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Sample records for picolinic acid n-oxide

  1. Picolinic and isonicotinic acids: a Fourier transform microwave spectroscopy study.

    PubMed

    Peña, Isabel; Varela, Marcelino; Franco, Vanina G; López, Juan C; Cabezas, Carlos; Alonso, José L

    2014-12-04

    The rotational spectra of laser ablated picolinic and isonicotinic acids have been studied using broadband chirped pulse (CP-FTMW) and narrowband molecular beam (MB-FTMW) Fourier transform microwave spectroscopies. Two conformers of picolinic acid, s-cis-I and s-cis-II, and one conformer of isonicotinic acid have been identified through the analysis of their rotational spectra. The values of the inertial defect and the quadrupole coupling constants obtained for the most stable s-cis-I conformer of picolinic acid, evidence the formation of an O-H···N hydrogen bond between the acid group and the endocyclic N atom. The stabilization provided by this hydrogen bond compensates the destabilization energy due to the adoption of a -COOH trans configuration in this conformer. Its rs structure has been derived from the rotational spectra of several (13)C, (15)N, and (18)O species observed in their natural abundances. Mesomeric effects have been revealed by comparing the experimental values of the (14)N nuclear quadrupole coupling constants in the isomeric series of picolinic, isonicotinic, and nicotinic acids.

  2. Crystal growth and physical characterization of picolinic acid cocrystallized with dicarboxylic acids

    NASA Astrophysics Data System (ADS)

    Somphon, Weenawan; Haller, Kenneth J.

    2013-01-01

    Pharmaceutical cocrystals are multicomponent materials containing an active pharmaceutical ingredient with another component in well-defined stoichiometry within the same unit cell. Such cocrystals are important in drug design, particularly for improving physicochemical properties such as solubility, bioavailability, or chemical stability. Picolinic acid is an endogenous metabolite of tryptophan and is widely used for neuroprotective, immunological, and anti-proliferative effects within the body. In this paper we present cocrystallization experiments of a series of dicarboxylic acids, oxalic acid, succinic acid, DL-tartaric acid, pimelic acid, and phthalic acid, with picolinic acid. Characterization by FT-IR and Raman spectroscopy, DSC and TG/DTG analysis, and X-ray powder diffraction show that new compounds are formed, including a 1:1 picolinium tartrate monohydrate, a 2:1 monohydrate adduct of picolinic acid and oxalic acid, and a 2:1 picolinic acid-succinic acid monohydrate cocrystal.

  3. Biodegradation of 5-chloro-2-picolinic acid by novel identified co-metabolizing degrader Achromobacter sp. f1.

    PubMed

    Wu, Zhi-Guo; Wang, Fang; Ning, Li-Qun; Stedtfeld, Robert D; Yang, Zong-Zheng; Cao, Jing-Guo; Sheng, Hong-Jie; Jiang, Xin

    2017-02-02

    Several bacteria have been isolated to degrade 4-chloronitrobenzene. Degradation of 4-chloronitrobenzene by Cupriavidus sp. D4 produces 5-chloro-2-picolinic acid as a dead-end by-product, a potential pollutant. To date, no bacterium that degrades 5-chloro-2-picolinic acid has been reported. Strain f1, isolated from a soil polluted by 4-chloronitrobenzene, was able to co-metabolize 5-chloro-2-picolinic acid in the presence of ethanol or other appropriate carbon sources. The strain was identified as Achromobacter sp. based on its physiological, biochemical characteristics, and 16S rRNA gene sequence analysis. The organism completely degraded 50, 100 and 200 mg L(-1) of 5-chloro-2-picolinic acid within 48, 60, and 72 h, respectively. During the degradation of 5-chloro-2-picolinic acid, Cl(-) was released. The initial metabolic product of 5-chloro-2-picolinic acid was identified as 6-hydroxy-5-chloro-2-picolinic acid by LC-MS and NMR. Using a mixed culture of Achromobacter sp. f1 and Cupriavidus sp. D4 for degradation of 4-chloronitrobenzen, 5-chloro-2-picolinic acid did not accumulate. Results infer that Achromobacter sp. f1 can be used for complete biodegradation of 4-chloronitrobenzene in remedial applications.

  4. Experimental and theoretical IR and Raman spectra of picolinic, nicotinic and isonicotinic acids

    NASA Astrophysics Data System (ADS)

    Koczoń, P.; Dobrowolski, J. Cz.; Lewandowski, W.; Mazurek, A. P.

    2003-07-01

    The experimental and theoretical (B3PW91/6-311++G**) vibrational (IR and Raman) spectra of picolinic, nicotinic and isonicotinic acids (pyridine-2-, -3-, and -4-carboxylic acid, respectively) were studied. Three stable calculated structures were found for picolinic acid: the structure with intramolecular hydrogen COOH⋯N bond, and the two without hydrogen bond. For the nicotinic acid two stable theoretical structures differ in orientation of the COOH group with respect to the nitrogen atom, whereas for the isonicotinic acid only one form was stable. The theoretical vibrational spectra of the three acids were interpreted by means of potential energy distributions (PEDs) using VEDA 3 program. Next, selected experimental bands were assigned based on the scaled theoretical wavenumbers. Finally, the wavenumbers and intensities for the three isomeric acids were compared and discussed in terms of location of the carboxylic group.

  5. 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

  6. Extraction of Palladium from Nitric Acid by Diamides of Di-picolinic Acid

    SciTech Connect

    Alyapyshev, M.Yu.; Babain, V.A.; Pokhitonov, Yu.A.; Esimantovskiy, V.M.

    2007-07-01

    The most complicated and urgent problem of atomic industry consists in the safe isolation and storage of radioactive wastes. The long-lived radionuclides presented in high-level liquid wastes (HLLW) pose a potential threat to environment for hundreds and thousands of years. One of the possible ways to reduce the danger of HLLW storages is concerned with treatment of HLLW intended to recovery of long-lived radionuclides and their partitioning into separate fractions. The separation of the most hazardous radionuclides (like transplutonium elements (TPE)) to the individual fraction of low volume leads to decrease of the total volume of HLLW and therefore to decrease of solidified waste storage costs. It should be noted that only in the case of reprocessing it can be possible to recover individual radionuclides (or their fractions) into separate flows with further special approach to each of them. Partitioning of different HLLW is under investigation in many countries now. Numerous processes for recovery of Cs, Sr, TPE and REE have been already developed and tested. At the same time partitioning is only the first step on the road to the following synthesis of materials providing the safe storage of long-lived radionuclides over many thousands of years. The metallic palladium contained in HLLW seems to be a promising material for producing of matrices for incorporation of radioactive wastes. Different methods for palladium recovery have been investigated: reductive precipitation, electrochemical precipitation, sorption and extraction. Of prime importance are extraction methods. Phosphine oxides, carbamoyl-phosphine oxides, crown-ethers, oximes, sulfides and some other compounds were proposed as extractants towards palladium from nitric acid media. It is reasonable to recover palladium into individual fraction during waste partitioning. Diamides of malonic, di-glycolic and pyridine-dicarboxylic (di-picolinic) acids are intensively investigated as extractants for HLLW

  7. Synthesis, Crystal Structure, and Thermal Decomposition of the Cobalt(II) Complex with 2-Picolinic Acid

    PubMed Central

    Li, Di

    2014-01-01

    The cobalt(II) complex of 2-picolinic acid (Hpic), namely, [Co(pic)2(H2O)2] · 2H2O, was synthesized with the reaction of cobalt acetate and 2-picolinic acid as the reactants by solid-solid reaction at room temperature. The composition and structure of the complex were characterized by elemental analysis, infrared spectroscopy, single crystal X-ray diffraction, and thermogravimetry-differential scanning calorimetry (TG-DSC). The crystal structure of the complex belongs to monoclinic system and space group P2(1)/n, with cell parameters of a = 9.8468(7) Å, b = 5.2013(4) Å, c = 14.6041(15) Å, β = 111.745(6)°, V = 747.96(11) Å3, Z = 2, Dc = 1.666 g cm−3, R1 = 0.0297, and wR2 = 0.0831. In the title complex, the Co(II) ion is six-coordinated by two pyridine N atoms and two carboxyl O atoms from two 2-picolinic acid anions, and two O atoms from two H2O molecules, and forming a slightly distorted octahedral geometry. The thermal decomposition processes of the complex under nitrogen include dehydration and pyrolysis of the ligand, and the final residue is cobalt oxalate at about 450°C. PMID:24578654

  8. Inhibition of Pseudomonas aeruginosa biofilm formation by 2,2’-bipyridyl, lipoic, kojic and picolinic acids

    PubMed Central

    Çevik, Kübra; Ulusoy, Seyhan

    2015-01-01

    Objective(s): The inhibitory effects of iron chelators, and FeCl3 chelation on biofilm formation and swarming motility were investigated against an opportunistic human pathogen Pseudomonas aeruginosa. Materials and Methods: The inhibitory activity of 2,2’-bipyridyl, lipoic acid, kojic acid and picolinic acid on biofilm formation of P. aeruginosa strain PAO1 and three clinical isolates (P. aeruginosa PAK01, P. aeruginosa PAK02 and P. aeruginosa PAK03) were investigated, based on crystal violet assay, and swarming motility test. Results: The kojic, lipoic and picolinic acid inhibited biofilm formation by 5-33% in all tested P. aeruginosa isolates. When chelated iron was added, biofilm inhibition rates were determined to be 39-57%. Among the tested chelators against P. aeruginosa, lipoic acid (84%) and kojic acid (68%) presented the highest inhibition of swarming motility. This is the first study to report the inhibitory effect of lipoic acid on biofilm formation and swarming motility of P. aeruginosa. Conclusion: It is considered that lipoic and picolinic acids can serve as alternatives for the treatment of the P. aeruginosa infections by inhibiting biofilm formation. PMID:26557964

  9. Biodegradation of Picolinic Acid by a Newly Isolated Bacterium Alcaligenes faecalis Strain JQ135.

    PubMed

    Qiu, Jiguo; Zhang, Junjie; Zhang, Yanting; Wang, Yuhong; Tong, Lu; Hong, Qing; He, Jian

    2017-04-01

    We isolated a bacterial strain JQ135 from municipal wastewater, which was capable of efficiently degrading picolinic acid (PA). Based on the physico-biochemical characteristics and 16S rDNA analysis, strain JQ135 was identified as Alcaligenes faecalis. In addition, strain JQ135 produced an orange pigment when cultured in the Luria-Bertani medium, which is different from the previously reported strains of A. faecalis. During the degradation of PA by the resting strain JQ135 cells, only one intermediate, 6-hydroxypicolinic acid (6HPA), was detected by ultraviolet spectrophotometry, high-pressure liquid chromatography, and liquid chromatography-mass spectrometry. A random transposon mutagenesis library of strain JQ135 was constructed. One mutant, Mut-G31, could convert PA into 6HPA without further degradation. The disrupted gene (orf2) was amplified from Mut-G31, and its product showed 32% identity to the 3-deoxy-D-manno-octulosonic acid kinase (KdkA) from Haemophilus influenzae. Results from complementation analysis confirmed that GTG was the initiation codon of the kdkA-like orf2, and that it was essential for PA biodegradation by strain JQ135. This study provides the first genetic evidence for the bacterial degradation of PA.

