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Sample records for acids amines amides

  1. Visible-Light-Mediated Synthesis of Amides from Aldehydes and Amines via in Situ Acid Chloride Formation.

    PubMed

    Iqbal, Naeem; Cho, Eun Jin

    2016-03-01

    An efficient visible-light photocatalysis-based one-pot amide synthesis method was developed; visible-light irradiation of a mixture of an aldehyde, tert-butyl hydrogen peroxide, and N-chlorosuccinimide using a Ru(bpy)3Cl2 photocatalyst afforded an acid chloride, which subsequently reacted with amine to yield the corresponding amide. The reaction was used to synthesize moclobemide and a D3 receptor intermediate. PMID:26836367

  2. Atom-economic catalytic amide synthesis from amines and carboxylic acids activated in situ with acetylenes.

    PubMed

    Krause, Thilo; Baader, Sabrina; Erb, Benjamin; Gooßen, Lukas J

    2016-01-01

    Amide bond-forming reactions are of tremendous significance in synthetic chemistry. Methodological research has, in the past, focused on efficiency and selectivity, and these have reached impressive levels. However, the unacceptable amounts of waste produced have led the ACS GCI Roundtable to label 'amide bond formation avoiding poor atom economy' as the most pressing target for sustainable synthetic method development. In response to this acute demand, we herein disclose an efficient one-pot amide coupling protocol that is based on simple alkynes as coupling reagents: in the presence of a dichloro[(2,6,10-dodecatriene)-1,12-diyl]ruthenium catalyst, carboxylate salts of primary or secondary amines react with acetylene or ethoxyacetylene to vinyl ester intermediates, which undergo aminolysis to give the corresponding amides along only with volatile acetaldehyde or ethyl acetate, respectively. The new amide synthesis is broadly applicable to the synthesis of structurally diverse amides, including dipeptides. PMID:27282773

  3. Atom-economic catalytic amide synthesis from amines and carboxylic acids activated in situ with acetylenes

    PubMed Central

    Krause, Thilo; Baader, Sabrina; Erb, Benjamin; Gooßen, Lukas J.

    2016-01-01

    Amide bond-forming reactions are of tremendous significance in synthetic chemistry. Methodological research has, in the past, focused on efficiency and selectivity, and these have reached impressive levels. However, the unacceptable amounts of waste produced have led the ACS GCI Roundtable to label ‘amide bond formation avoiding poor atom economy' as the most pressing target for sustainable synthetic method development. In response to this acute demand, we herein disclose an efficient one-pot amide coupling protocol that is based on simple alkynes as coupling reagents: in the presence of a dichloro[(2,6,10-dodecatriene)-1,12-diyl]ruthenium catalyst, carboxylate salts of primary or secondary amines react with acetylene or ethoxyacetylene to vinyl ester intermediates, which undergo aminolysis to give the corresponding amides along only with volatile acetaldehyde or ethyl acetate, respectively. The new amide synthesis is broadly applicable to the synthesis of structurally diverse amides, including dipeptides. PMID:27282773

  4. Hydrogen-deuterium exchange of aromatic amines and amides using deuterated trifluoroacetic acid

    PubMed Central

    Giles, Richard; Lee, Amy; Jung, Erica; Kang, Aaron; Jung, Kyung Woon

    2014-01-01

    The H-D exchange of aromatic amines and amides, including pharmaceutically relevant compounds such as acetaminophen and diclofenac, was investigated using CF3COOD as both the sole reaction solvent and source of deuterium label. The described method is amenable to efficient deuterium incorporation for a wide variety of substrates possessing both electron-donating and electron-withdrawing substituents. Best results were seen with less basic anilines and highly activated acetanilides, reflecting the likelihood of different mechanistic pathways. PMID:25641994

  5. Palladium-catalyzed C–N and C–O bond formation of N-substituted 4-bromo-7-azaindoles with amides, amines, amino acid esters and phenols

    PubMed Central

    Surasani, Rajendra; Rao, A V Dhanunjaya; Chandrasekhar, K B

    2012-01-01

    Summary Simple and efficient procedures for palladium-catalyzed cross-coupling reactions of N-substituted 4-bromo-7-azaindole (1H-pyrrole[2,3-b]pyridine), with amides, amines, amino acid esters and phenols through C–N and C–O bond formation have been developed. The C–N cross-coupling reaction of amides, amines and amino acid esters takes place rapidly by using the combination of Xantphos, Cs2CO3, dioxane and palladium catalyst precursors Pd(OAc)2/Pd2(dba)3. The combination of Pd(OAc)2, Xantphos, K2CO3 and dioxane was found to be crucial for the C–O cross-coupling reaction. This is the first report on coupling of amides, amino acid esters and phenols with N-protected 4-bromo-7-azaindole derivatives. PMID:23209536

  6. K-Nutrition, Growth Bud Formation, and Amine and Hydroxycinnamic Acid Amide Contents in Leaf Explants of Nicotiana tabacum Variety Xanthi n.c. Cultivated in Vitro1

    PubMed Central

    Klinguer, Serge; Martin-Tanguy, Josette; Martin, Claude

    1986-01-01

    The effects of K-nutrition on growth (increase of fresh weight), bud formation (time of emergence, number of buds), and amine and hydroxycinnamic acid amide contents in foliar explants of Nicotiana tabacum cv Xanthi n.c. cultivated in vitro were examined. In K-deficient medium and in high K medium growth and bud formation were markedly inhibited. Marked changes of amine content (a diamine, putrescine; a phenolic amine, phenethylamine) were observed after a few days of culture. No apparent relationship was found between these amines and growth or bud differentiation. In contrast, changes in hydroxycinnamic acid levels were shown to correlate well with growth and bud formation. The greatest stimulation of budding and growth was correlated with the greatest accumulation of these amides. The highest contents of hydroxycinnamic acid amides were found during the first 15 days in culture when intensive cell division took place. Then they declined sharply after 26 days in culture as the rate of cell division decreased and differentiation occurred. PMID:16665067

  7. New bitter-masking compounds: hydroxylated benzoic acid amides of aromatic amines as structural analogues of homoeriodictyol.

    PubMed

    Ley, Jakob P; Blings, Maria; Paetz, Susanne; Krammer, Gerhard E; Bertram, Heinz-Jürgen

    2006-11-01

    Starting from the known bitter-masking flavanones eriodictyol and homoeriodictyol from herba santa some structurally related hydroxybenzoic acid amides of benzylamines were synthesized and evaluated as masking agents toward bitterness of caffeine by sensory methods. The closest structural relatives of homoeriodictyol, the hydroxybenzoic acid vanillylamides 5-9, were the most active and were able to reduce the bitterness of a 500 mg L(-1) caffeine solution by about 30% at a concentration of 100 mg L(-1). 2,4-Dihydroxybenzoic acid vanillylamide 7 showed a clear dose-dependent activity as inhibitor of the bitter taste of caffein between 5 and 500 mg L(-1). Additionally, it was possible to reduce the bitterness of quinine and salicine but not of the bitter peptide N-l-leucyl-l-tryptophan. Combinations of homoeriodictyol and amide 7 showed no synergistic or antagonistic changes in activity. The results for model compound 7 suggested that the hitherto unknown masking mechanism is probably the same for flavanones and the new amides. In the future, the new amides may be alternatives for the expensive flavanones to create flavor solutions to mask bitterness of pharmaceuticals or foodstuffs. PMID:17061836

  8. Concerted Amidation of Activated Esters: Reaction Path and Origins of Selectivity in the Kinetic Resolution of Cyclic Amines via N-Heterocyclic Carbenes and Hydroxamic Acid Cocatalyzed Acyl Transfer

    PubMed Central

    2015-01-01

    The N-heterocyclic carbene and hydroxamic acid cocatalyzed kinetic resolution of cyclic amines generates enantioenriched amines and amides with selectivity factors up to 127. In this report, a quantum mechanical study of the reaction mechanism indicates that the selectivity-determining aminolysis step occurs via a novel concerted pathway in which the hydroxamic acid plays a key role in directing proton transfer from the incoming amine. This modality was found to be general in amide bond formation from a number of activated esters including those generated from HOBt and HOAt, reagents that are broadly used in peptide coupling. For the kinetic resolution, the proposed model accurately predicts the faster reacting enantiomer. A breakdown of the steric and electronic control elements shows that a gearing effect in the transition state is responsible for the observed selectivity. PMID:25050843

  9. Silver-catalyzed synthesis of amides from amines and aldehydes

    DOEpatents

    Madix, Robert J; Zhou, Ling; Xu, Bingjun; Friend, Cynthia M; Freyschlag, Cassandra G

    2014-11-18

    The invention provides a method for producing amides via the reaction of aldehydes and amines with oxygen adsorbed on a metallic silver or silver alloy catalyst. An exemplary reaction is shown in Scheme 1: (I), (II), (III). ##STR00001##

  10. Amide bond formation through iron-catalyzed oxidative amidation of tertiary amines with anhydrides.

    PubMed

    Li, Yuanming; Ma, Lina; Jia, Fan; Li, Zhiping

    2013-06-01

    A general and efficient method for amide bond synthesis has been developed. The method allows for synthesis of tertiary amides from readily available tertiary amines and anhydrides in the presence of FeCl2 as catalyst and tert-butyl hydroperoxide in water (T-Hydro) as oxidant. Mechanistic studies indicated that the in situ-generated α-amino peroxide of tertiary amine and iminium ion act as key intermediates in this oxidative transformation. PMID:23668222

  11. Modulation by APGW-amide, an Achatina endogenous inhibitory tetrapeptide, of currents induced by neuroactive compounds on Achatina neurons: amines and amino acids.

    PubMed

    Han, X Y; Salunga, T L; Zhang, W; Takeuchi, H; Matsunami, K

    1997-10-01

    1. Modulatory effects of APGW-amide (Ala-Pro-Gly-Trp-NH2), proposed as an inhibitory neurotransmitter of Achatina neurons, perfused at 3 x 10(-6) M on the currents induced by small-molecule putative neurotransmitters were examined by using Achatina giant neuron types, v-RCDN (ventral-right cerebral distinct neuron), TAN (tonically autoactive neuron) and RAPN (right anterior pallial nerve neuron), under voltage clamp. These putative neurotransmitters were ejected locally to the neuron by brief pneumatic pressure. 2. Outward current (Iout) induced by erythro-beta-hydroxy-L-glutamic acid (erythro-L-BHGA) on v-RCDN, which was probably K+ dependent, was enhanced with membrane conductance (g) increase under APGW-amide. From dose (pressure duration)-response curves of erythro-L-BHGA measured in physiological solution (control curve) and with APGW-amide (drug curve), ED50 values of the two curves were nearly comparable, whereas Emax of the drug curve was significantly larger than that of the other. From a Lineweaver-Burk plot of these data, the cross point of the control line and the drug line was on the abscissa. 3. K(+)-dependent Iout caused by dopamine (DA) on v-RCDN was inhibited with a g increase by APGW-amide. The inhibition of this current caused by APGW-amide was mainly in a noncompetitive and partly uncompetitive manner. 4. 5-Hydroxytryptamine (5-HT) produced an inward current (Iin) with two (fast and slow) components on TAN, which was probably Na+ dependent. The fast component of the Iin was inhibited by APGW-amide. The inhibition was mainly in a noncompetitive manner. 5. The currents induced by acetylcholine, gamma-aminobutyric acid and L-glutamic acid on Achatina neuron types were not affected by APGW-amide. 6. The inhibitory effects of APGW-amide on the Iin (fast component) induced by 5-HT were nearly equipotent or a bit stronger than those on the Iout caused by DA. 7. The g increase produced by APGW-amide would be a cause for inhibiting the Iout induced by DA

  12. Amides and Hydrazides from Amine and Hydrazine Hydrochlorides.

    ERIC Educational Resources Information Center

    Shama, Sami A.; Tran, Thuan L.

    1978-01-01

    This safe and efficient procedure for the synthesis of N-substituted amides and hydrazides is a modification of the Schotten-Bausmann procedure in which the amine or hydrazide is replaced by the corresponding hydrochloride salt, and the use of alkali is eliminated. (Author/BB)

  13. New Umami Amides: Structure-Taste Relationship Studies of Cinnamic Acid Derived Amides and the Natural Occurrence of an Intense Umami Amide in Zanthoxylum piperitum.

    PubMed

    Frerot, Eric; Neirynck, Nathalie; Cayeux, Isabelle; Yuan, Yoyo Hui-Juan; Yuan, Yong-Ming

    2015-08-19

    A series of aromatic amides were synthesized from various acids and amines selected from naturally occurring structural frameworks. These synthetic amides were evaluated for umami taste in comparison with monosodium glutamate. The effect of the substitution pattern of both the acid and the amine parts on umami taste was investigated. The only intensely umami-tasting amides were those made from 3,4-dimethoxycinnamic acid. The amine part was more tolerant to structural changes. Amides bearing an alkyl- or alkoxy-substituted phenylethylamine residue displayed a clean umami taste as 20 ppm solutions in water. Ultraperformance liquid chromatography coupled with a high quadrupole-Orbitrap mass spectrometer (UPLC/MS) was subsequently used to show the natural occurrence of these amides. (E)-3-(3,4-Dimethoxyphenyl)-N-(4-methoxyphenethyl)acrylamide was shown to occur in the roots and stems of Zanthoxylum piperitum, a plant of the family Rutaceae growing in Korea, Japan, and China. PMID:26230212

  14. Copper-catalyzed oxidative amidation of aldehydes with amine salts: synthesis of primary, secondary, and tertiary amides.

    PubMed

    Ghosh, Subhash Chandra; Ngiam, Joyce S Y; Seayad, Abdul M; Tuan, Dang Thanh; Chai, Christina L L; Chen, Anqi

    2012-09-21

    A practical method for the amidation of aldehydes with economic ammonium chloride or amine hydrochloride salts has been developed for the synthesis of a wide variety of amides by using inexpensive copper sulfate or copper(I) oxide as a catalyst and aqueous tert-butyl hydroperoxide as an oxidant. This amidation reaction is operationally straightforward and provides primary, secondary, and tertiary amides in good to excellent yields for most cases utilizing inexpensive and readily available reagents under mild conditions. In situ formation of amine salts from free amines extends the substrate scope of the reaction. Chiral amides are also synthesized from their corresponding chiral amines without detectable racemization. The practicality of this amide formation reaction has been demonstrated in an efficient synthesis of the antiarrhythmic drug N-acetylprocainamide. PMID:22894712

  15. Mild Metal-Free Hydrosilylation of Secondary Amides to Amines.

    PubMed

    Huang, Pei-Qiang; Lang, Qi-Wei; Wang, Yan-Rong

    2016-05-20

    The combination of amide activation by Tf2O with B(C6F5)3-catalyzed hydrosilylation with TMDS constitutes a method for the one-pot reduction of secondary amides to amines under mild conditions. The method displays a broad applicability for the reduction of many types of substrates, and shows good compatibility and excellent chemoselectivity for many sensitive functional groups. Reductions of a multifunctionalized α,β-unsaturated amide obtained from another synthetic methodology, and a C-H functionalization product produced the corresponding amines in good to excellent yield. Chemoselective reduction of enantiomeric pure (ee >99%) tetrahydro-5-oxo-2-furaneamides yielded 5-(aminomethyl)dihydrofuran-2(3H)-ones in a racemization-free manner. The latter were converted in one pot to N-protected 5-hydroxypiperidin-2-ones, which are building blocks for the synthesis of many natural products. Further elaboration of an intermediate led to a concise four-step synthesis of (-)-epi-pseudoconhydrine. PMID:27100232

  16. Diaminopimelic Acid Amidation in Corynebacteriales

    PubMed Central

    Levefaudes, Marjorie; Patin, Delphine; de Sousa-d'Auria, Célia; Chami, Mohamed; Blanot, Didier; Hervé, Mireille; Arthur, Michel; Houssin, Christine; Mengin-Lecreulx, Dominique

    2015-01-01

    A gene named ltsA was earlier identified in Rhodococcus and Corynebacterium species while screening for mutations leading to increased cell susceptibility to lysozyme. The encoded protein belonged to a huge family of glutamine amidotransferases whose members catalyze amide nitrogen transfer from glutamine to various specific acceptor substrates. We here describe detailed physiological and biochemical investigations demonstrating the specific role of LtsA protein from Corynebacterium glutamicum (LtsACg) in the modification by amidation of cell wall peptidoglycan diaminopimelic acid (DAP) residues. A morphologically altered but viable ΔltsA mutant was generated, which displays a high susceptibility to lysozyme and β-lactam antibiotics. Analysis of its peptidoglycan structure revealed a total loss of DAP amidation, a modification that was found in 80% of DAP residues in the wild-type polymer. The cell peptidoglycan content and cross-linking were otherwise not modified in the mutant. Heterologous expression of LtsACg in Escherichia coli yielded a massive and toxic incorporation of amidated DAP into the peptidoglycan that ultimately led to cell lysis. In vitro assays confirmed the amidotransferase activity of LtsACg and showed that this enzyme used the peptidoglycan lipid intermediates I and II but not, or only marginally, the UDP-MurNAc pentapeptide nucleotide precursor as acceptor substrates. As is generally the case for glutamine amidotransferases, either glutamine or NH4+ could serve as the donor substrate for LtsACg. The enzyme did not amidate tripeptide- and tetrapeptide-truncated versions of lipid I, indicating a strict specificity for a pentapeptide chain length. PMID:25847251

  17. Practical Synthesis of Amides via Copper/ABNO-Catalyzed Aerobic Oxidative Coupling of Alcohols and Amines.

    PubMed

    Zultanski, Susan L; Zhao, Jingyi; Stahl, Shannon S

    2016-05-25

    A modular Cu/ABNO catalyst system has been identified that enables efficient aerobic oxidative coupling of alcohols and amines to amides. All four permutations of benzylic/aliphatic alcohols and primary/secondary amines are viable in this reaction, enabling broad access to secondary and tertiary amides. The reactions exhibit excellent functional group compatibility and are complete within 30 min-3 h at rt. All components of the catalyst system are commercially available. PMID:27171973

  18. Chemo- and Stereoselective Transition-Metal-Free Amination of Amides with Azides

    PubMed Central

    2016-01-01

    The synthesis of α-amino carbonyl/carboxyl compounds is a contemporary challenge in organic synthesis. Herein, we present a stereoselective α-amination of amides employing simple azides that proceeds under mild conditions with release of nitrogen gas. The amide is used as the limiting reagent, and through simple variation of the azide pattern, various differently substituted aminated products can be obtained. The reaction is fully chemoselective for amides even in the presence of esters or ketones and lends itself to preparation of optically enriched products. PMID:27350334

  19. Iodine-Catalyzed Decarboxylative Amidation of β,γ-Unsaturated Carboxylic Acids with Chloramine Salts Leading to Allylic Amides.

    PubMed

    Kiyokawa, Kensuke; Kojima, Takumi; Hishikawa, Yusuke; Minakata, Satoshi

    2015-10-26

    The iodine-catalyzed decarboxylative amidation of β,γ-unsaturated carboxylic acids with chloramine salts is described. This method enables the regioselective synthesis of allylic amides from various types of β,γ-unsaturated carboxylic acids containing substituents at the α- and β-positions. In the reaction, N-iodo-N-chloroamides, generated by the reaction of a chloramine salt with I2 , function as a key active species. The reaction provides an attractive alternative to existing methods for the synthesis of useful secondary allylic amine derivatives. PMID:26493878

  20. One-Pot Amide Bond Formation from Aldehydes and Amines via a Photoorganocatalytic Activation of Aldehydes.

    PubMed

    Papadopoulos, Giorgos N; Kokotos, Christoforos G

    2016-08-19

    A mild, one-pot, and environmentally friendly synthesis of amides from aldehydes and amines is described. Initially, a photoorganocatalytic reaction of aldehydes with di-isopropyl azodicarboxylate leads to an intermediate carbonyl imide, which can react with a variety of amines to afford the desired amides. The initial visible light-mediated activation of a variety of monosubstituted or disubstituted aldehydes is usually fast, occurring in a few hours. Following the photocatalytic reaction, addition of the primary amine at room temperature or the secondary amine at elevated temperatures leads to the corresponding amide from moderate to excellent yields without epimerization. This methodology was applied in the synthesis of Moclobemide, a drug against depression and social anxiety. PMID:27227271

  1. Biocatalytic amidation of carboxylic acids and their antinemic activity.

    PubMed

    Bose, Abinesh; Shakil, Najam Akhtar; Pankaj; Kumar, Jitendra; Singh, Manish K

    2010-04-01

    A series of novel N-alkyl substituted amides, synthesized by enzyme catalysis, were evaluated against root-knot nematode, Meloidogyne incognita and found to have potential antinemic activity. The corresponding amides were prepared by the condensation of equimolar amounts of carboxylic acids with different alkyl amines in the presence of Candida antarctica lipase at 60-90 degrees C in 16-20 h. The reactions were carried out in a non - solvent system without the use of any activating agents. All the products were obtained in appreciable amounts and the yields for different compounds varied between 77.4-82.3%. The synthesized compounds were characterized using spectroscopy techniques namely Infra Red (IR) and Nuclear Magnetic Resonance (NMR) ((1)H and (13)C). Nematicidal activity of synthesized amides was evaluated against J(2)s of Meloidogyne incognita at 500, 250, 125 and 62.5 ppm concentrations after 24 h, 48 h and 72 h of exposure. Among all the tested compounds, N-propyl-butyramide, N-propyl-pentanamide and N-propyl-hexanamide were found to possess significant activity with LC(50) values of 67.46, 83.49 and 96.53 respectively. N-propyl-butyramide with LC(50) value of 67.46 ppm was found to be most active amide against J(2)s of Meloidogyne incognita. The bioactivity study showed that an increase in alkyl chain significantly decreased the activity of amides against root-knot nematode. PMID:20390959

  2. Facile amine formation by intermolecular catalytic amidation of carbon-hydrogen bonds.

    PubMed

    Fructos, Manuel R; Trofimenko, Swiatoslaw; Díaz-Requejo, M Mar; Pérez, Pedro J

    2006-09-13

    A simple copper-based catalytic system has been developed for the carbon-hydrogen amidation reaction. The copper-homoscorpionate complex Tp(Br3)Cu(NCMe) catalyzes the transfer of the nitrene unit NTs (Ts = p-toluenesulfonyl) and its subsequent insertion into the sp(3) C-H bonds of alkyl aromatic and cyclic ethers or the sp(2) C-H bonds of benzene using PhI=NTs as the nitrene source, affording the corresponding trisubstitued NR(1)HTs amines in moderate to high yields. The use of the environmentally friendly chloramine-T has also proven effective, with the advantage that sodium chloride is formed as the only byproduct. A tandem, one-pot consecutive nitrene-carbene insertion system has been developed to yield amino acid derivatives. PMID:16953617

  3. Supported Gold Nanoparticles for Efficient α-Oxygenation of Secondary and Tertiary Amines into Amides.

    PubMed

    Jin, Xiongjie; Kataoka, Kengo; Yatabe, Takafumi; Yamaguchi, Kazuya; Mizuno, Noritaka

    2016-06-13

    Although the α-oxygenation of amines is a highly attractive method for the synthesis of amides, efficient catalysts suited to a wide range of secondary and tertiary alkyl amines using O2 as the terminal oxidant have no precedent. This report describes a novel, green α-oxygenation of a wide range of linear and cyclic secondary and tertiary amines mediated by gold nanoparticles supported on alumina (Au/Al2 O3 ). The observed catalysis was truly heterogeneous, and the catalyst could be reused. The present α-oxygenation utilizes O2 as the terminal oxidant and water as the oxygen atom source of amides. The method generates water as the only theoretical by-product, which highlights the environmentally benign nature of the present reaction. Additionally, the present α-oxygenation provides a convenient method for the synthesis of (18) O-labeled amides using H2 (18) O as the oxygen source. PMID:27151621

  4. Characterization of fatty amides produced by lipase-catalyzed amidation of multihydroxylated fatty acids

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Novel multi-hydroxylated primary fatty amides produced by direct amidation of 7,10-dihydroxy-8(E)-octadecenoic acid (DOD) and 7,10,12-trihydroxy-8(E)-octadecenoic acid (TOD) were characterized by GC-MS and NMR. The amidation reactions were catalyzed by immobilized Pseudozyma (Candida) antarctica li...

  5. Pharmaceuticals and Surfactants from Alga-Derived Feedstock: Amidation of Fatty Acids and Their Derivatives with Amino Alcohols.

    PubMed

    Tkacheva, Anastasia; Dosmagambetova, Inkar; Chapellier, Yann; Mäki-Arvela, Päivi; Hachemi, Imane; Savela, Risto; Leino, Reko; Viegas, Carolina; Kumar, Narendra; Eränen, Kari; Hemming, Jarl; Smeds, Annika; Murzin, Dmitry Yu

    2015-08-24

    Amidation of renewable feedstocks, such as fatty acids, esters, and Chlorella alga based biodiesel, was demonstrated with zeolites and mesoporous materials as catalysts and ethanolamine, alaninol, and leucinol. The last two can be derived from amino acids present in alga. The main products were fatty alkanol amides and the corresponding ester amines, as confirmed by NMR and IR spectroscopy. Thermal amidation of technical-grade oleic acid and stearic acid at 180 °C with ethanolamine were non-negligible; both gave 61% conversion. In the amidation of stearic acid with ethanolamine, the conversion over H-Beta-150 was 80% after 3 h, whereas only 63% conversion was achieved for oleic acid; this shows that a microporous catalyst is not suitable for this acid and exhibits a wrinkled conformation. The highest selectivity to stearoyl ethanolamide of 92% was achieved with mildly acidic H-MCM-41 at 70% conversion in 3 h at 180 °C. Highly acidic catalysts favored the formation of the ester amine, whereas the amide was obtained with a catalyst that exhibited an optimum acidity. The conversion levels achieved with different fatty acids in the range C12-C18 were similar; this shows that the fatty acid length does not affect the amidation rate. The amidation of methyl palmitate and biodiesel gave low conversions over an acidic catalyst, which suggested that the reaction mechanism in the amidation of esters was different. PMID:26197759

  6. PLANT FATTY ACID (ETHANOL) AMIDE HYDROLASES

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Fatty acid amide hydrolase (FAAH) plays a central role in modulating endogenous N-acylethanolamine (NAE) levels in vertebrates, and, in part, constitutes an “endocannabinoid” signaling pathway that regulates diverse physiological and behavioral processes in animals. Recently, an Arabidopsis FAAH hom...

  7. Amide and amine nucleophiles in polar radical crossover cycloadditions: synthesis of γ-lactams and pyrrolidines.

    PubMed

    Gesmundo, Nathan J; Grandjean, Jean-Marc M; Nicewicz, David A

    2015-03-01

    In this work we present a direct catalytic synthesis of γ-lactams and pyrrolidines from alkenes and activated unsaturated amides or protected unsaturated amines, respectively. Using a mesityl acridinium single electron photooxidant and a thiophenol cocatalyst under irradiation, we are able to directly forge these important classes of heterocycles with complete regiocontrol. PMID:25695366

  8. Mosher Amides: Determining the Absolute Stereochemistry of Optically-Active Amines

    ERIC Educational Resources Information Center

    Allen, Damian A.; Tomaso, Anthony E., Jr.; Priest, Owen P.; Hindson, David F.; Hurlburt, Jamie L.

    2008-01-01

    The use of chiral reagents for the derivatization of optically-active amines and alcohols for the purpose of determining their enantiomeric purity or absolute configuration is a tool used by many chemists. Among the techniques used, Mosher's amide and Mosher's ester analyses are among the most reliable and one of the most often used. Despite this,…

  9. 40 CFR 721.10320 - Fatty acid amide (generic).

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Fatty acid amide (generic). 721.10320... Substances § 721.10320 Fatty acid amide (generic). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as fatty acid amide (PMN P-03-186) is...

  10. 40 CFR 721.10463 - Fatty acid amides (generic).

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Fatty acid amides (generic). 721.10463... Substances § 721.10463 Fatty acid amides (generic). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as fatty acid amides (PMN...

  11. Chemoselective Reduction of Tertiary Amides under Thermal Control: Formation of either Aldehydes or Amines.

    PubMed

    Tinnis, Fredrik; Volkov, Alexey; Slagbrand, Tove; Adolfsson, Hans

    2016-03-24

    The chemoselective reduction of amides in the presence of other more reactive reducible functional groups is a highly challenging transformation, and successful examples thereof are most valuable in synthetic organic chemistry. Only a limited number of systems have demonstrated the chemoselective reduction of amides over ketones. Until now, the aldehyde functionality has not been shown to be compatible in any catalytic reduction protocol. Described herein is a [Mo(CO)6 ]-catalyzed protocol with an unprecedented chemoselectivity and allows for the reduction of amides in the presence of aldehydes and imines. Furthermore, the system proved to be tunable by variation of the temperature, which enabled for either C-O or C-N bond cleavage that ultimately led to the isolation of both amines and aldehydes, respectively, in high chemical yields. PMID:26934055

  12. Synthesis and preliminary biological evaluations of (+)-isocampholenic acid-derived amides.

    PubMed

    Grošelj, Uroš; Golobič, Amalija; Knez, Damijan; Hrast, Martina; Gobec, Stanislav; Ričko, Sebastijan; Svete, Jurij

    2016-08-01

    The synthesis of two novel (+)-isocampholenic acid-derived amines has been realized starting from commercially available (1S)-(+)-10-camphorsulfonic acid. The novel amines as well as (+)-isocampholenic acid have been used as building blocks in the construction of a library of amides using various aliphatic, aromatic, and amino acid-derived coupling partners using BPC and CDI as activating agents. Amide derivatives have been assayed against several enzymes that hold potential for the development of new drugs to battle bacterial infections and Alzheimer's disease. Compounds 20c and 20e showed promising selective sub-micromolar inhibition of human butyrylcholinesterase [Formula: see text] ([Formula: see text] values [Formula: see text] and [Formula: see text], respectively). PMID:27017352

  13. Enzymatic chemoselective synthesis of secondary-amide surfactant from N-methylethanol amine.

    PubMed

    Sharma, Jitender; Batovska, Daniela; Kuwamori, Yuko; Asano, Yasuhisa

    2005-12-01

    Efficient selective synthesis of the secondary amide surfactant N-methyl lauroylethanolamide from methyl laurate and N-methylethanol amine by carrier-fixed Chirazyme L-2 (Candida antarctica) using a kinetic strategy has been demonstrated. When different solvents were screened for product yields using Chirazyme L-2, acetonitrile was found to be optimal. The rate of the reaction increased sharply by increasing the molar ratio of the reactants and the reaction temperature. When the reaction was performed at 50 degrees C for 36 h with 50 mmol ester and 100 mmol amine, the product was obtained in a 97.1% yield. With 50 mmol ester and 150 mmol amine, the highest yield (97.3%) was obtained after 16 h of incubation at 50 degrees C. It took only 5 h to get a yield of 95.8% at 60 degrees C using 50 mmol ester and 200 mmol amine. The enzyme activity in the amidation reaction mixture did not decrease notably even after six uses. PMID:16473777

  14. Mechanism of Oxidative Amidation of Nitroalkanes with Oxygen and Amine Nucleophiles by Using Electrophilic Iodine.

    PubMed

    Li, Jing; Lear, Martin J; Kwon, Eunsang; Hayashi, Yujiro

    2016-04-11

    Recently, we developed a direct method to oxidatively convert primary nitroalkanes into amides that entailed mixing an iodonium source with an amine, base, and oxygen. Herein, we systematically investigated the mechanism and likely intermediates of such methods. We conclude that an amine-iodonium complex first forms through N-halogen bonding. This complex reacts with aci-nitronates to give both α-iodo- and α,α-diiodonitroalkanes, which can act as alternative sources of electrophilic iodine and also generate an extra equimolar amount of I(+) under O2. In particular, evidence supports α,α-diiodonitroalkane intermediates reacting with molecular oxygen to form a peroxy adduct; alternatively, these tetrahedral intermediates rearrange anaerobically to form a cleavable nitrite ester. In either case, activated esters are proposed to form that eventually reacts with nucleophilic amines in a traditional fashion. PMID:26938791

  15. 40 CFR 721.6183 - Amides, from ammonium hydroxide - maleic anhydride polymer and hydrogenated tallow alkyl amines...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... - maleic anhydride polymer and hydrogenated tallow alkyl amines, sodium salts, compds. with ethanolamine... Substances § 721.6183 Amides, from ammonium hydroxide - maleic anhydride polymer and hydrogenated tallow... anhydride polymer and hydrogenated tallow alkyl amines, sodium salts, compds. with ethanolamine (PMN...

  16. 40 CFR 721.6183 - Amides, from ammonium hydroxide - maleic anhydride polymer and hydrogenated tallow alkyl amines...

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... - maleic anhydride polymer and hydrogenated tallow alkyl amines, sodium salts, compds. with ethanolamine... Substances § 721.6183 Amides, from ammonium hydroxide - maleic anhydride polymer and hydrogenated tallow... anhydride polymer and hydrogenated tallow alkyl amines, sodium salts, compds. with ethanolamine (PMN...

  17. Gas-Phase Amidation of Carboxylic Acids with Woodward's Reagent K Ions

    NASA Astrophysics Data System (ADS)

    Peng, Zhou; Pilo, Alice L.; Luongo, Carl A.; McLuckey, Scott A.

    2015-06-01

    Gas-phase amidation of carboxylic acids in multiply-charged peptides is demonstrated via ion/ion reactions with Woodward's reagent K (wrk) in both positive and negative mode. Woodward's reagent K, N-ethyl-3-phenylisoxazolium-3'-sulfonate, is a commonly used reagent that activates carboxylates to form amide bonds with amines in solution. Here, we demonstrate that the analogous gas-phase chemistry occurs upon reaction of the wrk ions and doubly protonated (or doubly deprotonated) peptide ions containing the carboxylic acid functionality. The reaction involves the formation of the enol ester intermediate in the electrostatic complex. Upon collisional activation, the ethyl amine on the reagent is transferred to the activated carbonyl carbon on the peptide, resulting in the formation of an ethyl amide (addition of 27 Da to the peptide) with loss of a neutral ketene derivative. Further collision-induced dissociation (CID) of the products and comparison with solution-phase amidation product confirms the structure of the ethyl amide.

  18. 40 CFR 721.10512 - Fatty acid maleic acid amides (generic).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Fatty acid maleic acid amides (generic... Specific Chemical Substances § 721.10512 Fatty acid maleic acid amides (generic). (a) Chemical substance... fatty acid maleic acid amides (PMNs P-07-563 and P-07-564) are subject to reporting under this...

  19. 40 CFR 721.10512 - Fatty acid maleic acid amides (generic).

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Fatty acid maleic acid amides (generic... Specific Chemical Substances § 721.10512 Fatty acid maleic acid amides (generic). (a) Chemical substance... fatty acid maleic acid amides (PMNs P-07-563 and P-07-564) are subject to reporting under this...

  20. Fatty acid amides from freshwater green alga Rhizoclonium hieroglyphicum.

    PubMed

    Dembitsky, V M; Shkrob, I; Rozentsvet, O A

    2000-08-01

    Freshwater green algae Rhizoclonium hieroglyphicum growing in the Ural Mountains were examined for their fatty acid amides using capillary gas chromatography-mass spectrometry (GC-MS). Eight fatty acid amides were identified by GC-MS. (Z)-9-octadecenamide was found to be the major component (2.26%). PMID:11014298

  1. Methods for attaching polymerizable ceragenins to water treatment membranes using amine and amide linkages

    DOEpatents

    Hibbs, Michael; Altman, Susan J.; Jones, Howland D.T.; Savage, Paul B.

    2013-10-15

    This invention relates to methods for chemically grafting and attaching ceragenin molecules to polymer substrates; methods for synthesizing ceragenin-containing copolymers; methods for making ceragenin-modified water treatment membranes and spacers; and methods of treating contaminated water using ceragenin-modified treatment membranes and spacers. Ceragenins are synthetically produced antimicrobial peptide mimics that display broad-spectrum bactericidal activity. Alkene-functionalized ceragenins (e.g., acrylamide-functionalized ceragenins) can be attached to polyamide reverse osmosis membranes using amine-linking, amide-linking, UV-grafting, or silane-coating methods. In addition, silane-functionalized ceragenins can be directly attached to polymer surfaces that have free hydroxyls.

  2. Controlled Reduction of Tertiary Amides to the Corresponding Alcohols, Aldehydes, or Amines Using Dialkylboranes and Aminoborohydride Reagents.

    PubMed

    Bailey, Christopher L; Joh, Alexander Y; Hurley, Zefan Q; Anderson, Christopher L; Singaram, Bakthan

    2016-05-01

    Dialkylboranes and aminoborohydrides are mild, selective reducing agents complementary to the commonly utilized amide reducing agents, such as lithium aluminum hydride (LiAlH4) and diisobutylaluminum hydride (DIBAL) reagents. Tertiary amides were reduced using 1 or 2 equiv of various dialkylboranes. The reduction of tertiary amides required 2 equiv of 9-borabicyclo[3.3.1]nonane (9-BBN) for complete reduction to give the corresponding tertiary amines. One equivalent of sterically hindered disiamylborane reacts with tertiary amides to afford the corresponding aldehydes. Aminoborohydrides are powerful and selective reducing agents for the reduction of tertiary amides. Lithium dimethylaminoborohydride and lithium diisopropylaminoborohydride are prepared from n-butyllithium and the corresponding amine-borane. Chloromagnesium dimethylaminoborohydride (ClMg(+)[H3B-NMe2](-), MgAB) is prepared by the reaction of dimethylamine-borane with methylmagnesium chloride. Solutions of aminoborohydride reduce aliphatic, aromatic, and heteroaromatic tertiary amides to give the corresponding alcohol, amine, or aldehyde depending on the steric requirement of the tertiary amide and the aminoborohydride used. PMID:27035215

  3. Aerobic oxidative amidation of aromatic and cinnamic aldehydes with secondary amines by CuI/2-pyridonate catalytic system.

    PubMed

    Zhu, Mingwen; Fujita, Ken-ichi; Yamaguchi, Ryohei

    2012-10-19

    A simple and convenient CuI/2-pyridonate catalytic system for the oxidative amidation of aldehydes with secondary amines has been developed. With this system, a variety of useful arylamides have been synthesized in moderate to good yields in the presence of small amount of copper catalyst and the pyridonate ligand, generating only water as a coproduct. Synthesis of cinnamamides was also achieved by the reactions of cinnamaldehydes with secondary amines in moderate yields. Air was successfully employed as a green oxidant in this catalytic system, achieving a safe and atom-efficient system for the synthesis of amides. PMID:23006061

  4. Extraction of carboxylic acids by amine extractants

    SciTech Connect

    Tamada, Janet Ayako; King, C.J.

    1989-01-01

    This work examines the chemistry of solvent extraction by long-chain amines for recovery of carboxylic acids from dilute aqueous solution. Long-chain amines act as complexing agents with the acid, which facilitates distribution of the acid into the organic phase. The complexation is reversible, allowing for recovery of the acid from the organic phase and regeneration of the extractant. Batch extraction experiments were performed to study the complexation of acetic, lactic, succinic, malonic, fumaric, and maleic acids with Alamine 336, an aliphatic, tertiary amine extractant, dissolved in various diluents. Results were interpreted by a ''chemical'' model, in which stoichiometric ratios of acid and amine molecules are assumed to form complexes in the solvent phase. From fitting of the extraction data, the stoichiometry of complexes formed and the corresponding equilibrium constants were obtained. The results of the model were combined with infrared spectroscopic experiments and results of past studies to analyze the chemical interactions that are responsible for extraction behavior. The information from the equilibrium studies was used to develop guidelines for large-scale staged extraction and regeneration schemes. A novel scheme, in which the diluent composition is shifted between extraction and regeneration, was developed which could achieve both high solute recovery and high product concentration. 169 refs., 57 figs., 15 tabs.

  5. Analysing the Temperature Effect on the Competitiveness of the Amine Addition versus the Amidation Reaction in the Epoxidized Oil/Amine System by MCR-ALS of FTIR Data

    PubMed Central

    del Río, Vanessa; Callao, M. Pilar; Larrechi, M. Soledad

    2011-01-01

    The evaluation of the temperature effect on the competitiveness between the amine addition and the amidation reaction in a model cure acid-catalysed reaction between the epoxidized methyl oleate (EMO), obtained from high oleic sunflower oil, and aniline is reported. The study was carried out analysing the kinetic profiles of the chemical species involved in the system, which were obtained applying multivariate curve resolution-alternating least squares (MCR-ALS) to the Fourier transform infrared spectra data obtained from the reaction monitoring at two different temperatures (60°C and 30°C). At both experimental temperatures, two mechanisms were postulated: non-autocatalytic and autocatalytic. The different behaviour was discussed considering not only the influence of the temperature on the amidation reaction kinetic, but also the presence of the homopolymerization of the EMO reagent. PMID:21765830

  6. Highly Enantioselective Fluorescent Recognition of Both Unfunctionalized and Functionalized Chiral Amines by a Facile Amide Formation from a Perfluoroalkyl Ketone.

    PubMed

    Wang, Chao; Anbaei, Parastoo; Pu, Lin

    2016-05-17

    The H8 BINOL-based perfluoroalkyl ketone (S)-2 is found to exhibit highly enantioselective fluorescent enhancements toward both unfunctionalized and functionalized chiral amines. It greatly expands the substrate scope of the corresponding BINOL-based sensor. A dramatic solvent effect was observed for the reaction of the amines with compound (S)-2. In DMF, cleavage of the perfluoroalkyl group of compound (S)-2 to form amides was observed but not in other solvents, such as methylene chloride, chloroform, THF, hexane, and perfluorohexane. Thus, the addition of another solvent, such as THF, can effectively quench the reaction of compound (S)-2 with amines in DMF to allow stable fluorescent measurement. This is the first example that the formation of strong amide bonds under very mild conditions is used for the enantioselective recognition of chiral amines. The mechanism of the reaction of compound (S)-2 with chiral amines is investigated by using various analytical methods including mass spectrometry as well as NMR and UV/Vis absorption spectroscopy. PMID:27061205

  7. 40 CFR 721.6140 - Dialkyldithiophosphoric acid, aliphatic amine salt.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ..., aliphatic amine salt. 721.6140 Section 721.6140 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY... Specific Chemical Substances § 721.6140 Dialkyldithiophosphoric acid, aliphatic amine salt. (a) Chemical... as a dialkyldithiophosphoric acid, aliphatic amine salt (P-90-1839) is subject to reporting...

  8. 40 CFR 721.6140 - Dialkyldithiophosphoric acid, aliphatic amine salt.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ..., aliphatic amine salt. 721.6140 Section 721.6140 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY... Specific Chemical Substances § 721.6140 Dialkyldithiophosphoric acid, aliphatic amine salt. (a) Chemical... as a dialkyldithiophosphoric acid, aliphatic amine salt (P-90-1839) is subject to reporting...

  9. 40 CFR 721.6140 - Dialkyldithiophosphoric acid, aliphatic amine salt.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ..., aliphatic amine salt. 721.6140 Section 721.6140 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY... Specific Chemical Substances § 721.6140 Dialkyldithiophosphoric acid, aliphatic amine salt. (a) Chemical... as a dialkyldithiophosphoric acid, aliphatic amine salt (P-90-1839) is subject to reporting...

  10. 40 CFR 721.6140 - Dialkyldithiophosphoric acid, aliphatic amine salt.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ..., aliphatic amine salt. 721.6140 Section 721.6140 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY... Specific Chemical Substances § 721.6140 Dialkyldithiophosphoric acid, aliphatic amine salt. (a) Chemical... as a dialkyldithiophosphoric acid, aliphatic amine salt (P-90-1839) is subject to reporting...

  11. 40 CFR 721.6140 - Dialkyldithiophosphoric acid, aliphatic amine salt.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ..., aliphatic amine salt. 721.6140 Section 721.6140 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY... Specific Chemical Substances § 721.6140 Dialkyldithiophosphoric acid, aliphatic amine salt. (a) Chemical... as a dialkyldithiophosphoric acid, aliphatic amine salt (P-90-1839) is subject to reporting...

  12. Synthesis and biological evaluation of piperic acid amides as free radical scavengers and α-glucosidase inhibitors.

    PubMed

    Takao, Koichi; Miyashiro, Takaki; Sugita, Yoshiaki

    2015-01-01

    A series of piperic acid amides (4-24, 29, 30) were synthesized and their 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging and α-glucosidase inhibitory activities were evaluated. Among the synthesized compounds, the amides 11, 13 and 15, which contain o-methoxyphenol, catechol or 5-hydroxyindole moieties, showed potent DPPH free radical scavenging activity (11: EC50 140 µM; 13: EC50 28 µM; 15: EC50 20 µM). The amides 10, 18 and 23 showed higher inhibitory activity of α-glucosidase (10: IC50 21 µM; 18: IC50 21 µM; 23: IC50 12 µM). These data suggest that the hydrophobicity of the conjugated amines is an important determinant of α-glucosidase inhibitory activity. In addition, the amides 13 and 15 showed both potent DPPH free radical scavenging activity and α-glucosidase inhibitory activity (13: IC50 46 µM; 15: IC50 46 µM). This is the first report identifying the DPPH free radical scavenging and α-glucosidase inhibitory activities of piperic acid amides and suggests that these amides may serve as lead compounds for the development of novel α-glucosidase inhibitors with antioxidant activity. PMID:25948326

  13. (E)-α,β-unsaturated amides from tertiary amines, olefins and CO via Pd/Cu-catalyzed aerobic oxidative N-dealkylation.

    PubMed

    Shi, Renyi; Zhang, Hua; Lu, Lijun; Gan, Pei; Sha, Yuchen; Zhang, Heng; Liu, Qiang; Beller, Matthias; Lei, Aiwen

    2015-02-21

    A novel Pd/Cu-catalyzed chemoselective aerobic oxidative N-dealkylation/carbonylation reaction has been developed. Tertiary amines are utilized as a "reservoir" of "active" secondary amines in this transformation, which inhibits the formation of undesired by-products and the deactivation of the catalysts. This protocol allows for an efficient and straightforward construction of synthetically useful and bioactive (E)-α,β-unsaturated amide derivatives from easily available tertiary amines, olefins and CO. PMID:25610923

  14. Chan-Evans-Lam Amination of Boronic Acid Pinacol (BPin) Esters: Overcoming the Aryl Amine Problem.

    PubMed

    Vantourout, Julien C; Law, Robert P; Isidro-Llobet, Albert; Atkinson, Stephen J; Watson, Allan J B

    2016-05-01

    The Chan-Evans-Lam reaction is a valuable C-N bond forming process. However, aryl boronic acid pinacol (BPin) ester reagents can be difficult coupling partners that often deliver low yields, in particular in reactions with aryl amines. Herein, we report effective reaction conditions for the Chan-Evans-Lam amination of aryl BPin with alkyl and aryl amines. A mixed MeCN/EtOH solvent system was found to enable effective C-N bond formation using aryl amines while EtOH is not required for the coupling of alkyl amines. PMID:27045570

  15. Mechanism of Boron-Catalyzed N-Alkylation of Amines with Carboxylic Acids.

    PubMed

    Zhang, Qi; Fu, Ming-Chen; Yu, Hai-Zhu; Fu, Yao

    2016-08-01

    Mechanistic study has been carried out on the B(C6F5)3-catalyzed amine alkylation with carboxylic acid. The reaction includes acid-amine condensation and amide reduction steps. In condensation step, the catalyst-free mechanism is found to be more favorable than the B(C6F5)3-catalyzed mechanism, because the automatic formation of the stable B(C6F5)3-amine complex deactivates the catalyst in the latter case. Meanwhile, the catalyst-free condensation is constituted by nucleophilic attack and the indirect H2O-elimination (with acid acting as proton shuttle) steps. After that, the amide reduction undergoes a Lewis acid (B(C6F5)3)-catalyzed mechanism rather than a Brønsted acid (B(C6F5)3-coordinated HCOOH)-catalyzed one. The B(C6F5)3)-catalyzed reduction includes twice silyl-hydride transfer steps, while the first silyl transfer is the rate-determining step of the overall alkylation catalytic cycle. The above condensation-reduction mechanism is supported by control experiments (on both temperature and substrates). Meanwhile, the predicted chemoselectivity is consistent with the predominant formation of the alkylation product (over disilyl acetal product). PMID:27441997

  16. Direct amidation of carboxylic acids catalyzed by ortho-iodo arylboronic acids: catalyst optimization, scope, and preliminary mechanistic study supporting a peculiar halogen acceleration effect.

    PubMed

    Gernigon, Nicolas; Al-Zoubi, Raed M; Hall, Dennis G

    2012-10-01

    The importance of amides as a component of biomolecules and synthetic products motivates the development of catalytic, direct amidation methods employing free carboxylic acids and amines that circumvent the need for stoichiometric activation or coupling reagents. ortho-Iodophenylboronic acid 4a has recently been shown to catalyze direct amidation reactions at room temperature in the presence of 4A molecular sieves as dehydrating agent. Herein, the arene core of ortho-iodoarylboronic acid catalysts has been optimized with regards to the electronic effects of ring substitution. Contrary to the expectation, it was found that electron-donating substituents are preferable, in particular, an alkoxy substituent positioned para to the iodide. The optimal new catalyst, 5-methoxy-2-iodophenylboronic acid (MIBA, 4f), was demonstrated to be kinetically more active than the parent des-methoxy catalyst 4a, providing higher yields of amide products in shorter reaction times under mild conditions at ambient temperature. Catalyst 4f is recyclable and promotes the formation of amides from aliphatic carboxylic acids and amines, and from heteroaromatic carboxylic acids and other functionalized substrates containing moieties like a free phenol, indole and pyridine. Mechanistic studies demonstrated the essential role of molecular sieves in this complex amidation process. The effect of substrate stoichiometry, concentration, and measurement of the catalyst order led to a possible catalytic cycle based on the presumed formation of an acylborate intermediate. The need for an electronically enriched ortho-iodo substituent in catalyst 4f supports a recent theoretical study (Marcelli, T. Angew. Chem. Int. Ed.2010, 49, 6840-6843) with a purported role for the iodide as a hydrogen-bond acceptor in the orthoaminal transition state. PMID:23013456

  17. New substituted amides and hydrazides of pectic acid

    SciTech Connect

    Lapenko, V.L.; Potapova, L.B.; Slivkin, A.I.; Razumnaya, Z.A.

    1988-05-10

    Structural variants of pectin amides and hydrazides are of practical value as flocculants in water treatment. The purpose of this work was to further investigate the synthesis of substituted amides and hydrazides of pectic acid and to study their activity as flocculants. They used pectin, methylation products of pectin, pectic acid, and methyl pectates. The synthesized analogs of pectinic materials containing nitrogen are essentially copolymers of hydrazido (amido) and carboxyl (methoxyl) derivatives of D-galacturonic acid. The flocculant activity of the new polymers was monitored with simulated drainage water containing kaolin or abrasive powder (for glass manufacture) in the presence of polyvalent metal ions. The use of the new ampholytic flocculants in the purification of water from suspended impurities permits a high degree of clarification with a sharp decrease in reagent consumption.

  18. Synthesis of imides via palladium-catalyzed decarboxylative amidation of α-oxocarboxylic acids with secondary amides.

    PubMed

    Xu, Ning; Liu, Jie; Li, Dengke; Wang, Lei

    2016-05-18

    An efficient synthesis of imides has been developed through a Pd-catalyzed decarboxylative amidation of α-oxocarboxylic acids with secondary amides. The reactions of N-substituted N-heteroarene-2-carboxamides with 2-oxo-2-arylacetic acids proceeded smoothly to generate the corresponding products in good yields in the presence of Pd(OAc)2 and K2S2O8. PMID:27143171

  19. Simple Amides of Oleanolic Acid as Effective Penetration Enhancers

    PubMed Central

    Bednarczyk-Cwynar, Barbara; Partyka, Danuta; Zaprutko, Lucjusz

    2015-01-01

    Transdermal transport is now becoming one of the most convenient and safe pathways for drug delivery. In some cases it is necessary to use skin penetration enhancers in order to allow for the transdermal transport of drugs that are otherwise insufficiently skin-permeable. A series of oleanolic acid amides as potential transdermal penetration enhancers was formed by multistep synthesis and the synthesis of all newly prepared compounds is presented. The synthetized amides of oleanolic acid were tested for their in vitro penetration promoter activity. The above activity was evaluated by means of using the Fürst method. The relationships between the chemical structure of the studied compounds and penetration activity are presented. PMID:26010090

  20. Antiproliferative activity of synthetic fatty acid amides from renewable resources.

    PubMed

    dos Santos, Daiane S; Piovesan, Luciana A; D'Oca, Caroline R Montes; Hack, Carolina R Lopes; Treptow, Tamara G M; Rodrigues, Marieli O; Vendramini-Costa, Débora B; Ruiz, Ana Lucia T G; de Carvalho, João Ernesto; D'Oca, Marcelo G Montes

    2015-01-15

    In the work, the in vitro antiproliferative activity of a series of synthetic fatty acid amides were investigated in seven cancer cell lines. The study revealed that most of the compounds showed antiproliferative activity against tested tumor cell lines, mainly on human glioma cells (U251) and human ovarian cancer cells with a multiple drug-resistant phenotype (NCI-ADR/RES). In addition, the fatty methyl benzylamide derived from ricinoleic acid (with the fatty acid obtained from castor oil, a renewable resource) showed a high selectivity with potent growth inhibition and cell death for the glioma cell line-the most aggressive CNS cancer. PMID:25510639

  1. Toxocara canis: Larvicidal activity of fatty acid amides.

    PubMed

    Mata-Santos, Taís; D'Oca, Caroline da Ros Montes; Mata-Santos, Hílton Antônio; Fenalti, Juliana; Pinto, Nitza; Coelho, Tatiane; Berne, Maria Elisabeth; da Silva, Pedro Eduardo Almeida; D'Oca, Marcelo Gonçalves Montes; Scaini, Carlos James

    2016-02-01

    Considering the therapeutic potential of fatty acid amides, the present study aimed to evaluate their in vitro activity against Toxocara canis larvae and their cytotoxicity for the first time. Linoleylpyrrolidilamide was the most potent, with a minimal larvicidal concentration (MLC) of 0.05 mg/mL and 27% cytotoxicity against murine peritoneal macrophages C57BL/6 mice, as assessed by the MTT assay. PMID:26783180

  2. The influence of amine/amide versus bisamide coordination in nickel superoxide dismutase.

    PubMed

    Neupane, Kosh P; Shearer, Jason

    2006-12-25

    Nickel superoxide dismutase (NiSOD) is a mononuclear nickel-containing metalloenzyme that catalyzes the disproportionation of superoxide by cycling between NiII and NiIII oxidation states. In the reduced NiII oxidation state, the metal center is ligated by two cysteinate sulfurs, one amide nitrogen, and one amine nitrogen (from the N-terminus), while in the oxidized NiIII state, an imidazole nitrogen coordinates to the metal center. Herein, we expand on a previous report in which we described a functional metallopeptide-based NiSOD model compound [NiII(SODM1)] (SODM1 = H2N-HCDLPCGVYDPA-COOH) by exploring how acylation of the N-terminus (producing [NiII(SODM1-Ac)]) influences the properties of the metallopeptide. Titration results, GPC data, and mass-spectrometry data demonstrate that NiII coordinates to SODM1-Ac in a 1:1 ratio, while variable pH studies show that NiII coordination is strong at a pH of 7.5 and above but not observed below a pH of 6.2. This is higher than [NiII(SODM1)] by approximately 1.0 pH unit consistent with bisamide ligation. Ni K-edge XAS demonstrates that the NiII center is coordinated in a square-planar NiN2S2 coordination environment with Ni-N distances of 1.846(4) A and Ni-S distances of 2.174(3) A. Comparison of the electronic absorption and CD spectrum of [NiII(SODM1)] versus [NiII(SODM1-Ac)] in conjunction with time-dependent DFT calculations suggests a decrease in Ni covalency in the acylated versus unacylated metallopeptide. This decrease in covalency was also supported by DFT calculations and Ni L-edge XAS. [NiII(SODM1-Ac)] has a quasireversible NiII/NiIII redox couple of 0.49(1) V vs Ag/AgCl, which represents a -0.2 V shift compared with [NiII(SODM1)], while the peak separation suggests a change in the coordination environment upon oxidation (i.e., axial imidazole ligation). Using the xanthine/xanthine oxidase assay, we determine that [NiII(SODM1-Ac)] is less active than [NiII(SODM1)] by over 2 orders of magnitude (IC50 = 3(1) x 10

  3. MATE Transporter-Dependent Export of Hydroxycinnamic Acid Amides.

    PubMed

    Dobritzsch, Melanie; Lübken, Tilo; Eschen-Lippold, Lennart; Gorzolka, Karin; Blum, Elke; Matern, Andreas; Marillonnet, Sylvestre; Böttcher, Christoph; Dräger, Birgit; Rosahl, Sabine

    2016-02-01

    The ability of Arabidopsis thaliana to successfully prevent colonization by Phytophthora infestans, the causal agent of late blight disease of potato (Solanum tuberosum), depends on multilayered defense responses. To address the role of surface-localized secondary metabolites for entry control, droplets of a P. infestans zoospore suspension, incubated on Arabidopsis leaves, were subjected to untargeted metabolite profiling. The hydroxycinnamic acid amide coumaroylagmatine was among the metabolites secreted into the inoculum. In vitro assays revealed an inhibitory activity of coumaroylagmatine on P. infestans spore germination. Mutant analyses suggested a requirement of the p-coumaroyl-CoA:agmatine N4-p-coumaroyl transferase ACT for the biosynthesis and of the MATE transporter DTX18 for the extracellular accumulation of coumaroylagmatine. The host plant potato is not able to efficiently secrete coumaroylagmatine. This inability is overcome in transgenic potato plants expressing the two Arabidopsis genes ACT and DTX18. These plants secrete agmatine and putrescine conjugates to high levels, indicating that DTX18 is a hydroxycinnamic acid amide transporter with a distinct specificity. The export of hydroxycinnamic acid amides correlates with a decreased ability of P. infestans spores to germinate, suggesting a contribution of secreted antimicrobial compounds to pathogen defense at the leaf surface. PMID:26744218

  4. Isolation and identification of fatty acid amides from Shengli coal

    SciTech Connect

    Ming-Jie Ding; Zhi-Min Zong; Ying Zong; Xiao-Dong Ou-Yang; Yao-Guo Huang; Lei Zhou; Feng Wang; Jiang-Pei Cao; Xian-Yong Wei

    2008-07-15

    Shengli coal, a Chinese brown coal, was extracted with carbon disulfide and the extract was gradiently eluted with n-hexane and ethyl acetate (EA)/n-hexane mixed solvents with different concentrations of EA in a silica gel-filled column. A series of fatty acid amides, including fourteen alkanamides (C{sub 15}-C{sub 28}) and three alkenamides (C{sub 18} and C{sub 22}), were isolated from the coal by this method and analyzed with a gas chromatography/mass spectrometry. 26 refs., 2 figs., 2 tabs.

  5. Relationship between chromatographic resolution and amide structure of chiral 2-hydroxy acids as O-(-)-menthoxycarbonylated diastereomeric derivatives for enantiomeric separation on achiral gas chromatography.

    PubMed

    Cha, Eunju; Kim, Sohee; Lee, Kang Mi; Kim, Ho Jun; Kim, Ki Hun; Kwon, Oh-Seung; Park, Ki Duk; Lee, Jaeick

    2016-02-15

    The relationship between chromatographic resolution and amide structure of chiral 2-hydroxy acids as O-(-)-menthoxycarbonylated diastereomeric derivatives on achiral gas chromatography was investigated to elucidate the best diastereomeric conformation for enantiomeric separation of chiral 2-hydroxy acids. Thirteen chiral 2-hydroxy acids were converted into nine different diastereomeric O-(-)-menthoxycarbonylated amide derivatives using the primary, secondary and cyclic amines to achieve complete enantiomeric separation through an achiral column. Each enantiomeric pair of 2-hydroxy acids as O-(-)-menthoxycarbonylated tert-butylamide derivatives was resolved on both the DB-5 and DB-17 columns with resolution factors ranging from 1.7 to 4.8 and 1.7 to 3.4, respectively. The results revealed that the structure of the amide moiety is shown to significantly affect chromatographic resolution. In addition, O-(-)-menthoxycarbonylated tert-butylamide derivatives were shown to be the best diastereomeric conformations for enantiomeric separation of 2-hydroxy acids. When comparing with our previous O-trifluoroacetylated(-)-menthyl ester derivatization method, the present results suggested that size differences between groups attached to the chiral center and conformational rigidity can have stronger effects on resolution than the distance between chiral centers. The elution of R- and S-stereoisomers was affected by the class of amine; i.e., primary, secondary, or cyclic, regardless of the substituents on the amine group, the structure of the 2-hydroxy acid, and the polarity of the column. PMID:26800225

  6. Acid-catalyzed dehydrogenation of amine-boranes

    DOEpatents

    Stephens, Frances Helen; Baker, Ralph Thomas

    2010-01-12

    A method of dehydrogenating an amine-borane using an acid-catalyzed reaction. The method generates hydrogen and produces a solid polymeric [R.sup.1R.sup.2B--NR.sup.3R.sup.4].sub.n product. The method of dehydrogenating amine-boranes may be used to generate H.sub.2 for portable power sources.

  7. Sterically-hindered amines for acid-gas absorption

    SciTech Connect

    Sartori, G.; Ho, W.S.; Savage, D.W.; Chludzinski, G.R.; Wiechert, S. )

    1988-01-01

    This paper describes sterically hindered amines for removal of acid gases such as CO/sub 2/ and H/sub 2/S from gaseous streams. Steric hindrance of amines reduces carbamate stability. Moderately hindered amines are characterized by high rates of CO/sub 2/ absorption and high capacities for CO/sub 2/. The moderately hindered amine in use with organic solvent has considerably higher capacity than the conventional amine-solvent system for simultaneous removal of CO/sub 2/ and H/sub 2/S from synthesis gas and natural gas. A severely-hindered-amine absorbent, characterized by a very low rate of CO/sub 2/ absorption, has much higher capacity and selectivity than the current industry standard absorbent, using the conventional methyldiethanolamine for selective removal of H/sub 2/S from CO/sub 2/-containing streams.

  8. Lipase-catalyzed synthesis of fatty acid amide (erucamide) using fatty acid and urea.

    PubMed

    Awasthi, Neeraj Praphulla; Singh, R P

    2007-01-01

    Ammonolysis of fatty acids to the corresponding fatty acid amides is efficiently catalysed by Candida antartica lipase (Novozym 435). In the present paper lipase-catalysed synthesis of erucamide by ammonolysis of erucic acid and urea in organic solvent medium was studied and optimal conditions for fatty amides synthesis were established. In this process erucic acid gave 88.74 % pure erucamide after 48 hour and 250 rpm at 60 degrees C with 1:4 molar ratio of erucic acid and urea, the organic solvent media is 50 ml tert-butyl alcohol (2-methyl-2-propanol). This process for synthesis is economical as we used urea in place of ammonia or other amidation reactant at atmospheric pressure. The amount of catalyst used is 3 %. PMID:17898456

  9. One-pot synthesis of amides by aerobic oxidative coupling of alcohols or aldehydes with amines using supported gold and base as catalysts.

    PubMed

    Kegnæs, Søren; Mielby, Jerrik; Mentzel, Uffe V; Jensen, Thomas; Fristrup, Peter; Riisager, Anders

    2012-02-28

    Synthesis of amides by aerobic oxidative coupling of alcohols or aldehydes with amines via intermediate formation of methyl esters is highly efficient and selective when using a catalytic system comprised of supported gold nanoparticles and added base in methanol. PMID:22274843

  10. [Activated Sludge Bacteria Transforming Cyanopyridines and Amides of Pyridinecarboxylic Acids].

    PubMed

    Demakov, V A; Vasil'ev, D M; Maksimova, Yu G; Pavlova, Yu A; Ovechkina, G V; Maksimov, A Yu

    2015-01-01

    Species diversity of bacteria from the activated sludge of Perm biological waste treatment facilities capable of transformation of cyanopyridines and amides of pyridinecarboxylic acids was investigated. Enrichment cultures in mineral media with 3-cyanopyridine as the sole carbon and nitrogen source were used to obtain 32 clones of gram-negative heterotrophic bacteria exhibiting moderate growth on solid and liquid media with 3- and 4-cyanopyridine. Sequencing of the 16S rRNA gene fragments revealed that the clones with homology of at least 99% belonged to the genera Acinetobacte, Alcaligenes, Delftia, Ochrobactrum, Pseudomonas, Stenotrophomonas, and Xanthobacter. PCR analysis showed that 13 out of 32 isolates contained the sequences (-1070 bp) homologous to the nitrilase genes reported previously in Alcaligenes faecalis JM3 (GenBank, D13419.1). Nine clones were capable of nitrile and amide transformation in minimal salt medium. Acinetobacter sp. 11 h and Alcaligenes sp. osv transformed 3-cyanopyridine to nicotinamide, while most of the clones possessed amidase activity (0.5 to 46.3 mmol/(g h) for acetamide and 0.1 to 5.6 mmol/(g h) for nicotinamide). Nicotinamide utilization by strain A. faecalis 2 was shown to result in excretion of a secondary metabolite, which was identified as dodecyl acrylate at 91% probability. PMID:26263697

  11. Amine Reactivity with Nanoclusters of Sulfuric Acid and Ammonia

    NASA Astrophysics Data System (ADS)

    Johnston, M. V.; Bzdek, B. R.; DePalma, J.

    2011-12-01

    Alkyl amines have emerged as key species in new particle formation and growth. This interest is reinforced by ambient measurements of amines (e.g. Smith et al., 2010) and enhanced levels of nitrogen (e.g. Bzdek et al., 2011) during growth of newly formed particles. An important mechanism of amine uptake is aminium salt formation, either by substituting for ammonium ions that already exist in the particle or by opening new channels for salt formation that are not favorable with ammonia. This presentation will focus on recent experimental and computational work in our group to study amine uptake into charged nanoclusters of sulfuric acid and ammonia. In the experimental work, clusters are produced by electrospray of an ammonium sulfate solution and then drawn into a Fourier transform ion cyclotron resonance mass spectrometer where a specific cluster is isolated and exposed to amine vapor. We find that amine reactivity is dependent on the size, composition and charge of the isolated cluster. For small clusters of either polarity, all ammonium ions reside on the surface and amine substitution occurs with near unit reaction probability. As the cluster size increases, an ammonium ion can be encapsulated in the center of the cluster, which provides a steric hindrance to amine substitution. Negatively charged clusters are more likely to be acidic than positively charged clusters. For acidic clusters, incoming amine molecules first substitute for preexisting ammonium ions and then add to the cluster until a "neutralized" aminium bisulfate composition is reached. Computational studies of these clusters provide fundamental insight into the thermodynamics and kinetics of amine uptake.

  12. 40 CFR 721.720 - Alkoxylated fatty acid amide, alkylsulfate salt.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ..., alkylsulfate salt. 721.720 Section 721.720 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED... Specific Chemical Substances § 721.720 Alkoxylated fatty acid amide, alkylsulfate salt. (a) Chemical... as an alkoxylated fatty acid amide, alkylsulfate salt (PMN P-97-136) is subject to reporting...

  13. 40 CFR 721.720 - Alkoxylated fatty acid amide, alkylsulfate salt.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ..., alkylsulfate salt. 721.720 Section 721.720 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED... Specific Chemical Substances § 721.720 Alkoxylated fatty acid amide, alkylsulfate salt. (a) Chemical... as an alkoxylated fatty acid amide, alkylsulfate salt (PMN P-97-136) is subject to reporting...

  14. 40 CFR 721.720 - Alkoxylated fatty acid amide, alkylsulfate salt.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ..., alkylsulfate salt. 721.720 Section 721.720 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED... Specific Chemical Substances § 721.720 Alkoxylated fatty acid amide, alkylsulfate salt. (a) Chemical... as an alkoxylated fatty acid amide, alkylsulfate salt (PMN P-97-136) is subject to reporting...

  15. 40 CFR 721.720 - Alkoxylated fatty acid amide, alkylsulfate salt.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ..., alkylsulfate salt. 721.720 Section 721.720 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED... Specific Chemical Substances § 721.720 Alkoxylated fatty acid amide, alkylsulfate salt. (a) Chemical... as an alkoxylated fatty acid amide, alkylsulfate salt (PMN P-97-136) is subject to reporting...

  16. 40 CFR 721.720 - Alkoxylated fatty acid amide, alkylsulfate salt.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ..., alkylsulfate salt. 721.720 Section 721.720 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED... Specific Chemical Substances § 721.720 Alkoxylated fatty acid amide, alkylsulfate salt. (a) Chemical... as an alkoxylated fatty acid amide, alkylsulfate salt (PMN P-97-136) is subject to reporting...

  17. Solubility calculations for acid gases in amine blends

    SciTech Connect

    Chakravarty, T.

    1985-01-01

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

  18. Sulfonyl fluoride inhibitors of fatty acid amide hydrolase.

    PubMed

    Alapafuja, Shakiru O; Nikas, Spyros P; Bharathan, Indu T; Shukla, Vidyanand G; Nasr, Mahmoud L; Bowman, Anna L; Zvonok, Nikolai; Li, Jing; Shi, Xiaomeng; Engen, John R; Makriyannis, Alexandros

    2012-11-26

    Sulfonyl fluorides are known to inhibit esterases. Early work from our laboratory has identified hexadecyl sulfonylfluoride (AM374) as a potent in vitro and in vivo inhibitor of fatty acid amide hydrolase (FAAH). We now report on later generation sulfonyl fluoride analogs that exhibit potent and selective inhibition of FAAH. Using recombinant rat and human FAAH, we show that 5-(4-hydroxyphenyl)pentanesulfonyl fluoride (AM3506) has similar inhibitory activity for both the rat and the human enzyme, while rapid dilution assays and mass spectrometry analysis suggest that the compound is a covalent modifier for FAAH and inhibits its action in an irreversible manner. Our SAR results are highlighted by molecular docking of key analogs. PMID:23083016

  19. Synthesis and structural characterisation of amides from picolinic acid and pyridine-2,6-dicarboxylic acid

    PubMed Central

    Devi, Prarthana; Barry, Sarah M.; Houlihan, Kate M.; Murphy, Michael J.; Turner, Peter; Jensen, Paul; Rutledge, Peter J.

    2015-01-01

    Coupling picolinic acid (pyridine-2-carboxylic acid) and pyridine-2,6-dicarboxylic acid with N-alkylanilines affords a range of mono- and bis-amides in good to moderate yields. These amides are of interest for potential applications in catalysis, coordination chemistry and molecular devices. The reaction of picolinic acid with thionyl chloride to generate the acid chloride in situ leads not only to the N-alkyl-N-phenylpicolinamides as expected but also the corresponding 4-chloro-N-alkyl-N-phenylpicolinamides in the one pot. The two products are readily separated by column chromatography. Chlorinated products are not observed from the corresponding reactions of pyridine-2,6-dicarboxylic acid. X-Ray crystal structures for six of these compounds are described. These structures reveal a general preference for cis amide geometry in which the aromatic groups (N-phenyl and pyridyl) are cis to each other and the pyridine nitrogen anti to the carbonyl oxygen. Variable temperature 1H NMR experiments provide a window on amide bond isomerisation in solution. PMID:25954918

  20. 40 CFR 721.3620 - Fatty acid amine condensate, polycarboxylic acid salts.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Fatty acid amine condensate, polycarboxylic acid salts. 721.3620 Section 721.3620 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY... Specific Chemical Substances § 721.3620 Fatty acid amine condensate, polycarboxylic acid salts....

  1. 40 CFR 721.3620 - Fatty acid amine condensate, polycarboxylic acid salts.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Fatty acid amine condensate, polycarboxylic acid salts. 721.3620 Section 721.3620 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY... Specific Chemical Substances § 721.3620 Fatty acid amine condensate, polycarboxylic acid salts....

  2. 40 CFR 721.3620 - Fatty acid amine condensate, polycarboxylic acid salts.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Fatty acid amine condensate, polycarboxylic acid salts. 721.3620 Section 721.3620 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY... Specific Chemical Substances § 721.3620 Fatty acid amine condensate, polycarboxylic acid salts....

  3. 40 CFR 721.3620 - Fatty acid amine condensate, polycarboxylic acid salts.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Fatty acid amine condensate, polycarboxylic acid salts. 721.3620 Section 721.3620 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY... Specific Chemical Substances § 721.3620 Fatty acid amine condensate, polycarboxylic acid salts....

  4. 40 CFR 721.3620 - Fatty acid amine condensate, polycarboxylic acid salts.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Fatty acid amine condensate, polycarboxylic acid salts. 721.3620 Section 721.3620 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY... Specific Chemical Substances § 721.3620 Fatty acid amine condensate, polycarboxylic acid salts....

  5. The Sugar Model: Catalysis by Amines and Amino Acid Products

    NASA Astrophysics Data System (ADS)

    Weber, Arthur L.

    2001-02-01

    Ammonia and amines (including amino acids) were shown to catalyze the formation of sugars from formaldehyde and glycolaldehyde, and the subsequent conversion of sugars to carbonyl-containing products under the conditions studied (pH 5.5 and 50°C). Sterically unhindered primary amines were better catalysts than ammonia, secondary amines, and sterically hindered primary amines (i.e. α-aminoisobutyric acid). Reactions catalyzed by primary amines initially consumed formaldehyde and glycolaldehyde about 15-20 times faster than an uncatalyzed control reaction. The amine-catalyzed reactions yielded aldotriose (glyceraldehyde), ketotriose (dihydroxyacetone), aldotetroses (erythrose and threose), ketotetrose (erythrulose), pyruvaldehyde, acetaldehyde, glyoxal, pyruvate, glyoxylate, and several unindentified carbonyl products. The concentrations of the carbonyl products, except pyruvate and ketotetrose, initially increased and then declined during the reaction, indicating their ultimate conversion to other products (like larger sugars or pyruvate). The uncatalyzed control reaction yielded no pyruvate or glyoxylate, and only trace amounts of pyruvaldehyde, acetaldehyde and glyoxal. In the presence of 15 mM catalytic primary amine, such as alanine, the rates of triose and pyruvaldehyde of synthesis were about 15-times and 1200-times faster, respectively, than the uncatalyzed reaction. Since previous studies established that alanine is synthesized from glycolaldehyde and formaldehyde via pyruvaldehyde as its direct precursor, the demonstration that the alanine catalyzes the conversion of glycolaldehyde and formaldehyde to pyruvaldehyde indicates that this synthetic pathway is capable of autocatalysis. The relevance of this synthetic process, named the Sugar Model, to the origin of life is discussed.

  6. The sugar model: catalysis by amines and amino acid products

    NASA Technical Reports Server (NTRS)

    Weber, A. L.

