, Hatfield 0028, Pretoria (South Africa)

    2012-06-12

    isotopically labelled ring substituted {sup 13}C{sub 12} -p,p Prime -DDT as an internal standard. Limits of detection were 0.07-0.35 ng m{sup -3} for p,p Prime -DDT, o,p Prime -DDT, p,p Prime -DDD, o,p Prime -DDD, p,p Prime -DDE and o,p Prime -DDE. Ratios of airborne p,p Prime -DDD/p,p Prime -DDT and of o,p Prime -DDT/p,p Prime -DDT are unusual and do not match the ideal certified ingredient composition required of commercial DDT. Results suggest that the DDT products used for indoor residual spraying (IRS) prior to, and during 2007, may have been compromised with regards to insecticidal efficacy, demonstrating the power of this new environmental forensics tool.

  6. Hybrid Theranostic Platforms for Cancer Nanomedical Treatment

    KAUST Repository

    Julfakyan, Khachatur

    2015-10-01

    Cancer is a leading case of mortality worldwide. Governments spent multibillion expenses on treatment and palliative care of diseased people. Despite these generous funding and intensive research with aim to find a cure or efficient treatment for cancer, until now there is a lack in selective cancer management strategies. Conventional treatment strategies for cancer, such as surgery, cytotoxic chemotherapy, radiation therapy, hormone therapy don’t have selectivity toward cancer – the property of discrimination of healthy organs and tissues from the diseased site. Chemotherapy is very challenging as the difference between effective and lethal doses is very minuscule in most cases. Moreover, devastating side effects dramatically changes the quality of life for cancer patients. To address these issues two main strategies are intensively utilized in chemistry: (I) the design and synthesis of novel anticancer organic compounds with higher selectivity and low toxicity profiles and the second, design and preparation of biocompatible nanocarriers for imaging and anticancer compound selective delivery nanomedicine. The following dissertation combines the above two strategies as bellows: First project is related to the design and synthetic route development toward novel nature-inspired group of heterocyclic compounds – iso-Phidianidines. The second project focused on design, preparation and evaluation of hybrid theranostics (therapeutic and diagnostic in a single entity). Chapter 1 is a general background review of the major topics that will be discussed in this dissertation. The first efficient and high-yielding synthetic route toward iso-phidianidines, containing regioisomeric form of 1,2,4-oxadiazole linked to the indole via methylene bridge is reported in Chapter 2. In vitro test of the synthesized library of iso-phidianidines revealed micromolar range of cytotoxicity toward human cervical cancer cell line. Structure activity relationship revealed the importance of