  10. Spectrophotometric study of the charge transfer complex between 2-amino-4-picoline with chloranilic acid

    NASA Astrophysics Data System (ADS)

    Alghanmi, Reem M.; Al-Attas, Amirah S.; Habeeb, Moustafa M.

    2013-02-01

    Charge transfer complex formation between 2-amino-4-picoline (2A4P) as the electron donor with chloranilic acid (CLA) as the electron acceptor has been studied spectrophotometrically in different polar solvents included acetone (AcN), ethanol (EtOH) and acetonitrile (AN). The molecular composition of the formed complex was recognized utilizing Job's, photometric and conductometric titration methods to be 1:1. The formation constants and molecular extinction coefficients were estimated using Benesi-Hildebrand equation; they recorded high values confirming high stability of the formed complex. Moreover, the results showed that the complex is more stable in acetone with lower electric permittivity compared with ethanol or acetonitrile of higher ones. The values of some spectroscopic physical parameters like oscillator strength f, transition dipole moment μ, resonance energy RN, charge transfer energy ECT, dissociation energy W, ionization potential IP and standard free energy ΔGo were determined and evaluated. The solid complex was isolated and its molecular composition was determined by elemental analysis to be 1:1. Furthermore, the solid complex was characterized using FTIR and 1H NMR measurements. They confirmed the presence of proton transfer beside charge transfer in the obtained complex. Molecular orbital calculations utilizing GAMESS computations were carried out to predict infrared spectra. They also confirmed the presence of proton transfer beside charge transfer in the formed complex.

  11. New complexes of cobalt(II) ions with pyridinecarboxylic acid N-oxides and 4,4‧-byp

    NASA Astrophysics Data System (ADS)

    Hnatejko, Zbigniew; Dutkiewicz, Grzegorz; Kubicki, Maciej; Lis, Stefan

    2013-02-01

    This paper reports a study concerning the isolation and characterization of mixed ligand complexes of the Co(II) ions with pyridinecarboxylic acids N-oxides (picolinic (PNO), nicotinic (NNO) and isonicotinic (INO)), [Co(PNO)2(4,4'-byp)]·6H2O 1, [Co(NNO)(4,4'-byp)NO3]·8H2O 2 and [Co(INO)(4,4'-byp)NO3]·7H2O 3; (4,4'-byp = 4,4'-bipyridine). The complexes 2 and 3 were prepared by the hydrothermal synthesis. The structures of the complexes were elucidated on the basis of elemental analysis, thermal decomposition, IR and mass spectroscopy. IR spectra show that N-oxides act as bidentate ligands, in which both the N-oxide and the carboxylate groups are involved in coordination. In 2 and 3 the Co(II) ion exists in the same coordination environment. For 1, the X-ray crystal structure has been determined and it turned out that it contains the coordination polymers, created by the chains of Co ions joined by 4,4'-byp ligands. The Co(II) ion occupies the center of symmetry in the space group C2/c. This ion is coordinated by two nitrogen atoms (from two 4,4'-byp ligands) and four oxygen atoms from two PNO anions. The extensive network of hydrogen bonds involving six different water molecules connects the one-dimensional polymers into three-dimensional crystal structure.

  12. Vanadyl complexes with dansyl-labelled di-picolinic acid ligands: synthesis, phosphatase inhibition activity and cellular uptake studies.

    PubMed

    Collins, Juliet; Cilibrizzi, Agostino; Fedorova, Marina; Whyte, Gillian; Mak, Lok Hang; Guterman, Inna; Leatherbarrow, Robin; Woscholski, Rudiger; Vilar, Ramon

    2016-04-28

    Vanadium complexes have been previously utilised as potent inhibitors of cysteine based phosphatases (CBPs). Herein, we present the synthesis and characterisation of two new fluorescently labelled vanadyl complexes (14 and 15) with bridged di-picolinic acid ligands. These compounds differ significantly from previous vanadyl complexes with phosphatase inhibition properties in that the metal-chelating part is a single tetradentate unit, which should afford greater stability and scope for synthetic elaboration than the earlier complexes. These new complexes inhibit a selection of cysteine based phosphatases (CBPs) in the nM range with some selectivity. Fluorescence spectroscopic studies (including fluorescence anisotropy) were carried out to demonstrate that the complexes are not simply acting as vanadyl delivery vehicles but they interact with the proteins. Finally, we present preliminary fluorescence microscopy studies to demonstrate that the complexes are cell permeable and localise throughout the cytoplasm of NIH3T3 cells.

  13. Application of Protocols Devised to Study Bi(III) Complex Formation by Voltammetry: The Bi(III)-Picolinic Acid System.

    PubMed

    Billing, Caren; Cukrowski, Ignacy

    2016-12-22

    Bi(III) coordination chemistry has been largely neglected due to the difficulties faced when studying these systems even though Bi(III) is used in various medicinal applications. This study of the Bi(III)-picolinic acid system by voltammetry applies the rigorous methodologies already developed to enable the study of Bi(III) systems starting in very acidic solutions to prevent precipitation. This includes calibrating the glass electrode accurately at these low pHs, compensating for the diffusion junction potential below pH 2 and determining the reduction potential of uncomplexed Bi(III) which cannot be directly measured. The importance of including nitrate from the background electrolyte as a competing species is highlighted, especially for data acquired below pH ∼ 2. From analysis of the voltammetric data, it was not clear whether a ML3OH species formed in solution or whether it was a combination of ML4 and ML4OH. Information from crystal structures and electrospray ionization-mass spectrometry measurements was thus used to propose the most probable species model. The log β values determined were 7.77 ± 0.07 for ML, 13.89 ± 0.07 for ML2, 18.61 ± 0.01 for ML3, 22.7 ± 0.2 for ML4, and 31.4 ± 0.2 for ML4OH. Application of these methodologies thus opens the door to broaden our understanding of Bi(III) complexation.

  14. Synthesis, spectroscopic, DFT calculations and biological activity studies of ruthenium carbonyl complexes with 2-picolinic acid and a secondary ligand

    NASA Astrophysics Data System (ADS)

    Shohayeb, Shahera M.; Mohamed, Rania G.; Moustafa, H.; El-Medani, Samir M.

    2016-09-01

    Thermal reaction of [Ru3(CO)12] with 2-picolinic acid (Hpic) in the absence and presence of a secondary ligand (pyridine, Py, bipyridine, Bipy, or thiourea, Tu) was investigated. Four complexes with molecular formulae: [Ru(CO)3(Hpic)], 1, [Ru2(CO)5(Hpic)(Py)], 2, [Ru2(CO)5(Hpic)(Tu)], 3 and [Ru2(CO)4(Hpic)(Bipy)], 4, were isolated. All complexes were characterized based on elemental analyses, IR, 1H NMR, magnetic studies, mass spectrometry and thermal analysis. The ligand and its complexes have been screened for antibacterial activities. Density Functional Theory (DFT) calculations at the B3LYP/6-311G (d,p)_ level of theory have been carried out to investigate the equilibrium geometry of the ligands. The optimized geometry parameters of the complexes were evaluated using B3LYP method and LANL2DZ basis set. The extent of natural charge population (core, valence and rydberg), exact electronic configuration, total Lewis and total non-Lewis are estimated and discussed in terms of natural bond orbitals (NBO) analysis.

  15. Screening and structural elucidation of the zwitterionic cocrystal o-picolinic acid with p-nitro aniline

    NASA Astrophysics Data System (ADS)

    Mekala, R.; Jagdish, P.; Mathammal, R.; Sangeetha, K.

    2017-04-01

    The cocrystal was screened by solvent drop grinding method and the crystals were grown by slow evaporation method at ambient conditions. The cocrystal formation of o-picolinic acid with p-nitro aniline was initially analysed by powder X-ray diffraction. Further the structural properties of the grown crystal were confirmed by the single X-ray diffraction which indicates that the cocrystal were connected by the strong N+sbnd H-⋯O hydrogen bond interaction. The cell parameters of the grown crystal were a = 14.2144(5) Å, b = 5.7558(2) Å, c = 16.0539(6) Å. The functional groups were identified using Fourier transform infrared and Raman spectral analysis. The excitation and emission state of the sample was analysed by the UV-Visible and Fluorescence studies. The red emission was observed from the Fluorescence studies. NMR studies revealed the chemical shift of the cocrystal. Thermal stability and its melting behaviour were studied by TGA and DSC analytical techniques. Electrical behaviour was studied using the dielectric studies. The intermolecular charge transfer within the molecule were analysed using HOMO- LUMO plots.

  16. Removal of alpha-picoline, beta-picoline, and gamma-picoline from synthetic wastewater using low cost activated carbons derived from coconut shell fibers.

    PubMed

    Mohan, Dinesh; Singh, Kunwar P; Ghosh, Deblina

    2005-07-01

    In the present study the ability of activated carbons developed from coconut shell fibers to remove alpha-picoline, beta-picoline, and gamma-picoline from aqueous solution in the broad range of concentrations (1-100 mg/L) is investigated. The derived carbons are designated as FAC (activated carbon derived from coconut shell fibers without any treatment) and ATFAC (activated carbon derived from acid treated coconut shell fibers). Systematic equilibrium and kinetic adsorption studies at different pH, temperatures, particle size, and solid-to-liquid ratio were carried out to determine various parameters necessary to establish the fixed bed reactors. The Langmuir and Freundlich models were applied and the data are not fitted well by the Freundlich and Langmuir equations, but the Langmuir model has an edge over Freundlich model. The monolayer adsorption capacity (Q0) as calculated using Langmuir adsorption isotherm of the activated carbons viz., FAC and ATFAC is found to increase with an increase in temperature confirming the endothermic process. The ATFAC has a higher sorption capacity than FAC. Overall the adsorption of alpha-picoline, beta-picoline, and y-picoline on FAC and ATFAC follow the order FACalpha-picoline < ATFACalpha-picoline < FAC gamma-picoline < ATFACbeta-picoline < FACbeta picoline < ATFAC gamma-picoline. The adsorption of alpha-,beta-, and gamma-picoline followed the pseudosecond-order rate kinetics. On the basis of these studies, various parameters such as effective diffusion coefficients, activation energy, and entropy of activation were evaluated to establish the mechanisms. It was concluded that the adsorption occurred through particle diffusion at low temperatures viz., 10 degrees C and 25 degrees C (except alpha-picoline where it was film diffusion), while at 40 degrees C it occurred through film diffusion. Similarly at concentrations of 25 and 50 mg/L the adsorption was particle diffusion controlled (except for alpha-picoline where it was film

  17. Deficit, but Not Nondeficit, Schizophrenia Is Characterized by Mucosa-Associated Activation of the Tryptophan Catabolite (TRYCAT) Pathway with Highly Specific Increases in IgA Responses Directed to Picolinic, Xanthurenic, and Quinolinic Acid.