    2001-01-01

    Ammonia and amines (including amino acids) were shown to catalyze the formation of sugars from formaldehyde and glycolaldehyde, and the subsequent conversion of sugars to carbonylcontaining products under the conditions studied (pH 5.5 and 50 degrees C). Sterically unhindered primary amines were better catalysts than ammonia, secondary amines, and sterically hindered primary amines (i.e. alpha-aminoisobutyric acid). Reactions catalyzed by primary amines initially consumed formaldehyde and glycolaldehyde about 15-20 times faster than an uncatalyzed control reaction. The amine-catalyzed reactions yielded aldotriose (glyceraldehyde), ketotriose (dihydroxyacetone), aldotetroses (erythrose and threose), ketotetrose (erythrulose), pyruvaldehyde, acetaldehyde, glyoxal, pyruvate, glyoxylate, and several unindentified carbonyl products. The concentrations of the carbonyl products, except pyruvate and ketotetrose, initially increased and then declined during the reaction, indicating their ultimate conversion to other products (like larger sugars or pyruvate). The uncatalyzed control reaction yielded no pyruvate or glyoxylate, and only trace amounts of pyruvaldehyde, acetaldehyde and glyoxal. In the presence of 15 mM catalytic primary amine, such as alanine, the rates of triose and pyruvaldehyde of synthesis were about 15-times and 1200-times faster, respectively, than the uncatalyzed reaction. Since previous studies established that alanine is synthesized from glycolaldehyde and formaldehyde via pyruvaldehyde as its direct precursor, the demonstration that the alanine catalyzes the conversion of glycolaldehyde and formaldehyde to pyruvaldehyde indicates that this synthetic pathway is capable of autocatalysis. The relevance of this synthetic process, named the Sugar Model, to the origin of life is discussed.

  7. One-pot assembly of metal/organic-acid sites on amine-functionalized ligands of MOFs for photocatalytic hydrogen peroxide splitting.

    PubMed

    Qin, Lei; Li, Zhaowen; Hu, Qiong; Xu, Zehai; Guo, Xinwen; Zhang, Guoliang

    2016-06-01

    A one-pot organic-acid-directed post-synthetic modification allows molecular iron/citric acid complexes to be anchored into amine-functionalized MOFs by a simple and rapid liquid spraying method. Amidation between organic acid and -NH2 groups of ligands can lead to more small nanoparticles (NPs) that are well-dispersed into MOFs and exhibit high activity for photocatalytic H2O2 splitting. PMID:27166081

  8. Two Dimensional Polyamides Prepared From Unsaturated Carboxylic Acids And Amines.

    DOEpatents

    McDonald, William F.; Huang, Zhi Heng; Wright, Stacy C.; Danzig, Morris; Taylor, Andrew C.

    2002-07-17

    A polyamide and a process for preparing the polyamide are disclosed. The process comprises reacting in a reaction mixture a monomer selected from unsaturated carboxylic acids, esters of unsaturated carboxylic acids, anhydrides of unsaturated carboxylic acids, and mixtures thereof, and a first amine to form an intermediate reaction product in the reaction mixture, wherein the first amine is selected from RR.sub.1 NH, RNH.sub.2, RR.sub.1 NH.sub.2.sup.+, RNH.sub.3.sup.+ and mixtures thereof, wherein R and R.sub.1 can be the same or different and each contain between about 1 and 50 carbon atoms and are optionally substituted with heteroatoms oxygen, nitrogen, sulfur, and phosphorus and combinations thereof, and reacting the intermediate reaction product and a second amine to form a polyamide, wherein the second amine is selected from R.sub.2 R.sub.3 NH, R.sub.2 NH.sub.2, R.sub.2 R.sub.3 NH.sub.2.sup.+, R.sub.2 NH.sub.3.sup.+ and mixtures thereof wherein R.sub.2 and R.sub.3 can be the same or different and each contain between about 1 and 50 carbon atoms and are optionally substituted with heteroatoms oxygen, nitrogen, sulfur, and phosphorus and combinations thereof, wherein multiple of the R, R.sub.1, R.sub.2, and R.sub.3 are in vertically aligned spaced relationship along a backbone formed by the polyamide. In one version of the invention, the monomer is selected from maleic anhydride, maleic acid esters, and mixtures thereof. In another version of the invention, the first amine is an alkylamine, such as tetradecylamine, and the second amine is a polyalkylene polyamine, such as pentaethylenehexamine. In yet another version of the invention, the first amine and the second amine are olefinic or acetylenic amines, such as the reaction products of an alkyldiamine and an acetylenic carboxylic acid. The first amine and the second amine may be the same or different depending on the desired polyamide polymer structure.

  9. Heterogeneous Cu(II) -catalysed solvent-controlled selective N-arylation of cyclic amides and amines with bromo-iodoarenes.

    PubMed

    Kundu, Debasish; Bhadra, Sukalyan; Mukherjee, Nirmalya; Sreedhar, Bojja; Ranu, Brindaban C

    2013-11-11

    A selective N-arylation of cyclic amides and amines in DMF and water, respectively, catalysed by Cu(II) /Al2 O3 has been achieved. This protocol has been employed for the synthesis of a library of arenes bearing a cyclic amide and an amine moiety at two ends, including a few scaffolds of therapeutic importance. The mechanism has been established based on detailed electron paramagnetic resonance (EPR) spectroscopy, X-ray photoelectron spectroscopy (XPS), UV diffuse reflectance spectroscopy (DRS) and inductively coupled plasma-mass spectrometry (ICP-MS) studies of the catalyst at different stages of the reaction. The Cu(II) /Al2 O3 catalyst was recovered and recycled for subsequent reactions. PMID:24123356

  10. Dissolving Carboxylic Acids and Primary Amines on the Overhead Projector

    ERIC Educational Resources Information Center

    Solomon, Sally D.; Rutkowsky, Susan A.

    2010-01-01

    Liquid carboxylic acids (or primary amines) with limited solubility in water are dissolved by addition of aqueous sodium hydroxide (or hydrochloric acid) on the stage of an overhead projector using simple glassware and very small quantities of chemicals. This effective and colorful demonstration can be used to accompany discussions of the…

  11. Amine, Melamine, and Amide N-Halamines as Antimicrobial Additives for Polymers

    PubMed Central

    Sun, Xinbo; Cao, Zhengbing; Porteous, Nuala; Sun, Yuyu

    2010-01-01

    N-chloro-2,2,6,6-tetramethyl-4-piperidinol laurate (Cl-TMPL) was prepared by reacting 2,2,6,6-tetramethyl-4-piperidinol hydrochloride (TMP·HCl) with lauroyl chloride, followed by chlorination with sodium dichloroisocyanurate. The chemical structure of Cl-TMPL was characterized with FT-IR, NMR, DSC, and TGA analyses. The antimicrobial performance of Cl-TMPL against Gram-positive and Gram-negative bacteria was compared with 1-chloro-3-dodecyl-5,5-dimethylhydantoin (Cl-DDMH), a amide N-halamine, and chloro-2,4-diamino-6-dodecyl-1,3,5-triazine (Cl-DADT), a melamine (imino) N-halamine. The three classes of N-halamines were used as additives for polyurethane (PU). Visible light transparency data indicated that up to 6% of Cl-DDMH or Cl-DADT could be compatibly mixed with PU, but Cl-TMPL had low compatibility with PU at higher than 2% of Cl-TMPL. With the same additive content, Cl-DDMH and Cl-DADT provided more powerful antimicrobial and biofilm-controlling effects than Cl-TMPL. In stability studies, however, PU samples with Cl-TMPL released the lowest amount of active chlorine into the immersing solution, suggesting the highest stability of the antimicrobial and biofilm-controlling efficacy. PMID:21088762

  12. Amine, Melamine, and Amide N-Halamines as Antimicrobial Additives for Polymers.

    PubMed

    Sun, Xinbo; Cao, Zhengbing; Porteous, Nuala; Sun, Yuyu

    2010-01-01

    N-chloro-2,2,6,6-tetramethyl-4-piperidinol laurate (Cl-TMPL) was prepared by reacting 2,2,6,6-tetramethyl-4-piperidinol hydrochloride (TMP·HCl) with lauroyl chloride, followed by chlorination with sodium dichloroisocyanurate. The chemical structure of Cl-TMPL was characterized with FT-IR, NMR, DSC, and TGA analyses. The antimicrobial performance of Cl-TMPL against Gram-positive and Gram-negative bacteria was compared with 1-chloro-3-dodecyl-5,5-dimethylhydantoin (Cl-DDMH), a amide N-halamine, and chloro-2,4-diamino-6-dodecyl-1,3,5-triazine (Cl-DADT), a melamine (imino) N-halamine. The three classes of N-halamines were used as additives for polyurethane (PU). Visible light transparency data indicated that up to 6% of Cl-DDMH or Cl-DADT could be compatibly mixed with PU, but Cl-TMPL had low compatibility with PU at higher than 2% of Cl-TMPL. With the same additive content, Cl-DDMH and Cl-DADT provided more powerful antimicrobial and biofilm-controlling effects than Cl-TMPL. In stability studies, however, PU samples with Cl-TMPL released the lowest amount of active chlorine into the immersing solution, suggesting the highest stability of the antimicrobial and biofilm-controlling efficacy. PMID:21088762

  13. Fatty acid sulphoalkyl amides and esters as cosmetic surfactants.

    PubMed

    Petter, P J

    1984-10-01

    Synopsis A review is given of the manufacture, properties and applications of the anionic surfactants commonly known as taurates and isethionates (fatty acid sulphoalkyl amides and esters, respectively). Originally developed in the 1930s for textile processing, these surfactants are used increasingly in the cosmetic field, particularly those derived from coconut fatty acid. Both types are produced from sodium isethionate, HO degrees C(2)H(4)SO(3)Na. The acyl isethionate, R degrees COO degrees C(2)H(4)SO(3)Na, is obtained by reaction with a fatty acid ('direct process'). or fatty acid chloride ('indirect process'). The direct process is cheaper but requires extreme conditions which can lead to discoloration of the product and a loss of shorter chain fatty acid components. The N-methyl-N-acyltaurate, R degrees CON(R(1))C(2)H(4)SO(3)Na, is obtained by Schotten-Baumann reaction of a fatty acid chloride with N-methyltaurine, which is derived from sodium isethionate via methylamine. Taurates and isethionates retain the benefits of the soaps to which they are structurally similar, but chemical modifications have eliminated many undesirable features. Thus they combine good detergency and wetting with high foaming, and maintain their performance in hard or salt water. Taurates are stable to hydrolysis over the whole pH range. Isethionates are prone to hydrolysis at high (>8) or low (<5) pH, but this does not normally present a problem in cosmetic formulations. Above all, these surfactants are characterized by their extreme mildness to skin. Syndet and syndet/soap bars based on isethionate can be formulated at neutral pH ('Dove type'bars) instead of the alkaline pH of soap, and have been shown in various studies to be milder than soap and better tolerated by the young, the old and those with sensitive skins. Similarly, isethionates have been shown to be less irritating than other anionic or amphoteric surfactants used in cosmetics. The difference has been related to the

  14. Kynurenic acid amides as novel NR2B selective NMDA receptor antagonists.

    PubMed

    Borza, István; Kolok, Sándor; Galgóczy, Kornél; Gere, Anikó; Horváth, Csilla; Farkas, Sándor; Greiner, István; Domány, György

    2007-01-15

    A novel series of kynurenic acid amides, ring-enlarged derivatives of indole-2-carboxamides, was prepared and identified as in vivo active NR2B subtype selective NMDA receptor antagonists. The synthesis and SAR studies are discussed. PMID:17074483

  15. Microbial Transformation of Nitriles to High-Value Acids or Amides

    NASA Astrophysics Data System (ADS)

    Chen, Jing; Zheng, Ren-Chao; Zheng, Yu-Guo; Shen, Yin-Chu

    Biotransformation of nitriles mediated by nitrile-amide converting enzymes has attracted considerable attention and developed tremendously in the recent years in China since it offers a valuable alternative to traditional chemical reaction which requires harsh conditions. As a result, an upsurge of these promising enzymes (including nitrile hydratase, nitrilase and amidase) has been taking place. This review aims at describing these enzymes in detail. A variety of microorganisms harboring nitrile-amide converting activities have been isolated and identified in China, some of which have already applied with moderate success. Currently, a wide range of high-value compounds such as aliphatic, alicyclic, aromatic and heterocyclic amides and their corresponding acids were provided by these nitrile-amide degra-ding organisms. Simultaneously, with the increasing demand of chiral substances, the enantioselectivity of the nitrilase superfamily is widely investigated and exploited in China, especially the bioconversion of optically active α-substituted phenylacetamides, acids and 2,2-dimethylcyclopropanecarboxamide and 2,2-dimethylcyclopropanecarboxylic acid by means of the catalysts exhibiting excellent stereoselectivity. Besides their synthetic value, the nitrile-amide converting enzymes also play an important role in environmental protection. In this context, cloning of the genes and expression of these enzymes are presented. In the near future in China, an increasing number of novel nitrile-amide converting organisms will be screened and their potential in the synthesis of useful acids and amides will be further exploited.

  16. Ultrasound-assisted direct oxidative amidation of benzyl alcohols catalyzed by graphite oxide.

    PubMed

    Mirza-Aghayan, Maryam; Ganjbakhsh, Nahid; Molaee Tavana, Mahdieh; Boukherroub, Rabah

    2016-09-01

    Ultrasound irradiation was successfully applied for the direct oxidative amidation of benzyl alcohols with amines into the corresponding amides using graphite oxide (GO) as an oxidative and reusable solid acid catalyst in acetonitrile as solvent at 50°C under air atmosphere. The direct oxidative amidation of benzyl alcohols takes place under mild conditions yielding the corresponding amides in good to high yields (69-95%) and short reaction times under metal-free conditions. PMID:27150743

  17. Retinoic acid amide inhibits JAK/STAT pathway in lung cancer which leads to apoptosis.

    PubMed

    Li, Hong-Xing; Zhao, Wei; Shi, Yan; Li, Ya-Na; Zhang, Lian-Shuang; Zhang, Hong-Qin; Wang, Dong

    2015-11-01

    Small cell lung cancer (SCLC) accounts for 12 to 16% of lung neoplasms and has a high rate of metastasis. The present study demonstrates the antiproliferative effect of retinoic acid amide in vitro and in vivo against human lung cancer cells. The results from MTT assay showed a significant growth inhibition of six tested lung cancer cell lines and inhibition of clonogenic growth at 30 μM. Retinoic acid amide also leads to G2/M-phase cell cycle arrest and apoptosis of lung cancer cells. It caused inhibition of JAK2, STAT3, and STAT5, increased the level of p21WAF1, and decreased cyclin A, cyclin B1, and Bcl-XL expression. Retinoic acid amide exhibited a synergistic effect on antiproliferative effects of methotrexate in lung cancer cells. In lung tumor xenografts, the tumor volume was decreased by 82.4% compared to controls. The retinoic acid amide-treated tumors showed inhibition of JAK2/STAT3 activation and Bcl-XL expression. There was also increase in expression of caspase-3 and caspase-9 in tumors on treatment with retinoic acid amide. Thus, retinoic acid amide exhibits promising antiproliferative effects against human lung cancer cells in vitro and in vivo and enhances the antiproliferative effect of methotrexate. PMID:26044560

  18. An Experimental and Computational Study of the Gas-Phase Acidities of the Common Amino Acid Amides.

    PubMed

    Plummer, Chelsea E; Stover, Michele L; Bokatzian, Samantha S; Davis, John T M; Dixon, David A; Cassady, Carolyn J

    2015-07-30

    Using proton-transfer reactions in a Fourier transform ion cyclotron resonance mass spectrometer and correlated molecular orbital theory at the G3(MP2) level, gas-phase acidities (GAs) and the associated structures for amides corresponding to the common amino acids have been determined for the first time. These values are important because amino acid amides are models for residues in peptides and proteins. For compounds whose most acidic site is the C-terminal amide nitrogen, two ions populations were observed experimentally with GAs that differ by 4-7 kcal/mol. The lower energy, more acidic structure accounts for the majority of the ions formed by electrospray ionization. G3(MP2) calculations predict that the lowest energy anionic conformer has a cis-like orientation of the [-C(═O)NH](-) group whereas the higher energy, less acidic conformer has a trans-like orientation of this group. These two distinct conformers were predicted for compounds with aliphatic, amide, basic, hydroxyl, and thioether side chains. For the most acidic amino acid amides (tyrosine, cysteine, tryptophan, histidine, aspartic acid, and glutamic acid amides) only one conformer was observed experimentally, and its experimental GA correlates with the theoretical GA related to side chain deprotonation. PMID:26196065

  19. 40 CFR 721.3625 - Fatty acid amine salt (generic name).

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Fatty acid amine salt (generic name... Substances § 721.3625 Fatty acid amine salt (generic name). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as fatty acid amine salt (PMN...

  20. 40 CFR 721.3625 - Fatty acid amine salt (generic name).

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Fatty acid amine salt (generic name... Substances § 721.3625 Fatty acid amine salt (generic name). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as fatty acid amine salt (PMN...

  1. 40 CFR 721.5465 - Amine salt of organic acid (generic).

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Amine salt of organic acid (generic... Substances § 721.5465 Amine salt of organic acid (generic). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as amine salt of organic acid...

  2. 40 CFR 721.5465 - Amine salt of organic acid (generic).

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Amine salt of organic acid (generic... Substances § 721.5465 Amine salt of organic acid (generic). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as amine salt of organic acid...

  3. 40 CFR 721.3625 - Fatty acid amine salt (generic name).

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Fatty acid amine salt (generic name... Substances § 721.3625 Fatty acid amine salt (generic name). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as fatty acid amine salt (PMN...

  4. 40 CFR 721.5465 - Amine salt of organic acid (generic).

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Amine salt of organic acid (generic... Substances § 721.5465 Amine salt of organic acid (generic). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as amine salt of organic acid...

  5. 40 CFR 721.3625 - Fatty acid amine salt (generic name).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Fatty acid amine salt (generic name... Substances § 721.3625 Fatty acid amine salt (generic name). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as fatty acid amine salt (PMN...

  6. 40 CFR 721.5465 - Amine salt of organic acid (generic).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Amine salt of organic acid (generic... Substances § 721.5465 Amine salt of organic acid (generic). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as amine salt of organic acid...

  7. 40 CFR 721.3625 - Fatty acid amine salt (generic name).

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Fatty acid amine salt (generic name... Substances § 721.3625 Fatty acid amine salt (generic name). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as fatty acid amine salt (PMN...

  8. 40 CFR 721.5465 - Amine salt of organic acid (generic).

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Amine salt of organic acid (generic... Substances § 721.5465 Amine salt of organic acid (generic). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as amine salt of organic acid...

  9. Phenylethynyl amine

    NASA Technical Reports Server (NTRS)

    Hergenrother, Paul M. (Inventor); Bryant, Robert G. (Inventor); Jensen, Brian J. (Inventor); Havens, Stephen J. (Inventor)

    1997-01-01

    Four phenylethynyl amine compounds--3 and 4-aminophenoxy-4'-phenylethynylbenzophenone, and 3 and 4-amino-4'-phenylethynylbenzophenone--were readily prepared and were used to endcap imide oligomers. Phenylethynyl-terminated amide acid oligomers and phenylethynyl-terminated imide oligomers with various molecular weights and compositions were prepared and characterized. These oligomers were cured at 300.degree. C. to 400.degree. C. to provide crosslinked polyimides with excellent solvent resistance, high strength and modulus and good high temperature properties. Adhesive panels, composites, films and moldings from these phenylethynyl terminated imide oligomers gave excellent mechanical performance.

  10. Binding of Fatty Acid Amide Amphiphiles to Bovine Serum Albumin: Role of Amide Hydrogen Bonding.

    PubMed

    Ghosh, Subhajit; Dey, Joykrishna

    2015-06-25

    The study of protein-surfactant interactions is important because of the widespread use of surfactants in industry, medicine, and pharmaceutical fields. Sodium N-lauroylsarcosinate (SL-Sar) is a widely used surfactant in cosmetics, shampoos. In this paper, we studied the interactions of bovine serum albumin (BSA) with SL-Sar and sodium N-lauroylglycinate (SL-Gly) by use of a number of techniques, including fluorescence and circular dichroism spectroscopy and isothermal titration calorimetry. The binding strength of SL-Sar is stronger than that of structurally similar SL-Gly, which differs only by the absence of a methyl group in the amide nitrogen atom. Also, these two surfactants exhibit different binding patterns with the BSA protein. The role of the amide bond and hence the surfactant headgroup in the binding mechanism is discussed in this paper. It was observed that while SL-Sar destabilized, SL-Gly stabilized the protein structure, even at concentrations less than the critical micelle concentration (cmc) value. The thermodynamics of surfactant binding to BSA was studied by use of ITC. From the ITC results, it is concluded that three molecules of SL-Sar in contrast to only one molecule of SL-Gly bind to BSA in one set of binding sites at room temperature. However, on increasing temperature four molecules of SL-Gly bind to the BSA through H-bonding and van der Waals interactions, due to loosening of the BSA structure. In contrast, with SL-Sar the binding process is enthalpy driven, and very little structural change of BSA was observed at higher temperature. PMID:26023820

  11. Cysteine amide adduct formation from carboxylic acid drugs via UGT-mediated bioactivation in human liver microsomes.

    PubMed

    Harada, H; Toyoda, Y; Endo, T; Kobayashi, M

    2015-10-01

    Although chemical trapping has been widely used to evaluate cytochrome P450-mediated drug bioactivation, thus far, only a few in vitro-trapping studies have been performed on UDP-glucuronosyltransferase (UGT)-mediated drug bioactivation. In this study, we used cysteine (Cys) as trapping agent to gain new insights into the UGT-mediated bioactivation involving acyl glucuronides of carboxylic acid drugs. Diclofenac, ketoprofen and ibuprofen were incubated in human liver microsomes with UDPGA and Cys, followed by analysis using ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTOF/MS). The N-acyl-Cys amide adduct of diclofenac was characterized by mass analysis and was detectable even in photodiode array analysis. Our data indicated that the formation of such adducts reflects the reactivity of the corresponding acyl glucuronides. In addition, it was suggested that the adduct formation requires an N-terminal Cys moiety with both a free amine and a free thiol group, from the results using various cysteine derivatives. We propose that the S-acyl-Cys thioester adduct can form via transacylation of an acyl glucuronide and can then form to an N-acyl-Cys amide adduct through intramolecular S- to N-acyl rearrangement. This series of the reactions has important implications as a possible bioactivation mechanism for covalent binding of carboxylic acid drugs to macromolecules. PMID:26601426

  12. Process for chemical reaction of amino acids and amides yielding selective conversion products

    DOEpatents

    Holladay, Jonathan E.

    2006-05-23

    The invention relates to processes for converting amino acids and amides to desirable conversion products including pyrrolidines, pyrrolidinones, and other N-substituted products. L-glutamic acid and L-pyroglutamic acid provide general reaction pathways to numerous and valuable selective conversion products with varied potential industrial uses.

  13. Efficient Amide Bond Formation through a Rapid and Strong Activation of Carboxylic Acids in a Microflow Reactor**

    PubMed Central

    Fuse, Shinichiro; Mifune, Yuto; Takahashi, Takashi

    2014-01-01

    The development of highly efficient amide bond forming methods which are devoid of side reactions, including epimerization, is important, and such a method is described herein and is based on the concept of rapid and strong activation of carboxylic acids. Various carboxylic acids are rapidly (0.5 s) converted into highly active species, derived from the inexpensive and less-toxic solid triphosgene, and then rapidly (4.3 s) reacted with various amines to afford the desired peptides in high yields (74 %–quant.) without significant epimerization (≤3 %). Our process can be carried out at ambient temperature, and only CO2 and HCl salts of diisopropylethyl amine are generated. In the long history of peptide synthesis, a significant number of active coupling reagents have been abandoned because the highly active electrophilic species generated are usually susceptible to side reactions such as epimerization. The concept presented herein should renew interest in the use of these reagents. PMID:24402801

  14. Prediction of acute in vivo toxicity of some amine and amide drugs to rats by multiple linear regression, partial least squares and an artificial neural network.

    PubMed

    Mahani, Mohamad Khayatzadeh; Chaloosi, Marzieh; Maragheh, Mohamad Ghanadi; Khanchi, Ali Reza; Afzali, Daryoush

    2007-09-01

    The oral acute in vivo toxicity of 32 amine and amide drugs was related to their structural-dependent properties. Genetic algorithm-partial least-squares and stepwise variable selection was applied to select of meaningful descriptors. Multiple linear regression (MLR), artificial neural network (ANN) and partial least square (PLS) models were created with selected descriptors. The predictive ability of all three models was evaluated and compared on a set of five drugs, which were not used in modeling steps. Average errors of 0.168, 0.169 and 0.259 were obtained for MLR, ANN and PLS, respectively. PMID:17878584

  15. Synthesis and effect of fatty acid amides as friction modifiers in petroleum base stock.

    PubMed

    Khalkar, Sharmishtha; Bhowmick, DiptiNarayan; Pratap, Amit

    2013-01-01

    Fatty acid amides were prepared by using Lewis acid as a catalyst. The products from reaction was subjected to solvent extraction with chloroform and then followed by purification with n-hexane, ethanol and acetonitrile. Fatty acid amide, characterized by various physicochemical and tribological properties like wear scar, weld load and coefficient of friction. These compounds found good antiwear (AW) and extreme pressure (EP) additive. The addition of various EP and AW additives in lubricating oil is an important and effective way to reduce friction and wear. Fatty acid amides were used as antiwear and friction modifier additive and a comparative study was carried out for 1%, 3%, 5% additive blend with commercial petroleum base stocks 150N and 500N. PMID:24200937

  16. Amine bearing polymeric particles as acid neutralizers for engine oils

    SciTech Connect

    Theodore, A.N.; Chattha, M.S.

    1986-02-04

    This patent describes a lubricating oil composition consisting of a major proportion of a lubricating base oil and about 0.1 to 15 weight percent of an acid neutralizing additive which consists of polymer particles (a) bearing pendant amine groups, and (b) having a diameter of about 500 A and 10,000 A. The amine functional particles are formed by reacting polymer particles bearing pendant epoxide groups with a secondary amine in an amount so as to react essentially all of the epoxide groups on the epoxide bearing polymer particles with the secondary amine. The polymer particles bearing pendant epoxide groups are formed by the free radical addition polymerization of: (a) between about 50 and about 100 weight percent of an ethylenically unsaturated monomers bearing an epoxide group, and (b) 0 up to about 50 weight percent of other monoethylenically unsaturated monomers; in the presence of: (I) a non-polar organic liquid which is a solvent for the polymerizable monomers, but a non-solvent for the resultant polymer, and (II) polymeric dispersion stabilizer containing at least two segments, with one segment being solvated by the non-polar organic liquid and the second segment being of different polarity than the first segment and relatively insoluble in the non-polar organic liquid. The second segment of the stabilizer is chemically attached to the polymerized particle.

  17. Fuel and lubricant additives from acid treated mixtures of vegetable oil derived amides and esters

    SciTech Connect

    Bonazza, B.R.; Devault, A.N.

    1981-05-26

    Vegetable oils such as corn oil, peanut oil, and soy oil are reacted with polyamines to form a mixture containing amides, imides, half esters, and glycerol with subsequent treatment with a strong acid such as sulfonic acid to produce a product mix that has good detergent properties in fuels and lubricants.

  18. Choline Chloride Catalyzed Amidation of Fatty Acid Ester to Monoethanolamide: A Green Approach.

    PubMed

    Patil, Pramod; Pratap, Amit

    2016-01-01

    Choline chloride catalyzed efficient method for amidation of fatty acid methyl ester to monoethanolamide respectively. This is a solvent free, ecofriendly, 100% chemo selective and economically viable path for alkanolamide synthesis. The Kinetics of amidation of methyl ester were studied and found to be first order with respect to the concentration of ethanolamine. The activation energy (Ea) for the amidation of lauric acid methyl ester catalyzed by choline chloride was found to be 50.20 KJ mol(-1). The 98% conversion of lauric acid monoethanolamide was obtained at 110°C in 1 h with 6% weight of catalyst and 1:1.5 molar ratio of methyl ester to ethanolamine under nitrogen atmosphere. PMID:26666271

  19. Approaches for regeneration of amine-carboxylic acid extracts

    SciTech Connect

    Dai, Y.; King, C.J.

    1995-07-01

    Extraction processes based on reversible chemical complexation can be useful for separation of polar organics from dilute solution. Tertiary amines are effective extractants for the recovery of carboxylic acids from aqueous solution. The regeneration of aminecarboxylic acid extracts is an important step which strongly influences the economic viability of the separation process. Several regeneration methods are critically reviewed, and the factors that affect swing regeneration processes, including temperature-swing, diluent composition-swing and pH-swing with a volatile base are discussed. Interest in this area comes from interest in treatment of waste streams, particularly in petrochemical and fermentation manufacture.

  20. A comparative study of the complexation of uranium(VI) withoxydiacetic acid and its amide derivatives

    SciTech Connect

    Rao, Linfeng; Tian, Guoxin

    2005-05-01

    There has been significant interest in recent years in the studies of alkyl-substituted amides as extractants for actinide separation because the products of radiolytic and hydrolytic degradation of amides are less detrimental to separation processes than those of organophosphorus compounds traditionally used in actinide separations. Stripping of actinides from the amide-containing organic solvents is relatively easy. In addition, the amide ligands are completely incinerable so that the amount of secondary wastes generated in nuclear waste treatment could be significantly reduced. One group of alkyl-substituted oxa-diamides have been shown to be promising in the separation of actinides from nuclear wastes. For example, tetraoctyl-3-oxa-glutaramide and tetraisobutyl-oxa-glutaramide form actinide complexes that can be effectively extracted from nitric acid solutions. To understand the thermodynamic principles governing the complexation of actinides with oxa-diamides, we have studied the complexation of U(VI) with dimethyl-3-oxa-glutaramic acid (DMOGA) and tetramethyl-3-oxa-glutaramide (TMOGA) in aqueous solutions, in comparison with oxydiacetic acid (ODA) (Figure 1). Previous studies have indicated that the complexation of U(VI) with ODA is strong and entropy-driven. Comparing the results for DMOGA and TMOGA with those for ODA could provide insight into the energetics of amide complexation with U(VI) and the relationship between the thermodynamic properties and the ligand structure.

  1. Complexation of di-amides of dipicolinic acid with neodymium

    SciTech Connect

    Lapka, J.L.; Paulenova, A.

    2013-07-01

    Di-amides have undergone significant studies as possible ligands for use in the partitioning of trivalent minor actinides and lanthanides. The binding affinities of three isomeric ligands with neodymium in acetonitrile solution have been investigated. The stability constants of the metal-ligand complexes formed between different isomers of N,N'-diethyl-N,N'- ditolyl-di-picolinamide (EtTDPA) and trivalent neodymium in acetonitrile have been determined by spectrophotometric and calorimetric methods. Each isomer of EtTDPA has been found to be capable of forming three complexes with trivalent neodymium, Nd(EtTDPA), Nd(EtTDPA){sub 2}, and Nd(EtTDPA){sub 3}. Values from spectrophotometric and calorimetric titrations are within reasonable agreement with each other. The order of stability constants for each metal:ligand complex decreases in the order Et(m)TDPA > Et(p)TDPA > Et(o)TDPA. The obtained values are comparable to other di-amidic ligands obtained under similar system conditions and mirror previously obtained solvent extraction data for EtTDPA at low ionic strengths. (authors.

  2. Highly Enantioselective Direct Alkylation of Arylacetic Acids with Chiral Lithium Amides as Traceless Auxiliaries

    PubMed Central

    Stivala, Craig E.; Zakarian, Armen

    2012-01-01

    A direct, highly enantioselective alkylation of arylacetic acids via enediolates using a readily available chiral lithium amide as a stereodirecting reagent has been developed. This approach circumvents the traditional attachment and removal of chiral auxiliaries used currently for this type of transformation. The protocol is operationally simple, and the chiral reagent is readily recoverable. PMID:21744818

  3. 40 CFR 721.9620 - Aromatic sulfonic acid compound with amine.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Aromatic sulfonic acid compound with... Specific Chemical Substances § 721.9620 Aromatic sulfonic acid compound with amine. (a) Chemical substance... aromatic sulfonic acid compound with amine (PMN P-93-832) is subject to reporting under this section...

  4. 40 CFR 721.9620 - Aromatic sulfonic acid compound with amine.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Aromatic sulfonic acid compound with... Specific Chemical Substances § 721.9620 Aromatic sulfonic acid compound with amine. (a) Chemical substance... aromatic sulfonic acid compound with amine (PMN P-93-832) is subject to reporting under this section...

  5. 40 CFR 721.9620 - Aromatic sulfonic acid compound with amine.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Aromatic sulfonic acid compound with... Specific Chemical Substances § 721.9620 Aromatic sulfonic acid compound with amine. (a) Chemical substance... aromatic sulfonic acid compound with amine (PMN P-93-832) is subject to reporting under this section...

  6. 40 CFR 721.9620 - Aromatic sulfonic acid compound with amine.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Aromatic sulfonic acid compound with... Specific Chemical Substances § 721.9620 Aromatic sulfonic acid compound with amine. (a) Chemical substance... aromatic sulfonic acid compound with amine (PMN P-93-832) is subject to reporting under this section...

  7. 40 CFR 721.9620 - Aromatic sulfonic acid compound with amine.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Aromatic sulfonic acid compound with... Specific Chemical Substances § 721.9620 Aromatic sulfonic acid compound with amine. (a) Chemical substance... aromatic sulfonic acid compound with amine (PMN P-93-832) is subject to reporting under this section...

  8. Syntheses of hydroxamic acid-containing bicyclic β-lactams via palladium-catalyzed oxidative amidation of alkenes.

    PubMed

    Jobbins, Maria O; Miller, Marvin J

    2014-02-21

    Palladium-catalyzed oxidative amidation has been used to synthesize hydroxamic acid-containing bicyclic β-lactam cores. Oxidative cleavage of the pendant alkene provides access to the carboxylic acid in one step. PMID:24483144

  9. Sequestration of biogenic amines by alginic and fulvic acids.

    PubMed

    De Stefano, Concetta; Gianguzza, Antonio; Piazzese, Daniela; Porcino, Nunziatina; Sammartano, Silvio

    2006-08-01

    The interaction of natural (alginic and fulvic acids) and synthetic (polyacrylic acid 2.0 kDa) polyelectrolytes with some protonated polyamines [diamines: ethylendiamine, 1,4-diaminobutane (or putrescine), 1,5-diaminopentane (or cadaverine); triamines: N-(3-aminopropyl)-1,4-diaminobutane (or spermidine), diethylenetriamine; tetramine: N,N'-bis(3-aminopropyl)-1,4-diaminobutane (or spermine); pentamine: tetraethylene-pentamine; hexamine: pentaethylenehexamine] was studied at T=25 degrees C by potentiometry and calorimetry. Measurements were performed without supporting electrolyte, in order to avoid interference, and results were reported at I=0 mol L(-)(1). For all the systems, the formation of (am)L(2)H(i) species was found (am=amine; L=polyelectrolyte; i=1...4, depending on the amine considered). The stability of polyanion-polyammonium cation complexes is always significant, and for high-charged polycations, we observe a stability comparable to that of strong metal complexes. For example, by considering the formation reaction (am)H(i)+2L=(am)L(2)H(i) we found log K(i)=6.0, 6.5 and 10.8 for i=1, 2 and 3, respectively, in the system alginate-spermidine. Low and positive formation DeltaH(degrees) values indicate that the main contribution to the stability is entropic in nature. The sequestering ability of polyelectrolytes toward amines was modelled by a sigmoid Boltzman type equation. Some empirical relationships between stability, charges and DeltaG(degrees) and TDeltaS(degrees) are reported. Mean values per salt bridge of formation thermodynamic parameters (DeltaX(degrees) (n)) are DeltaG(degrees) (n)=-5.8+/-0.4, DeltaH degrees (n)=0.7+/-0.5 and TDeltaS(degrees) (n)=6.5+/-0.5 kJmol(-)(1) for all the systems studied in this work. PMID:16690202

  10. Possible Evidence of Amide Bond Formation Between Sinapinic Acid and Lysine-Containing Bacterial Proteins by Matrix-Assisted Laser Desorption/Ionization (MALDI) at 355 nm

    NASA Astrophysics Data System (ADS)

    Fagerquist, Clifton K.; Sultan, Omar; Carter, Michelle Q.

    2012-12-01

    We previously reported the apparent formation of matrix adducts of 3,5-dimethoxy-4-hydroxy-cinnamic acid (sinapinic acid or SA) via covalent attachment to disulfide bond-containing proteins (HdeA, Hde, and YbgS) from bacterial cell lysates ionized by matrix-assisted laser desorption/ionization (MALDI) time-of-flight-time-of-flight tandem mass spectrometry (TOF-TOF-MS/MS) and post-source decay (PSD). We also reported the absence of adduct formation when using α-cyano-4-hydroxycinnamic acid (CHCA) matrix. Further mass spectrometric analysis of disulfide-intact and disulfide-reduced over-expressed HdeA and HdeB proteins from lysates of gene-inserted E. coli plasmids suggests covalent attachment of SA occurs not at cysteine residues but at lysine residues. In this revised hypothesis, the attachment of SA is preceded by formation of a solid phase ammonium carboxylate salt between SA and accessible lysine residues of the protein during sample preparation under acidic conditions. Laser irradiation at 355 nm of the dried sample spot results in equilibrium retrogradation followed by nucleophilic attack by the amine group of lysine at the carbonyl group of SA and subsequent amide bond formation and loss of water. The absence of CHCA adducts suggests that the electron-withdrawing effect of the α-cyano group of this matrix may inhibit salt formation and/or amide bond formation. This revised hypothesis is supported by dissociative loss of SA (-224 Da) and the amide-bound SA (-206 Da) from SA-adducted HdeA and HdeB ions by MS/MS (PSD). It is proposed that cleavage of the amide-bound SA from the lysine side-chain occurs via rearrangement involving a pentacyclic transition state followed by hydrogen abstraction/migration and loss of 3-(4-hydroxy-3,5-dimethoxyphenyl)prop-2-ynal (-206 Da).

  11. Direct enantioselective conjugate addition of carboxylic acids with chiral lithium amides as traceless auxiliaries.

    PubMed

    Lu, Ping; Jackson, Jeffrey J; Eickhoff, John A; Zakarian, Armen

    2015-01-21

    Michael addition is a premier synthetic method for carbon-carbon and carbon-heteroatom bond formation. Using chiral dilithium amides as traceless auxiliaries, we report the direct enantioselective Michael addition of carboxylic acids. A free carboxyl group in the product provides versatility for further functionalization, and the chiral reagent can be readily recovered by extraction with aqueous acid. The method has been applied in the enantioselective total synthesis of the purported structure of pulveraven B. PMID:25562717

  12. Infrared spectroscopic study of the amidation reaction of aminophenyl modified Au surfaces and p-nitrobenzoic acid as model system.

    PubMed

    Zhang, Xin; Sun, Guoguang; Hinrichs, Karsten; Janietz, Silvia; Rappich, Joerg

    2010-10-21

    We have investigated the fundamental amidation reaction by a model system consisting of an electrochemically functionalised Au surface by aminophenyl and 4-nitrobenzoic acid activated by EEDQ. The development of the NO(2) related stretching vibrations with time reveals that the amidation process is very slow at Au surfaces and is completed after about 2 days. PMID:20737098

  13. A Metal and Base-Free Chemoselective Primary Amination of Boronic Acids Using Cyanamidyl/Arylcyanamidyl Radical as Aminating Species: Synthesis and Mechanistic Studies by Density Functional Theory.

    PubMed

    Chatterjee, Nachiketa; Arfeen, Minhajul; Bharatam, Prasad V; Goswami, Avijit

    2016-06-17

    An efficient, metal and base-free, chemoselective synthesis of aryl-, heteroaryl-, and alkyl primary amines from the corresponding boronic acids has been achieved at ambient temperature mediated by [bis(trifluoroacetoxy)iodo]benzene (PIFA) and N-bromosuccinimide (NBS) using cyanamidyl/arylcyanamidyl radicals as the aminating species. The primary amine compounds were initially obtained as their corresponding ammonium trifluoroacetate salts which, on treatment with aq NaOH, provide the free amines. Finally, the primary amines were isolated through column chromatography over silica-gel using hexane-EtOAc solvent system as the eluent. The reactions are sufficiently fast, completing within 1 h. Quantum chemical calculations in combination with experimental observations validate that the ipso amination of substituted boronic acids involves the formation of cyanamidyl/arylcyanamidyl radical, followed by regiospecific interaction of its nitrile-N center with boron atom of the boronic acids, leading to chemoselective primary amination. PMID:27182931

  14. CUTICULAR LIPIDS OF THE STORED FOOD PEST, LIPOSCELIS BOSTRYCHOPHILA BADONNEL (PSOCOPTERA: LIPOSCELIDIDAE): HYDROCARBONS, ALDEHYDES, FATTY ACIDS AND FATTY ACID AMIDES

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The booklouse, Liposcelis bostrychophila, has increasingly become a common pest of stored food products worldwide. We report here the cuticular hydrocarbon composition of this pest (the first report of the hydrocarbons of any member of the Order Psocoptera) and the first report of fatty acid amides...

  15. Synthesis, Properties and Applications of Biodegradable Polymers Derived from Diols and Dicarboxylic Acids: From Polyesters to Poly(ester amide)s

    PubMed Central

    Díaz, Angélica; Katsarava, Ramaz; Puiggalí, Jordi

    2014-01-01

    Poly(alkylene dicarboxylate)s constitute a family of biodegradable polymers with increasing interest for both commodity and speciality applications. Most of these polymers can be prepared from biobased diols and dicarboxylic acids such as 1,4-butanediol, succinic acid and carbohydrates. This review provides a current status report concerning synthesis, biodegradation and applications of a series of polymers that cover a wide range of properties, namely, materials from elastomeric to rigid characteristics that are suitable for applications such as hydrogels, soft tissue engineering, drug delivery systems and liquid crystals. Finally, the incorporation of aromatic units and α-amino acids is considered since stiffness of molecular chains and intermolecular interactions can be drastically changed. In fact, poly(ester amide)s derived from naturally occurring amino acids offer great possibilities as biodegradable materials for biomedical applications which are also extensively discussed. PMID:24776758

  16. Investigation of the complex reaction coordinate of acid catalyzed amide hydrolysis from molecular dynamics simulations

    NASA Astrophysics Data System (ADS)

    Zahn, Dirk

    2004-05-01

    The rate-determining step of acid catalyzed peptide hydrolysis is the nucleophilic attack of a water molecule to the carbon atom of the amide group. Therein the addition of the hydroxyl group to the amide carbon atom involves the association of a water molecule transferring one of its protons to an adjacent water molecule. The protonation of the amide nitrogen atom follows as a separate reaction step. Since the nucleophilic attack involves the breaking and formation of several bonds, the underlying reaction coordinate is rather complex. We investigate this reaction step from path sampling Car-Parrinello molecular dynamics simulations. This approach does not require the predefinition of reaction coordinates and is thus particularly suited for investigating reaction mechanisms. From our simulations the most relevant components of the reaction coordinate are elaborated. Though the C⋯O distance of the oxygen atom of the water molecule performing the nucleophilic attack and the corresponding amide carbon atom is a descriptor of the reaction progress, a complete picture of the reaction coordinate must include all three molecules taking part in the reaction. Moreover, the proton transfer is found to depend on favorable solvent configurations. Thus, also the arrangement of non-reacting, i.e. solvent water molecules needs to be considered in the reaction coordinate.

  17. Bifunctional Brønsted Base Catalyzes Direct Asymmetric Aldol Reaction of α-Keto Amides.

    PubMed

    Echave, Haizea; López, Rosa; Palomo, Claudio

    2016-03-01

    The first enantioselective direct cross-aldol reaction of α-keto amides with aldehydes, mediated by a bifunctional ureidopeptide-based Brønsted base catalyst, is described. The appropriate combination of a tertiary amine base and an aminal, and urea hydrogen-bond donor groups in the catalyst structure promoted the exclusive generation of the α-keto amide enolate which reacted with either non-enolizable or enolizable aldehydes to produce highly enantioenriched polyoxygenated aldol adducts without side-products resulting from dehydration, α-keto amide self-condensation, aldehyde enolization, and isotetronic acid formation. PMID:26835655

  18. MATE Transporter-Dependent Export of Hydroxycinnamic Acid Amides[OPEN

    PubMed Central

    Eschen-Lippold, Lennart; Gorzolka, Karin; Matern, Andreas; Marillonnet, Sylvestre; Böttcher, Christoph; Rosahl, Sabine

    2016-01-01

    The ability of Arabidopsis thaliana to successfully prevent colonization by Phytophthora infestans, the causal agent of late blight disease of potato (Solanum tuberosum), depends on multilayered defense responses. To address the role of surface-localized secondary metabolites for entry control, droplets of a P. infestans zoospore suspension, incubated on Arabidopsis leaves, were subjected to untargeted metabolite profiling. The hydroxycinnamic acid amide coumaroylagmatine was among the metabolites secreted into the inoculum. In vitro assays revealed an inhibitory activity of coumaroylagmatine on P. infestans spore germination. Mutant analyses suggested a requirement of the p-coumaroyl-CoA:agmatine N4-p-coumaroyl transferase ACT for the biosynthesis and of the MATE transporter DTX18 for the extracellular accumulation of coumaroylagmatine. The host plant potato is not able to efficiently secrete coumaroylagmatine. This inability is overcome in transgenic potato plants expressing the two Arabidopsis genes ACT and DTX18. These plants secrete agmatine and putrescine conjugates to high levels, indicating that DTX18 is a hydroxycinnamic acid amide transporter with a distinct specificity. The export of hydroxycinnamic acid amides correlates with a decreased ability of P. infestans spores to germinate, suggesting a contribution of secreted antimicrobial compounds to pathogen defense at the leaf surface. PMID:26744218

  19. Synthesis, biological activity, and bioavailability of moschamine, a safflomide-type phenylpropenoic acid amide found in Centaurea cyanus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Moschamine is a safflomide-type phenylpropenoic acid amide originally isolated from Centaurea cyanus. This paper describes the synthesis, detection of serotoninergic and COX inhibitory activities, and bioavailability of moschamine. Moschamine was chemically synthesized and identified using NMR spect...

  20. Boron-Catalyzed N-Alkylation of Amines using Carboxylic Acids.

    PubMed

    Fu, Ming-Chen; Shang, Rui; Cheng, Wan-Min; Fu, Yao

    2015-07-27

    A boron-based catalyst was found to catalyze the straightforward alkylation of amines with readily available carboxylic acids in the presence of silane as the reducing agent. Various types of primary and secondary amines can be smoothly alkylated with good selectivity and good functional-group compatibility. This metal-free amine alkylation was successfully applied to the synthesis of three commercial medicinal compounds, Butenafine, Cinacalcet. and Piribedil, in a one-pot manner without using any metal catalysts. PMID:26150397

  1. Acid gas absorption in aqueous solutions of mixed amines

    SciTech Connect

    Rinker, E.B.; Ashour, S.S.; Sandall, O.C.

    1996-12-31

    A mass transfer model has been developed to describe the rate of absorption (or desorption) of H{sub 2}S and CO{sub 2} in aqueous blends of a tertiary and a secondary or a primary amine. The model is based on penetration theory, and all significant chemical reactions are incorporated in the model. The reactions are taken to be reversible, with reactions involving only a proton transfer considered to be at equilibrium. The particular amines studied in this research were methyldiethanolamine (MDEA), a tertiary amine, and diethanolamine (DEA), a secondary amine. Key physicochemical data needed in the model, such as diffusion coefficients, kinetic rate constants, and gas solubilities, were measured. Experimental absorption rates of CO{sub 2} and H{sub 2}S were measured in a model gas-liquid contacting device and were compared with model predictions. Experiments were carried out for single amine solutions (both MDEA and DEA) and for amine blends.

  2. Observation of neutral sulfuric acid-amine containing clusters in laboratory and ambient measurements

    SciTech Connect

    Kuang C.; Zhao, J.; Smith, J. N.; Eisele, F. L.; Chen, M.; McMurry, P. H.

    2011-11-02

    Recent ab initio calculations showed that amines can enhance atmospheric sulfuric acid-water nucleation more effectively than ammonia, and this prediction has been substantiated in laboratory measurements. Laboratory studies have also shown that amines can effectively displace ammonia in several types of ammonium clusters. However, the roles of amines in cluster formation and growth at a microscopic molecular scale (from molecular sizes up to 2 nm) have not yet been well understood. Processes that must be understood include the incorporation of amines into sulfuric acid clusters and the formation of organic salts in freshly nucleated particles, which contributes significantly to particle growth rates. We report the first laboratory and ambient measurements of neutral sulfuric acid-amine clusters using the Cluster CIMS, a recently-developed mass spectrometer designed for measuring neutral clusters formed in the atmosphere during nucleation. An experimental technique, which we refer to as Semi-Ambient Signal Amplification (SASA), was employed. Sulfuric acid was added to ambient air, and the concentrations and composition of clusters in this mixture were analyzed by the Cluster CIMS. This experimental approach led to significantly higher cluster concentrations than are normally found in ambient air, thereby increasing signal-to-noise levels and allowing us to study reactions between gas phase species in ambient air and sulfuric acid containing clusters. Mass peaks corresponding to clusters containing four H{sub 2}SO{sub 4} molecules and one amine molecule were clearly observed, with the most abundant sulfuric acid-amine clusters being those containing a C2- or C4-amine (i.e. amines with masses of 45 and 73 amu). Evidence for C3- and C5-amines (i.e. amines with masses of 59 and 87 amu) was also found, but their correlation with sulfuric acid tetramer was not as strong as was observed for the C2- and C4-amines. The formation mechanisms for those sulfuric acid-amine

  3. Probing acid-amide intermolecular hydrogen bonding by NMR spectroscopy and DFT calculations

    NASA Astrophysics Data System (ADS)

    Chaudhari, Sachin Rama; Suryaprakash, N.

    2012-05-01

    Benzene carboxylic acids and benzamide act as their self-complement in molecular recognition to form inter-molecular hydrogen bonded dimers between amide and carboxylic acid groups, which have been investigated by 1H, 13C and 15N NMR spectroscopy. Extensive NMR studies using diffusion ordered spectroscopy (DOSY), variable temperature 1D, 2D NMR, established the formation of heterodimers of benzamide with benzoic acid, salicylic acid and phenyl acetic acid in deuterated chloroform solution. Association constants for the complex formation in the solution state have been determined. The results are ascertained by X-ray diffraction in the solid state. Intermolecular interactions in solution and in solid state were found to be similar. The structural parameters obtained by X-ray diffraction studies are compared with those obtained by DFT calculations.

  4. Stereoselective synthesis of (E)-trisubstituted alpha,beta-unsaturated amides and acids.

    PubMed

    Feuillet, Fred J P; Cheeseman, Matt; Mahon, Mary F; Bull, Steven D

    2005-08-21

    Potassium alkoxides of N-acyl-oxazolidin-2-one-syn-aldols undergo stereoselective elimination reactions to afford a range of trisubstituted (E)-alpha,beta-unsaturated amides in >95% de, that may be subsequently converted into their corresponding (E)-alpha,beta-unsaturated acids or (E)-alpha,beta-unsaturated oxazolines in good yield. syn-Aldols derived from alpha,beta-unsaturated aldehydes gave their corresponding trisubstituted (E)-alpha,beta-unsaturated-amides with poorer levels of diastereocontrol, whilst there was a similar loss in (E)-selectivity during elimination of syn-aldols derived from chiral aldehydes. These elimination reactions proceed via rearrangement of the potassium alkoxide of the syn-aldol to a 1,3-oxazinane-2,4-dione enolate intermediate that subsequently eliminates carbon dioxide to afford a trisubstituted (E)-alpha,beta-unsaturated amide. The (E)-selectivity observed during the E1cB-type elimination step has been rationalised using a simple conformational model that employs a chair-like transition state to explain the observed stereocontrol. PMID:16186928

  5. Synthesis, structural, conformational and pharmacological study of some amides derived from 3 -methyl-2,4-diphenyl-3-azabicyclo[3.3.1]nonan-9α-amine

    NASA Astrophysics Data System (ADS)

    Iriepa, I.; Bellanato, J.; Gálvez, E.; Gil-Alberdi, B.

    2010-07-01

    Some mono-substituted amides ( 2- 5) derived from 3-methyl-2,4-diphenyl-3-azabicyclo[3.3.1]nonan-9α-amine were synthesized and studied by IR, 1H and 13C NMR spectroscopy. The crystal structure of 3-methyl-2,4-diphenyl-9α-(3,5-dichlorobenzamido)-3-azabicyclo[3.3.1]nonane ( 3) was determined by X-ray diffraction. NMR data showed that all compounds adopt in CDCl 3 a preferred flattened chair-chair conformation with the N-CH 3 group in equatorial disposition. X-ray data agreed with this conformation in the case of compound 3. IR data revealed that compounds 2 and 3 present a C dbnd O⋯HN intermolecular bond in the solid state. This conclusion was also confirmed by X-ray data of compound 3. In the case of compound 5, IR results suggested intermolecular NH⋯N-heterocyclic bonding. On the contrary, in the pyrazine derivative ( 4), IR, 1H and 13C NMR data showed the presence of an intramolecular NH⋯N1″-heterocyclic hydrogen bond in the solid state and solution. Moreover, NMR and IR data showed a preferred trans disposition for the NH-C dbnd O group. NMR also revealed free rotation of the -NH-CO-R group around C9-NH bond. Pharmacological assays on mice were drawn to evaluate analgesic activity.

  6. Tandem bis-aza-Michael addition reaction of amines in aqueous medium promoted by polystyrenesulfonic Acid

    EPA Science Inventory

    An efficient and environmentally benign tandem bis-aza-Michael addition of amines catalyzed by polystyrene sulfonic acid (PSSA) is described. This operationally simple high yielding microwave assisted synthetic protocol proceeded in water in the absence of any organic solvent.

  7. Synthesis and properties of amides of 1-benzyl-3-methyl- and 1-butyl-3-phenyl-7-methyl-4-oxo-2-thioxo (2,4-dioxo)-1,2,3,4-tetrahydropyrido-[2,3-d]pyrimidine-6-carboxy lic acids.

    PubMed

    Sladowska, H; Zawisza, T

    1986-12-01

    Amides of 1-benzyl-3,7-dimethyl-4-oxo-2-thioxo-1,2,3,4- tetrahydropyrido[2,3]pyrimidine-6-carboxylic acid were obtained by the condensation of ammonia, primary and secondary cyclic amines with the corresponding acid chloride. As by - products amides of 1-benzyl-3,7-dimethyl-2,4-dioxo-1,2,3,4-tetrahydropyrido[2,3-d]pyr imidine-6- carboxylic acid were isolated as a result of desulfuration. The same reaction performed with chloride of 1-butyl-7-methyl-3-phenyl-4-oxo-2-thioxo-1,2,3,4-tetrahydropyri do[2,3- d]pyrimidine-6-carboxylic acid gave mainly the corresponding 2,4-dioxo-amides. PMID:3556569

  8. Raman Scattering Sensor for On-Line Monitoring of Amines and Acid Gases

    SciTech Connect

    Uibel, Rory; Smith, Lee

    2010-05-20

    Sulfur and CO2 removal from hydrocarbon streams and power plant effluents are a major problem. The sulfur is normally in the form of H2S. These two acid gases are scrubbed using aqueous amine solutions that are difficult to control with conventional technology. Process Instruments Inc. developed Raman scattering technology for on-line, real-time monitoring of amine streams to improve their efficiency in scrubbing H2S and CO2 from hydrocarbon streams and power plant effluents. Improved control of amine and acid gas concentrations will allow refineries, natural gas processes and power plants to more efficiently scrub Sulfur and CO2, saving energy, time and financial resources.

  9. Isomer-sensitive deboronation in reductive aminations of aryl boronic acids

    SciTech Connect

    Jones, Brad Howard; Wheeler, David R.; Wheeler, Jill S.; Miller, Lance Lee; Alam, Todd M.; Spoerke, Erik David

    2015-09-05

    Deboronation is observed during the reductive amination of formylphenylboronic acid (FPBA) to the amine termini and side chains of peptides. This deboronation is sensitive to the isomerism of the boronic acid (BA), with ortho-FPBA yielding complete deboronation in the preparation of an N-terminally-modified dipeptide. The observed behavior is also clearly mediated by the chemical identity of the amine substrate. These results reveal a previously undocumented subtlety of BA functionalization and highlight the importance of thorough spectroscopic characterization in the preparation of peptide and small molecule BAs.

  10. Isomer-sensitive deboronation in reductive aminations of aryl boronic acids

    DOE PAGESBeta

    Jones, Brad Howard; Wheeler, David R.; Wheeler, Jill S.; Miller, Lance Lee; Alam, Todd M.; Spoerke, Erik David

    2015-09-05

    Deboronation is observed during the reductive amination of formylphenylboronic acid (FPBA) to the amine termini and side chains of peptides. This deboronation is sensitive to the isomerism of the boronic acid (BA), with ortho-FPBA yielding complete deboronation in the preparation of an N-terminally-modified dipeptide. The observed behavior is also clearly mediated by the chemical identity of the amine substrate. These results reveal a previously undocumented subtlety of BA functionalization and highlight the importance of thorough spectroscopic characterization in the preparation of peptide and small molecule BAs.

  11. Formation rates, stability and reactivity of sulfuric acid - amine clusters predicted by computational chemistry

    NASA Astrophysics Data System (ADS)

    Kurtén, Theo; Ortega, Ismael; Kupiainen, Oona; Olenius, Tinja; Loukonen, Ville; Reiman, Heidi; McGrath, Matthew; Vehkamäki, Hanna

    2013-04-01

    Despite the importance of atmospheric particle formation for both climate and air quality, both experiments and non-empirical models using e.g. sulfuric acid, ammonia and water as condensing vapors have so far been unable to reproduce atmospheric observations using realistic trace gas concentrations. Recent experimental and theoretical evidence has shown that this mystery is likely resolved by amines. Combining first-principles evaporation rates for sulfuric acid - dimethylamine clusters with cluster kinetic modeling, we show that even sub-ppt concentrations of amines, together with atmospherically realistic concentrations of sulfuric acid, result in formation rates close to those observed in the atmosphere. Our simulated cluster formation rates are also close to, though somewhat larger than, those measured at the CLOUD experiment in CERN for both sulfuric acid - ammonia and sulfuric acid - dimethylamine systems. A sensitivity analysis indicates that the remaining discrepancy for the sulfuric acid - amine particle formation rates is likely caused by steric hindrances to cluster formation (due to alkyl groups of the amine molecules) rather than by significant errors in the evaporation rates. First-principles molecular dynamic and reaction kinetic modeling shed further light on the microscopic physics and chemistry of sulfuric acid - amine clusters. For example, while the number and type of hydrogen bonds in the clusters typically reach their equilibrium values on a picosecond timescale, and the overall bonding patterns predicted by traditional "static" quantum chemical calculations seem to be stable, the individual atoms participating in the hydrogen bonds continuously change at atmospherically realistic temperatures. From a chemical reactivity perspective, we have also discovered a surprising phenomenon: clustering with sulfuric acid molecules slightly increases the activation energy required for the abstraction of alkyl hydrogens from amine molecules. This implies

  12. Pyrazole phenylcyclohexylcarbamates as inhibitors of human fatty acid amide hydrolases (FAAH).

    PubMed

    Aghazadeh Tabrizi, Mojgan; Baraldi, Pier Giovanni; Ruggiero, Emanuela; Saponaro, Giulia; Baraldi, Stefania; Romagnoli, Romeo; Martinelli, Adriano; Tuccinardi, Tiziano

    2015-06-01

    Fatty acid amide hydrolase (FAAH) inhibitors have gained attention as potential therapeutic targets in the management of neuropathic pain. Here, we report a series of pyrazole phenylcyclohexylcarbamate derivatives standing on the known carbamoyl FAAH inhibitor URB597. Structural modifications led to the recognition of compound 22 that inhibited human recombinant FAAH (hrFAAH) in the low nanomolar range (IC50 = 11 nM). The most active compounds of this series showed significant selectivity toward monoacylglycerol lipase (MAGL) enzyme. In addition, molecular modeling and reversibility behavior of the new class of FAAH inhibitors are presented in this article. PMID:26002335

  13. Antimicrobial effects of esters and amides of 3-(5-nitro-2-furyl)acrylic acid.

    PubMed

    Kellová, G; Sturdík, E; Stibrányi, L; Drobnica, L; Augustín, J

    1984-01-01

    The effect of 18 newly synthesized esters and amides of 3-(5-nitro-2-furyl)acrylic acid on bacteria (Escherichia coli, Staphylococcus aureus), yeasts (Saccharomyces cerevisiae, Candida albicans), molds (Aspergillus niger, Penicillium cyclopium, Rhizopus oryzae) and algae (Chlorella pyrenoidosa, Euglena gracilis, Scenedesmus obliquus) was investigated. The MIC values revealed antimycotic, antialgal and antibacterial activity of the studied derivatives. The antimycotic activity was found to decrease with increasing the length of the alkyl chain of esters and after introduction of amino nitrogen into the furylethylene backbone. The inhibitory effect on growth is caused by blocking bioenergetic processes, glycolysis in particular. PMID:6714854

  14. Discovery of MK-3168: A PET Tracer for Imaging Brain Fatty Acid Amide Hydrolase.

    PubMed

    Liu, Ping; Hamill, Terence G; Chioda, Marc; Chobanian, Harry; Fung, Selena; Guo, Yan; Chang, Linda; Bakshi, Raman; Hong, Qingmei; Dellureficio, James; Lin, Linus S; Abbadie, Catherine; Alexander, Jessica; Jin, Hong; Mandala, Suzanne; Shiao, Lin-Lin; Li, Wenping; Sanabria, Sandra; Williams, David; Zeng, Zhizhen; Hajdu, Richard; Jochnowitz, Nina; Rosenbach, Mark; Karanam, Bindhu; Madeira, Maria; Salituro, Gino; Powell, Joyce; Xu, Ling; Terebetski, Jenna L; Leone, Joseph F; Miller, Patricia; Cook, Jacquelynn; Holahan, Marie; Joshi, Aniket; O'Malley, Stacey; Purcell, Mona; Posavec, Diane; Chen, Tsing-Bau; Riffel, Kerry; Williams, Mangay; Hargreaves, Richard; Sullivan, Kathleen A; Nargund, Ravi P; DeVita, Robert J

    2013-06-13

    We report herein the discovery of a fatty acid amide hydrolase (FAAH) positron emission tomography (PET) tracer. Starting from a pyrazole lead, medicinal chemistry efforts directed toward reducing lipophilicity led to the synthesis of a series of imidazole analogues. Compound 6 was chosen for further profiling due to its appropriate physical chemical properties and excellent FAAH inhibition potency across species. [(11)C]-6 (MK-3168) exhibited good brain uptake and FAAH-specific signal in rhesus monkeys and is a suitable PET tracer for imaging FAAH in the brain. PMID:24900701

  15. Fatty acid amide supplementation decreases impulsivity in young adult heavy drinkers.

    PubMed

    van Kooten, Maria J; Veldhuizen, Maria G; de Araujo, Ivan E; O'Malley, Stephanie S; Small, Dana M

    2016-03-01

    Compromised dopamine signaling in the striatum has been associated with the expression of impulsive behaviors in addiction, obesity and alcoholism. In rodents, intragastric infusion of the fatty acid amide oleoylethanolamide increases striatal extracellular dopamine levels via vagal afferent signaling. Here we tested whether supplementation with PhosphoLean™, a dietary supplement that contains the precursor of the fatty acid amide oleoylethanolamide (N-oleyl-phosphatidylethanolamine), would reduce impulsive responding and alcohol use in heavy drinking young adults. Twenty-two individuals were assigned to a three-week supplementation regimen with PhosphoLean™ or placebo. Impulsivity was assessed with self-report questionnaires and behavioral tasks pre- and post-supplementation. Although self-report measures of impulsivity did not change, supplementation with PhosphoLean™, but not placebo, significantly reduced false alarm rate on a Go/No-Go task. In addition, an association was found between improved sensitivity on the Go/No-Go task and reduced alcohol intake. These findings provide preliminary evidence that promoting fatty acid derived gut-brain dopamine communication may have therapeutic potential for reducing impulsivity in heavy drinkers. PMID:26656766

  16. Isolation, identification and quantification of unsaturated fatty acids, amides, phenolic compounds and glycoalkaloids from potato peel.

    PubMed

    Wu, Zhi-Gang; Xu, Hai-Yan; Ma, Qiong; Cao, Ye; Ma, Jian-Nan; Ma, Chao-Mei

    2012-12-15

    Eleven compounds were isolated from potato peels and identified. Their structures were determined by interpretation of UV, MS, 1D, and 2D NMR spectral data and by comparison with reported data. The main components of the potato peels were found to be chlorogenic acid and other phenolic compounds, accompanied by 2 glycoalkaloids, 3 low-molecular-weight amide compounds, and 2 unsaturated fatty acids, including an omega-3 fatty acid. The potato peels showed more potent radical scavenging activity than the flesh. The quantification of the 11 components indicated that the potato peels contained a higher amount of phenolic compounds than the flesh. These results suggest that peel waste from the industry of potato chips and fries may be a source of useful compounds for human health. PMID:22980823

  17. Cinnamic acid amides from Tribulus terrestris displaying uncompetitive α-glucosidase inhibition.

    PubMed

    Song, Yeong Hun; Kim, Dae Wook; Curtis-Long, Marcus J; Park, Chanin; Son, Minky; Kim, Jeong Yoon; Yuk, Heung Joo; Lee, Keun Woo; Park, Ki Hun

    2016-05-23

    The α-glucosidase inhibitory potential of Tribulus terrestris extracts has been reported but as yet the active ingredients are unknown. This study attempted to isolate the responsible metabolites and elucidate their inhibition mechanism of α-glucosidase. By fractionating T. terristris extracts, three cinnamic acid amide derivatives (1-3) were ascertained to be active components against α-glucosidase. The lead structure, N-trans-coumaroyltyramine 1, showed significant inhibition of α-glucosidase (IC50 = 0.42 μM). Moreover, all active compounds displayed uncompetitive inhibition mechanisms that have rarely been reported for α-glucosidase inhibitors. This kinetic behavior was fully demonstrated by showing a decrease of both Km and Vmax, and Kik/Kiv ratio ranging between 1.029 and 1.053. We progressed to study how chemical modifications to the lead structure 1 may impact inhibition. An α, β-unsaturation carbonyl group and hydroxyl group in A-ring of cinnamic acid amide emerged to be critical functionalities for α-glucosidase inhibition. The molecular modeling study revealed that the inhibitory activities are tightly related to π-π interaction as well as hydrogen bond interaction between enzyme and inhibitors. PMID:26974386

  18. Computational insights into function and inhibition of fatty acid amide hydrolase.

    PubMed

    Palermo, Giulia; Rothlisberger, Ursula; Cavalli, Andrea; De Vivo, Marco

    2015-02-16

    The Fatty Acid Amide Hydrolase (FAAH) enzyme is a membrane-bound serine hydrolase responsible for the deactivating hydrolysis of a family of naturally occurring fatty acid amides. FAAH is a critical enzyme of the endocannabinoid system, being mainly responsible for regulating the level of its main cannabinoid substrate anandamide. For this reason, pharmacological inhibition of FAAH, which increases the level of endogenous anandamide, is a promising strategy to cure a variety of diseases including pain, inflammation, and cancer. Much structural, mutagenesis, and kinetic data on FAAH has been generated over the last couple of decades. This has prompted several informative computational investigations to elucidate, at the atomic-level, mechanistic details on catalysis and inhibition of this pharmaceutically relevant enzyme. Here, we review how these computational studies - based on classical molecular dynamics, full quantum mechanics, and hybrid QM/MM methods - have clarified the binding and reactivity of some relevant substrates and inhibitors of FAAH. We also discuss the experimental implications of these computational insights, which have provided a thoughtful elucidation of the complex physical and chemical steps of the enzymatic mechanism of FAAH. Finally, we discuss how computations have been helpful for building structure-activity relationships of potent FAAH inhibitors. PMID:25240419

  19. An Investigation of Solid-State Amidization and Imidization Reactions in Vapor Deposited Poly (amic acid)

    SciTech Connect

    Anthamatten, M; Letts, S A; Day, K; Cook, R C; Gies, A P; Hamilton, T P; Nonidez, W K

    2004-06-28

    The condensation polymerization reaction of 4,4'-oxydianiline (ODA) with pyromellitic dianhydride (PMDA) to form poly(amic acid) and the subsequent imidization reaction to form polyimide were investigated for films prepared using vapor deposition polymerization techniques. Fourier-transform infrared spectroscopy (FT-IR), thermal analysis, and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) of films at different temperatures indicate that additional solid-state polymerization occurs prior to imidization reactions. Experiments reveal that, upon vapor deposition, poly(amic acid) oligomers form that have a number-average molecular weight of about 1500 Daltons. Between 100 - 130 C these chains undergo additional condensation reaction to form slightly higher molecular weight oligomers. Calorimetry measurements show that this reaction is exothermic ({Delta}H {approx} -30 J/g) with an activation energy of about 120 kJ/mol. Experimental reaction enthalpies are compared to results from ab initio molecular modeling calculations to estimate the number of amide groups formed. At higher temperatures (150 - 300 C) imidization of amide linkages occurs as an endothermic reaction ({Delta}H {approx} +120 J/g) with an activation energy of about 130 kJ/mol. Solid-state kinetics were found to depend on reaction conversion as well as the processing conditions used to deposit films.

  20. N-acyl amines of docosahexaenoic acid and other n–3 polyunsatured fatty acids – from fishy endocannabinoids to potential leads

    PubMed Central

    Meijerink, Jocelijn; Balvers, Michiel; Witkamp, Renger

    2013-01-01

    N–3 long-chain polyunsaturated fatty acids (n–3 LC-PUFAs), in particular α-linolenic acid (18:3n-3), eicosapentaenoic acid (EPA; 20:5n-3) and docosahexaenoic acid (DHA; 22:6n-3) are receiving much attention because of their presumed beneficial health effects. To explain these, a variety of mechanisms have been proposed, but their interactions with the endocannabinoid system have received relatively little attention so far. However, it has already been shown some time ago that consumption of n–3 LC-PUFAs not only affects the synthesis of prototypic endocannabinoids like anandamide but also stimulates the formation of specific n–3 LC-PUFA-derived conjugates with ethanolamine, dopamine, serotonin or other amines. Some of these fatty amides show overlapping biological activities with those of typical endocannabinoids, whereas others possess distinct and sometimes largely unknown receptor affinities and other properties. The ethanolamine and dopamine conjugates of DHA have been the most investigated thus far. These mediators may provide promising new leads to the field of inflammatory and neurological disorders and for other pharmacological applications, including their use as carrier molecules for neurotransmitters to target the brain. Furthermore, combinations of n–3 LC-PUFA-derived fatty acid amides, their precursors and FAAH inhibitors offer possibilities to optimise their effects in health and disease. Linked Articles This article is part of a themed section on Cannabinoids. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2013.169.issue-4 & http://dx.doi.org/10.1111/bph.2012.167.issue-8 PMID:23088259

  1. The effect of pH on the toxicity of fatty acids and fatty acid amides to rainbow trout gill cells.

    PubMed

    Bertin, Matthew J; Voronca, Delia C; Chapman, Robert W; Moeller, Peter D R

    2014-01-01

    Harmful algal blooms (HABs) expose aquatic organisms to multiple physical and chemical stressors during an acute time period. Algal toxins themselves may be altered by water chemistry parameters affecting their bioavailability and resultant toxicity. The purpose of this study was to determine the effects of two abiotic parameters (pH, inorganic metal salts) on the toxicity of fatty acid amides and fatty acids, two classes of lipids produced by harmful algae, including the golden alga, Prymnesium parvum, that are toxic to aquatic organisms. Rainbow trout gill cells were used as a model of the fish gill and exposed to single compounds and mixtures of compounds along with variations in pH level and concentration of inorganic metal salts. We employed artificial neural networks (ANNs) and standard ANOVA statistical analysis to examine and predict the effects of these abiotic parameters on the toxicity of fatty acid amides and fatty acids. Our results demonstrate that increasing pH levels increases the toxicity of fatty acid amides and inhibits the toxicity of fatty acids. This phenomenon is reversed at lower pH levels. Exposing gill cells to complex mixtures of chemical factors resulted in dramatic increases in toxicity compared to tests of single compounds for both the fatty acid amides and fatty acids. These findings highlight the potential of physicochemical factors to affect the toxicity of chemicals released during algal blooms and demonstrate drastic differences in the effect of pH on fatty acid amides and fatty acids. PMID:24240104

  2. Rapid simultaneous determination of amines and organic acids in citrus using high-performance liquid chromatography.

    PubMed

    Uckoo, Ram M; Jayaprakasha, Guddadarangavvanahally K; Nelson, Shad D; Patil, Bhimanagouda S

    2011-01-15

    Rapid analytical method for the simultaneous separation and determination of amines and organic acids is a vital interest for quality control of citrus and their products. In the present study, a simultaneous high performance liquid chromatography (HPLC) method for the rapid separation of three amines and two organic acids was developed. Chromatographic separation of compounds was achieved using Xbridge C(18) column at ambient temperature, with an isocratic mobile phase of 3mM phosphoric acid at a flow rate of 1.0 mL min(-1). A photodiode array (PDA) detector was used to monitor the eluent at 223 nm and 254 nm with a total analysis time of 10 min. Extraction of amines and organic acids from citrus juice was optimized. The method was validated by tests of linearity, recovery, precision and ruggedness. The limit of detection (LOD) and limit of quantification (LOQ) for amines and ascorbic acid were determined to be 5 ng and 9.8 ng, respectively. All calibration curves showed good linearity (R(2) ≥ 0.9999) within the test ranges. The recoveries of the amines and organic acids ranged between 84% and 117%. The identity of each peak was confirmed by mass spectral (MS) analysis. The developed method was successfully applied to analyze the content of amines and organic acids in six different species and two varieties of citrus. Results indicate that mandarin and Marrs sweet orange contain high level of amines, while pummelo and Rio Red grapefruit had high content of ascorbic acid (137-251 μg mL(-1)) and citric acid (5-22 mg mL(-1)). Synephrine was the major amine present in Clementine (114 μg mL(-1)) and Marrs sweet orange (85 μg mL(-1)). To the best of our knowledge, this is the first report on simultaneous separation and quantification of amines and organic acids in Marrs sweet orange, Meyer lemon, Nova tangerine, Clementine, Ugli tangelo and Wekiwa tangelo. PMID:21147342

  3. Discovery and molecular basis of potent noncovalent inhibitors of fatty acid amide hydrolase (FAAH)

    PubMed Central

    Min, Xiaoshan; Thibault, Stephen T.; Porter, Amy C.; Gustin, Darin J.; Carlson, Timothy J.; Xu, Haoda; Lindstrom, Michelle; Xu, Guifen; Uyeda, Craig; Ma, Zhihua; Li, Yihong; Kayser, Frank; Walker, Nigel P. C.; Wang, Zhulun

    2011-01-01

    Fatty acid amide hydrolase (FAAH), an amidase-signature family member, is an integral membrane enzyme that degrades lipid amides including the endogenous cannabinoid anandamide and the sleep-inducing molecule oleamide. Both genetic knock out and pharmacological administration of FAAH inhibitors in rodent models result in analgesic, anxiolytic, and antiinflammatory phenotypes. Targeting FAAH activity, therefore, presents a promising new therapeutic strategy for the treatment of pain and other neurological-related or inflammatory disorders. Nearly all FAAH inhibitors known to date attain their binding potency through a reversible or irreversible covalent modification of the nucleophile Ser241 in the unusual Ser-Ser-Lys catalytic triad. Here, we report the discovery and mechanism of action of a series of ketobenzimidazoles as unique and potent noncovalent FAAH inhibitors. Compound 2, a representative of these ketobenzimidazoles, was designed from a series of ureas that were identified from high-throughput screening. While urea compound 1 is characterized as an irreversible covalent inhibitor, the cocrystal structure of FAAH complexed with compound 2 reveals that these ketobenzimidazoles, though containing a carbonyl moiety, do not covalently modify Ser241. These inhibitors achieve potent inhibition of FAAH activity primarily from shape complementarity to the active site and through numerous hydrophobic interactions. These noncovalent compounds exhibit excellent selectivity and good pharmacokinetic properties. The discovery of this distinctive class of inhibitors opens a new avenue for modulating FAAH activity through nonmechanism-based inhibition. PMID:21502526

  4. Structure–Activity Relationships of α-Keto Oxazole Inhibitors of Fatty Acid Amide Hydrolase

    PubMed Central

    Hardouin, Christophe; Kelso, Michael J.; Romero, F. Anthony; Rayl, Thomas J.; Leung, Donmienne; Hwang, Inkyu; Cravatt, Benjamin F.; Boger, Dale L.