    PubMed

    Kanchanatawan, Buranee; Sirivichayakul, Sunee; Ruxrungtham, Kiat; Carvalho, André F; Geffard, Michel; Ormstad, Heidi; Anderson, George; Maes, Michael

    2017-02-08

    Evidence suggests that activation of the tryptophan catabolite (TRYCAT) pathway is involved in the pathophysiology of schizophrenia. However, no previous study examined whether TRYCAT pathway activation is associated with deficit schizophrenia. We measured IgA responses to TRYCATs, namely quinolinic acid, picolinic acid, kynurenic acid, xanthurenic acid, and anthranilic acid and 3-OH-kynurenine, in 40 healthy controls and in schizophrenic patients with (n = 40) and without (n = 40) deficit, defined according to the Schedule for the Deficit Syndrome (SDS). Primary deficit schizophrenia is accompanied by an activated TRYCAT pathway as compared to controls and nondeficit schizophrenia. Participants with deficit schizophrenia show increased IgA responses to xanthurenic acid, picolinic acid, and quinolinic acid and relatively lowered IgA responses to kynurenic and anthranilic acids, as compared to patients with nondeficit schizophrenia. Both schizophrenia subgroups show increased IgA responses to 3-OH-kynurenine as compared to controls. The IgA responses to noxious TRYCATs, namely xanthurenic acid, picolinic acid, quinolinic acid, and 3-OH-kynurenine, but not protective TRYCATS, namely anthranilic acid and kunyrenic acid, are significantly higher in deficit schizophrenia than in controls. The negative symptoms of schizophrenia are significantly and positively associated with increased IgA responses directed against picolinic acid and inversely with anthranilic acid, whereas no significant associations between positive symptoms and IgA responses to TRYCATs were found. In conclusion, primary deficit schizophrenia is characterized by TRYCAT pathway activation and differs from nondeficit schizophrenia by a highly specific TRYCAT pattern suggesting increased excitotoxicity, cytotoxicity, and neurotoxicity, as well as inflammation and oxidative stress. The specific alterations in IgA responses to TRYCATs provide further insight for the biological delineation of deficit

  18. Mutual Exclusion of Urea and Trimethylamine N-Oxide from Amino Acids in Mixed Solvent Environment.

    PubMed

    Ganguly, Pritam; Hajari, Timir; Shea, Joan-Emma; van der Vegt, Nico F A

    2015-02-19

    We study the solvation of amino acids in pure-osmolyte and mixed-osmolyte urea and trimethylamine N-oxide (TMAO) solutions using molecular dynamics simulations. Analysis of Kirkwood-Buff integrals between the solution components provides evidence that in the mixed osmolytic solution, both urea and TMAO are mutually excluded from the amino acid surface, accompanied by an increase in osmolyte-osmolyte aggregation. Similar observations are made in simulations of a model protein backbone, represented by triglycine, and suggest that TMAO stabilizes proteins under urea denaturation conditions by effectively removing urea from the protein surface. The effects of the mixed osmolytes on the solvation of the amino acids and the backbone are found to be highly nonlinear in terms of the effects of the individual osmolytes and independent of differences in the strength of the TMAO-water interactions, as observed with different TMAO force fields.

  19. Genomic and Functional Analyses of the 2-Aminophenol Catabolic Pathway and Partial Conversion of Its Substrate into Picolinic Acid in Burkholderia xenovorans LB400

    PubMed Central

    Agulló, Loreine; González, Myriam; Seeger, Michael

    2013-01-01

    2-aminophenol (2-AP) is a toxic nitrogen-containing aromatic pollutant. Burkholderia xenovorans LB400 possess an amn gene cluster that encodes the 2-AP catabolic pathway. In this report, the functionality of the 2-aminophenol pathway of B. xenovorans strain LB400 was analyzed. The amnRJBACDFEHG cluster located at chromosome 1 encodes the enzymes for the degradation of 2-aminophenol. The absence of habA and habB genes in LB400 genome correlates with its no growth on nitrobenzene. RT-PCR analyses in strain LB400 showed the co-expression of amnJB, amnBAC, amnACD, amnDFE and amnEHG genes, suggesting that the amn cluster is an operon. RT-qPCR showed that the amnB gene expression was highly induced by 2-AP, whereas a basal constitutive expression was observed in glucose, indicating that these amn genes are regulated. We propose that the predicted MarR-type transcriptional regulator encoded by the amnR gene acts as repressor of the amn gene cluster using a MarR-type regulatory binding sequence. This report showed that LB400 resting cells degrade completely 2-AP. The amn gene cluster from strain LB400 is highly identical to the amn gene cluster from P. knackmussi strain B13, which could not grow on 2-AP. However, we demonstrate that B. xenovorans LB400 is able to grow using 2-AP as sole nitrogen source and glucose as sole carbon source. An amnBA− mutant of strain LB400 was unable to grow with 2-AP as nitrogen source and glucose as carbon source and to degrade 2-AP. This study showed that during LB400 growth on 2-AP this substrate was partially converted into picolinic acid (PA), a well-known antibiotic. The addition of PA at lag or mid-exponential phase inhibited LB400 growth. The MIC of PA for strain LB400 is 2 mM. Overall, these results demonstrate that B. xenovorans strain LB400 posses a functional 2-AP catabolic central pathway, which could lead to the production of picolinic acid. PMID:24124510

  20. Significant enhancement of 11-Hydroxy-THC detection by formation of picolinic acid esters and application of liquid chromatography/multi stage mass spectrometry (LC-MS(3) ): Application to hair and oral fluid analysis.

    PubMed

    Thieme, Detlef; Sachs, Ulf; Sachs, Hans; Moore, Christine

    2015-07-01

    Formation of picolinic acid esters of hydroxylated drugs or their biotransformation products is a promising tool to improve their mass spectrometric ionization efficiency, alter their fragmentation behaviour and enhance sensitivity and specificity of their detection. The procedure was optimized and tested for the detection of cannabinoids, which proved to be most challenging when dealing with alternative specimens, for example hair and oral fluid. In particular, the detection of the THC metabolites hydroxyl-THC and carboxy-THC requires ultimate sensitivity because of their poor incorporation into hair or saliva. Both biotransformation products are widely accepted as incorporation markers to distinguish drug consumption from passive contamination. The derivatization procedure was carried out by adding a mixture of picolinic acid, 4-(dimethylamino)pyridine and 2-methyl-6-nitrobenzoic anhydride in tetrahydrofuran/triethylamine to the dry extraction residues. Resulting derivatives were found to be very stable and could be reconstituted in aqueous or organic buffers and subsequently analyzed by liquid chromatography-mass spectrometry (LC-MS). Owing to the complex consecutive fragmentation patterns, the application of multistage MS3 proved to be extremely useful for a sensitive identification of doubly picolinated hydroxy-THC in complex matrices. The detection limits - estimated by comparison of corresponding signal-to-noise ratios - increased by a factor of 100 following picolination. All other species examined, like cannabinol, THC, cannabidiol, and carboxy-THC, could also be derivatized exhibiting only moderate sensitivity improvements. The assay was systematically tested using hair samples and exemplarily applied to oral fluid. Concentrations of OH-THC identified in THC-positive hair samples ranged from 0.02 to 0.29pg/mg.

  1. Two-dimensional assembly of [Mn(III)₂Mn(II)₂] single-molecule magnets and [Cu(pic)₂] linking units (Hpic = picolinic acid).

    PubMed

    Jeon, Ie-Rang; Ababei, Rodica; Lecren, Lollita; Li, Yang-Guang; Wernsdorfer, Wolfgang; Roubeau, Olivier; Mathonière, Corine; Clérac, Rodolphe

    2010-05-28

    In an attempt to develop novel coordination networks of SMMs, a Cu(II) picolinate complex has been used to coordinate S(T) = 9 tetranuclear Mn-based SMMs resulting in an intriguing 2D framework exhibiting a magnet-like behavior at low temperature.

  2. Trimethylamine N-oxide impairs pyruvate and fatty acid oxidation in cardiac mitochondria.

    PubMed

    Makrecka-Kuka, Marina; Volska, Kristine; Antone, Unigunde; Vilskersts, Reinis; Grinberga, Solveiga; Bandere, Dace; Liepinsh, Edgars; Dambrova, Maija

    2017-02-05

    Increased plasma concentration of trimethylamine N-oxide (TMAO), a proatherogenic metabolite, has been linked to adverse cardiovascular outcomes; however, it remains unclear whether TMAO is a biomarker or whether it induces direct detrimental cardiovascular effects. Because altered cardiac energy metabolism and mitochondrial dysfunction play crucial roles in the development of cardiovascular diseases, we hypothesized that increased TMAO concentration may alter mitochondrial energy metabolism. The aim of the present study was to determine the effects of TMAO on cardiac mitochondrial energy metabolism. Acute exposure of cardiac fibers to TMAO decreased LEAK (substrate-dependent) and OXPHOS (oxidative phosphorylation-dependent) mitochondrial respiration with pyruvate and impaired substrate flux via pyruvate dehydrogenase. The administration of TMAO at a dose of 120mg/kg for 8 weeks increased TMAO concentration in plasma and cardiac tissues 22-23 times to about 15μM and 11nmol/g, respectively. Long-term TMAO administration decreased mitochondrial LEAK state respiration with pyruvate by 30% without affecting OXPHOS state respiration. However, no significant changes in mitochondrial reactive oxygen species production were observed after acute exposure of cardiac fibers to TMAO under physiological conditions. In addition, both long-term TMAO administration and acute exposure to TMAO decreased respiration with palmitoyl-CoA indicating impaired β-oxidation. Taken together, our results demonstrate that increased TMAO concentration impairs pyruvate and fatty acid oxidation in cardiac mitochondria. Thus, the accumulation of TMAO in cardiac tissues leads to disturbances in energy metabolism that can increase the severity of cardiovascular events.