    2008-01-01

    A systematic study of the structure–activity relationships (SAR) of 2b (OL-135), a potent inhibitor of fatty acid amide hydrolase (FAAH), is detailed targeting the C2 acyl side chain. A series of aryl replacements or substituents for the terminal phenyl group provided effective inhibitors (e.g., 5c, aryl = 1-napthyl, Ki = 2.6 nM) with 5hh (aryl = 3-Cl-Ph, Ki = 900 pM) being 5-fold more potent than 2b. Conformationally-restricted C2 side chains were examined and many provided exceptionally potent inhibitors of which 11j (ethylbiphenyl side chain) was established to be a 750 pM inhibitor. A systematic series of heteroatoms (O, NMe, S), electron-withdrawing groups (SO, SO2), and amides positioned within and hydroxyl substitutions on the linking side chain were investigated which typically led to a loss in potency. The most tolerant positions provided effective inhibitors (12p, 6-position S, Ki = 3 nM or 13d, 2-position OH, Ki = 8 nM) comparable in potency to 2b. Proteomic-wide screening of selected inhibitors from the systematic series of >100 candidates prepared revealed that they are selective for FAAH over all other mammalian serine proteases. PMID:17559203

  5. Kinetic resolution of acids in acylation reactions in the presence of chiral tertiary amines

    SciTech Connect

    Potapov, V.M.; Dem'yanovich, V.M.; Khlebnikov, V.A.

    1988-07-10

    Asymmetric synthesis has now become an important method for the production of optically active compounds, and its most attractive form is asymmetric catalysis. This work was devoted to an investigation into asymmetric catalysis with chiral tertiary amines in acylation reactions. During the acylation of alcohols and amines by the action of racemic 2-phenylpropionic and 2-methyl-3-phenylpropionic acids in the presence of S-nicotine the initial acids are resolved kinetically. The (R)-2-phenylpropionic acid obtained in this way had an optical purity of 0.5-1.5%.

  6. Hydroxycinnamic acid amides from Scopolia tangutica inhibit the activity of M1 muscarinic acetylcholine receptor in vitro.

    PubMed

    Zhang, Yan; Long, Zhen; Guo, Zhimou; Wang, Zhiwei; Zhang, Xiuli; Ye, Richard D; Liang, Xinmiao; Civelli, Olivier

    2016-01-01

    Scopolia tangutica Maxim (S. tangutica) extracts have been traditionally used as antispasmodic, sedative, and analgesic agents in Tibet and in the Qinghai province of China. Their active compositions are however poorly understood. We have recently isolated five new hydroxycinnamic acid (HCA) amides along with two known HCA amides, one cinnamic acid amide from these extracts. In this study, we evaluate their abilities to inhibit carbacol-induced activity of M1 muscarinic acetylcholine receptor along with the crude extracts. Chinese hamster ovary cells stably expressing the recombinant human M1 receptor (CHO-M1 cells) were employed to evaluate the anticholinergic potentials. Intracellular Ca(2+) changes were monitored using the FLIPR system. Five HCA amides as well as the crude S. tangutica extract displayed dose-dependent inhibitory effects against M1 receptor. These findings demonstrate that HCA amides are part of the M1 receptor-inhibiting principles of S. tangutica. Since blockade of parasympathetic nerve impulse transmission through the inhibition of the M1 receptor lessens smooth muscle spasms, our findings provided a molecular explanation for the traditional use of S. tangutica against spasm. PMID:26586621

  7. Targeting leukemic side population cells by isatin derivatives of nicotinic acid amide.

    PubMed

    Naglah, A M; Shinwari, Z; Bhat, M A; Al-Tahhan, M; Al-Omar, M A; Al-Dhfyan, A

    2016-01-01

    Side population (SP) cells mediate chemoresistance in leukemia. However, chemical inhibition approach to target SP cells has been poorly studied. Herein, we report the discovery of isatin derivatives of nicotinic acid amide as potent side population cell inhibitors. The selected derivatives showed superior potency over the reference drug verapamil. Furthermore, the treatment increased chemosensitivity and inhibited the cell proliferation on three different leukemic cell lines, K562, THP-1 and U937, suggesting that both SP and the bulk of leukemic cells are affected. Moreover, treatment with the most potent compound Nic9 reduced the expression of ABCG2, demonstrating that side population inhibition effect of the target derivatives is at least via ABCG2 inhibition. Importantly, the target derivatives induced erythrocyte/dendritic differentiation to leukemic cells mainly through Musashi/Numb pathway modulation. PMID:27358121

  8. Cellular viability effects of fatty acid amide hydrolase inhibition on cerebellar neurons

    PubMed Central

    2011-01-01

    The endocannabinoid anandamide (ANA) participates in the control of cell death inducing the formation of apoptotic bodies and DNA fragmentation. The aim of this study was to evaluate whether the ANA degrading enzyme, the fatty acid amide hydrolase (FAAH), would induce cellular death. Experiments were performed in cerebellar granule neurons cultured with the FAAH inhibitor, URB597 (25, 50 or 100 nM) as well as endogenous lipids such as oleoylethanolamide (OEA) or palmitoylethanolamide (PEA) and cellular viability was determined by MTT test. Neurons cultured with URB597 (25, 50 or 100 nM) displayed a decrease in cellular viability. In addition, if cultured with OEA (25 nM) or PEA (100 nM), cellular death was found. These results further suggest that URB597, OEA or PEA promote cellular death. PMID:21854612

  9. Free fatty acid determination in plasma by GC-MS after conversion to Weinreb amides.

    PubMed

    Ubhayasekera, Sarojini J K A; Staaf, Johan; Forslund, Anders; Bergsten, Peter; Bergquist, Jonas

    2013-02-01

    Circulating free fatty acids (FFAs) play important physiological roles as contributing components in cellular structure as well as energy utilization. Elevated levels of circulating FFAs are associated with metabolic aberrations in humans. FFAs differ in chain length and saturation and may be altered in metabolically dysregulated conditions, such as type 2 diabetes mellitus. Potentially, alterations in circulating levels of specific FFAs could also be important in terms of prognostic value. Various methods have been used to analyze FFAs. In this study, a straightforward and accurate method for the determination of FFAs in plasma has been established and evaluated, through conversion of plasma FFAs into acid fluorides followed by conversion to Weinreb amides (dimethylamide). The method is mild, efficient, selective, and quantitative for FFAs, when analyzed with capillary gas chromatography tandem mass spectrometry. Standard curves were linear over the range of 1,000-20,000 ng/mL with a correlation coefficient (r(2)) of 0.998, and coefficient of variation of triplicate analysis was <10 %. The gas chromatography-mass spectrometry (GC-MS) technique was reproducible and repeatable, and recoveries were above 90 %. From the generated MS spectra, five specific FFAs were identified. An explicit interest was the quantification of palmitate (C16:0) and palmitoleate (C16:1), which have been connected with detrimental and positive effects on the insulin-producing beta cells, respectively. The results demonstrate the suitability of Weinreb amides for efficient and rapid isolation of FFAs in plasma, prior to quantitative GC-MS analysis. We suggest that the method can be used as a routine standardized way of quantifying FFAs. PMID:23307129

  10. Inhibition of endocannabinoid-degrading enzyme fatty acid amide hydrolase increases atherosclerotic plaque vulnerability in mice.

    PubMed

    Hoyer, Friedrich Felix; Khoury, Mona; Slomka, Heike; Kebschull, Moritz; Lerner, Raissa; Lutz, Beat; Schott, Hans; Lütjohann, Dieter; Wojtalla, Alexandra; Becker, Astrid; Zimmer, Andreas; Nickenig, Georg

    2014-01-01

    The role of endocannabinoids such as anandamide during atherogenesis remains largely unknown. Fatty acid amide hydrolase (FAAH) represents the key enzyme in anandamide degradation, and its inhibition is associated with subsequent higher levels of anandamide. Here, we tested whether selective inhibition of FAAH influences the progression of atherosclerosis in mice. Selective inhibition of FAAH using URB597 resulted in significantly increased plasma levels of anandamide compared to control, as assessed by mass spectrometry experiments in mice. Apolipoprotein E-deficient (ApoE(-/-)) mice were fed a high-fat, cholesterol-rich diet to induce atherosclerotic conditions. Simultaneously, mice received either the pharmacological FAAH inhibitor URB597 1mg/kg body weight (n=28) or vehicle (n=25) via intraperitoneal injection three times a week. After eight weeks, mice were sacrificed, and experiments were performed. Vascular superoxide generation did not differ between both groups, as measured by L012 assay. To determine whether selective inhibition of FAAH affects atherosclerotic plaque inflammation, immunohistochemical staining of the aortic root was performed. Atherosclerotic plaque formation, vascular macrophage accumulation, as well as vascular T cell infiltration did not differ between both groups. Interestingly, neutrophil cell accumulation was significantly increased in mice receiving URB597 compared to control. Vascular collagen structures in atherosclerotic plaques were significantly diminished in mice treated with URB597 compared to control, as assessed by picro-sirius-red staining. This was accompanied by an increased aortic expression of matrix metalloproteinase-9, as determined by quantitative RT-PCR and western blot analysis. Inhibition of fatty acid amide hydrolase does not influence plaque size but increases plaque vulnerability in mice. PMID:24286707

  11. Role of the delta 8 double bond of agroclavine in lysergic acid amide biosynthesis by Claviceps purpurea.

    PubMed

    Willingale, J; Manzarpour, A; Mantle, P G

    1985-08-15

    Agroclavine, given to actively-growing sclerotial tissue of a strain of Claviceps purpurea which can not normally elaborate ergot alkaloids, was transformed by this tissue into lysergic acid amide with overall efficiency of approximately 40%. By contrast, festuclavine (8,9-dihydro-agroclavine) was not transformed, indicating specificity in the mechanism of lysergyl biosynthesis. PMID:4018228

  12. Fatty Acid Amide Hydrolase (FAAH) Inhibition Enhances Memory Acquisition through Activation of PPAR-alpha Nuclear Receptors

    ERIC Educational Resources Information Center

    Mazzola, Carmen; Medalie, Julie; Scherma, Maria; Panlilio, Leigh V.; Solinas, Marcello; Tanda, Gianluigi; Drago, Filippo; Cadet, Jean Lud; Goldberg, Steven R.; Yasar, Sevil

    2009-01-01

    Inhibitors of fatty acid amide hydrolase (FAAH) increase endogenous levels of anandamide (a cannabinoid CB[subscript 1]-receptor ligand) and oleoylethanolamide and palmitoylethanolamide (OEA and PEA, ligands for alpha-type peroxisome proliferator-activated nuclear receptors, PPAR-alpha) when and where they are naturally released in the brain.…

  13. Lipase-catalyzed production of a bioactive fatty amide derivative of 7,10-dihydroxy-8(E)-octadecenoic acid

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Fatty amides are of considerable interest due to their wide ranging industrial applications in detergents, shampoo, cosmetics and surfactant formulations. They are produced commercially from fatty acids by reacting with anhydrous ammonia at approximately 200 deg C and 345-690 KPa pressure. We inve...

  14. GC AND LC CHROMATOGRAPHIC AND EI, CE, +/- CI, AND ES MASS SPECTRAL CHARACTERISTICS OF SALTS AND AMIDES OF PERFLUOROOCTANESULFONIC ACID

    EPA Science Inventory

    In 1976, fluorine in human blood serum was thought to be present as perfluorooctanic acid; however, in the 1990s it was correctly identified by LC/MS as perfluorooctanesulfonate (PFOS). PFOS was both a commercial product and an end-stage metabolite of numerous substituted amides ...

  15. Structural, conformational and pharmacological study of some amides derived from 3-methyl-2,4-diphenyl-3-azabicyclo[3.3.1]nonan-9 β-amine as potential analgesics

    NASA Astrophysics Data System (ADS)

    Iriepa, I.; Gil-Alberdi, B.; Gálvez, E.; Herranz, M. J.; Bellanato, J.; Carmona, P.; Orjales, A.; Berisa, A.; Labeaga, L.

    1999-05-01

    A series of amides derived from 3-methyl-2,4-diphenyl-3-azabicyclo[3.3.1]nonan-9 β-amine were synthesized and studied by IR, Raman, 1H and 13C NMR spectroscopy. The compounds studied displayed in CDCl 3 a preferred flattened chair-chair conformation. IR (at room and variable temperature) and 1H and 13C NMR data showed the presence of an intramolecular NH⋯N-heterocyclic hydrogen bond in the pirazine derivative ( IV). Pharmacological assays on mice were drawn to evaluate drug-induced behavioral alteration peripheral or central acute toxicity and analgesic activity.

  16. Probing Variable Amine/Amide Ligation in NiIIN2S2 Complexes Using Sulfur K-Edge and Nickel L-Edge X-ray Absorption Spectroscopies: Implications for the Active Site of Nickel Superoxide Dismutase

    SciTech Connect

    Shearer,J.; Dehestani, A.; Abanda, F.

    2008-01-01

    Nickel superoxide dismutase (NiSOD) is a recently discovered metalloenzyme that catalyzes the disproportionation of O2* into O2 and H2O2. In its reduced state, the mononuclear NiII ion is ligated by two cis-cysteinate sulfurs, an amine nitrogen (from the protein N-terminus), and an amide nitrogen (from the peptide backbone). Unlike many small molecule and metallopeptide-based NiN2S2 complexes, S-based oxygenation is not observed in NiSOD. Herein we explore the spectroscopic properties of a series of three NiIIN2S2 complexes (bisamine-ligated (bmmp-dmed)NiII, amine/amide-ligated (NiII(BEAAM)), and bisamide-ligated (NiII(emi))2) with varying amine/amide ligation to determine the origin of the dioxygen stability of NiSOD. Ni L-edge X-ray absorption spectroscopy (XAS) demonstrates that there is a progression in ligand-field strength with (bmmp-dmed)NiII having the weakest ligand field and (NiII(emi)2) having the strongest ligand field. Furthermore, these Ni L-edge XAS studies also show that all three complexes are highly covalent with (NiII(BEEAM)) having the highest degree of metal-ligand covalency of the three compounds studied. S K-edge XAS also shows a high degree of NiS covalency in all three complexes. The electronic structures of the three complexes were probed using both hybrid-DFT and multiconfigurational SORCI calculations. These calculations demonstrate that the nucleophilic Ni(3d)/S()* HOMO of these NiN2S2 complexes progressively decreases in energy as the amide-nitrogens are replaced with amine nitrogens. This decrease in energy of the HOMO deactivates the Ni-center toward O2 reactivity. Thus, the NiS bond is protected from S-based oxygenation explaining the enhanced stability of the NiSOD active-site toward oxygenation by dioxygen.

  17. Amino acid amides of piperic acid (PA) and 4-ethylpiperic acid (EPA) as NorA efflux pump inhibitors of Staphylococcus aureus.

    PubMed

    Wani, Naiem Ahmad; Singh, Samsher; Farooq, Saleem; Shankar, Sudha; Koul, Surrinder; Khan, Inshad Ali; Rai, Rajkishor

    2016-09-01

    A total of eighteen piperic acid (PA) and 4-ethylpiperic acid (EPA) amides (C1-C18) with α-, β- and γ-amino acids were synthesized, characterized and evaluated for their efflux pump inhibitory activity against ciprofloxacin resistant Staphylococcus aureus. The amides were screened against NorA overexpressing S. aureus SA-1199B and wild type S. aureus SA-1199 using ethidium bromide as NorA efflux pump substrate. EPI C6 was found to be most potent and reduced the MIC of ciprofloxacin by 16 fold followed by C18 which showed 4 fold reduction of MIC. Ethidium bromide efflux inhibition and accumulation assay proved these compounds as NorA inhibitors. PMID:27503686

  18. Fine-Tuning of Lewis Acidity: The Case of Borenium Hydride Complexes Derived from Bis(phosphinimino)amide Boron Precursors.

    PubMed

    Jaiswal, Kuldeep; Prashanth, Billa; Singh, Sanjay

    2016-07-25

    Reactions of bis(phosphinimino)amines LH and L'H with Me2 S⋅BH2 Cl afforded chloroborane complexes LBHCl (1) and L'BHCl (2), and the reaction of L'H with BH3 ⋅Me2 S gave a dihydridoborane complex L'BH2 (3) (LH=[{(2,4,6-Me3 C6 H2 N)P(Ph2 )}2 N]H and L'H=[{(2,6-iPr2 C6 H3 N)P(Ph2 )}2 N]H). Furthermore, abstraction of a hydride ion from L'BH2 (3) and LBH2 (4) mediated by Lewis acid B(C6 F5 )3 or the weakly coordinating ion pair [Ph3 C][B(C6 F5 )4 ] smoothly yielded a series of borenium hydride cations: [L'BH](+) [HB(C6 F5 )3 ](-) (5), [L'BH](+) [B(C6 F5 )4 ](-) (6), [LBH](+) [HB(C6 F5 )3 ](-) (7), and [LBH](+) [B(C6 F5 )4 ](-) (8). Synthesis of a chloroborenium species [LBCl](+) [BCl4 ](-) (9) without involvement of a weakly coordinating anion was also demonstrated from a reaction of LBH2 (4) with three equivalents of BCl3 . It is clear from this study that the sterically bulky strong donor bis(phosphinimino)amide ligand plays a crucial role in facilitating the synthesis and stabilization of these three-coordinated cationic species of boron. Therefore, the present synthetic approach is not dependent on the requirement of weakly coordinating anions; even simple BCl4 (-) can act as a counteranion with borenium cations. The high Lewis acidity of the boron atom in complex 8 enables the formation of an adduct with 4-dimethylaminopyridine (DMAP), [LBH⋅(DMAP)](+) [B(C6 F5 )4 ](-) (10). The solid-state structures of complexes 1, 5, and 9 were investigated by means of single-crystal X-ray structural analysis. PMID:27351275

  19. Rapid, Structure-Based Exploration of Pipecolic Acid Amides as Novel Selective Antagonists of the FK506-Binding Protein 51.

    PubMed

    Gaali, Steffen; Feng, Xixi; Hähle, Andreas; Sippel, Claudia; Bracher, Andreas; Hausch, Felix

    2016-03-24

    The FK506-binding protein 51 (FKBP51) is a key regulator of stress hormone receptors and an established risk factor for stress-related disorders. Drug development for FKBP51 has been impaired by the structurally similar but functionally opposing homologue FKBP52. High selectivity between FKBP51 and FKBP52 can be achieved by ligands that stabilize a recently discovered FKBP51-favoring conformation. However, drug-like parameters for these ligands remained unfavorable. In the present study, we replaced the potentially labile pipecolic ester group of previous FKBP51 ligands by various low molecular weight amides. This resulted in the first series of pipecolic acid amides, which had much lower molecular weights without affecting FKBP51 selectivity. We discovered a geminally substituted cyclopentyl amide as a preferred FKBP51-binding motif and elucidated its binding mode to provide a new lead structure for future drug optimization. PMID:26954324

  20. The Molecular Basis for Dual Fatty Acid Amide Hydrolase (FAAH)/Cyclooxygenase (COX) Inhibition.

    PubMed

    Palermo, Giulia; Favia, Angelo D; Convertino, Marino; De Vivo, Marco

    2016-06-20

    The design of multitarget-directed ligands is a promising strategy for discovering innovative drugs. Here, we report a mechanistic study that clarifies key aspects of the dual inhibition of the fatty acid amide hydrolase (FAAH) and the cyclooxygenase (COX) enzymes by a new multitarget-directed ligand named ARN2508 (2-[3-fluoro-4-[3-(hexylcarbamoyloxy)phenyl]phenyl]propanoic acid). This potent dual inhibitor combines, in a single scaffold, the pharmacophoric elements often needed to block FAAH and COX, that is, a carbamate moiety and the 2-arylpropionic acid functionality, respectively. Molecular modeling and molecular dynamics simulations suggest that ARN2508 uses a noncovalent mechanism of inhibition to block COXs, while inhibiting FAAH via the acetylation of the catalytic Ser241, in line with previous experimental evidence for covalent FAAH inhibition. This study proposes the molecular basis for the dual FAAH/COX inhibition by this novel hybrid scaffold, stimulating further experimental studies and offering new insights for the rational design of novel anti-inflammatory agents that simultaneously act on FAAH and COX. PMID:26593700

  1. Genetic Engineering Activates Biosynthesis of Aromatic Fumaric Acid Amides in the Human Pathogen Aspergillus fumigatus

    PubMed Central

    Kalb, Daniel; Heinekamp, Thorsten; Lackner, Gerald; Scharf, Daniel H.; Dahse, Hans-Martin; Brakhage, Axel A.

    2014-01-01

    The Aspergillus fumigatus nonribosomal peptide synthetase FtpA is among the few of this species whose natural product has remained unknown. Both FtpA adenylation domains were characterized in vitro. Fumaric acid was identified as preferred substrate of the first and both l-tyrosine and l-phenylalanine as preferred substrates of the second adenylation domain. Genetically engineered A. fumigatus strains expressed either ftpA or the regulator gene ftpR, encoded in the same cluster of genes, under the control of the doxycycline-inducible tetracycline-induced transcriptional activation (tet-on) cassette. These strains produced fumaryl-l-tyrosine and fumaryl-l-phenylalanine which were identified by liquid chromatography and high-resolution mass spectrometry. Modeling of the first adenylation domain in silico provided insight into the structural requirements to bind fumaric acid as peptide synthetase substrate. This work adds aromatic fumaric acid amides to the secondary metabolome of the important human pathogen A. fumigatus which was previously not known as a producer of these compounds. PMID:25527545

  2. Monoamine Oxidase Inhibitory Activity of Ferulic Acid Amides: Curcumin-Based Design and Synthesis.

    PubMed

    Badavath, Vishnu N; Baysal, İpek; Uçar, Gülberk; Mondal, Susanta K; Sinha, Barij N; Jayaprakash, Venkatesan

    2016-01-01

    Ferulic acid has structural similarity with curcumin which is being reported for its monoamine oxidase (MAO) inhibitory activity. Based on this similarity, we designed a series of ferulic acid amides 6a-m and tested for their inhibitory activity on human MAO (hMAO) isoforms. All the compounds were found to inhibit the hMAO isoforms either selectively or non-selectively. Nine compounds (6a, 6b, 6g-m) were found to inhibit hMAO-B selectively, whereas the other four (6c-f) were found to be non-selective. There is a gradual shift from hMAO-B selectivity (6a,b) to non-selectivity (6c-f) as there is an increase in chain length at the amino terminus. In case of compounds having an aromatic nucleus at the amino terminus, increasing the carbon number between N and the aromatic ring increases the potency as well as selectivity toward hMAO-B. Compounds 6f, 6j, and 6k were subjected to membrane permeability and metabolic stability studies by in vitro assay methods. They were found to have a better pharmacokinetic profile than curcumin, ferulic acid, and selegiline. In order to understand the structural features responsible for the potency and selectivity of 6k, we carried out a molecular docking simulation study. PMID:26592858

  3. Complex investigation of the effects of lambertianic acid amide in female mice under conditions of social discomfort.

    PubMed

    Avgustinovich, D F; Fomina, M K; Sorokina, I V; Tolstikova, T G

    2014-09-01

    The effects of chronic administration of a new substance lambertianic acid amide and previously synthesized methyl ester of this acid were compared in female mice living under conditions of social discomfort. For modeling social discomfort, female mouse was housed for 30 days in a cage with aggressive male mouse kept behind a transparent perforated partition and observed its confrontations with another male mouse daily placed to the cage. The new agent more effectively than lambertianic acid methyl ester improved communicativeness and motor activity of animals, reduced hypertrophy of the adrenal glands, and enhanced catalase activity in the blood. These changes suggest that lambertianic acid amide produces a pronounced stress-protective effect under conditions of social discomfort. PMID:25257419

  4. Effects of synthetic alkamides on Arabidopsis fatty acid amide hydrolase activity and plant development.

    PubMed

    Faure, Lionel; Cavazos, Ronaldo; Khan, Bibi Rafeiza; Petros, Robby A; Koulen, Peter; Blancaflor, Elison B; Chapman, Kent D

    2015-02-01

    Alkamides and N-acylethanolamines (NAEs) are bioactive, amide-linked lipids that influence plant development. Alkamides are restricted to several families of higher plants and some fungi, whereas NAEs are widespread signaling molecules in both plants and animals. Fatty acid amide hydrolase (FAAH) has been described as a key contributor to NAE hydrolysis; however, no enzyme has been associated with alkamide degradation in plants. Herein reported is synthesis of 12 compounds structurally similar to a naturally occurring alkamide (N-isobutyl-(2E,6Z,8E)decatrienamide or affinin) with different acyl compositions more similar to plant NAEs and various amino alkyl head groups. These "hybrid" synthetic alkamides were tested for activity toward recombinant Arabidopsis FAAH and for their effects on plant development (i.e., cotyledon expansion and primary root length). A substantial increase in FAAH activity was discovered toward NAEs in vitro in the presence of some of these synthetic alkamides, such as N-ethyllauroylamide (4). This "enhancement" effect was found to be due, at least in part, to relief from product inhibition of FAAH by ethanolamine, and not due to an alteration in the oligomerization state of the FAAH enzyme. For several of these alkamides, an inhibition of seedling growth was observed with greater results in FAAH knockouts and less in FAAH over-expressing plants, suggesting that these alkamides could be hydrolyzed by FAAH in planta. The tight regulation of NAE levels in vivo appears to be important for proper seedling establishment, and as such, some of these synthetic alkamides may be useful pharmacological tools to manipulate the effects of NAEs in situ. PMID:25491532

  5. Specificity and formation of unusual amino acids of an amide ligation strategy for unprotected peptides.

    PubMed

    Tam, J P; Rao, C; Liu, C F; Shao, J

    1995-03-01

    An important step in the recently developed ligation strategy known as domain ligation strategy to link unprotected peptide segments without activation is the ring formation between the C-terminal ester aldehyde and the N-terminal amino acid bearing a beta-thiol or beta-hydroxide. A new method was developed to define the specificity of this reaction using a dye-labeled alanyl ester aldehyde to react with libraries of 400 dipeptides which contained all dipeptide combinations of the 20 genetically coded amino acids. Three different ester aldehydes of the dye-labeled alanine: alpha-formylmethyl (FM), beta-formylethyl (FE), and beta,beta,beta-dimethyl and formylethyl esters (DFE), were examined. The DFE ester was overly hindered and reacted with N-terminal Cys dipeptides (Cys-X). Interestingly, it also reacted slowly with the sequences of X-Gly where Gly was the second amino acid and the X-Gly amide bond participated in the ring formation. Although the FE ester reacted similarly as the FM ester in the ring formation, the subsequent O,N-acyl transfer was at least 30-fold slower than those of the FM-ester. The FM alpha-formyl methyl ester was the most suitable ester and was reactive with dipeptides of six N-terminal amino acids: Cys, Thr, Trp, Ser, His and Asn. The order and extent of their reactivity were highly dependent on pH, solvent and neighboring participation by the adjacent amino acid. In general, they could be divided into three categories. (1) N-Terminal Cys and Thr were the most reactive.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7775013

  6. A pro-nociceptive phenotype unmasked in mice lacking fatty-acid amide hydrolase

    PubMed Central

    Carey, Lawrence M; Slivicki, Richard A; Leishman, Emma; Cornett, Ben; Mackie, Ken; Bradshaw, Heather

    2016-01-01

    Fatty-acid amide hydrolase (FAAH) is the major enzyme responsible for degradation of anandamide, an endocannabinoid. Pharmacological inhibition or genetic deletion of FAAH (FAAH KO) produces antinociception in preclinical pain models that is largely attributed to anandamide-induced activation of cannabinoid receptors. However, FAAH metabolizes a wide range of structurally related, biologically active lipid signaling molecules whose functions remain largely unknown. Some of these endogenous lipids, including anandamide itself, may exert pro-nociceptive effects under certain conditions. In our study, FAAH KO mice exhibited a characteristic analgesic phenotype in the tail flick test and in both formalin and carrageenan models of inflammatory nociception. Nonetheless, intradermal injection of the transient receptor potential channel V1 (TRPV1) agonist capsaicin increased nocifensive behavior as well as mechanical and heat hypersensitivity in FAAH KO relative to wild-type mice. This pro-nociceptive phenotype was accompanied by increases in capsaicin-evoked Fos-like immunoreactive (FLI) cells in spinal dorsal horn regions implicated in nociceptive processing and was attenuated by CB1 (AM251) and TRPV1 (AMG9810) antagonists. When central sensitization was established, FAAH KO mice displayed elevated levels of anandamide, other fatty-acid amides, and endogenous TRPV1 agonists in both paw skin and lumbar spinal cord relative to wild-type mice. Capsaicin decreased spinal cord 2-AG levels and increased arachidonic acid and prostaglandin E2 levels in both spinal cord and paw skin irrespective of genotype. Our studies identify a previously unrecognized pro-nociceptive phenotype in FAAH KO mice that was unmasked by capsaicin challenge. The heightened nociceptive response was mediated by CB1 and TRPV1 receptors and accompanied by enhanced spinal neuronal activation. Moreover, genetic deletion of FAAH has a profound impact on the peripheral and central lipidome. Thus, genetic

  7. A pro-nociceptive phenotype unmasked in mice lacking fatty-acid amide hydrolase.

    PubMed

    Carey, Lawrence M; Slivicki, Richard A; Leishman, Emma; Cornett, Ben; Mackie, Ken; Bradshaw, Heather; Hohmann, Andrea G

    2016-02-01

    Fatty-acid amide hydrolase (FAAH) is the major enzyme responsible for degradation of anandamide, an endocannabinoid. Pharmacological inhibition or genetic deletion of FAAH (FAAH KO) produces antinociception in preclinical pain models that is largely attributed to anandamide-induced activation of cannabinoid receptors. However, FAAH metabolizes a wide range of structurally related, biologically active lipid signaling molecules whose functions remain largely unknown. Some of these endogenous lipids, including anandamide itself, may exert pro-nociceptive effects under certain conditions. In our study, FAAH KO mice exhibited a characteristic analgesic phenotype in the tail flick test and in both formalin and carrageenan models of inflammatory nociception. Nonetheless, intradermal injection of the transient receptor potential channel V1 (TRPV1) agonist capsaicin increased nocifensive behavior as well as mechanical and heat hypersensitivity in FAAH KO relative to wild-type mice. This pro-nociceptive phenotype was accompanied by increases in capsaicin-evoked Fos-like immunoreactive (FLI) cells in spinal dorsal horn regions implicated in nociceptive processing and was attenuated by CB1 (AM251) and TRPV1 (AMG9810) antagonists. When central sensitization was established, FAAH KO mice displayed elevated levels of anandamide, other fatty-acid amides, and endogenous TRPV1 agonists in both paw skin and lumbar spinal cord relative to wild-type mice. Capsaicin decreased spinal cord 2-AG levels and increased arachidonic acid and prostaglandin E2 levels in both spinal cord and paw skin irrespective of genotype. Our studies identify a previously unrecognized pro-nociceptive phenotype in FAAH KO mice that was unmasked by capsaicin challenge. The heightened nociceptive response was mediated by CB1 and TRPV1 receptors and accompanied by enhanced spinal neuronal activation. Moreover, genetic deletion of FAAH has a profound impact on the peripheral and central lipidome. Thus, genetic

  8. Cytotoxic Glycosylated Fatty Acid Amides from a Stelletta sp. Marine Sponge.

    PubMed

    Peddie, Victoria; Takada, Kentaro; Okuda, Shujiro; Ise, Yuji; Morii, Yasuhiro; Yamawaki, Nobuhiro; Takatani, Tomohiro; Arakawa, Osamu; Okada, Shigeru; Matsunaga, Shigeki

    2015-11-25

    We have discovered new glycosylated fatty acid amides, stellettosides, from a Stelletta sp. marine sponge. They were detected through LC-MS analysis of the extract combined with the cytotoxicity assay of the prefractionated sample. Their planar structures were determined by analyses of the NMR and tandem FABMS data. Stellettosides A1 and A2 (1 and 2) as well as stellettosides B1-B4 (3-6) were obtained as inseparable mixtures. Careful analysis of the NMR and tandem FABMS data of each mixture, along with comparison of the tandem FABMS data with that of a synthetic model compound, permitted us to assign the structure of the constituents in the mixture. The absolute configuration of the monosaccharide unit was determined by LC-MS after chiral derivatization. The relative configurations of the vicinal oxygenated methines in the fatty acid chains were assigned by the (1)H NMR data of the isopropylidene derivative. The mixture of stellettosides B1-B4 (3-6) exhibit moderate cytotoxic activity against HeLa cells with an IC50 value of 9 μM, whereas the mixture of stellettosides A1 and A2 (1 and 2) was not active at a concentration of 10 μM. PMID:26558480

  9. Synthesis of tertiary arylamines: Lewis acid-catalyzed direct reductive N-alkylation of secondary amines with ketones through an alternative pathway.

    PubMed

    Nayal, Onkar S; Thakur, Maheshwar S; Bhatt, Vinod; Kumar, Manoranjan; Kumar, Neeraj; Singh, Bikram; Sharma, Upendra

    2016-08-11

    We report herein a highly efficient, tin(ii)/PMHS catalyzed reductive N-alkylation of arylamines with ketones affording tertiary arylamines. A very wide substrate scope was observed for the current catalytic method as all six permutations of ketones/aldehydes/heterocyclic carbonyls and primary/secondary/heterocyclic amines were well tolerated, enabling access to secondary, tertiary and heterocyclic amines. The method is also convenient for the synthesis of N-substituted isoindolinones and phthalazinones via a tandem amination-amidation sequence. Mechanistic investigations revealed a carbocationic pathway instead of an ordinary direct reductive amination pathway. PMID:27363507

  10. Plant and Soil Emissions of Amines and Amino Acids: A Source of Secondary Aerosol Precursors

    NASA Astrophysics Data System (ADS)

    Jackson, M. L.; Doskey, P. V.; Pypker, T. G.

    2011-12-01

    Ammonia (NH3) is the most abundant alkaline gas in the atmosphere and forms secondary aerosol by neutralizing sulfuric and nitric acids that are released during combustion of fossil fuels. Ammonia is primarily emitted by cropping and livestock operations. However, C2 and C3 amines (pKb 3.3-3.4), which are stronger bases than NH3 (pKb 4.7) have been observed in nuclei mode aerosol that is the precursor to secondary aerosol. Mixtures of amines and amino acids have been identified in diverse environments in aerosol, fog water, cloud water, the soluble fraction of precipitation, and in dew. Glycine (pKb 4.2), serine (pKb 4.8) and alanine (pKb 3.7 and 4.1 for the D and L forms, respectively) are typically the most abundant species. The only reported values of gas-phase glycine, serine and alanine were in marine air and ranged from 6-14 pptv. The origin of atmospheric amines and amino acids has not been fully identified, although sources are likely similar to NH3. Nitrate assimilation in plants forms glycine, serine, and L-alanine, while D-alanine is present in bacterial cell walls. Glycine is converted to serine during C3 plant photorespiration, producing CO2 and NH3. Bacteria metabolize glycine and alanine to methylamine and ethylamine via decarboxylation. Likely sources of amino acids are plants and bacteria, thus concentrations near continental sources are likely greater than those measured in marine air. The overall goal of the research is to examine seasonal variations and relationships between the exchange of CO2, NH3, amines, and amino acids with a corn/soybean rotation in the Midwest Corn Belt. The study presents gaseous profiles of organic amine compounds from various species of vegetation using a mist chamber trapping technique and analysis of the derivatized species by high pressure liquid chromatography with fluorescence detection. Amino acid and amine profiles were obtained for red oak (Quercus rubra), sugar maple (Acer saccharinum), white pine (Pinus

  11. Qualitative identification of carboxylic acids, boronic acids, and amines using cruciform fluorophores.

    PubMed

    Schwaebel, Thimon; Lirag, Rio Carlo; Davey, Evan A; Lim, Jaebum; Bunz, Uwe H F; Miljanić, Ognjen Š

    2013-01-01

    Molecular cruciforms are X-shaped systems in which two conjugation axes intersect at a central core. If one axis of these molecules is substituted with electron-donors, and the other with electron-acceptors, cruciforms' HOMO will localize along the electron-rich and LUMO along the electron-poor axis. This spatial isolation of cruciforms' frontier molecular orbitals (FMOs) is essential to their use as sensors, since analyte binding to the cruciform invariably changes its HOMO-LUMO gap and the associated optical properties. Using this principle, Bunz and Miljanić groups developed 1,4-distyryl-2,5-bis(arylethynyl)benzene and benzobisoxazole cruciforms, respectively, which act as fluorescent sensors for metal ions, carboxylic acids, boronic acids, phenols, amines, and anions. The emission colors observed when these cruciform are mixed with analytes are highly sensitive to the details of analyte's structure and - because of cruciforms' charge-separated excited states - to the solvent in which emission is observed. Structurally closely related species can be qualitatively distinguished within several analyte classes: (a) carboxylic acids; (b) boronic acids, and (c) metals. Using a hybrid sensing system composed from benzobisoxazole cruciforms and boronic acid additives, we were also able to discern among structurally similar: (d) small organic and inorganic anions, (e) amines, and (f) phenols. The method used for this qualitative distinction is exceedingly simple. Dilute solutions (typically 10(-6) M) of cruciforms in several off-the-shelf solvents are placed in UV/Vis vials. Then, analytes of interest are added, either directly as solids or in concentrated solution. Fluorescence changes occur virtually instantaneously and can be recorded through standard digital photography using a semi-professional digital camera in a dark room. With minimal graphic manipulation, representative cut-outs of emission color photographs can be arranged into panels which permit quick naked

  12. Pd-Catalyzed Coupling of γ-C(sp(3))-H Bonds of Oxalyl Amide-Protected Amino Acids with Heteroaryl and Aryl Iodides.

    PubMed

    Han, Jian; Zheng, Yongxiang; Wang, Chao; Zhu, Yan; Huang, Zhi-Bin; Shi, Da-Qing; Zeng, Runsheng; Zhao, Yingsheng

    2016-07-01

    Pd-catalyzed regioselective coupling of γ-C(sp(3))-H bonds of oxalyl amide-protected amino acids with heteroaryl and aryl iodides is reported. A wide variety of iodides are tolerated, giving the corresponding products in moderate to good yields. Various oxalyl amide-protected amino acids were compatible in this C-H transformation, thus representing a practical method for constructing non-natural amino acid derivatives. PMID:27286881

  13. Inhibitors of Fatty Acid Amide Hydrolase and Monoacylglycerol Lipase: New Targets for Future Antidepressants.

    PubMed

    Ogawa, Shintaro; Kunugi, Hiroshi

    2015-01-01

    Cannabis and analogs of Δ9-tetrahydrocannabinol have been used for therapeutic purposes, but their therapeutic use remains limited because of various adverse effects. Endogenous cannabinoids have been discovered, and dysregulation of endocannabinoid signaling is implicated in the pathophysiology of major depressive disorder (MDD). Recently, endocannabinoid hydrolytic enzymes such as fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL) have become new therapeutic targets in the treatment of MDD. Several FAAH or MAGL inhibitors are reported to have no cannabimimetic side effects and, therefore, are new potential therapeutic options for patients with MDD who are resistant to first-line antidepressants (selective serotonin and serotonin-norepinephrine reuptake inhibitors). In this review, we focus on the possible relationships between MDD and the endocannabinoid system as well as the inhibitors' therapeutic potential. MAGL inhibitors may reduce inflammatory responses through activation of cannabinoid receptor type 2. In the hypothalamic-pituitary-adrenal axis, repeated FAAH inhibitor administration may be beneficial for reducing circulating glucocorticoid levels. Both FAAH and MAGL inhibitors may contribute to dopaminergic system regulation. Recently, several new inhibitors have been developed with strong potency and selectivity. FAAH inhibitor, MAGL inhibitor, or dual blocker use would be promising new treatments for MDD. Further pre-clinical studies and clinical trials using these inhibitors are warranted. PMID:26630956

  14. Amide-conjugated indole-3-acetic acid and adventitious root formation in mung bean cuttings

    SciTech Connect

    Norcini, J.G.

    1986-01-01

    The purpose of this research was to investigate further the relationship between amide-conjugated auxin and adventitious root formation. Indoleacetylaspartic acid (IAA-aspartate) was positively identified as the predominant conjugate isolated from mung bean cuttings after the cuttings has been treated with 10/sup -3/ M IAA. In cuttings treated with (1-/sup 14/C)IAA immediately after excision (0 hr), the percent of extractable /sup 14/C in IAA-aspartate in the hypocotyl sharply increased until 36 hr, then steadily declined. (/sup 14/C)IAA was completely metabolized between 12 and 24 hr. The rooting activities of IAA-L-aspartate, IAA-L-alanine, and IAA-glycine were determined at various stages of root formation; some cuttings were pretreated with 10/sup -3/ M IAA at 0 hr. Pretreated cuttings that were treated with IAA-glycine at 12, 24, 36 hr exhibited the greatest consistency between replications, the greatest number of long roots, and the longest roots. The conjugates did not stimulate rooting as effectively as IAA, yet like IAA, generally enhanced rooting the greatest when applied before the first cell division (24 hr).

  15. Immunohistochemical distribution of the cannabinoid receptor 1 and fatty acid amide hydrolase in the dog claustrum.

    PubMed

    Pirone, Andrea; Cantile, Carlo; Miragliotta, Vincenzo; Lenzi, Carla; Giannessi, Elisabetta; Cozzi, Bruno

    2016-07-01

    Cannabinoid receptor 1 (CB1R) and fatty acid amide hydrolase (FAAH) are part of the endocannabinoid system (ECB) which exerts a neuromodulatory activity on different brain functions and plays a key role in neurogenesis. Although many studies have reported FAAH and CB1R expression in the brain of different animal species, to the best of our knowledge they have never been described in the canine claustrum. Claustrum samples, obtained from necropsy of four neurologically normal dogs, were formalin fixed for paraffin embedding. Sections were either stained for morpho-histological analysis or immunostained for CB1R and FAAH. Analysis of adjacent sections incubated with the two antisera showed a complementary labeling pattern in the claustrum, with CB1R antibody staining fibers while anti-FAAH antibody stained cell bodies and the proximal portion of dendrites; this particular anatomical relationship suggests a retrograde endocannabinoid action via CB1R. CB1R and FAAH complementary immunostaining and their cellular localization reported here provide the first anatomical evidence for existence of the ECB in the dog claustrum. PMID:26907575

  16. Fatty-acid amide hydrolase polymorphisms and post-traumatic stress disorder after penetrating brain injury

    PubMed Central

    Pardini, M; Krueger, F; Koenigs, M; Raymont, V; Hodgkinson, C; Zoubak, S; Goldman, D; Grafman, J

    2012-01-01

    The past few years have seen an increase in the clinical awareness of post-traumatic stress disorder (PTSD), one of the most disabling and least understood behavioral disorders. Although the biological bases of PTSD are poorly understood, fatty-acid amide hydrolase (FAAH) activity has been linked with arousability and aversive-memories extinction, that is, two key features of PTSD. In this study, we investigated the association between the FAAH genetic polymorphisms and PTSD development and maintenance. We assessed PTSD frequency in a group of male Vietnam war veterans who suffered combat-related penetrating traumatic brain injury, that is, a relatively homogeneous population regarding the nature of the events that led to PTSD. We showed that rs2295633, a single-nucleotide polymorphism of FAAH, was significantly associated with PTSD diagnosis in subjects without lesions in the ventromedial prefrontal cortex. Moreover, the presence of the C allele was associated with more severe re-experiencing of trauma and more negative reported childhood experiences. In conclusion, our data suggest that FAAH has an important role in PTSD through modulation of aversive memories and point to both a novel therapeutic target and a possible risk marker for this condition. PMID:22832737

  17. Synthesis of Phenoxyacyl-Ethanolamides and Their Effects on Fatty Acid Amide Hydrolase Activity*

    PubMed Central

    Faure, Lionel; Nagarajan, Subbiah; Hwang, Hyeondo; Montgomery, Christa L.; Khan, Bibi Rafeiza; John, George; Koulen, Peter; Blancaflor, Elison B.; Chapman, Kent D.

    2014-01-01

    N-Acylethanolamines (NAEs) are involved in numerous biological activities in plant and animal systems. The metabolism of these lipids by fatty acid amide hydrolase (FAAH) is a key regulatory point in NAE signaling activity. Several active site-directed inhibitors of FAAH have been identified, but few compounds have been described that enhance FAAH activity. Here we synthesized two sets of phenoxyacyl-ethanolamides from natural products, 3-n-pentadecylphenolethanolamide and cardanolethanolamide, with structural similarity to NAEs and characterized their effects on the hydrolytic activity of FAAH. Both compounds increased the apparent Vmax of recombinant FAAH proteins from both plant (Arabidopsis) and mammalian (Rattus) sources. These NAE-like compounds appeared to act by reducing the negative feedback regulation of FAAH activity by free ethanolamine. Both compounds added to seedlings relieved, in part, the negative growth effects of exogenous NAE12:0. Cardanolethanolamide reduced neuronal viability and exacerbated oxidative stress-mediated cell death in primary cultured neurons at nanomolar concentrations. This was reversed by FAAH inhibitors or exogenous NAE substrate. Collectively, our data suggest that these phenoxyacyl-ethanolamides act to enhance the activity of FAAH and may stimulate the turnover of NAEs in vivo. Hence, these compounds might be useful pharmacological tools for manipulating FAAH-mediated regulation of NAE signaling in plants or animals. PMID:24558037

  18. Synthesis of phenoxyacyl-ethanolamides and their effects on fatty acid amide hydrolase activity.

    PubMed

    Faure, Lionel; Nagarajan, Subbiah; Hwang, Hyeondo; Montgomery, Christa L; Khan, Bibi Rafeiza; John, George; Koulen, Peter; Blancaflor, Elison B; Chapman, Kent D

    2014-03-28

    N-Acylethanolamines (NAEs) are involved in numerous biological activities in plant and animal systems. The metabolism of these lipids by fatty acid amide hydrolase (FAAH) is a key regulatory point in NAE signaling activity. Several active site-directed inhibitors of FAAH have been identified, but few compounds have been described that enhance FAAH activity. Here we synthesized two sets of phenoxyacyl-ethanolamides from natural products, 3-n-pentadecylphenolethanolamide and cardanolethanolamide, with structural similarity to NAEs and characterized their effects on the hydrolytic activity of FAAH. Both compounds increased the apparent Vmax of recombinant FAAH proteins from both plant (Arabidopsis) and mammalian (Rattus) sources. These NAE-like compounds appeared to act by reducing the negative feedback regulation of FAAH activity by free ethanolamine. Both compounds added to seedlings relieved, in part, the negative growth effects of exogenous NAE12:0. Cardanolethanolamide reduced neuronal viability and exacerbated oxidative stress-mediated cell death in primary cultured neurons at nanomolar concentrations. This was reversed by FAAH inhibitors or exogenous NAE substrate. Collectively, our data suggest that these phenoxyacyl-ethanolamides act to enhance the activity of FAAH and may stimulate the turnover of NAEs in vivo. Hence, these compounds might be useful pharmacological tools for manipulating FAAH-mediated regulation of NAE signaling in plants or animals. PMID:24558037

  19. Inhibitors of Fatty Acid Amide Hydrolase and Monoacylglycerol Lipase: New Targets for Future Antidepressants

    PubMed Central

    Ogawa, Shintaro; Kunugi, Hiroshi

    2015-01-01

    Cannabis and analogs of Δ9-tetrahydrocannabinol have been used for therapeutic purposes, but their therapeutic use remains limited because of various adverse effects. Endogenous cannabinoids have been discovered, and dysregulation of endocannabinoid signaling is implicated in the pathophysiology of major depressive disorder (MDD). Recently, endocannabinoid hydrolytic enzymes such as fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL) have become new therapeutic targets in the treatment of MDD. Several FAAH or MAGL inhibitors are reported to have no cannabimimetic side effects and, therefore, are new potential therapeutic options for patients with MDD who are resistant to first-line antidepressants (selective serotonin and serotonin-norepinephrine reuptake inhibitors). In this review, we focus on the possible relationships between MDD and the endocannabinoid system as well as the inhibitors’ therapeutic potential. MAGL inhibitors may reduce inflammatory responses through activation of cannabinoid receptor type 2. In the hypothalamic–pituitary–adrenal axis, repeated FAAH inhibitor administration may be beneficial for reducing circulating glucocorticoid levels. Both FAAH and MAGL inhibitors may contribute to dopaminergic system regulation. Recently, several new inhibitors have been developed with strong potency and selectivity. FAAH inhibitor, MAGL inhibitor, or dual blocker use would be promising new treatments for MDD. Further pre-clinical studies and clinical trials using these inhibitors are warranted. PMID:26630956

  20. Determination of free and amidated bile acids by high-performance liquid chromatography with evaporative light-scattering mass detection.

    PubMed

    Roda, A; Cerrè, C; Simoni, P; Polimeni, C; Vaccari, C; Pistillo, A

    1992-09-01

    A simple reverse phase high-performance liquid chromatographic method for a simultaneous analysis of free, glycine- and taurine-amidated bile acids is described. The resolution of ursodeoxycholic, cholic, chenodeocycholic, deoxycholic, and lithocholic acids, either free or amidated with glycine and taurine, is achieved using a C-18 octadecylsilane column (30 cm length, 4 micron particle size) with a gradient elution of aqueous methanol (65----75%) containing 15 mM ammonium acetate, pH 5.40, at 37 degrees C. The separated bile acids are detected with a new evaporative light-scattering mass detector and by absorbance at 200 nm. A complete resolution of the 16 bile acids, including the internal standard nor-deoxycholic acid, is obtained within 55 min. Using the light-scattering mass detector, amidated bile acids and, for the first time, free bile acids can be detected with similar detection limits in the order of 2-7 nmol. The new detector improves the baseline and the signal-to-noise ratio over the UV detection as it is not affected by impurities present in the samples with higher molar absorptivity than bile acids or by the change in the mobile phase composition during the gradient. The method fulfills all the standard requirements of precision and accuracy and the linearity of the mass detector is over 5 decade the detection limit. The new method has been used for the direct analysis of bile acid in stools and bile with only a preliminary clean-up procedure using a C-18 reverse phase extraction. PMID:1402406

  1. Hepatoprotective properties of betulonic acid amide and heptral in toxic liver injury induced by carbon tetrachloride in combination with ethanol.

    PubMed

    Semenov, D E; Zhukova, N A; Ivanova, E P; Sorokina, I V; Baiev, D S; Nepomnyashchikh, G I; Tolstikova, T G; Biryukova, M S

    2015-01-01

    Toxic liver injury with the development of fibrosis and cirrhosis was modeled in Wistar rats by intragastric administration of 0.1 ml/kg CCl4 in combination with 5% ethanol with glucose 3 times a week for 6 weeks. The animals were treated with betulonic acid amide (50 mg/kg in Tween aqueous solution) and heptral (6 mg/kg) as hepatoprotective compounds. It was found that betulonic acid amide stimulated the regenerative response in hepatocytes under conditions of combined toxic exposure and promoted recovery of their qualitative and quantitative characteristics, which was accompanied by a significant decrease in the severity of liver fibrosis and the absence of cirrhotic transformation of the liver. PMID:25573364

  2. Melonoside A: An ω-Glycosylated Fatty Acid Amide from the Far Eastern Marine Sponge Melonanchora kobjakovae.

    PubMed

    Guzii, Alla G; Makarieva, Tatyana N; Denisenko, Vladimir A; Dmitrenok, Pavel S; Kuzmich, Aleksandra S; Dyshlovoy, Sergey A; von Amsberg, Gunhild; Krasokhin, Vladimir B; Stonik, Valentin A

    2016-07-15

    Melonoside A (1), the first representative of a new class of ω-glycosylated fatty acid amides, was isolated from the Far Eastern marine sponge Melonanchora kobjakovae. The structure of 1, including absolute configuration, was established using detailed analysis of 1D and 2D NMR, CD, and mass spectra as well as chemical transformations. Compound 1 induces autophagy of human cisplatin-resistant germinal tumor cells NCCIT-R. PMID:27358020

  3. A billion-fold range in acidity for the solvent-exposed amides of Pyrococcus furiosus rubredoxin.

    PubMed

    Anderson, Janet S; Hernández, Griselda; Lemaster, David M

    2008-06-10

    The exchange rates of the static solvent-accessible amide hydrogens of Pyrococcus furiosus rubredoxin range from near the diffusion-limited rate to a billion-fold slower for the non-hydrogen-bonded Val 38 (eubacterial numbering). Hydrogen exchange directly monitors the kinetic acidity of the peptide nitrogen. Electrostatic solvation free energies were calculated by Poisson-Boltzmann methods for the individual peptide anions that form during the hydroxide-catalyzed exchange reaction to examine how well the predicted thermodynamic acidities match the experimentally determined kinetic acidities. With the exception of the Ile 12 amide, the differential exchange rate constant for each solvent-exposed amide proton that is not hydrogen bonded to a backbone carbonyl can be predicted within a factor of 6 (10 (0.78)) root-mean-square deviation (rmsd) using the CHARMM22 electrostatic parameter set and an internal dielectric value of 3. Under equivalent conditions, the PARSE parameter set yields a larger rmsd value of 1.28 pH units, while the AMBER parm99 parameter set resulted in a considerably poorer correlation. Either increasing the internal dielectric value to 4 or reducing it to a value of 2 significantly degrades the quality of the prediction. Assigning the excess charge of the peptide anion equally between the peptide nitrogen and the carbonyl oxygen also reduces the correlation to the experimental data. These continuum electrostatic calculations were further analyzed to characterize the specific structural elements that appear to be responsible for the wide range of peptide acidities observed for these solvent-exposed amides. The striking heterogeneity in the potential at sites along the protein-solvent interface should prove germane to the ongoing challenge of quantifying the contribution that electrostatic interactions make to the catalytic acceleration achieved by enzymes. PMID:18479148

  4. Amine Chemistry at Aqueous Interfaces: The Study of Organic Amines in Neutralizing Acidic Gases at an Air/Water Surface Using Vibrational Sum Frequency Spectroscopy

    NASA Astrophysics Data System (ADS)

    McWilliams, L.; Wren, S. N.; Valley, N. A.; Richmond, G.

    2014-12-01

    Small organic bases have been measured in atmospheric samples, with their sources ranging from industrial processing to animal husbandry. These small organic amines are often highly soluble, being found in atmospheric condensed phases such as fogwater and rainwater. Additionally, they display acid-neutralization ability often greater than ammonia, yet little is known regarding their kinetic and thermodynamic properties. This presentation will describe the molecular level details of a model amine system at the vapor/liquid interface in the presence of acidic gas. We find that this amine system shows very unique properties in terms of its bonding, structure, and orientation at aqueous surfaces. The results of our studies using a combination of computation, vibrational sum frequency spectroscopy, and surface tension will report the properties inherent to these atmospherically relevant species at aqueous surfaces.

  5. Templating route for mesostructured calcium phosphates with carboxylic acid- and amine-type surfactants.

    PubMed

    Ikawa, Nobuaki; Hori, Hideki; Kimura, Tatsuo; Oumi, Yasunori; Sano, Tsuneji

    2008-11-18

    Mesostructured calcium phosphates constructed by ionic frameworks were synthesized using carboxylic acid- and amine-type surfactants in mixed solvent systems of ethanol and water. A lamellar mesostructured calcium phosphate was prepared using palmitic acid as an anionic surfactant, as in the case using n-alkylamines. A wormhole-like mesostructured calcium phosphate can be obtained using dicarboxyl N-lauroyl- l-glutamic acid, whose headgroup is larger than that of palmitic acid. Similar mesostructured product was obtained using 4-dodecyldiethylenetriamine with a large headgroup containing two primary amine groups. Interactions of carboxyl and primary amino groups in the surfactant molecules with inorganic species are quite important for the formation of mesostructured calcium phosphates. The Ca/P molar ratio of mesostructured calcium phosphates was strongly affected by the molecular structure of surfactants containing carboxyl and primary amino groups. Ca-rich materials can be obtained using carboxylic acid-type surfactants (Ca/P approximately 1.7) rather than amine-type surfactants (Ca/P approximately 1.0). PMID:18947246

  6. Poly(carbonate–amide)s Derived from Bio-Based Resources: Poly(ferulic acid-co-tyrosine)

    PubMed Central

    2015-01-01

    Ferulic acid (FA), a bio-based resource found in fruits and vegetables, was coupled with a hydroxyl-amino acid to generate a new class of monomers to afford poly(carbonate–amide)s with potential to degrade into natural products. l-Serine was first selected as the hydroxyl-amino partner for FA, from which the activated p-nitrophenyl carbonate monomer was synthesized. Unfortunately, polymerizations were unsuccessful, and the elimination product was systematically obtained. To avoid elimination, we revised our strategy and used l-tyrosine ethyl ester, which lacks an acidic proton on the α position of the ethyl ester. Four new monomers were synthesized and converted into the corresponding poly(carbonate–amide)s with specific regioselectivities. The polymers were fully characterized through thermal and spectroscopic analyses. Preliminary fluorescent studies revealed interesting photophysical properties for the monomers and their corresponding poly(carbonate–amide)s, beyond the fluorescence characteristics of l-tyrosine and FA, making these materials potentially viable for sensing and/or imaging applications, in addition to their attractiveness as engineering materials derived from renewable resources. PMID:24839309

  7. AN EFFICIENT AND CHEMOSELECTIVE CBZ-PROTECTION OF AMINES USING SILICA-SULFURIC ACID AT ROOM TEMPERATURE

    EPA Science Inventory

    A simple, facile, and chemoselective N-benzyloxycarbonylation of amines using silica-sulfuric acid that proceeds under solvent-free conditions at room temperature has been achieved. These reactions are applicable to a wide variety of primary (aliphatic, cyclic) secondary amines, ...

  8. Molecular understanding of sulphuric acid-amine particle nucleation in the atmosphere.

    PubMed

    Almeida, João; Schobesberger, Siegfried; Kürten, Andreas; Ortega, Ismael K; Kupiainen-Määttä, Oona; Praplan, Arnaud P; Adamov, Alexey; Amorim, Antonio; Bianchi, Federico; Breitenlechner, Martin; David, André; Dommen, Josef; Donahue, Neil M; Downard, Andrew; Dunne, Eimear; Duplissy, Jonathan; Ehrhart, Sebastian; Flagan, Richard C; Franchin, Alessandro; Guida, Roberto; Hakala, Jani; Hansel, Armin; Heinritzi, Martin; Henschel, Henning; Jokinen, Tuija; Junninen, Heikki; Kajos, Maija; Kangasluoma, Juha; Keskinen, Helmi; Kupc, Agnieszka; Kurtén, Theo; Kvashin, Alexander N; Laaksonen, Ari; Lehtipalo, Katrianne; Leiminger, Markus; Leppä, Johannes; Loukonen, Ville; Makhmutov, Vladimir; Mathot, Serge; McGrath, Matthew J; Nieminen, Tuomo; Olenius, Tinja; Onnela, Antti; Petäjä, Tuukka; Riccobono, Francesco; Riipinen, Ilona; Rissanen, Matti; Rondo, Linda; Ruuskanen, Taina; Santos, Filipe D; Sarnela, Nina; Schallhart, Simon; Schnitzhofer, Ralf; Seinfeld, John H; Simon, Mario; Sipilä, Mikko; Stozhkov, Yuri; Stratmann, Frank; Tomé, Antonio; Tröstl, Jasmin; Tsagkogeorgas, Georgios; Vaattovaara, Petri; Viisanen, Yrjo; Virtanen, Annele; Vrtala, Aron; Wagner, Paul E; Weingartner, Ernest; Wex, Heike; Williamson, Christina; Wimmer, Daniela; Ye, Penglin; Yli-Juuti, Taina; Carslaw, Kenneth S; Kulmala, Markku; Curtius, Joachim; Baltensperger, Urs; Worsnop, Douglas R; Vehkamäki, Hanna; Kirkby, Jasper

    2013-10-17

    Nucleation of aerosol particles from trace atmospheric vapours is thought to provide up to half of global cloud condensation nuclei. Aerosols can cause a net cooling of climate by scattering sunlight and by leading to smaller but more numerous cloud droplets, which makes clouds brighter and extends their lifetimes. Atmospheric aerosols derived from human activities are thought to have compensated for a large fraction of the warming caused by greenhouse gases. However, despite its importance for climate, atmospheric nucleation is poorly understood. Recently, it has been shown that sulphuric acid and ammonia cannot explain particle formation rates observed in the lower atmosphere. It is thought that amines may enhance nucleation, but until now there has been no direct evidence for amine ternary nucleation under atmospheric conditions. Here we use the CLOUD (Cosmics Leaving OUtdoor Droplets) chamber at CERN and find that dimethylamine above three parts per trillion by volume can enhance particle formation rates more than 1,000-fold compared with ammonia, sufficient to account for the particle formation rates observed in the atmosphere. Molecular analysis of the clusters reveals that the faster nucleation is explained by a base-stabilization mechanism involving acid-amine pairs, which strongly decrease evaporation. The ion-induced contribution is generally small, reflecting the high stability of sulphuric acid-dimethylamine clusters and indicating that galactic cosmic rays exert only a small influence on their formation, except at low overall formation rates. Our experimental measurements are well reproduced by a dynamical model based on quantum chemical calculations of binding energies of molecular clusters, without any fitted parameters. These results show that, in regions of the atmosphere near amine sources, both amines and sulphur dioxide should be considered when assessing the impact of anthropogenic activities on particle formation. PMID:24097350

  9. Chiral Nanoparticles/Lewis Acids as Cooperative Catalysts for Asymmetric 1,4-Addition of Arylboronic Acids to α,β-Unsaturated Amides.

    PubMed

    Yasukawa, Tomohiro; Saito, Yuuki; Miyamura, Hiroyuki; Kobayashi, Shū

    2016-07-01

    Cooperative catalysts consisting of chiral Rh/Ag nanoparticles and Sc(OTf)3 have been developed that catalyze asymmetric 1,4-addition reactions of arylboronic acids with α,β-unsaturated amides efficiently. The reaction has been considered one of the most challenging reactions because of the low reactivity of the amide substrates. The new catalysts provide the desired products with outstanding enantioselectivities (>98 % ee) in the presence of low loadings (<0.5 mol %) of the catalyst. PMID:27193210

  10. Postprandial Differences in the Amino Acid and Biogenic Amines Profiles of Impaired Fasting Glucose Individuals after Intake of Highland Barley

    PubMed Central

    Liu, Liyan; Wang, Xinyang; Li, Ying; Sun, Changhao

    2015-01-01

    The aim of this study was to measure the postprandial changes in amino acid and biogenic amine profiles in individuals with impaired fasting glucose (IFG) and to investigate the changes of postprandial amino acid and biogenic amine profiles after a meal of highland barley (HB). Firstly, 50 IFG and 50 healthy individuals were recruited for the measurement of 2 h postprandial changes of amino acid and biogenic amine profiles after a glucose load. Secondly, IFG individuals received three different loads: Glucose (GL), white rice (WR) and HB. Amino acid and biogenic amine profiles, glucose and insulin were assayed at time zero and 30, 60, 90 and 120 min after the test load. The results showed fasting and postprandial amino acid and biogenic amine profiles were different between the IFG group and the controls. The level of most amino acids and their metabolites decreased after an oral glucose tolerance test, while the postprandial level of γ-aminobutyric acid (GABA) increased significantly in IFG individuals. After three different test loads, the area under the curve for glucose, insulin, lysine and GABA after a HB load decreased significantly compared to GL and WR loads. Furthermore, the postprandial changes in the level of GABA between time zero and 120 min during a HB load were associated positively with 2 h glucose and fasting insulin secretion in the IFG individuals. Thus, the HB load produced low postprandial glucose and insulin responses, which induced changes in amino acid and biogenic amine profiles and improved insulin sensitivity. PMID:26184292

  11. Synthesis and structural studies of amino amide salts derived from 2-(aminomethyl)benzimidazole and α-amino acids

    NASA Astrophysics Data System (ADS)

    Avila-Montiel, Concepción; Tapia-Benavides, Antonio R.; Falcón-León, Martha; Ariza-Castolo, Armando; Tlahuext, Hugo; Tlahuextl, Margarita

    2015-11-01

    2-{[(Ammoniumacetyl)amino]methyl}-1H-benzimidazol-3-ium dichloride 4, 2-{[(2-ammoniumpropanoyl)amino]methyl}-1H-benzimidazol-3-ium dichloride 5, and 2-{[(2-ammonium-3-phenylpropanoyl)amino]methyl}-1H-benzimidazol-3-ium dichloride 6 amino amides were synthesized via condensation of 2AMBZ dihydrochloride with the corresponding amino acid. Compounds 7-12 were obtained by replacing chloride ions (in salts 4-6) with nitrate or tetrachlorozincate ions. The results of X-ray diffraction crystallographic studies indicated that the geometries, charges and sizes of the anions are essential for the formation of the strong hydrogen bond interactions of compounds 4, 5, 9-12. Moreover, in most cases, the presence of water and solvent molecules stabilizes the supramolecular structures of these compounds. Nuclear magnetic resonance (NMR) and infrared (IR) spectroscopy indicated that the presence of chloride or tetrachlorozincate anions increases the acidity of the benzimidazolic and amide groups more significantly than the presence of nitrate anions. However, Quantum Theory of Atoms in Molecules (QTAIM) computations of the crystal structures demonstrate that amino amides interact more strongly with NO3- than with Cl- and ZnCl42- anions; this difference explains the spectroscopic results.

  12. Reactions of Methanesulfonic Acid with Amines and Ammonia as a Source of New Particles in Air.

    PubMed

    Chen, Haihan; Varner, Mychel E; Gerber, R Benny; Finlayson-Pitts, Barbara J

    2016-03-01

    New particle formation (NPF) from gaseous precursors as a significant source of aerosol needs to be better understood to accurately predict the impacts on visibility, climate change, and human health. While ternary nucleation of sulfuric acid, amines/NH3, and water is recognized as a significant driver for NPF, increasing evidence suggests a contribution from methanesulfonic acid (MSA) and amines under certain conditions. Here we report the formation of particles 2.5-10 nm in diameter from the reactions of MSA with methylamine (MA), dimethylamine (DMA), and NH3 at reaction times of 2.3-7.8 s in a flow reactor and compare these particles with those previously reported to be formed from reaction with trimethylamine (TMA). The effects of water vapor and concentrations of gaseous precursors on the particle number concentration and particle size were studied. The presence of water significantly enhances particle formation and growth. Under similar experimental conditions, particle number concentrations decrease in the order MA ≫ TMA ≈ DMA ≫ NH3, where NH3 is 2-3 orders of magnitude less efficient than DMA. Quantum chemical calculations of likely intermediate clusters were carried out to provide insights into the role of water and the different capacities of amines/NH3 in particle formation. Both gas-phase basicity and hydrogen-bonding capacity of amines/NH3 contribute to the potential for particles to form and grow. Our results indicate that, although amines typically have concentrations 1-3 orders of magnitude lower than that of NH3 in the atmosphere, they still play an important role in driving NPF. PMID:26379061

  13. Fatty acid amide hydrolase inhibitors confer anti-invasive and antimetastatic effects on lung cancer cells

    PubMed Central

    Winkler, Katrin; Ramer, Robert; Dithmer, Sophie; Ivanov, Igor; Merkord, Jutta; Hinz, Burkhard

    2016-01-01

    Inhibition of endocannabinoid degradation has been suggested as tool for activation of endogenous tumor defense. One of these strategies lies in blockade of fatty acid amide hydrolase (FAAH) which catalyzes the degradation of endocannabinoids (anandamide [AEA], 2-arachidonoylglycerol [2-AG]) and endocannabinoid-like substances (N-oleoylethanolamine [OEA], N-palmitoylethanolamine [PEA]). This study addressed the impact of two FAAH inhibitors (arachidonoyl serotonin [AA-5HT], URB597) on A549 lung cancer cell metastasis and invasion. LC-MS analyses revealed increased levels of FAAH substrates (AEA, 2-AG, OEA, PEA) in cells incubated with either FAAH inhibitor. In athymic nude mice FAAH inhibitors were shown to elicit a dose-dependent antimetastatic action yielding a 67% and 62% inhibition of metastatic lung nodules following repeated administration of 15 mg/kg AA-5HT and 5 mg/kg URB597, respectively. In vitro, a concentration-dependent anti-invasive action of either FAAH inhibitor was demonstrated, accompanied with upregulation of tissue inhibitor of matrix metalloproteinases-1 (TIMP-1). Using siRNA approaches, a causal link between the TIMP-1-upregulating and anti-invasive action of FAAH inhibitors was confirmed. Moreover, knockdown of FAAH by siRNA was shown to confer decreased cancer cell invasiveness and increased TIMP-1 expression. Inhibitor experiments point toward a role of CB2 and transient receptor potential vanilloid 1 in conferring anti-invasive effects of FAAH inhibitors and FAAH siRNA. Finally, antimetastatic and anti-invasive effects were confirmed for all FAAH substrates with AEA and OEA causing a TIMP-1-dependent anti-invasive action. Collectively, the present study provides first-time proof for an antimetastatic action of FAAH inhibitors. As mechanism of its anti-invasive properties an upregulation of TIMP-1 was identified. PMID:26930716

  14. Amine salt of n-triazolyl-hydrocarbyl succinamic acid and lubricating oil composition containing same

    SciTech Connect

    Nebzydoski, J.W.; Patmore, E.L.

    1981-08-11

    An amine salt of n-triazolyl-hydrocarbyl succinamic acid represented by the formula: 3-(HOOC-R''''-CO-NH-)-1,2,4-triazole. R'''-NH-R''' in which R'''' is an alkylene radical having from 2 to 24 carbon atoms and R''' is hydrogen or a hydrocarbyl radical having from 1 to 24 carbon atoms at least one R''' being a hydrocarbyl radical and a lubricating oil composition containing same is provided.

  15. A computational study of the chlorination and hydroxylation of amines by hypochlorous acid.

    PubMed

    Šakić, Davor; Hanževački, Marko; Smith, David M; Vrček, Valerije

    2015-12-28

    The reactions of hypochlorous acid (HOCl) with ammonia, (di)methylamine, and heterocyclic amines have been studied computationally using double-hybrid DFT methods (B2PLYP-D and BK-PLYP) and a G3B3 composite scheme. In the gas phase the calculated energy barriers for N- and/or C-hydroxylation are ca. 100 kJ mol(-1) lower than the barrier for N-chlorination of amines. In the model solvent, however, the latter process becomes kinetically more favored. The explicit solvent effects are crucial for determination of the reaction mechanism. The N-chlorination is extremely susceptible to the presence of explicit water molecules, while no beneficial solvation effect has been found for the N- or C-hydroxylation of amines. The origin of the observed solvent effects arises from differential solvation of the respective transition states for chlorine- and oxygen-transfers, respectively. The nature of solvation of the transition state structures has been explored in more detail by classical molecular dynamics (MD) simulation. In agreement with the quantum mechanical approach, the most stable structural motif, which includes the amine, HOCl, and two reactive waters, has been identified during the MD simulation. The inclusion of 5 or 6 explicit water molecules is required to reproduce the experimental barriers for HOCl-induced formation of N-chloramines in an aqueous environment. PMID:26486691

  16. Synergistic effects in solvent-extraction systems based on alkylsalicylic acids. I. Extraction of trivalent rare-earth metals in the presence of aliphatic amides

    SciTech Connect

    Preston, J.S.; Preez, A.C. du

    1995-07-01

    Aliphatic carboxylic acid amides were found to cause synergistic shifts in the pH{sub 50} values for the extraction of the trivalent rare-earth metals from chloride media by solutions of alkylsalicylic acids in xylene. For the different types of amide examined, the synergistic shifts for the extraction of neodymium by 3,5-diisopropylsalicylic acid (DIPSA) generally decrease in the order: R.CO.NR{sub 2}` > R.CO.NHR` > R.CO.NH{sub 2}, where R and R` are alkyl groups. With the N,N-dialkyl amides (R.CO.NR{sub 2}`) and the N-alkyl amides (R.CO.NHR`), the extent of the synergistic effect decreases with increasing chain-branching in either of the alkyl groups R and R`. For additions to 0.25 M alkylsalicylic acid, the synergistic effect increases with concentrations of up to 0.1 M amide, and decreases with higher concentrations. The extent of the synergistic shift produced by a given amide, as well as the separation in pH{sub 50} values from lanthanum to lutetium, increases with increasing steric bulk of the alkylsalicylic acid used. The separations between adjacent lanthanides are too small to be of any practical interest, however. Measurement of the solubility of salicylic acids (HA) in xylene containing various amounts of N,N-dialkyl amide (L) indicate that essentially complete formation of the HA.L adduct takes place. Treatment of metal-distribution data by slope analysis, and measurement of the solubility of the neodymium-DIPSA complex in xylene in the presence of amide suggest that the mixed-ligand complex has the stoichiometry NdA{sub 3}L{sub 2}. 18 refs., 6 figs., 3 refs.

  17. Cp*Rh(iii)-catalyzed electrophilic amination of arylboronic acids with azo compounds for synthesis of arylhydrazides.

    PubMed

    Lau, Yan-Fung; Chan, Chun-Ming; Zhou, Zhongyuan; Yu, Wing-Yiu

    2016-07-12

    A [Cp*Rh(iii)]-catalyzed electrophilic amination of arylboronic acids with diethyl azodicarboxylate (DEAD) was developed, and arylhydrazides were produced in excellent yields and selectivity. The analogous amination with the arylazocarboxylates afforded the corresponding N,N-diarylhydrazides. The electrophilic amination of arylboronic acids with azocarboxylates proceeds readily under mild conditions with excellent functional group tolerance. Up to 99% yields were obtained. Preliminary mechanistic studies revealed that prior formation of an arylrhodium(iii) intermediate for the azo coupling reaction can be ruled out. PMID:27339710

  18. Citric Acid Enhanced Copper Removal by a Novel Multi-amines Decorated Resin

    NASA Astrophysics Data System (ADS)

    Ling, Chen; Liu, Fuqiang; Pei, Zhiguo; Zhang, Xiaopeng; Wei, Mengmeng; Zhang, Yanhong; Zheng, Lirong; Zhang, Jing; Li, Aimin; Xing, Baoshan

    2015-05-01

    Cu removal by a novel multi-amines decorated resin (PAMD) from wastewater in the absence or presence of citric acid (CA) was examined. Adsorption capacity of Cu onto PAMD markedly increased by 186% to 5.07 mmol/g in the presence of CA, up to 7 times of that onto four commercial resins under the same conditions. Preloaded and kinetic studies demonstrated adsorption of [Cu-CA] complex instead of CA site-bridging and variations of adsorbate species were qualitatively illustrated. The interaction configuration was further studied with ESI-MS, FTIR, XPS and XANES characterizations. The large enhancement of Cu adsorption in Cu-CA bi-solutes systems was attributed to mechanism change from single-site to dual-sites interaction in which cationic or neutral Cu species (Cu2+ and CuHL0) coordinated with neutral amine sites and anionic complex species (CuL- and Cu2L22-) directly interacted with protonated amine sites via electrostatic attraction, and the ratio of the two interactions was approximately 0.5 for the equimolar bi-solutes system. Moreover, commonly coexisting ions in wastewaters had no obvious effect on the superior performance of PAMD. Also, Cu and CA could be recovered completely with HCl. Therefore, PAMD has a great potential to efficiently remove heavy metal ions from wastewaters in the presence of organic acids.

  19. Citric Acid Enhanced Copper Removal by a Novel Multi-amines Decorated Resin

    PubMed Central

    Ling, Chen; Liu, Fuqiang; Pei, Zhiguo; Zhang, Xiaopeng; Wei, Mengmeng; Zhang, Yanhong; Zheng, Lirong; Zhang, Jing; Li, Aimin; Xing, Baoshan

    2015-01-01

    Cu removal by a novel multi-amines decorated resin (PAMD) from wastewater in the absence or presence of citric acid (CA) was examined. Adsorption capacity of Cu onto PAMD markedly increased by 186% to 5.07 mmol/g in the presence of CA, up to 7 times of that onto four commercial resins under the same conditions. Preloaded and kinetic studies demonstrated adsorption of [Cu-CA] complex instead of CA site-bridging and variations of adsorbate species were qualitatively illustrated. The interaction configuration was further studied with ESI-MS, FTIR, XPS and XANES characterizations. The large enhancement of Cu adsorption in Cu-CA bi-solutes systems was attributed to mechanism change from single-site to dual-sites interaction in which cationic or neutral Cu species (Cu2+ and CuHL0) coordinated with neutral amine sites and anionic complex species (CuL− and Cu2L22−) directly interacted with protonated amine sites via electrostatic attraction, and the ratio of the two interactions was approximately 0.5 for the equimolar bi-solutes system. Moreover, commonly coexisting ions in wastewaters had no obvious effect on the superior performance of PAMD. Also, Cu and CA could be recovered completely with HCl. Therefore, PAMD has a great potential to efficiently remove heavy metal ions from wastewaters in the presence of organic acids. PMID:25962970

  20. PET imaging of fatty acid amide hydrolase with [(18)F]DOPP in nonhuman primates.

    PubMed

    Rotstein, Benjamin H; Wey, Hsiao-Ying; Shoup, Timothy M; Wilson, Alan A; Liang, Steven H; Hooker, Jacob M; Vasdev, Neil

    2014-11-01

    Fatty acid amide hydrolase (FAAH) regulates endocannabinoid signaling. [(11)C]CURB, an irreversibly binding FAAH inhibitor, has been developed for clinical research imaging with PET. However, no fluorine-18 labeled radiotracer for FAAH has yet advanced to human studies. [(18)F]DOPP ([(18)F]3-(4,5-dihydrooxazol-2-yl)phenyl (5-fluoropentyl)carbamate) has been identified as a promising (18)F-labeled analogue based on rodent studies. The goal of this work is to evaluate [(18)F]DOPP in nonhuman primates to support its clinical translation. High specific activity [(18)F]DOPP (5-6 Ci·μmol(-1)) was administered intravenously (iv) to three baboons (2M/1F, 3-4 years old). The distribution and pharmacokinetics were quantified following a 2 h dynamic imaging session using a simultaneous PET/MR scanner. Pretreatment with the FAAH-selective inhibitor, URB597, was carried out at 200 or 300 μg/kg iv, 10 min prior to [(18)F]DOPP administration. Rapid arterial blood sampling for the first 3 min was followed by interval sampling with metabolite analysis to provide a parent radiotracer plasma input function that indicated ∼95% baseline metabolism at 60 min and a reduced rate of metabolism after pretreatment with URB597. Regional distribution data were analyzed with 1-, 2-, and 3-tissue compartment models (TCMs), with and without irreversible trapping since [(18)F]DOPP covalently links to the active site of FAAH. Consistent with previous findings for [(11)C]CURB, the 2TCM with irreversible binding was found to provide the best fit for modeling the data in all regions. The composite parameter λk3 was therefore used to evaluate whole brain (WB) and regional binding of [(18)F]DOPP. Pretreatment studies showed inhibition of λk3 across all brain regions (WB baseline: 0.112 mL/cm(3)/min; 300 μg/kg URB597: 0.058 mL/cm(3)/min), suggesting that [(18)F]DOPP binding is specific for FAAH, consistent with previous rodent data. PMID:25004399

  1. Synthesis of novel naphthoquinone aliphatic amides and esters and their anticancer evaluation.

    PubMed

    Kongkathip, Boonsong; Akkarasamiyo, Sunisa; Hasitapan, Komkrit; Sittikul, Pichamon; Boonyalai, Nonlawat; Kongkathip, Ngampong

    2013-02-01

    Fourteen new naphthoquinone aliphatic amides and seventeen naphthoquinone aliphatic esters were synthesized in nine to ten steps from 1-hydroxy-2-naphthoic acid with 9-25% overall yield for the amides, and 16-21% overall yield for the esters. The key step of the amide synthesis is a coupling reaction between amine and various aliphatic acids using 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride (DMTMM) as a coupling agent while for the ester synthesis, DCC/DMAP or CDI was used as the coupling reagent between aliphatic acids and naphthoquinone alcohol. Both naphthoquinone amides and esters were evaluated for their anticancer activity against KB cells. It was found that naphthoquinone aliphatic amides showed stronger anticancer activity than those of the esters when the chains are longer than 7-carbon atoms. The optimum chain of amides is expected to be 16-carbon atoms. In addition, naphthoquinone aliphatic esters with α-methyl on the ester moiety possessed much stronger anticancer activity than the straight chains. Decatenation assay revealed that naphthoquinone amide with 16-carbon atoms chain at 15 μM and 20 μM can completely inhibit hTopoIIα activity while at 10 μM the enzyme activity was moderately inhibited. Molecular docking result also showed the same trend as the cytotoxicity and decatenation assay. PMID:23313636

  2. Quantification and enzyme targets of fatty acid amides from duckweed root exudates involved in the stimulation of denitrification.

    PubMed

    Sun, Li; Lu, Yufang; Kronzucker, Herbert J; Shi, Weiming

    2016-07-01

    Fatty acid amides from plant root exudates, such as oleamide and erucamide, have the ability to participate in strong plant-microbe interactions, stimulating nitrogen metabolism in rhizospheric bacteria. However, mechanisms of secretion of such fatty acid amides, and the nature of their stimulatory activities on microbial metabolism, have not been examined. In the present study, collection, pre-treatment, and determination methods of oleamide and erucamide in duckweed root exudates are compared. The detection limits of oleamide and erucamide by gas chromatography (GC) (10.3ngmL(-1) and 16.1ngmL(-1), respectively) are shown to be much lower than those by liquid chromatography (LC) (1.7 and 5.0μgmL(-1), respectively). Quantitative GC analysis yielded five times larger amounts of oleamide and erucamide in root exudates of Spirodela polyrrhiza when using a continuous collection method (50.20±4.32 and 76.79±13.92μgkg(-1) FW day(-1)), compared to static collection (10.88±0.66 and 15.27±0.58μgkg(-1) FW day(-1)). Furthermore, fatty acid amide secretion was significantly enhanced under elevated nitrogen conditions (>300mgL(-1)), and was negatively correlated with the relative growth rate of duckweed. Mechanistic assays were conducted to show that erucamide stimulates nitrogen removal by enhancing denitrification, targeting two key denitrifying enzymes, nitrate and nitrite reductases, in bacteria. Our findings significantly contribute to our understanding of the regulation of nitrogen dynamics by plant root exudates in natural ecosystems. PMID:27152459

  3. Synthesis and evaluation of fatty acid amides on the N-oleoylethanolamide-like activation of peroxisome proliferator activated receptor α.

    PubMed

    Takao, Koichi; Noguchi, Kaori; Hashimoto, Yosuke; Shirahata, Akira; Sugita, Yoshiaki

    2015-01-01

    A series of fatty acid amides were synthesized and their peroxisome proliferator-activated receptor α (PPAR-α) agonistic activities were evaluated in a normal rat liver cell line, clone 9. The mRNAs of the PPAR-α downstream genes, carnitine-palmitoyltransferase-1 and mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase, were determined by real-time reverse transcription-polymerase chain reaction (RT-PCR) as PPAR-α agonistic activities. We prepared nine oleic acid amides. Their PPAR-α agonistic activities were, in decreasing order, N-oleoylhistamine (OLHA), N-oleoylglycine, Oleamide, N-oleoyltyramine, N-oleoylsertonin, and Olvanil. The highest activity was found with OLHA. We prepared and evaluated nine N-acylhistamines (N-acyl-HAs). Of these, OLHA, C16:0-HA, and C18:1Δ(9)-trans-HA showed similar activity. Activity due to the different chain length of the saturated fatty acid peaked at C16:0-HA. The PPAR-α antagonist, GW6471, inhibited the induction of the PPAR-α downstream genes by OLHA and N-oleoylethanolamide (OEA). These data suggest that N-acyl-HAs could be considered new PPAR-α agonists. PMID:25832022

  4. Capillary electrophoresis analysis of organic amines and amino acids in saline and acidic samples using the Mars organic analyzer.

    PubMed

    Stockton, Amanda M; Chiesl, Thomas N; Lowenstein, Tim K; Amashukeli, Xenia; Grunthaner, Frank; Mathies, Richard A

    2009-11-01

    The Mars Organic Analyzer (MOA) has enabled the sensitive detection of amino acid and amine biomarkers in laboratory standards and in a variety of field sample tests. However, the MOA is challenged when samples are extremely acidic and saline or contain polyvalent cations. Here, we have optimized the MOA analysis, sample labeling, and sample dilution buffers to handle such challenging samples more robustly. Higher ionic strength buffer systems with pK(a) values near pH 9 were developed to provide better buffering capacity and salt tolerance. The addition of ethylaminediaminetetraacetic acid (EDTA) ameliorates the negative effects of multivalent cations. The optimized protocol utilizes a 75 mM borate buffer (pH 9.5) for Pacific Blue labeling of amines and amino acids. After labeling, 50 mM (final concentration) EDTA is added to samples containing divalent cations to ameliorate their effects. This optimized protocol was used to successfully analyze amino acids in a saturated brine sample from Saline Valley, California, and a subcritical water extract of a highly acidic sample from the Río Tinto, Spain. This work expands the analytical capabilities of the MOA and increases its sensitivity and robustness for samples from extraterrestrial environments that may exhibit pH and salt extremes as well as metal ions. PMID:19968460

  5. Isotopic analyses of nitrogenous compounds from the Murchison meteorite: ammonia, amines, amino acids, and polar hydrocarbons

    NASA Technical Reports Server (NTRS)

    Pizzarello, S.; Feng, X.; Epstein, S.; Cronin, J. R.

    1994-01-01

    The combined volatile bases (ammonia, aliphatic amines, and possibly other bases), ammonia, amino acids, and polar hydrocarbons were prepared from the Murchison meteorite for isotopic analyses. The volatile bases were obtained by cryogenic transfer after acid-hydrolysis of a hot-water extract and analyzed by combined gas chromatography-mass spectrometry of pentafluoropropionyl derivatives. The aliphatic amines present in this preparation comprise a mixture that includes both primary and secondary isomers through C5 at a total concentration of > or = 100 nmoles g-1. As commonly observed for meteoritic organic compounds, almost all isomers through C5 are present, and the concentrations within homologous series decrease with increasing chain length. Ammonia was chromatographically separated from the other volatile bases and found at a concentration of 1.1-1.3 micromoles g-1 meteorite. The ammonia analyzed includes contributions from ammonium salts and the hydrolysis of extractable organic compounds, e.g., carboxamides. Stable isotope analyses showed the volatile bases to be substantially enriched in the heavier isotopes, relative to comparable terrestrial compounds delta D < or = +1221%; delta 13C = +22%; delta 15N = +93%). Ammonia, per se, was found to have a somewhat lower delta 15N value (+69%) than the total volatile bases; consequently, a higher delta 15N (>93%) can be inferred for the other bases, which include the amines. Solvent-extractable polar hydrocarbons obtained separately were found to be enriched in 15N (delta 15N = +104%). Total amino acids, prepared from a hydrolyzed hot-water extract by cation exchange chromatography, gave a delta 15N of +94%, a value in good agreement with that obtained previously. Nitrogen isotopic data are also given for amino acid fractions separated chromatographically. The delta 15N values of the Murchison soluble organic compounds analyzed to date fall within a rather narrow range (delta 15N = +94 +/- 8%), an observation

  6. New Particle Formation and Growth from Methanesulfonic Acid, Amines, Water, and Organics

    NASA Astrophysics Data System (ADS)

    Arquero, K. D.; Ezell, M. J.; Finlayson-Pitts, B. J.

    2014-12-01

    Particles in the atmosphere can influence visibility, negatively impact human health, and affect climate. The largest uncertainty in determining global radiative forcing is attributed to atmospheric aerosols. While new particle formation in many locations is correlated with sulfuric acid in air, neither the gas-phase binary nucleation of H2SO4-H2O nor the gas-phase ternary nucleation of H2SO4-NH3-H2O alone can fully explain observations. An additional potential particle source, based on previous studies in this laboratory, is methanesulfonic acid (MSA) with amines and water vapor. However, organics are ubiquitous in the atmosphere, with secondary organic aerosol (SOA) being a major component of particles. Organics could be involved in the initial stages of particle formation by enhancing or inhibiting nucleation from sulfuric acid or MSA, in addition to contributing to their growth to form SOA. Experiments to measure the effects of a series of organics of varying structure on particle formation and growth from MSA, amines, and water were performed in a custom-built small volume aerosol flow tube reactor. Analytical instruments and techniques include a scanning mobility particle sizer to measure particle size distributions, sampling onto a weak cation exchange resin with analysis by ion chromatography to measure amine concentrations, and filter collection and analysis by ultra-high performance liquid chromatography tandem mass spectrometry to measure MSA concentrations. Organics were measured by atmospheric pressure chemical ionization tandem mass spectrometry. The impact of these organics on the initial particle formation as well as growth will be reported. The outcome is an improved understanding of fundamental chemistry of nucleation and growth to ultimately be incorporated into climate models to better predict how particles affect the global climate budget.

  7. Condensation Reactions and Formation of Amides, Esters, and Nitriles Under Hydrothermal Conditions

    NASA Astrophysics Data System (ADS)

    Rushdi, Ahmed I.; Simoneit, Bernd R. T.

    2004-06-01

    Hydrothermal pyrolysis experiments were performed to assess condensation (dehydration) reactions to amide, ester, and nitrile functionalities from lipid precursors. Beside product formation, organic compound alteration and stability were also evaluated. Mixtures of nonadecanoic acid, hexadecanedioic acid, or hexadecanamide with water, ammonium bicarbonate, and oxalic acid were heated at 300°C for 72 h. In addition, mixtures of ammonium bicarbonate and oxalic acid solutions were used to test the abiotic formation of organic nitrogen compounds at the same temperature. The resulting products were condensation compounds such as amides, nitriles, and minor quantities of N-methylalkyl amides, alkanols, and esters. Mixtures of alkyl amide in water or oxalic acid yielded mainly hydrolysis and dehydration products, and with ammonium bicarbonate and oxalic acid the yield of condensation products was enhanced. The synthesis experiments with oxalic acid and ammonium bicarbonate solutions yielded homologous series of alkyl amides, alkyl amines, alkanes, and alkanoic acids, all with no carbon number predominances. These organic nitrogen compounds are stable and survive under the elevated temperatures of hydrothermal fluids.

  8. Lewis Acid Catalyzed Regiospecific Cross-Dehydrative Coupling Reaction of 2-Furylcarbinols with β-Keto Amides or 4-Hydroxycoumarins: A Route to Furyl Enols.

    PubMed

    Miao, Maozhong; Luo, Yi; Li, Hongli; Xu, Xin; Chen, Zhengkai; Xu, Jianfeng; Ren, Hongjun

    2016-06-17

    Lewis acid catalyzed directly dehydrative carbon-carbon bond formation reaction of 2-furylcarbinols with β-keto amides provides a straightforward method for regioselective synthesis of (Z)-furyl enols. Moreover, this Lewis acid catalyzed cross-coupling reaction can be extended to an interesting heterocyclic version featuring a functionalized 3-furyl-4-hydroxycoumarin synthesis. PMID:27224045

  9. X-ray Crystallographic Analysis of α-Ketoheterocycle Inhibitors Bound to a Humanized Variant of Fatty Acid Amide Hydrolase

    PubMed Central

    Mileni, Mauro; Garfunkle, Joie; Ezzili, Cyrine; Kimball, F. Scott; Cravatt, Benjamin F.; Stevens, Raymond C.; Boger, Dale L.

    2009-01-01

    Three cocrystal X-ray structures of the α-ketoheterocycle inhibitors 3–5 bound to a humanized variant of fatty acid amide hydrolase (FAAH) are disclosed and comparatively discussed alongside those of 1 (OL-135) and its isomer 2. These five X-ray structures systematically probe each of the three active site regions key to substrate or inhibitor binding: (1) the conformationally mobile acyl chain-binding pocket and membrane access channel responsible for fatty acid amide substrate and inhibitor acyl chain binding, (2) the atypical active site catalytic residues and surrounding oxyanion hole that covalently binds the core of the α-ketoheterocycle inhibitors captured as deprotonated hemiketals mimicking the tetrahedral intermediate of the enzyme catalyzed reaction, and (3) the cytosolic port and its uniquely important imbedded ordered water molecules and a newly identified anion binding site. The detailed analysis of their key active site interactions and their implications on the interpretation of the available structure–activity relationships are discussed providing important insights for future design. PMID:19924997

  10. X-ray Crystallographic Analysis of [alpha]-Ketoheterocycle Inhibitors Bound to a Humanized Variant of Fatty Acid Amide Hydrolase

    SciTech Connect

    Mileni, Mauro; Garfunkle, Joie; Ezzili, Cyrine; Kimball, F.Scott; Cravatt, Benjamin F.; Stevens, Raymond C.; Boger, Dale L.

    2010-11-03

    Three cocrystal X-ray structures of the {alpha}-ketoheterocycle inhibitors 3-5 bound to a humanized variant of fatty acid amide hydrolase (FAAH) are disclosed and comparatively discussed alongside those of 1 (OL-135) and its isomer 2. These five X-ray structures systematically probe each of the three active site regions key to substrate or inhibitor binding: (1) the conformationally mobile acyl chain-binding pocket and membrane access channel responsible for fatty acid amide substrate and inhibitor acyl chain binding, (2) the atypical active site catalytic residues and surrounding oxyanion hole that covalently binds the core of the {alpha}-ketoheterocycle inhibitors captured as deprotonated hemiketals mimicking the tetrahedral intermediate of the enzyme-catalyzed reaction, and (3) the cytosolic port and its uniquely important imbedded ordered water molecules and a newly identified anion binding site. The detailed analysis of their key active site interactions and their implications on the interpretation of the available structure-activity relationships are discussed providing important insights for future design.

  11. Synthesis and structure--activity relationships of substituted cinnamic acids and amide analogues: a new class of herbicides.

    PubMed

    Vishnoi, Shipra; Agrawal, Vikash; Kasana, Virendra K

    2009-04-22

    In the present investigation, substituted cinnamic acids (3-hydroxy, 4-hydroxy, 2-nitro, 3-nitro, 4-nitro, 3-chloro, and 4-methoxy) and their amide analogues with four different types of substituted anilines have been synthesized. The synthesized compounds have been screened for their germination inhibition activity on radish (Raphanus sativus L. var. Japanese White) seeds at 50, 100, and 200 ppm concentrations, and the activity was compared with standard herbicide, metribuzin formulation (sencor). Significant activity was exhibited by all of the compounds. It was observed that with the increase in concentration of the test solution, the activity also increased. All of the compounds showed more than 70% inhibition at 100 ppm concentration except 4-hydroxy cinnamanilide. The compound, 2-chloro (4'-hydroxy) cinnamanilide was the best among the tested compounds, and it was found to be at par with the standard, metribuzin at all concentrations. Thus, it can be concluded that substituted cinnamic acids and their amide analogues may be developed as potential herbicides. PMID:19368353

  12. Strong Fluorescent Smart Organogel as a Dual Sensing Material for Volatile Acid and Organic Amine Vapors.

    PubMed

    Xue, Pengchong; Yao, Boqi; Wang, Panpan; Gong, Peng; Zhang, Zhenqi; Lu, Ran

    2015-11-23

    An L-phenylalanine derivative (C12PhBPCP) consisting of a strong emission fluorophore with benzoxazole and cyano groups is designed and synthesized to realize dual responses to volatile acid and organic amine vapors. The photophysical properties and self-assembly of the said derivative in the gel phase are also studied. C12PhBPCP can gelate organic solvents and self-assemble into 1 D nanofibers in the gels. UV/Vis absorption spectral results show H-aggregate formation during gelation, which indicates strong exciton coupling between fluorophores. Both wet gel and xerogel emit strong green fluorescence because the cyano group suppresses fluorescence quenching in the self-assemblies. Moreover, the xerogel film with strong green fluorescence can be used as a dual chemosensor for quantitative detection of volatile acid and organic amine vapors with fast response times and low detection limits owing to its large surface area and amplified fluorescence quenching. The detection limits are 796 ppt and 25 ppb for gaseous aniline and trifluoroacetic acid (TFA), respectively. PMID:26449736

  13. Impact of gluconic fermentation of strawberry using acetic acid bacteria on amino acids and biogenic amines profile.

    PubMed

    Ordóñez, J L; Sainz, F; Callejón, R M; Troncoso, A M; Torija, M J; García-Parrilla, M C

    2015-07-01

    This paper studies the amino acid profile of beverages obtained through the fermentation of strawberry purée by a surface culture using three strains belonging to different acetic acid bacteria species (one of Gluconobacter japonicus, one of Gluconobacter oxydans and one of Acetobacter malorum). An HPLC-UV method involving diethyl ethoxymethylenemalonate (DEEMM) was adapted and validated. From the entire set of 21 amino acids, multiple linear regressions showed that glutamine, alanine, arginine, tryptophan, GABA and proline were significantly related to the fermentation process. Furthermore, linear discriminant analysis classified 100% of the samples correctly in accordance with the microorganism involved. G. japonicus consumed glucose most quickly and achieved the greatest decrease in amino acid concentration. None of the 8 biogenic amines were detected in the final products, which could serve as a safety guarantee for these strawberry gluconic fermentation beverages, in this regard. PMID:25704705

  14. 11-Keto-boswellic acid derived amides and monodesmosidic saponins induce apoptosis in breast and cervical cancers cells.

    PubMed

    Csuk, René; Barthel-Niesen, Anja; Barthel, Alexander; Schäfer, Renate; Al-Harrasi, Ahmed

    2015-07-15

    Beta-boswellic acids are considered the main bioactive components of frankincense. Their potential to act as cytotoxic agents, as well as that of their derivatives remained unexploited so far. In this study we were able to prepare derivatives of 11-keto-β-boswellic acid (KBA) that showed lower IC50 values as determined by a sulphorhodamine B (SRB) assay using several different human tumour cell lines. Monodesmosidic saponins of KBA are as cytotoxic as 3-acetyl-KBA. The presence of a free hydroxyl group at position C-3 seems to lower cytotoxicity while the presence of an amide function at C-24 improves cytotoxicity. The most active compound of this series gave IC50 values as low as 4.5 μM. Cell death proceeded mainly via apoptosis. PMID:26073487

  15. CATABOLISM OF AROMATIC BIOGENIC AMINES BY 'PSEUDOMONAS AERUGINOSA' PA01 VIA META CLEAVAGE OF HOMOPROTOCATECHUIC ACID (JOURNAL VERSION)

    EPA Science Inventory

    Pseudomonas aruginosa PA01 catabolized the aromatic amines tyramine and octopamine through 4-hydroxyphenylacetic acid and 3,4-dihydroxyphenylacetic acid (HPA). Meta ring cleavage was mediated by 3-4-dihydroxyphenylacetate 2,3-dioxygenase (HPADO), producing 2-hydroxy-5-carboxymeth...

  16. PROCESS FOR EXTRACTING NEPTUNIUM AND PLUTONIUM FROM NITRIC ACID SOLUTIONS OF SAME CONTAINING URANYL NITRATE WITH A TERTIARY AMINE

    DOEpatents

    Sheppard, J.C.

    1962-07-31

    A process of selectively extracting plutonium nitrate and neptunium nitrate with an organic solution of a tertiary amine, away from uranyl nitrate present in an aqueous solution in a maximum concentration of 1M is described. The nitric acid concentration is adjusted to about 4M and nitrous acid is added prior to extraction. (AEC)

  17. The Elusive Metal-Free Primary Amination of Arylboronic Acids: Synthetic Studies and Mechanism by Density Functional Theory

    PubMed Central

    Zhu, Chen; Li, Gongqiang; Ess, Daniel H.; Falck, John R.; Kürti, László

    2012-01-01

    Herein, we disclose the first metal-free synthesis of primary aromatic amines from arylboronic acids, a reaction that has eluded synthetic chemists for decades. This remarkable transformation affords structurally diverse primary arylamines in good chemical yields, including a variety of halogenated primary anilines that often cannot be prepared via transition metal-catalyzed amination. The reaction is operationally simple, requires only a slight excess of aminating agent, proceeds under neutral or basic conditions and, importantly, it can be scaled up to provide multigram quantities of primary anilines. Density functional calculations reveal that the most likely mechanism involves a facile 1,2-aryl migration and that the presence of an ortho nitro group in the aminating agent plays a critical role in lowering the free energy barrier of the 1,2-aryl migration step. PMID:23082853

  18. Direct Catalytic Chemoselective α-Amination of Acylpyrazoles: A Concise Route to Unnatural α-Amino Acid Derivatives.

    PubMed

    Tokumasu, Keisuke; Yazaki, Ryo; Ohshima, Takashi

    2016-03-01

    A direct copper-catalyzed highly chemoselective α-amination is described. Acylpyrazole proved to be a highly efficient enolate precursor of a carboxylic acid oxidation state substrate, while preactivation by a stoichiometric amount of strong base has been used in catalytic α-aminations. The simultaneous activation of both coupling partners, enolization and metal nitrenoid formation, was crucial for obtaining the product, and wide functional group compatibility highlighted the mildness of the present catalysis. The bidentate coordination mode was amenable to highly chemoselective activation over ketone and much more acidic nitroalkyl functionality. Deuterium exchange experiments clearly demonstrated that exclusive enolization of acylpyrazole was achieved without the formation of a nitronate. The present catalysis was applied to late-stage α-amination, allowing for concise access to highly versatile α-amino acid derivatives. The product could be transformed into variety of useful building blocks. PMID:26859788

  19. Intracellular Self-Assembly of Cyclic d-Luciferin Nanoparticles for Persistent Bioluminescence Imaging of Fatty Acid Amide Hydrolase.

    PubMed

    Yuan, Yue; Wang, Fuqiang; Tang, Wei; Ding, Zhanling; Wang, Lin; Liang, Lili; Zheng, Zhen; Zhang, Huafeng; Liang, Gaolin

    2016-07-26

    Fatty acid amide hydrolase (FAAH) overexpression induces several disorder symptoms in nerve systems, and therefore long-term tracing of FAAH activity in vivo is of high importance but remains challenging. Current bioluminescence (BL) methods are limited in detecting FAAH activity within 5 h. Herein, by rational design of a latent BL probe (d-Cys-Lys-CBT)2 (1), we developed a "smart" method of intracellular reduction-controlled self-assembly and FAAH-directed disassembly of its cyclic d-luciferin-based nanoparticles (i.e., 1-NPs) for persistent BL imaging of FAAH activity in vitro, in cells, and in vivo. Using aminoluciferin methyl amide (AMA), Lys-amino-d-luciferin (Lys-Luc), and amino-d-luciferin (NH2-Luc) as control BL probes, we validated that the persistent BL of 1 from luciferase-expressing cells or tumors was controlled by the activity of intracellular FAAH. With the property of long-term tracing of FAAH activity in vivo of 1, we envision that our BL precursor 1 could probably be applied for in vivo screening of FAAH inhibitors and the diagnosis of their related diseases (or disorders) in the future. PMID:27348334

  20. Fatty acid amide hydrolase as a potential therapeutic target for the treatment of pain and CNS disorders

    PubMed Central

    Ahn, Kay; Johnson, Douglas S.; Cravatt, Benjamin F.

    2009-01-01

    Background Fatty acid amide hydrolase (FAAH) is an integral membrane enzyme that hydrolyzes the endocannabinoid anandamide and related amidated signaling lipids. Genetic or pharmacological inactivation of FAAH produces analgesic, anti-inflammatory, anxiolytic, and antidepressant phenotypes without showing the undesirable side effects of direct cannabinoid receptor agonists, indicating that FAAH may be a promising therapeutic target. Objectives This review highlights advances in the development of FAAH inhibitors of different mechanistic classes and their in vivo efficacy. Also highlighted are advances in technology for the in vitro and in vivo selectivity assessment of FAAH inhibitors employing activity-based protein profiling (ABPP) and click chemistry-ABPP, respectively. Recent reports on structure-based drug design for human FAAH generated by protein engineering using interspecies active site conversion are also discussed. Methods: The literature searches of Medline and SciFinder databases were used. Conclusions There has been tremendous progress in our understanding in FAAH and development of FAAH inhibitors with in vivo efficacy, selectivity, and drug like pharmacokinetic properties. PMID:20544003

  1. Carbohydrate-interactive pDNA and siRNA gene vectors based on boronic acid functionalized poly(amido amine)s.

    PubMed

    Piest, Martin; Ankoné, Marc; Engbersen, Johan F J

    2013-08-10

    In order to evaluate the influence of incorporation of boronic acid groups on the properties of poly(amido amine)s as gene vectors, a novel poly(amido amine) copolymer p(CBA-ABOL/2AMPBA) containing ortho-aminomethylphenylboronic acid (2AMPBA) moieties was prepared by Michael-type polyaddition of a mixture of 1,4-aminobutanol (ABOL) and 2-((4-aminobutylamino)methyl)phenyl boronic acid to N,N'-cystamine bisacrylamide (CBA). It appeared that the presence of the boronic acid moieties as side groups along the polymer chain strongly enhances the stability of the self-assembled nanoparticles and nanosized polyplexes formed from this polymer; no aggregation was observed after storage for 6days at 37°C. This strong stabilization can be attributed to intermolecular Lewis acid-base interactions between the 2AMPBA groups and the alcohol and amine groups present in the polymer, leading to dynamical (reversible) crosslinking in the nanoparticles. Moreover, since the boronic acids can reversibly form boronic esters with vicinal diol groups, the presence of the 2AMPBA groups add carbohydrate-interactive properties to these polymers that strongly influence their behavior as gene delivery vectors. DNA transfection with p(CBA-ABOL/2AMPBA) polyplexes gave transfection efficiencies that were approximately similar to commercial PEI in different cell lines (COS-7, HUH-6 and H1299-Fluc), but lower than those obtained with reference polyplexes from p(CBA-ABOL). It is hypothesized that the uptake of the boronated polyplexes is suppressed by binding to the glycocalyx of the cells. This is supported by the observation that addition of sorbitol or dextran to the transfection medium significantly enhances the transfection efficiency, which can be attributed to increased cellular uptake of the polyplexes due to boronic ester formation with these agents. AFM, SEM and confocal microscopy showed that polyplexes of p(CBA-ABOL/2AMPBA) become decorated with a dextran layer in the presence of 0.9% (w

  2. Cooling rate effects on the microstructure, solid content, and rheological properties of organogels of amides derived from stearic and (R)-12-hydroxystearic acid in vegetable oil.

    PubMed

    Toro-Vazquez, Jorge F; Morales-Rueda, Juan; Torres-Martínez, Adriana; Charó-Alonso, Miriam A; Mallia, V Ajay; Weiss, Richard G

    2013-06-25

    Using safflower oil as the liquid phase, we investigated the organogelation properties of stearic acid (SA), (R)-12-hydroxystearic acid (HSA), and different primary and secondary amides synthesized from SA and HSA. The objective was to establish the relationship between the gelator's molecular structure, solid content, and gels' microstructure that determines the rheological properties of organogels developed at two cooling rates, 1 and 20 °C/min. The results showed that the presence of a 12-OH group in the gelator molecule makes its crystallization kinetics cooling rate dependent and modifies its crystallization behavior. Thus, SA crystallizes as large platelets, while HSA crystallizes as fibers forming gels with higher solid content, particularly at 20 °C/min. The addition to HSA of a primary or a secondary amide bonded with an alkyl group resulted in gelator molecules that crystallized as fibrillar spherulites at both cooling rates. Independent of the cooling rate, gels of HSA and its amide derivatives showed thixotropic behavior. The rheological properties of the amide's organogels depend on a balance between hydrogen-bonding sites and the alkyl chain length bonded to the amide group. However, it might also be associated with the effect that the gelators' molecular weight has on crystal growth and its consequence on fiber interpenetration among vicinal spherulites. These results were compared with those obtained with candelilla wax (CW), a well-known edible gelling additive used by the food industry. CW organogels had higher elasticity than HSA gels but lower than the gels formed by amides. Additionally, CW gels showed similar or even higher thixotropic behavior than HSA and the amide's gels. These remarkable rheological properties resulted from the microstructural organization of CW organogels. We concluded that microstructure has a more important role determining the organogels' rheology than the solid content. The fitting models developed to describe the

  3. Structure of six organic acid-base adducts from 6-bromobenzo[d]thiazol-2-amine and acidic compounds

    NASA Astrophysics Data System (ADS)

    Jin, Shouwen; Zhang, Jing; Wang, Daqi; Tao, Lin; Zhou, Mengjian; Shen, Yinyan; Chen, Quan; Lin, Zhanghui; Gao, Xingjun

    2014-05-01

    Six anhydrous organic acid-base adducts of 6-bromobenzo[d]thiazol-2-amine were prepared with organic acids as 2,4,6-trinitrophenol, salicylic acid, 3,5-dinitrobenzoic acid, 3,5-dinitrosalicylic acid, malonic acid and sebacic acid. The compounds 1-6 were characterized by X-ray diffraction analysis, IR, and elemental analysis. The melting points of all the adducts were given. Of the six adducts, 1, 3, 4, and 5 are organic salts, while 2, and 6 are cocrystals. The supramolecular arrangement in the crystals 2-6 is based on the R22(8) synthon. Analysis of the crystal packing of 1-6 suggests that there are strong NH⋯O, OH⋯N, and OH⋯O hydrogen bonds (charge assisted or neutral) between acid and base components in the supramolecular assemblies. When the hydroxyl group is present in the ortho position of the carboxy, the intramolecular S6 synthon is present, as expected. Besides the classical hydrogen bonding interactions, other noncovalent interactions also play important roles in structure extension. Due to the synergetic effect of these weak interactions, compounds 1-6 display 1D-3D framework structure.

  4. Synthesis and Structure-Activity Relationships of N-Dihydrocoptisine-8-ylidene Aromatic Amines and N-Dihydrocoptisine-8-ylidene Aliphatic Amides as Antiulcerative Colitis Agents Targeting XBP1.

    PubMed

    Xie, Meng; Zhang, Hai-Jing; Deng, An-Jun; Wu, Lian-Qiu; Zhang, Zhi-Hui; Li, Zhi-Hong; Wang, Wen-Jie; Qin, Hai-Lin

    2016-04-22

    In this study, natural quaternary coptisine was used as a lead compound to design and synthesize structurally stable and actively potent coptisine analogues. Of the synthesized library, 13 N-dihydrocoptisine-8-ylidene amines/amides were found not only to be noncytotoxic toward intestinal epithelial cells (IECs), but they were also able to activate the transcription of X-box-binding protein 1 (XBP1) targets to varying extents in vitro. Antiulcerative colitis (UC) activity levels were assessed at the in vitro molecular level as well as in vivo in animals using multiple biomarkers as indices. In an in vitro XBP1 transcriptional activity assay, four compounds demonstrated good dose-effect relationships with EC50 values of 0.0708-0.0132 μM. Moreover, two compounds were confirmed to be more potent in vivo than a positive control, demonstrating a curative effect for UC in experimental animals. Thus, the findings of this study suggest that these coptisine analogues are promising candidates for the development of anti-UC drugs. PMID:26981782

  5. Novel endogenous N-acyl amides activate TRPV1-4 receptors, BV-2 microglia, and are regulated in brain in an acute model of inflammation

    PubMed Central

    Raboune, Siham; Stuart, Jordyn M.; Leishman, Emma; Takacs, Sara M.; Rhodes, Brandon; Basnet, Arjun; Jameyfield, Evan; McHugh, Douglas; Widlanski, Theodore; Bradshaw, Heather B.

    2014-01-01

    A family of endogenous lipids, structurally analogous to the endogenous cannabinoid, N-arachidonoyl ethanolamine (Anandamide), and called N-acyl amides have emerged as a family of biologically active compounds at TRP receptors. N-acyl amides are constructed from an acyl group and an amine via an amide bond. This same structure can be modified by changing either the fatty acid or the amide to form potentially hundreds of lipids. More than 70 N-acyl amides have been identified in nature. We have ongoing studies aimed at isolating and characterizing additional members of the family of N-acyl amides in both central and peripheral tissues in mammalian systems. Here, using a unique in-house library of over 70 N-acyl amides we tested the following three hypotheses: (1) Additional N-acyl amides will have activity at TRPV1-4, (2) Acute peripheral injury will drive changes in CNS levels of N-acyl amides, and (3) N-acyl amides will regulate calcium in CNS-derived microglia. Through these studies, we have identified 20 novel N-acyl amides that collectively activate (stimulating or inhibiting) TRPV1-4. Using lipid extraction and HPLC coupled to tandem mass spectrometry we showed that levels of at least 10 of these N-acyl amides that activate TRPVs are regulated in brain after intraplantar carrageenan injection. We then screened the BV2 microglial cell line for activity with this N-acyl amide library and found overlap with TRPV receptor activity as well as additional activators of calcium mobilization from these lipids. Together these data provide new insight into the family of N-acyl amides and their roles as signaling molecules at ion channels, in microglia, and in the brain in the context of inflammation. PMID:25136293

  6. A Double Whammy: Targeting Both Fatty Acid Amide Hydrolase (FAAH) and Cyclooxygenase (COX) To Treat Pain and Inflammation.

    PubMed

    Scarpelli, Rita; Sasso, Oscar; Piomelli, Daniele

    2016-06-20

    Pain states that arise from non-resolving inflammation, such as inflammatory bowel disease or arthritis, pose an unusually difficult challenge for therapy because of the complexity and heterogeneity of their underlying mechanisms. It has been suggested that key nodes linking interactive pathogenic pathways of non-resolving inflammation might offer novel targets for the treatment of inflammatory pain. Nonsteroidal anti-inflammatory drugs (NSAIDs), which inhibit the cyclooxygenase (COX)-mediated production of pain- and inflammation-inducing prostanoids, are a common first-line treatment for this condition, but their use is limited by mechanism-based side effects. The endogenous levels of anandamide, an endocannabinoid mediator with analgesic and tissue-protective functions, are regulated by fatty acid amide hydrolase (FAAH). This review outlines the pharmacological and chemical rationale for the simultaneous inhibition of COX and FAAH activities with designed multitarget agents. Preclinical studies indicate that such agents may combine superior anti-inflammatory efficacy with reduced toxicity. PMID:26486424

  7. A nonsynonymous polymorphism in the human fatty acid amide hydrolase gene did not associate with either methamphetamine dependence or schizophrenia.

    PubMed

    Morita, Yukitaka; Ujike, Hiroshi; Tanaka, Yuji; Uchida, Naohiko; Nomura, Akira; Ohtani, Kyohei; Kishimoto, Makiko; Morio, Akiko; Imamura, Takaki; Sakai, Ayumu; Inada, Toshiya; Harano, Mutsuo; Komiyama, Tokutaro; Yamada, Mitsuhiko; Sekine, Yoshimoto; Iwata, Nakao; Iyo, Masaomi; Sora, Ichiro; Ozaki, Norio; Kuroda, Shigetoshi

    2005-03-16

    Genetic contributions to the etiology of substance abuse and dependence are topics of major interest. Acute and chronic cannabis use can produce drug-induced psychosis resembling schizophrenia and worsen positive symptoms of schizophrenia. The endocannabinoid system is one of the most important neural signaling pathways implicated in substance abuse and dependence. The fatty acid amide hydrolase (FAAH) is a primary catabolic enzyme of endocannabinoids. To clarify a possible involvement of FAAH in the etiology of methamphetamine dependence/psychosis or schizophrenia, we examined the genetic association of a nonsynonymous polymorphism of the FAAH gene (Pro129Thr) by a case-control study. We found no significant association in allele and genotype frequencies of the polymorphism with either disorder. Because the Pro129Thr polymorphism reduces enzyme instability, it is unlikely that dysfunction of FAAH and enhanced endocannabinoid system induce susceptibility to either methamphetamine dependence/psychosis or schizophrenia. PMID:15721218

  8. Toward Fluorescence-Based High-Throughput Screening for Enantiomeric Excess in Amines and Amino Acid Derivatives.

    PubMed

    Shcherbakova, Elena G; Brega, Valentina; Minami, Tsuyoshi; Sheykhi, Sara; James, Tony D; Anzenbacher, Pavel

    2016-07-11

    A highly accurate and reliable screening method for enantiomeric excess of amine derivatives in the presence of water is reported. The fluorescence-based screening system has been realized by self-assembly of chiral diol-type dyes (BINOL, VANOL and VAPOL), 2-formylphenylboronic acid, and chiral amines forming iminoboronate esters. The structure and chirality of the amine analytes determine the stability of the diastereomeric iminoboronate esters, which in turn display differential fluorescence. The fluorescence signal reflects the enantiomeric purity of the chiral amines and was utilized in high-throughput arrays. The arrays were able to recognize enantiomeric excess of amines, amino esters, and amino alcohols. In addition to qualitative analysis, quantitative experiments were successfully performed. Studies of the role of additives such as water or citrate were carried out to gain insight into the stability of the iminoboronate esters. It is shown that the above additives destabilize less stable esters while the stable esters remain unchanged. Thus, the presence of water and citrate leads to increased difference between the diastereomeric iminoboronates and contributes to the enantiodiscrimination of the chiral amines. PMID:27271215

  9. Contamination monitoring for ammonia, amines, and acid gases utilizing ion mobility spectroscopy (IMS)

    NASA Astrophysics Data System (ADS)

    Bacon, Tad; Webber, Kurt; Carpio, Ronald A.

    1998-06-01

    The effect of ammonia (NH3) and n-methyl pyrrolidinone (NMP) contamination on chemically amplified DUV resists is well documented. Other amines and related compounds are under suspicion as well. In addition, the concentration levels that are of concern have steadily decreased from approximately 10 ppbv down to levels as low as 0.1 ppbv. While some techniques such as ion chromotagraphy (IC) have been demonstrated to have limits of detection at these levels, the analysis times are rather long and cumbersome. This paper describes the use of IMS to perform these measurements, in a totally automated, continuous instrument. IMS is a simplified time-of-flight technique that requires no liquid reagents and has been demonstrated to be a reliable method for monitoring for ammonia and NMP in cleanrooms. This paper demonstrates the ability of the technique to monitor for amines such as dimethylamine, methylamine, methanolamine, ethanolamine, diethanolamine, butylamine and others. Detection limits of 0.1 ppbv and below are clearly demonstrated. Also discussed are methods of monitoring multiple points with a single analyzer. Ability to detect corrosive gases such as hydrogen fluoride (HF), hydrogen chloride (HCl), sulfur dioxide (SO2), sulfur trioxide (SO3), nitrogen dioxide (NO2), chlorine (Cl2), bromine (Br2), phosphoric acid (H3PO4) are also demonstrated.

  10. A near infrared colorimetric and fluorometric probe for organophosphorus nerve agent mimics by intramolecular amidation.

    PubMed

    Hu, Xiao-Xiao; Su, Yue-Ting; Ma, Yun-Wei; Zhan, Xin-Qi; Zheng, Hong; Jiang, Yun-Bao

    2015-10-21

    A near infrared probe for sensitive colorimetric and fluorimetric detection of nerve agent mimics, DCP and DCNP, was reported based on the activation of a carboxylic acid group by the mimics to conduct an intramolecular amidation reaction in the heptamethine chromophore, where its absorption or excitation maximum wavelength could be greatly red-shifted by attenuating the electron-donating ability of the amine group in the bridgehead site of heptamethine cyanine. PMID:26323249

  11. Polyphosphate Hydrolysis within Acidic Vacuoles in Response to Amine-Induced Alkaline Stress in the Halotolerant Alga Dunaliella salina

    PubMed Central

    Pick, Uri; Weiss, Meira

    1991-01-01

    The location and mobilization of polyphosphates in response to an amine-induced alkaline stress were studied in the halotolerant alga Dunaliella salina. The following observations suggest that polyphosphates accumulate in acidic vacuoles: (a) Accumulation of large amounts of polyphosphates is manifested as intravacuolar dense osmiophilic bodies in electron micrographs. (b) Uptake of amines into the vacuoles induces massive hydrolysis of polyphosphates, demonstrated by in vivo 31P-nuclear magnetic resonance, and by analysis of hydrolytic products on thin layer chromatograms. The analysis indicates that: (a) Polyphosphate hydrolysis is kinetically correlated with amine accumulation and with the recovery of cytoplasmic pH. (b) The major hydrolytic product is tripolyphosphate. (c) The peak position of the tripolyphosphate terminal phosphate in nuclear magnetic resonance spectra is progressively shifted as the cells recover, indicating that the pH inside the vacuoles increases while the pH in the cytoplasm decreases. (d) In lysed cell preparations, in which vacuoles become exposed to the external pH, mild alkalinization in the absence of amines induces polyphosphate hydrolysis to tripolyphosphates. It is suggested that amine accumulation within vacuoles activates a specific phosphatase, which hydrolyzes long-chain polyphosphates to tripolyphosphates. The hydrolysis increases the capacity of the vacuoles to sequester amines from the cytoplasm probably by releasing protons required to buffer the amine, and leads to recovery of cytoplasmic pH. Thus, polyphosphate hydrolysis provides a high-capacity buffering system that sustains amine compartmentation into vacuoles and protects cytoplasmic pH. ImagesFigure 1Figure 7 PMID:16668514

  12. Using spin labels to study molecular processes in soils: Covalent binding of aromatic amines to humic acids of soils

    NASA Astrophysics Data System (ADS)

    Aleksandrova, O. N.; Kholodov, V. A.; Perminova, I. V.

    2015-08-01

    Interactions of aliphatic and aromatic amines with soil and humic acids isolated from it are studied by means of spin labels and electron paramagnetic resonance (EPR) spectroscopy. Nitroxyl radicals containing amino groups are used as spin labels. It is found experimentally that aromatic amines are instantaneously converted to the bound state. It is shown that the microareas of their incorporation are characterized by a significant delay in the reduction of the nitroxyl fragment of spin-label molecules, indicating the formation of condensed structures typical of an oxidative binding mechanism. It is concluded that aliphatic amines do not bind to humic acids. It is noted that the studied process allows elucidating the formation of bound xenobiotic residues in soils.

  13. 15N NMR investigation of the covalent binding of reduced TNT amines to soil humic acid, model compounds, and lignocellulose.

    PubMed

    Thorn, K A; Kennedy, K R

    2002-09-01

    The five major reductive degradation products of TNT-4ADNT (4-amino-2,6-dinitrotoluene), 2ADNT (2-amino-4,6-dinitrotoluene), 2,4DANT (2,4-diamino-6-nitrotoluene), 2,6DANT (2,6-diamino-4-nitrotoluene), and TAT (2,4,6-triaminotoluene)-labeled with 15N in the amine positions, were reacted with the IHSS soil humic acid and analyzed by 15N NMR spectrometry. In the absence of catalysts, all five amines underwent nucleophilic addition reactions with quinone and other carbonyl groups in the soil humic acid to form both heterocyclic and nonheterocyclic condensation products. Imine formation via 1,2-addition of the amines to quinone groups in the soil humic acid was significant with the diamines and TAT but not the monoamines. Horseradish peroxidase (HRP) catalyzed an increase in the incorporation of all five amines into the humic acid. In the case of the diamines and TAT, HRP also shifted the binding away from heterocyclic condensation product toward imine formation. A comparison of quantitative liquid phase with solid-state CP/MAS 15N NMR indicated that the CP experiment underestimated imine and heterocyclic nitrogens in humic acid, even with contact times optimal for observation of these nitrogens. Covalent binding of the mono- and diamines to 4-methylcatechol, the HRP catalyzed condensation of 4ADNT and 2,4DANT to coniferyl alcohol, and the binding of 2,4DANT to lignocellulose with and without birnessite were also examined. PMID:12322752

  14. 15N NMR investigation of the covalent binding of reduced TNT amines to soil humic acid, model compounds, and lignocellulose

    USGS Publications Warehouse

    Thorn, K.A.; Kennedy, K.R.

    2002-01-01

    The five major reductive degradation products of TNT-4ADNT (4-amino-2,6-dinitrotoluene), 2ADNT (2-amino-4,6-dinitrotoluene), 2,4DANT (2,4-diamino-6-nitrotoluene), 2,6DANT (2,6-diamino-4-nitrotoluene), and TAT (2,4,6-triaminotoluene)-labeled with 15N in the amine positions, were reacted with the IHSS soil humic acid and analyzed by 15N NMR spectrometry. In the absence of catalysts, all five amines underwent nucleophilic addition reactions with quinone and other carbonyl groups in the soil humic acid to form both heterocyclic and nonheterocyclic condensation products. Imine formation via 1,2-addition of the amines to quinone groups in the soil humic acid was significant with the diamines and TAT but not the monoamines. Horseradish peroxidase (HRP) catalyzed an increase in the incorporation of all five amines into the humic acid. In the case of the diamines and TAT, HRP also shifted the binding away from heterocyclic condensation product toward imine formation. A comparison of quantitative liquid phase with solid-state CP/MAS 15N NMR indicated that the CP experiment underestimated imine and heterocyclic nitrogens in humic acid, even with contact times optimal for observation of these nitrogens. Covalent binding of the mono- and diamines to 4-methylcatechol, the HRP catalyzed condensation of 4ADNT and 2,4DANT to coniferyl alcohol, and the binding of 2,4DANT to lignocellulose with and without birnessite were also examined.

  15. Amine-modified hyaluronic acid-functionalized porous silicon nanoparticles for targeting breast cancer tumors

    NASA Astrophysics Data System (ADS)

    Almeida, Patrick V.; Shahbazi, Mohammad-Ali; Mäkilä, Ermei; Kaasalainen, Martti; Salonen, Jarno; Hirvonen, Jouni; Santos, Hélder A.

    2014-08-01

    Active targeting of nanoparticles to receptor-overexpressing cancer cells has great potential for enhancing the cellular uptake of nanoparticles and for reducing fast clearance of the nanoparticles from the body. Herein, we present a preparation method of a porous silicon (PSi)-based nanodelivery system for breast cancer targeting, by covalently conjugating a synthesized amide-modified hyaluronic acid (HA+) derived polymer on the surface of undecylenic acid-modified thermally hydrocarbonized PSi (UnTHCPSi) nanoparticles. The resulting UnTHCPSi-HA+ nanoparticles showed relatively small size, reduced polydispersibility, high biocompatibility, improved colloidal and human plasma stability, as well as enhanced cellular interactions and internalization. Moreover, we demonstrated that the enhanced cellular association of UnTHCPSi-HA+ relies on the capability of the conjugated HA+ to bind and consequently target CD44 receptors expressed on the surface of breast cancer cells, thus making the HA+-functionalized UnTHCPSi nanoparticles a suitable and promising nanoplatform for the targeting of CD44-overexpressing breast tumors and for drug delivery.Active targeting of nanoparticles to receptor-overexpressing cancer cells has great potential for enhancing the cellular uptake of nanoparticles and for reducing fast clearance of the nanoparticles from the body. Herein, we present a preparation method of a porous silicon (PSi)-based nanodelivery system for breast cancer targeting, by covalently conjugating a synthesized amide-modified hyaluronic acid (HA+) derived polymer on the surface of undecylenic acid-modified thermally hydrocarbonized PSi (UnTHCPSi) nanoparticles. The resulting UnTHCPSi-HA+ nanoparticles showed relatively small size, reduced polydispersibility, high biocompatibility, improved colloidal and human plasma stability, as well as enhanced cellular interactions and internalization. Moreover, we demonstrated that the enhanced cellular association of Un

  16. Synthesis and QSAR of Fatty Acid Amide Hydrolase Inhibitors: Modulation at the N-Portion of Biphenyl-3-yl Alkylcarbamates

    PubMed Central

    Mor, Marco; Lodola, Alessio; Rivara, Silvia; Vacondio, Federica; Duranti, Andrea; Tontini, Andrea; Sanchini, Silvano; Piersanti, Giovanni; Clapper, Jason R.; King, Alvin R.; Tarzia, Giorgio; Piomelli, Daniele

    2013-01-01

    Alkylcarbamic acid biphenyl-3-yl esters are a class of fatty acid amide hydrolase (FAAH) inhibitors that comprises cyclohexylcarbamic acid 3′-carbamoylbiphenyl-3-yl ester (URB597), a compound with analgesic, anxiolytic-like and antidepressant-like properties in rat and mouse models. Here, we extended the structure-activity relationships (SARs) for this class of compounds by replacing the cyclohexyl ring of the parent compound cyclohexylcarbamic acid biphenyl-3-yl ester (URB524) (IC50, for FAAH = 63 nM) with a selected set of substituents of different size, shape, flexibility and lipophilicity. Docking experiments and Linear Interaction Energy (LIE) calculations indicated that the N-terminal group of O-arylcarbamates fits within the lipophilic region of the substrate-binding site, mimicking the arachidonoyl chain of anandamide. Significant potency improvements were observed for the β-naphthylmethyl derivative 4q (IC50 = 5.3 nM) and its 3′-carbamoylbiphenyl-3-yl ester 4z (URB880, IC50 = 0.63 nM), indicating that shape complementarity and hydrogen bonds are crucial to obtain highly potent inhibitors. PMID:18507372

  17. An azobenzene-containing metal-organic framework as an efficient heterogeneous catalyst for direct amidation of benzoic acids: synthesis of bioactive compounds.

    PubMed

    Hoang, Linh T M; Ngo, Long H; Nguyen, Ha L; Nguyen, Hanh T H; Nguyen, Chung K; Nguyen, Binh T; Ton, Quang T; Nguyen, Hong K D; Cordova, Kyle E; Truong, Thanh

    2015-12-14

    An azobenzene-containing zirconium metal-organic framework was demonstrated to be an effective heterogeneous catalyst for the direct amidation of benzoic acids in tetrahydrofuran at 70 °C. This finding was applied to the synthesis of several important, representative bioactive compounds. PMID:26455380

  18. Organocatalytic enantioselective decarboxylative reaction of malonic acid half thioesters with cyclic N-sulfonyl ketimines by using N-heteroarenesulfonyl cinchona alkaloid amides.

    PubMed

    Nakamura, Shuichi; Sano, Masahide; Toda, Ayaka; Nakane, Daisuke; Masuda, Hideki

    2015-03-01

    The organocatalytic enantioselective decarboxylative Mannich reaction of malonic acid half thioesters (MAHTs) with cyclic N-sulfonyl ketimines by using N-heteroarenesulfonyl cinchona alkaloid amides afforded products with high enantioselectivity. Both enantiomers of the products could be obtained by using pseudoenantiomeric chiral catalysts. The reaction proceeds through a nucleophilic addition of the MAHTs to the ketimines prior to decarboxylation. PMID:25614368

  19. 40 CFR 721.10570 - Cyclic amine reaction product with acetophenone and formaldehyde acid salt (generic).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... SUBSTANCES Significant New Uses for Specific Chemical Substances § 721.10570 Cyclic amine reaction product... subject to reporting. (1) The chemical substance identified generically as cyclic amine reaction product... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Cyclic amine reaction product...

  20. 40 CFR 721.10570 - Cyclic amine reaction product with acetophenone and formaldehyde acid salt (generic).

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... SUBSTANCES Significant New Uses for Specific Chemical Substances § 721.10570 Cyclic amine reaction product... subject to reporting. (1) The chemical substance identified generically as cyclic amine reaction product... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Cyclic amine reaction product...

  1. Amidation inhibitors 4-phenyl-3-butenoic acid and 5-(acetylamino)-4-oxo-6-phenyl-2-hexenoic acid methyl ester are novel HDAC inhibitors with anti-tumorigenic properties.

    PubMed

    Ali, Amna; Burns, Timothy J; Lucrezi, Jacob D; May, Sheldon W; Green, George R; Matesic, Diane F

    2015-08-01

    4-Phenyl-3-butenoic acid (PBA) is an inhibitor of peptidylglycine alpha-amidating monooxygenase with anti-inflammatory properties that has been shown to inhibit the growth of ras-mutated epithelial and human lung carcinoma cells. In this report, we show that PBA also increases the acetylation levels of selected histone subtypes in a dose and time dependent manner, an effect that is attributable to the inhibition of histone deacetylase (HDAC) enzymes. Comparison studies with the known HDAC inhibitor suberoylanilide hydroxamic acid (SAHA) using high resolution two-dimensional polyacrylamide gels and Western analysis provide evidence that PBA acts as an HDAC inhibitor within cells. PBA and a more potent amidation inhibitor, 5-(acetylamino)-4-oxo-6-phenyl-2-hexenoic acid methyl ester (AOPHA-Me), inhibit HDAC enzymes in vitro at micromolar concentrations, with IC50 values approximately 30 fold lower for AOPHA-Me than PBA for selected HDAC isoforms. Overall, these results indicate that PBA and AOPHA-Me are novel anti-tumorigenic HDAC inhibitors. PMID:26065689

  2. Catalyst-Free Three-Component Tandem CDC Cyclization: Convenient Access to Isoindolinones from Aromatic Acid, Amides, and DMSO by a Pummerer-Type Rearrangement.

    PubMed

    Wang, Peng-Min; Pu, Fan; Liu, Ke-Yan; Li, Chao-Jun; Liu, Zhong-Wen; Shi, Xian-Ying; Fan, Juan; Yang, Ming-Yu; Wei, Jun-Fa

    2016-04-25

    A catalyst-free multicomponent CDC reaction is rarely reported, especially for the intermolecular tandem CDC cyclization, which represents an important strategy for constructing cyclic compounds. Herein, a three-component tandem CDC cyclization by a Pummerer-type rearrangement to afford biologically relevant isoindolinones from aromatic acids, amides, and DMSO, is described. This intermolecular tandem reaction undergoes a C(sp(2) )-H/C(sp(3) )-H cross-dehydrogenative coupling, C-N bond formation, and intramolecular amidation. A notable feature of this novel protocol is avoiding a catalyst and additive (apart from oxidant). PMID:26998754

  3. Grey relational analysis of amine inhibition of mild steel corrosion in acids

    SciTech Connect

    Li, P.; Tan, T.C.; Lee, J.Y.

    1997-03-01

    Grey relational analysis makes use of relatively simple mathematical procedures to arrive at salient relationships in a complex system. It uses a relatively small amount of data and works with great variability in factors. Grey relational analysis was used to investigate the relationship between inhibitor structure and inhibitor performance for a series of amines of different structures in the corrosion of mild steel in acids. Results showed the molecular weight (MW), the negative of the logarithm of the dissociation constant (pK{sub a}), and the number of nitrogen donor atoms influenced inhibitor effectiveness in the active region. The number of NH bonds was an additional factor for inhibition in the passive region. Trends in these factors were rationalized in terms of adsorptive interactions between the inhibitor molecules and the substrate. Results conformed to findings in the literature and were verified by additional measurements using hexamine as the inhibitor.

  4. Towards novel 5-HT7versus 5-HT1A receptor ligands among LCAPs with cyclic amino acid amide fragments: design, synthesis, and antidepressant properties. Part II.

    PubMed

    Canale, Vittorio; Kurczab, Rafał; Partyka, Anna; Satała, Grzegorz; Witek, Jagna; Jastrzębska-Więsek, Magdalena; Pawłowski, Maciej; Bojarski, Andrzej J; Wesołowska, Anna; Zajdel, Paweł

    2015-03-01

    A 26-membered library of novel long-chain arylpiperazines, which contained primary and tertiary amides of cyclic amino acids (proline and 1,2,3,4-tetrahydroisoquinoline-3-carboxamide) in the terminal fragment was synthesized and biologically evaluated for binding affinity for 5-HT7 and 5-HT1A receptors. Docking studies confirmed advantages of Tic-amide over Pro-amide fragment for interaction with 5-HT7 receptors. Selected compounds 32 and 28, which behaved as 5-HT7Rs antagonist and 5-HT1A partial agonist, respectively, produced antidepressant-like effects in the forced swim test in mice after acute treatment in doses of 10 mg/kg (32) and 1.25 mg/kg (28). Compound 32 reduced immobility in a manner similar to the selective 5-HT7 antagonist SB-269970. PMID:25555143

  5. Identification of the Amidotransferase AsnB1 as Being Responsible for meso-Diaminopimelic Acid Amidation in Lactobacillus plantarum Peptidoglycan ▿ †

    PubMed Central

    Bernard, Elvis; Rolain, Thomas; Courtin, Pascal; Hols, Pascal; Chapot-Chartier, Marie-Pierre

    2011-01-01

    The peptidoglycan (PG) of Lactobacillus plantarum contains amidated meso-diaminopimelic acid (mDAP). The functional role of this PG modification has never been characterized in any bacterial species, except for its impact on PG recognition by receptors of the innate immune system. In silico analysis of loci carrying PG biosynthesis genes in the L. plantarum genome revealed the colocalization of the murE gene, which encodes the ligase catalyzing the addition of mDAP to UDP-N-muramoyl-d-glutamate PG precursors, with asnB1, which encodes a putative asparagine synthase with an N-terminal amidotransferase domain. By gene disruption and complementation experiments, we showed that asnB1 is the amidotransferase involved in mDAP amidation. PG structural analysis revealed that mDAP amidation plays a key role in the control of the l,d-carboxypeptidase DacB activity. In addition, a mutant strain with a defect in mDAP amidation is strongly affected in growth and cell morphology, with filamentation and cell chaining, while a DacB-negative strain displays a phenotype very similar to that of a wild-type strain. These results suggest that mDAP amidation may play a critical role in the control of the septation process. PMID:21949063

  6. Bioactive Molecules Released in Food by Lactic Acid Bacteria: Encrypted Peptides and Biogenic Amines

    PubMed Central

    Pessione, Enrica; Cirrincione, Simona

    2016-01-01

    Lactic acid bacteria (LAB) can produce a huge amount of bioactive compounds. Since their elective habitat is food, especially dairy but also vegetal food, it is frequent to find bioactive molecules in fermented products. Sometimes these compounds can have adverse effects on human health such as biogenic amines (tyramine and histamine), causing allergies, hypertensive crises, and headache. However, some LAB products also display benefits for the consumers. In the present review article, the main nitrogen compounds produced by LAB are considered. Besides biogenic amines derived from the amino acids tyrosine, histidine, phenylalanine, lysine, ornithine, and glutamate by decarboxylation, interesting peptides can be decrypted by the proteolytic activity of LAB. LAB proteolytic system is very efficient in releasing encrypted molecules from several proteins present in different food matrices. Alpha and beta-caseins, albumin and globulin from milk and dairy products, rubisco from spinach, beta-conglycinin from soy and gluten from cereals constitute a good source of important bioactive compounds. These encrypted peptides are able to control nutrition (mineral absorption and oxidative stress protection), metabolism (blood glucose and cholesterol lowering) cardiovascular function (antithrombotic and hypotensive action), infection (microbial inhibition and immunomodulation) and gut-brain axis (opioids and anti-opioids controlling mood and food intake). Very recent results underline the role of food-encrypted peptides in protein folding (chaperone-like molecules) as well as in cell cycle and apoptosis control, suggesting new and positive aspects of fermented food, still unexplored. In this context, the detailed (transcriptomic, proteomic, and metabolomic) characterization of LAB of food interest (as starters, biocontrol agents, nutraceuticals, and probiotics) can supply a solid evidence-based science to support beneficial effects and it is a promising approach as well to obtain

  7. Bioactive Molecules Released in Food by Lactic Acid Bacteria: Encrypted Peptides and Biogenic Amines.

    PubMed

    Pessione, Enrica; Cirrincione, Simona

    2016-01-01

    Lactic acid bacteria (LAB) can produce a huge amount of bioactive compounds. Since their elective habitat is food, especially dairy but also vegetal food, it is frequent to find bioactive molecules in fermented products. Sometimes these compounds can have adverse effects on human health such as biogenic amines (tyramine and histamine), causing allergies, hypertensive crises, and headache. However, some LAB products also display benefits for the consumers. In the present review article, the main nitrogen compounds produced by LAB are considered. Besides biogenic amines derived from the amino acids tyrosine, histidine, phenylalanine, lysine, ornithine, and glutamate by decarboxylation, interesting peptides can be decrypted by the proteolytic activity of LAB. LAB proteolytic system is very efficient in releasing encrypted molecules from several proteins present in different food matrices. Alpha and beta-caseins, albumin and globulin from milk and dairy products, rubisco from spinach, beta-conglycinin from soy and gluten from cereals constitute a good source of important bioactive compounds. These encrypted peptides are able to control nutrition (mineral absorption and oxidative stress protection), metabolism (blood glucose and cholesterol lowering) cardiovascular function (antithrombotic and hypotensive action), infection (microbial inhibition and immunomodulation) and gut-brain axis (opioids and anti-opioids controlling mood and food intake). Very recent results underline the role of food-encrypted peptides in protein folding (chaperone-like molecules) as well as in cell cycle and apoptosis control, suggesting new and positive aspects of fermented food, still unexplored. In this context, the detailed (transcriptomic, proteomic, and metabolomic) characterization of LAB of food interest (as starters, biocontrol agents, nutraceuticals, and probiotics) can supply a solid evidence-based science to support beneficial effects and it is a promising approach as well to obtain

  8. Brønsted acid cocatalysis in photocatalytic intramolecular coupling of tertiary amines: efficient synthesis of 2-arylindols.

    PubMed

    Yuan, Xiaoqian; Wu, Xinxin; Dong, Shupeng; Wu, Guibing; Ye, Jinxing

    2016-08-21

    We report herein a highly efficient intramolecular coupling reaction of tertiary amines and ketones (α,β-unsaturated ketones) by using a Brønsted acid as a cocatalyst, affording 2-arylindols in good to excellent yields (up to 92%) under visible light irradiation at room temperature. PMID:27431277

  9. A Neat Trick Using Oxalic Acid Dihydrate and Potassium Permanganate and Other Experiments with Small Organic Amine or Oxygenated Compounds

    ERIC Educational Resources Information Center

    Kelland, Malcolm A.

    2011-01-01

    Solid potassium permanganate (KMnO[subscript 4]) is shown to react in a variety of ways with small organic amines or oxygenated compounds depending on whether they are liquids or solids and whether water is present. In particular, its reaction with solid oxalic acid dihydrate can be initiated by the moisture in one's breath, making an intriguing…

  10. Microwave-assisted decarboxylative three-component coupling of a 2-oxoacetic acid, an amine, and an alkyne.

    PubMed

    Feng, Huangdi; Ermolat'ev, Denis S; Song, Gonghua; Van der Eycken, Erik V

    2011-09-16

    A novel and efficient microwave-assisted decarboxylative three-component coupling of a 2-oxoacetic acid, an amine, and an alkyne (OA(2)-coulpling) has been developed. This new multicomponent coupling constitutes an efficient approach for the synthesis of polysubstituted propargylamines in the presence of a catalytic amount of copper(I) catalyst. PMID:21823621

  11. 40 CFR 721.9220 - Reaction products of secondary alkyl amines with a substituted benzenesulfonic acid and sulfuric...

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Reaction products of secondary alkyl... SIGNIFICANT NEW USES OF CHEMICAL SUBSTANCES Significant New Uses for Specific Chemical Substances § 721.9220 Reaction products of secondary alkyl amines with a substituted benzenesulfonic acid and sulfuric...

  12. 40 CFR 721.9220 - Reaction products of secondary alkyl amines with a substituted benzenesulfonic acid and sulfuric...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Reaction products of secondary alkyl... SIGNIFICANT NEW USES OF CHEMICAL SUBSTANCES Significant New Uses for Specific Chemical Substances § 721.9220 Reaction products of secondary alkyl amines with a substituted benzenesulfonic acid and sulfuric...

  13. 40 CFR 721.9220 - Reaction products of secondary alkyl amines with a substituted benzenesulfonic acid and sulfuric...

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Reaction products of secondary alkyl... SIGNIFICANT NEW USES OF CHEMICAL SUBSTANCES Significant New Uses for Specific Chemical Substances § 721.9220 Reaction products of secondary alkyl amines with a substituted benzenesulfonic acid and sulfuric...

  14. 40 CFR 721.9220 - Reaction products of secondary alkyl amines with a substituted benzenesulfonic acid and sulfuric...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Reaction products of secondary alkyl... SIGNIFICANT NEW USES OF CHEMICAL SUBSTANCES Significant New Uses for Specific Chemical Substances § 721.9220 Reaction products of secondary alkyl amines with a substituted benzenesulfonic acid and sulfuric...

  15. 40 CFR 721.9220 - Reaction products of secondary alkyl amines with a substituted benzenesulfonic acid and sulfuric...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Reaction products of secondary alkyl... SIGNIFICANT NEW USES OF CHEMICAL SUBSTANCES Significant New Uses for Specific Chemical Substances § 721.9220 Reaction products of secondary alkyl amines with a substituted benzenesulfonic acid and sulfuric...

  16. CHEMISTRY OF FOG WATER IN CALIFORNIA'S CENTRAL VALLEY: 2. PHOTOCHEMICAL TRANSFORMATIONS OF AMINO ACIDS AND ALKYL AMINES. (R825433)

    EPA Science Inventory

    Although amino compounds are seemingly ubiquitous in atmospheric particles and deposition, little is known of their fate in the troposphere. We report here on the fate of 21 amino acids and alkyl amines in fog waters from Davis, California, illuminated with simulated sunlight ...

  17. Detection and qualitative analysis of fatty acid amides in the urine of alcoholics using HPLC-QTOF-MS.

    PubMed

    Dabur, Rajesh; Mittal, Ashwani

    2016-05-01

    Fatty acid amides (FAAs) in alcoholism lead to liver diseases. These amides have been reported in plasma and in other organs of the body, while their detection or presence in the urine is still unknown. Therefore, the focus of the current study was to detect and analyze FAAs qualitatively in urine samples of alcoholics. Furthermore, the effects of Tinospora cordifolia (hepatoprotective medicinal plant) intervention on FAA levels in moderate alcoholics were also analyzed. In the study, asymptomatic chronic alcoholics (n = 22) without chronic liver disease and nonalcoholic healthy volunteers (n = 24) with a mean age of 39 ± 2.0 years were selected. The first-pass urine and fasting blood samples were collected in the morning on day 0 and day 14 after T. cordifolia water extract (TCE) treatment and analyzed using automated biochemistry analyzer and HPLC-QTOF-MS. Results indicated the increased levels of serum triglycerides, cholesterol, and liver function enzymes in alcoholic subjects, which were significantly down-regulated by TCE intervention. Multivariate discrimination analysis of QTOF-MS data showed increased urinary levels of oleoamide (2.55-fold), palmitamide (5.6-fold), and erucamide (1.6-fold) in alcoholics as compared to control subjects. Levels of oleamide (1.8-fold), palmitamide (1.7-fold), and linoleamide (1.5-fold) were found to be increased in plasma. Treatment with TCE in alcoholics (3.0 g lyophilized water extract/day) significantly decreased the plasma and urinary levels of all FAAs except linoleamide. The HPLC-QTOF-MS approach for FAAs analysis in both urinary and plasma samples of alcoholics worked very well. Moreover, findings (i.e., increased levels of FAAs in urine and in plasma) further support other findings that these amides play a very important role in alcoholism. Further, like our previous findings, TCE proved its hepatoprotective effect against alcoholism not only by lowering the levels of these detected FAAs, but also by decreasing the

  18. HPLC/ELSD analysis of amidated bile acids: an effective and rapid way to assist continuous flow chemistry processes.

    PubMed

    Sardella, Roccaldo; Gioiello, Antimo; Ianni, Federica; Venturoni, Francesco; Natalini, Benedetto

    2012-10-15

    The employment of the flow N-acyl amidation of natural bile acids (BAs) required the in-line connection with suitable analytical tools enabling the determination of reaction yields as well as of the purity grade of the synthesized glyco- and tauro-conjugated derivatives. In this framework, a unique HPLC method was successfully established and validated for ursodeoxycholic (UDCA), chenodeoxycholic (CDCA), deoxycholic (DCA) and cholic (CA) acids, as well as the corresponding glyco- and tauro-conjugated forms. Because of the shared absence of relevant chromophoric moieties in the sample structure, an evaporative light scattering detector (ELSD) was profitably utilized for the analysis of such steroidal species. For each of the investigated compounds, all the runs were contemporarily carried out on the acidic free and the two relative conjugated variants. The different ELSD response of the free and the corresponding conjugated BAs, imposed to build-up separate calibration curves. In all the cases, very good precision (RSD% values ranging from 1.04 to 6.40% in the long-period) and accuracy (Recovery% values ranging from 96.03 to 111.14% in the long-period) values along with appreciably low LOD and LOQ values (the former being within the range 1-27 ng mL(-1) and the latter within the range 2-44 ng mL(-1)) turned out. PMID:23141350

  19. Halogenated Fatty Acid Amides and Cyclic Depsipeptides from an Eastern Caribbean Collection of the Cyanobacterium Lyngbya majuscula†

    PubMed Central

    Jiménez, Jorge I.; Vansach, Tifanie; Yoshida, Wesley Y.; Sakamoto, Bryan; Pörzgen, Peter; Horgen, F. David

    2009-01-01

    A lipophilic extract of an eastern Caribbean collection of Lyngbya majuscula yielded two new halogenated fatty acid amides, grenadamides B (1) and C (2), and two new depsipeptides, itralamides A (3) and B (4), along with the known compounds hectochlorin and deacetylhectochlorin. The recently reported depsipeptide carriebowmide (5) was also present in the extract and isolated as its sulfone artifact (6). Compounds 1–4 were identified by spectroscopic methods. The configurations of the amino acid residues of 3, 4, and 6 were determined by LC-MS analyses of diastereomeric derivatives of the acid hydrolysates (advanced Marfey’s method). Based on the configurational analysis of 6, in direct comparison with authentic carriebowmide (5), a minor structural revision of 5 is proposed. Compounds 1 and 2 displayed marginal activity against the beet armyworm (Spodoptera exigua). Compounds 1–4, and 6 were assessed for general cell toxicity in human embryonic kidney (HEK293) cells. Only itralamide B (4) displayed significant cytotoxicity, showing an IC50 value of 6 ± 1 μM. PMID:19739598

  20. Physical Nature of Fatty Acid Amide Hydrolase Interactions with Its Inhibitors: Testing a Simple Nonempirical Scoring Model.