  3. The effect of chromium picolinate on serum cholesterol and apolipoprotein fractions in human subjects.

    PubMed Central

    Press, R. I.; Geller, J.; Evans, G. W.

    1990-01-01

    Chromium has been implicated as a cofactor in the maintenance of normal lipid and carbohydrate metabolism. A deficiency of chromium results from diets low in biologically available chromium. Picolinic acid, a metabolite of tryptophan, forms stable complexes with transitional metal ions, which results in an improved bioavailability of the metal ion chromium. To determine whether or not chromium picolinate is effective in humans, 28 volunteer subjects were given either chromium tripicolinate (3.8 micromol [200 micrograms] chromium) or a placebo daily for 42 days in a double-blind crossover study. A 14-day period off capsules was used between treatments. Levels of total cholesterol, low-density lipoprotein (LDL) cholesterol, and apolipoprotein B, the principal protein of the LDL fraction, decreased significantly while the subjects were ingesting chromium picolinate. The concentration of apolipoprotein A-I, the principal protein of the high-density lipoprotein (HDL) fraction, increased substantially during treatment with chromium picolinate. The HDL-cholesterol level was elevated slightly but not significantly during ingestion of chromium picolinate. Only apolipoprotein B, of the variables measured, was altered significantly during supplementation with the placebo. These observations show that chromium picolinate is efficacious in lowering blood lipids in humans. PMID:2408233

  4. The reaction of [Fe(pic)3] with hydrogen peroxide: a UV-visible and EPR spectroscopic study (Hpic = picolinic acid).

    PubMed

    Jain, Sneh L; Bhattacharyya, Pravat

    2005-08-21

    The Gif family of catalysts, based on an iron salt and O2 or H2O2 in pyridine, allows the oxygenation of cyclic saturated hydrocarbons to ketones and alcohols under mild conditions. The reaction between [Fe(pic)3] and hydrogen peroxide in pyridine under GoAgg(III)(Fe(III)/Hpic catalyst) conditions was investigated by UV-visible spectrophotometry. Reactions were monitored at 430 and 520 nm over periods ranging from a few minutes to several hours at 20 degrees C. A number of kinetically stable intermediates were detected, and their relevance to the processes involved in the assembly of the active GoAgg(III) catalyst was determined by measuring the kinetics in the presence and absence of cyclohexane. EPR measurements at 110 K using hydrogen peroxide and t-BuOOH as oxidants were used to further probe these intermediates. Our results indicate that in wet pyridine [Fe(pic)3] undergoes reversible dissociation of one picolinate ligand, establishing an equilibrium with [Fe(pic)2(py)(OH)]. Addition of aqueous hydrogen peroxide rapidly generates the high-spin complex [Fe(pic)2(py)(eta1-OOH)] from the labilised hydroxy species. Subsequently the hydroperoxy species undergoes homolysis of the Fe-O bond, generating HOO. and [Fe(pic)2(py)2], the active oxygenation catalyst.

  5. Chromium picolinate supplementation for diabetes mellitus.

    PubMed

    Fox, G N; Sabovic, Z

    1998-01-01

    Chromium picolinate is a widely available nutritional supplement marketed for a plethora of afflictions. There is some evidence, including results from human studies, that it has a role in glucose homeostasis. We report the case of a 28-year-old woman with an 18-year history of type 1 diabetes mellitus whose glycosylated hemoglobin (Hb A1c) declined from 11.3% to 7.9% 3 months after initiation of chromium picolinate, 200 micrograms 3 times daily. Chromium picolinate continues to fall squarely within the scope of "alternative medicine," with both unproven benefits and unknown risks. It deserves closer scrutiny with additional prospective, randomized, double-blind, placebo-controlled trials to evaluate its efficacy in improving outcomes in patients with diabetes. A brief review of the literature was done to assist physicians who are being called upon to counsel and treat patients who are engaging in alternative therapies.

  6. Enantiomeric in vitro DNA binding, pBR322 DNA cleavage and molecular docking studies of chiral L- and D-ternary copper(II) complexes of histidine and picolinic acid.

    PubMed

    Parveen, Shazia; Arjmand, Farukh; Ahmad, Iqbal

    2014-01-05

    Novel chiral ternary Cu(II) and Ni(II) complexes of l/d-histidine and picolinic acid, 1 and 2(a and b) were synthesized and characterized by elemental analysis, molar conductance and spectroscopic data (IR, NMR, EPR, UV-vis). In vitro DNA binding profile of both Cu(II) and Ni(II) complexes have been investigated by UV-vis titrations, while fluorescence spectroscopy, circular dichroism and viscosity measurements were carried out for Cu(II) complexes 1(a and b). Both the enantiomers of 1 and 2(a and b) bind to CT DNA via electrostatic interactions and the intrinsic binding constant, Kb values for complexes 1 and 2(a and b) were found to be 5.6×10(4), 9.8×10(3), 8.2×10(3) and 6.7×10(3)M(-1), respectively suggesting greater binding propensity of l-form of Cu(II) complex 1a. The DNA cleavage activity of complexes 1(a and b), investigated by agarose gel electrophoresis suggested an oxidative pathway for DNA cleavage. Further, the molecular docking studies of complexes 1(a and b) were carried out with B-DNA revealing that the complexes bind to the adenine-thymine residues in the minor groove of the DNA. The resulting binding energies of docked metal complexes 1(a and b) were found to be -265.1 and -218.9KJmol(-1), respectively. Furthermore, enantiomeric complexes 1 and 2(a and b) were screened for in vitro antimicrobial activity.

  7. Thermally Reactive Phenylethynyl-Terminated Bis (benzylester) and Bis (amide) Monomers Based on Semi-Enzymatically Produced 6-Phenylethynyl Picolinic Acid

    DTIC Science & Technology

    2005-12-01

    electron-withdrawing properties of the pyridine moiety would increase the reactivity of PEPCA in a Diels – Alder reaction if PEPCA were to serve as a...valid OMB control number. 1. REPORT DATE DEC 2005 2. REPORT TYPE 3. DATES COVERED 00-00-2005 to 00-00-2005 4. TITLE AND SUBTITLE Thermally...addition funnel, a condenser and nitrogen inlet and outlet were added 6-bromopicolinic acid (Aldrich; 2.02 g, 10 mmol) and methanol (50 mL). Thionyl

  8. Tertiary amine N-oxides as bioreductive drugs: DACA N-oxide, nitracrine N-oxide and AQ4N.

    PubMed Central

    Wilson, W. R.; Denny, W. A.; Pullen, S. M.; Thompson, K. M.; Li, A. E.; Patterson, L. H.; Lee, H. H.

    1996-01-01

    Tertiary amine N-oxides of DNA intercalators with alkylamino sidechains are a new class of bioreductive drugs. N-oxidation masks the cationic charge of the amines, forming prodrugs with low DNA binding affinity and low toxicity which can be activated selectively by metabolic reduction under hypoxic conditions. This study compares three intercalator N-oxides (NC-NO, DACA-NO and AQ4N), which, respectively, give nitracrine (NC), DACA and AQ4 on reduction. In aerobic cell culture all three N-oxide were much less toxic than the corresponding amines, and showed large increases in cytotoxicity under hypoxia. The topoisomerase poisons DACA and AQ4 (and their N-oxides) were less active against non-cycling than cycling cells. However, only AQ4N was active against the mouse mammary tumour MDAH-MCa-4. This dialkylaminoanthraquinone-di-N-oxide has activity at least as great as the reference bioreductive drug RB 6145 against this tumour, both with and without radiation and when combined with the tumour blood flow inhibitor 5,6-dimethylxanthenone-4-acetic acid (DMXAA). It is suggested that the high in vivo activity of AQ4N relative to the other topoisomerase-targeted N-oxide, DACA-NO, may be in part due to release in hypoxic cells of an intracalator with sufficiently high DNA binding affinity that it is retained long enough to kill non-cycling cells when they eventually re-enter the cell cycle. PMID:8763844

  9. Quantum chemical calculation (electronic and topologic) and experimental (FT-IR, FT-Raman and UV) analysis of isonicotinic acid N-oxide

    NASA Astrophysics Data System (ADS)

    Karaca, Caglar; Atac, Ahmet; Karabacak, Mehmet

    2015-04-01

    In this work, the molecular conformation, vibrational and electronic analysis of isonicotinic acid N-oxide (iso-NANO) were presented in the ground state using experimental techniques (FT-IR, FT-Raman and UV) and density functional theory (DFT) employing B3LYP exchange correlation with the 6-311++G(d,p) basis set. The geometry optimization and energies associated possible two conformers (Rot-I and Rot-II) were computed. The vibrational spectra were calculated and fundamental vibrations were assigned on the basis of the total energy distribution (TED) of the vibrational modes, calculated with scaled quantum mechanics (SQM) method and PQS program. The obtained structures were analyzed with the Atoms in Molecules (AIMs) methodology. The computational results diagnose the most stable conformer of iso-NANO as the Rot-I form. Total density of state (TDOS) and partial density of state (PDOS) and also overlap population density of state (OPDOS) diagrams analysis for the most stable conformer (Rot-I) were calculated using the same method. Thermodynamic properties (heat capacity, entropy and enthalpy) of the title compound at different temperatures were calculated. As a result, the optimized geometry and calculated spectroscopic data show a good agreement with the experimental results.

  10. Quantum chemical calculation (electronic and topologic) and experimental (FT-IR, FT-Raman and UV) analysis of isonicotinic acid N-oxide.

    PubMed

    Karaca, Caglar; Atac, Ahmet; Karabacak, Mehmet

    2015-04-05

    In this work, the molecular conformation, vibrational and electronic analysis of isonicotinic acid N-oxide (iso-NANO) were presented in the ground state using experimental techniques (FT-IR, FT-Raman and UV) and density functional theory (DFT) employing B3LYP exchange correlation with the 6-311++G(d,p) basis set. The geometry optimization and energies associated possible two conformers (Rot-I and Rot-II) were computed. The vibrational spectra were calculated and fundamental vibrations were assigned on the basis of the total energy distribution (TED) of the vibrational modes, calculated with scaled quantum mechanics (SQM) method and PQS program. The obtained structures were analyzed with the Atoms in Molecules (AIMs) methodology. The computational results diagnose the most stable conformer of iso-NANO as the Rot-I form. Total density of state (TDOS) and partial density of state (PDOS) and also overlap population density of state (OPDOS) diagrams analysis for the most stable conformer (Rot-I) were calculated using the same method. Thermodynamic properties (heat capacity, entropy and enthalpy) of the title compound at different temperatures were calculated. As a result, the optimized geometry and calculated spectroscopic data show a good agreement with the experimental results.