    PubMed

    Giedroyć-Piasecka, Wiktoria; Dyguda-Kazimierowicz, Edyta; Beker, Wiktor; Mor, Marco; Lodola, Alessio; Sokalski, W Andrzej

    2014-12-26

    Fatty acid amide hydrolase (FAAH) is an enzyme responsible for the deactivating hydrolysis of fatty acid ethanolamide neuromodulators. FAAH inhibitors have gained considerable interest due to their possible application in the treatment of anxiety, inflammation, and pain. In the context of inhibitor design, the availability of reliable computational tools for predicting binding affinity is still a challenging task, and it is now well understood that empirical scoring functions have several limitations that in principle could be overcome by quantum mechanics. Herein, systematic ab initio analyses of FAAH interactions with a series of inhibitors belonging to the class of the N-alkylcarbamic acid aryl esters have been performed. In contrast to our earlier studies of other classes of enzyme-inhibitor complexes, reasonable correlation with experimental results required us to consider correlation effects along with electrostatic term. Therefore, the simplest comprehensive nonempirical model allowing for qualitative predictions of binding affinities for FAAH ligands consists of electrostatic multipole and second-order dispersion terms. Such a model has been validated against the relative stabilities of the benchmark S66 set of biomolecular complexes. As it does not involve parameters fitted to experimentally derived data, this model offers a unique opportunity for generally applicable inhibitor design and virtual screening. PMID:25420234

  1. Amine-modified hyaluronic acid-functionalized porous silicon nanoparticles for targeting breast cancer tumors

    PubMed Central

    Almeida, Patrick V.; Shahbazi, Mohammad-Ali; Mäkilä, Ermei; Kaasalainen, Martti; Salonen, Jarno; Hirvonen, Jouni; Santos, Hélder A.

    2014-01-01

    Active targeting of nanoparticles to receptor-overexpressing cancer cells has great potential for enhancing the cellular uptake of nanoparticles and for reducing fast clearance of the nanoparticles from the body. Herein, we present a preparation method of a porous silicon (PSi)-based nanodelivery system for breast cancer targeting, by covalently conjugating a synthesized amide-modified hyaluronic acid (HA+) derived polymer on the surface of undecylenic acid-modified thermally hydrocarbonized PSi (UnTHCPSi) nanoparticles. The resulting UnTHCPSi–HA+ nanoparticles showed relatively small size, reduced polydispersibility, high biocompatibility, improved colloidal and human plasma stability, as well as enhanced cellular interactions and internalization. Moreover, we demonstrated that the enhanced cellular association of UnTHCPSi–HA+ relies on the capability of the conjugated HA+ to bind and consequently target CD44 receptors expressed on the surface of breast cancer cells, thus making the HA+-functionalized UnTHCPSi nanoparticles a suitable and promising nanoplatform for the targeting of CD44-overexpressing breast tumors and for drug delivery. PMID:25074521

  2. Synthesis of 1,3-Amino Alcohols, 1,3-Diols, Amines, and Carboxylic Acids from Terminal Alkynes.

    PubMed

    Zeng, Mingshuo; Herzon, Seth B

    2015-09-01

    The half-sandwich ruthenium complexes 1-3 activate terminal alkynes toward anti-Markovnikov hydration and reductive hydration under mild conditions. These reactions are believed to proceed via addition of water to metal vinylidene intermediates (4). The functionalization of propargylic alcohols by metal vinylidene pathways is challenging owing to decomposition of the starting material and catalytic intermediates. Here we show that catalyst 2 can be employed to convert propargylic alcohols to 1,3-diols in high yield and with retention of stereochemistry at the propargylic position. The method is also amenable to propargylic amine derivatives, thereby establishing a route to enantioenriched 1,3-amino alcohol products. We also report the development of formal anti-Markovnikov reductive amination and oxidative hydration reactions to access linear amines and carboxylic acids, respectively, from terminal alkynes. This chemistry expands the scope of products that can be prepared from terminal alkynes by practical and high-yielding metal-catalyzed methods. PMID:26203776

  3. Application of cyanuric chloride-based six new chiral derivatizing reagents having amino acids and amino acid amides as chiral auxiliaries for enantioresolution of proteinogenic amino acids by reversed-phase high-performance liquid chromatography.

    PubMed

    Bhushan, Ravi; Dixit, Shuchi

    2012-04-01

    Six dichloro-s-triazine (DCT) reagents having L-Leu, D-Phg, L-Val, L-Met, L-Ala and L-Met-NH(2) as chiral auxiliaries in cyanuric chloride were introduced for enantioseparation of 13 proteinogenic amino acids. Four other DCTs and six monochloro-s-triazine (MCT) reagents having amino acid amides as chiral auxiliaries were also synthesized. These 16 chiral derivatizing reagents (CDRs) were used for synthesis of diastereomers of all the 13 analytes using microwave irradiation, which were resolved by reversed-phase high-performance liquid chromatography (RP-HPLC) using C18 column and gradient eluting mixture of aqueous TFA and acetonitrile with UV detection at 230 nm. It required only 60-90 s for derivatization using microwave irradiation. Better resolution and lower retention times were observed for the diastereomers prepared with CDRs having amino acids as chiral auxiliaries as compared to counterparts prepared with reagents having amino acid amides as chiral auxiliaries. As the best resolution of all the 13 analytes was observed for their diastereomers prepared using the DCT reagent having L-Leu as chiral auxiliary, this CDR was further employed for derivatization of Lys, Tyr, His and Arg followed by RP-HPLC analysis of resulting diastereomers. The results are discussed in light of acid and amide groups of chiral auxiliaries constituting CDRs, electronegativities of the atoms of achiral moieties constituting CDRs and hydrophobicities of side chains of amino acids constituting CDRs and analytes. PMID:21246226

  4. Fatty acid composition and biogenic amines in acidified and fermented fish silage: a comparison study.

    PubMed

    Özyurt, Gülsün; Gökdoğan, Saadet; Şimşek, Ayşe; Yuvka, Ilknur; Ergüven, Merve; Kuley Boga, Esmeray

    2016-01-01

    In the presented study, ensiling of discard fish by acidification or fermentation was evaluated. Klunzinger's ponyfish which is a discard fish was used for the production of fish silage by acidification (3% formic acid for Method FA; 1.5% formic and 1.5% sulphuric acid for Method FASA) and fermentation (Lactobacillus plantarum for Method LP and Streptococcus thermophilus for Method ST). The chemical, microbiological and nutritional properties of the differently preserved fish silages were estimated during a storage period of 60 d at ambient temperature. Compared to the raw material, a slight increase in saturated fatty acids and a slight decrease in polyunsaturated fatty acids were observed in all silages. At the end of the storage period, the aerobic bacteria counts after applying Methods FA, FASA, LP and ST amounted to 2.35, 2.39, 5.77 and 5.43 log cfu/g, respectively. The analysis of thiobarbituric acid revealed that acidification of silages accelerated the lipid oxidation. Nine biogenic amines were found in raw fish and different silages. The initial histamine concentration in raw fish was 0.17 mg/100 g and in all silages it remained at low levels during the storage period. The initial tyramine content was found to be 1.56 mg/100 g in raw fish and increased significantly in all silages. The increase of the tyramine content in fermented silages was considerably higher than in acidified silages (23-48 mg/100 g and 5-10 mg/100 g, respectively). It can be concluded that acidified or fermented fish silage should be considered as potential feed component for animals because of its high nutritional value and appropriate microbiological and chemical quality. PMID:26635094

  5. Synthesis of quinaldinic acid amide derivative of styrene-divinylbenzene copolymer and its application in preconcentration of mercury(II)

    SciTech Connect

    Das, J.; Das, N.

    1988-09-01

    A new chelating resin has been synthesized by introducing a quinaldinic acid amide group into styrene-divinyl benzene (8%) copolymer beads. The resin is stable in fairly strong acids or alkali and has been characterized by elemental analysis for nitrogen and from i.r. spectra. The water regain value is 0.37g/g. The sorption patterns of Na(I), K(I), Ca(II), Mg(II), Pb(II), Cu(II), Ni(II), Zn(II), Cd(II), Hg(II) and Fe(III) on the chelating resin have been studied as a function of pH. The resin selectively sorbs Hg(II) over a wide pH-range of 2.5 - 7.6 with high efficiency. The maximum exchange capacity for Hg(II) is 1.98 mmols g/sup -1/ at pH 5.5. Over 99% of Hg(II) sorbed has been recovered by using 10% thiourea in 1M HClO/sub 4/ both by batch and column operations. The method has been utilized in the preconcentration and recovery of Hg(II) from industrial and laboratory waste water.

  6. Identification of N-acylethanolamines in Dictyostelium discoideum and confirmation of their hydrolysis by fatty acid amide hydrolase[S

    PubMed Central

    Hayes, Alexander C.; Stupak, Jacek; Li, Jianjun; Cox, Andrew D.

    2013-01-01

    N-acylethanolamines (NAEs) are endogenous lipid-based signaling molecules best known for their role in the endocannabinoid system in mammals, but they are also known to play roles in signaling pathways in plants. The regulation of NAEs in vivo is partly accomplished by the enzyme fatty acid amide hydrolase (FAAH), which hydrolyses NAEs to ethanolamine and their corresponding fatty acid. Inhibition of FAAH has been shown to increase the levels of NAEs in vivo and to produce desirable phenotypes. This has led to the development of pharmaceutical-based therapies for a variety of conditions targeting FAAH. Recently, our group identified a functional FAAH homolog in Dictyostelium discoideum, leading to our hypothesis that D. discoideum also possesses NAEs. In this study, we provide a further characterization of FAAH and identify NAEs in D. discoideum for the first time. We also demonstrate the ability to modulate their levels in vivo through the use of a semispecific FAAH inhibitor and confirm that these NAEs are FAAH substrates through in vitro studies. We believe the demonstration of the in vivo modulation of NAE levels suggests that D. discoideum could be a good simple model organism in which to study NAE-mediated signaling. PMID:23187822

  7. [Study of the circular dichroism for tribasic complex of amine derivative of beta-cyclodextrindien-Cu2+ -benzoic acid].

    PubMed

    Hu, J; Zhang, H; Shen, B

    1998-02-01

    The circular dichroism spectra of beta-cyclodextrindien, beta-cyclodextrindien-Cu2+ complex, beta-cyclodextrindien-benzoic acid complex, tribasic complex of beta-cyclodextrindien-Cu2+ -benzoic acid were determined by using JASCO J-20C automatic recording spectropolarimeter. The attribution of the bands obtained were made according to the order of orbit energy of Cu2+ complex and benzoic acid, and the coordination structure of tribasic complex of amine derivative of beta-cyclodextrindien-Cu2+ -benzoic acid were decided acording to the structure character of Cu2+ complex and KAJART sector rule of inclusion complex of beta-cyclodextrindien with aromatic compounds. PMID:15810322

  8. Fluorescence Turn-on Enantioselective Recognition of both Chiral Acidic Compounds and α-Amino Acids by a Chiral Tetraphenylethylene Macrocycle Amine.

    PubMed

    Feng, Hai-Tao; Zhang, Xing; Zheng, Yan-Song

    2015-08-21

    New chiral tetraphenylethylene (TPE) macrocycles bearing optically pure amine groups were synthesized and found to have a discriminating ability between the two enantiomers of not only chiral acidic compounds but also α-amino acids by enantioselective aggregation and aggregation-induced emission (AIE) effects. NMR spectra, including 2D-NOESY, disclosed that the host-guest interaction of the macrocycle receptor played a key role in addition to the acid-base interactions. PMID:26197038

  9. Regioselective Copper-Catalyzed Amination of Chlorobenzoic Acids: Synthesis and Solid-State Structures of N-Aryl Anthranilic Acid Derivatives

    PubMed Central

    Mei, Xuefeng; August, Adam T.; Wolf, Christian

    2008-01-01

    A chemo- and regioselective copper-catalyzed cross-coupling reaction for effective amination of 2-chlorobenzoic acids with aniline derivatives has been developed. The method eliminates the need for acid protection and produces a wide range of N-aryl anthranilic acid derivatives in up to 99%. The amination was found to proceed with both electron-rich and electron-deficient aryl chlorides and anilines and also utilizes sterically hindered anilines such as 2,6-dimethylaniline and 2-tert-butylaniline. The conformational isomerism of appropriately substituted N-aryl anthranilic acids has been investigated in the solid state. Crystallographic analysis of seven anthranilic acid derivatives showed formation of two distinct supramolecular architectures exhibiting trans-anti- and unprecedented trans-syn-dimeric structures. PMID:16388629

  10. Role of amidation in bile acid effect on DNA synthesis by regenerating mouse liver.

    PubMed

    Barbero, E R; Herrera, M C; Monte, M J; Serrano, M A; Marin, J J

    1995-06-01

    Effect of bile acids on DNA synthesis by the regenerating liver was investigated in mice in vivo after partial hepatectomy (PH). Radioactivity incorporation into DNA after [14C]thymidine intraperitoneal administration peaked at 48 h after PH. At this time a significant taurocholate-induced dose-dependent reduction in DNA synthesis without changes in total liver radioactivity content was found (half-maximal effect at approximately 0.1 mumol/g body wt). Effect of taurocholate (0.5 mumol/g body wt) was mimicked by chocolate, ursodeoxycholate, deoxycholate, dehydrocholate, tauroursodeoxycholate, taurochenodeoxycholate, and taurodeoxycholate. In contrast, chenodeoxycholate, glycocholate, glycochenodeoxycholate, glycoursodeoxycholate, glycodeoxycholate, 5 beta-cholestane, bromosulfophthalein, and free taurine lacked this effect. No relationship between hydrophobic-hydrophilic balance and inhibitory effect was observed. Analysis by high-performance liquid chromatography indicated that inhibition of thymidine incorporation into DNA was not accompanied by an accumulation of phosphorylated DNA precursors in the liver but rather by a parallel increase in nucleotide catabolism. Bile acid-induced modifications in DNA synthesis were observed in vivo even in the absence of changes in toxicity tests, which suggests that the inhibitory effect shared by most unconjugated and tauroconjugated bile acids but not by glycoconjugated bile acids should be accounted for by mechanisms other than nonselective liver cell injury. PMID:7611405

  11. Potent and Selective α-Ketoheterocycle-Based Inhibitors of the Anandamide and Oleamide Catabolizing Enzyme, Fatty Acid Amide Hydrolase

    PubMed Central

    Romero, F. Anthony; Du, Wu; Hwang, Inkyu; Rayl, Thomas J.; Kimball, F. Scott; Leung, Donmienne; Hoover, Heather S.; Apodaca, Richard L.; Breitenbucher, J. Guy; Cravatt, Benjamin F.; Boger, Dale L.

    2008-01-01

    A study of the structure–activity relationships (SAR) of 2f (OL-135), a potent inhibitor of fatty acid amide hydrolase (FAAH), is detailed targeting the 5-position of the oxazole. Examination of a series of substituted benzene derivatives (12–14) revealed that the optimal position for substitution was the meta-position with selected members approaching or exceeding the potency of 2f. Concurrent with these studies, the effect of substitution on the pyridine ring of 2f was also examined. A series of small, non-aromatic C5-substituents was also explored and revealed that the Ki follows a well-defined correlation with the Hammett σp constant (ρ = 3.01, R2 = 0.91) in which electron-withdrawing substituents enhance potency leading to inhibitors with Ki’s as low as 400 pM (20n). Proteomic-wide screening of the inhibitors revealed that most are exquisitely selective for FAAH over all other mammalian proteases reversing the 100-fold preference of 20a (C5 substituent = H) for the enzyme TGH. PMID:17279740

  12. Synthesis and antiproliferative activity of two diastereomeric lignan amides serving as dimeric caffeic acid-l-DOPA hybrids.

    PubMed

    Magoulas, George E; Rigopoulos, Andreas; Piperigkou, Zoi; Gialeli, Chrysostomi; Karamanos, Nikos K; Takis, Panteleimon G; Troganis, Anastassios N; Chrissanthopoulos, Athanassios; Maroulis, George; Papaioannou, Dionissios

    2016-06-01

    Two new diastereomeric lignan amides (4 and 5) serving as dimeric caffeic acid-l-DOPA hybrids were synthesized. The synthesis involved the FeCl3-mediated phenol oxidative coupling of methyl caffeate to afford trans-diester 1a as a mixture of enantiomers, protection of the catechol units, regioselective saponification, coupling with a suitably protected l-DOPA derivative, separation of the two diastereomers thus obtained by flash column chromatography and finally global chemoselective deprotection of the catechol units. The effect of hybrids 4 and 5 and related compounds on the proliferation of two breast cancer cell lines with different metastatic potential and estrogen receptor status (MDA-MB-231 and MCF-7) and of one epithelial lung cancer cell line, namely A-549, was evaluated for concentrations ranging from 1 to 256μM and periods of treatment of 24, 48 and 72h. Both hybrids showed interesting and almost equipotent antiproliferative activities (IC50 64-70μM) for the MDA-MB-231 cell line after 24-48h of treatment, but they were more selective and much more potent (IC50 4-16μM) for the MCF-7 cells after 48h of treatment. The highest activity for both hybrids and both breast cancer lines was observed after 72h of treatment (IC50 1-2μM), probably as the result of slow hydrolysis of their methyl ester functions. PMID:27155809

  13. Inhibition of LN-308 glioma cell proliferation and migration by retinoic acid amide through activation of Akt pathway

    PubMed Central

    Zhu, Jun; Lu, Xiang-Dong; Si, Feng; Song, Chun-Yu; Meng, Qing-Hai

    2015-01-01

    The present study was performed to investigate the effect of retinoic acid amide (RAA) on the expression of integrin α3β1, rate of cell proliferation and migration in p53-deficient glioma cell line, LN-308. The results revealed promotion of integrin α3 expression, reduction in proliferation and migration in RAA treated cells compared to the control LN-308 glioma cells. Promotion of RAA induced integrin α3β1 expression led to the enhancement in cyclin-dependent kinase nuclear localization and activation of Akt pathway. In addition, RAA treatment inhibited the expression of nuclear factor-κB, Bcl-2 and epidermal growth factor receptor (EGFR). These factors are responsible for promoting the rate of cell proliferation and survival in the carcinoma cells. Thus RAA treatment inhibits rate of LN-308 glioma cell proliferation and migration through increase in integrin α3β1 expression and activation of Akt pathway. Therefore, RAA can be of therapeutic importance for the treatment of glioma. PMID:26823704

  14. The macamide N-3-methoxybenzyl-linoleamide is a time-dependent fatty acid amide hydrolase (FAAH) inhibitor.

    PubMed

    Almukadi, Haifa; Wu, Hui; Böhlke, Mark; Kelley, Charles J; Maher, Timothy J; Pino-Figueroa, Alejandro

    2013-10-01

    The Peruvian plant Lepidium meyenii (Maca) has been shown to possess neuroprotective activity both in vitro and in vivo. Previous studies have also demonstrated the activity of the pentane extract and its macamides, the most representative lipophilic constituents of Maca, in the endocannabinoid system as fatty acid amide hydrolase (FAAH) inhibitors. One of the most active macamides, N-3-methoxybenzyl-linoleamide, was studied to determine its mechanism of interaction with FAAH and whether it has inhibitory activity on mono-acyl glycerol lipase (MAGL), the second enzyme responsible for endocannabinoid degradation. Macamide concentrations from 1 to 100 μM were tested using FAAH and MAGL inhibitor assay methods and showed no effect on MAGL. Tests with other conditions were performed in order to characterize the inhibitory mechanism of FAAH inhibition. N-3-methoxybenzyl-linoleamide displayed significant time-dependent and dose-dependent FAAH inhibitory activity. The mechanism of inhibition was most likely irreversible or slowly reversible. These results suggest the potential application of macamides isolated from Maca as FAAH inhibitors, as they might act on the central nervous system to provide analgesic, anti-inflammatory, or neuroprotective effects, by modulating the release of neurotransmitters. PMID:23853040

  15. Cardioprotective effects of fatty acid amide hydrolase inhibitor URB694, in a rodent model of trait anxiety

    PubMed Central

    Carnevali, Luca; Vacondio, Federica; Rossi, Stefano; Macchi, Emilio; Spadoni, Gilberto; Bedini, Annalida; Neumann, Inga D.; Rivara, Silvia; Mor, Marco; Sgoifo, Andrea

    2015-01-01

    In humans, chronic anxiety represents an independent risk factor for cardiac arrhythmias and sudden death. Here we evaluate in male Wistar rats bred for high (HAB) and low (LAB) anxiety-related behavior, as well as non-selected (NAB) animals, the relationship between trait anxiety and cardiac electrical instability and investigate whether pharmacological augmentation of endocannabinoid anandamide-mediated signaling exerts anxiolytic-like and cardioprotective effects. HAB rats displayed (i) a higher incidence of ventricular tachyarrhythmias induced by isoproterenol, and (ii) a larger spatial dispersion of ventricular refractoriness assessed by means of an epicardial mapping protocol. In HAB rats, acute pharmacological inhibition of the anandamide-degrading enzyme, fatty acid amide hydrolase (FAAH), with URB694 (0.3 mg/kg), (i) decreased anxiety-like behavior in the elevated plus maze, (ii) increased anandamide levels in the heart, (iii) reduced isoproterenol-induced occurrence of ventricular tachyarrhythmias, and (iv) corrected alterations of ventricular refractoriness. The anti-arrhythmic effect of URB694 was prevented by pharmacological blockade of the cannabinoid type 1 (CB1), but not of the CB2, receptor. These findings suggest that URB694 exerts anxiolytic-like and cardioprotective effects in HAB rats, the latter via anandamide-mediated activation of CB1 receptors. Thus, pharmacological inhibition of FAAH might be a viable pharmacological strategy for the treatment of anxiety-related cardiac dysfunction. PMID:26656183

  16. The formation of lipid hydroperoxide-derived amide-type lysine adducts on proteins: a review of current knowledge.

    PubMed

    Kato, Yoji

    2014-01-01

    Lipid peroxidation is an important biological reaction. In particular, polyunsaturated fatty acid (PUFA) can be oxidized easily. Peroxidized lipids often react with other amines accompanied by the formation of various covalent adducts. Novel amide-type lipid-lysine adducts have been identified from an in vitro reaction mixture of lipid hydroperoxide with a protein, biological tissues exposed to conditions of oxidative stress and human urine from a healthy person. In this chapter, the current knowledge of amide type adducts is reviewed with a focus on the evaluation of functional foods and diseases with a history of discovery of hexanoyl-lysine (HEL). Although there is extensive research on HEL and other amide-type adducts, the mechanism of generation of the amide bond remains unclear. We have found that the decomposed aldehyde plus peroxide combined with a lysine moiety does not fully explain the formation of the amide-type lipid-lysine adduct that is generated by lipid hydroperoxide. Singlet oxygen or an excited state of the ketone generated from the lipid hydroperoxide may also contribute to the formation of the amide linkage. The amide-adducts may prove useful not only for the detection of oxidative stress induced by disease but also for the estimation of damage caused by an excess intake of PUFA. PMID:24374915

  17. Dianthosaponins G-I, triterpene saponins, an anthranilic acid amide glucoside and a flavonoid glycoside from the aerial parts of Dianthus japonicus and their cytotoxicity.

    PubMed

    Kanehira, Yuka; Kawakami, Susumu; Sugimoto, Sachiko; Matsunami, Katsuyoshi; Otsuka, Hideaki

    2016-10-01

    Extensive isolation work on the 1-BuOH-soluble fraction of a MeOH extract of the aerial parts of Dianthus japonicus afforded three further triterpene glycosyl estsers, termed dianthosaponins G-I, an anthranilic acid amide glucoside and a C-glycosyl flavonoid along with one known triterpene saponin. Their structures were elucidated from spectroscopic evidence. The cytotoxicity of the isolated compounds toward A549 cells was evaluated. PMID:27351981

  18. Rapid HPLC analysis of amino acids and biogenic amines in wines during fermentation and evaluation of matrix effect.

    PubMed

    Wang, Ya-Qin; Ye, Dong-Qing; Zhu, Bao-Qing; Wu, Guang-Feng; Duan, Chang-Qing

    2014-11-15

    A rapid HPLC method has been developed for the simultaneous determination of 23 amino acids, 10 biogenic amines and the ammonium ion in wine. Samples were pre-column derivatised with diethyl ethoxymethylenemalonate and separated using reversed-phase HPLC within 30 min. The matrix effect was evaluated when measuring samples taken from different stages of fermentation. Most compounds showed no obvious matrix effect, whereas proline, ethanolamine and spermine had remarkably different responses to variable concentrations of sugar. High concentrations of sugar affected the pH of the derivatisation reaction system; proline, ethanolamine and spermine derivatives were sensitive to this effect. Matrix-matched calibration was used for the quantification of these compounds. Validation of the method showed that it was accurate, reproducible and efficient for the simultaneous determination of amino acids and biogenic amines in wines during fermentation. As a specific application of the method, red wine samples taken from different stages of fermentation were analysed. PMID:24912689

  19. Modeling the simultaneous transport of two acid gases in tertiary amines with reversible reactions

    SciTech Connect

    Al-Ghawas, H.A.; Sandall, O.C.

    1988-10-01

    The objective of this work is to develop a model for the simultaneous mass transfer of two acid gases in tertiary amines accompanied by reversible chemical reactions. The model has been applied to the industrially important system of simultaneous absorption or desorption of CO/sub 2/ and H/sub 2/S in aqueous methyldiethanolamine (MDEA). In most applications the treated gas must be virtually free of H/sub 2/S; however, it is often not necessary or economical to remove substantial amounts of CO/sub 2/. Hence, selective removal of H/sub 2/S from gas streams such as natural or synthetic gases which contain CO/sub 2/ is desirable. In this research a film theory model describing the simultaneous diffusion and reversible reaction of two gases into reactive liquid has been used to predict the mass transfer enhancement factors of CO/sub 2/ and H/sub 2/S in aqueous MDEA solutions. The resulting unstable two point boundary value problem has been solved numerically for a range of the dimensionless parameters that characterize an important application for this system. In studying the simultaneous transport of CO/sub 2/ and H/sub 2/S, it is found that the reversibility of the reactions, under certain conditions, causes desorption to take place although absorption would be expected on the basis of overall driving forces. This showed that not only enhancement factors larger but also smaller than unity and even negative values are possible.

  20. Trans- and cis-urocanic acid, biogenic amine and amino acid contents in ikan pekasam (fermented fish) produced from Javanese carp (Puntius gonionotus) and black tilapia (Oreochromis mossambicus).

    PubMed

    Ezzat, M A; Zare, D; Karim, R; Ghazali, H M

    2015-04-01

    Ikan pekasam is a fermented fish product produced in Malaysia and is usually made from freshwater fish with ground roasted uncooked rice as the main source of carbohydrate. In this study, the amino acid, biogenic amine, and trans- and cis-urocanic acid (UCA) contents of fifteen commercial samples of Ikan pekasam made from Javanese carp and black tilapia, that had undergone either natural or acid-assisted fermentation, were quantified. The latter includes either tamarind (Tamarindus indica) pulp or dried slices of Garcinia atroviridis fruit in the fermentation process. Results showed that there are no significant differences in most of the biogenic amines including histamine, while there are significant differences in total UCA content, and trans- and cis-UCA contents between the two samples. Differences in the amino acid contents were largely fish-dependent. PMID:25442635

  1. Keys to Lipid Selection in Fatty Acid Amide Hydrolase Catalysis: Structural Flexibility, Gating Residues and Multiple Binding Pockets

    PubMed Central

    Palermo, Giulia; Bauer, Inga; Campomanes, Pablo; Cavalli, Andrea; Armirotti, Andrea; Girotto, Stefania; Rothlisberger, Ursula; De Vivo, Marco

    2015-01-01

    The fatty acid amide hydrolase (FAAH) regulates the endocannabinoid system cleaving primarily the lipid messenger anandamide. FAAH has been well characterized over the years and, importantly, it represents a promising drug target to treat several diseases, including inflammatory-related diseases and cancer. But its enzymatic mechanism for lipid selection to specifically hydrolyze anandamide, rather than similar bioactive lipids, remains elusive. Here, we clarify this mechanism in FAAH, examining the role of the dynamic paddle, which is formed by the gating residues Phe432 and Trp531 at the boundary between two cavities that form the FAAH catalytic site (the “membrane-access” and the “acyl chain-binding” pockets). We integrate microsecond-long MD simulations of wild type and double mutant model systems (Phe432Ala and Trp531Ala) of FAAH, embedded in a realistic membrane/water environment, with mutagenesis and kinetic experiments. We comparatively analyze three fatty acid substrates with different hydrolysis rates (anandamide > oleamide > palmitoylethanolamide). Our findings identify FAAH’s mechanism to selectively accommodate anandamide into a multi-pocket binding site, and to properly orient the substrate in pre-reactive conformations for efficient hydrolysis that is interceded by the dynamic paddle. Our findings therefore endorse a structural framework for a lipid selection mechanism mediated by structural flexibility and gating residues between multiple binding cavities, as found in FAAH. Based on the available structural data, this exquisite catalytic strategy for substrate specificity seems to be shared by other lipid-degrading enzymes with similar enzymatic architecture. The mechanistic insights for lipid selection might assist de-novo enzyme design or drug discovery efforts. PMID:26111155

  2. Impaired neurogenesis by HIV-1-Gp120 is rescued by genetic deletion of fatty acid amide hydrolase enzyme

    PubMed Central

    Avraham, H K; Jiang, S; Fu, Y; Rockenstein, E; Makriyannis, A; Wood, J; Wang, L; Masliah, E; Avraham, S

    2015-01-01

    Background and Purpose The HIV-envelope glycoprotein Gp120 is involved in neuronal injury and is associated with neuro-AIDS pathogenesis in the brain. Endocannabinoids are important lipid ligands in the CNS regulating neural functions, and their degeneration is controlled by hydrolysing enzymes such as the fatty acid amide hydrolase (FAAH). Here, we examined whether in vivo genetic deletion of Faah gene prevents HIV-1 Gp120-mediated effects on neurogenesis. Experimental Approach We generated new GFAP/Gp120 transgenic (Tg) mice that have genetic deletion of Faah gene by mating glial fribillary acidic protein (GFAP)/Gp120 Tg mice with Faah−/− mice. Neurogenesis and cell death were assessed by immunocytochemical analysis. Key Results Endocannabinoid levels in the brain of the double GFAP/Gp120//Faah−/− mice were similar to those observed in Faah−/− mice. However, unlike the impaired neurogenesis observed in GFAP/Gp120 Tg mice and Faah−/− mice, these GFAP/Gp120//Faah-/ mice showed significantly improved neurogenesis in the hippocampus, indicated by a significant increase in neuroblasts and neuronal cells, an increase in BrdU+ cells and doublecortin positive cells (DCX+), and an increase in the number of PCNA. Furthermore, a significant decrease in astrogliosis and gliogenesis was observed in GFAP/Gp120//Faah−/−mice and neurogenesis was stimulated by neural progenitor cells (NPCs) and/or the newly formed NPC niches characterized by increased COX-2 expression and elevated levels of PGE2. Conclusions and Implications In vivo genetic ablation of Faah, resulted in enhanced neurogenesis through modulation of the newly generated NPC niches in GFAP/Gp120//Faah−/− mice. This suggests a novel approach of using FAAH inhibitors to enhance neurogenesis in HIV-1 infected brain. PMID:24571443

  3. Effects of Fatty Acid Amide Hydrolase (FAAH) Inhibitors in Non-Human Primate Models of Nicotine Reward and Relapse.

    PubMed

    Justinova, Zuzana; Panlilio, Leigh V; Moreno-Sanz, Guillermo; Redhi, Godfrey H; Auber, Alessia; Secci, Maria E; Mascia, Paola; Bandiera, Tiziano; Armirotti, Andrea; Bertorelli, Rosalia; Chefer, Svetlana I; Barnes, Chanel; Yasar, Sevil; Piomelli, Daniele; Goldberg, Steven R

    2015-08-01

    Inhibition of the enzyme fatty acid amide hydrolase (FAAH) counteracts reward-related effects of nicotine in rats, but it has not been tested for this purpose in non-human primates. Therefore, we studied the effects of the first- and second-generation O-arylcarbamate-based FAAH inhibitors, URB597 (cyclohexyl carbamic acid 3'-carbamoyl-3-yl ester) and URB694 (6-hydroxy-[1,1'-biphenyl]-3-yl-cyclohexylcarbamate), in squirrel monkeys. Both FAAH inhibitors: (1) blocked FAAH activity in brain and liver, increasing levels of endogenous ligands for cannabinoid and α-type peroxisome proliferator-activated (PPAR-α) receptors; (2) shifted nicotine self-administration dose-response functions in a manner consistent with reduced nicotine reward; (3) blocked reinstatement of nicotine seeking induced by reexposure to either nicotine priming or nicotine-associated cues; and (4) had no effect on cocaine or food self-administration. The effects of FAAH inhibition on nicotine self-administration and nicotine priming-induced reinstatement were reversed by the PPAR-α antagonist, MK886. Unlike URB597, which was not self-administered by monkeys in an earlier study, URB694 was self-administered at a moderate rate. URB694 self-administration was blocked by pretreatment with an antagonist for either PPAR-α (MK886) or cannabinoid CB1 receptors (rimonabant). In additional experiments in rats, URB694 was devoid of THC-like or nicotine-like interoceptive effects under drug-discrimination procedures, and neither of the FAAH inhibitors induced dopamine release in the nucleus accumbens shell--consistent with their lack of robust reinforcing effects in monkeys. Overall, both URB597 and URB694 show promise for the initialization and maintenance of smoking cessation because of their ability to block the rewarding effects of nicotine and prevent nicotine priming-induced and cue-induced reinstatement. PMID:25754762

  4. Effects of Fatty Acid Amide Hydrolase (FAAH) Inhibitors in Non-Human Primate Models of Nicotine Reward and Relapse

    PubMed Central

    Justinova, Zuzana; Panlilio, Leigh V; Moreno-Sanz, Guillermo; Redhi, Godfrey H; Auber, Alessia; Secci, Maria E; Mascia, Paola; Bandiera, Tiziano; Armirotti, Andrea; Bertorelli, Rosalia; Chefer, Svetlana I; Barnes, Chanel; Yasar, Sevil; Piomelli, Daniele; Goldberg, Steven R

    2015-01-01

    Inhibition of the enzyme fatty acid amide hydrolase (FAAH) counteracts reward-related effects of nicotine in rats, but it has not been tested for this purpose in non-human primates. Therefore, we studied the effects of the first- and second-generation O-arylcarbamate-based FAAH inhibitors, URB597 (cyclohexyl carbamic acid 3'-carbamoyl-3-yl ester) and URB694 (6-hydroxy-[1,1'-biphenyl]-3-yl-cyclohexylcarbamate), in squirrel monkeys. Both FAAH inhibitors: (1) blocked FAAH activity in brain and liver, increasing levels of endogenous ligands for cannabinoid and α-type peroxisome proliferator-activated (PPAR-α) receptors; (2) shifted nicotine self-administration dose–response functions in a manner consistent with reduced nicotine reward; (3) blocked reinstatement of nicotine seeking induced by reexposure to either nicotine priming or nicotine-associated cues; and (4) had no effect on cocaine or food self-administration. The effects of FAAH inhibition on nicotine self-administration and nicotine priming-induced reinstatement were reversed by the PPAR-α antagonist, MK886. Unlike URB597, which was not self-administered by monkeys in an earlier study, URB694 was self-administered at a moderate rate. URB694 self-administration was blocked by pretreatment with an antagonist for either PPAR-α (MK886) or cannabinoid CB1 receptors (rimonabant). In additional experiments in rats, URB694 was devoid of THC-like or nicotine-like interoceptive effects under drug-discrimination procedures, and neither of the FAAH inhibitors induced dopamine release in the nucleus accumbens shell—consistent with their lack of robust reinforcing effects in monkeys. Overall, both URB597 and URB694 show promise for the initialization and maintenance of smoking cessation because of their ability to block the rewarding effects of nicotine and prevent nicotine priming-induced and cue-induced reinstatement. PMID:25754762

  5. Palladium-Catalyzed Carbonylation of β-Arylethylamide Directed by Oxalyl Amide in the Presence of Carbon Monoxide.

    PubMed

    Zhang, Li; Wang, Chao; Han, Jian; Huang, Zhi-Bin; Zhao, Yingsheng

    2016-06-17

    Pd-catalyzed regioselective coupling of β-C(sp(2))-H bonds in aromatic amines protected by oxalyl amide with carbon monoxide is reported. The reaction could tolerate various functional groups and could afford good to excellent yields of the corresponding 3,4-dihydroisoquinolinone derivatives. Remarkably, it could also tolerate β-arylethylamino acid and thiopheneethylamine derivatives, thus showing their potential for producing several important units for bioactive compound synthesis. PMID:27213988

  6. Identification of a novel enzymatic activity from lactic acid bacteria able to degrade biogenic amines in wine.

    PubMed

    Callejón, S; Sendra, R; Ferrer, S; Pardo, I

    2014-01-01

    The main objectives of this study were the search for enzymatic activities responsible for biogenic amine (BA) degradation in lactic acid bacteria (LAB) strains isolated from wine, their identification, and the evaluation of their applicability for reducing BAs in wine. Fifty-three percent of the 76 LAB cell extracts showed activity against a mixture of histamine, tyramine, and putrescine when analyzed in-gel. The quantification of the degrading ability for each individual amine was tested in a synthetic medium and wine. Most of the bacteria analyzed were able to degrade the three amines in both conditions. The highest percentages of degradation in wine were those of putrescine: up to 41% diminution in 1 week. Enzymes responsible for amine degradation were isolated and purified from Lactobacillus plantarum J16 and Pediococcus acidilactici CECT 5930 strains and were identified as multicopper oxidases. This is the first report of an efficient BA reduction in wine by LAB. Furthermore, the identity of the enzymes involved has been revealed. PMID:23515835

  7. Distillate fuels containing an amine salt of a sulfonic acid and a low volatility carrier fluid (PNE-554)

    SciTech Connect

    Ashcraft, T.L.; Schilowitz, A.M.; Talley, L.D.; Berlowitz, P.J.

    1993-06-01

    A distillate fuel composition is described comprising a major amount of gasoline and a minor synergistic amount of an additive combination of (a) an amine salt of a sulfonic acid wherein the amine moiety is a monoamine, a polyamine, a monoamine or a polyamine containing ether linkages, or mixtures thereof, said amine moiety containing from 2 to 100 carbon atoms and from 1 to 3 nitrogen atoms, and the sulfonic acid moiety is an alkyl benzyl sulfonic acid in which the alkyl group contains from 20 to 50 carbon atoms, and (b) a carrier fluid that is mineral oil base stock, a polyol ester, and mixtures thereof, wherein less than 10 volume % of the carrier fluid in vaporized at a temperature of 125 C., provided that the amount of component (a) in the fuel composition is from about 40 to about 1500 ppm and the amount of component (b) is from about 0.1 to about 10 times the amount of component (a).

  8. Chromate adsorption on acid-treated and amines-modified clay

    NASA Astrophysics Data System (ADS)

    Hajjaji, M.; Beraa, A.

    2015-03-01

    Acid-treated montmorillonite-rich clay and amines (methylamine, morpholine, and aniline)-modified clay adsorbents were investigated and their abilities to remove chromate from aqueous solution were studied. For the later purpose, kinetic studies were carried out under different operating conditions (chromate concentration, adsorbent content, and temperature), and adsorption isotherm measurements were performed. It was found that the kinetic of adsorption was fast and the data followed the pseudo-second rate equation. The rate of adsorption was controlled by the intra-particle diffusion and mass transfer through the liquid film, and the relative importance of these limiting steps depended on the operating conditions. Chromate adsorption was an endothermic process and took place spontaneously by physisorption. The free energy at 25 ≤ T ≤ 40 °C varied from -1.5 to -46 kJ/mol. Adsorption isotherms of Na+-saturated clay (AN), acid-treated clay (AA), and methylamine-clay and morpholine-clay (A-Me, A-Mo) were type V, whereas those of aniline-clay (A-An) were type III. The estimated maximum uptakes were 105, 29, 15, 11, and 10 mmol/kg for A-An, AN, A-Mo, AA, and A-Me, respectively. The mechanism of chromate adsorption was discussed based on the shape of the isotherms. Considering for instance the most efficient absorbent (A-An), the isotherm followed the Freundlich equation and hydrogen chromate (the main stable form at working pH) adsorbed to solid particles once aniline species were entirely desorbed.

  9. Hyaluronic acid based hydroxamate and conjugates with biologically active amines: In vitro effect on matrix metalloproteinase-2.

    PubMed

    Ponedel'kina, Irina Yu; Gaskarova, Aigul R; Khaybrakhmanova, Elvira A; Lukina, Elena S; Odinokov, Victor N

    2016-06-25

    In this study, water soluble hyaluronic acid (HA) based hydroxamate and conjugates with biologically active amines and hydrazides such as p- and o-aminophenols, anthranilic, 4- and 5-aminosalicylic acids, nicotinic, N-benzylnicotinic and isonicotinic hydrazides, p-aminobenzenesulfonamide (Streptocide), p-aminobenzoic acid diethylaminoethyl ester (Procaine), and 4-amino-2,3-dimethyl-1-phenyl-3-pyrazolin-5-one (4-aminoantipyrene) were examined as matrix metalloproteinase-2 inhibitors (MMPIs). In a dose of 0.27-270μM, the most efficient MMPIs were HA conjugates with o-aminophenol=4-aminoantipyrine>4-aminosalicylic acid>5-aminosalicylic acid. Conjugates with Streptocide, Procaine and HA hydroxamate showed 40-50% inhibitory effect at all used concentrations. Conjugates with anthranilic acid and isonicotinic hydrazide (Isoniazid) in a dose of 0.27μM inhibited enzyme activity by ∼70%, but with the concentration increase their inhibitory effect was decreased. PMID:27083788

  10. Primordial synthesis of amines and amino acids in a 1958 Miller H2S-rich spark discharge experiment.

    PubMed

    Parker, Eric T; Cleaves, Henderson J; Dworkin, Jason P; Glavin, Daniel P; Callahan, Michael; Aubrey, Andrew; Lazcano, Antonio; Bada, Jeffrey L

    2011-04-01

    Archived samples from a previously unreported 1958 Stanley Miller electric discharge experiment containing hydrogen sulfide (H(2)S) were recently discovered and analyzed using high-performance liquid chromatography and time-of-flight mass spectrometry. We report here the detection and quantification of primary amine-containing compounds in the original sample residues, which were produced via spark discharge using a gaseous mixture of H(2)S, CH(4), NH(3), and CO(2). A total of 23 amino acids and 4 amines, including 7 organosulfur compounds, were detected in these samples. The major amino acids with chiral centers are racemic within the accuracy of the measurements, indicating that they are not contaminants introduced during sample storage. This experiment marks the first synthesis of sulfur amino acids from spark discharge experiments designed to imitate primordial environments. The relative yield of some amino acids, in particular the isomers of aminobutyric acid, are the highest ever found in a spark discharge experiment. The simulated primordial conditions used by Miller may serve as a model for early volcanic plume chemistry and provide insight to the possible roles such plumes may have played in abiotic organic synthesis. Additionally, the overall abundances of the synthesized amino acids in the presence of H(2)S are very similar to the abundances found in some carbonaceous meteorites, suggesting that H(2)S may have played an important role in prebiotic reactions in early solar system environments. PMID:21422282

  11. Primordial Synthesis of Amines and Amino Acids in a 1958 Miller H2S-Rich Spark Discharge Experiment

    NASA Technical Reports Server (NTRS)

    Parker, Eric T.; Cleaves, Henderson J.; Dworkin, Jason P.; Glavin, Daniel P.; Callahan, Michael; Aubrey, Andrew; Lazcano, Antonio; Bada, Jeffrey L.

    2011-01-01

    Archived samples from a previously unreported 1958 Stanley Miller electric discharge experiment containing hydrogen sulfide (H2S) were recently discovered and analyzed using high-performance liquid chromatography and time-of-flight mass spectrometry. We report here the detection and quantification of primary amine-containing compounds in the original sample residues, which were produced via spark discharge using a gaseous mixture of H2S, CH4, NH3, and CO2. A total of 23 amino acids and 4 amines, including 7 organosulfur compounds, were detected in these samples. The major amino acids with chiral centers are racemic within the accuracy of the measurements, indicating that they are not contaminants introduced during sample storage. This experiment marks the first synthesis of sulfur amino acids from spark discharge experiments designed to imitate primordia! environments. The relative yield of some amino acids, in particular the isomers of aminobutyric acid, are the highest ever found in a spark discharge experiment. The simulated primordial conditions used by Miller may serve as a model for early volcanic plume chemistry and provide insight to the possible roles such plumes may have played in abiotic organic synthesis. Additionally, the overall abundances of the synthesized amino acids in the presence of H2S are very similar to the abundances found in some carbonaceous meteorites, suggesting that H2S may have played an important role in prebiotic reactions in early solar system environments.

  12. The general anesthetic propofol increases brain N-arachidonylethanolamine (anandamide) content and inhibits fatty acid amide hydrolase

    PubMed Central

    Patel, Sachin; Wohlfeil, Eric R; Rademacher, David J; Carrier, Erica J; Perry, LaToya J; Kundu, Abhijit; Falck, J R; Nithipatikom, Kasem; Campbell, William B; Hillard, Cecilia J

    2003-01-01

    Propofol (2,6-diisopropylphenol) is widely used as a general anesthetic and for the maintenance of long-term sedation. We have tested the hypothesis that propofol alters endocannabinoid brain content and that this effect contributes to its sedative properties. A sedating dose of propofol in mice produced a significant increase in the whole-brain content of the endocannabinoid, N-arachidonylethanolamine (anandamide), when administered intraperitoneally in either Intralipid or emulphor-ethanol vehicles. In vitro, propofol is a competitive inhibitor (IC50 52 μM; 95% confidence interval 31, 87) of fatty acid amide hydrolase (FAAH), which catalyzes the degradation of anandamide. Within a series of propofol analogs, the critical structural determinants of FAAH inhibition and sedation were found to overlap. Other intravenous general anesthetics, including midazolam, ketamine, etomidate, and thiopental, do not affect FAAH activity at sedative-relevant concentrations. Thiopental, however, is a noncompetitive inhibitor of FAAH at a concentration of 2 mM. Pretreatment of mice with the CB1 receptor antagonist SR141716 (1 mg kg−1, i.p.) significantly reduced the number of mice that lost their righting reflex in response to propofol. Pretreatment of mice with the CB1 receptor agonist, Win 55212-2 (1 mg kg−1, i.p.), significantly potentiated the loss of righting reflex produced by propofol. These data indicate that CB1 receptor activity contributes to the sedative properties of propofol. These data suggest that propofol activation of the endocannabinoid system, possibly via inhibition of anandamide catabolism, contributes to the sedative properties of propofol and that FAAH could be a novel target for anesthetic development. PMID:12839875

  13. Binding and Inactivation Mechanism of a Humanized Fatty Acid Amide Hydrolase by [alpha]-Ketoheterocycle Inhibitors Revealed from Cocrystal Structures

    SciTech Connect

    Mileni, Mauro; Garfunkle, Joie; DeMartino, Jessica K.; Cravatt, Benjamin F.; Boger, Dale L.; Stevens, Raymond C.

    2010-08-17

    The cocrystal X-ray structures of two isomeric {alpha}-ketooxazole inhibitors (1 (OL-135) and 2) bound to fatty acid amide hydrolase (FAAH), a key enzymatic regulator of endocannabinoid signaling, are disclosed. The active site catalytic Ser241 is covalently bound to the inhibitors electrophilic carbonyl groups, providing the first structures of FAAH bound to an inhibitor as a deprotonated hemiketal mimicking the enzymatic tetrahedral intermediate. The work also offers a detailed view of the oxyanion hole and an exceptional 'in-action' depiction of the unusual Ser-Ser-Lys catalytic triad. These structures capture the first picture of inhibitors that span the active site into the cytosolic port providing new insights that help to explain FAAH's interaction with substrate leaving groups and their role in modulating inhibitor potency and selectivity. The role for the activating central heterocycle is clearly defined and distinguished from that observed in prior applications with serine proteases, reconciling the large electronic effect of attached substituents found unique to this class of inhibitors with FAAH. Additional striking active site flexibility is seen upon binding of the inhibitors, providing insights into the existence of a now well-defined membrane access channel with the disappearance of a spatially independent portion of the acyl chain-binding pocket. Finally, comparison of the structures of OL-135 (1) and its isomer 2 indicates that they bind identically to FAAH, albeit with reversed orientations of the central activating heterocycle, revealing that the terminal 2-pyridyl substituent and the acyl chain phenyl group provide key anchoring interactions and confirming the distinguishing role of the activating oxazole.

  14. Effect of cannabidiol on sepsis-induced motility disturbances in mice: involvement of CB receptors and fatty acid amide hydrolase.

    PubMed

    de Filippis, D; Iuvone, T; d'amico, A; Esposito, G; Steardo, L; Herman, A G; Pelckmans, P A; de Winter, B Y; de Man, J G

    2008-08-01

    Sepsis is an inflammatory condition that is associated with reduced propulsive gastrointestinal motility (ileus). A therapeutic option to treat sepsis is to promote intestinal propulsion preventing bacterial stasis, overgrowth and translocation. Recent evidence suggests that anti-oxidants improve sepsis-induced ileus. Cannabidiol, a non-psychotropic component of Cannabis sativa, exerts strong anti-oxidant and anti-inflammatory effects without binding to cannabinoid CB(1) or CB(2) receptors. Cannabidiol also regulates the activity of fatty acid amide hydrolase (FAAH) which is the main enzyme involved in endocannabinoid breakdown and which modulates gastrointestinal motility. Because of the therapeutic potential of cannabidiol in several pathologies, we investigated its effect on sepsis-induced ileus and on cannabinoid receptor and FAAH expression in the mouse intestine. Sepsis was induced by treating mice with lipopolysaccharides for 18 h. Sepsis led to a decrease in gastric emptying and intestinal transit. Cannabidiol further reduced gastrointestinal motility in septic mice but did not affect gastrointestinal motility in control mice. A low concentration of the CB(1) antagonist AM251 did not affect gastrointestinal motility in control mice but reversed the effect of cannabidiol in septic mice. Sepsis was associated with a selective upregulation of intestinal CB(1) receptors without affecting CB(2) receptor expression and with increased FAAH expression. The increase in FAAH expression was completely reversed by cannabidiol but not affected by AM251. Our results show that sepsis leads to an imbalance of the endocannabinoid system in the mouse intestine. Despite its proven anti-oxidant and anti-inflammatory properties, cannabidiol may be of limited use for the treatment of sepsis-induced ileus. PMID:18373655

  15. Development and characterization of a promising fluorine-18 labelled radiopharmaceutical for in vivo imaging of fatty acid amide hydrolase.

    PubMed

    Sadovski, Oleg; Hicks, Justin W; Parkes, Jun; Raymond, Roger; Nobrega, José; Houle, Sylvain; Cipriano, Mariateresa; Fowler, Christopher J; Vasdev, Neil; Wilson, Alan A

    2013-07-15

    Fatty acid amide hydrolase (FAAH), the enzyme responsible for terminating signaling by the endocannabinoid anandamide, plays an important role in the endocannabinoid system, and FAAH inhibitors are attractive drugs for pain, addiction, and neurological disorders. The synthesis, radiosynthesis, and evaluation, in vitro and ex vivo in rat, of an (18)F-radiotracer designed to image FAAH using positron emission tomography (PET) is described. Fluorine-18 labelled 3-(4,5-dihydrooxazol-2-yl)phenyl (5-fluoropentyl)carbamate, [(18)F]5, was synthesized at high specific activity in a one-pot three step reaction using a commercial module with a radiochemical yield of 17-22% (from [(18)F]fluoride). In vitro assay using rat brain homogenates showed that 5 inhibited FAAH in a time-dependent manner, with an IC50 value of 0.82nM after a preincubation of 60min. Ex vivo biodistribution studies and ex vivo autoradiography in rat brain demonstrated that [(18)F]5 had high brain penetration with standard uptake values of up to 4.6 and had a regional distribution which correlated with reported regional FAAH enzyme activity. Specificity of binding to FAAH with [(18)F]5 was high (>90%) as demonstrated by pharmacological challenges with potent and selective FAAH inhibitors and was irreversible as demonstrated by radioactivity measurements on homogenized brain tissue extracts. We infer from these results that [(18)F]5 is a highly promising candidate radiotracer with which to image FAAH in human subjects using PET and clinical studies are proceeding. PMID:23712084

  16. Metallurgical and Biological Activity of Peroxo Complexes of Molybdenum (VI) Containing Organic Acid and Amine Bases

    NASA Astrophysics Data System (ADS)

    Nasrin, Jahanara; Saidul Islam, M.

    This study describes with the preparation, characterization and bioactivity of peroxo complexes [A: MoO(O2)(gly)(Q); B: MoO(O2)(ala)(2-pic)]of Mo(VI)] containing organic acid and amine bases. Both the complexes A and B were characterized by a variety of physicochemical techniques, viz., elemental analyses, molar conductivity, IR, NMR and electronic spectral studies. The analytical data were in good agreement with the proposed emperical formulae of both the complexes. The molar conductance values indicated both the complexes are non-electrolytes in DMF revealing that the anions are covalently bonded in all the cases. The magnetic moment values indicated that both the complexes were dimagnetic in nature suggesting that there were no changes in the oxidation states of the metal ions upon complexation. The electronic spectral data of the complexes A and B showed bands at 315-355 nm region due to the charge transfers band only. The antimicrobial properties of the peroxo complexes of Mo(VI) indicated that both the complexes were stronger antibacterial and antifungal agents. However, the highest antifungal activity was shown in the complex B against A. niger (16 mm) while the complex A of Mo(VI) showed lowest activity (10 mm). The MIC experiment showed that the complex B of Mo(VI) were more potent against all the bacteria tested than the complex A. Results showed that the complex A of Mo(VI) exhibits more toxic to brine shrimp compared to complex B of Mo(VI) indicating the lower values of LC50 for both the exposure 16 and 36 h.

  17. Oxidant-free conversion of primary amines to nitriles.

    PubMed

    Tseng, Kuei-Nin T; Rizzi, Andrew M; Szymczak, Nathaniel K

    2013-11-01

    An amide-derived NNN-Ru(II) hydride complex catalyzes oxidant-free, acceptorless, and chemoselective dehydrogenation of primary and secondary amines to the corresponding nitriles and imines with liberation of dihydrogen. The catalyst system tolerates oxidizable functionality and is selective for the dehydrogenation of primary amines (-CH2NH2) in the presence of amines without α-CH hydrogens. PMID:24144014

  18. Cloning of a Novel Arylamidase Gene from Paracoccus sp. Strain FLN-7 That Hydrolyzes Amide Pesticides

    PubMed Central

    Zhang, Jun; Yin, Jin-Gang; Hang, Bao-Jian; Cai, Shu; Li, Shun-Peng

    2012-01-01

    The bacterial isolate Paracoccus sp. strain FLN-7 hydrolyzes amide pesticides such as diflubenzuron, propanil, chlorpropham, and dimethoate through amide bond cleavage. A gene, ampA, encoding a novel arylamidase that catalyzes the amide bond cleavage in the amide pesticides was cloned from the strain. ampA contains a 1,395-bp open reading frame that encodes a 465-amino-acid protein. AmpA was expressed in Escherichia coli BL21 and homogenously purified using Ni-nitrilotriacetic acid affinity chromatography. AmpA is a homodimer with an isoelectric point of 5.4. AmpA displays maximum enzymatic activity at 40°C and a pH of between 7.5 and 8.0, and it is very stable at pHs ranging from 5.5 to 10.0 and at temperatures up to 50°C. AmpA efficiently hydrolyzes a variety of secondary amine compounds such as propanil, 4-acetaminophenol, propham, chlorpropham, dimethoate, and omethoate. The most suitable substrate is propanil, with Km and kcat values of 29.5 μM and 49.2 s−1, respectively. The benzoylurea insecticides (diflubenzuron and hexaflumuron) are also hydrolyzed but at low efficiencies. No cofactor is needed for the hydrolysis activity. AmpA shares low identities with reported arylamidases (less than 23%), forms a distinct lineage from closely related arylamidases in the phylogenetic tree, and has different biochemical characteristics and catalytic kinetics with related arylamidases. The results in the present study suggest that AmpA is a good candidate for the study of the mechanism for amide pesticide hydrolysis, genetic engineering of amide herbicide-resistant crops, and bioremediation of amide pesticide-contaminated environments. PMID:22544249

  19. Cloning of a novel arylamidase gene from Paracoccus sp. strain FLN-7 that hydrolyzes amide pesticides.

    PubMed

    Zhang, Jun; Yin, Jin-Gang; Hang, Bao-Jian; Cai, Shu; He, Jian; Zhou, Shun-Gui; Li, Shun-Peng

    2012-07-01

    The bacterial isolate Paracoccus sp. strain FLN-7 hydrolyzes amide pesticides such as diflubenzuron, propanil, chlorpropham, and dimethoate through amide bond cleavage. A gene, ampA, encoding a novel arylamidase that catalyzes the amide bond cleavage in the amide pesticides was cloned from the strain. ampA contains a 1,395-bp open reading frame that encodes a 465-amino-acid protein. AmpA was expressed in Escherichia coli BL21 and homogenously purified using Ni-nitrilotriacetic acid affinity chromatography. AmpA is a homodimer with an isoelectric point of 5.4. AmpA displays maximum enzymatic activity at 40°C and a pH of between 7.5 and 8.0, and it is very stable at pHs ranging from 5.5 to 10.0 and at temperatures up to 50°C. AmpA efficiently hydrolyzes a variety of secondary amine compounds such as propanil, 4-acetaminophenol, propham, chlorpropham, dimethoate, and omethoate. The most suitable substrate is propanil, with K(m) and k(cat) values of 29.5 μM and 49.2 s(-1), respectively. The benzoylurea insecticides (diflubenzuron and hexaflumuron) are also hydrolyzed but at low efficiencies. No cofactor is needed for the hydrolysis activity. AmpA shares low identities with reported arylamidases (less than 23%), forms a distinct lineage from closely related arylamidases in the phylogenetic tree, and has different biochemical characteristics and catalytic kinetics with related arylamidases. The results in the present study suggest that AmpA is a good candidate for the study of the mechanism for amide pesticide hydrolysis, genetic engineering of amide herbicide-resistant crops, and bioremediation of amide pesticide-contaminated environments. PMID:22544249

  20. Chemical reactivity of graphene oxide towards amines elucidated by solid-state NMR

    NASA Astrophysics Data System (ADS)

    Vacchi, Isabella A.; Spinato, Cinzia; Raya, Jésus; Bianco, Alberto; Ménard-Moyon, Cécilia

    2016-07-01

    Graphene oxide (GO) is an attractive nanomaterial for many applications. Controlling the functionalization of GO is essential for the design of graphene-based conjugates with novel properties. But, the chemical composition of GO has not been fully elucidated yet. Due to the high reactivity of the oxygenated moieties, mainly epoxy, hydroxyl and carboxyl groups, several derivatization reactions may occur concomitantly. The reactivity of GO with amine derivatives has been exploited in the literature to design graphene-based conjugates, mainly through amidation. However, in this study we undoubtedly demonstrate using magic angle spinning (MAS) solid-state NMR that the reaction between GO and amine functions occurs via ring opening of the epoxides, and not by amidation. We also prove that there is a negligible amount of carboxylic acid groups in two GO samples obtained by a different synthesis process, hence eliminating the possibility of amidation reactions with amine derivatives. This work brings additional insights into the chemical reactivity of GO, which is fundamental to control its functionalization, and highlights the major role of MAS NMR spectroscopy for a comprehensive characterization of derivatized GO.Graphene oxide (GO) is an attractive nanomaterial for many applications. Controlling the functionalization of GO is essential for the design of graphene-based conjugates with novel properties. But, the chemical composition of GO has not been fully elucidated yet. Due to the high reactivity of the oxygenated moieties, mainly epoxy, hydroxyl and carboxyl groups, several derivatization reactions may occur concomitantly. The reactivity of GO with amine derivatives has been exploited in the literature to design graphene-based conjugates, mainly through amidation. However, in this study we undoubtedly demonstrate using magic angle spinning (MAS) solid-state NMR that the reaction between GO and amine functions occurs via ring opening of the epoxides, and not by

  1. Fatty Acid Amide Hydrolase-Dependent Generation of Antinociceptive Drug Metabolites Acting on TRPV1 in the Brain

    PubMed Central

    Blomgren, Anders; Simonsen, Charlotte; Daulhac, Laurence; Libert, Frédéric; Chapuy, Eric; Etienne, Monique; Högestätt, Edward D.; Zygmunt, Peter M.; Eschalier, Alain

    2013-01-01

    The discovery that paracetamol is metabolized to the potent TRPV1 activator N-(4-hydroxyphenyl)-5Z,8Z,11Z,14Z-eicosatetraenamide (AM404) and that this metabolite contributes to paracetamol’s antinociceptive effect in rodents via activation of TRPV1 in the central nervous system (CNS) has provided a potential strategy for developing novel analgesics. Here we validated this strategy by examining the metabolism and antinociceptive activity of the de-acetylated paracetamol metabolite 4-aminophenol and 4-hydroxy-3-methoxybenzylamine (HMBA), both of which may undergo a fatty acid amide hydrolase (FAAH)-dependent biotransformation to potent TRPV1 activators in the brain. Systemic administration of 4-aminophenol and HMBA led to a dose-dependent formation of AM404 plus N-(4-hydroxyphenyl)-9Z-octadecenamide (HPODA) and arvanil plus olvanil in the mouse brain, respectively. The order of potency of these lipid metabolites as TRPV1 activators was arvanil = olvanil>>AM404> HPODA. Both 4-aminophenol and HMBA displayed antinociceptive activity in various rodent pain tests. The formation of AM404, arvanil and olvanil, but not HPODA, and the antinociceptive effects of 4-aminophenol and HMBA were substantially reduced or disappeared in FAAH null mice. The activity of 4-aminophenol in the mouse formalin, von Frey and tail immersion tests was also lost in TRPV1 null mice. Intracerebroventricular injection of the TRPV1 blocker capsazepine eliminated the antinociceptive effects of 4-aminophenol and HMBA in the mouse formalin test. In the rat, pharmacological inhibition of FAAH, TRPV1, cannabinoid CB1 receptors and spinal 5-HT3 or 5-HT1A receptors, and chemical deletion of bulbospinal serotonergic pathways prevented the antinociceptive action of 4-aminophenol. Thus, the pharmacological profile of 4-aminophenol was identical to that previously reported for paracetamol, supporting our suggestion that this drug metabolite contributes to paracetamol’s analgesic activity via activation

  2. Zinc(II) complexes with heterocyclic ether, acid and amide. Crystal structure, spectral, thermal and antibacterial activity studies

    NASA Astrophysics Data System (ADS)

    Jabłońska-Wawrzycka, Agnieszka; Rogala, Patrycja; Czerwonka, Grzegorz; Hodorowicz, Maciej; Stadnicka, Katarzyna

    2016-02-01

    The reaction of zinc salts with heterocyclic ether (1-ethoxymethyl-2-methylimidazole (1-ExMe-2-MeIm)), acid (pyridine-2,3-dicarboxylic acid (2,3-pydcH2)) and amide (3,5-dimethylpyrazole-1-carboxamide (3,5-DMePzCONH2)) yielded three new zinc complexes formulated as [Zn(1-ExMe-2-MeIm)2Cl2] 1, fac-[Zn(H2O)6][Zn(2,3-pydcH)3]22 and [Zn(3,5-DMePz)2(NCO)2] 3. Complexes of 1 and 3 are four-coordinated with a tetrahedron as coordination polyhedron. However, compound 2 forms an octahedral cation-anion complex. The complex 3 was prepared by eliminating of the carboxamide group from the ligand and then the 3,5-dimethylpyrazole (3,5-DMePz) and isocyanates formed were employed as new ligands. The IR and X-ray studies have confirmed a bidentate fashion of coordination of the 2,3-pydcH and monodentate fashion of coordination of the 1-ExMe-2-MeIm and 3,5-DMePz to the Zn(II) ions. The crystal packing of Zn(II) complexes are stabilized by intermolecular classical hydrogen bonds of O-H⋯O and N-H⋯O types. The most interesting feature of the supramolecular architecture of complexes is the existence of C-H⋯O, C-H⋯Cl and C-H⋯π interactions and π⋯π stacking, which also contributes to structural stabilisation. The correlation between crystal structure and thermal stability of zinc complexes is observed. In all compounds the fragments of ligands donor-atom containing go in the last steps. Additionally, antimicrobial activities of compounds were carried out against certain Gram-positive and Gram-negative bacteria and counts of CFU (colony forming units) were also determined. The achieved results confirmed a significant antibacterial activity of some tested zinc complexes. On the basis of the Δ log CFU values the antibacterial activity of zinc complexes follows the order: 3 > 2 > 1. Influence a number of N-donor atoms in zinc environment on antibacterial activity is also observed.

  3. Simultaneous Inhibition of Fatty Acid Amide Hydrolase and Monoacylglycerol Lipase Shares Discriminative Stimulus Effects with Δ9-Tetrahydrocannabinol in Mice

    PubMed Central

    Hruba, Lenka; Seillier, Alexandre; Zaki, Armia; Cravatt, Benjamin F.; Lichtman, Aron H.; Giuffrida, Andrea

    2015-01-01

    Monoacylglycerol lipase (MAGL) and fatty acid amide hydrolase (FAAH) inhibitors exert preclinical effects indicative of therapeutic potential (i.e., analgesia). However, the extent to which MAGL and FAAH inhibitors produce unwanted effects remains unclear. Here, FAAH and MAGL inhibition was examined separately and together in a Δ9-tetrahydrocannabinol (Δ9-THC; 5.6 mg/kg i.p.) discrimination assay predictive of subjective effects associated with cannabis use, and the relative contribution of N-arachidonoyl ethanolamine (AEA) and 2-arachidonoylglycerol (2-AG) in the prefrontal cortex, hippocampus, and caudate putamen to those effects was examined. Δ9-THC dose-dependently increased Δ9-THC appropriate responses (ED50 value = 2.8 mg/kg), whereas the FAAH inhibitors PF-3845 [N-3-pyridinyl-4-[[3-[[5-(trifluoromethyl)-2-pyridinyl]oxy]phenyl]methyl]-1-piperidinecarboxamide] and URB597 [(3′-​(aminocarbonyl)[1,​1′-​biphenyl]-​3-​yl)-​cyclohexylcarbamate] or a MAGL inhibitor JZL184 [4-​nitrophenyl-​4-​(dibenzo[d][1,​3]dioxol-​5-​yl(hydroxy)methyl)piperidine-​1-​carboxylate] alone did not substitute for the Δ9-THC discriminative stimulus. The nonselective FAAH/MAGL inhibitors SA-57 [4-[2-(4-chlorophenyl)ethyl]-1-piperidinecarboxylic acid 2-(methylamino)-2-oxoethyl ester] and JZL195 [4-​nitrophenyl 4-​(3-​phenoxybenzyl)piperazine-​1-​carboxylate] fully substituted for Δ9-THC with ED50 values equal to 2.4 and 17 mg/kg, respectively. Full substitution for Δ9-THC was also produced by a combination of JZL184 and PF-3845, but not by a combination of JZL184 and URB597 (i.e., 52% maximum). Cannabinoid receptor type 1 antagonist rimonabant attenuated the discriminative stimulus effects of Δ9-THC, SA-57, JZL195, and the combined effects of JZL184 and PF-3845. Full substitution for the Δ9-THC discriminative stimulus occurred only when both 2-AG and AEA were significantly elevated, and the patterns of increased endocannabinoid content were

  4. Silicone boronates reversibly crosslink using Lewis acid-Lewis base amine complexes.

    PubMed

    Dodge, Laura; Chen, Yunqing; Brook, Michael A

    2014-07-21

    Silicone elastomers are normally thermosets, which are not readily recycled or repurposed. The few examples of thermoplastic silicone elastomers depend on reversible covalent and non-covalent molecular interactions. It is demonstrated that amine-boronate complex formation provides a simple and flexible route to reversible crosslinked silicones. A variety of network structures were prepared by use of terminal and pendantly functionalised silicone boronates and amines. The crosslink density was quantified using a combination of Shore-hardness measurements, swelling, and rheological analyses. Stress induced by compressive force could be relieved through dynamic B-N bond reformation at 60 °C. Materials could be fully disassembled through introduction of n-butylamine and successfully reformed upon removal of the monofunctional amine by evaporation. PMID:24986574

  5. Simplified mechanism for new particle formation from methanesulfonic acid, amines, and water via experiments and ab initio calculations

    PubMed Central

    Dawson, Matthew L.; Varner, Mychel E.; Perraud, Véronique; Ezell, Michael J.; Gerber, R. Benny; Finlayson-Pitts, Barbara J.

    2012-01-01

    Airborne particles affect human health and significantly influence visibility and climate. A major fraction of these particles result from the reactions of gaseous precursors to generate low-volatility products such as sulfuric acid and high-molecular weight organics that nucleate to form new particles. Ammonia and, more recently, amines, both of which are ubiquitous in the environment, have also been recognized as important contributors. However, accurately predicting new particle formation in both laboratory systems and in air has been problematic. During the oxidation of organosulfur compounds, gas-phase methanesulfonic acid is formed simultaneously with sulfuric acid, and both are found in particles in coastal regions as well as inland. We show here that: (i) Amines form particles on reaction with methanesulfonic acid, (ii) water vapor is required, and (iii) particle formation can be quantitatively reproduced by a semiempirical kinetics model supported by insights from quantum chemical calculations of likely intermediate clusters. Such an approach may be more broadly applicable in models of outdoor, indoor, and industrial settings where particles are formed, and where accurate modeling is essential for predicting their impact on health, visibility, and climate. PMID:23090988

  6. Enhanced Photocatalytic Performance of ZnS for Reversible Amination of α-oxo Acids by Hydrothermal Treatment

    NASA Astrophysics Data System (ADS)

    Wang, Wei; Li, Qiliang; Liu, Xiaoyang; Yang, Yanqiang; Su, Wenhui

    2012-08-01

    To understand how life could have originated on early Earth, it is essential to know what biomolecules and metabolic pathways are shared by extant organisms and what organic compounds and their chemical reaction channels were likely to have been primordially available during the initial phase of the formation of prebiotic metabolism. In a previous study, we demonstrated for the first time the reversible amination of α-oxo acids on the surface of photo-illuminated ZnS. The sulfide mineral is a typical component at the periphery of submarine hydrothermal vents which has been frequently argued as a very attractive venue for the origin of life. In this work, in order to simulate more closely the precipitation environments of ZnS in the vent systems, we treated newly-precipitated ZnS with hydrothermal conditions and found that its photocatalytic power was significantly enhanced because the relative crystallinity of the treated sample was markedly increased with increasing temperature. Since the reported experimental conditions are believed to have been prevalent in shallow-water hydrothermal vents of early Earth and the reversible amination of α-oxo acids is a key metabolic pathway in all extant life forms, the results of this work provide a prototypical model of the prebiotic amino acid redox metabolism. The amino acid dehydrogenase-like chemistry on photo-irradiated ZnS surfaces may advance our understanding of the establishment of archaic non-enzymatic metabolic systems.

  7. Simplified mechanism for new particle formation from methanesulfonic acid, amines, and water via experiments and ab initio calculations.

    PubMed

    Dawson, Matthew L; Varner, Mychel E; Perraud, Véronique; Ezell, Michael J; Gerber, R Benny; Finlayson-Pitts, Barbara J

    2012-11-13

    Airborne particles affect human health and significantly influence visibility and climate. A major fraction of these particles result from the reactions of gaseous precursors to generate low-volatility products such as sulfuric acid and high-molecular weight organics that nucleate to form new particles. Ammonia and, more recently, amines, both of which are ubiquitous in the environment, have also been recognized as important contributors. However, accurately predicting new particle formation in both laboratory systems and in air has been problematic. During the oxidation of organosulfur compounds, gas-phase methanesulfonic acid is formed simultaneously with sulfuric acid, and both are found in particles in coastal regions as well as inland. We show here that: (i) Amines form particles on reaction with methanesulfonic acid, (ii) water vapor is required, and (iii) particle formation can be quantitatively reproduced by a semiempirical kinetics model supported by insights from quantum chemical calculations of likely intermediate clusters. Such an approach may be more broadly applicable in models of outdoor, indoor, and industrial settings where particles are formed, and where accurate modeling is essential for predicting their impact on health, visibility, and climate. PMID:23090988

  8. Hydrogen bonded supramolecular architectures of organic salts based on 5,7-dimethyl-1,8-naphthyridine-2-amine and acidic compounds

    NASA Astrophysics Data System (ADS)

    Jin, Shouwen; Zhang, Wenbiao; Liu, Li; Gao, Hongfang; Wang, Daqi; Chen, Rongpo; Xu, Xiaolei

    2010-06-01

    Studies concentrating on hydrogen bonding between the base of 5,7-dimethyl-1,8-naphthyridine-2-amine and acidic compounds have led to an increased understanding of the role 5,7-dimethyl-1,8-naphthyridine-2-amine has in binding with acidic compounds. Here anhydrous and hydrated multicomponent crystals of 5,7-dimethyl-1,8-naphthyridine-2-amine have been prepared with oxalic acid, 2,4,6-trinitrophenol, terephthalic acid, and phthalic acid. The four crystalline forms reported are organic salts of which the crystal structures have all been determined by X-ray diffraction. All products were formed in solution and obtained by the slow evaporation technique. The role of weak and strong hydrogen bonding in the crystal packing is ascertained.