  11. A quantitative comparison of spectroscopic and energy data, in solution, of NHO and OHO hydrogen bonds and gas-phase proton affinities: complexes of pyridines and pyridine N-oxides with acetic acids

    NASA Astrophysics Data System (ADS)

    Dega-Szafran, Zofia; Hrynio, Andrzej; Szafran, Miroslaw

    1990-11-01

    The correlations between the centre of gravity (ν H) of the broad IR vibrations, chemical shifts (δ H) of hydrogen-bonded protons and enthalpies of hydroben bonds (-Δ H) of two series of complexes (pyridines and pyridine N-oxides) with trifluoroacetic, dichloroacetic, chloroacetic and acetic acids, and the difference between the gas-phase proton affinity of bases ( PA(B)) and that of conjugate bases ( PA(A -)) were investigated. Complexes of pyridines with all these acids can be treated as one category and complexes of pyridine N-oxides as another. On the other hand, correlations of ν H and δ H with aqueous p Ka values consist of separate lines for each acid. The PA(A -) and PA(B) values provide an excellent basicity scale for hydrogen bonds in solvents of low and medium polarity.

  12. Two series of reactant's ratio-dependent lanthanide organic frameworks derived from nicotinic acid N-oxide and oxalate: synthesis, crystal structures and luminescence properties.

    PubMed

    Yu, Yanyan; Zhang, Lijuan; Zhou, Yunshan; Zuhra, Zareen

    2015-03-14

    Two series of lanthanide(III)–organic frameworks with the molecular formula [Ln2(NNO)2(OX)2(H2O)4]n (Ln = Eu 1, Tb 2, Sm 3, Dy 4, Gd 5) and [Ln2(NNO)4(OX)(H2O)2]n (Ln = Eu 6, Tb 7, Sm 8, Dy 9, Gd 10) were synthesized successfully under the same hydrothermal conditions with nicotinic N-oxide (HNNO) and oxalic acid (H2OX) as the mixed ligands merely through varying the molar ratio of the reactants. The compounds were characterized by IR, elemental analysis, UV, TG-DTA and powder X-ray diffraction (XRD). X-ray single-crystal diffraction analyses of compounds 1 and 7 selected as representatives and powder XRD analysis of the compounds revealed that both the series of compounds feature three-dimensional (3-D) open frameworks, and crystallize in the triclinic P1 space group while with different unit cell parameters. In compound 1, pairs of Eu(3+) ions and pairs of NNO(−) ligands connect with each other alternately to form a 1-D infinite Eu-NNO double chain, the adjacent 1-D double-chains are then joined together through OX(2−) ligands leading to a 2D layer, the 2-D layers are further ‘pillared’ by OX(2−) ligands resulting in a 3-D framework. In compound 7, the 1-D Tb-NNO infinite chain and its 2-D layer are formed in an almost similar fashion to that in compound 1. The difference between the structures of the two compounds 1 and 7 is that the adjacent 2-D layers in compound 7 are further connected by NNO(−) ligands resulting in a 3-D framework. The photoluminescence properties and energy transfer mechanism of the compounds were studied systematically. The energy level of the lowest triplet states of the HNNO ligand (23148 cm(−1)) was determined based on the phosphorescence spectrum of compound 5 at 77 K. The (5)D0 (Eu(3+)) and (5)D4 (Tb(3+)) emission lifetimes are 0.46 ms, 0.83 ms, 0.69 ms and 0.89 ms and overall quantum yields are 1.03%, 3.29%, 2.58% and 3.78% for the compounds 1, 2, 6 and 7, respectively.

  13. The remote-oxyfunctionalization of unactivated carbons in (5 beta)-3-oxobile acids by 2,6-dichloropyridine N-oxide catalyzed by ruthenium-porphyrin and HBr: a direct lactonization at C-20.

    PubMed

    Ogawa, Shoujiro; Iida, Takashi; Goto, Takaaki; Mano, Nariyasu; Goto, Junichi; Nambara, Toshio

    2004-04-07

    Remote-oxyfunctionalization induced by 2,6-dichloropyridine N-oxide (DCP N-oxide) as an oxygen donor and a (5,10,15,20-tetramesitylporphyrinate) ruthenium(II) carbonyl complex (Ru-porphyrin) and HBr as catalysts was examined for a series of methyl ester-peracetylated derivatives of (5 beta)-3-oxobile acids. Using the DCP-N-oxide/Ru-porphyrin/HBr system, 5 beta-hydroxylation predominated for the substrates having a 12-acetoxyl substituent due to steric hindrance, but the presence of a 7-acetoxyl substituent decreased the reactivity of the 5 beta-position allowing for the competitive (20S)-20-oxyfunctionalization, subject to electronic constraints. A variety of novel 5 beta-hydroxylation and (20S)-24,20-gamma-lactonization products, as well as their double-oxyfunctionalization and dehydration products, were obtained in one-step. The alkaline hydrolysis of the gamma-lactones gave the corresponding stereoselective (20S)-20-hydroxy-carboxylic acids.

  14. Social isomers of picolines in a small space.

    PubMed

    Ajami, Dariush; Theodorakopoulos, Giannoula; Petsalakis, Ioannis D; Rebek, Julius

    2013-12-09

    Encapsulation complexes permit the observation of molecules under conditions of limited motion. Inside capsules, molecular encounters are prolonged, prearranged, and protected from the medium, in contrast to the short-lived and random encounters that occur in bulk solution. Herein, the interaction of α-, β-, and γ-picolines in a cylindrical capsule is described. Two picolines were taken up, and NMR spectra indicated dynamic combinations of various social isomers. The stabilities of the complexes are interpreted through computational methods. The shape of the space in the capsule allowed the alignment of molecules and revealed delicate, atom-to-atom interactions and attractive forces that elude observation in dilute solution. These weak forces were amplified in the isolated small space of the capsule.

  15. Oxidative demethylation of 2-picolines on vanadium oxide catalysts

    SciTech Connect

    Suvorov, B.V.; Glubokovskikh, L.K.; Demin, V.V.; Kan, I.I.

    1988-07-10

    One of the known methods for the preparation of pyridine is based on the dealkylation of alkylpyridines in the presence of vanadium-containing catalysts, molecular oxygen and steam. By using the oxidative demethylation of 2-picoline in the presence of steam on a fused vanadium(V) oxide, pyridine can be obtained in a yield of up to 88% of theory. To lower the consumption of vanadium(V) oxide and increase the thermostability of the catalyst, they studied the possible use of V/sub 2/O/sub 5/ catalysts on various carriers (diatomite, silica gel, porcelain balls), including the industrially produced brand SVD and SVS catalysts. The SVS brand catalyst has a satisfactory activity and selectivity in the oxidation demethylation of 2-picoline into pyridine. Under optimal conditions, pyridine is formed on this catalyst in a yield of 88% of the theoretical.

  16. 4,4',4"-trimethyl-2,2':6',2"-terpyridine by oxidative coupling of 4-picoline.

    PubMed

    Robo, Michael T; Prinsell, Michael R; Weix, Daniel J

    2014-11-07

    Alkylated terpyridine ligands are an increasingly important component of catalysis and dyes but are costly because their synthesis is challenging and often low-yielding. We report an improved method for the Pd/C-catalyzed dehydrogenative coupling of 4-picoline to form the bi- and terpyridine. The addition of MnO2 improves the yield of the reaction, making the reaction useful on a large scale (up to 200 mmol). The use of Pd(OAc)2 or Pd/C/pivalic acid leads to the selective formation of bipyridine.

  17. Asymmetric allylation of α-ketoester-derived N-benzoylhydrazones promoted by chiral sulfoxides/N-oxides Lewis bases: highly enantioselective synthesis of quaternary α-substituted α-allyl-α-amino acids.

    PubMed

    Reyes-Rangel, Gloria; Bandala, Yamir; García-Flores, Fred; Juaristi, Eusebio

    2013-09-01

    Chiral sulfoxides/N-oxides (R)-1 and (R,R)-2 are effective chiral promoters in the enantioselective allylation of α-keto ester N-benzoylhydrazone derivatives 3a-g to generate the corresponding N-benzoylhydrazine derivatives 4a-g, with enantiomeric excesses as high as 98%. Representative hydrazine derivatives 4a-b were subsequently treated with SmI2, and the resulting amino esters 5a-b with LiOH to obtain quaternary α-substituted α-allyl α-amino acids 6a-b, whose absolute configuration was assigned as (S), with fundament on chemical correlation and electronic circular dichroism (ECD) data.

  18. 40 CFR 721.10718 - Substituted picolinic acid (generic).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ...) TOXIC SUBSTANCES CONTROL ACT SIGNIFICANT NEW USES OF CHEMICAL SUBSTANCES Significant New Uses for... than as a pesticide intermediate. (ii) (b) Specific requirements. The provisions of subpart A of...

  19. Insulin sensitising action of chromium picolinate in various experimental models of diabetes mellitus.

    PubMed

    Shindea, Urmila A; Sharma, Geeta; Xu, Yan J; Dhalla, Naranjan S; Goyal, Ramesh K

    2004-01-01

    Although chromium is an essential element for carbohydrate and lipid metabolism, its effects in diabetic patients are still debated. We have studied the effect of 6 week treatment with chromium picolinate (8 microg/ml in drinking water) in streptozotocin (STZ)-induced type 1 and type 2 diabetic rat models. The mechanism of anti-diabetic action of chromium picolinate was studied using C2C12 myoblasts and 3T3-L1 adipocytes. Chromium picolinate significantly decreased the area under the curve over 120 min for glucose of both STZ-induced type 1 (40mg/kg, i.v. in adult rats) and type 2 (90 mg/kg, i.p. in 2 day old rat neonates) diabetic rats without any significant change in area under the curve over 120 min for insulin as compared to controls. The composite insulin sensitivity index and insulin sensitivity index (KITT) values of both type 1 and type 2 diabetic rats were increased significantly by chromium picolinate. Treatment with chromium picolinate produced a significant decrease in elevated cholesterol and triglyceride levels in both types of diabetic rats. In 3T3-L1 adipocytes, chromium picolinate (0-10 micromol) per se did not produce any effect, however, when co-incubated with insulin it significantly increased the intracellular triglyceride synthesis (EC50 = 363.7nmol/1). Similarly in C2C12 myoblasts, chromium picolinate alone did not produce any effect, however, it significantly increased insulin-induced transport of 14C-glucose. In conclusion, chromium picolinate significantly improves deranged carbohydrate and lipid metabolism of experimental chemically induced diabetes in rats. The mechanism of in vivo anti-diabetic action appears to be peripheral (skeletal muscle and adipose tissue) insulin enhancing action of chromium.