  9. Novel Regenerated Solvent Extraction Processes for the Recovery of Carboxylic Acids or Ammonia from Aqueous Solutions Part I. Regeneration of Amine-Carboxylic Acid Extracts

    SciTech Connect

    Poole, L.J.; King, C.J.

    1990-03-01

    Two novel regenerated solvent extraction processes are examined. The first process has the potential to reduce the energy costs inherent in the recovery of low-volatility carboxylic acids from dilute aqueous solutions. The second process has the potential for reducing the energy costs required for separate recovery of ammonia and acid gases (e.g. CO{sub 2} and H{sub 2}S) from industrial sour waters. The recovery of carboxylic acids from dilute aqueous solution can be achieved by extraction with tertiary amines. An approach for regeneration and product recovery from such extracts is to back-extract the carboxylic acid with a water-soluble, volatile tertiary amine, such as trimethylamine. The resulting trimethylammonium carboxylate solution can be concentrated and thermally decomposed, yielding the product acid and the volatile amine for recycle. Experimental work was performed with lactic acid, succinic acid, and fumaric acid. Equilibrium data show near-stoichiometric recovery of the carboxylic acids from an organic solution of Alamine 336 into aqueous solutions of trimethylamine. For fumaric and succinic acids, partial evaporation of the aqueous back extract decomposes the carboxylate and yields the acid product in crystalline form. The decomposition of aqueous solutions of trimethylammonium lactates was not carried out to completion, due to the high water solubility of lactic acid and the tendency of the acid to self-associate. The separate recovery of ammonia and acid gases from sour waters can be achieved by combining steam-stripping of the acid gases with simultaneous removal of ammonia by extraction with a liquid cation exchanger. The use of di-2,4,4-trimethylpentyl phosphinic acid as the liquid cation exchanger is explored in this work. Batch extraction experiments were carried out to measure the equilibrium distribution ratio of ammonia between an aqueous buffer solution and an organic solution of the phosphinic acid (0.2N) in Norpar 12. The concentration

  10. Copper-catalyzed α-amination of phosphonates and phosphine oxides: a direct approach to α-amino phosphonic acids and derivatives.

    PubMed

    McDonald, Stacey L; Wang, Qiu

    2014-02-10

    A direct approach to important α-amino phosphonic acids and its derivatives has been developed by using copper-catalyzed electrophilic amination of α-phosphonate zincates with O-acyl hydroxylamines. This amination provides the first example of CN bond formation which directly introduces acyclic and cyclic amines to the α-position of phosphonates in one step. The reaction is readily promoted at room temperature with as little as 0.5 mol % of catalyst, and demonstrates high efficiency on a broad substrate scope. PMID:24474326

  11. The Effect of Temperature and Acid Gas Loading on Corrosion Behavior of API 5L X52 Carbon Steel in Amine Unit

    NASA Astrophysics Data System (ADS)

    Javidi, M.; Lalehparvar, M. M.; Ghassemi, A.

    2016-05-01

    The effect of temperature and H2S concentration on amine corrosion of API 5L X52 carbon steel in a CO2-saturated 25 wt.% diethanolamine solution was investigated via electrochemical techniques. It was found that increase in temperature from 25 to 80 °C resulted in severe increase in corrosion rate from 0.88 to 16.24 mpy due to increase in degradation rate of amine. Also, it was concluded that increase in H2S concentration led to increase in corrosion rate because of formation of more heat stable amine salts. The effect of temperature on corrosion rate was more significant than acid gas loading.

  12. Evidence of acid-base interactions between amines and model indoor surfaces by ATR-FTIR spectroscopy

    NASA Astrophysics Data System (ADS)

    Destaillats, Hugo; Singer, Brett C.; Gundel, Lara A.

    Molecular associations of pyridine with cellulose and gypsum, surrogates for common indoor surface materials, were studied using an attenuated total reflection (ATR)-Fourier transform infrared (FTIR) spectrophotometric method. The purpose of this study was to gain insight into the molecular interactions of amines with well-characterized materials that affect their partitioning between indoor air and surfaces. The experimental results suggest the presence of at least two sorptive states for volatile and semivolatile amines, attributed to the chemisorbed species and to a more labile surface state (i.e., physisorbed pyridine). Both exhibited spectroscopic signatures corresponding to aromatic C-H stretching modes (2950-3100 cm -1) in the studied spectral region. Chemisorbed pyridine could be identified by the presence of additional IR signals in the N-H and O-H stretching region of the spectrum (2900-3600 cm -1). During desorption under a stream of N 2, surface enrichment in the chemisorbed species was evidenced by a slower reduction of the absorbance of the broad band at 2900-3600 cm -1 in relation to the total pyridine absorbance change. This spectroscopic evidence for acid-base interactions between amines and surfaces is consistent with the desorption behavior observed in previous work for nicotine from model surfaces.

  13. Caffeic acid phenethyl amide improves glucose homeostasis and attenuates the progression of vascular dysfunction in Streptozotocin-induced diabetic rats

    PubMed Central

    2013-01-01

    Background Glucose intolerance and cardiovascular complications are major symptoms in patients with diabetes. Many therapies have proven beneficial in treating diabetes in animals by protecting the cardiovascular system and increasing glucose utilization. In this study, we evaluated the effects of caffeic acid phenethyl amide (CAPA) on glucose homeostasis and vascular function in streptozotocin (STZ)-induced type 1 diabetic rats. Methods Diabetes (blood glucose levels > 350 mg/dL), was induced in Wistar rats by a single intravenous injection of 60 mg/kg STZ. Hypoglycemic effects were then assessed in normal and type 1 diabetic rats. In addition, coronary blood flow in Langendorff-perfused hearts was evaluated in the presence or absence of nitric oxide synthase (NOS) inhibitor. The thoracic aorta was used to measure vascular response to phenylephrine. Finally, the effect of chronic treatment of CAPA and insulin on coronary artery flow and vascular response to phenylephrine were analyzed in diabetic rats. Results Oral administration of 0.1 mg/kg CAPA decreased plasma glucose in normal (32.9 ± 2.3% decrease, P < 0.05) and diabetic rats (11.8 ± 5.5% decrease, P < 0.05). In normal and diabetic rat hearts, 1–10 μM CAPA increased coronary flow rate, and this increase was abolished by 10 μM NOS inhibitor. In the thoracic aorta, the concentration/response curve of phenylephrine was right-shifted by administration of 100 μM CAPA. Coronary flow rate was reduced to 7.2 ± 0.2 mL/min at 8 weeks after STZ-induction. However, 4 weeks of treatment with CAPA (3 mg/kg, intraperitoneal, twice daily) started at 4 weeks after STZ induction increased flow rate to 11.2 ± 0.5 mL/min (P < 0.05). In addition, the contractile response induced by 1 μM phenylephrine increased from 6.8 ± 0.6 mN to 11.4 ± 0.4 mN (P < 0.05) and 14.9 ± 1.4 mN (P < 0.05) by insulin (1 IU/kg, intraperitoneal) or CAPA treatment, respectively. Conclusions CAPA induced hypoglycemic activity, increased

  14. (E)-4-aryl-4-oxo-2-butenoic acid amides, chalcone–aroylacrylic acid chimeras: Design, antiproliferative activity and inhibition of tubulin polymerization

    PubMed Central

    Vitorović-Todorović, Maja D.; Erić-Nikolić, Aleksandra; Kolundžija, Branka; Hamel, Ernest; Ristić, Slavica; Juranić, Ivan O.; Drakulić, Branko J.

    2013-01-01

    Antiproliferative activity of twenty-nine (E)-4-aryl-4-oxo-2-butenoic acid amides against three human tumor cell lines (HeLa, FemX, and K562) is reported. Compounds showed antiproliferative activity in one-digit micromolar to submicromolar concentrations. The most active derivatives toward all the cell lines tested bear alkyl substituents on the aroyl moiety of the molecules. Fourteen compounds showed tubulin assembly inhibition at concentrations <20 μM. The most potent inhibitor of tubulin assembly was unsubstituted compound 1, with IC50 = 2.9 μM. Compound 23 had an oral LD50 in vivo of 45 mg/kg in mice. Cell cycle analysis on K562 cells showed that compounds 1, 2 and 23 caused accumulation of cells in the G2/M phase, but inhibition of microtubule polymerization is not the principal mode of action of the compounds. Nevertheless, they may be useful leads for the design of a new class of antitubulin agents. PMID:23353745

  15. Aminocarbonylation of 4-iodo-1H-imidazoles with an amino acid amide nucleophile: synthesis of constrained H-Phe-Phe-NH2 analogues.

    PubMed

    Skogh, Anna; Fransson, Rebecca; Sköld, Christian; Larhed, Mats; Sandström, Anja

    2013-12-01

    A simple and an expedient process to prepare 5-aryl-1-benzyl-1H-imidazole-4-carboxamides by the aminocarbonylation of 5-aryl-4-iodo-1H-imidazoles using ex situ generation of CO from Mo(CO)6 with an amino acid amide nucleophile is reported. Furthermore, a microwave-assisted protocol for the direct C-5 arylation of 1-benzyl-1H-imidazole and a regioselective C-4 iodination method to acquire starting material for our aminocarbonylation are presented. The method can be used to prepare imidazole based peptidomimetics, herein exemplified by the synthesis of constrained H-Phe-Phe-NH2 analogues. PMID:24171628

  16. Inhibitors of HIV-1 maturation: Development of structure-activity relationship for C-28 amides based on C-3 benzoic acid-modified triterpenoids.

    PubMed

    Swidorski, Jacob J; Liu, Zheng; Sit, Sing-Yuen; Chen, Jie; Chen, Yan; Sin, Ny; Venables, Brian L; Parker, Dawn D; Nowicka-Sans, Beata; Terry, Brian J; Protack, Tricia; Rahematpura, Sandhya; Hanumegowda, Umesh; Jenkins, Susan; Krystal, Mark; Dicker, Ira B; Meanwell, Nicholas A; Regueiro-Ren, Alicia

    2016-04-15

    We have recently reported on the discovery of a C-3 benzoic acid (1) as a suitable replacement for the dimethyl succinate side chain of bevirimat (2), an HIV-1 maturation inhibitor that reached Phase II clinical trials before being discontinued. Recent SAR studies aimed at improving the antiviral properties of 2 have shown that the benzoic acid moiety conferred topographical constraint to the pharmacophore and was associated with a lower shift in potency in the presence of human serum albumin. In this manuscript, we describe efforts to improve the polymorphic coverage of the C-3 benzoic acid chemotype through modifications at the C-28 position of the triterpenoid core. The dimethylaminoethyl amides 17 and 23 delivered improved potency toward bevirimat-resistant viruses while increasing C24 in rat oral PK studies. PMID:26988305

  17. Synthesis and structure-activity relationship studies of O-biphenyl-3-yl carbamates as peripherally restricted fatty acid amide hydrolase inhibitors.

    PubMed

    Moreno-Sanz, Guillermo; Duranti, Andrea; Melzig, Laurin; Fiorelli, Claudio; Ruda, Gian Filippo; Colombano, Giampiero; Mestichelli, Paola; Sanchini, Silvano; Tontini, Andrea; Mor, Marco; Bandiera, Tiziano; Scarpelli, Rita; Tarzia, Giorgio; Piomelli, Daniele

    2013-07-25

    The peripherally restricted fatty acid amide hydrolase (FAAH) inhibitor URB937 (3, cyclohexylcarbamic acid 3'-carbamoyl-6-hydroxybiphenyl-3-yl ester) is extruded from the brain and spinal cord by the Abcg2 efflux transporter. Despite its inability to enter the central nervous system (CNS), 3 exerts profound antinociceptive effects in mice and rats, which result from the inhibition of FAAH in peripheral tissues and the consequent enhancement of anandamide signaling at CB1 cannabinoid receptors localized on sensory nerve endings. In the present study, we examined the structure-activity relationships (SAR) for the biphenyl region of compound 3, focusing on the carbamoyl and hydroxyl groups in the distal and proximal phenyl rings. Our SAR studies generated a new series of peripherally restricted FAAH inhibitors and identified compound 35 (cyclohexylcarbamic acid 3'-carbamoyl-5-hydroxybiphenyl-3-yl ester) as the most potent brain-impermeant FAAH inhibitor disclosed to date. PMID:23822179

  18. Reactions of hypochlorous acid with biological substrates are activated catalytically by tertiary amines.

    PubMed

    Prütz, W A

    1998-09-15

    The activation of reactions of HOCl with a variety of model substrates by tertiary amines was investigated spectroscopically by tandem-mix and stopped-flow techniques. HOCl-induced chlorination of salicylate can be sped up by several orders of magnitude by catalytic amounts of trimethylamine (TMN). The effect is obviously due to the fast generation of reactive quarternary chloramonium ions, TMN+ Cl, which act as chain carrier in a catalytic reaction cycle. Of various catalysts tested, quinine shows the highest activity; this is attributable to the quinuclidine (QN) substituent, a bicyclic tertiary amine, forming a particularly reactive chloro derivative, QN+ Cl, which does not decompose autocatalytically. The rate of catalytic salicylate chlorination as a function of pH (around pH 7) depends not at least on the basicity of the tertiary amine; the rate increases with pH in the cases of TMN and quinuclidine (high basicity), but decreases with pH in the case of MES (low basicity). Tertiary amines also catalyze the interaction between HOCl and alkenes, as shown using sorbate as model. Reaction of HOCl with the nucleotides GMP and CMP is sped up remarkably by catalytic amounts of tertiary amines. In the case of GMP the same product spectrum is produced by HOCl in absence and presence of catalyst, but a change in the product spectra is obtained when AMP and CMP are reacted with HOCl in presence of catalyst. Using poly(dA-dT).poly(dA-dT) as DNA model, it is shown that HOCl primarily induces an absorbance increase at 263 nm, which indicates unfolding of the double strand due to fast chlorination of thymidine; a subsequent secondary absorbance decrease can be explained by slow chlorination of adenosine. Both the primary and secondary processes are activated by catalytic amounts of quinine. No evidence was found for a radical pathway in TMN-mediated oxidation of formate by HOCl. The present results suggest that low concentrations of certain tertiary amines have the potential

  19. Bacillus anthracis ω-amino acid:pyruvate transaminase employs a different mechanism for dual substrate recognition than other amine transaminases.

    PubMed

    Steffen-Munsberg, Fabian; Matzel, Philipp; Sowa, Miriam A; Berglund, Per; Bornscheuer, Uwe T; Höhne, Matthias

    2016-05-01

    Understanding the metabolic potential of organisms or a bacterial community based on their (meta) genome requires the reliable prediction of an enzyme's function from its amino acid sequence. Besides a remarkable development in prediction algorithms, the substrate scope of sequences with low identity to well-characterized enzymes remains often very elusive. From a recently conducted structure function analysis study of PLP-dependent enzymes, we identified a putative transaminase from Bacillus anthracis (Ban-TA) with the crystal structure 3N5M (deposited in the protein data bank in 2011, but not yet published). The active site residues of Ban-TA differ from those in related (class III) transaminases, which thereby have prevented function predictions. By investigating 50 substrate combinations its amine and ω-amino acid:pyruvate transaminase activity was revealed. Even though Ban-TA showed a relatively narrow amine substrate scope within the tested substrates, it accepts 2-propylamine, which is a prerequisite for industrial asymmetric amine synthesis. Structural information implied that the so-called dual substrate recognition of chemically different substrates (i.e. amines and amino acids) differs from that in formerly known enzymes. It lacks the normally conserved 'flipping' arginine, which enables dual substrate recognition by its side chain flexibility in other ω-amino acid:pyruvate transaminases. Molecular dynamics studies suggested that another arginine (R162) binds ω-amino acids in Ban-TA, but no side chain movements are required for amine and amino acid binding. These results, supported by mutagenesis studies, provide functional insights for the B. anthracis enzyme, enable function predictions of related proteins, and broadened the knowledge regarding ω-amino acid and amine converting transaminases. PMID:26795966

  20. Determination of acid dissociation constant of 20 coumarin derivatives by capillary electrophoresis using the amine capillary and two different methodologies.

    PubMed

    Nowak, Paweł Mateusz; Woźniakiewicz, Michał; Piwowarska, Monika; Kościelniak, Paweł

    2016-05-13

    In this work capillary electrophoresis has been used to determine acid dissociation constant of 20 structurally diverse coumarin derivatives. For a majority of compounds pKa value has been determined for the first time. The obtained values vary between 4.16-9.10pH unit, pointing to the interesting structure-acidity relationships. The amine permanently coated capillary has been applied for that purpose, because it has turned out to be more effective in pKa determination than the bare silica and other coated capillaries, ensuring good precision and shorter migration times. A traditional methodology relying on measurements in a broad pH range and fitting of a sigmoidal function has been compared to an alternative simplified approach, reported for the first time, where only two electrophoretic mobility values suffice for pKa estimation. The first value corresponds to the partially ionized form and it is measured experimentally, while the second one to the totally ionized form - it is measured experimentally (two-values method) or estimated directly from molecular mass (one-value method). We show that despite a limited measurements number, the alternative approach may be consistent with the traditional methodology, yielding the relatively low pKa deviation. Its reliability has also been confirmed by the analytical predictions, comprising resolution, migration order, migration times and peaks overlapping. Therefore, combination of the amine capillary with the simplified calculation method is an attractive tool for fast and reliable pKa estimation. PMID:27083264

  1. Determination of dansylated amino acids and biogenic amines in Cannonau and Vermentino wines by HPLC-FLD.

    PubMed

    Tuberoso, Carlo Ignazio Giovanni; Congiu, Francesca; Serreli, Gabriele; Mameli, Stefano

    2015-05-15

    Free amino acids (AA) and biogenic amines (BA) were quantified for the first time in Cannonau and Vermentino wines, the two most popular "Controlled Designation of Origin" wines from Sardinia (Italy). An analytical method for the simultaneous determination of AA and BA was developed, using selective derivatization with dansyl chloride followed by HPLC with fluorescence detection. Thirty-two compounds were identified in the wines analysed. High levels of AA were found, with proline being the most abundant with average levels of 1244 ± 398 and 1008 ± 281 mg/L in Cannonau and Vermentino wines, respectively. BA were detected at average concentrations <10mg/L, except putrescine which reached 20.5 ± 10.2mg/L in Cannonau wines. Histamine was never detected in any Vermentino wines. γ-Aminobutyric acid, 4-hydroxyproline, glycine, leucine+isoleucine and putrescine proved to be useful for differentiating Cannonau wines from Vermentino wines. PMID:25577047

  2. Structure-property relationships of a class of carbamate-based Fatty Acid Amide Hydrolase (FAAH) inhibitors: chemical and biological stability

    PubMed Central

    Vacondio, Federica; Silva, Claudia; Lodola, Alessio; Fioni, Alessandro; Rivara, Silvia; Duranti, Andrea; Tontini, Andrea; Sanchini, Silvano; Clapper, Jason; Piomelli, Daniele; Tarzia, Giorgio

    2012-01-01

    Cyclohexylcarbamic acid aryl esters are a class of Fatty Acid Amide Hydrolase (FAAH) inhibitors, which includes the reference compound URB597. The reactivity of their carbamate fragment is involved in pharmacological activity and may affect pharmacokinetic and toxicological properties. We conducted in vitro stability experiments in chemical and biological environments to investigate the structure-stability relationships in this class of compounds. The results show that electrophilicity of the carbamate influences its chemical stability, as suggested by the relation between the rate constant of alkaline hydrolysis (log kpH9) and the energy of lowest unoccupied molecular orbital (LUMO). Introduction of small, electron donor substituents at conjugated positions of the O-aryl moiety increased overall hydrolytic stability of the carbamate group without affecting FAAH inhibitory potency, whereas peripheral nonconjugated hydrophilic groups, which favor FAAH recognition, helped reducing oxidative metabolism in the liver. PMID:19554599

  3. Chemical reactivity of graphene oxide towards amines elucidated by solid-state NMR.

    PubMed

    Vacchi, Isabella A; Spinato, Cinzia; Raya, Jésus; Bianco, Alberto; Ménard-Moyon, Cécilia

    2016-07-14

    Graphene oxide (GO) is an attractive nanomaterial for many applications. Controlling the functionalization of GO is essential for the design of graphene-based conjugates with novel properties. But, the chemical composition of GO has not been fully elucidated yet. Due to the high reactivity of the oxygenated moieties, mainly epoxy, hydroxyl and carboxyl groups, several derivatization reactions may occur concomitantly. The reactivity of GO with amine derivatives has been exploited in the literature to design graphene-based conjugates, mainly through amidation. However, in this study we undoubtedly demonstrate using magic angle spinning (MAS) solid-state NMR that the reaction between GO and amine functions occurs via ring opening of the epoxides, and not by amidation. We also prove that there is a negligible amount of carboxylic acid groups in two GO samples obtained by a different synthesis process, hence eliminating the possibility of amidation reactions with amine derivatives. This work brings additional insights into the chemical reactivity of GO, which is fundamental to control its functionalization, and highlights the major role of MAS NMR spectroscopy for a comprehensive characterization of derivatized GO. PMID:27411370

  4. Corrosion inhibition of aminated hydroxyl ethyl cellulose on mild steel in acidic condition.

    PubMed

    Sangeetha, Y; Meenakshi, S; Sairam Sundaram, C

    2016-10-01

    Aminated hydroxyethyl cellulose (AHEC) was synthesized, characterized using Fourier Transform Infrared spectroscopy (FTIR) and the corrosion inhibition of AHEC on mild steel in 1M HCl was studied using chemical and electrochemical studies. Results obtained in weight loss method showed that inhibition efficiency increased with increase in concentration of AHEC. The adsorption of the inhibitor on metal surface followed Frumkin isotherm. Polarization studies revealed that the AHEC inhibits through mixed mode. Thermodynamic parameters and activation energy were calculated and discussed. FTIR and X-ray diffraction studies (XRD) confirmed the adsorption of the inhibitor. The surface morphology was studied using Scanning Electron Microscope (SEM) and Atomic Force Microscopy (AFM). PMID:27312608

  5. Alteration of amino acid and biogenic amine metabolism in hepatobiliary cancers: Findings from a prospective cohort study.

    PubMed

    Stepien, Magdalena; Duarte-Salles, Talita; Fedirko, Veronika; Floegel, Anne; Barupal, Dinesh Kumar; Rinaldi, Sabina; Achaintre, David; Assi, Nada; Tjønneland, Anne; Overvad, Kim; Bastide, Nadia; Boutron-Ruault, Marie-Christine; Severi, Gianluca; Kühn, Tilman; Kaaks, Rudolf; Aleksandrova, Krasimira; Boeing, Heiner; Trichopoulou, Antonia; Bamia, Christina; Lagiou, Pagona; Saieva, Calogero; Agnoli, Claudia; Panico, Salvatore; Tumino, Rosario; Naccarati, Alessio; Bueno-de-Mesquita, H B As; Peeters, Petra H; Weiderpass, Elisabete; Quirós, J Ramón; Agudo, Antonio; Sánchez, María-José; Dorronsoro, Miren; Gavrila, Diana; Barricarte, Aurelio; Ohlsson, Bodil; Sjöberg, Klas; Werner, Mårten; Sund, Malin; Wareham, Nick; Khaw, Kay-Tee; Travis, Ruth C; Schmidt, Julie A; Gunter, Marc; Cross, Amanda; Vineis, Paolo; Romieu, Isabelle; Scalbert, Augustin; Jenab, Mazda

    2016-01-15

    Perturbations in levels of amino acids (AA) and their derivatives are observed in hepatocellular carcinoma (HCC). Yet, it is unclear whether these alterations precede or are a consequence of the disease, nor whether they pertain to anatomically related cancers of the intrahepatic bile duct (IHBC), and gallbladder and extrahepatic biliary tract (GBTC). Circulating standard AA, biogenic amines and hexoses were measured (Biocrates AbsoluteIDQ-p180Kit) in a case-control study nested within a large prospective cohort (147 HCC, 43 IHBC and 134 GBTC cases). Liver function and hepatitis status biomarkers were determined separately. Multivariable conditional logistic regression was used to calculate odds ratios and 95% confidence intervals (OR; 95%CI) for log-transformed standardised (mean = 0, SD = 1) serum metabolite levels and relevant ratios in relation to HCC, IHBC or GBTC risk. Fourteen metabolites were significantly associated with HCC risk, of which seven metabolites and four ratios were the strongest predictors in continuous models. Leucine, lysine, glutamine and the ratio of branched chain to aromatic AA (Fischer's ratio) were inversely, while phenylalanine, tyrosine and their ratio, glutamate, glutamate/glutamine ratio, kynurenine and its ratio to tryptophan were positively associated with HCC risk. Confounding by hepatitis status and liver enzyme levels was observed. For the other cancers no significant associations were observed. In conclusion, imbalances of specific AA and biogenic amines may be involved in HCC development. PMID:26238458

  6. A modified electrode for the electrochemical detection of biogenic amines and their amino acid precursors separated by microchip capillary electrophoresis.

    PubMed

    Dossi, Nicolò; Toniolo, Rosanna; Pizzariello, Andrea; Susmel, Sabina; Bontempelli, Gino

    2011-04-01

    The use of a mixed-valent ruthenium oxide/hexacyanoruthenate polymeric film electrochemically deposited onto glassy carbon electrodes is proposed here for the detection of biogenic amines and their amino acid precursors, following their separation by microchip capillary electrophoresis. The ability of this ruthenium coating to electrocatalyze the oxidation of aliphatic and heterocyclic amines, as well as their amino acid precursors, was checked by using ethanolamine, tryptamine and tryptophane as prototype compounds and adopting a 25 mM sulphuric acid as the electrolyte in the detection cell, where a constant potential of 1.05 V versus Ag/AgCl, 3 M KCl was applied to the modified working electrode. Optimization of parameters affecting both detection and separation steps led to satisfactory separations when performed by using a 20 mM phosphate running buffer (pH 2.5) and applying a high voltage of 2.5 kV both in the separation and in the electrokinetic injection (duration 4 s). The recorded peaks were characterized by good repeatability (RSD ≤ 3.6%), high sensitivity and a wide linear range. Detection limits of 23 μM (1.4 mg/L), 27 μM (4.3 mg/L) and 34 μM (6.8 mg/L) were inferred for ethanolamine, tryptamine and tryptophane, respectively. The approach proposed here was also applied for the analysis of some double malt dark beers spiked with a controlled amount of the analytes considered. PMID:21437919

  7. Occurrence of N-phenylpropenoyl-L-amino acid amides in different herbal drugs and their influence on human keratinocytes, on human liver cells and on adhesion of Helicobacter pylori to the human stomach.

    PubMed

    Hensel, A; Deters, A M; Müller, G; Stark, T; Wittschier, N; Hofmann, T

    2007-02-01

    Thirty commonly used medicinal plants were screened by a selective and specific LC-MS/MS method for the occurrence of N-phenylpropenoyl- L-amino acid amides, a new homologous class of secondary products. In 15 plants, one or more of the respective derivatives (1 to 12) were found and quantitated. Especially roots from Angelica archangelica, fruits of Cassia angustifolia, C. senna, Coriandrum sativum, leaves from Hedera helix, flowers from Lavandula spec. and from Sambucus nigra contained high amounts (1 to 11 microg/g) of mixtures of the different amides 1 to 12. For functional investigations on potential activity in cellular physiology, two amides with an aliphatic (8) and an aromatic amino acid residue (5) were used. N-(E)-Caffeic acid L-aspartic acid amide (8) and N-(E)-caffeic acid L-tryptophan amide (5) stimulated mitochondrial activity as well as the proliferation rate of human liver cells (HepG2) at 10 microg/mL significantly. When monitoring the influence of selected phase I and II metabolizing enzymes, both compounds did not influence CYP3A4 gene expression, but stimulated CYP1A2 gene expression and inhibited GST expression. Also, the proliferation of human keratinocytes (NHK) was increased up to 150% by both amides 5 and 8; this stimulation was also detectable on the level of gene expression by an up-regulation of the transcription factor STAT6. The aliphatic aspartic compound 8 showed strong antiadhesive properties on the adhesion of Helicobacter pylori to human stomach tissue. PMID:17295182

  8. Visual observation and characterization of fluorescent poly(amido amine) dendrimer in film state.

    PubMed

    Saravanan, Govindachetty; Imae, Toyoko

    2011-06-01

    The fluorescent property of PAMAM dendrimers were examined at film state rather than in solution. The O2-treated PAMAM dendrimer displayed strong blue fluorescence due to its conservation of luminance in the film state and diminished its intensity with degas. The fluorescent property of PAMAM dendrimers was utilized as a fluorescent probe on functional patterned substrates for visual observation by a fluorescence microscope. G4 and G4.5 PAMAM dendrimers having peripheral groups of functional amine and carboxylate, respectively, were adsorbed selectively by electrostatic interactions on patterned carboxylic acid and amine terminated surfaces, respectively resulting in strong fluorescent patterns. This suggests the possible application of fluorescent PAMAM dendrimers as a fluorophor for the visualizable reactions. It was confirmed from an X-ray photoelectron spectroscopy that O2 molecules interact with tertiary amine moiety in PAMAM dendrimers but not amide group. These results give us an important support for the principle of fluorescence phenomenon. PMID:21770112

  9. Bioregeneration of mono-amine modified silica and granular activated carbon loaded with Acid Orange 7 in batch system.

    PubMed

    Al-Amrani, Waheeba Ahmed; Lim, Poh-Eng; Seng, Chye-Eng; Ngah, Wan Saime Wan

    2012-08-01

    The objectives of this study were: (1) to investigate the role of mixed culture of biomass in the regeneration of mono-amine modified silica (MAMS) and granular activated carbon (GAC) loaded with Acid Orange 7 (AO7), (2) to quantify and compare the bioregeneration efficiencies of AO7-loaded MAMS and GAC using the sequential adsorption and biodegradation approach and (3) to evaluate the reusability of bioregenerated MAMS. The results show that considerably higher bioregeneration efficiency of AO7-loaded MAMS as compared to that of AO7-loaded GAC was achieved due to higher reversibility of adsorption of MAMS for AO7 and favorable pH factor resulting in more AO7 desorption. The progressive loss of adsorption capacity of MAMS for AO7 with multiple cycles of use suggests possible chemical and microbial fouling of the adsorption sites. PMID:22704829

  10. The effect of aromatic amines and phenols in the thiyl-induced reactions of polyunsaturated fatty acids

    NASA Astrophysics Data System (ADS)

    Tartaro Bujak, Ivana; Chatgilialoglu, Chryssostomos; Ferreri, Carla; Valgimigli, Luca; Amorati, Riccardo; Mihaljević, Branka

    2016-07-01

    Thiols are well known for their role in cellular redox homeostasis, while aromatic amines and phenols are the best known classes of chain-breaking antioxidants. On the other hand, thiyl radicals are known to catalyse the double bond isomerization in PUFA. We investigated the role and interplay of 2-mercaptoethanol and diphenylamine in the parallel processes of peroxidation and cis-trans isomerization of linoleic acid (LA) during gamma radiolysis, both in solution and micelles. Both compounds, used alone were able to protect LA from oxidation; however pro-oxidant activity and enhanced isomerization was observed when they were used together, depending on the experimental settings. Instead, α-tocopherol protected LA from both oxidation and isomerization in the presence of thiols under any tested settings. The mechanistic scenario is discussed highlighting the role of diphenylaminyl radicals in promoting thiyl-radical-induced cis-trans isomerization in the presence of oxygen.

  11. Ultrasensitive and simultaneous determination of twenty-one amino acids and amines in culture media, red wine and beer.

    PubMed

    Hu, Zhongqiu; Li, Lin; Yuan, Yahong; Yue, Tianli

    2014-09-01

    Ultrasensitive and simultaneous determination of amino acids and amines (AAs) in media and winemaking products is very important for evaluating the relationship profile between the depletion of AAs and aroma compounds formation. In this work, by combing the advantages of Taguchi's scheme with Pareto graphs and Range analysis pattern, an analytical method with efficiently improving fluorescence intensity and resolutions of AAs while saving the time and resources is developed to simultaneously and ultrasensitively detect 21 AAs in media, wine and beer. The results indicate the detection limit (DL) could be reached at ng L(-1) level (3.34-284.3 ng L(-1)), which is 10(6) higher than that of DL obtained by general method. Furthermore, the linear ranges are also established so that the proposed method could be accurately applied. These results demonstrate the method provides an easy and effective way to ultrasensitively and simultaneously analyse AAs in complex products. PMID:24731314

  12. Synthetic Studies on Tricyclic Diterpenoids: Direct Allylic Amination Reaction of Isopimaric Acid Derivatives.

    PubMed

    Timoshenko, Mariya A; Kharitonov, Yurii V; Shakirov, Makhmut M; Bagryanskaya, Irina Yu; Shults, Elvira E

    2016-02-01

    A selective synthesis of 7- or 14-nitrogen containing tricyclic diterpenoids was completed according to a strategy in which the key step was the catalyzed direct allylic amination of methyl 14α-hydroxy-15,16-dihydroisopimarate with a wide variety of nitrogenated nucleophiles. It was revealed that the selectivity of the reaction depends on the nature of nucleophile. The catalyzed reaction of the mentioned diterpenoid allylic alcohol with 3-nitroaniline, 3-(trifluoromethyl)aniline, and 4-(trifluoromethyl)aniline yield the subsequent 7α-, 7β- and 14αnitrogen-containing diterpenoids. The reaction with 2-nitroaniline, 4-nitro-2-chloroaniline, 4-methoxy-2-nitroaniline, phenylsulfamide, or tert-butyl carbamate proceeds with the formation of 7α-nitrogen-substituted diterpenoids as the main products. PMID:27308214

  13. Synthetic Studies on Tricyclic Diterpenoids: Direct Allylic Amination Reaction of Isopimaric Acid Derivatives†

    PubMed Central

    Timoshenko, Mariya A.; Kharitonov, Yurii V.; Shakirov, Makhmut M.; Bagryanskaya, Irina Yu.

    2015-01-01

    Abstract A selective synthesis of 7‐ or 14‐nitrogen containing tricyclic diterpenoids was completed according to a strategy in which the key step was the catalyzed direct allylic amination of methyl 14α‐hydroxy‐15,16‐dihydroisopimarate with a wide variety of nitrogenated nucleophiles. It was revealed that the selectivity of the reaction depends on the nature of nucleophile. The catalyzed reaction of the mentioned diterpenoid allylic alcohol with 3‐nitroaniline, 3‐(trifluoromethyl)aniline, and 4‐(trifluoromethyl)aniline yield the subsequent 7α‐, 7β‐ and 14αnitrogen‐containing diterpenoids. The reaction with 2‐nitroaniline, 4‐nitro‐2‐chloroaniline, 4‐methoxy‐2‐nitroaniline, phenylsulfamide, or tert‐butyl carbamate proceeds with the formation of 7α‐nitrogen‐substituted diterpenoids as the main products. PMID:27308214

  14. Optically active poly(amide-imide)/TiO2 nanocomposites containing amino acid moieties: synthesis and properties.

    PubMed

    Rafiee, Zahra; Zare, Elham

    2015-11-01

    The novel optically active poly(amide-imide) (PAI)/TiO2 nanocomposites containing fluorene moieties have been successfully synthesized through ultrasonic irradiation. The surface of nanoparticles was chemically modified with γ-aminopropyltriethoxyl silane to enhance the compatibility with polymeric matrix and to avoid the aggregation of nanoparticles. The dispersion of surface-modified TiO2 in PAI film was confirmed by the transmission electron microscope (TEM) analysis showing the well-dispersed nanosized TiO2 nanoparticles. The thermal stabilities and optical properties of PAI/surface-modified TiO2 nanocomposite films were also investigated. The thermogravimetric analysis data showed an improvement of thermal stability of novel nanocomposite films as compared to the pure polymer. PMID:26002811

  15. The fatty acid amide hydrolase C385A variant affects brain binding of the positron emission tomography tracer [11C]CURB

    PubMed Central

    Boileau, Isabelle; Tyndale, Rachel F; Williams, Belinda; Mansouri, Esmaeil; Westwood, Duncan J; Foll, Bernard Le; Rusjan, Pablo M; Mizrahi, Romina; De Luca, Vincenzo; Zhou, Qian; Wilson, Alan A; Houle, Sylvain; Kish, Stephen J; Tong, Junchao

    2015-01-01

    The common functional single-nucleotide polymorphism (rs324420, C385A) of the endocannabinoid inactivating enzyme fatty acid amide hydrolase (FAAH) has been associated with anxiety disorder relevant phenotype and risk for addictions. Here, we tested whether the FAAH polymorphism affects in vivo binding of the FAAH positron emission tomography (PET) probe [11C]CURB ([11C-carbonyl]-6-hydroxy-[1,10-biphenyl]-3-yl cyclohexylcarbamate (URB694)). Participants (n=24) completed one [11C]CURB/PET scan and were genotyped for rs324420. Relative to C/C (58%), A-allele carriers (42%) had 23% lower [11C]CURB binding (λk3) in brain. We report evidence that the genetic variant rs324420 in FAAH is associated with measurable differences in brain FAAH binding as per PET [11C]CURB measurement. PMID:26036940

  16. Redox regulation of protein tyrosine phosphatase 1B (PTP1B): Importance of steric and electronic effects on the unusual cyclization of the sulfenic acid intermediate to a sulfenyl amide

    NASA Astrophysics Data System (ADS)

    Sarma, Bani Kanta

    2013-09-01

    The redox regulation of protein tyrosine phosphatase 1B (PTP1B) via the unusual transformation of its sulfenic acid (PTP1B-SOH) to a cyclic sulfenyl amide intermediate is studied by using small molecule chemical models. These studies suggest that the sulfenic acids derived from the H2O2-mediated reactions o-amido thiophenols do not efficiently cyclize to sulfenyl amides and the sulfenic acids produced in situ can be trapped by using methyl iodide. Theoretical calculations suggest that the most stable conformer of such sulfenic acids are stabilized by nO → σ*S-OH orbital interactions, which force the -OH group to adopt a position trans to the S⋯O interaction, leading to an almost linear arrangement of the O⋯S-O moiety and this may be the reason for the slow cyclization of such sulfenic acids to their corresponding sulfenyl amides. On the other hand, additional substituents at the 6-position of o-amido phenylsulfenic acids that can induce steric environment and alter the electronic properties around the sulfenic acid moiety by S⋯N or S⋯O nonbonded interactions destabilize the sulfenic acids by inducing strain in the molecule. This may lead to efficient the cyclization of such sulfenic acids. This model study suggests that the amino acid residues in the close proximity of the sulfenic acid moiety in PTP1B may play an important role in the cyclization of PTP1B-SOH to produce the corresponding sulfenyl amide.

  17. Multitarget fatty acid amide hydrolase/cyclooxygenase blockade suppresses intestinal inflammation and protects against nonsteroidal anti-inflammatory drug-dependent gastrointestinal damage

    PubMed Central

    Sasso, Oscar; Migliore, Marco; Habrant, Damien; Armirotti, Andrea; Albani, Clara; Summa, Maria; Moreno-Sanz, Guillermo; Scarpelli, Rita; Piomelli, Daniele

    2015-01-01

    The ability of nonsteroidal anti-inflammatory drugs (NSAIDs) to inhibit cyclooxygenase (Cox)-1 and Cox-2 underlies the therapeutic efficacy of these drugs, as well as their propensity to damage the gastrointestinal (GI) epithelium. This toxic action greatly limits the use of NSAIDs in inflammatory bowel disease (IBD) and other chronic pathologies. Fatty acid amide hydrolase (FAAH) degrades the endocannabinoid anandamide, which attenuates inflammation and promotes GI healing. Here, we describe the first class of systemically active agents that simultaneously inhibit FAAH, Cox-1, and Cox-2 with high potency and selectivity. The class prototype 4 (ARN2508) is potent at inhibiting FAAH, Cox-1, and Cox-2 (median inhibitory concentration: FAAH, 0.031 ± 0.002 µM; Cox-1, 0.012 ± 0.002 µM; and Cox-2, 0.43 ± 0.025 µM) but does not significantly interact with a panel of >100 off targets. After oral administration in mice, ARN2508 engages its intended targets and exerts profound therapeutic effects in models of intestinal inflammation. Unlike NSAIDs, ARN2508 causes no gastric damage and indeed protects the GI from NSAID-induced damage through a mechanism that requires FAAH inhibition. Multitarget FAAH/Cox blockade may provide a transformative approach to IBD and other pathologies in which FAAH and Cox are overactive.—Sasso, O., Migliore, M., Habrant, D., Armirotti, A., Albani, C., Summa, M., Moreno-Sanz, G., Scarpelli, R., Piomelli, D. Multitarget fatty acid amide hydrolase/cyclooxygenase blockade suppresses intestinal inflammation and protects against nonsteroidal anti-inflammatory drug-dependent gastrointestinal damage. PMID:25757568

  18. 40 CFR 721.9595 - Alkyl benzene sulfonic acids and alkyl sulfates, amine salts (generic).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Alkyl benzene sulfonic acids and alkyl... Significant New Uses for Specific Chemical Substances § 721.9595 Alkyl benzene sulfonic acids and alkyl...) The chemical substances identified generically as alkyl benzene sulfonic acids and alkyl...

  19. 40 CFR 721.9595 - Alkyl benzene sulfonic acids and alkyl sulfates, amine salts (generic).

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Alkyl benzene sulfonic acids and alkyl... Significant New Uses for Specific Chemical Substances § 721.9595 Alkyl benzene sulfonic acids and alkyl...) The chemical substances identified generically as alkyl benzene sulfonic acids and alkyl...

  20. 40 CFR 721.9595 - Alkyl benzene sulfonic acids and alkyl sulfates, amine salts (generic).

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Alkyl benzene sulfonic acids and alkyl... Significant New Uses for Specific Chemical Substances § 721.9595 Alkyl benzene sulfonic acids and alkyl...) The chemical substances identified generically as alkyl benzene sulfonic acids and alkyl...

  1. 40 CFR 721.9595 - Alkyl benzene sulfonic acids and alkyl sulfates, amine salts (generic).

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Alkyl benzene sulfonic acids and alkyl... Significant New Uses for Specific Chemical Substances § 721.9595 Alkyl benzene sulfonic acids and alkyl...) The chemical substances identified generically as alkyl benzene sulfonic acids and alkyl...

  2. 40 CFR 721.9595 - Alkyl benzene sulfonic acids and alkyl sulfates, amine salts (generic).

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Alkyl benzene sulfonic acids and alkyl... Significant New Uses for Specific Chemical Substances § 721.9595 Alkyl benzene sulfonic acids and alkyl...) The chemical substances identified generically as alkyl benzene sulfonic acids and alkyl...

  3. Effects of the Fatty Acid Amide Hydrolase (FAAH) Inhibitor URB597 on Pain-Stimulated and Pain-Depressed Behavior in Rats

    PubMed Central

    Kwilasz, Andrew J.; Abdullah, Rehab A.; Poklis, Justin L.; Lichtman, Aron H.; Negus, S. Stevens

    2014-01-01

    Cannabinoid receptor (CBR) agonists produce antinociception in conventional preclinical assays of pain-stimulated behavior but are not effective in preclinical assays of pain-depressed behavior. Fatty acid amide hydrolase (FAAH) inhibitors increase physiological levels of the endocannabinoid anandamide (AEA), which may confer improved efficacy and/or safety relative to direct CBR agonists. To further evaluate FAAH inhibitors as candidate analgesics, this study assessed effects of the FAAH inhibitor URB597 in assays of acute pain-stimulated and pain-depressed behavior in male Sprague Dawley rats. Intraperitoneal injection of dilute lactic acid served as a noxious stimulus to stimulate a stretching response or depress positively reinforced operant behavior (intracranial self-stimulation; ICSS), and URB597 was tested 1 and 4 h after administration. Consistent with FAAH inhibitor effects in other assays of pain-stimulated behavior, URB597 (1–10 mg/kg IP) produced dose-related and CB1R-mediated decreases in acid-stimulated stretching. Conversely, in the assay of acid-depressed ICSS, URB597 produced a delayed, partial and non-CBR-mediated antinociceptive effect. The antinociceptive dose of URB597 (10 mg/kg) increased plasma and brain AEA levels. These results suggest that URB597 produces antinociception in these models of “pain stimulated” and “pain depressed” behavior, but with different rates of onset and differential involvement of CBRs. PMID:24583930

  4. Application of Roof-Shape Amines as Chiral Solvating Agents for Discrimination of Optically Active Acids by NMR Spectroscopy: Study of Match-Mismatch Effect and Crystal Structure of the Diastereomeric Salts.

    PubMed

    Gupta, Riddhi; Gonnade, Rajesh G; Bedekar, Ashutosh V

    2016-09-01

    Optically active roof-shape amines were prepared and scanned as chiral solvating agents to study molecular recognition of acids by NMR analysis. Three types of amines were studied to establish a match-mismatch effect for structurally diverse acid analytes. Single-crystal X-ray diffraction analysis was performed on the diastereomeric salts of roof-shape amines and both isomers of mandelic acid to establish molecular conformation and correlate the absolute configuration with the observed NMR shift. The present system also recognizes the two isomers of weakly acidic BINOL and its derivatives. PMID:27484455

  5. Synthesis of new polysialic acid derivatives.

    PubMed

    Su, Yi; Kasper, Cornelia; Kirschning, Andreas; Dräger, Gerald; Berski, Silke

    2010-09-01

    In this paper we report the first synthesis of novel polysialic acid derivatives which is initiated by treatment of polysialic acid with EDC-HCl to yield the inter-residual delta-lactone. Subsequent reaction with amines or hydrazine gives the corresponding polysialic acid amides and hydrazide. Alkylation of the tetrabutylammonium salt of polysialic acid yields polysialic acid esters. In contrast a variety of N-derivatives of polysialic acid can be prepared starting from deacetylated polysialic acid. The N-derivatives prepared in this communication can be used for the Cu-catalyzed as well as Cu-free "click" chemistry. PMID:20602419

  6. Acetylene-mediated alkylation of monoalkyl carbonates and carbamic acids with tert-amines

    SciTech Connect

    Sasaki, Yoshiyuki

    1996-12-31

    Carbonic acid diesters and carbamic acid esters are useful organic substances as intermediates for the syntheses of several chemicals. They are currently synthesized in industry using the processes based on phosgene or carbon monoxide. On the other hand, since carbon dioxide is an abundant and cheap carbonyl carbon source, and is much less toxic than those raw materials, substantial efforts have been focused on its fixation into carbonyl compounds including carbonic acid diesters and carbamic acid esters. However, their syntheses based on carbon dioxide reported so far require rather expensive substrates like alkyl halides, and are not competitive with the currently adopted industrial processes.

  7. 40 CFR 721.10410 - Polyether ester acid compound with a polyamine amide (generic) (P-05-714).

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Polyether ester acid compound with a... Significant New Uses for Specific Chemical Substances § 721.10410 Polyether ester acid compound with a.... (1) The chemical substance identified generically as polyether ester acid compound with a...

  8. 40 CFR 721.10410 - Polyether ester acid compound with a polyamine amide (generic) (P-05-714).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Polyether ester acid compound with a... Significant New Uses for Specific Chemical Substances § 721.10410 Polyether ester acid compound with a.... (1) The chemical substance identified generically as polyether ester acid compound with a...

  9. 40 CFR 721.10410 - Polyether ester acid compound with a polyamine amide (generic) (P-05-714).

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Polyether ester acid compound with a... Significant New Uses for Specific Chemical Substances § 721.10410 Polyether ester acid compound with a.... (1) The chemical substance identified generically as polyether ester acid compound with a...

  10. Synthesis and Structure–Activity Relationships of N-(2-Oxo-3-oxetanyl)amides as N-Acylethanolamine-hydrolyzing Acid Amidase Inhibitors

    PubMed Central

    Solorzano, Carlos; Antonietti, Francesca; Duranti, Andrea; Tontini, Andrea; Rivara, Silvia; Lodola, Alessio; Vacondio, Federica; Tarzia, Giorgio; Piomelli, Daniele; Mor, Marco

    2010-01-01

    The fatty acid ethanolamides (FAEs) are a family of bioactive lipid mediators that include the endogenous agonist of peroxisome proliferator-activated receptor-α, palmitoylethanolamide (PEA). FAEs are hydrolyzed intracellularly by either fatty acid amide hydrolase or N-acylethanolamine-hydrolyzing acid amidase (NAAA). Selective inhibition of NAAA by (S)-N-(2-oxo-3-oxetanyl)-3-phenylpropionamide [(S)-OOPP, 7a] prevents PEA degradation in mouse leukocytes and attenuates responses to proinflammatory stimuli. Starting from the structure of 7a a series of β-lactones was prepared and tested on recombinant rat NAAA to explore structure-activity relationships (SARs) for this class of inhibitors and improve their in vitro potency. Following the hypothesis that these compounds inhibit NAAA by acylation of the catalytic cysteine, we identified several requirements for recognition at the active site and obtained new potent inhibitors. In particular, (S)-N-(2-oxo-3-oxetanyl)biphenyl-4-carboxamide (7h) was more potent than 7a at inhibiting recombinant rat NAAA activity (7a, IC50 = 420 nM; 7h, IC50 = 115 nM) in vitro and at reducing carrageenan-induced leukocyte infiltration in vivo. PMID:20604568

  11. 40 CFR 721.7770 - Alkylphenoxypoly(oxyethylene) sulfuric acid ester, substituted amine salt.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... Significant New Uses for Specific Chemical Substances § 721.7770 Alkylphenoxypoly(oxyethylene) sulfuric acid...) The chemical substance identified as alkyl phenoxypoly(oxyethylene) sulfuric acid ester, substituted... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Alkylphenoxypoly(oxyethylene)...

  12. 40 CFR 721.7770 - Alkylphenoxypoly(oxyethylene) sulfuric acid ester, substituted amine salt.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Significant New Uses for Specific Chemical Substances § 721.7770 Alkylphenoxypoly(oxyethylene) sulfuric acid...) The chemical substance identified as alkyl phenoxypoly(oxyethylene) sulfuric acid ester, substituted... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Alkylphenoxypoly(oxyethylene)...

  13. 40 CFR 721.7770 - Alkylphenoxypoly(oxyethylene) sulfuric acid ester, substituted amine salt.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... Significant New Uses for Specific Chemical Substances § 721.7770 Alkylphenoxypoly(oxyethylene) sulfuric acid...) The chemical substance identified as alkyl phenoxypoly(oxyethylene) sulfuric acid ester, substituted... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Alkylphenoxypoly(oxyethylene)...

  14. 40 CFR 721.7770 - Alkylphenoxypoly(oxyethylene) sulfuric acid ester, substituted amine salt.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... Significant New Uses for Specific Chemical Substances § 721.7770 Alkylphenoxypoly(oxyethylene) sulfuric acid...) The chemical substance identified as alkyl phenoxypoly(oxyethylene) sulfuric acid ester, substituted... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Alkylphenoxypoly(oxyethylene)...

  15. 40 CFR 721.7770 - Alkylphenoxypoly(oxyethylene) sulfuric acid ester, substituted amine salt.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... Significant New Uses for Specific Chemical Substances § 721.7770 Alkylphenoxypoly(oxyethylene) sulfuric acid...) The chemical substance identified as alkyl phenoxypoly(oxyethylene) sulfuric acid ester, substituted... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Alkylphenoxypoly(oxyethylene)...

  16. A capillary electrophoresis method for the determination of selected biogenic amines and amino acids in mammalian decomposition fluid.

    PubMed

    Swann, L M; Forbes, S L; Lewis, S W

    2010-06-15

    A simple capillary zone electrophoresis method for the determination of selected biogenic amines (tyramine and tryptamine) and amino acids (tryptophan, phenylalanine and tyrosine) in mammalian decomposition fluids is presented. Separations were carried out in a fused silica capillary (75microm i.d., total length 65cm, effective length 56cm) with detection by ultraviolet absorbance spectrophotometry at 200nm. In order to improve resolution and total analysis time, the method was subjected to optimisation utilising a chemometric approach. A screening design was carried out followed by a central composite design (CCD), using peak resolution and total analysis time as response factors. The influences of four experimental variables (pH, background electrolyte concentration, percentage of organic modifier (methanol) and applied voltage) were investigated. Optimum separation conditions were determined to be; a background electrolyte of boric acid (70mM) adjusted to pH 9.5 with 0.1M sodium hydroxide with 32% methanol (v/v). Applied voltage was 30kV, with the resulting current being less than 26microA. Under these conditions the analytes were separated within 12min. Tryptamine, tyramine, tryptophan, tyrosine and phenylalanine were identified by migration time and spiking in porcine decomposition fluids. PMID:20441960

  17. Synthesis, Structural Characterization and Biological Activity of Peroxo Complexes of Zirconium (IV) Containing Organic Acid and Amine Bases

    NASA Astrophysics Data System (ADS)

    Nasrin, Jahanara; Saidul Islam, M.

    The study was extended to isolate the peroxo complexes of Zr (IV) containing organic acid and amine bases. The Zr (IV) complexes have been found to oxidize allyl alcohol and triphenylphosphine as well as triphenylarsine to their respective oxides. The analytical data are in good agreement with the proposed empirical formulae of the present complexes. The complexes display v(C = O) bands at ~1630 cm-1 and v(C-O) bands at ~1412 cm-1 significantly lower than the values of amino acid (~1650 and ~1450 cm-1). These indicate the coordination of amino acid through their carboxylate anion. The broad band observed at about 3217-3350 cm-1 for v (N-H) modes indicate the coordination of amino group through nitrogen atom of amino acid. The metal peroxo grouping gives rise to three IR active vibrational modes. These are predominantly O-O stretching v1, the symmetric M-O stretch v2 and the antisymmetric M-O stretch v3. The magnetic moment values indicated that these complexes were diamagnetic in nature suggesting no changes in their oxidation states of the metal ions upon complexation. These data also consistent with six fold coordination of Zr (IV). The electronic spectral data of the complexes showed bands in the region 230-372 nm due to the charge transfer band only. All the complexes of Zr (IV) did not show any remarkable antibacterial activity. It is interesting to note that these complexes were found to be fully inactive against the three pathogenic fungi A. niger, A. fumigatus and A. flarus. Moreover, all the complexes of Zr (IV) metals showed toxic effect against the brine shrimp.

  18. The role of hydroxyl group acidity on the activity of silica-supported secondary amines for the self-condensation of n-butanal.

    PubMed

    Shylesh, Sankaranarayanapillai; Hanna, David; Gomes, Joseph; Canlas, Christian G; Head-Gordon, Martin; Bell, Alexis T

    2015-02-01

    The catalytic activity of secondary amines supported on mesoporous silica for the self-condensation of n-butanal to 2-ethylhexenal can be altered significantly by controlling the Brønsted acidity of M--OH species present on the surface of the support. In this study, M--OH (M=Sn, Zr, Ti, and Al) groups were doped onto the surface of SBA-15, a mesoporous silica, prior to grafting secondary propyl amine groups on to the support surface. The catalytic activity was found to depend critically on the synthesis procedure, the nature and amount of metal species introduced and the spatial separation between the acidic sites and amine groups. DFT analysis of the reaction pathway indicates that, for weak Brønsted acid groups, such as Si--OH, the rate-limiting step is C--C bond formation, whereas for stronger Brønsted acid groups, such as Ti and Al, hydrolysis of iminium species produced upon C--C bond formation is the rate-limiting step. Theoretical analysis shows further that the apparent activation energy decreases with increasing Brønsted acidity of the M--OH groups, consistent with experimental observation. PMID:25314616

  19. Anticonvulsant and antinociceptive activity of new amides derived from 3-phenyl-2,5-dioxo-pyrrolidine-1-yl-acetic acid in mice.

    PubMed

    Rapacz, Anna; Obniska, Jolanta; Wiklik-Poudel, Beata; Rybka, Sabina; Sałat, Kinga; Filipek, Barbara

    2016-06-15

    The aim of the present experiments was to examine the anticonvulsant and antinociceptive activity of five new amides derived from 3-phenyl-2,5-dioxo-pyrrolidine-1-yl-acetic acid in animal models of seizures and pain. The antiseizure activity was investigated in three acute models of seizures, namely, the maximal electroshock (MES), the subcutaneous pentylenetetrazole (scPTZ), and 6Hz psychomotor seizure tests in mice. The antinociceptive properties were estimated in the formalin model of tonic pain, and in the oxaliplatin-induced neuropathic pain model in mice. Considering drug safety evaluation, acute neurological toxicity was determined in the rotarod test. Three tested compounds (3, 4, and 7) displayed a broad spectrum of anticonvulsant activity and showed better protective indices than those obtained for MES/scPTZ/6Hz active reference drug - valproic acid. Furthermore, three compounds (3, 4, and 6) demonstrated a significant antinociceptive effect in the formalin test, as well as antiallodynic activity in the oxaliplatin-induced neuropathic pain model. Among the tested agents, compounds 3 and 4 displayed not only antiseizure properties, but also collateral prominent analgesic properties. The in vitro binding study indicated that the plausible mechanism of action of chosen compound (4) was the influence on neuronal voltage-sensitive sodium (site 2) and L-type calcium channels. PMID:27089821

  20. Experimental colitis in mice is attenuated by changes in the levels of endocannabinoid metabolites induced by selective inhibition of fatty acid amide hydrolase (FAAH)

    PubMed Central

    Sałaga, M; Mokrowiecka, A; Zakrzewski, P K; Cygankiewicz, A; Leishman, E; Sobczak, M; Zatorski, H; Małecka-Panas, E; Kordek, R; Storr, M; Krajewska, W M; Bradshaw, H B; Fichna, J

    2014-01-01

    Background and aims Pharmacological treatment and/or maintenance of remission in inflammatory bowel diseases (IBD) is currently one of the biggest challenge in the field of gastroenterology. Available therapies are mostly limited to overcoming the symptoms, but not the cause of the disease. Recently, the endocannabinoid system has been proposed as a novel target in the treatment of IBD. Here we aimed to assess the anti-inflammatory action of the novel fatty acid amide hydrolase (FAAH) inhibitor PF-3845 and its effect on the endocannabinoid and related lipid metabolism during the course of experimental colitis. Methods We used two models of experimental colitis in mice (TNBS- and DSS-induced) and additionally, we employed LC/MS/MS spectrometry to determine the changes in biolipid levels in the mouse colon during inflammation. Results We showed that the FAAH inhibitor PF-3845 reduced experimental TNBS-induced colitis in mice and its anti-inflammatory action is associated with altering the levels of selected biolipids (arachidonic and oleic acid derivatives, prostaglandins and biolipids containing glycine in the mouse colon). Conclusions We show that FAAH is a promising pharmacological target and the FAAH-dependent biolipids play a major role in colitis. Our results highlight and promote therapeutic strategy based on targeting FAAH-dependent metabolic pathways in order to alleviate intestinal inflammation. PMID:24530133

  1. Effect of propane-2-sulfonic acid octadec-9-enyl-amide on the expression of adhesion molecules in human umbilical vein endothelial cells.

    PubMed

    Chen, Cai-Xia; Yang, Li-Chao; Xu, Xu-Dong; Wei, Xiao; Gai, Ya-Ting; Peng, Lu; Guo, Han; Hao-Zhou; Wang, Yi-Qing; Jin, Xin

    2015-06-01

    Oleoylethanolamide (OEA), an endogenous agonist of PPARα, has been reported to have anti-atherosclerotic properties. However, OEA can be enzymatically hydrolyzed to oleic acid and ethanolamine and, thus, is not expected to be orally active. In the present study, we designed and synthesized an OEA analog, propane-2-sulfonic acid octadec-9-enyl-amide (N15), which is resistant to enzymatic hydrolysis. The purpose of this study was to investigate the effects of N15 on the expression of adhesion molecules in human umbilical vein endothelial cells (HUVECs). The results showed that N15 inhibited TNFα-induced production of vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 and the adhesion of monocytes to TNFα-induced HUVECs. Furthermore, the protective effect of N15 on inflammation is dependent upon a PPAR-α/γ-mediated mechanism. In conclusion, N15 protects against TNFα-induced vascular endothelial inflammation. This anti-inflammatory effect of N15 is dependent on PPAR-α/γ dual targets. PMID:25797284

  2. Kinetics of the reactions of the acid anhydrides with aromatic amines in aprotic solvents. M.S. Thesis. Final Report

    NASA Technical Reports Server (NTRS)

    Sugg, E.; Mason, J. G.

    1983-01-01

    Work has revealed that diamine derivatives of diphenylmethane (IV), diphenyl ether (V), benzophenone (IV), fluorene (VII), and fluorenone (VIII) polymerizations with pyromellitic dianhydride in DMA were dependent on the basicity of the amine compound. The correlation between the basicity of the amine and its reactivity with phthalic anhydride was determined. Basicity measurements were made by potentiometric titration of each amine in an acetonitrile-water solvent system, from which the pKa of the amine could be determined. Reactivity was defined in terms of the second order rate constant derived form spectrophotometric examination of the reaction between each amine and phthalic anhydride in DMA. This reaction was expected to proceed in either one (for a monoamine) or two (for a diamine) stages.

  3. Amino Acid and Biogenic Amine Profile Deviations in an Oral Glucose Tolerance Test: A Comparison between Healthy and Hyperlipidaemia Individuals Based on Targeted Metabolomics.

    PubMed

    Li, Qi; Gu, Wenbo; Ma, Xuan; Liu, Yuxin; Jiang, Lidan; Feng, Rennan; Liu, Liyan

    2016-01-01

    Hyperlipidemia (HLP) is characterized by a disturbance in lipid metabolism and is a primary risk factor for the development of insulin resistance (IR) and a well-established risk factor for cardiovascular disease and atherosclerosis. The aim of this work was to investigate the changes in postprandial amino acid and biogenic amine profiles provoked by an oral glucose tolerance test (OGTT) in HLP patients using targeted metabolomics. We used ultra-high-performance liquid chromatography-triple quadrupole mass spectrometry to analyze the serum amino acid and biogenic amine profiles of 35 control and 35 HLP subjects during an OGTT. The amino acid and biogenic amine profiles from 30 HLP subjects were detected as independent samples to validate the changes in the metabolites. There were differences in the amino acid and biogenic amine profiles between the HLP individuals and the healthy controls at baseline and after the OGTT. The per cent changes of 13 metabolites from fasting to the 2 h samples during the OGTT in the HLP patients were significantly different from those of the healthy controls. The lipid parameters were associated with the changes in valine, isoleucine, creatine, creatinine, dimethylglycine, asparagine, serine, and tyrosine (all p < 0.05) during the OGTT in the HLP group. The postprandial changes in isoleucine and γ-aminobutyric acid (GABA) during the OGTT were positively associated with the homeostasis model assessment of insulin resistance (HOMA-IR; all p < 0.05) in the HLP group. Elevated oxidative stress and disordered energy metabolism during OGTTs are important characteristics of metabolic perturbations in HLP. Our findings offer new insights into the complex physiological regulation of metabolism during the OGTT in HLP. PMID:27338465

  4. Amino Acid and Biogenic Amine Profile Deviations in an Oral Glucose Tolerance Test: A Comparison between Healthy and Hyperlipidaemia Individuals Based on Targeted Metabolomics

    PubMed Central

    Li, Qi; Gu, Wenbo; Ma, Xuan; Liu, Yuxin; Jiang, Lidan; Feng, Rennan; Liu, Liyan

    2016-01-01

    Hyperlipidemia (HLP) is characterized by a disturbance in lipid metabolism and is a primary risk factor for the development of insulin resistance (IR) and a well-established risk factor for cardiovascular disease and atherosclerosis. The aim of this work was to investigate the changes in postprandial amino acid and biogenic amine profiles provoked by an oral glucose tolerance test (OGTT) in HLP patients using targeted metabolomics. We used ultra-high-performance liquid chromatography-triple quadrupole mass spectrometry to analyze the serum amino acid and biogenic amine profiles of 35 control and 35 HLP subjects during an OGTT. The amino acid and biogenic amine profiles from 30 HLP subjects were detected as independent samples to validate the changes in the metabolites. There were differences in the amino acid and biogenic amine profiles between the HLP individuals and the healthy controls at baseline and after the OGTT. The per cent changes of 13 metabolites from fasting to the 2 h samples during the OGTT in the HLP patients were significantly different from those of the healthy controls. The lipid parameters were associated with the changes in valine, isoleucine, creatine, creatinine, dimethylglycine, asparagine, serine, and tyrosine (all p < 0.05) during the OGTT in the HLP group. The postprandial changes in isoleucine and γ-aminobutyric acid (GABA) during the OGTT were positively associated with the homeostasis model assessment of insulin resistance (HOMA-IR; all p < 0.05) in the HLP group. Elevated oxidative stress and disordered energy metabolism during OGTTs are important characteristics of metabolic perturbations in HLP. Our findings offer new insights into the complex physiological regulation of metabolism during the OGTT in HLP. PMID:27338465

  5. Analysis of cholinergic markers, biogenic amines, and amino acids in the CNS of two APP overexpression mouse models.

    PubMed

    Van Dam, Debby; Marescau, Bart; Engelborghs, Sebastiaan; Cremers, Thomas; Mulder, Jan; Staufenbiel, Matthias; De Deyn, Peter Paul

    2005-04-01

    Two transgenic mouse models expressing mutated human amyloid precursor protein and previously found to display cognitive and behavioural alterations, reminiscent of Alzheimer patients' symptomatology, were scrutinised for putative brain region-specific changes in neurochemical parameters. Brains of NSE-hAPP751m-57, APP23 and wild-type mice were microdissected to perform brain region-specific neurochemical analyses. Impairment of cholinergic transmission, the prominent neurochemical deficit in Alzheimer brain, was examined; acetylcholinesterase and choline acetyltransferase activity levels were determined as markers of the cholinergic system. Since Alzheimer neurodegeneration is not restricted to the cholinergic system, brain levels of biogenic amines and metabolites, and amino acidergic neurotransmitters and systemic amino acids were analysed as well. Cholinergic dysfunction, reflected in reduced enzymatic activity in the basal forebrain nuclei, was restricted to the APP23 model, which also exhibited more outspoken and more widespread changes in other neurotransmitter systems. Significant changes in compounds of the noradrenergic and serotonergic system were observed, as well as alterations in levels of the inhibitory neurotransmitter glycine and systemic amino acids. These observations were clearly in occurrence with the more pronounced histopathological and behavioural phenotype of the APP23 model. As transgenic models often do not represent an end-stage of the disease, some discrepancies with results from post-mortem human Alzheimer brain analyses were apparent; in particular, no significant alterations in excitatory amino acid levels were detected. Our findings of brain region-specific alterations in compound levels indicate disturbed neurotransmission pathways, and greatly add to the validity of APP23 mice as a model for Alzheimer's disease. Transgenic mouse models may be employed as a tool to study early-stage neurochemical changes, which are often not

  6. Hexamethyldisilazane as an acylation generator for perfluorocarboxylic acids in quantitative derivatization of primary phenylalkyl amines confirmed by GC/MS and computations.

    PubMed

    Molnár, Borbála; Csámpai, Antal; Molnár-Perl, Ibolya

    2015-01-20

    A novel, selective acylation of primary phenylalkyl amines (PPAAs) using hexamethyldisilazane (HMDS) and perfluorocarboxylic acids (PFCAs) is noted. Couples, like HMDS and trifluoroacetic acid, HMDS and pentafluoropropionic acid, or HMDS and heptafluorobutyric acid trigger PPAAs’ quantitative acylation. Processes’ selectivity was characterized by applying all couples to derivatize benzyl, 2-phenylethyl, 3-phenylpropyl, 4-phenylbutyl amines, and their relevant substituted versions. Aliphatic amines were unreactive. Identification, quantification, proportionality, and stoichiometry in derivatization processes were determined by gas chromatography/mass spectrometry. Reaction conditions were optimized depending on reagents’ molar ratios, solvents, and temperatures applied. The new acylation method, in comparison to the traditional ones, obtained with trifluoroacetic anhydride, heptafluorobutyric anhydride, and N-methyl-bis(trifluoroacetamide), offers numerous advantages. Derivatives, provided by couples, can be directly injected onto the column, avoiding loss of species, saving time, work, and cost in the preparation process. Due to traditional reagents’ excess evaporation by nitrogen drying, the loss of trifluoroacylated species proved to be 65% or less. Regarding heptafluorobutyryl species, their losses varied between 25% and 5%. Unified huge responses, obtained with the HMDS and PFCA couples are attributable to their direct injection onto the column and to fragments sourced from the molecular ions and from their self-chemical ionization ([M]•+, [M+147]+, i.e., [M+(CH3)2–Si═O–Si–(CH3)3]+). The reaction mechanism, due to the HMDS symmetrical structure, acting HMDS as acylation generator for PFCAs, was confirmed by density functional theory (DFT) computation. PMID:25493612

  7. Amino Acids from Icy Amines: A Radiation-Chemical Approach to Extraterrestrial Synthesis

    NASA Technical Reports Server (NTRS)

    Dworkin, J. P.; Moore, M. H.

    2010-01-01

    Detections of amino acids in meteorites go back several decades, with at least 100 such compounds being reported for the Murchison meteorite alone. The presence of these extraterrestrial molecules raises questions as to their formation, abundance, thermal stability, racemization, and possible subsequent reactions. Although all of these topics have been studied in laboratories, such work often involves many variables and unknowns. This has led us to seek out model systems with which to uncover reaction products, test chemical predictions, and sited light on underlying reaction mechanisms. This presentation will describe one such study, focusing on amino-acid formation in ices.

  8. Hydrophilic and blue fluorescent N-doped carbon dots from tartaric acid and various alkylol amines under microwave irradiation

    NASA Astrophysics Data System (ADS)

    Xu, Minghan; Xu, Shusheng; Yang, Zhi; Shu, Mengjun; He, Guili; Huang, Da; Zhang, Liling; Li, Li; Cui, Daxiang; Zhang, Yafei

    2015-09-01

    The desired control of particle size, doping element composition, and surface structure of carbon dots (CDs) are vital for understanding the fluorescence mechanism and exploring their potential applications. Herein, nitrogen-doped CDs (N-doped CDs) have been synthesized with tartaric acid and various alkylol amines (monoethanolamine, biethanolamine and triethanolamine) under microwave irradiation. A systematic investigation was performed to characterize the N-doped CDs. It is found that with increasing nitrogen proportion, the fluorescent quantum yield and lifetime of N-doped CDs increases, whereas cell toxicity decreases. In other words, N-doped CDs synthesized by tartaric acid and monoethanolamine have the highest nitrogen content, the highest fluorescent quantum yield, the longest lifetime and the lowest cell toxicity. A corresponding mechanism has been proposed. Moreover, as-synthesized N-doped CDs have been applied for selectively detecting the Fe3+ ion and writing letters as a fluorescent ink.The desired control of particle size, doping element composition, and surface structure of carbon dots (CDs) are vital for understanding the fluorescence mechanism and exploring their potential applications. Herein, nitrogen-doped CDs (N-doped CDs) have been synthesized with tartaric acid and various alkylol amines (monoethanolamine, biethanolamine and triethanolamine) under microwave irradiation. A systematic investigation was performed to characterize the N-doped CDs. It is found that with increasing nitrogen proportion, the fluorescent quantum yield and lifetime of N-doped CDs increases, whereas cell toxicity decreases. In other words, N-doped CDs synthesized by tartaric acid and monoethanolamine have the highest nitrogen content, the highest fluorescent quantum yield, the longest lifetime and the lowest cell toxicity. A corresponding mechanism has been proposed. Moreover, as-synthesized N-doped CDs have been applied for selectively detecting the Fe3+ ion and writing

  9. Enantioselective synthesis of α-oxy amides via Umpolung amide synthesis.

    PubMed

    Leighty, Matthew W; Shen, Bo; Johnston, Jeffrey N

    2012-09-19

    α-Oxy amides are prepared through enantioselective synthesis using a sequence beginning with a Henry addition of bromonitromethane to aldehydes and finishing with Umpolung Amide Synthesis (UmAS). Key to high enantioselection is the finding that ortho-iodo benzoic acid salts of the chiral copper(II) bis(oxazoline) catalyst deliver both diastereomers of the Henry adduct with high enantiomeric excess, homochiral at the oxygen-bearing carbon. Overall, this approach to α-oxy amides provides an innovative complement to alternatives that focus almost entirely on the enantioselective synthesis of α-oxy carboxylic acids. PMID:22967461

  10. Production of biogenic amines by lactic acid bacteria: screening by PCR, thin-layer chromatography, and high-performance liquid chromatography of strains isolated from wine and must.

    PubMed

    Costantini, Antonella; Cersosimo, Manuela; Del Prete, Vincenzo; Garcia-Moruno, Emilia

    2006-02-01

    Biogenic amines are frequently found in wine and other fermented food. We investigated the ability of 133 strains of lactic acid bacteria isolated from musts and wines of different origins to produce histamine, tyramine, and putrescine. We detected the genes responsible for encoding the corresponding amino acid decarboxylases through PCR assays using two primer sets for every gene: histidine decarboxylase (hdc), tyrosine decarboxylase (tdc), and ornithine decarboxylase (odc); these primers were taken from the literature or designed by us. Only one strain of Lactobacillus hilgardii was shown to possess the hdc gene, whereas four strains of Lactobacillus brevis had the tdc gene. None of the Oenococcus oeni strains, the main agents of malolactic fermentation, was a biogenic amine producer. All PCR amplicon band-positive results were confirmed by thin-layer chromatography and high-performance liquid chromatography analyses. PMID:16496581

  11. Synthesis and characterization of secondary nitrosamines from secondary amines using sodium nitrite and p-toluenesulfonic acid.

    PubMed

    Miró Sabaté, Carles; Delalu, Henri

    2015-03-01

    We synthesized nitrosamines (R2N-NO) with R = iPr (1), nPr (2), nBu (3), and hydroxyethyl (4) from the amine using sodium nitrite/p-toluenesulfonic acid in CH2Cl2. The rate of formation of 1-4 increases in the direction iPr

  12. Volatile and biogenic amines, microbiological counts, and bacterial amino acid decarboxylase activity throughout the salt-ripening process of anchovies (Engraulis encrasicholus).