  20. Humoral and cellular immunity in chromium picolinate-supplemented lambs.

    PubMed

    Dallago, B S L; McManus, C M; Caldeira, D F; Campeche, A; Burtet, R T; Paim, T P; Gomes, E F; Branquinho, R P; Braz, S V; Louvandini, H

    2013-08-01

    The effects of oral supplementation of chromium picolinate (CrPic) on humoral and cellular immunity in sheep were investigated. Twenty-four male lambs divided into four treatments and received different dosages of CrPic: placebo (0), 0.250, 0.375, and 0.500 mg of chromium/animal/day during 84 days. The base ration was Panicum maximum cv Massai hay and concentrate. Blood samples were collected fortnightly for total and differential leukocyte counts. On days 28 and 56, the lambs were challenged with chicken ovalbumin I.M. Serum samples were collected on days 46 and 74 and subjected to an indirect enzyme-linked immunosorbent assay to measure IgG anti-ovalbumin. The cell-mediated immune response was determined by a delay-type hypersensitivity test using phytohemagglutinin. CrPic did not significantly affect humoral immunity in lambs but there was a negative effect on cellular immunity (P < 0.05) as Cr supplementation increased. Therefore, the level of Cr supplementation for lambs must be better studied to address its effect on stressed animals or the possible toxic effects of Cr on the animal itself or its immune system.

  1. Synthesis, crystal structure, spectroscopic characterization and nonlinear optical properties of manganese (II) complex of picolinate: A combined experimental and computational study

    NASA Astrophysics Data System (ADS)

    Tamer, Ömer; Avcı, Davut; Atalay, Yusuf; Çoşut, Bünyemin; Zorlu, Yunus; Erkovan, Mustafa; Yerli, Yusuf

    2016-02-01

    A novel manganese (II) complex with picolinic acid (pyridine 2-carboxylic acid, Hpic), namely, [Mn(pic)2(H2O)2] was prepared and its crystal structure was fully characterized by using single crystal X-ray diffraction. Picolinate (pic) ligands were coordinated to the central manganese(II) ion as bidentate N,O-donors through the nitrogen atoms of pyridine rings and the oxygen atoms of carboxylate groups forming five-membered chelate rings. The spectroscopic characterization of Mn(II) complex was performed by the applications of FT-IR, Raman, UV-vis and EPR techniques. In order to support these studies, density functional theory (DFT) calculations were carried out by using B3LYP level. IR and Raman spectra were simulated at B3LYP level, and obtained results indicated that DFT calculations generally give compatible results to the experimental ones. The electronic structure of the Mn(II) complex was predicted using time dependent DFT (TD-DFT) method with polarizable continuum model (PCM). Molecular stability, hyperconjugative interactions, intramolecular charge transfer (ICT) and bond strength were investigated by applying natural bond orbital (NBO) analysis. Nonlinear optical properties of Mn(II) complex were investigated by the determining of molecular polarizability (α) and hyperpolarizability (β) parameters.

  2. Organometallic osmium(II) arene anticancer complexes containing picolinate derivatives.

    PubMed

    van Rijt, Sabine H; Peacock, Anna F A; Johnstone, Russell D L; Parsons, Simon; Sadler, Peter J

    2009-02-16

    Chlorido osmium(II) arene [(eta(6)-biphenyl)Os(II)(X-pico)Cl] complexes containing X = Br (1), OH (2), and Me (3) as ortho, or X = Cl (4), CO(2)H (5), and Me (6) as para substituents on the picolinate (pico) ring have been synthesized and characterized. The X-ray crystal structures of 1 and 6 show typical "piano-stool" geometry with intermolecular pi-pi stacking of the biphenyl outer rings of 6. At 288 K the hydrolysis rates follow the order 2 > 6 > 4 > 3 > 5 > 1 with half-lives ranging from minutes to 4.4 h illustrating the influence of both electronic and steric effects of the substituents. The pK(a) values of the aqua adducts 3A, 4A, 5A, and 6A were all in the range of 6.3-6.6. The para-substituted pico complexes 4-6 readily formed adducts with both 9-ethyl guanine (9EtG) and 9-ethyl adenine (9EtA), but these were less favored for the ortho-substituted complexes 1 and 3 showing little reaction with 9EtG and 9EtA, respectively. Density-functional theory calculations confirmed the observed preferences for nucleobase binding for complex 1. In cytotoxicity assays with A2780, cisplatin-resistant A2780cis human ovarian, A549 human lung, and HCT116 colon cancer cells, only complexes 4 (p-Cl) and 6 (p-Me) exhibited significant activity (IC(50) values < 25 microM). Both of these complexes were as active as cisplatin in A2780 (ovarian) and HCT116 (colon) cell lines, and even overcome cisplatin resistance in the A2780cis (ovarian) cell line. The inactivity of 5 is attributed to the negative charge on its para carboxylate substituent. These data illustrate how the chemical reactivity and cancer cell cytotoxicity of osmium arene complexes can be controlled and "fine-tuned" by the use of steric and electronic effects of substituents on a chelating ligand to give osmium(II) arene complexes which are as active as cisplatin but have a different mechanism of action.

  3. Bis(oxazoline) Lewis acid catalyzed aldol reactions of pyridine N-oxide aldehydes--synthesis of optically active 2-(1-hydroxyalkyl)pyridine derivatives: development, scope, and total synthesis of an indolizine alkaloid.

    PubMed

    Landa, Aitor; Minkkilä, Anna; Blay, Gonzalo; Jørgensen, Karl Anker

    2006-04-24

    A new, short, and simplified procedure for the synthesis of optically active pyridine derivatives from pro-chiral pyridine-N-oxides is presented. The catalytic and asymmetric Mukaiyama aldol reaction between ketene silyl acetals and 1-oxypyridine-2-carbaldehyde derivatives catalyzed by chiral copper(II)-bis(oxazoline) complexes gave optically active 2-(hydroxyalkyl)- and 2-(anti-1,2-dihydroxyalkyl)pyridine derivatives in good yields and diastereoselectivities, and in excellent enantioselectivities-up to 99 % enantiomeric excess. As a synthetic application of the developed method, a full account for the asymmetric total synthesis of a nonnatural indolizine alkaloid is provided.

  4. Stable Mn(2+), Cu(2+) and Ln(3+) complexes with cyclen-based ligands functionalized with picolinate pendant arms.

    PubMed

    Rodríguez-Rodríguez, Aurora; Garda, Zoltán; Ruscsák, Erika; Esteban-Gómez, David; de Blas, Andrés; Rodríguez-Blas, Teresa; Lima, Luís M P; Beyler, Maryline; Tripier, Raphaël; Tircsó, Gyula; Platas-Iglesias, Carlos

    2015-03-21

    In this study we present the results of the equilibrium, dissociation kinetics, DFT and X-ray crystallographic studies performed on the complexes of metal ions of biomedical importance (Mn(2+), Cu(2+) and Gd(3+)) formed with octadentate ligands based on a cyclen platform incorporating two picolinate pendant arms (dodpa(2-) and Medodpa(2-)). The stability constants of the complexes were accessed by multiple methods (pH-potentiometry, direct and competition UV-vis spectrophotometry and (1)H-relaxometry). The stability constants of the complexes formed with dodpa(2-) and Medodpa(2-) do not differ significantly (e.g. log K[Mn(dodpa)] = 17.40 vs. log K[Mn(Medodpa)] = 17.46, log K[Cu(dodpa)] = 24.34-25.17 vs. log K[Cu(Medodpa)] = 24.74 and log K[Gd(dodpa)](+) = 17.27 vs. log K[Gd(Medodpa)](+) = 17.59), which indicates that the steric hindrance brought by the methyl groups has no significant effect on the stability of the complexes. The stability constants of the Mn(2+) complexes formed with the cyclen dipicolinates were found to be ca. 3 log K units higher than those determined for the complex of the cyclen monopicolinate (dompa(-)), which indicates that the second picolinate moiety attached to the backbone of the macrocycle is very likely coordinated to the Mn(2+) ion. However, the stability of the [Cu(dodpa)] and [Cu(Medodpa)] complexes agrees well with the stability constant of [Cu(dompa)](+), in line with the hexadentate coordination around the metal ion observed in the X-ray structure of [Cu(Medodpa)]. The [Gd(dodpa)](+) and [Gd(Medodpa)](+) complexes display a fairly high kinetic inertness, as the rate constants of acid catalysed dissociation (k1 = 2.5(4) × 10(-3) and 8.3(4) × 10(-4) M(-1) s(-1) for [Gd(dodpa)](+) and [Gd(Medodpa)](+), respectively) are smaller than the value reported for [Gd(do3a)] (k1 = 2.5 × 10(-2) M(-1) s(-1)). The [Mn(dodpa)] complex was found to be more inert than [Mn(Medodpa)]. The results of the diffusion-ordered NMR

  5. Regioselective introduction of heteroatoms at the C-8 position of quinoline N-oxides: remote C-H activation using N-oxide as a stepping stone.

    PubMed

    Hwang, Heejun; Kim, Jinwoo; Jeong, Jisu; Chang, Sukbok

    2014-07-30

    Reported herein is the metal-catalyzed regioselective C-H functionalization of quinoline N-oxides at the 8-position: direct iodination and amidation were developed using rhodium and iridium catalytic systems, respectively. Mechanistic study of the amidation revealed that the unique regioselectivity is achieved through the smooth formation of N-oxide-chelated iridacycle and that an acid additive plays a key role in the rate-determining protodemetalation step. While this approach of remote C-H activation using N-oxide as a directing group could readily be applied to a wide range of heterocyclic substrates under mild conditions with high functional group tolerance, an efficient synthesis of zinquin ester (a fluorescent zinc indicator) was demonstrated.

  6. The methyl group as a source of structural diversity in heterocyclic chemistry: side chain functionalization of picolines and related heterocycles.