    PubMed

    Pons-Sánchez-Cascado, S; Veciana-Nogués, M T; Bover-Cid, S; Mariné-Font, A; Vidal-Carou, M C

    2005-08-01

    Chemical and microbiological parameters were studied during the industrial production of salt-ripened anchovies (Engraulis encrasicholus). Gradual acidification and increases in the proteolysis index and in total volatile basic nitrogen were observed. At the end of the maturing process, the values reached pH 5.55 +/- 0.03, 21.33 +/- 5.82%, and 44.06 +/- 12.47 mg/ 100 g, respectively. In the three studied anchovy batches, the biogenic amines tyramine, histamine, putrescine, cadaverine, and agmatine increased during ripening. The highest values were found in the batch where initial microbial load was highest (batch 1), especially for enterobacteria and enterococci. Tyramine was the most abundant amine, reaching values from nondetectable to 90 mg/kg, whereas histamine did not surpass 20 mg/kg. Among the microorganisms isolated, Enterobacter cloacae, Aerococcus viridans, Kocuria varians, and Staphylococcus chromogenes were able to decarboxylate amino acids and produce biogenic amines in vitro. Most (70.59%) of the microorganisms identified were able to produce histamine, 23.53% were able to produce the diamines putrescine and cadaverine, and only 11.76% were able to produce tyramine, although this substance was the major biogenic amine found in anchovy samples. PMID:21132979

  13. Characterisation of (R)-2-(2-Fluorobiphenyl-4-yl)-N-(3-Methylpyridin-2-yl)Propanamide as a Dual Fatty Acid Amide Hydrolase: Cyclooxygenase Inhibitor

    PubMed Central

    Gouveia-Figueira, Sandra; Karlsson, Jessica; Deplano, Alessandro; Hashemian, Sanaz; Svensson, Mona; Fredriksson Sundbom, Marcus; Congiu, Cenzo; Onnis, Valentina; Fowler, Christopher J.

    2015-01-01

    Background Increased endocannabinoid tonus by dual-action fatty acid amide hydrolase (FAAH) and substrate selective cyclooxygenase (COX-2) inhibitors is a promising approach for pain-relief. One such compound with this profile is 2-(2-fluorobiphenyl-4-yl)-N-(3-methylpyridin-2-yl)propanamide (Flu-AM1). These activities are shown by Flu-AM1 racemate, but it is not known whether its two single enantiomers behave differently, as is the case towards COX-2 for the parent flurbiprofen enantiomers. Further, the effects of the compound upon COX-2-derived lipids in intact cells are not known. Methodology/Principal Findings COX inhibition was determined using an oxygraphic method with arachidonic acid and 2-arachidonoylglycerol (2-AG) as substrates. FAAH was assayed in mouse brain homogenates using anandamide (AEA) as substrate. Lipidomic analysis was conducted in unstimulated and lipopolysaccharide + interferon γ- stimulated RAW 264.7 macrophage cells. Both enantiomers inhibited COX-2 in a substrate-selective and time-dependent manner, with IC50 values in the absence of a preincubation phase of: (R)-Flu-AM1, COX-1 (arachidonic acid) 6 μM; COX-2 (arachidonic acid) 20 μM; COX-2 (2-AG) 1 μM; (S)-Flu-AM1, COX-1 (arachidonic acid) 3 μM; COX-2 (arachidonic acid) 10 μM; COX-2 (2-AG) 0.7 μM. The compounds showed no enantiomeric selectivity in their FAAH inhibitory properties. (R)-Flu-AM1 (10 μM) greatly inhibited the production of prostaglandin D2 and E2 in both unstimulated and lipopolysaccharide + interferon γ- stimulated RAW 264.7 macrophage cells. Levels of 2-AG were not affected either by (R)-Flu-AM1 or by 10 μM flurbiprofen, either alone or in combination with the FAAH inhibitor URB597 (1 μM). Conclusions/Significance Both enantiomers of Flu-AM1 are more potent inhibitors of 2-AG compared to arachidonic acid oxygenation by COX-2. Inhibition of COX in lipopolysaccharide + interferon γ- stimulated RAW 264.7 cells is insufficient to affect 2-AG levels despite the

  14. Aliphatic amines in the Murchison meteorite

    NASA Technical Reports Server (NTRS)

    Jungclaus, G.; Cronin, J. R.; Moore, C. B.; Yuen, G. U.

    1976-01-01

    The paper reports on the determination of aliphatic amines in water extracts of the Murchison meteorite. The amines were analyzed by gas chromatography both as the free amines and as 2,4-dinitrophenyl (DNP) derivatives. The results give evidence for the presence of all of the possible primary aliphatic monoamines (eight) with fewer than five carbon atoms. Two of the seven possible secondary or tertiary aliphatic monoamines were identified. The identified primary amines total 80 nmol per g meteorite, and seem to be chemically or physically trapped in the meteorite. Similarities between the water-extractable amines and amino acids suggest that (1) a simple carbon compound, methane, for example, is the precursor of meteorite amines and amino acids, and (2) both amines and amino acids are extracted from the meteorite both as such and in the form of acid-hydrolyzable derivative or precursor species.

  15. A 2:1 co-crystal of p-nitro­benzoic acid and N,N′-bis­(pyridin-3-ylmeth­yl)ethanedi­amide: crystal structure and Hirshfeld surface analysis

    PubMed Central

    Syed, Sabrina; Halim, Siti Nadiah Abdul; Jotani, Mukesh M.; Tiekink, Edward R. T.

    2016-01-01

    The title 2:1 co-crystal, 2C7H5NO4·C14H14N4O2, in which the complete di­amide mol­ecule is generated by crystallographic inversion symmetry, features a three-mol­ecule aggregate sustained by hydroxyl-O—H⋯N(pyrid­yl) hydrogen bonds. The p-nitro­benzoic acid mol­ecule is non-planar, exhibiting twists of both the carb­oxy­lic acid and nitro groups, which form dihedral angles of 10.16 (9) and 4.24 (4)°, respectively, with the benzene ring. The di­amide mol­ecule has a conformation approximating to a Z shape, with the pyridyl rings lying to either side of the central, almost planar di­amide residue (r.m.s. deviation of the eight atoms being 0.025 Å), and forming dihedral angles of 77.22 (6)° with it. In the crystal, three-mol­ecule aggregates are linked into a linear supra­molecular ladder sustained by amide-N—H⋯O(nitro) hydrogen bonds and orientated along [10-4]. The ladders are connected into a double layer via pyridyl- and benzene-C—H⋯O(amide) inter­actions, which, in turn, are connected into a three-dimensional architecture via π–π stacking inter­actions between pyridyl and benzene rings [inter-centroid distance = 3.6947 (8) Å]. An evaluation of the Hirshfeld surfaces confirm the importance of inter­molecular inter­actions involving oxygen atoms as well as the π–π inter­actions. PMID:26870591

  16. A 2:1 co-crystal of p-nitro-benzoic acid and N,N'-bis-(pyridin-3-ylmeth-yl)ethanedi-amide: crystal structure and Hirshfeld surface analysis.

    PubMed

    Syed, Sabrina; Halim, Siti Nadiah Abdul; Jotani, Mukesh M; Tiekink, Edward R T

    2016-01-01

    The title 2:1 co-crystal, 2C7H5NO4·C14H14N4O2, in which the complete di-amide mol-ecule is generated by crystallographic inversion symmetry, features a three-mol-ecule aggregate sustained by hydroxyl-O-H⋯N(pyrid-yl) hydrogen bonds. The p-nitro-benzoic acid mol-ecule is non-planar, exhibiting twists of both the carb-oxy-lic acid and nitro groups, which form dihedral angles of 10.16 (9) and 4.24 (4)°, respectively, with the benzene ring. The di-amide mol-ecule has a conformation approximating to a Z shape, with the pyridyl rings lying to either side of the central, almost planar di-amide residue (r.m.s. deviation of the eight atoms being 0.025 Å), and forming dihedral angles of 77.22 (6)° with it. In the crystal, three-mol-ecule aggregates are linked into a linear supra-molecular ladder sustained by amide-N-H⋯O(nitro) hydrogen bonds and orientated along [10-4]. The ladders are connected into a double layer via pyridyl- and benzene-C-H⋯O(amide) inter-actions, which, in turn, are connected into a three-dimensional architecture via π-π stacking inter-actions between pyridyl and benzene rings [inter-centroid distance = 3.6947 (8) Å]. An evaluation of the Hirshfeld surfaces confirm the importance of inter-molecular inter-actions involving oxygen atoms as well as the π-π inter-actions. PMID:26870591

  17. NMR chemical shifts in amino acids: Effects of environments, electric field, and amine group rotation

    SciTech Connect

    Yoon, Young-Gui; Pfrommer, Bernd G.; Louie, Steven G.; Canning, Andrew

    2002-03-03

    The authors present calculations of NMR chemical shifts in crystalline phases of some representative amino acids such as glycine, alanine, and alanyl-alanine. To get an insight on how different environments affect the chemical shifts, they study the transition from the crystalline phase to completely isolated molecules of glycine. In the crystalline limit, the shifts are dominated by intermolecular hydrogen-bonds. In the molecular limit, however, dipole electric field effects dominate the behavior of the chemical shifts. They show that it is necessary to average the chemical shifts in glycine over geometries. Tensor components are analyzed to get the angle dependent proton chemical shifts, which is a more refined characterization method.

  18. Arachidonoyl ethanolamide (AEA)-induced Apoptosis is Mediated by J-series Prostaglandins and is Enhanced by Fatty Acid Amide Hydrolase (FAAH) Blockade

    PubMed Central

    Kuc, Christian; Jenkins, Audrey; Van Dross, R. T.

    2011-01-01

    The endocannabinoid arachidonoyl ethanolamide (AEA) is a potent inducer of tumor cell apoptosis however its mechanism of cytotoxicity is unclear. A previous report from our laboratory showed that AEA induced cell death in a COX-2-dependent manner and in this report our data indicate that AEA-induced apoptosis is mediated by COX-2 metabolic products of the J-series. In experiments conducted with JWF2 keratinocytes which overexpress COX-2, AEA caused a concentration-regulated increase in J-series prostaglandin production and apoptosis. Similarly, cell treatment with exogenously added J-series prostaglandins (15-deoxy, Δ12,14 PGJ2 and PGJ2) induced apoptosis. AEA-induced apoptosis was inhibited by the antioxidant, N-acetyl cysteine, indicating that reactive oxygen species generation was required for apoptosis. Using antagonists of cannabinoid receptor 1, cannabinoid receptor 2, or TRPV1, it was observed that cannabinoid receptor inhibition did not block AEA-mediated cell death. In contrast, an inhibitor of fatty acid amide hydrolase (FAAH) potentiated AEA-induced J-series PG synthesis and apoptosis. These results suggest that the metabolism of AEA to J-series PGs regulates the induction of apoptosis in cells with elevated COX-2 levels. Our data further indicate that the proapoptotic activity of AEA can be enhanced by combining it with an inhibitor of FAAH. As such, AEA may be an effective agent to eliminate tumor cells that overexpress COX-2. PMID:21432910

  19. The case for the development of novel analgesic agents targeting both fatty acid amide hydrolase and either cyclooxygenase or TRPV1

    PubMed Central

    Fowler, CJ; Naidu, PS; Lichtman, A; Onnis, V

    2009-01-01

    Although the dominant approach to drug development is the design of compounds selective for a given target, compounds targeting more than one biological process may have superior efficacy, or alternatively a better safety profile than standard selective compounds. Here, this possibility has been explored with respect to the endocannabinoid system and pain. Compounds inhibiting the enzyme fatty acid amide hydrolase (FAAH), by increasing local endocannabinoid tone, produce potentially useful effects in models of inflammatory and possibly neuropathic pain. Local increases in levels of the endocannabinoid anandamide potentiate the actions of cyclooxygenase inhibitors, raising the possibility that compounds inhibiting both FAAH and cyclooxygenase can be as effective as non-steroidal anti-inflammatory drugs but with a reduced cyclooxygenase inhibitory ‘load’. An ibuprofen analogue active in models of visceral pain and with FAAH and cyclooxygenase inhibitory properties has been identified. Another approach, built in to the experimental analgesic compound N-arachidonoylserotonin, is the combination of FAAH inhibitory and transient receptor potential vanilloid type 1 antagonist properties. Although finding the right balance of actions upon the two targets is a key to success, it is hoped that dual-action compounds of the types illustrated in this review will prove to be useful analgesic drugs. PMID:19226258

  20. ω-Imidazolyl- and ω-Tetrazolylalkylcarbamates as Inhibitors of Fatty Acid Amide Hydrolase: Biological Activity and in vitro Metabolic Stability.

    PubMed

    Terwege, Tobias; Hanekamp, Walburga; Garzinsky, David; König, Simone; Koch, Oliver; Lehr, Matthias

    2016-02-17

    Fatty acid amide hydrolase (FAAH) is a serine hydrolase that terminates the analgesic and anti-inflammatory effects of endocannabinoids such as anandamide. Herein, structure-activity relationship studies on a new series of aryl N-(ω-imidazolyl- and ω-tetrazolylalkyl)carbamate inhibitors of FAAH were investigated. As one result, a pronounced increase in inhibitory potency was observed if a phenyl residue attached to the carbamate oxygen atom was replaced by a pyridin-3-yl moiety. The most active compounds exhibited IC50 values in the low nanomolar range. In addition, investigations on the metabolic properties of these inhibitors were performed. In rat liver homogenate and in porcine plasma, the extent of their degradation was shown to be strongly dependent on the kind of aryl residue bound to the carbamate as well as on the length and type of the alkyl spacer connecting the carbamate group with the heterocyclic system. With the aid of esterase inhibitors it was shown that in porcine plasma, carboxylesterase-like enzymes and paraoxonase are involved in carbamate cleavage. Moreover, it was found that highly active pyridin-3-yl carbamates reacted with albumin, which led to covalent albumin adducts. PMID:26732805

  1. Anandamide transport is independent of fatty-acid amide hydrolase activity and is blocked by the hydrolysis-resistant inhibitor AM1172

    PubMed Central

    Fegley, D.; Kathuria, S.; Mercier, R.; Li, C.; Goutopoulos, A.; Makriyannis, A.; Piomelli, D.

    2004-01-01

    The endogenous cannabinoid anandamide is removed from the synaptic space by a high-affinity transport system present in neurons and astrocytes, which is inhibited by N-(4-hydroxyphenyl)-arachidonamide (AM404). After internalization, anandamide is hydrolyzed by fatty-acid amide hydrolase (FAAH), an intracellular membrane-bound enzyme that also cleaves AM404. Based on kinetic evidence, it has recently been suggested that anandamide internalization may be mediated by passive diffusion driven by FAAH activity. To test this possibility, in the present study, we have investigated anandamide internalization in wild-type and FAAH-deficient (FAAH–/–) mice. Cortical neurons from either mouse strain internalized [3H]anandamide through a similar mechanism, i.e., via a rapid temperature-sensitive and saturable process, which was blocked by AM404. Moreover, systemic administration of AM404 to either wild-type or FAAH–/– mice enhanced the hypothermic effects of exogenous anandamide, a response that was prevented by the CB1 cannabinoid antagonist rimonabant (SR141716A). The results indicate that anandamide internalization in mouse brain neurons is independent of FAAH activity. In further support of this conclusion, the compound N-(5Z, 8Z, 11Z, 14Z eicosatetraenyl)-4-hydroxybenzamide (AM1172) blocked [3H]anandamide internalization in rodent cortical neurons and human astrocytoma cells without acting as a FAAH substrate or inhibitor. AM1172 may serve as a prototype for novel anandamide transport inhibitors with increased metabolic stability. PMID:15138300

  2. Crystal Structure of Fatty Acid Amide Hydrolase Bound to the Carbamate Inhibitor URB597: Discovery of a Deacylating Water Molecule and Insight into Enzyme Inactivation

    SciTech Connect

    Mileni, Mauro; Kamtekar, Satwik; Wood, David C.; Benson, Timothy E.; Cravatt, Benjamin F.; Stevens, Raymond C.

    2010-08-12

    The endocannabinoid system regulates a wide range of physiological processes including pain, inflammation, and cognitive/emotional states. URB597 is one of the best characterized covalent inhibitors of the endocannabinoid-degrading enzyme fatty acid amide hydrolase (FAAH). Here, we report the structure of the FAAH-URB597 complex at 2.3 {angstrom} resolution. The structure provides insights into mechanistic details of enzyme inactivation and experimental evidence of a previously uncharacterized active site water molecule that likely is involved in substrate deacylation. This water molecule is part of an extensive hydrogen-bonding network and is coordinated indirectly to residues lining the cytosolic port of the enzyme. In order to corroborate our hypothesis concerning the role of this water molecule in FAAH's catalytic mechanism, we determined the structure of FAAH conjugated to a urea-based inhibitor, PF-3845, to a higher resolution (2.4 {angstrom}) than previously reported. The higher-resolution structure confirms the presence of the water molecule in a virtually identical location in the active site. Examination of the structures of serine hydrolases that are non-homologous to FAAH, such as elastase, trypsin, or chymotrypsin, shows a similarly positioned hydrolytic water molecule and suggests a functional convergence between the amidase signature enzymes and serine proteases.

  3. Synthesis, and anticonvulsant activity of new amides derived from 3-methyl- or 3-ethyl-3-methyl-2,5-dioxo-pyrrolidin-1-yl-acetic acids.

    PubMed

    Obniska, Jolanta; Rapacz, Anna; Rybka, Sabina; Góra, Małgorzata; Kamiński, Krzysztof; Sałat, Kinga; Żmudzki, Paweł

    2016-04-15

    This paper describes the synthesis of the library of 22 new 3-methyl- and 3-ethyl-3-methyl-2,5-dioxo-pyrrolidin-1-yl-acetamides as potential anticonvulsant agents. The maximal electroshock (MES) and the subcutaneous pentylenetetrazole (scPTZ) seizure models were used for screening all the compounds. The 6Hz model of pharmacoresistant limbic seizures was applied for studying selected derivatives. Six amides were chosen for pharmacological characterization of their antinociceptive activity in the formalin model of tonic pain as well as local anesthetic activity was assessed in mice. The pharmacological data indicate on the broad spectra of activity across the preclinical seizure models. Compounds 10 (ED50=32.08mg/kg, MES test) and 9 (ED50=40.34mg/kg, scPTZ test) demonstrated the highest potency. These compounds displayed considerably better safety profiles than clinically relevant antiepileptic drugs phenytoin, ethosuximide, or valproic acid. Several molecules showed antinociceptive and local anesthetic properties. The in vitro radioligand binding studies demonstrated that the influence on the sodium and calcium channels may be one of the essential mechanisms of action. PMID:26970661

  4. Design and synthesis of phosphonoacetic acid (PPA) ester and amide bioisosters of ribofuranosylnucleoside diphosphates as potential ribonucleotide reductase inhibitors and evaluation of their enzyme inhibitory, cytostatic and antiviral activity.

    PubMed

    Manfredini, Stefano; Solaroli, Nicola; Angusti, Angela; Nalin, Federico; Durini, Elisa; Vertuani, Silvia; Pricl, Sabrina; Ferrone, Marco; Spadari, Silvio; Focher, Federico; Verri, Annalisa; De Clercq, Erik; Balzarini, Jan

    2003-07-01

    Continuing our investigations on inhibitors of ribonucleotide reductase (RNR), the crucial enzyme that catalyses the reduction of ribonucleotides to deoxyribonucleotides, we have now prepared and evaluated 5'-phosphonoacetic acid, amide and ester analogues of adenosine, uridine and cytidine with the aim to verify both substrate specificity and contribution to biological activity of diphosphate mimic moieties. A molecular modelling study has been conducted on the RNR R1 subunit, in order to verify the possible interaction of the proposed bioisosteric moieties. The study compounds were finally tested on the recombinant murine RNR showing a degree of inhibition that ranged from 350 microM for the UDP analogue 5'-deoxy-5'-N-(phosphon-acetyl)uridine sodium salt (amide) to 600 microM for the CDP analogue 5'-O-[(diethyl-phosphon)acetyl]cytidine (ester). None of the tested compounds displayed noteworthy cytostatic activity at 100-500 microM concentrations, whereas ADP analogue 5'-N-[(diethyl-phosphon) acetyl]adenosine (amide) and 5'-deoxy-5'-N-(phosphon-acetyl)adenosine sodium salt (amide) showed a moderate inhibitory activity (EC50: 48 microM) against HSV-2 and a modest inhibitory activity (EC50: 110 microM) against HIV-1, respectively. PMID:14582847

  5. Ion Clusters in Nucleation Experiments in the CERN Cloud Chamber: Sulfuric Acid + Ammonia + Dimethyl Amine + Oxidized Organics

    NASA Astrophysics Data System (ADS)

    Worsnop, D. R.; Schobesberger, S.; Bianchi, F.; Ehrhart, S.; Junninen, H.; Kulmala, M. T.

    2012-12-01

    Nucleation from gaseous precursors is an important source of aerosol particles in the atmosphere. The CLOUD experiment at CERN provides exceptionally clean and well-defined experimental conditions for studies of atmospheric nucleation and initial growth, in a 26 m3 stainless-steel chamber. In addition, the influence of cosmic rays on nucleation and nanoparticle growth can be simulated by exposing the chamber to a pion beam produced by the CERN Proton Synchrotron. A key to understanding the mechanism by which nucleation proceeds in the CLOUD chamber is the use of state-of-the-art instrumentation, including the Atmospheric Pressure interface Time-Of-Flight (APi-TOF) mass spectrometer. The APi-TOF is developed by Tofwerk AG, and Aerodyne Research, Inc., and typically obtains resolutions between 4000 and 6000 Th/Th and mass accuracies < 10 ppm. Sampling occurs directly from atmospheric pressure through a critical orifice. Ions are then focused and guided to the time-of-flight mass spectrometer, while passing through differentially pumped chambers. No ionization of the sampled aerosol is performed; only ions charged in the chamber are detected in the current configuration. For all studied chemical systems, the APi-TOF detected ion clusters that could directly be linked to nucleation. The composition of these ion clusters could be determined based on their exact masses and isotopic patterns. Aided by the chamber's cleanliness and the possibility of enhancing ion concentrations by using CERN's pion beam, a remarkably large fraction of the ion spectra could be identified, even for more complex chemical systems studied. For the ammonia-sulfuric acid-water system, for instance, growing clusters containing ammonia (NH3) and sulfuric acid (H2SO4) were observed up to 3300 Th. Adding dimethyl amine and/or pinanediol into the CLOUD chamber, altered the chemical compositions of the observed ion clusters accordingly. Cluster growth then included mixtures of sulfuric acid and

  6. Synthesis and pharmacological properties of 1-(4-substituted)butyl derivatives of amides of 7-methyl-3-phenyl-2,4-dioxo-1,2,3,4-tetrahydropyrido[2,3-d]pyrimi dine-5 -carboxylic acid.

    PubMed

    Sladowska, H; Sieklucka-Dziuba, M; Rejdak, R; Kleinrok, Z

    2000-01-01

    The synthesis of 1-(4-substituted)butyl derivatives of amides of 7-methyl-3-phenyl-2,4-dioxo-1,2,3,4-tetrahydropyrido[2,3-d]pyrimid ine-5- carboxylic acid and the results of the preliminary pharmacological screening are described in this paper. Some of them showed a weak analgesic action and caused suppression of the spontaneous locomotor activity of mice. PMID:10755225

  7. Recognition of the folded conformation of plant hormone (auxin, IAA) conjugates with glutamic and aspartic acids and their amides

    NASA Astrophysics Data System (ADS)

    Antolić, S.; Kveder, M.; Klaić, B.; Magnus, V.; Kojić-Prodić, B.

    2001-01-01

    The molecular structure of the endogenous plant hormone (auxin) conjugate, N-(indol-3-ylacetyl)- L-glutamic acid, is deduced by comparison with N2-(indol-3-ylacetyl)glutamine (IAA-Gln), N2-(indol-3-ylacetyl)asparagine (IAA-Asn) and N-(indol-3-ylacetyl)- L-aspartic acid using X-ray structure analysis, 1H-NMR spectroscopy (NOE measurements) and molecular modelling. The significance of the overall molecular shape, and of the resulting amphiphilic properties, of the compounds studied are discussed in terms of possible implications for trafficking between cell compartments. Both in the solid state and in solution, the molecules are in the hair-pin (folded) conformation in which the side chain is folded over the indole ring. While extended conformations can be detected by molecular dynamics simulations, they are so short-lived that any major influence on the biological properties of the compounds studied is unlikely.

  8. BODIPY catalyzed amide synthesis promoted by BHT and air under visible light.

    PubMed

    Wang, Xiao-Fei; Yu, Shu-Sheng; Wang, Chao; Xue, Dong; Xiao, Jianliang

    2016-08-01

    A novel and efficient protocol for the synthesis of amides is reported which employs a BODIPY catalyzed oxidative amidation reaction between aromatic aldehydes and amines under visible light. Compared with the known Ru or Ir molecular catalysts and other organic dyes, the BODIPY catalyst showed higher reactivity toward this reaction. Mechanistic studies reveal that dioxygen could be activated through an ET and a SET pathway, forming active peroxides in situ, which are vital for the key step of the reaction, i.e. the oxidation of hemiaminal to amide. The broad substrate scope and mild reaction conditions make this reaction practically useful and environmentally friendly for the synthesis of amide compounds. PMID:27363514

  9. Synthesis of structurally defined scaffolds for bivalent ligand display based on glucuronic acid anilides. The degree of tertiary amide isomerism and folding depends on the configuration of a glycosyl azide.

    PubMed

    Tosin, Manuela; Murphy, Paul V

    2005-05-13

    [structures: see text] Syntheses and structural analyses of bivalent carbohydrates based on anilides of glucuronic acid are described. Secondary anilides predominantly adopted the Z-anti structure; there is also evidence for population of the Z-syn isomer. Bivalent tertiary anilides displayed two signal sets in their NMR spectra, consistent with the presence of (i) a major isomer where both amides have E configurations (EE) and (ii) a minor isomer where one amide is E and the other Z (EZ). Qualitative NOE/ROE spectroscopic studies in solution support the proposal that the anti conformation is preferred for E amides. The crystal structure of one bivalent tertiary anilide showed E-anti and E-syn structural isomers; intramolecular carbohydrate-carbohydrate stacking was observed and mediated by carbonyl-pyranose, azide-azide, and pyranose-aromatic interactions. The EE to EZ isomer ratio, or the degree of folding, for tertiary amides, was greatest for a bivalent compound containing two alpha-glycosyl azide groups; this was enhanced in water, suggesting that hydrophobic interactions are partially but not wholly responsible. Computational methods predicted azide-aromatic (N...H-C interaction) and azide-azide interactions for folded isomers. The close contact of the azide and aromatic protons (N...H-C interaction) was observed upon examination of the close packing in the crystal structure of a related monomer. It is proposed that the alpha-azide group is more optimally aligned, compared to the beta-azide, to facilitate interaction and minimize the surface area of the hydrophobic groups exposed to water, and this leads to the increased folding. The alkylation of bivalent secondary anilides induces a switch from Z to E amide that alters the scaffold orientation. The synthesis of a bivalent mannoside, based on a secondary anilide scaffold, for investigation of mannose-binding receptor cross-linking and lattice formation is described. PMID:15876103

  10. Structural characterization of synthetic poly(ester amide) from sebacic acid and 4-amino-1-butanol by matrix-assisted laser desorption ionization time-of-flight/time-of-flight tandem mass spectrometry.

    PubMed

    Rizzarelli, Paola; Puglisi, Concetto

    2008-01-01

    Matrix-assisted laser desorption/ionization time-of-flight/time-of-flight tandem mass spectrometry (MALDI-TOF/TOF-MS/MS) was employed to analyze a poly(ester amide) sample (PEA-Bu) from the melt condensation of sebacic acid and 4-amino-1-butanol. In particular, we investigated the fragmentation pathways, the ester/amide bond sequences and the structure of species derived from side reactions during the synthesis. MALDI-TOF/TOF-MS/MS analysis was performed on cyclic species and linear oligomers terminated by dicarboxyl groups, carboxyl and hydroxyl groups and diamino alcohol groups. The sodium adducts of these oligomers were selected as precursor ions. Different end groups do not influence the fragmentation of sodiated poly(ester amide) oligomers and similar series of product ions were observed in the MALDI-TOF/TOF-MS/MS spectra. According to the structures of the most abundant product ions identified, the main cleavages proceed through a beta-hydrogen-transfer rearrangement, leading to the selective scission of the --O--CH2-- bonds. Abundant product ions originating from --CH2--CH2-- (beta-gamma) bond cleavage in the sebacate moiety were also detected. Their formation should be promoted by the presence of an alpha,beta-unsaturated ester or amide end group. MALDI-TOF/TOF-MS/MS provided structural information concerning the ester/amide sequences in the polymer chains. In the MALDI-TOF/TOF-MS/MS spectra acquired, using argon as the collision gas, of cyclic species and linear oligomers terminated by diamino alcohol groups, product ions in the low-mass range, undetected in the mass spectra acquired using air as the collision gas, proved to be diagnostic and made it possible to establish the presence of random sequences of ester and amide bonds in the poly(ester amide) sample. Furthermore, MALDI-TOF/TOF-MS/MS provided useful information to clarify the structures of precursor ions derived from side reactions during the synthesis. PMID:18278818

  11. A 2:1 co-crystal of 2-methyl­benzoic acid and N,N′-bis­(pyridin-4-ylmeth­yl)ethanedi­amide: crystal structure and Hirshfeld surface analysis

    PubMed Central

    Syed, Sabrina; Jotani, Mukesh M.; Halim, Siti Nadiah Abdul; Tiekink, Edward R. T.

    2016-01-01

    The asymmetric unit of the title 2:1 co-crystal, 2C8H8O2·C14H14N4O2, comprises an acid mol­ecule in a general position and half a di­amide mol­ecule, the latter being located about a centre of inversion. In the acid, the carb­oxy­lic acid group is twisted out of the plane of the benzene ring to which it is attached [dihedral angle = 28.51 (8)°] and the carbonyl O atom and methyl group lie approximately to the same side of the mol­ecule [hy­droxy-O—C—C—C(H) torsion angle = −27.92 (17)°]. In the di­amide, the central C4N2O2 core is almost planar (r.m.s. deviation = 0.031 Å), and the pyridyl rings are perpendicular, lying to either side of the central plane [central residue/pyridyl dihedral angle = 88.60 (5)°]. In the mol­ecular packing, three-mol­ecule aggregates are formed via hy­droxy-O—H⋯N(pyrid­yl) hydrogen bonds. These are connected into a supra­molecular layer parallel to (12) via amide-N—H⋯O(carbon­yl) hydrogen bonds, as well as methyl­ene-C—H⋯O(amide) inter­actions. Significant π–π inter­actions occur between benzene/benzene, pyrid­yl/benzene and pyrid­yl/pyridyl rings within and between layers to consolidate the three-dimensional packing. PMID:27006815

  12. A 2:1 co-crystal of 2-methyl-benzoic acid and N,N'-bis-(pyridin-4-ylmeth-yl)ethanedi-amide: crystal structure and Hirshfeld surface analysis.

    PubMed

    Syed, Sabrina; Jotani, Mukesh M; Halim, Siti Nadiah Abdul; Tiekink, Edward R T

    2016-03-01

    The asymmetric unit of the title 2:1 co-crystal, 2C8H8O2·C14H14N4O2, comprises an acid mol-ecule in a general position and half a di-amide mol-ecule, the latter being located about a centre of inversion. In the acid, the carb-oxy-lic acid group is twisted out of the plane of the benzene ring to which it is attached [dihedral angle = 28.51 (8)°] and the carbonyl O atom and methyl group lie approximately to the same side of the mol-ecule [hy-droxy-O-C-C-C(H) torsion angle = -27.92 (17)°]. In the di-amide, the central C4N2O2 core is almost planar (r.m.s. deviation = 0.031 Å), and the pyridyl rings are perpendicular, lying to either side of the central plane [central residue/pyridyl dihedral angle = 88.60 (5)°]. In the mol-ecular packing, three-mol-ecule aggregates are formed via hy-droxy-O-H⋯N(pyrid-yl) hydrogen bonds. These are connected into a supra-molecular layer parallel to (12[Formula: see text]) via amide-N-H⋯O(carbon-yl) hydrogen bonds, as well as methyl-ene-C-H⋯O(amide) inter-actions. Significant π-π inter-actions occur between benzene/benzene, pyrid-yl/benzene and pyrid-yl/pyridyl rings within and between layers to consolidate the three-dimensional packing. PMID:27006815

  13. Immobilization of alpha-[di-(beta-chloroethyl)-amide]-N-(m-nitrobenzoyl)-D,L-asparagic acid on xanthan.

    PubMed

    Marcel, Popa; Lăcrămioara, Bălăită Rusu; Valeriu, Sunel

    2003-10-01

    The paper studies the coupling reaction, through ester-type covalent bonds, of an oxazolone derived from the N-(m-nitrobenzoyl)-L-asparagic acid, the cycle of which is opened with an N-mustard derivative, on xanthan (a polysaccharide of microbian synthesis), in conditions of activation with dicyclohexyl carbodiimide. The coupling product has been characterized through elemental analysis and IR spectroscopy. For the establishment of the capacity of the active principle's controlled release by the polymer-active principle system thus obtained, active principle's release kinetics from the polysaccharide support, in conditions of basic hydrolysis, is studied. In vivo tests realized on mice proved the antitumoral activity of the compounds resulted by chemical bonding of the N-mustard derivative on xanthan. PMID:14621335

  14. Fuel additives from SO/sub 2/ treated mixtures of amides and esters derived from vegetable oil, tall oil acid, or aralkyl acid

    SciTech Connect

    Efner, H. F.; Schiff, S.

    1985-03-12

    Vegetable oils, particularly soybean oil, tall oil acid, or aralkyl acids, particularly phenylstearic acid, are reacted with multiamines, particularly tetraethylenepentamine, to form a product mixture for subsequent reaction with SO/sub 2/ to produce a product mix that has good detergent properties in fuels.

  15. Friedel-Crafts Acylation with Amides

    PubMed Central

    Raja, Erum K.; DeSchepper, Daniel J.; Nilsson Lill, Sten O.; Klumpp, Douglas A.

    2012-01-01

    Friedel-Crafts acylation has been known since the 1870s and it is an important organic synthetic reaction leading to aromatic ketone products. Friedel-Crafts acylation is usually done with carboxylic acid chlorides or anhydrides while amides are generally not useful substrates in these reactions. Despite being the least reactive carboxylic acid derivative, we have found a series of amides capable of providing aromatic ketones in good yields (55–96%, 17 examples). We propose a mechanism involving diminished C-N resonance through superelectrophilic activation and subsequent cleavage to acyl cations. PMID:22690740

  16. Influence of packaging conditions on biogenic amines and fatty acids evolution during 15months storage of a typical spreadable salami ('Nduja).

    PubMed

    Loizzo, Monica Rosa; Spizzirri, U Gianfranco; Bonesi, Marco; Tundis, Rosa; Picci, Nevio; Restuccia, Donatella

    2016-12-15

    The study evaluated the fatty acids and the biogenic amines (BAs) in 'Nduja of Spilinga stored in different packaging materials (i.e. natural casing under vacuum, glass jar, aluminum tube and OVTENE®) during 15months of shelf-life. Raw materials and pepper mixture were analysed as well. BAs concentrations increased with time, tyramine (TYR), putrescine (PUT) and cadaverine (CAD) were the most abundant. BAs in natural casing were always higher than those found in glass jar, aluminum tube and OVTENE®. Total fatty acids were characterized by higher level of unsaturated fatty acid that decreased with time (glass jar>natural casing under vacuum>aluminum tube>OVTENE®). The reduction of PUFA is the consequence of the increase of peroxides and carbonyls reacting with amino acids to form BAs. This was confirmed by Pearson's correlation matrices implying that lipid oxidation processes were in some way linked to the chemical production of BAs. PMID:27451162

  17. Reductively degradable α-amino acid-based poly(ester amide)-graft-galactose copolymers: facile synthesis, self-assembly, and hepatoma-targeting doxorubicin delivery.

    PubMed

    Lv, Jiaolong; Sun, Huanli; Zou, Yan; Meng, Fenghua; Dias, Aylvin A; Hendriks, Marc; Feijen, Jan; Zhong, Zhiyuan

    2015-07-01

    Novel reductively degradable α-amino acid-based poly(ester amide)-graft-galactose (SSPEA-Gal) copolymers were designed and developed to form smart nano-vehicles for active hepatoma-targeting doxorubicin (DOX) delivery. SSPEA-Gal copolymers were readily synthesized via solution polycondensation reaction of di-p-toluenesulfonic acid salts of bis-l-phenylalanine 2,2-thiodiethanol diester and bis-vinyl sulfone functionalized cysteine hexanediol diester with dinitrophenyl ester of adipic acid, followed by conjugating with thiol-functionalized galactose (Gal-SH) via the Michael addition reaction. SSPEA-Gal formed unimodal nanoparticles (PDI = 0.10 - 0.12) in water, in which average particle sizes decreased from 138 to 91 nm with increasing Gal contents from 31.6 wt% to 42.5 wt%. Notably, in vitro drug release studies showed that over 80% DOX was released from SSPEA-Gal nanoparticles within 12 h under an intracellular mimicking reductive conditions, while low DOX release (<20%) was observed for reduction-insensitive PEA-Gal nanoparticles under otherwise the same conditions and SSPEA-Gal nanoparticles under non-reductive conditions. Notably, SSPEA-Gal nanoparticles exhibited high specificity to asialoglycoprotein receptor (ASGP-R)-overexpressing HepG2 cells. MTT assays using HepG2 cells showed that DOX-loaded SSPEA-Gal had a low half maximal inhibitory concentration (IC50) of 1.37 μg mL(-1), approaching that of free DOX. Flow cytometry and confocal laser scanning microscopy studies confirmed the efficient uptake of DOX-loaded SSPEA-Gal nanoparticles by HepG2 cells as well as fast intracellular DOX release. Importantly, SSPEA-Gal and PEA-Gal nanoparticles were non-cytotoxic to HepG2 and MCF-7 cells up to a tested concentration of 1.0 mg mL(-1). These tumor-targeting and reduction-responsive degradable nanoparticles have appeared as an interesting multi-functional platform for advanced drug delivery. PMID:26221946

  18. Prolonged Monoacylglycerol Lipase Blockade Causes Equivalent Cannabinoid Receptor Type 1 Receptor–Mediated Adaptations in Fatty Acid Amide Hydrolase Wild-Type and Knockout Mice

    PubMed Central

    Kinsey, Steven G.; Ignatowska-Jankowska, Bogna; Ramesh, Divya; Abdullah, Rehab A.; Tao, Qing; Booker, Lamont; Long, Jonathan Z.; Selley, Dana E.; Cravatt, Benjamin F.; Lichtman, Aron H.

    2014-01-01

    Complementary genetic and pharmacological approaches to inhibit monoacylglycerol lipase (MAGL) and fatty acid amide hydrolase (FAAH), the primary hydrolytic enzymes of the respective endogenous cannabinoids 2-arachidonoylglycerol (2-AG) and N-arachidonoylethanolamine, enable the exploration of potential therapeutic applications and physiologic roles of these enzymes. Complete and simultaneous inhibition of both FAAH and MAGL produces greatly enhanced cannabimimetic responses, including increased antinociception, and other cannabimimetic effects, far beyond those seen with inhibition of either enzyme alone. While cannabinoid receptor type 1 (CB1) function is maintained following chronic FAAH inactivation, prolonged excessive elevation of brain 2-AG levels, via MAGL inhibition, elicits both behavioral and molecular signs of cannabinoid tolerance and dependence. Here, we evaluated the consequences of a high dose of the MAGL inhibitor JZL184 [4-nitrophenyl 4-(dibenzo[d][1,3]dioxol-5-yl(hydroxy)methyl)piperidine-1-carboxylate; 40 mg/kg] given acutely or for 6 days in FAAH(−/−) and (+/+) mice. While acute administration of JZL184 to FAAH(−/−) mice enhanced the magnitude of a subset of cannabimimetic responses, repeated JZL184 treatment led to tolerance to its antinociceptive effects, cross-tolerance to the pharmacological effects of Δ9-tetrahydrocannabinol, decreases in CB1 receptor agonist–stimulated guanosine 5′-O-(3-[35S]thio)triphosphate binding, and dependence as indicated by rimonabant-precipitated withdrawal behaviors, regardless of genotype. Together, these data suggest that simultaneous elevation of both endocannabinoids elicits enhanced cannabimimetic activity but MAGL inhibition drives CB1 receptor functional tolerance and cannabinoid dependence. PMID:24849924

  19. Influence of the degree of unsaturation of the acyl side chain upon the interaction of analogues of 1-arachidonoylglycerol with monoacylglycerol lipase and fatty acid amide hydrolase

    SciTech Connect

    Vandevoorde, Severine; Saha, Bijali; Mahadevan, Anu; Razdan, Raj K.; Pertwee, Roger G.; Martin, Billy R.; Fowler, Christopher J. . E-mail: cf@pharm.umu.se

    2005-11-11

    Little is known as to the structural requirements of the acyl side chain for interaction of acylglycerols with monoacylglycerol lipase (MAGL), the enzyme chiefly responsible for the metabolism of the endocannabinoid 2-arachidonoylglycerol (2-AG) in the brain. In the present study, a series of twelve analogues of 1-AG (the more stable regioisomer of 2-AG) were investigated with respect to their ability to inhibit the metabolism of 2-oleoylglycerol by cytosolic and membrane-bound MAGL. In addition, the ability of the compounds to inhibit the hydrolysis of anandamide by fatty acid amide hydrolase (FAAH) was investigated. For cytosolic MAGL, compounds with 20 carbon atoms in the acyl chain and 2-5 unsaturated bonds inhibited the hydrolysis of 2-oleoylglycerol with similar potencies (IC{sub 50} values in the range 5.1-8.2 {mu}M), whereas the two compounds with a single unsaturated bond were less potent (IC{sub 50} values 19 and 21 {mu}M). The fully saturated analogue 1-monoarachidin did not inhibit the enzyme, whereas the lower side chain analogues 1-monopalmitin and 1-monomyristin inhibited the enzyme with IC{sub 50} values of 12 and 32 {mu}M, respectively. The 22-carbon chain analogue of 1-AG was also potent (IC{sub 50} value 4.5 {mu}M). Introduction of an {alpha}-methyl group for the C20:4, C20:3, and C22:4 compounds did not affect potency in a consistent manner. For the FAAH and the membrane-bound MAGL, there was no obvious relationship between the degree of unsaturation of the acyl side chain and the ability to inhibit the enzymes. It is concluded that increasing the number of unsaturated bonds on the acyl side chain of 1-AG from 1 to 5 has little effect on the affinity of acylglycerols for cytosolic MAGL.

  20. Full Fatty Acid Amide Hydrolase Inhibition Combined with Partial Monoacylglycerol Lipase Inhibition: Augmented and Sustained Antinociceptive Effects with Reduced Cannabimimetic Side Effects in Mice

    PubMed Central

    Ghosh, Sudeshna; Kinsey, Steven G.; Liu, Qing-song; Hruba, Lenka; McMahon, Lance R.; Grim, Travis W.; Merritt, Christina R.; Wise, Laura E.; Abdullah, Rehab A.; Selley, Dana E.; Sim-Selley, Laura J.; Cravatt, Benjamin F.

    2015-01-01

    Inhibition of fatty acid amide hydrolase (FAAH) or monoacylglycerol lipase (MAGL), the primary hydrolytic enzymes for the respective endocannabinoids N-arachidonoylethanolamine (AEA) and 2-arachidonylglycerol (2-AG), produces antinociception but with minimal cannabimimetic side effects. Although selective inhibitors of either enzyme often show partial efficacy in various nociceptive models, their combined blockade elicits augmented antinociceptive effects, but side effects emerge. Moreover, complete and prolonged MAGL blockade leads to cannabinoid receptor type 1 (CB1) receptor functional tolerance, which represents another challenge in this potential therapeutic strategy. Therefore, the present study tested whether full FAAH inhibition combined with partial MAGL inhibition would produce sustained antinociceptive effects with minimal cannabimimetic side effects. Accordingly, we tested a high dose of the FAAH inhibitor PF-3845 (N-​3-​pyridinyl-​4-​[[3-​[[5-​(trifluoromethyl)-​2-​pyridinyl]oxy]phenyl]methyl]-​1-​piperidinecarboxamide; 10 mg/kg) given in combination with a low dose of the MAGL inhibitor JZL184 [4-nitrophenyl 4-(dibenzo[d][1,3]dioxol-5-yl(hydroxy)methyl)piperidine-1-carboxylate] (4 mg/kg) in mouse models of inflammatory and neuropathic pain. This combination of inhibitors elicited profound increases in brain AEA levels (>10-fold) but only 2- to 3-fold increases in brain 2-AG levels. This combination produced significantly greater antinociceptive effects than single enzyme inhibition and did not elicit common cannabimimetic effects (e.g., catalepsy, hypomotility, hypothermia, and substitution for Δ9-tetrahydrocannabinol in the drug-discrimination assay), although these side effects emerged with high-dose JZL184 (i.e., 100 mg/kg). Finally, repeated administration of this combination did not lead to tolerance to its antiallodynic actions in the carrageenan assay or CB1 receptor functional tolerance. Thus, full FAAH inhibition combined

  1. Antidepressant-like activity and cardioprotective effects of fatty acid amide hydrolase inhibitor URB694 in socially stressed Wistar Kyoto rats.

    PubMed

    Carnevali, Luca; Vacondio, Federica; Rossi, Stefano; Callegari, Sergio; Macchi, Emilio; Spadoni, Gilberto; Bedini, Annalida; Rivara, Silvia; Mor, Marco; Sgoifo, Andrea

    2015-11-01

    In humans, depression is often triggered by prolonged exposure to psychosocial stressors and is often associated with cardiovascular comorbidity. Mounting evidence suggests a role for endocannabinoid signaling in the regulation of both emotional behavior and cardiovascular function. Here, we examined cardiac activity in a rodent model of social stress-induced depression and investigated whether pharmacological inhibition of the enzyme fatty acid amide hydrolase (FAAH), which terminates signaling of the endocannabinoid anandamide, exerts antidepressant-like and cardioprotective effects. Male Wistar Kyoto rats were exposed to five weeks of repeated social stress or control procedure. Starting from the third week, they received daily administration of the selective FAAH inhibitor URB694 (0.1 mg/kg, i.p.) or vehicle. Cardiac electrical activity was recorded by radiotelemetry. Repeated social stress triggered biological and behavioral changes that mirror symptoms of human depression, such as (i) reductions in body weight gain and sucrose solution preference, (ii) hyperactivity of the hypothalamic-pituitary-adrenocortical axis, and (iii) increased immobility in the forced swim test. Moreover, stressed rats showed (i) alterations in heart rate daily rhythm and cardiac autonomic neural regulation, (ii) a larger incidence of spontaneous arrhythmias, and (iii) signs of cardiac hypertrophy. Daily treatment with URB694 (i) increased central and peripheral anandamide levels, (ii) corrected stress-induced alterations of biological and behavioral parameters, and (iii) protected the heart against the adverse effects of social stress. Repeated social stress in Wistar Kyoto rats reproduces aspects of human depression/cardiovascular comorbidity. Pharmacological enhancement of anandamide signaling might be a promising strategy for the treatment of these comorbid conditions. PMID:26391492

  2. Localization of the endocannabinoid-degrading enzyme fatty acid amide hydrolase in rat dorsal root ganglion cells and its regulation after peripheral nerve injury.

    PubMed

    Lever, Isobel J; Robinson, Michelle; Cibelli, Mario; Paule, Cleoper; Santha, Peter; Yee, Louis; Hunt, Stephen P; Cravatt, Benjamin F; Elphick, Maurice R; Nagy, Istvan; Rice, Andrew S C

    2009-03-25

    Fatty acid amide hydrolase (FAAH) is a degradative enzyme for a group of endogenous signaling lipids that includes anandamide (AEA). AEA acts as an endocannabinoid and an endovanilloid by activating cannabinoid and vanilloid type 1 transient receptor potential (TRPV1) receptors, respectively, on dorsal root ganglion (DRG) sensory neurons. Inhibition of FAAH activity increases AEA concentrations in nervous tissue and reduces sensory hypersensitivity in animal pain models. Using immunohistochemistry, Western blotting, and reverse transcription-PCR, we demonstrate the location of the FAAH in adult rat DRG, sciatic nerve, and spinal cord. In naive rats, FAAH immunoreactivity localized to the soma of 32.7 +/- 0.8% of neurons in L4 and L5 DRG. These were small-sized (mean soma area, 395.96 +/- 5.6 mum(2)) and predominantly colabeled with peripherin and isolectin B4 markers of unmyelinated C-fiber neurons; 68% colabeled with antibodies to TRPV1 (marker of nociceptive DRG neurons), and <2% colabeled with NF200 (marker of large myelinated neurons). FAAH-IR was also present in small, NF200-negative cultured rat DRG neurons. Incubation of these cultures with the FAAH inhibitor URB597 increased AEA-evoked cobalt uptake in a capsazepine-sensitive manner. After sciatic nerve axotomy, there was a rightward shift in the cell-size distribution of FAAH-immunoreactive (IR) DRG neurons ipsilateral to injury: FAAH immunoreactivity was detected in larger-sized cells that colabeled with NF200. An ipsilateral versus contralateral increase in both the size and proportion of FAAH-IR DRG occurred after spinal nerve transection injury but not after chronic inflammation of the rat hindpaw 2 d after injection of complete Freund's adjuvant. This study reveals the location of FAAH in neural tissue involved in peripheral nociceptive transmission. PMID:19321773

  3. Pharmacological blockade of the fatty acid amide hydrolase (FAAH) alters neural proliferation, apoptosis and gliosis in the rat hippocampus, hypothalamus and striatum in a negative energy context

    PubMed Central

    Rivera, Patricia; Bindila, Laura; Pastor, Antoni; Pérez-Martín, Margarita; Pavón, Francisco J.; Serrano, Antonia; de la Torre, Rafael; Lutz, Beat; Rodríguez de Fonseca, Fernando; Suárez, Juan

    2015-01-01

    Endocannabinoids participate in the control of neurogenesis, neural cell death and gliosis. The pharmacological effect of the fatty acid amide hydrolase (FAAH) inhibitor URB597, which limits the endocannabinoid degradation, was investigated in the present study. Cell proliferation (phospho-H3+ or BrdU+ cells) of the main adult neurogenic zones as well as apoptosis (cleaved caspase-3+), astroglia (GFAP+), and microglia (Iba1+ cells) were analyzed in the hippocampus, hypothalamus and striatum of rats intraperitoneally treated with URB597 (0.3 mg/kg/day) at one dose/4-days resting or 5 doses (1 dose/day). Repeated URB597 treatment increased the plasma levels of the N-acylethanolamines oleoylethanolamide, palmitoylethanolamide and arachidonoylethanolamine, reduced the plasma levels of glucose, triglycerides and cholesterol, and induced a transitory body weight decrease. The hippocampi of repeated URB597-treated rats showed a reduced number of phospho-H3+ and BrdU+ subgranular cells as well as GFAP+, Iba1+ and cleaved caspase-3+ cells, which was accompanied with decreased hippocampal expression of the cannabinoid CB1 receptor gene Cnr1 and Faah. In the hypothalami of these rats, the number of phospho-H3+, GFAP+ and 3-weeks-old BrdU+ cells was specifically decreased. The reduced striatal expression of CB1 receptor in repeated URB597-treated rats was only associated with a reduced apoptosis. In contrast, the striatum of acute URB597-treated rats showed an increased number of subventricular proliferative, astroglial and apoptotic cells, which was accompanied with increased Faah expression. Main results indicated that FAAH inhibitor URB597 decreased neural proliferation, glia and apoptosis in a brain region-dependent manner, which were coupled to local changes in Faah and/or Cnr1 expression and a negative energy context. PMID:25870539

  4. The fatty acid amide hydrolase inhibitor PF-3845 promotes neuronal survival, attenuates inflammation and improves functional recovery in mice with traumatic brain injury

    PubMed Central

    Tchantchou, Flaubert; Tucker, Laura B.; Fu, Amanda H.; Bluett, Rebecca J.; McCabe, Joseph T.; Patel, Sachin; Zhang, Yumin

    2015-01-01

    Traumatic brain injury (TBI) is the leading cause of death in young adults in the United States, but there is still no effective agent for treatment. N-arachidonoylethanolamine (anandamide, AEA) is a major endocannabinoid in the brain. Its increase after brain injury is believed to be protective. However, the compensatory role of AEA is transient due to its rapid hydrolysis by the fatty acid amide hydrolase (FAAH). Thus, inhibition of FAAH can boost the endogenous levels of AEA and prolong its protective effect. Using a TBI mouse model, we found that post-injury chronic treatment with PF3845, a selective and potent FAAH inhibitor, reversed TBI-induced impairments in fine motor movement, hippocampus dependent working memory and anxiety-like behavior. Treatment with PF3845 inactivated FAAH activity and enhanced the AEA levels in the brain. It reduced neurodegeneration in the dentate gyrus, and up-regulated the expression of Bcl-2 and Hsp70/72 in both cortex and hippocampus. PF3845 also suppressed the increased production of amyloid precursor protein, prevented dendritic loss and restored the levels of synaptophysin in the ipsilateral dentate gyrus. Furthermore, PF3845 suppressed the expression of inducible nitric oxide synthase and cyclooxygenase-2 and enhanced the expression of arginase-1 post-TBI, suggesting a shift of microglia/macrophages from M1 to M2 phenotype. The effects of PF3845 on TBI-induced behavioral deficits and neurodegeneration were mediated by activation of cannabinoid type 1 and 2 receptors and might be attributable to the phosphorylation of ERK1/2 and AKT. These results suggest that selective inhibition of FAAH is likely to be beneficial for TBI treatment. PMID:24937045

  5. Involvement of endocannabinoids in alcohol “binge” drinking: studies of mice with human fatty acid amide hydrolase genetic variation and after CB1 receptor antagonists

    PubMed Central

    Zhou, Yan; Huang, Ted; Lee, Francis; Kreek, Mary Jeanne

    2016-01-01

    Background The endocannabinoid system has been found to play an important role in modulating alcohol intake. Inhibition or genetic deletion of fatty acid amide hydrolase (FAAH, a key catabolic enzyme for endocannabinoids) leads to increased alcohol consumption and preference in rodent models. A common human single-nucleotide polymorphism (SNP; C385A, rs324420) in the FAAH gene is associated with decreased enzymatic activity of FAAH, resulting in increased anandamide levels in both humans and FAAH C385A knock-in mice. Methods As this FAAH SNP has been reported to be associated with altered alcohol abuse, the present study used these genetic knock-in mice containing the human SNP C385A to determine the impact of variant FAAH gene on alcohol “binge” drinking in the drinking-in-the-dark (DID) model. Results We found that the FAAHA/A mice had greater alcohol intake and preference than the wild-type FAAHC/C mice, suggesting that increased endocannabinoid signaling in FAAHA/A mice led to increased alcohol “binge” consumption. The specificity on alcohol vulnerability was suggested by the lack of any FAAH genotype difference on sucrose or saccharin intake. Using the “binge” DID model, we confirmed that selective CB1 receptor antagonist AM251 reduced alcohol intake in the wild-type mice. Conclusions These data suggest that there is direct and selective involvement of the human FAAH C385A SNP and CB1 receptors in alcohol “binge” drinking. PMID:26857901

  6. Therapeutic effect of the endogenous fatty acid amide, palmitoylethanolamide, in rat acute inflammation: inhibition of nitric oxide and cyclo-oxygenase systems

    PubMed Central

    Costa, Barbara; Conti, Silvia; Giagnoni, Gabriella; Colleoni, Mariapia

    2002-01-01

    The anti-inflammatory activity of the endogenous fatty acid amide palmitoylethanolamide and its relationship to cyclo-oxygenase (COX) activity, nitric oxide (NO) and oxygen free radical production were investigated in the rat model of carrageenan-induced acute paw inflammation and compared with the nonsteroidal anti-inflammatory drug (NSAID) indomethacin. Palmitoylethanolamide (1, 3, 5, 10 mg kg−1; p.o.) and indomethacin (5 mg kg−1; p.o.) were administered daily after the onset of inflammation for three days and the paw oedema was measured daily; 24 h after the last dose (fourth day) the rats were killed and the COX activity and the content of nitrite/nitrate (NO2−/NO3−), malondialdehyde (MDA), endothelial and inducible nitric oxide synthase (eNOS and iNOS) were evaluated in the paw tissues. Palmitoylethanolamide had a curative effect on inflammation, inhibiting the carrageenan-induced oedema in a dose- and time-dependent manner. This effect was not reversed by the selective CB2 receptor antagonist (N-[(1S)-endo-1,3,3-trimethylbicyclo[2.2.1]heptan-2yl]-5-(4-chloro-3-methylphenyl)-1-(4-methylbenzyl)pyrazole-3 carboxamide) (SR144528), 3 mg kg−1 p.o. On the fourth day after carrageenan injection, COX activity and the level of NO2−/NO3−, eNOS and MDA were increased in the inflamed paw, but iNOS was not present. Palmitoylethanolamide (10 mg kg−1) and indomethacin markedly reduced these increases. Our findings show, for the first time, that palmitoylethanolamide has a curative effect in a model of acute inflammation. The inhibition of COX activity and of NO and free radical production at the site of inflammation might account for this activity. PMID:12359622

  7. Pharmacological blockade of the fatty acid amide hydrolase (FAAH) alters neural proliferation, apoptosis and gliosis in the rat hippocampus, hypothalamus and striatum in a negative energy context.

    PubMed

    Rivera, Patricia; Bindila, Laura; Pastor, Antoni; Pérez-Martín, Margarita; Pavón, Francisco J; Serrano, Antonia; de la Torre, Rafael; Lutz, Beat; Rodríguez de Fonseca, Fernando; Suárez, Juan

    2015-01-01

    Endocannabinoids participate in the control of neurogenesis, neural cell death and gliosis. The pharmacological effect of the fatty acid amide hydrolase (FAAH) inhibitor URB597, which limits the endocannabinoid degradation, was investigated in the present study. Cell proliferation (phospho-H3(+) or BrdU(+) cells) of the main adult neurogenic zones as well as apoptosis (cleaved caspase-3(+)), astroglia (GFAP(+)), and microglia (Iba1(+) cells) were analyzed in the hippocampus, hypothalamus and striatum of rats intraperitoneally treated with URB597 (0.3 mg/kg/day) at one dose/4-days resting or 5 doses (1 dose/day). Repeated URB597 treatment increased the plasma levels of the N-acylethanolamines oleoylethanolamide, palmitoylethanolamide and arachidonoylethanolamine, reduced the plasma levels of glucose, triglycerides and cholesterol, and induced a transitory body weight decrease. The hippocampi of repeated URB597-treated rats showed a reduced number of phospho-H3(+) and BrdU(+) subgranular cells as well as GFAP(+), Iba1(+) and cleaved caspase-3(+) cells, which was accompanied with decreased hippocampal expression of the cannabinoid CB1 receptor gene Cnr1 and Faah. In the hypothalami of these rats, the number of phospho-H3(+), GFAP(+) and 3-weeks-old BrdU(+) cells was specifically decreased. The reduced striatal expression of CB1 receptor in repeated URB597-treated rats was only associated with a reduced apoptosis. In contrast, the striatum of acute URB597-treated rats showed an increased number of subventricular proliferative, astroglial and apoptotic cells, which was accompanied with increased Faah expression. Main results indicated that FAAH inhibitor URB597 decreased neural proliferation, glia and apoptosis in a brain region-dependent manner, which were coupled to local changes in Faah and/or Cnr1 expression and a negative energy context. PMID:25870539

  8. Inhibition of carbohydrate-mediated glucagon-like peptide-1 (7-36)amide secretion by circulating non-esterified fatty acids.

    PubMed

    Ranganath, L; Norris, F; Morgan, L; Wright, J; Marks, V

    1999-04-01

    Two studies were performed to assess the entero-insular axis in simple obesity and the possible effect of variations in the level of circulating non-esterified fatty acids (NEFA) on one of the components of the entero-insular axis, glucagon-like peptide-1 [(7-36) amide]. In the first study, we compared the entero-pancreatic hormone response to oral carbohydrate in obese and lean women. Obese subjects demonstrated hyperinsulinaemia and impaired glucose tolerance but this was not associated with an increased secretion of either glucose-dependent insulinotropic polypeptide or glucagon-like peptide-1 (GLP-1). These findings therefore provide no support for the hypothesis that overactivity of the entero-insular axis contributes to the hyperinsulinaemia seen in obesity. Indeed, the plasma GLP-1 response to carbohydrate was markedly attenuated in obese subjects, confirming previous observations. In the second study, in which carbohydrate-stimulated GLP-1 responses were again evaluated in obese and lean women, circulating NEFA levels were modulated using either heparin (to increase serum NEFA) or acipimox (to reduce serum NEFA). Treatment with acipimox resulted in complete suppression of NEFA levels and in a markedly higher GLP-1 response than the response to carbohydrate alone or to carbohydrate plus heparin. We suggest that higher fasting and postprandial NEFA levels in obesity may tonically inhibit nutrient-mediated GLP-1 secretion, and that this results in attenuation of the GLP-1 response to carbohydrate. However, although serum NEFA levels post-acipimox were similarly suppressed in both lean and obese subjects, the GLP-1 response was again significantly lower in obese subjects, suggesting the possibility of an intrinsic defect of GLP-1 secretion in obesity. The reduction of GLP-1 levels in obesity may be important both in relation to its insulinotropic effect and to its postulated role as a satiety factor. PMID:10087239

  9. Electrochemical reduction of nitrate in the presence of an amide

    DOEpatents

    Dziewinski, Jacek J.; Marczak, Stanislaw

    2002-01-01

    The electrochemical reduction of nitrates in aqueous solutions thereof in the presence of amides to gaseous nitrogen (N.sub.2) is described. Generally, electrochemical reduction of NO.sub.3 proceeds stepwise, from NO.sub.3 to N.sub.2, and subsequently in several consecutive steps to ammonia (NH.sub.3) as a final product. Addition of at least one amide to the solution being electrolyzed suppresses ammonia generation, since suitable amides react with NO.sub.2 to generate N.sub.2. This permits nitrate reduction to gaseous nitrogen to proceed by electrolysis. Suitable amides include urea, sulfamic acid, formamide, and acetamide.

  10. Effect of γ-Aminobutyric Acid (GABA) Producing Bacteria on In vitro Rumen Fermentation, Biogenic Amine Production and Anti-oxidation Using Corn Meal as Substrate

    PubMed Central

    Ku, Bum Seung; Mamuad, Lovelia L.; Kim, Seon-Ho; Jeong, Chang Dae; Soriano, Alvin P.; Lee, Ho-Il; Nam, Ki-Chang; Ha, Jong K.; Lee, Sang Suk

    2013-01-01

    The effects and significance of γ-amino butyric acid (GABA) producing bacteria (GPB) on in vitro rumen fermentation and reduction of biogenic amines (histamine, methylamine, ethylamine, and tyramine) using corn meal as a substrate were determined. Ruminal samples collected from ruminally fistulated Holstein cows served as inoculum and corn was used as substrate at 2% dry matter (DM). Different inclusion rates of GPB and GABA were evaluated. After incubation, addition of GPB had no significant effect on in vitro fermentation pH and total gas production, but significantly increased the ammonia nitrogen (NH3-N) concentration and reduced the total biogenic amines production (p<0.05). Furthermore, antioxidation activity was improved as indicated by the significantly higher concentration of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) among treated samples when compared to the control (p<0.05). Additionally, 0.2% GPB was established as the optimum inclusion level. Taken together, these results suggest the potential of utilizing GPB as feed additives to improve growth performance in ruminants by reducing biogenic amines and increasing anti-oxidation. PMID:25049853

  11. Synthesis and quantitation of six phenolic amides in Amaranthus spp.

    PubMed

    Pedersen, Hans A; Steffensen, Stine K; Christophersen, Carsten; Mortensen, Anne G; Jørgensen, Lise N; Niveyro, Selene; de Troiani, Rosa M; Rodríguez-Enríquez, Ricardo José; Barba-de la Rosa, Ana Paulina; Fomsgaard, Inge S

    2010-05-26

    Cinnamoylphenethylamines are phenolic amides in which cinnamic acid provides the acid moiety and phenethylamine the amine moiety. Single ion monitoring (SIM) in LC-MS was performed on amaranth leaf extracts. Masses corresponding to sets of regioisomers, including previously reported compounds, were examined. Six peaks were detected and their corresponding standards synthesized for a quantitative LC-MS/MS investigation of cinnamoylphenethylamines in amaranth. Four cinnamoylphenethylamines (caffeoyltyramine, feruloyldopamine, sinapoyltyramine, and p-coumaroyltyramine) are reported in the Amaranthaceae for the first time; also, one rare compound, feruloyl-4-O-methyldopamine, appeared to be quite common in the genus Amaranthus. Feruloyldopamine showed moderate antifungal activity toward an isolate of Fusarium culmorum. Our LC-MS approach, in conjunction with the straightforward synthesis, provides a simple, reliable way of quantitatively investigating cinnamoylphenethylamines in plants. Concentrations of cinnamoylphenethylamines vary widely: feruloyltyramine was present in quantities of 5.26 to 114.31 microg/g and feruloyldopamine in quantities of 0.16 to 10.27 microg/g, depending on the plant sample. PMID:20438062

  12. Direct Reaction of Amides with Nitric Oxide To Form Diazeniumdiolates

    PubMed Central

    2015-01-01

    We report the apparently unprecedented direct reaction of nitric oxide (NO) with amides to generate ions of structure R(C=O)NH–N(O)=NO–, with examples including R = Me (1a) or 3-pyridyl (1b). The sodium salts of both released NO in pH 7.4 buffer, with 37 °C half-lives of 1–3 min. As NO-releasing drug candidates, diazeniumdiolated amides would have the advantage of generating only 1 equiv of base on hydrolyzing exhaustively to NO, in contrast to their amine counterparts, which generate 2 equiv of base. PMID:25210948

  13. Brønsted acid mediated N-O bond cleavage for α-amination of ketones through the aromatic nitroso aldol reaction.

    PubMed

    Ramakrishna, Isai; Sahoo, Harekrishna; Baidya, Mahiuddin

    2016-02-11

    A Brønsted acid mediated N-O bond cleavage for α-amination of ketones has been developed through the nitroso aldol reaction of less-reactive aromatic nitroso compounds and silyl enol ethers having a disilane (-SiMe2TMS) backbone. This transformation is operationally simple and scalable, offering structurally diverse α-amino ketones in high yields (up to 98%) with complete regioselectivity. It represents a mechanistically unique and rare example of a metal-free N-O bond cleavage process. PMID:26810365

  14. Incorporation of hydrogen atoms from deuterated water and stereospecifically deuterium-labeled nicotin amide nucleotides into fatty acids with the Escherichia coli fatty acid synthetase system.

    PubMed

    Saito, K; Kawaguchi, A; Okuda, S; Seyama, Y; Yamakawa, T

    1980-05-28

    The mechanism of hydrogen incorporation into fatty acids was investigated with intact Escherichia coli cells, a crude enzyme preparation and purified reductases of fatty acid synthetase system. The distributions of deuterium atoms incorporated into fatty acids from 2H2O and stereospecifically deuterium-labeled NADPH or NADH were determined by mass spectrometry. When E. coli was grown in 2H2O, almost every hydrogen atom of cellular fatty acids was incorporated from the medium. When fatty acids were synthesized from acetyl-CoA, malonyl-CoA and NADPH in the presence of a crude enzyme preparation of either E. coli or Bacillus subtilis, almost every hydrogen atom was also incorporated from the medium. In contrast to these results, purified beta-ketoacyl acyl carrier reductase directly transferred the HB hydrogen of NADPH to beta-ketoacyl acyl carrier protein, and purified enoyl acyl carrier protein reductase also transferred the HB hydrogen of NADPH and NADH directly to enoyl acyl carrier protein. In the crude enzyme preparation of E. coli, we found high activities which exchanged the HB hydrogen of NADPH with the deuterium of 2h2o. the conflicting results of the origin of hydrogen atoms of fatty acids mentioned above are explained by the presence of enzymes, which catalyzed the rapid exchange of NADPH with the deterium of 2H2O prior to the reaction of fatty acid synthetase. PMID:6990992

  15. X-ray crystallographic, FT-IR and NMR studies as well as anticancer and antibacterial activity of the salt formed between ionophore antibiotic Lasalocid acid and amines

    NASA Astrophysics Data System (ADS)

    Huczyński, Adam; Rutkowski, Jacek; Wietrzyk, Joanna; Stefańska, Joanna; Maj, Ewa; Ratajczak-Sitarz, Małgorzata; Katrusiak, Andrzej; Brzezinski, Bogumil; Bartl, Franz

    2013-01-01

    Two new complexes of the ionophore antibiotic Lasalocid acid (LAS) with phenylamine (PhA) and butylamine (BuA) were synthesized and their molecular structures were studied using single crystal X-ray diffraction and spectroscopic methods. In the solid state both amines are protonated and all NH3+ protons are hydrogen bonded to etheric, hydroxyl and carboxylic oxygen atoms of the LAS anion. In chloroform solutions the structure observed in the crystal of LAS-BuA complex is preserved and an equilibrium between the LAS-PhA complex and dissociated Lasalocid acid and phenylamine is observed. In vitro antimicrobial tests of the complexes showed a significant activity towards some strains of Gram-positive bacteria. For the first time Lasalocid acid and its complexes with amines were tested in vitro for cytotoxic activity against human cancer cell lines: A-549 (lung), MCF-7 (breast), HT-29 (colon) and mouse cancer cell line P-388 (leukemia). We found that LAS and its complexes are strong cytotoxic agents towards all tested cell lines. The cytostatic activity of the compounds studied is greater than that of cisplatin, indicating that Lasalocid and its complexes are promising candidates for new anticancer drugs.

  16. Excited state electron distribution and role of the terminal amine in acidic and basic tryptophan dipeptide fluorescence

    NASA Astrophysics Data System (ADS)

    Eisenberg, Azaria S.; Nathan, Moshe; Juszczak, Laura J.

    2016-08-01

    The results of quantum yield (QY) study of tryptophanyl glutamate (Trp-Glu), tryptophanyl lysine (Trp-Lys) and lysinyl tryptophan (Lys-Trp) dipeptides over the pH range, 1.5-13, show that the charge state of the N-terminal amine, and not the nominal molecular charge determines the QY. When the terminal amine is protonated, QY is low (10-2) for all three dipeptides. As the terminal amine cation is found proximal to the indole ring in Trp-Glu and Trp-Lys conformers but not in those for Lys-Trp, its effect may lie only in the partitioning of energy between nonradiative processes, not on QY reduction. QY is also low when both the N-terminal amine and indole amine are deprotonated. These two low QY states can be distinguished by fluorescence lifetime measurement. Molecular dynamics simulation shows that the Chi 1 conformers persist for tens of nanoseconds such that 100-101 ns lifetimes may be associated with individual Chi 1 conformers. The ground state electron density or isosurface of high QY (0.30) 3-methyindole has a uniform electron density over the indole ring as do the higher QY Trp dipeptide conformers. This validates the association of ground state isosurfaces with QY. Excited state orbitals from calculated high intensity, low energy absorption transitions are typically centered over the indole ring for higher QY dipeptide species and off the ring in lower QY species. Thus excited state orbitals substantiate the earlier finding that the ground state isosurface charge density pattern on the indole ring can be predictive of QY.

  17. Microwave-Assisted Syntheses of Amino Acid Ester Substituted Benzoic Acid Amides: Potential Inhibitors of Human CD81-Receptor HCV-E2 Interaction.

    PubMed

    Holzer, Marcel; Ziegler, Sigrid; Kronenberger, Bernd; Klein, Christian D; Hartmann, Rolf W

    2008-01-01

    Results from our group showed benzyl salicylate to be a moderate inhibitor of the CD81-LEL-HCV-E2 interaction. To increase the biological activity, heterocyclic substituted benzoic acids were coupled to amino acid esters via microwave assisted DCC-reaction. The prepared compounds were tested for their inhibitory potency by means of a fluorescence labeled antibody assay system using HUH7.5 cells. PMID:19662141

  18. Siro(haem)amide in Allochromatium vinosum and relevance of DsrL and DsrN, a homolog of cobyrinic acid a,c-diamide synthase, for sulphur oxidation.

    PubMed

    Lübbe, Yvonne J; Youn, Hyung-Sun; Timkovich, Russell; Dahl, Christiane

    2006-08-01

    In the purple sulphur bacterium Allochromatium vinosum, the prosthetic group of dissimilatory sulphite reductase (DsrAB) was identified as siroamide, an amidated form of the classical sirohaem. The genes dsrAB are the first two of a large cluster of genes necessary for the oxidation of sulphur globules stored intracellularly during growth on sulphide and thiosulphate. DsrN is homologous to cobyrinic acid a,c diamide synthase and may therefore catalyze glutamine-dependent amidation of sirohaem. Indeed, an A. vinosumDeltadsrN in frame deletion mutant showed a significantly reduced sulphur oxidation rate that was fully restored upon complementation with dsrN in trans. Sulphite reductase was still present in the DeltadsrN mutant. DsrL is a homolog of the small subunits of bacterial glutamate synthases and was proposed to deliver glutamine for sirohaem amidation. However, recombinant DsrL does not exhibit glutamate synthase activity nor does the gene complement a glutamate synthase-deficient Escherichia coli strain. Deletion of dsrL showed that the encoded protein is absolutely essential for sulphur oxidation in A. vinosum. PMID:16907720

  19. Enantioresolution of five β-blockers by reversed-phase high-performance liquid chromatography using fifteen chiral derivatizing reagents having amino acids or their amides as chiral auxiliaries on a cyanuric chloride platform.

    PubMed

    Bhushan, Ravi; Dixit, Shuchi

    2012-02-01

    Enantioseparation of five β-blockers, namely, (R,S)-atenolol, (R,S)-propranolol, (R,S)-bisoprolol, (R,S)-metoprolol and (R,S)-carvedilol, was achieved as their diastereomers prepared with chiral derivatizing reagents (CDRs) synthesized on a cyanuric chloride platform. Fifteen CDRs were synthesized by nucleophilic substitution of the Cl atom in cyanuric chloride or its 6-methoxy derivative with amino acids (namely, L-Leu, L-Val, D-Phg, L-Met and L-Ala) or their amides as chiral auxiliaries. The diastereomers were synthesized under microwave irradiation for 70 or 100 s at 85% power. Separation of diastereomers was carried out on a C(18) column and gradient eluting mixtures of methanol with aqueous trifluoroacetic acid with UV detection at 230 nm. Separation efficiencies of the reagents were compared on the basis of effect of chiral auxiliaries (i.e. amino acids or amino acid amides) and achiral substituents (i.e. chlorine or methoxy group) in the CDRs. The method was validated for detection limit, linearity, accuracy and precision. PMID:21678456

  20. Reaction of folic acid with single-walled carbon nanotubes

    NASA Astrophysics Data System (ADS)

    Ellison, Mark D.; Chorney, Matthew

    2016-10-01

    The oxygen-containing functional groups on oxidized single-walled carbon nanotubes (SWNTs) are used to covalently bond folic acid molecules to the SWNTs. Infrared spectroscopy confirms intact molecular binding to the SWNTs through the formation of an amide bond between a carboxylic acid group on an SWNT and the primary amine group of folic acid. The folic acid-functionalized SWNTs are readily dispersible in water and phosphate-buffered saline, and the dispersions are stable for a period of two weeks or longer. These folic acid-functionalized SWNTs offer potential for use as biocompatible SWNTs.