    PubMed

    Mamane, Victor; Aubert, Emmanuel; Fort, Yves

    2007-09-14

    The reaction of 2-picoline at the methyl group with NDA and KDA followed by dimethyldisulfide trapping furnished, respectively, dithioacetals and trithioortho esters with high selectivity. The method was successfully applied to other methyl-substituted pyridines, quinolines, and pyrazines. Dithioketals were prepared by a one-pot procedure involving the reaction of metalated 2-picoline with 2 equiv of dimethyldisulfide followed by in situ trapping with a second electrophile. All of the generated thio-substituted compounds were efficiently transformed in presence of mercury salts or under oxidizing conditions to other functional groups comprising aldehydes, ketones, ketals, thiol esters, orthoesters, and esters.

  7. Effects of dietary supplementation of organic chromium (picolinate) on physical and biochemical characteristics of semen and carcass traits of male turkeys.

    PubMed

    Biswas, Avishek; Divya, Sharma; Mandal, A B; Majumdar, S; Singh, Ram

    2014-12-30

    This experiment investigated the effect of dietary chromium (Cr as picolinate) on physical and biochemical characteristics of semen and carcass traits of adult male turkey. Seventy-two (72) male turkeys (16 weeks old) were randomly distributed into four dietary treatment groups (4×3×6) for a period of 24 weeks. Three experimental diets were supplemented with 250, 500 and 750μg Cr/kg (T2, T3 and T4 respectively) in basal diet (T1 considered as control). Semen physical characteristics viz. sperm concentration, progressive motility, live and dead count of spermatozoa and fertility differed significantly (P<0.05). Sperm concentration, progressive motility and fertility were higher and dead count was lower in T4 (750μg) group than control (T1) or other dietary treatments (T2 or T3) group. Semen biochemical parameters like creatinine, acid phosphatase (ACP) and alkaline phosphatase (ALP) concentration did not differ significantly among the dietary treatment groups, whereas, total protein, glucose, malondialdehyde (MAD) and cholesterol concentration differed significantly (P<0.05) amongst the treatment groups. Protein and MAD were higher while glucose and cholesterol concentrations were lower in T3 and T4 group than control or T1 group. The shrinkage loss, eviscerated yield, relative weight (as percent of body weight) of breast, thigh and liver improved on supplementation of Cr leading to significantly higher in T4 group in comparison to control. From this study, it could be concluded that supplementation of chromium as chromium picolinate, at 750μg/kg level in diet was beneficial for improving physical characteristics of semen, carcass yield and breast yield of adult male turkeys. However, Cr levels of 500 or 750μg/kg in diet were beneficial for semen biochemical parameters of adult male turkeys.

  8. Phytotoxicity of fusaric acid and analogues to cotton

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We developed a bioassay to test the phytotoxicity of chemicals to cotton and used it to determine the relative toxicity of fusaric acid (3-butylpicolinic acid), picolinic acid, and related analogs. In contrast to previous studies, we found the carboxylic acid group is essential for phytotoxicity. ...

  9. Metachelins, mannosylated and N-oxidized coprogen-type siderophores from Metarhizium robertsii.

    PubMed

    Krasnoff, Stuart B; Keresztes, Ivan; Donzelli, Bruno G G; Gibson, Donna M

    2014-07-25

    Under iron-depleted culture conditions, the entomopathogenic fungus Metarhizium robertsii (Bischoff, Humber, and Rehner) (= M. anisopliae) produces a complex of extracellular siderophores including novel O-glycosylated and N-oxidized coprogen-type compounds as well as the known fungal siderophores N(α)-dimethylcoprogen (NADC) and dimerumic acid (DA). Metachelin A (1), the most abundant component in the M. robertsii siderophore mixture, was characterized as a 1094 Da analogue of NADC that is O-glycosylated by β-mannose at both terminal hydroxyl groups and N-oxidized at the dimethylated α-nitrogen. The mixture also contained a 1078 Da analogue, metachelin B (2), which lacks the N-oxide modification. Also characterized were the aglycone of 1, i.e., the N-oxide of NADC (3), and the monomannoside of DA (6). N-Oxide and O-glycosyl substituents are unprecedented among microbial siderophores. At high ESIMS source energy and at room temperature in DMSO, 1 underwent Cope elimination, resulting in loss of the N(α)-dimethyl group and dehydration of the α-β bond. High-resolution ESIMS data confirmed that all tri- and dihydroxamate siderophores (1-6) complex with trivalent Fe, Al, and Ga. In a chrome azurol S assay, all of the M. robertsii siderophores showed iron-binding activity roughly equivalent to that of desferrioxamine B.

  10. Developing the family of picolinate ligands for Mn(2+) complexation.

    PubMed

    Forgács, Attila; Pujales-Paradela, Rosa; Regueiro-Figueroa, Martín; Valencia, Laura; Esteban-Gómez, David; Botta, Mauro; Platas-Iglesias, Carlos

    2017-01-31

    We have reported here a series of ligands containing pentadentate 6,6'-(azanediylbis(methylene))dipicolinic acid units that differ in the substituent present at the amine nitrogen atom (acetate: H3DPAAA; phenyl: H2DPAPhA; dodecyl: H2DPAC12A; 4-hexylphenyl: H2DPAC6PhA). The protonation constants of the hexadentate DPAAA(3-) and pentadentate DPAPhA(2-) ligands and the stability constants of their Mn(2+) complexes were determined using pH-potentiometry (25 °C, 0.15 M NaCl). The mono-hydrated [Mn(DPAAA)](-) complex (log KMnL = 13.19(5)) was found to be considerably more stable than the bis-hydrated [Mn(DPAPhA)] analogue (log KMnL = 9.55(1)). A detailed (1)H and (17)O NMR relaxometric study was carried out to determine the parameters that govern the proton relaxivities of these complexes. The [Mn(DPAC12A)] complex, which contains a dodecyl lipophilic chain, forms micelles in solution characterized by a critical micellar concentration (cmc) of 96(9) μM. The lipophilic [Mn(DPAC6PhA)] and [Mn(DPAC12A)] derivatives form rather strong adducts with Human Serum Albumin (HSA) with association constants of 7.1 ± 0.1 × 10(3) and 1.3 ± 0.4 × 10(5) M(-1), respectively. The X-ray structure of the complex {K(H2O)4}{[Mn(DPAAA)(H2O)]}2 shows that the Mn(2+) ion in [Mn(DPAAA)](-) is coordinated to the six donor atoms of the ligand, a coordinated water molecule completing the pentagonal bipyramidal coordination environment.

  11. Gastrointestinal function in chronic radiation enteritis--effects of loperamide-N-oxide.

    PubMed Central

    Yeoh, E K; Horowitz, M; Russo, A; Muecke, T; Robb, T; Chatterton, B E

    1993-01-01

    The effects of loperamide-N-oxide, a new peripheral opiate agonist precursor, on gastrointestinal function were evaluated in 18 patients with diarrhoea caused by chronic radiation enteritis. Each patient was given, in double-blind randomised order, loperamide-N-oxide (3 mg orally twice daily) and placebo for 14 days, separated by a washout period of 14 days. Gastrointestinal symptoms; absorption of bile acid, vitamin B12, lactose, and fat; gastric emptying; small intestinal and whole gut transit; and intestinal permeability were measured during placebo and loperamide-N-oxide phases. Data were compared with those obtained in 18 normal subjects. In the patients, in addition to an increased frequency of bowel actions (p < 0.001), there was reduced bile acid absorption, (p < 0.001) a higher prevalence of lactose malabsorption (p < 0.05) associated with a reduced dietary intake of dairy products (p < 0.02), and faster small intestinal (p < 0.001) and whole gut transit (p < 0.05) when compared with the normal subjects. There was no significant difference in gastric emptying between the two groups. Treatment with loperamide-N-oxide was associated with a reduced frequency of bowel actions (p < 0.001), slower small intestinal (p < 0.001), and total gut transit (p < 0.01), more rapid gastric emptying (p < 0.01), improved absorption of bile acid (p < 0.01), and increased permeability to 51Cr EDTA (p < 0.01). These observations indicate that: (1) diarrhoea caused by chronic radiation enteritis is associated with more rapid intestinal transit and a high prevalence of bile acid and lactose malabsorption, and (2) loperamide-N-oxide slows small intestinal transit, increases bile acid absorption, and is effective in the treatment of diarrhoea associated with chronic radiation enteritis. PMID:8491393

  12. Reduction of Amine N-Oxides by Diboron Reagents

    PubMed Central

    Kokatla, Hari Prasad; Thomson, Paul F.; Bae, Suyeal; Doddi, Venkata Ramana; Lakshman, Mahesh K.

    2011-01-01

    Facile reduction of alkylamino-, anilino-, and pyridyl-N-oxides can be achieved via the use of diboron reagents, predominantly bis(pinacolato)- and in some cases bis(catecholato)diboron [(pinB)2 and (catB)2, respectively]. Reductions occur upon simply mixing the amine N-oxide and the diboron reagent in a suitable solvent, at a suitable temperature. Extremely fast reductions of alkylamino- and anilino-N-oxides occur, whereas pyridyl-N-oxides undergo slower reduction. The reaction is tolerant of a variety of functionalities such as hydroxyl, thiol, and cyano groups, as well as halogens. Notably, a sensitive nucleoside N-oxide has also been reduced efficiently. The different rates with which alkylamino- and pyridyl-N-oxides are reduced has been used to perform stepwise reduction of the N,N’-dioxide of (S)-(–)-nicotine. Because it was observed that (pinB)2 was unaffected by the water of hydration in amine oxides, the feasibility of using water as solvent was evaluated. These reactions also proceeded exceptionally well, giving high product yields. In constrast to the reactions with (pinB)2, triethylborane reduced alkylamino-N-oxides, but pyridine N-oxide did not undergo efficient reduction even at elevated temperature. Finally, the mechanism of the reductive process by (pinB)2 has been probed by 1H and 11B NMR. PMID:21812467

  13. Methyl rotor quantum states and the effect of chemical environment in organic crystals: γ -picoline and toluene

    NASA Astrophysics Data System (ADS)

    Khazaei, Somayeh; Sebastiani, Daniel

    2016-12-01

    Using a set of first-principles calculations, we have studied the methyl tunnel splitting for molecular crystals of γ-picoline and toluene. The effective rotational potential energy surface of the probe methyl rotor along the tunneling path is evaluated using first-principles electronic structure calculations combined with the nudged elastic band method. The tunnel splitting is calculated by an explicit diagonalization of the one-dimensional time-independent Hamiltonian matrix. The effects of chemical environment and rotor-rotor coupling on the rotational energy barriers were investigated. It is found that more dense packing of the molecules in toluene compared to that in γ-picoline gives rise to a larger rotational barrier which in turn yields a considerably smaller tunnel splitting. Moreover, it turned out that coupled motion of the face-to-face methyl groups in γ-picoline has a significant effect on the reduction of the rotational barrier. Our results are in good agreement with the experimentally observed tunnel splitting.