  1. ZSM-5-SO3H: An Efficient Catalyst for Acylation of Sulfonamides Amines, Alcohols, and Phenols under Solvent-Free Conditions

    PubMed Central

    Massah, Ahmad Reza; Kalbasi, Roozbeh Javad; Khalifesoltani, Mahdiehsadat; Moshtagh Kordesofla, Fariba

    2013-01-01

    Sulfonamides amines, alcohols, and phenols were efficiently acylated with carboxylic acid anhydrides and chlorides using ZSM-5-SO3H as catalyst under mild and solvent-free conditions. Also, direct esterification of alcohols with carboxylic acids occurred readily in the presence of this catalyst. Different types of amides and esters were obtained in moderate to high yields and purity after a simple workup. No chromatographic separation is needed for isolation of the acylated product. The catalyst was recovered and reused for up to four times without a noticeable decrease in catalytic activity. PMID:24381765

  2. Salt forms of the pharmaceutical amide dihydrocarbamazepine.

    PubMed

    Buist, Amanda R; Kennedy, Alan R

    2016-02-01

    Carbamazepine (CBZ) is well known as a model active pharmaceutical ingredient used in the study of polymorphism and the generation and comparison of cocrystal forms. The pharmaceutical amide dihydrocarbamazepine (DCBZ) is a less well known material and is largely of interest here as a structural congener of CBZ. Reaction of DCBZ with strong acids results in protonation of the amide functionality at the O atom and gives the salt forms dihydrocarbamazepine hydrochloride {systematic name: [(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)(hydroxy)methylidene]azanium chloride, C15H15N2O(+)·Cl(-)}, dihydrocarbamazepine hydrochloride monohydrate {systematic name: [(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)(hydroxy)methylidene]azanium chloride monohydrate, C15H15N2O(+)·Cl(-)·H2O} and dihydrocarbamazepine hydrobromide monohydrate {systematic name: [(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)(hydroxy)methylidene]azanium bromide monohydrate, C15H15N2O(+)·Br(-)·H2O}. The anhydrous hydrochloride has a structure with two crystallographically independent ion pairs (Z' = 2), wherein both cations adopt syn conformations, whilst the two hydrated species are mutually isostructural and have cations with anti conformations. Compared to neutral dihydrocarbamazepine structures, protonation of the amide group is shown to cause changes to both the molecular (C=O bond lengthening and C-N bond shortening) and the supramolecular structures. The amide-to-amide and dimeric hydrogen-bonding motifs seen for neutral polymorphs and cocrystalline species are replaced here by one-dimensional polymeric constructs with no direct amide-to-amide bonds. The structures are also compared with, and shown to be closely related to, those of the salt forms of the structurally similar pharmaceutical carbamazepine. PMID:26846502

  3. Conformation-Specific IR and UV Spectroscopy of the Amino Acid Glutamine: Amide-Stacking and Hydrogen Bonding in AN Important Residue in Neurodegenerative Diseases

    NASA Astrophysics Data System (ADS)

    Walsh, Patrick S.; Dean, Jacob C.; Zwier, Timothy S.

    2014-06-01

    Glutamine plays an important role in several neurodegenerative diseases including Huntington's disease (HD) and Alzheimer's disease (AD). An intriguing aspect of the structure of glutamine is its incorporation of an amide group in its side chain, thereby opening up the possibility of forming amide-amide H-bonds between the peptide backbone and side chain. In this study the conformational preferences of two capped gluatamines Z(carboxybenzyl)-Glutamine-X (X=OH, NHMe) are studied under jet-cooled conditions in the gas phase in order to unlock the intrinsic structural motifs that are favored by this flexible sidechain. Conformational assignments are made by comparing the hydride stretch ( 3100-3700 cm-1) and amide I and II ( 1400-1800 cm-1) resonant ion-dip infrared spectra with predictions from harmonic frequency calculations. Assigned structures will be compared to previously published results on both natural and unnatural residues. Particular emphasis will be placed on the comparison between glutamine and unconstrained γ-peptides due to the similar three-carbon spacing between backbone and side chain in glutamine to the backbone spacing in γ-peptides. The ability of the glutamine side-chain to form amide stacked conformations will be a main focus, along with the prevalence of extended backbone type structures. W. H. James, III, C W. Müller, E. G. Buchanan, M. G. D. Nix, L. Guo, L. Roskop, M. S. Gordon, L. V. Slipchenko, S. H. Gellman, and T. S. Zwier, J. Am. Chem. Soc., 2009, 131(40), 14243-14245.

  4. The blockade of the transient receptor potential vanilloid type 1 and fatty acid amide hydrolase decreases symptoms and central sequelae in the medial prefrontal cortex of neuropathic rats

    PubMed Central

    2011-01-01

    Background Neuropathic pain is a chronic disease resulting from dysfunction within the "pain matrix". The basolateral amygdala (BLA) can modulate cortical functions and interactions between this structure and the medial prefrontal cortex (mPFC) are important for integrating emotionally salient information. In this study, we have investigated the involvement of the transient receptor potential vanilloid type 1 (TRPV1) and the catabolic enzyme fatty acid amide hydrolase (FAAH) in the morphofunctional changes occurring in the pre-limbic/infra-limbic (PL/IL) cortex in neuropathic rats. Results The effect of N-arachidonoyl-serotonin (AA-5-HT), a hybrid FAAH inhibitor and TPRV1 channel antagonist, was tested on nociceptive behaviour associated with neuropathic pain as well as on some phenotypic changes occurring on PL/IL cortex pyramidal neurons. Those neurons were identified as belonging to the BLA-mPFC pathway by electrical stimulation of the BLA followed by hind-paw pressoceptive stimulus application. Changes in their spontaneous and evoked activity were studied in sham or spared nerve injury (SNI) rats before or after repeated treatment with AA-5-HT. Consistently with the SNI-induced changes in PL/IL cortex neurons which underwent profound phenotypic reorganization, suggesting a profound imbalance between excitatory and inhibitory responses in the mPFC neurons, we found an increase in extracellular glutamate levels, as well as the up-regulation of FAAH and TRPV1 in the PL/IL cortex of SNI rats. Daily treatment with AA-5-HT restored cortical neuronal activity, normalizing the electrophysiological changes associated with the peripheral injury of the sciatic nerve. Finally, a single acute intra-PL/IL cortex microinjection of AA-5-HT transiently decreased allodynia more effectively than URB597 or I-RTX, a selective FAAH inhibitor or a TRPV1 blocker, respectively. Conclusion These data suggest a possible involvement of endovanilloids in the cortical plastic changes

  5. Rapid Access to 3-Aminoindazoles from Tertiary Amides.

    PubMed

    Cyr, Patrick; Régnier, Sophie; Bechara, William S; Charette, André B

    2015-07-17

    A two-step synthesis of structurally diverse 3-aminoindazoles from readily available starting materials was developed. This sequence includes a one-pot synthesis of aminohydrazones through chemoselective Tf2O-mediated activation of tertiary amides and subsequent addition of nucleophilic hydrazides. These precursors then participate in an intramolecular ligand-free Pd-catalyzed C-H amination reaction. The azaheterocycles synthesized via this approach were further diversified through subsequent deprotection/functionalization reactions. PMID:26154712

  6. Mild and selective Et2Zn-catalyzed reduction of tertiary amides under hydrosilylation conditions.

    PubMed

    Kovalenko, Oleksandr O; Volkov, Alexey; Adolfsson, Hans

    2015-02-01

    Diethylzinc (Et2Zn) can be used as an efficient and chemoselective catalyst for the reduction of tertiary amides under mild reaction conditions employing cost-effective polymeric silane (PMHS) as the hydride source. Crucial for the catalytic activity was the addition of a substoichiometric amount of lithium chloride to the reaction mixture. A series of amides containing different additional functional groups were reduced to their corresponding amines, and the products were isolated in good-to-excellent yields. PMID:25587664

  7. Catalytic Ester–Amide Exchange Using Group (IV) Metal Alkoxide–Activator Complexes

    PubMed Central

    Han, Chong; Lee, Jonathan P.; Lobkovsky, Emil; Porco, John A.

    2005-01-01

    A process for preparation of amides from unactivated esters and amines has been developed using a catalytic system comprised of group (IV) metal alkoxides in conjunction with additives including 1-hydroxy-7-azabenzotriazole (HOAt). In general, ester–amide exchange proceeds using a variety of structurally diverse esters and amines without azeotropic reflux to remove the alcohol byproduct. Initial mechanistic studies on the Zr(Ot-Bu)4–HOAt system revealed that the active catalyst is a novel, dimeric zirconium complex as determined by X-ray crystallography. PMID:16011366

  8. A New Derivative of Valproic Acid Amide Possesses a Broad-spectrum Antiseizure Profile and Unique Activity Against Status Epilepticus and Organophosphate Neuronal Damage

    PubMed Central

    White, H. Steve; Alex, Anitha B.; Pollock, Amanda; Hen, Naama; Shekh-Ahmad, Tawfeeq; Wilcox, Karen S.; McDonough, John H.; Stables, James P.; Kaufmann, Dan; Yagen, Boris; Bialer, Meir

    2011-01-01

    Summary Purpose sec-Butyl-propylacetamide (SPD) is a one-carbon homologue of valnoctamide (VCD), a CNS-active amide derivative of valproic acid (VPA) currently in phase II clinical trials. The current study evaluated the anticonvulsant activity of SPD in a battery of rodent seizure and epilepsy models and assessed its efficacy in rat and guinea pig models of status epilepticus (SE) and neuroprotection in an organotypic hippocampal slice model of excitotoxic cell death. Methods SPD’s anticonvulsant activity was evaluated in several rodent seizure and epilepsy models including: maximal electroshock (MES), 6Hz psychomotor, subcutaneous (s.c.) metrazol-, s.c., picrotoxin, s.c. bicuculline, audiogenic and corneal and hippocampal kindled seizures following intraperitoneal administration. Results obtained with SPD are discussed in relationship to those obtained with VPA and VCD. SPD was also evaluated for its ability to block benzodiazepine-resistant SE induced by pilocarpine (rats) and soman (rats and guinea pigs) following intraperitoneal administration. SPD was tested for its ability to block excitotoxic cell death induced by the glutamate agonists N-methyl-D-Aspartate (NMDA) and kainic acid (KA) using organotypic hippocampal slices and SE-induced hippocampal cell death using FluoroJade B staining. The cognitive function of SPD-treated rats that were protected against pilocarpine-induced convulsive SE was examined 10-14 days post SE using the Morris water maze (MWM). The relationship between the pharmacokinetic profile of SPD and its efficacy against soman-induced SE was evaluated in two parallel studies following SPD (60 mg/kg, i.p.) administration in the soman SE rat model. Key Findings SPD was highly effective and displayed a wide protective index (PI=TD50/ED50) in the standardized seizure and epilepsy models employed. SPD’s wide PI values demonstrate that it is effective at doses well below those that produce behavioral impairment. Unlike VCD, SPD also

  9. The Apoplastic Copper AMINE OXIDASE1 Mediates Jasmonic Acid-Induced Protoxylem Differentiation in Arabidopsis Roots1

    PubMed Central

    Ghuge, Sandip A.; Carucci, Andrea; Rodrigues-Pousada, Renato A.; Tisi, Alessandra; Franchi, Stefano; Tavladoraki, Paraskevi; Cona, Alessandra

    2015-01-01

    Polyamines are involved in key developmental processes and stress responses. Copper amine oxidases oxidize the polyamine putrescine (Put), producing an aldehyde, ammonia, and hydrogen peroxide (H2O2). The Arabidopsis (Arabidopsis thaliana) amine oxidase gene At4g14940 (AtAO1) encodes an apoplastic copper amine oxidase expressed at the early stages of vascular tissue differentiation in roots. Here, its role in root development and xylem differentiation was explored by pharmacological and forward/reverse genetic approaches. Analysis of the AtAO1 expression pattern in roots by a promoter::green fluorescent protein-β-glucuronidase fusion revealed strong gene expression in the protoxylem at the transition, elongation, and maturation zones. Methyl jasmonate (MeJA) induced AtAO1 gene expression in vascular tissues, especially at the transition and elongation zones. Early protoxylem differentiation was observed upon MeJA treatment along with Put level decrease and H2O2 accumulation in wild-type roots, whereas Atao1 loss-of-function mutants were unresponsive to the hormone. The H2O2 scavenger N,N1-dimethylthiourea reversed the MeJA-induced early protoxylem differentiation in wild-type seedlings. Likewise, Put, which had no effect on Atao1 mutants, induced early protoxylem differentiation in the wild type, this event being counteracted by N,N1-dimethylthiourea treatment. Consistently, AtAO1-overexpressing plants showed lower Put levels and early protoxylem differentiation concurrent with H2O2 accumulation in the root zone where the first protoxylem cells with fully developed secondary wall thickenings are found. These results show that the H2O2 produced via AtAO1-driven Put oxidation plays a role in MeJA signaling leading to early protoxylem differentiation in root. PMID:25883242

  10. Conjugation of insulin onto the sidewalls of single-walled carbon nanotubes through functionalization and diimide-activated amidation

    PubMed Central

    Ng, Chee Meng; Loh, Hwei-San; Muthoosamy, Kasturi; Sridewi, Nanthini; Manickam, Sivakumar

    2016-01-01

    Purpose The high aspect ratio of carbon nanotubes (CNTs) allows the attachment of compounds that enhance the functionality of the drug vehicle. Considering this, use of CNTs as a multifunctional insulin carrier may be an interesting prospect to explore. Materials and methods The carboxylic acid groups were functionalized on the sidewalls of single-walled CNTs (SWCNTs) followed by diimidation to form amide bonds with the amine groups of the insulin. Results Scanning transmission electron microscopy and transmission electron microscopy establish clear conjugation of insulin onto the surface of nanotube sidewalls. The incorporation of insulin further increased the solubility of SWCNTs in biological solution for the tested period of 5 months. Bicinchoninic acid assay confirms that 0.42 mg of insulin could be attached to every 1 mg of carboxylated SWCNTs. Conclusion With the successful conjugation of insulin to SWCNTs, it opens up the potential use of SWCNTs as an insulin carrier which in need of further biological studies. PMID:27143882

  11. Total synthesis of palau'amine

    PubMed Central

    Namba, Kosuke; Takeuchi, Kohei; Kaihara, Yukari; Oda, Masataka; Nakayama, Akira; Nakayama, Atsushi; Yoshida, Masahiro; Tanino, Keiji

    2015-01-01

    Palau'amine has received a great deal of attention in the past two decades as an attractive synthetic target by virtue of its intriguing molecular architecture and significant immunosuppressive activity. Here we report the total synthesis of palau'amine characterized by the construction of an ABDE tetracyclic ring core including a trans-bicylo[3.3.0]octane skeleton at a middle stage of total synthesis. The ABDE tetracyclic ring core is constructed by a cascade reaction of a cleavage of the N–N bond, including simultaneous formation of imine, the addition of amide anion to the resulting imine (D-ring formation) and the condensation of pyrrole with methyl ester (B-ring formation) in a single step. The synthetic palau'amine is confirmed to exhibit excellent immunosuppressive activity. The present synthetic route has the potential to help elucidate a pharmacophore as well as the mechanistic details of immunosuppressive activity. PMID:26530707

  12. Impact of primary amine group from aminophospholipids and amino acids on marine phospholipids stability: non-enzymatic browning and lipid oxidation.

    PubMed

    Lu, F S H; Nielsen, N S; Baron, C P; Diehl, B W K; Jacobsen, C

    2013-11-15

    The main objective of this study was to investigate the oxidative stability and non-enzymatic browning reactions of marine PL in the presence or in the absence of primary amine group from aminophospholipids and amino acids. Marine phospholipids liposomal dispersions were prepared from two authentic standards (phosphatidylcholine and phosphatidylethanolamine) and two purified PL from marine sources with and without addition of amino acids (leucine, methionine and lysine). Samples were incubated at 60°C for 0, 2, 4 and 6days. Non-enzymatic browning reactions were investigated through measurement of (i) Strecker derived volatiles, (ii) yellowness index (YI), (iii) hydrophobic and (iv) hydrophilic pyrroles content. The oxidative stability of the samples was assessed through measurement of secondary lipid derived volatile oxidation products. The result showed that the presence of PE and amino acids caused the formation of pyrroles, generated Strecker derived volatiles, decreased the YI development and lowered lipid oxidation. The lower degree of lipid oxidation in liposomal dispersions containing amino acids might be attributed to antioxidative properties of pyrroles or amino acids. PMID:23790862

  13. Stereoselective Arene-Forming Aldol Condensation: Synthesis of Axially Chiral Aromatic Amides.

    PubMed

    Fäseke, Vincent C; Sparr, Christof

    2016-06-13

    The increasing awareness of the importance of amide atropisomers prompts the development of novel strategies for their selective preparation. Described herein is a method for the enantioselective synthesis of atropisomeric aromatic amides by an amine-catalyzed arene-forming aldol condensation. The high reactivity of the glyoxylic amide substrates enables a remarkably efficient construction of a new aromatic ring, which proceeds within minutes at ambient temperature to afford products with excellent stereoselectivity. The high rotational barriers of the reduced products highlight the utility of this stable, spatially organized chiral scaffold. PMID:27166995

  14. Application of amino acid amides as chiral auxiliaries in difluoro dinitro benzene and cyanuric chloride moieties for high-performance liquid-chromatographic enantioseparation of selenomethionine and its mixture with methionine and cysteine.

    PubMed

    Bhushan, Ravi; Dubey, Rituraj

    2012-04-01

    L-Ala-NH(2), L-Val-NH(2), L-Leu-NH(2), and D-Phg-NH(2) were used as chiral auxiliaries to synthesize four chiral derivatizing reagents (CDRs) of each of the three categories, viz., difluoro dinitro benzene (DFDNB) based chiral variants, and cyanuric chloride (CC) based monochloro-s-triazine reagents (MCTs) and dichloro-s-triazine reagents (DCTs). DFDNB based chiral variants were synthesized by substituting one of the fluorine atoms of DFDNB with respective amino acid amides. The MCTs and DCTs were synthesized by substituting chlorine atom with aforesaid amino acid amide moieties in 6-methoxy dichloro-s-triazine and in CC, respectively. In total, 12 CDRs were characterized and used for microwave-assisted synthesis (45 s at 80% of 800 W using DFDNB-based chiral variants, 80 s at 90% of 800 W power using MCTs, and 50 s at 80% of 800 W power using DCTs) of diastereomers of (A) SeMet, and (B) mixture of (1) SeMet and Met, and (2) SeMet, Met, and Cys. The diastereomers were enantioseparated by reversed-phase high-performance liquid chromatography using gradient elution with mobile phases containing aq. TFA (0.1%)--MeCN in different compositions. The method was validated for accuracy, precision, and limit of detection. PMID:21293889

  15. Characteristic conformation of Mosher's amide elucidated using the cambridge structural database.

    PubMed

    Ichikawa, Akio; Ono, Hiroshi; Mikata, Yuji

    2015-01-01

    Conformations of the crystalline 3,3,3-trifluoro-2-methoxy-2-phenylpropanamide derivatives (MTPA amides) deposited in the Cambridge Structural Database (CSD) were examined statistically as Racid-enantiomers. The majority of dihedral angles (48/58, ca. 83%) of the amide carbonyl groups and the trifluoromethyl groups ranged from -30° to 0° with an average angle θ1 of -13°. The other conformational properties were also clarified: (1) one of the fluorine atoms was antiperiplanar (ap) to the amide carbonyl group, forming a staggered conformation; (2) the MTPA amides prepared from primary amines showed a Z form in amide moieties; (3) in the case of the MTPA amide prepared from a primary amine possessing secondary alkyl groups (i.e., Mosher-type MTPA amide), the dihedral angles between the methine groups and the carbonyl groups were syn and indicative of a moderate conformational flexibility; (4) the phenyl plane was inclined from the O-Cchiral bond of the methoxy moiety with an average dihedral angle θ2 of +21°; (5) the methyl group of the methoxy moiety was ap to the ipso-carbon atom of the phenyl group. PMID:26193245

  16. Precolumn derivatization reagents for high-speed analysis of amines and amino acids in biological fluid using liquid chromatography/electrospray ionization tandem mass spectrometry.

    PubMed

    Shimbo, Kazutaka; Oonuki, Takashi; Yahashi, Akihisa; Hirayama, Kazuo; Miyano, Hiroshi

    2009-05-01

    A rapid analytical method for amines and amino acids was developed, involving derivatization with the novel reagent 3-aminopyridyl-N-hydroxysuccinimidyl carbamate (APDS), followed by reversed-phase high-performance liquid chromatography and electrospray ionization tandem mass spectrometry (HPLC/ESI-MS/MS). More than 100 different analytes with amino groups, including amino acids in biological fluids such as mammalian plasma, could be measured within 10 min. The analytes were easily derivatized with APDS under the mild conditions. Selective reaction monitoring of ESI-MS/MS in positive mode was carried out to include the transitions of all of the protonated molecular ions of analytes derivatized with APDS to the common fragment at m/z 121, which was derived from the amino pyridyl moiety of the reagent. We evaluated the retention time precision, the quantification limits, the linearity, the intra- and inter-day precisions and the accuracy of 22 typical amino acids found in biological fluids, by analyzing a standard amino acid mixture and rat plasma. The intra-day relative standard deviations (RSDs) of the retention times of the 22 amino acids and their internal standards were within 0.9% and the inter-day RSDs were less than 1.1%, except for asparagines, with an RSD of 1.9%. The intra-day and inter-day RSDs of amino acid analyses in rat plasma were within 8.0% and 4.5%, respectively. The method, which facilitates the amino acid analysis of more than 100 samples in a day, represents an alternative to traditional amino acid analysis techniques, such as chromatography using postcolumn derivatization by ninhydrin. PMID:19350529

  17. Amide bond cleavage initiated by coordination with transition metal ions and tuned by an auxiliary ligand.

    PubMed

    Yang, Yongpo; Lu, Chunxin; Wang, Hailong; Liu, Xiaoming

    2016-06-21

    The reaction of ligand , N,N-bis(pyridin-2-ylmethyl)acetamide, with five transition metal salts, FeCl3·6H2O, CuCl2·2H2O, Cu(ClO4)2·6H2O, ZnCl2 and K2PtCl4/KI, produced five metal complexes, [(μ-O)(FeClL')(FeCl3)] (), [CuLCl2] (), [CuBPA(ClO4)(CHCN)] ClO4 (), [ZnLCl2] () and [PtLI2] (), where = 1-(2,4,5-tri(pyridin-2-yl)-3-(pyridin-2-ylmethyl)imidazolidin-1-yl)ethanone which formed in situ, and BPA = bis(pyridin-2-ylmethyl)amine. The ligand and complexes were characterized by a variety of spectroscopic techniques including X-ray single crystal diffraction where applicable. Depending on the metal ion and auxiliary ligand of the complex, the acetyl group of the ligand could be either intact or cleaved. When ferric chloride hexahydrate was used, the deacetylation proceeded even further and a novel heterocyclic compound () was formed in situ. A possible mechanism was proposed for the formation of the heterocyclic compound found in complex . Our results indicate that to cleave effectively an amide bond, it is essential for a metal centre to bind to the amide bond and the metal centre is of sufficient Lewis acidity. PMID:27241864

  18. Cyclodextrin-modified MEKC method for quantification of selected acidic metabolites of catecholamines in the presence of various biogenic amines. Application to diagnosis of neuroblastoma.

    PubMed

    Miękus, Natalia; Kowalski, Piotr; Olędzka, Ilona; Plenis, Alina; Bień, Ewa; Miękus, Aleksandra; Krawczyk, Małgorzata; Adamkiewicz-Drożyńska, Elżbieta; Bączek, Tomasz

    2015-10-15

    The main aim of the presented study was to develop a reliable and non-time-consuming method for the simultaneous separation of biogenic amines (BAs) like noradrenalin, adrenalin, dopamine and their main metabolites - homovanillic acid (HVA), vanillylmandelic acid (VMA), 3,4-dihydroxyphenylacetic acid (DOPAC) - in urine samples. To achieve this, the validated α-cyclodextrin (α-CD)-modified micellar electrokinetic chromatography method with DAD was proposed. The optimized separation parameters were as follows: background electrolyte was composed of 10mM sodium tetraborate decahydrate, 30mM SDS, 15% (v/v) methanol and 25mM α-CD, adjusted to pH 9.36 with 1N NaOH; uncoated fused silica capillary (75μm i.d.×60.2cm length); λ=200nm; injection time 5s, applied voltage 25kV; temperature 25 (±0.1)°C. Next, the developed MEKC method was practically applied to evaluate the levels of selected acidic metabolites of catecholamines like HVA, VMA and DOPAC in urine samples collected from patients diagnosed with neuroblastoma (NB), melanotic neuroectodermal tumor of infancy (MNTI). PMID:26402573

  19. Combined use of starter cultures and preservatives to control production of biogenic amines and improve sensorial profile in low-acid salami.

    PubMed

    Coloretti, Fabio; Chiavari, Cristiana; Armaforte, Emanuele; Carri, Simone; Castagnetti, Gian Battista

    2008-12-10

    The combined effect of starter culture, nitrites, and nitrates has been studied in low-acidity salamis, typical products of northern Italy. Nine batches have been prepared, combining three different inoculations of starter cultures (control, Lactobacillus plantarum , and Lactobacillus plantarum together with Kocuria varians ) with three different preservatives (control, sodium nitrate, and sodium nitrite). All of the batches showed a good fermentation process with a proper pH decrease, which was quicker in batches inoculated with L. plantarum. The use of starter cultures and in particular the use of nitrites allowed the control of the proliferation of Enterobacteriaceae and enterococci. The accumulation of biogenic amines, especially putrescine, cadaverine, tryptamine, and tyramine, in salami ready for consumption (60 days of ripening) was strongly affected by the presence of Enterobacteriaceae and enterococci. Results obtained showed that the combined use of adequate preservatives and starter cultures allows the production of safer products with improved sensorial profile. PMID:18986149

  20. Biogenic amines in seafood: a review.

    PubMed

    Biji, K B; Ravishankar, C N; Venkateswarlu, R; Mohan, C O; Gopal, T K Srinivasa

    2016-05-01

    The biogenic amines are low molecular weight organic bases present normally in the body with biological activity influencing important physiological functions. The physiological functions of these molecules are achieved by very low concentrations in the tissues. However, significantly high amounts of biogenic amines are produced during processing and storage of seafood as a result of microbial contamination and inadequate storage conditions. Microorganisms having decarboxylase enzyme activity convert amino acids to their respective biogenic amines. Biogenic amines in seafood have been implicated as a major causative agent of food borne illness, where intoxication results from the ingestion of foods containing higher amount of biogenic amines. Hence its identification, quantitation and awareness of this food borne toxin are important in relation to food safety and spoilage. The aim of this paper is to review the basic concepts of seafood quality and safety in relation to biogenic amines along with its control measures and future areas for research. PMID:27407186

  1. Nine of 16 stereoisomeric polyhydroxylated proline amides are potent β-N-acetylhexosaminidase inhibitors.

    PubMed

    Ayers, Benjamin J; Glawar, Andreas F G; Martínez, R Fernando; Ngo, Nigel; Liu, Zilei; Fleet, George W J; Butters, Terry D; Nash, Robert J; Yu, Chu-Yi; Wormald, Mark R; Nakagawa, Shinpei; Adachi, Isao; Kato, Atsushi; Jenkinson, Sarah F

    2014-04-18

    All 16 stereoisomeric N-methyl 5-(hydroxymethyl)-3,4-dihydroxyproline amides have been synthesized from lactones accessible from the enantiomers of glucuronolactone. Nine stereoisomers, including all eight with a (3R)-hydroxyl configuration, are low to submicromolar inhibitors of β-N-acetylhexosaminidases. A structural correlation between the proline amides is found with the ADMDP-acetamide analogues bearing an acetamidomethylpyrrolidine motif. The proline amides are generally more potent than their ADMDP-acetamide equivalents. β-N-Acetylhexosaminidase inhibition by an azetidine ADMDP-acetamide analogue is compared to an azetidine carboxylic acid amide. None of the amides are good α-N-acetylgalactosaminidase inhibitors. PMID:24641544

  2. Symmetrical and unsymmetrical α,ω-nucleobase amide-conjugated systems

    PubMed Central

    Boncel, Sławomir; Mączka, Maciej; Koziol, Krzysztof K K; Motyka, Radosław

    2010-01-01

    Summary We present the synthesis and selected physicochemical properties of several novel symmetrical and unsymmetrical α,ω-nucleobase mono- and bis-amide conjugated systems containing aliphatic, aromatic or saccharidic linkages. The final stage of the synthesis involves condensation of a subunit bearing carboxylic group with an amine subunit. 4-(4,6-Dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride (DMT-MM) was found to be a particularly effective condensing agent. The subunits containing carboxylic groups were obtained by acidic hydrolysis of N-1 Michael adducts of uracils or N-9 Michael adducts of 6-chloropurine with methyl acrylate. The amines used were aliphatic/aromatic diamines, adenine, 5-substituted 1-(ω-aminoalkyl)uracils and 5′-amino-2′,5′-dideoxythymidine. The title compounds may find application as antiprotozoal agents. Moreover, preliminary microscopy TEM studies of supramolecular behaviour showed that target molecules with bolaamphiphilic structures were capable of forming highly ordered assemblies, mainly nanofibres. PMID:20502605

  3. Influence of amine-grafted multi-walled carbon nanotubes on physical and rheological properties of PMMA-based nanocomposites

    SciTech Connect

    Kim, Ki-Seok; Park, Soo-Jin

    2011-11-15

    In this work, poly(methyl methacrylate) (PMMA) was grafted onto amine treated multi-walled carbon nanotubes (NH-MWNTs) and the physical and rheological properties of the NH-MWNTs-g-PMMA nanocomposites were investigated. The graft reaction of NH-MWNTs and the PMMA matrix was confirmed from the change of the N{sub 1S} peaks, including those of amine oxygen and amide oxygen, by X-ray photoelectron spectroscopy (XPS). The thermal and mechanical properties of the NH-MWNT-g-PMMA nanocomposites were enhanced by the graft reaction between NH-MWNTs and PMMA matrix. In addition, the viscosity of the nanocomposites was increased with the addition of NH-MWNTs. Storage (G') and loss modulus (G'') were significantly increased by increase in the NH-MWNT content compared to acid-treated MWNTs/PMMA nanocomposites. This increase was attributed to the strong interaction by the grafting reaction between NH-MWNTs and the PMMA matrix. - Graphical abstract: This describes the increase of mechanical properties in NH-MWNTs-g-PMMA hybrid composites with different NH-MWNT contents. Highlights: > Aminized carbon nanotubes are used as reinforcement for poly(methylmethacrylate). > Poly(methylmethacrylate) is grafted on aminized carbon nanotubes by thermal reaction. > Grafting of carbon nanotubes and polymer provide enhanced physical properties. > It was due to the strong interaction between carbon nanotubes and polymer matrix.

  4. Phenylboronic Acid Solid Phase Extraction Cleanup and Isotope Dilution Liquid Chromatography-Tandem Mass Spectrometry for the Determination of Florfenicol Amine in Fish Muscles.

    PubMed

    Sin, Della Wai-Mei; Ho, Clare; Wong, Yiu-Tung

    2015-01-01

    Florfenicol (FFC) residues in foods are regulated as the sum of florfenicol and its metabolites measured as florfenicol amine (FFA). An isotope dilution LC-MS/MS method utilizing phenylboronic acid (PBA) SPE cleanup is established for the accurate determination of FFA in fish muscles (i.e., salmon and tilapia) after acid catalyzed hydrolysis. Comparisons of the PBA SPE cleanup procedure with other cleanup procedures such as mixed-mode cationic (MCX) SPE and solid supported liquid-liquid extraction were performed. Quantification of FFA in fish muscles was accomplished by using matrix-matched calibration with FFA-D3 as the internal standard. The method was validated with FFA fortified fish muscles at three different levels (50, 100, and 200 μg/kg). Conversion of FFC to FFA by acid catalyzed hydrolysis was evaluated and found to be ≥88%. The recoveries of FFA in fish muscles at the three fortification levels ranged from 89 to 106%, and RSDs were ≤9% in all cases. The LOD values in salmon and tilapia muscles were 0.13 and 1.64 μg/kg, respectively. The LOQ values in salmon and tilapia muscles were 0.29 and 4.13 μg/kg, respectively. This method is suitable for the application in routine control of FFC in fishes according to its residue definition. PMID:26025252

  5. Synthesis and pharmacological properties of N,N-dialkyl(dialkenyl)amides of 7-methyl-3-phenyl-1-[2-hydroxy-3-(4-phenyl-1-piperazinyl)propyl]-2,4-dioxo-1,2,3,4-tetrahydropyrido[2,3-d]pyrimidine-5-carboxylic acid.

    PubMed

    Sladowska, Helena; Sabiniarz, Aleksandra; Filipek, Barbara; Kardasz, Małgorzata; Maciag, Dorota

    2003-01-01

    Synthesis of N,N-dialkyl(dialkenyl)amides of 7-methyl-3-phenyl-2,4-dioxo-1,2,3,4-tetrahydropyrido[2,3-d]pyrimidine-5-carboxylic acid (5-9) and their 1-[2-hydroxy-3-(4-phenyl-1-piperazinyl)propyl] derivatives (10-14) is described. Compounds 10-14 were tested for analgesic and sedative activities as well as for mu-opioid receptors binding affinities. All the amides, being the object of investigation, displayed an interesting analgesic action, which in case of the compounds 10-12 and 14 was superior to that of acetylsalicylic acid in two different tests. Furthermore all the amides (10-14) significantly suppressed the spontaneous locomotor activity, prolonged barbiturate sleep in mice and showed a weak affinity to mu-opioid receptors. PMID:12595034

  6. S(N)2' reaction of allylic difluorides with lithium amides and thiolates.

    PubMed

    Bergeron, Maxime; Guyader, David; Paquin, Jean-François

    2012-12-01

    The synthesis of monofluoroalkenes using an S(N)2' reaction of lithium amides derived from aromatic amines or lithium thiolates with 3,3-difluoropropenes is reported. This transformation features the use of fluoride as a leaving group. PMID:23145465

  7. Substitution of glutamine for lysine at the pyridoxal phosphate binding site of bacterial D-amino acid transaminase. Effects of exogenous amines on the slow formation of intermediates.

    PubMed

    Futaki, S; Ueno, H; Martinez del Pozo, A; Pospischil, M A; Manning, J M; Ringe, D; Stoddard, B; Tanizawa, K; Yoshimura, T; Soda, K

    1990-12-25

    In bacterial D-amino acid transaminase, Lys-145, which binds the coenzyme pyridoxal 5'-phosphate in Schiff base linkage, was changed to Gln-145 by site-directed mutagenesis (K145Q). The mutant enzyme had 0.015% the activity of the wild-type enzyme and was capable of forming a Schiff base with D-alanine; this external aldimine was formed over a period of minutes depending upon the D-alanine concentration. The transformation of the pyridoxal-5'-phosphate form of the enzyme to the pyridoxamine-5'-phosphate form (i.e. the half-reaction of transamination) occurred over a period of hours with this mutant enzyme. Thus, information on these two steps in the reaction and on the factors that influence them can readily be obtained with this mutant enzyme. In contrast, these reactions with the wild-type enzyme occur at much faster rates and are not easily studied separately. The mutant enzyme shows distinct preference for D- over L-alanine as substrates but it does so about 50-fold less effectively than the wild-type enzyme. Thus, Lys-145 probably acts in concert with the coenzyme and other functional side chain(s) to lead to efficient and stereochemically precise transamination in the wild-type enzyme. The addition of exogenous amines, ethanolamine or methyl amine, increased the rate of external aldimine formation with D-alanine and the mutant enzyme but the subsequent transformation to the pyridoxamine-5'-phosphate form of the enzyme was unaffected by exogenous amines. The wild-type enzyme displayed a large negative trough in the circular dichroic spectrum at 420 nm, which was practically absent in the mutant enzyme. However, addition of D-alanine to the mutant enzyme generated this negative Cotton effect (due to formation of the external aldimine with D-alanine). This circular dichroism band gradually collapsed in parallel with the transformation to the pyridoxamine-5'-phosphate enzyme. Further studies on this mutant enzyme, which displays the characteristics of the wild

  8. Synthesis of a novel biologically active amide ester of 7,10-dihydroxy-8(E)-octadecanoic acid (DOD) using lipase

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Hydroxy fatty acids (HFA) are known to have industrial potential because of their special properties such as high viscosity and reactivity. Among the hydroxy fatty acids, 7,10-dihydroxy-8(E)-octadecenoic acid (DOD) was successfully produced from oleic acid and lipid containing oleic acid by a bacter...

  9. Simultaneous efficient adsorption of Pb2+ and MnO4- ions by MCM-41 functionalized with amine and nitrilotriacetic acid anhydride

    NASA Astrophysics Data System (ADS)

    Chen, Feiyun; Hong, Mingzhu; You, Weijie; Li, Chong; Yu, Yan

    2015-12-01

    A novel adsorbent NH2/MCM-41/NTAA, capable of simultaneous adsorption of cations and anions from aqueous solution, was prepared by immobilization of amine and nitrilotriacetic acid anhydride (NTAA) onto MCM-41. The structures and properties before and after surface modification were systematically investigated through X-ray diffraction (XRD), transmission electron microscope (TEM) and scanning electron microscope (SEM), nitrogen adsorption-desorption, and infrared spectroscopy (FTIR), thermogravimetry (TGA) and X-ray photoelectron spectroscopy (XPS). They together confirm that the amine and NTAA group were chemically bonded to the internal surface of the mesoporous. The NH2/MCM-41/NTAA were used to adsorb Pb2+ and MnO4- in an aqueous solution in a batch system, and the maximum adsorption efficiency was found to occur at pH 5.0 and 3.0, respectively. NH2/MCM-41/NTAA exhibit preferable removal of Pb2+ through electrostatic interactions and chelation, whereas it captures MnO4- by means of electrostatic interactions. The experimental data are fitted the Langmuir isotherm model reasonably well, with the maximum adsorption capacity of 147 mg/g for Pb2+ and of 156 mg/g for MnO4-. The adsorption rates of both Pb2+ and MnO4- are found to follow the pseudo-second order kinetics. Furthermore, the NH2/MCM-41/NTAA adsorbent performs good recyclability and reusability for 5 cycles use. This study indicates a potential applicability of NH2/MCM-41/NTAA as new absorbents for effective simultaneous adsorption of hazardous metal ions and anions from wastewater.

  10. Amine-Amine Exchange in Aminium-Methanesulfonate Aerosols

    SciTech Connect

    Dawson, Matthew L.; Varner, Mychel E.; Perraud, Veronique M.; Ezell, Michael J.; Wilson, Jacqueline M.; Zelenyuk, Alla; Gerber, Robert B.; Finlayson-Pitts, Barbara J.

    2014-12-18

    Aerosol particles are ubiquitous in the atmosphere and have been shown to impact the Earth’s climate, reduce visibility, and adversely affect human health. Modeling the evolution of aerosol systems requires an understanding of the species and mechanisms involved in particle growth, including the complex interactions between particle- and gas-phase species. Here we report studies of displacement of amines (methylamine, dimethylamine or trimethylamine) in methanesulfonate salt particles by exposure to a different gas-phase amine, using a single particle mass spectrometer, SPLAT II. The variation of the displacement with the nature of the amine suggests that behavior is dependent on water in or on the particles. Small clusters of methanesulfonic acid with amines are used as a model in quantum chemical calculations to identify key structural elements that are expected to influence water uptake, and hence the efficiency of displacement by gas-phase molecules in the aminium salts. Such molecular-level understanding of the processes affecting the ability of gas-phase amines to displace particle-phase aminium species is important for modeling the growth of particles and their impacts in the atmosphere.

  11. Structure-activity relationship studies on 1-heteroaryl-3-phenoxypropan-2-ones acting as inhibitors of cytosolic phospholipase A2α and fatty acid amide hydrolase: replacement of the activated ketone group by other serine traps.

    PubMed

    Sundermann, Tom; Hanekamp, Walburga; Lehr, Matthias

    2016-08-01

    Cytosolic phospholipase A2α (cPLA2α) and fatty acid amide hydrolase (FAAH) are serine hydrolases. cPLA2α is involved in the generation of pro-inflammatory lipid mediators, FAAH terminates the anti-inflammatory effects of endocannabinoids. Therefore, inhibitors of these enzymes may represent new drug candidates for the treatment of inflammation. We have reported that certain 1-heteroarylpropan-2-ones are potent inhibitors of cPLA2α and FAAH. The serine reactive ketone group of these compounds, which is crucial for enzyme inhibition, is readily metabolized resulting in inactive alcohol derivatives. In order to obtain metabolically more stable inhibitors, we replaced this moiety by α-ketoheterocyle, cyanamide and nitrile serine traps. Investigations on activity and metabolic stability of these substances revealed that in all cases an increased metabolic stability was accompanied by a loss of inhibitory potency against cPLA2α and FAAH, respectively. PMID:26153239

  12. Synthesis of thiocarbamate salts from amines, sulfur, and carbon monoxide

    SciTech Connect

    Manov-Yuvenskii, V.I.; Kuznetsov, S.L.

    1992-05-20

    Sulfur reacts with carbon monoxide and amines without a catalyst at 100-160{degrees}C and 10-100 atm for 1-4 h. The reaction products of primary amines are symmetric ureas. Under the same conditions, secondary amines form thiocarbamic acid salts, which are not converted to tetrasubstituted ureas. In the presence of primary amines at 100-160{degrees}C, they afford trisubstituted ureas, some of whose representatives are pesticides. The same products are formed directly in the carbonylation of a mixture of primary and secondary amines without isolation of intermediate thiocarbamic acid salts. In the presence of catalytic amounts of selenium, the reaction of sulfur with carbon monoxide and amines occurs at atmospheric pressure and affords N-substituted thiocarbamic acid salts from both secondary and primary amines. In the current work the authors present some of the characteristics of these processes. 10 refs., 5 figs., 2 tabs.

  13. Investigations on the synthesis and pharmacological properties of amides of 7-methyl-3-phenyl-1-[2-hydroxy-3-(4-phenyl-1-piperazinyl)propyl]-2,4- dioxo-1,2,3,4-tetrahydropyrido[2,3-d]-pyrimidine-5-carboxylic acid.

    PubMed

    Sladowska, H; Sieklucka-Dziuba, M; Rajtar, G; Sadowski, M; Kleinrok, Z

    1999-01-01

    Synthesis of amides of 7-methyl-3-phenyl-2,4-dioxo-1,2,3,4- tetrahydropyrido[2,3-d]pyrimidine-5-carboxylic acid (6-10) and their 1-[2-hydroxy-3(4-phenyl-1-piperazinyl)propyl] derivatives (11-15) are described. Some of them displayed strong analgesic activity. PMID:10668178

  14. Role of Amine Functionality for CO2 Chemisorption on Silica.

    PubMed

    Hahn, Maximilian W; Jelic, Jelena; Berger, Edith; Reuter, Karsten; Jentys, Andreas; Lercher, Johannes A

    2016-03-01

    The mechanism of CO2 adsorption on primary, secondary, and bibasic aminosilanes synthetically functionalized in porous SiO2 was qualitatively and quantitatively investigated by a combination of IR spectroscopy, thermogravimetry, and quantum mechanical modeling. The mode of CO2 adsorption depends particularly on the nature of the amine group and the spacing between the aminosilanes. Primary amines bonded CO2 preferentially through the formation of intermolecular ammonium carbamates, whereas CO2 was predominantly stabilized as carbamic acid, when interacting with secondary amines. Ammonium carbamate formation requires the transfer of the carbamic acid proton to a second primary amine group to form the ammonium ion and hence two (primary) amine groups are required to bind one CO2 molecule. The higher base strength of secondary amines enables the stabilization of carbamic acid, which is thereby hindered to interact further with nearby amine functions, because their association with Si-OH groups (either protonation or hydrogen bonding) does not allow further stabilization of carbamic acid as carbamate. Steric hindrance of the formation of intermolecular ammonium carbamates leads to higher uptake capacities for secondary amines functionalized in porous SiO2 at higher amine densities. In aminosilanes possessing a primary and a secondary amine group, the secondary amine group tends to be protonated by Si-OH groups and therefore does not substantially interact with CO2. PMID:26700549

  15. Amide coordination effects in organolithiums

    SciTech Connect

    Bachrach, S.M.; Ritchie, J.P. )

    1989-04-26

    Organolithiums containing the amide group are examined by ab initio molecular orbital calculations with the 3-21G basis set. Amide coordination with the metal cation results in a large thermodynamic stabilization of the ion pair. Basis set superposition errors at 3-21G are estimated to favor the complex by 10-15 kcal mol{sup {minus}1}; nevertheless, qualitative trends at this level are believed to be reliable. The calculations stabilization energy due to the amide drops off depending upon whether lithiation occurs {alpha}, {beta}, or {gamma} to the amide - provided the cation is accessible to the amide oxygen. Without correction for basis set superposition error, stabilization energies at 3-21G (in kcal mol{sup {minus}1}) are 45 in acetamide, 40 in benzamide, and 38 in syn-bicyclo(1.1.1)-pentane-2-carboxamide. Amide coordination effects in lithiocubanes are also estimated and found to be large. Thus, thermodynamics plays an important role in amide-assisted metalations. In addition, formation of an acetamide-methyllithium complex is found to be 37.5 kcal mol{sup {minus}1} exothermic relative to separated molecules, suggesting that formation of this complex lies along the metalation reaction pathways. This complexation facilitates the reaction kinetically. Analysis of electron density distributions and electrostatic potentials shows that the carbanion-lithium and the amide-lithium interactions are primarily closed-shell ones, being essentially ionic bonds.

  16. [Amides of creatine: perspectives of neuroprotection].

    PubMed

    Vlasov, T D; Chefu, S G; Baĭsa, A E; Leko, M V; Burov, S V; Veselkina, O S

    2011-07-01

    We evaluated the efficacy of derivatives of creatine and amino acids (CrAA) for decreasing cerebral injury in rats with transient middle cerebral artery occlusion (MCAO). Neuroprotective effects of amides of creatine and glycine (CrGlyOEt), phenylalanine (CrPheNH2), thyrosine (CrTyrNH2), and GABA (CrGABAOEt) were investigated. Brain injury was evaluated on day 2 after transient MCAO using a TTC staining of brain slices. Compared with the MCAO control group, all the CrAms showed decreased cerebral injury (p < 0.05). However CrPheNH2, CrTyrNH2, and CrGABAOEt were toxic after intravenous administration and investigated only after intraperitoneal injection. CrGlyOEt did not show any toxicity at dose of 1 mmol/kg. These data evidenced that creatinyl amides can represent promising candidates for the development of new drugs useful in brain ischemia treatment. PMID:21961295

  17. Oxidative versus Non-oxidative Decarboxylation of Amino Acids: Conditions for the Preferential Formation of Either Strecker Aldehydes or Amines in Amino Acid/Lipid-Derived Reactive Carbonyl Model Systems.

    PubMed

    Zamora, Rosario; León, M Mercedes; Hidalgo, Francisco J

    2015-09-16

    Comparative formation of both 2-phenylethylamine and phenylacetaldehyde as a consequence of phenylalanine degradation by carbonyl compounds was studied in an attempt to understand if the amine/aldehyde ratio can be changed as a function of reaction conditions. The assayed carbonyl compounds were selected because of the presence in the chain of both electron-donating and electron-withdrawing groups and included alkenals, alkadienals, epoxyalkenals, oxoalkenals, and hydroxyalkenals as well as lipid hydroperoxides. The obtained results showed that the 2-phenylethylamine/phenylacetaldehyde ratio depended upon both the carbonyls and the reaction conditions. Thus, it can be increased using electron-donating groups in the chain of the carbonyl compound, small amounts of carbonyl compound, low oxygen content, increasing the pH, or increasing the temperature at pH 6. Opposed conditions (use of electron-withdrawing groups in the chain of the carbonyl compound, large amounts of carbonyl compound, high oxygen contents, low pH values, and increasing temperatures at low pH values) would decrease the 2-phenylethylamine/phenylacetaldehyde ratio, and the formation of aldehydes over amines in amino acid degradations would be favored. PMID:26189462

  18. Filtrates & Residues. Acid Pickling with Amines: An Experiment in Applied Chemistry for High School or Freshman Chemistry.

    ERIC Educational Resources Information Center

    Spears, Steven G.; And Others

    1988-01-01

    This article gives a brief description of the process of the removal of corrosion and millscale from the surfaces of ferrous metals by acid pickling. It suggests an experiment to illustrate this process including the procedure and a discussion of the results. (CW)

  19. Aerosol and cloud chemistry of amines from CCS - reactivity experiments and numerical modeling

    NASA Astrophysics Data System (ADS)

    Weller, Christian; Tilgner, Andreas; Herrmann, Hartmut

    2013-04-01

    Capturing CO2 from the exhaust of power plants using amine scrubbing is a common technology. Therefore, amines can be released during the carbon capture process. To investigate the tropospheric chemical fate of amines from CO2 capturing processes and their oxidation products, the impact of aqueous aerosol particles and cloud droplets on the amine chemistry has been considered. Aqueous phase reactivity experiments of NO3 radicals and ozone with relevant amines and their corresponding nitrosamines were performed. Furthermore, nitrosamine formation and nitrosamine photolysis was investigated during laboratory experiments. These experiments implicated that aqueous phase photolysis can be an effective sink for nitrosamines and that ozone is unreactive towards amines and nitrosamines. Multiphase phase oxidation schemes of amines, nitrosamines and amides were developed, coupled to the existing multiphase chemistry mechanism CAPRAM and built into the Lagrangian parcel model SPACCIM using published and newly measured data. As a result, both deliquescent particles and cloud droplets are important compartments for the multiphase processing of amines and their products. Amines can be readily oxidised by OH radicals in the gas and cloud phase during daytime summer conditions. However, amine oxidation is restricted during winter conditions with low photochemical activity leading to long lifetimes of amines. The importance of the gas and aqueous phase depends strongly on the partitioning of the different amines. Furthermore, the simulations revealed that the aqueous formation of nitrosamines in aerosol particles and could droplets is not a relevant process under tropospheric conditions.

  20. Combining Amine-Reactive Cross-Linkers and Photo-Reactive Amino Acids for 3D-Structure Analysis of Proteins and Protein Complexes.

    PubMed

    Lössl, Philip; Sinz, Andrea

    2016-01-01

    During the last 15 years, the combination of chemical cross-linking and high-resolution mass spectrometry (MS) has matured into an alternative approach for analyzing 3D-structures of proteins and protein complexes. Using the distance constraints imposed by the cross-links, models of the protein or protein complex under investigation can be created. The majority of cross-linking studies are currently conducted with homobifunctional amine-reactive cross-linkers. We extend this "traditional" cross-linking/MS strategy by adding complementary photo-cross-linking data. For this, the diazirine-containing unnatural amino acids photo-leucine and photo-methionine are incorporated into the proteins and cross-link formation is induced by UV-A irradiation. The advantage of the photo-cross-linking strategy is that it is not restricted to lysine residues and that hydrophobic regions in proteins can be targeted, which is advantageous for investigating membrane proteins. We consider the strategy of combining cross-linkers with orthogonal reactivities and distances to be ideally suited for maximizing the amount of structural information that can be gained from a cross-linking experiment. PMID:26700045

  1. The influence of aliphatic amines, diamines, and amino acids on the polymorph of calcium carbonate precipitated by the introduction of carbon dioxide gas into calcium hydroxide aqueous suspensions

    NASA Astrophysics Data System (ADS)

    Chuajiw, Wittaya; Takatori, Kazumasa; Igarashi, Teruki; Hara, Hiroki; Fukushima, Yoshiaki

    2014-01-01

    The influence of aliphatic organic additives including amines, diamines and amino acids, on the polymorph of calcium carbonate (CaCO3) precipitated from a calcium hydroxide (Ca(OH)2) suspensions and carbon dioxide gas (CO2) was studied by X-Ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR) and scanning electron microscopy (SEM). The amorphous calcium carbonate, vaterite, aragonite and calcite were observed for the precipitated samples with organic additives. While the precipitation without organic additive, only the stable phase; calcite was obtained. The observed crystal phases were related with the alkyl chain length in the aliphatic part of additives. These results suggested that hydrophobic interactions due to the van der Waals force between organic additives and surface of inorganic precipitates could not be ignored. We concluded that covering or adsorbing of these organic additives on the precipitates surfaces retarded the successive dissolution/recrystallisation process in the aqueous systems. The results revealed that not only the polar interaction from the hydrophilic functional groups, as the former reports proposed, but also the van der Waals interactions from the hydrophobic alkyl groups played the important role in the phase transformation of CaCO3.

  2. Structural and spectroscopic characterizations on the charge-transfer interactions of the second generation poly(propylene amine) dendrimers with iodine and picric acid acceptors.

    PubMed

    El-Sayed, Mohamed Y; Refat, Moamen S

    2015-02-25

    Herein, this study was focused to get a knowledge about the intermolecular charge transfer complexes between the second generation of poly(propylene amine) dendrimer (PPD2) with picric acid (PA) and iodine (I2) as π and σ-acceptors. The charge-transfer interaction of the PPD2 electron donor and the PA acceptor has been studied in CHCl3. The resulted data refereed to the formation of the new CT-complex with the general formula [(PPD2)(PA)4]. The 1:4 stoichiometry of the reaction was discussed upon the on elemental analysis and photometric titration. On the other hand, the 1:3½ iodine-PPD2 heptaiodide (I7(-)) charge-transfer complex has been studied spectrophotometrically in chloroform at room temperature with general formula [(PPD2)](+)I7(-). The electronic absorption bands of 2I2·I3(-) (I7(-)) are observed at 358 and 294 nm. Raman laser spectrum of the brown solid heptaiodide complex has two clearly vibration bands at 155 and 110 cm(-1) due to symmetric stretching νs(II) outer and inner bonds, respectively. The (1)H NMR spectra and differential scanning calorimetry (DSC) data of PPD2 charge-transfer complexes were discussed. PMID:25305621

  3. Accurate determination of aldehydes in amine catalysts or amines by 2,4-dinitrophenylhydrazine derivatization.

    PubMed

    Barman, Bhajendra N

    2014-01-31

    Carbonyl compounds, specifically aldehydes, present in amine catalysts or amines are determined by reversed-phase liquid chromatography using ultraviolet detection of their corresponding 2,4-dinitrophenylhydrazones. The primary focus has been to establish optimum conditions for determining aldehydes accurately because these add exposure concerns when the amine catalysts are used to manufacture polyurethane products. Concentrations of aldehydes determined by this method are found to vary with the pH of the aqueous amine solution and the derivatization time, the latter being problematic when the derivatization reaction proceeds slowly and not to completion in neutral and basic media. Accurate determination of aldehydes in amines through derivatization can be carried out at an effective solution pH of about 2 and with derivatization time of 20min. Hydrochloric acid has been used for neutralization of an amine. For complete derivatization, it is essential to protonate all nitrogen atoms in the amine. An approach for the determination of an adequate amount of acid needed for complete derivatization has been described. Several 0.2M buffer solutions varying in pH from 4 to 8 have also been used to make amine solutions for carrying out derivatization of aldehydes. These solutions have effective pHs of 10 or higher and provide much lower aldehyde concentrations compared to their true values. Mechanisms for the formation of 2,4-dinitrophenylhydrazones in both acidic and basic media are discussed. PMID:24411140

  4. Reversible Alkene Insertion into the Pd–N Bond of Pd(II)-Sulfonamidates and Implications for Catalytic Amidation Reactions

    PubMed Central

    White, Paul B.; Stahl, Shannon S.

    2011-01-01

    Alkene insertion into Pd–N bonds is a key step in Pd-catalyzed oxidative amidation of alkenes. A series of well-defined Pd(II)-sulfonamidate complexes have been prepared and shown to react via insertion of a tethered alkene. The Pd–amidate and resulting Pd–alkyl species have been crystallographically characterized. The alkene insertion reaction is found to be reversible, but complete conversion to oxidative amination products is observed in the presence of O2. Electronic-effect studies reveal that alkene insertion into the Pd–N bond is favored kinetically and thermodynamically with electron-rich amidates. PMID:22007610

  5. Dual Catalysis Using Boronic Acid and Chiral Amine: Acyclic Quaternary Carbons via Enantioselective Alkylation of Branched Aldehydes with Allylic Alcohols.

    PubMed

    Mo, Xiaobin; Hall, Dennis G

    2016-08-31

    A ferrocenium boronic acid salt activates allylic alcohols to generate transient carbocations that react with in situ-generated chiral enamines from branched aldehydes. The optimized conditions afford the desired acyclic products embedding a methyl-aryl quaternary carbon center with up to 90% yield and 97:3 enantiomeric ratio, with only water as the byproduct. This noble-metal-free method complements alternative methods that are incompatible with carbon-halogen bonds and other sensitive functional groups. PMID:27518200

  6. Dispersive liquid-liquid microextraction based on amine-functionalized Fe₃O₄ nanoparticles for the determination of phenolic acids in vegetable oils by high-performance liquid chromatography with UV detection.

    PubMed

    Shi, Zhihong; Qiu, Lingna; Zhang, Dan; Sun, Mengyuan; Zhang, Hongyi

    2015-08-01

    A novel dispersive liquid-liquid microextraction method based on amine-functionalized Fe3O4 magnetic nanoparticles was developed for the determination of six phenolic acids in vegetable oils by high-performance liquid chromatography. Amine-functionalized Fe3O4 was synthesized by a one-pot solvothermal reaction between Fe3O4 and 1,6-hexanediamine and characterized by transmission electron microscopy and Fourier transform infrared spectrophotometry. A trace amount of phosphate buffer solution (extractant) was adsorbed on bare Fe3O4-NH2 nanoparticles by hydrophilic interaction to form the "magnetic extractant". Rapid extraction could be achieved while the "magnetic extractant" on amine-functionalized Fe3O4 nanoparticles was dispersed in the sample solution by vortexing. After extraction, the "magnetic extractant" was collected by application of an external magnet. Some important parameters, such as pH and volume of extraction and desorption solvents, the extraction and desorption time needed were carefully investigated and optimized to achieve the best extraction efficiency. Under the optimal conditions, satisfactory extraction recoveries were obtained for the six phenolic acids in the range of 84.2-106.3%. Relative standard deviations for intra- and inter-day precisions were less than 6.3 and 10.0%, respectively. Finally, the established method was successfully applied for the determination of six phenolic acids in eight kinds of vegetable oils. PMID:26109040

  7. Cytotoxic effects of Jay Amin hydroxamic acid (JAHA), a ferrocene-based class I histone deacetylase inhibitor, on triple-negative MDA-MB231 breast cancer cells.

    PubMed

    Librizzi, Mariangela; Longo, Alessandra; Chiarelli, Roberto; Amin, Jahanghir; Spencer, John; Luparello, Claudio

    2012-11-19

    The histone deacetylase inhibitors (HDACis) are a class of chemically heterogeneous anticancer agents of which suberoylanilide hydroxamic acid (SAHA) is a prototypical member. SAHA derivatives may be obtained by three-dimensional manipulation of SAHA aryl cap, such as the incorporation of a ferrocene unit like that present in Jay Amin hydroxamic acid (JAHA) and homo-JAHA [ Spencer , et al. ( 2011 ) ACS Med. Chem. Lett. 2 , 358 - 362 ]. These metal-based SAHA analogues have been tested for their cytotoxic activity toward triple-negative MDA-MB231 breast cancer cells. The results obtained indicate that of the two compounds tested, only JAHA was prominently active on breast cancer cells with an IC(50) of 8.45 μM at 72 h of treatment. Biological assays showed that exposure of MDA-MB231 cells to the HDACi resulted in cell cycle perturbation with an alteration of S phase entry and a delay at G(2)/M transition and in an early reactive oxygen species production followed by mitochondrial membrane potential (MMP) dissipation and autophagy inhibition. No annexin binding was observed after short- (5 h) and longer (24 and 48 h) term incubation with JAHA, thereby excluding the promotion of apoptosis by the HDACi. Although caution must be exercised in extrapolation of in vitro results to the in vivo situation for which research on animals and human trials are needed, nevertheless JAHA treatment possesses the potential for its development as an agent for prevention and/or therapy of "aggressive" breast carcinoma, thus prompting us to get more insight into the molecular basis of its antibreast cancer activity. PMID:23094795

  8. Solvent-extraction and purification of uranium(VI) and molybdenum(VI) by tertiary amines from acid leach solutions

    SciTech Connect

    La Gamma, Ana M.G.; Becquart, Elena T.; Chocron, Mauricio

    2008-07-01

    Considering international interest in the yellow-cake price, Argentina is seeking to exploit new uranium ore bodies and processing plants. A study of similar plants would suggest that solvent- extraction with Alamine 336 is considered the best method for the purification and concentration of uranium present in leaching solutions. In order to study the purification of these leach liquors, solvent-extraction tests under different conditions were performed with simulated solutions which containing molybdenum and molybdenum-uranium mixtures. Preliminary extraction tests carried out on mill acid-leaching liquors are also presented. (authors)

  9. Possible evidence of amide bond formation between sinapinic acid and lysine-containing bacterial proteins by matrix-assisted laser desorption/ionization (MALDI) at 355 nm

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We previously reported the apparent formation of matrix adducts of 3,5-dimethoxy-4-hydroxy-cinnamic acid (sinapinic acid or SA) via covalent attachment to disulfide bond-containing proteins (HdeA, HdeB and YbgS) from bacterial cell lysates ionized by matrix-assisted laser desorption/ionization (MALD...

  10. Tandem dissolution of UO3 in amide-based acidic ionic liquid and in situ electrodeposition of UO2 with regeneration of the ionic liquid: a closed cycle.

    PubMed

    Wanigasekara, Eranda; Freiderich, John W; Sun, Xiao-Guang; Meisner, Roberta A; Luo, Huimin; Delmau, Lætitia H; Dai, Sheng; Moyer, Bruce A

    2016-06-21

    A closed cycle is demonstrated for the tandem dissolution and electroreduction of UO3 to UO2 with regeneration of the acidic ionic liquid. The dissolution is achieved by use of the acidic ionic liquid [DMAH][NTf2] in [EMIM][NTf2] serving as the diluent. A sequential dissolution, electroreduction, and regeneration cycle is presented. PMID:27255672

  11. Solvent-free functionalization of carbon nanotube buckypaper with amines

    NASA Astrophysics Data System (ADS)

    Basiuk, Elena V.; Ramírez-Calera, Itzel J.; Meza-Laguna, Victor; Abarca-Morales, Edgar; Pérez-Rey, Luis A.; Re, Marilena; Prete, Paola; Lovergine, Nico; Álvarez-Zauco, Edgar; Basiuk, Vladimir A.

    2015-12-01

    We demonstrate the possibility of fast and efficient solvent-free functionalization of buckypaper (BP) mats prefabricated from oxidized multiwalled carbon nanotubes (MWCNTs-ox), by using three representative amines of different structure: one monofunctional aliphatic amine, octadecylamine (ODA), one monofunctional aromatic amine, 1-aminopyrene (AP), and one aromatic diamine, 1,5-diaminonaphthalene (DAN). The functionalization procedure, which relies on the formation of amide bonds with carboxylic groups of MWCNTs-ox, is performed at 150-180 °C under reduced pressure and takes about 4 h including auxiliary degassing. The amine-treated BP samples (BP-ODA, BP-AP and BP-DAN, respectively) were characterized by means of a variety of analytical techniques such as Fourier-transform infrared and Raman spectroscopy, thermogravimetric and differential thermal analysis, scanning and transmission electron microscopy, scanning helium ion microscopy, and atomic force microscopy. The highest amine content was found for BP-ODA, and the lowest one was observed for BP-DAN, with a possible contribution of non-covalently bonded amine molecules in all three cases. Despite of some differences in spectral and morphological characteristics for amine-functionalized BP samples, they have in common a dramatically increased stability in water as compared to pristine BP and, on the other hand, a relatively invariable electrical conductivity.

  12. Tandem dissolution of UO 3 in amide-based acidic ionic liquid and in situ electrodeposition of UO 2 with regeneration of the ionic liquid: a closed cycle

    DOE PAGESBeta

    Wanigasekara, Eranda; Freiderich, John W.; Sun, Xiao-Guang; Meisner, Roberta A.; Luo, Huimin; Delmau, Lætitia H.; Dai, Sheng; Moyer, Bruce A.

    2016-05-19

    A closed cycle is demonstrated for the tandem dissolution and electroreduction of UO3 to UO2 with regeneration of the acidic ionic liquid. The dissolution is achieved by use of the acidic ionic liquid N,N-dimethylacetimidium bis(trifluoromethanesulfonimide) in 1-ethyl-3-methylimidazolium bis(trifluoromethanesulfonimide) serving as the diluent. Bulk electrolysis performed at 1.0 V vs. Ag reference yields a dark brown-black uranium deposit (UO2) on the cathode. Anodic oxidation of water in the presence of dimethylacetamide regenerates the acidic ionic liquid. We have demonstrated the individual steps in the cycle together with a sequential dissolution, electroreduction, and regeneration cycle.

  13. One-Shot Double Amination of Sondheimer-Wong Diynes: Synthesis of Photoluminescent Dinaphthopentalenes.

    PubMed

    Xu, Feng; Peng, Lifen; Shinohara, Kenta; Nishida, Takanori; Wakamatsu, Kan; Uejima, Motoyuki; Sato, Tohru; Tanaka, Kazuyoshi; Machida, Norihiko; Akashi, Haruo; Orita, Akihiro; Otera, Junzo

    2015-06-19

    Photoluminescent diamino-substituted dinaphthopentalenes were synthesized successfully by the treatment of in situ prepared dinaphthocyclooctadiyne with lithium amide. This reaction involves a series of transformations including the nucleophilic addition of the lithium amide to a triple bond of the cyclooctadiyne moiety, transannulation, protonation of the resulting pentalene anion, and the nucleophilic substitution of the pentalene core with the lithium amide. In this procedure, a novel double amination step plays a key role. When the diamino-substituted dinaphthopentalenes were irradiated with UV light in toluene, fluorescence was observed at around 580 nm (ΦF < 0.03). PMID:26053042

  14. Amine Measurements in Boreal Forest Air

    NASA Astrophysics Data System (ADS)

    Hemmilä, Marja; Hellén, Heidi; Makkonen, Ulla; Hakola, Hannele

    2015-04-01

    Amines are reactive, volatile bases in the air with a general formula of RNH2, R2NH or R3N. Especially small amines can stabilize sulphuric acid clusters and hence affect nucleation. Amines react rapidly with hydroxyl radical (OH˙) thus affecting oxidative capacity of the atmosphere. The amine concentrations are higher in forest air than in urban air (Hellén et al., 2014), but the sources are not known. In order to get more information concerning amine sources, we conducted a measurement campaign in a boreal forest. At SMEAR II station at Hyytiälä, Southern Finland (61°510'N, 24°170'E, 180 m a.s.l.) The measurements cover seven months, from June to December 2014. For sampling and measuring we used MARGA (The instrument for Measuring AeRosols and Gases in Ambient air) which is an on-line ion chromatograph (IC) connected to a sampling system. The IC component of the MARGA system was coupled to an electrospray ionization quadrupole mass spectrometer (MS) to improve sensitivity of amine measurements. This new set-up enabled amine concentration measurements in ambient air both in aerosol and gas phases with a time resolution of only 1 hour. With MARGA-MS we analysed 7 different amines: monomethylamine (MMA), dimethylamine (DMA), trimethylamine (TMA), ethylamine (EA), diethylamine (DEA), propylamine (PA) and butylamine (BA). In preliminary data-analysis we found out, that in June and July most of the measured amines were in gas phase, and particle phase amine concentrations were mostly under detection limits (<1.7 pptv). In June the gaseous amine concentrations were higher than in July. The measured concentrations of gaseous amines followed temperature variation, which could indicate that amines are produced and emitted from the environment or re-emitted from the surfaces as temperature rises after deposition during night-time. All measured amines had similar diurnal variation with maxima during afternoon and minima during night. Results from other months will also

  15. Comparison of analytical protein separation characteristics for three amine-based capillary-channeled polymer (C-CP) stationary phases.

    PubMed

    Jiang, Liuwei; Marcus, R Kenneth

    2016-02-01

    Capillary-channeled polymer (C-CP) fiber stationary phases are finding utility in the realms of protein analytics as well as downstream processing. We have recently described the modification of poly(ethylene terephthalate) (PET) C-CP fibers to affect amine-rich phases for the weak anion-exchange (WAX) separation of proteins. Polyethylenimine (PEI) is covalently coupled to the PET surface, with subsequent cross-linking imparted by treatment with 1,4-butanediol diglycidyl ether (BUDGE). These modifications yield vastly improved dynamic binding capacities over the unmodified fibers. We have also previously employed native (unmodified) nylon 6 C-CP fibers as weak anion/cation-exchange (mixed-mode) and hydrophobic interaction chromatography (HIC) phases for protein separations. Polyamide, nylon 6, consists of amide groups along the polymer backbone, with primary amines and carboxylic acid end groups. The analytical separation characteristics of these three amine-based C-CP fiber phases are compared here. Each of the C-CP fiber columns in this study was shown to be able to separate a bovine serum albumin/hemoglobin/lysozyme mixture at high mobile phase linear velocity (∼70 mm s(-1)) but with different elution characteristics. These differences reflect the types of protein-surface interactions that are occurring, based on the active group composition of the fiber surfaces. This study provides important fundamental understanding for the development of surface-modified C-CP fiber columns for protein separation. PMID:26345444

  16. Two coordination polymers constructed from a multidentate carboxylic acid ligand with a tertiary amine serve as acid-base catalysts for the synthesis of chloropropene carbonate from CO2 under atmospheric pressure.

    PubMed

    Chen, Chao; Zhang, Jun; Li, Guanghua; Shen, Pan; Jin, Haichao; Zhang, Ning

    2014-10-01

    Two new coordination polymers, [Ni(H2O)(Hpdcd)(H2O)2]·DMF (1) and [Co(H2O)(Hpdcd)(H2O)2]·DMF (2) (H3pdcd = 1-(4-carboxyphenyl)-2,5-dimethyl, 1H-pyrrole-3,4-dicarboxylic acid), which were designed based on a tertiary amine ligand, were synthesized and characterized using multiple spectroscopy techniques, including single-crystal X-ray diffraction. These two 1D linear chains possess the properties of both a Lewis acid and organic base, which was confirmed by temperature programmed desorption of ammonia and on-line mass spectrometry (NH3-TPD-MS), and selective sorption for carbon dioxide. Due to their acid-base properties, the compounds exhibited high catalytic activity, in the absence of co-catalysts, for solvent-free synthesis of chloropropene carbonate from CO2 and epichlorohydrin under atmospheric CO2 pressure. The yields of chloropropene carbonate were 88% and 87% for 1 and 2, respectively, under the optimized conditions. PMID:25113602

  17. Synthesis and evaluation of backbone/amide-modified analogs of leualacin.

    PubMed

    Hu, M K; Yang, F C; Chou, C C; Yen, M H

    1999-02-22

    Leualacin (1), a cyclic depsi-pentapeptide, and its backbone/amide-modified analogs 2-4 were synthesized. Amide analogue 3 exhibited stronger vasodilatory effects. It also strongly inhibited collagen- and arachidonic acid (AA)-induced platelet aggregations with IC50s of 0.6 microM and 2.0 microM, respectively. PMID:10098664

  18. Biosynthesis of peptide neurotransmitters: studies on the formation of peptide amides.

    PubMed

    Bradbury, A F; Smyth, D G

    1988-01-01

    A high proportion of peptide transmitters and peptide hormones terminate their peptide chain in a C-terminal amide group which is essential for their biological activity. The specificity of an enzyme that catalyses the formation of the amide was investigated with the aid of synthetic peptide substrates. With peptides containing l-amino acids the enzyme exhibited an essential requirement for glycine in the C-terminal position; amidation did not take place with peptides that had leucine, alanine, glutamic acid, lysine or N-methylglycine at the C-terminus and a peptide extended by the attachment of lysine to the C-terminal glycine did not act as a substrate. Amidation did occur with a peptide containing C-terminal D-alanine but no reaction was detected with peptides having C-terminal, D-serine or D-leucine. In tripeptides with a neutral amino acid in the penultimate position, amidation, took place readily but the reaction was slower when this position was occupied by an acidic or a basic residue. A series of overlapping peptides with C-terminal glycine, based on partial sequences of calcitonin, underwent amidation at similar rates, indicating that the amidating enzyme recognizes only a limited sequence at the C-terminus of its substrates. The results provide evidence that the amidating enzyme has a highly compact substrate binding site. PMID:2906151

  19. A review of proton transfer reactions between various carbon-acids and amine bases in aprotic solvents

    NASA Astrophysics Data System (ADS)

    Jarczewski, Arnold; Hubbard, Colin D.

    2003-04-01

    The subject of proton transfer between carbon acids and nitrogen bases in aprotic solvents is reviewed. Equilibrium and rate constants that characterize such reactions are most often determined utilizing UV-visible spectrophotometry. At ambient temperature reaction rates are sufficiently rapid that fast reaction methods, for example, the stopped-flow and temperature-jump techniques are required in many cases. Variation of the properties of the donor and acceptor reaction pairs enables electronic and steric effects upon thermodynamic and kinetic parameters of proton transfer to be assessed. Determination of the kinetic isotope effect (KIE), i.e. k(protium)/ k(deuterium) led to the conclusion that, under certain circumstances and when the KIE is greater than seven, the proton undergoes reaction with a significant degree of quantum mechanical tunneling, consistent with a theoretical prediction advanced several decades earlier. In fact this aspect may be one of the most significant outgrowths of these studies. Many reactions have been characterized (by tunneling) but rarely are the reacting systems experimentally amenable to obtaining all the experimental criteria that support tunneling. Controversy that has arisen regarding treatment of experimental data and resulting conclusions from them is visited in this review. The structural nature of the product state of reaction is formulated based on spectroscopic evidence, in favorable cases, and probable structures of the transition state can be inferred.

  20. Alkylamine-Dependent Amino-Acid Oxidation by Lysine Monooxygenase—Fragmented Substrate of Oxygenase

    PubMed Central

    Yamamoto, Shozo; Yamauchi, Takashi; Hayaishi, Osamu

    1972-01-01

    Lysine monooxygenase catalyzes the oxygenative decarboxylation of L-lysine and produces a corresponding acid amide. L-Alanine was inactive as substrate. However, when propylamine was present, oxidation, but not oxygenation, of alanine was demonstrated with the oxygenase. Alanine was converted to pyruvate, with the liberation of ammonia and hydrogen peroxide, but propylamine remained unchanged. Other α-monoamino acids were also oxidized in the presence of alkylamines with various carbon chain lengths. The highest oxidase activity was observed when the total chain length of both amino acid and amine was nearly identical with that of lysine. Available evidence indicates that the amine-dependent amino-acid oxidase activity is associated with the lysine oxygenase activity. PMID:4509334