  14. An analytical method for the measurement of acid metabolites of tryptophan-NAD pathway and related acids in urine.

    PubMed

    Liao, Xiangjun; Zhu, Jiping; Rubab, Mamoona; Feng, Yong-Lai; Poon, Raymond

    2010-04-15

    An analytical method has been developed for the measurements of five urinary acids namely, quinolinic acid, picolinic acid, nicotinic acid, 2-pyridylacetic acid and 3-pyridylacetic acid. The high performance liquid chromatograph-electrospray ionization mass spectrometry was operated in positive polarity under selected ion monitoring mode, with a column flow rate of 0.2 ml/min and an injection volume of 20 microl. The method used isotope-labelled picolinic acid (PA-d(4)) and nicotinic acid (NA-d(4)) as internal standards for the quantification. The sample preparation involved parallel use of two different types of mixed-mode solid phase extraction cartridges (Strata-X-AW for the extraction of quinolinic acid, and Strata-X-C for the remaining acids). Quantitative analysis of five target acids in several human and rat urine samples showed that the levels of acids were relatively uniform among rats while larger variations were observed for human samples.

  15. Simultaneous analysis of Cr(III), Cr(VI), and chromium picolinate in foods using capillary electrophoresis-inductively coupled plasma mass spectrometry.

    PubMed

    Chen, YiQuan; Chen, JinFa; Xi, Zhiming; Yang, Guidi; Wu, Zujian; Li, JianRong; Fu, FengFu

    2015-05-01

    We herein reported a method for the simultaneous detection of trace Cr(VI), Cr(III), and chromium(III) picolinate (CrPic) in foods using CE-ICP-MS together with ultrasonic-assisted extraction. The Cr(III) (Cr(3+) ) was chelated with trans-1,2-diaminocyclohexane-N,N,N´,N´-tetraacetic acid (DCTA) to form a single charged Cr-DCTA(-) complex. Then, Cr(VI) (CrO4 (2-) ), Cr-DCTA(-) , and CrPic were separated by CE within 8 min under a separation voltage of -13 KV followed by their monitoring with ICP mass spectrometer (ICP-MS). The proposed method is simple, effective, and sensitive. It has an instrument detection limit of 0.10, 0.18, and 0.20 ngCr/mL for Cr(VI), Cr(III), and CrPic, respectively. With the help of the methods, we have successfully determined Cr(VI), Cr(III), and CrPic in nutritional supplement (CrPic yeast tablet) with an RSD (n = 5) <6% and a recovery of 93-103%. The experimental results showed that CrPic was the main speciation of chromium in the nutritional supplement, with a concentration of 1514.6 μg Cr/g.

  16. Tissue accumulation and urinary excretion of Cr in chromium picolinate (CrPic)-supplemented lambs.

    PubMed

    Dallago, Bruno Stéfano Lima; Lima, Bárbara Alcântara Ferreira; Braz, Shélida Vasconcelos; Mustafa, Vanessa da Silva; McManus, Concepta; Paim, Tiago do Prado; Campeche, Aline; Gomes, Edgard Franco; Louvandini, Helder

    2016-05-01

    Chromium (Cr) concentrations in liver, kidney, spleen, heart, lymph node, skeletal muscle, bone, testis and urine of lambs were measured to trace the biodistribution and bioaccumulation of Cr after oral supplementation with chromium picolinate (CrPic). Twenty-four Santa Inês lambs were treated with four different concentrations of CrPic: placebo, 0.250, 0.375 and 0.500 mg of CrPic/animal/day for 84 days. The basal diet consisted of Panicum maximum cv Massai hay and concentrate. Cr concentrations were measured by ICP-MS measuring (52)Cr as collected mass. There was a positive linear relationship between dose administered and the accumulation of Cr in the heart, lungs and testis. Urinary excretion of Cr occurred in a time and dose-dependent manner, so the longer or more dietary Cr provided, the greater excretion of the element. As some non-carcass components (such as lungs or heart) are added to bone and visceral meal to feed animals, there is a risk of bioaccumulation and biomagnification due to Cr offered as CrPic in the diet.

  17. Modeling of the fundamental Raman and infrared CH stretching spectra of CHD{sub 2} picolines

    SciTech Connect

    Lapouge, C.; Cavagnat, D.

    1996-12-31

    The quasi-free internal rotation of the methyl group in the {alpha}, {Beta} and {gamma} CHD{sub 2} picolines leads to complex features observed in the Raman and infrared CH stretching spectra. A quantum theory has been developed to model these spectra, taking explicitly into account the coupling between the slow internal motion and the much faster CH stretching vibration. In the ground vibrational state (v=0), the effective potential of internal rotation is calculated by adding to the methyl rotation potential energy, the variation of the zero point vibrational energy during the internal motion, determined by ab-initio. In the CH stretching excited state, this effective potential is added to the CH stretching vibrational contribution, determined from the conformational dependence of the CH bond length. The CH transitions between the effective potentials in the ground (v=0) and the first excited (v=1) CH stretching states are then calculated to reconstruct the fundamental Raman and IR spectra. The Raman intensities are determined from simple Franck-Condom factors, and the IR intensities are calculated from dipole moment derivatives determined by ab-initio. The so calculated spectra agree well with the experimental ones.

  18. Blood Parameters and Toxicity of Chromium Picolinate Oral Supplementation in Lambs.

    PubMed

    Dallago, Bruno Stéfano Lima; Braz, ShélidaVasconcelos; Marçola, Tatiana Guerrero; McManus, Concepta; Caldeira, Denise Ferreira; Campeche, Aline; Gomes, Edgard Franco; Paim, Tiago Prado; Borges, Bárbara Oliveira; Louvandini, Helder

    2015-11-01

    The effects of oral supplementation of chromium picolinate (CrPic) on various blood parameters and their possible toxicity on the liver, kidneys, lungs, heart, and testis were investigated. Twenty-four Santa Inês (SI) lambs were treated with four different concentrations of CrPic (six animals/treatment): placebo, 0.250, 0.375, and 0.500 mg CrPic/animal/day for 84 days. The basal diet consisted of hay Panicum maximum cv Massai and concentrate. Blood and serum were collected fortnightly for analysis. On day 84, the animals were euthanized, and histopathological analysis in the liver, kidney, heart, lung, and testis was made. The liver and kidney were also submitted to electronic microscopy analysis. Differences between treatments (P < 0.05) were observed for packed cell volume (day 84), hemoglobin (day 84), total plasm protein (day 56 and day 84), and triglycerides (day 70). There was no statistically significant relationship between Cr supplementation and histopathology findings, although some animals treated with supplementary Cr showed morphological changes in the liver, kidney, and testis. Thus, the effectiveness of supplementation with Cr remains in doubt as to its physiological action and toxicity in sheep.

  19. Chromium picolinate induced apoptosis of lymphocytes and the signaling mechanisms thereof

    SciTech Connect

    Jana, Mahadevan; Rajaram, Anantanarayanan; Rajaram, Rama

    2009-06-15

    Cr(III)(picolinate){sub 3} [Cr(III)(pic){sub 3}] is currently used as a nutritional supplement and for treating Type-2 diabetes. The effect of Cr(III)(pic){sub 3} uptake in peripheral blood lymphocytes is investigated in this study. From the cytotoxicity data, DNA fragmentation pattern, Annexin V staining, TUNEL positivity and the ultrastructural characteristics such as chromatin condensation and formation of apoptotic bodies, it is clear that Cr(III)(pic){sub 3} induces a concentration dependent apoptosis. It is shown that reactive oxygen species (ROS) produced by treatment with Cr(III)(pic){sub 3} leads to apoptosis, since we find that pretreatment with N-acetyl cysteine inhibits the process. Using Western blotting technique and fluorescence measurements, the downstream signaling molecules have also been identified. Cr(III)(pic){sub 3} treatment leads to collapse of the mitochondrial membrane potential, Bax expression, increase in cytosolic cytochrome c content and active caspase-3 and DNA fragmentation and all these manifestations are reduced by pretreating the lymphocytes with N-acetyl cysteine. Thus, it is shown that Cr(III)(pic){sub 3} is cytotoxic to lymphocytes with ROS and mitochondrial events playing a role in bringing about apoptosis.

  20. Clinical studies on chromium picolinate supplementation in diabetes mellitus--a review.

    PubMed

    Broadhurst, C Leigh; Domenico, Philip

    2006-12-01

    Chromium (Cr) picolinate (CrPic) is a widely used nutritional supplement for optimal insulin function. A relationship among Cr status, diabetes, and associated pathologies has been established. Virtually all trials using CrPic supplementation for subjects with diabetes have demonstrated beneficial effects. Thirteen of 15 clinical studies (including 11 randomized, controlled studies) involving a total of 1,690 subjects (1,505 in CrPic group) reported significant improvement in at least one outcome of glycemic control. All 15 studies showed salutary effects in at least one parameter of diabetes management, including dyslipidemia. Positive outcomes from CrPic supplementation included reduced blood glucose, insulin, cholesterol, and triglyceride levels and reduced requirements for hypoglycemic medication. The greater bioavailability of CrPic compared with other forms of Cr (e.g., niacin-bound Cr or CrCl(3)) may explain its comparatively superior efficacy in glycemic and lipidemic control. The pooled data from studies using CrPic supplementation for type 2 diabetes mellitus subjects show substantial reductions in hyperglycemia and hyperinsulinemia, which equate to a reduced risk for disease complications. Collectively, the data support the safety and therapeutic value of CrPic for the management of cholesterolemia and hyperglycemia in subjects with diabetes.

  1. Chromium picolinate modulates serotonergic properties and carbohydrate metabolism in a rat model of diabetes.

    PubMed

    Komorowski, James R; Tuzcu, Mehmet; Sahin, Nurhan; Juturu, Vijaya; Orhan, Cemal; Ulas, Mustafa; Sahin, Kazim

    2012-10-01

    Chromium picolinate (CrPic) has shown both antidepressant and antidiabetic properties. In this study, the effects of CrPic on serotonergic properties and carbohydrate metabolism in diabetic rats were evaluated. Sixty male Sprague-Dawley rats were divided into four groups. (1) The control group received only standard diet (8 % fat). (2) The CrPic group was fed standard diet and CrPic (80 μg CrPic per kilogram body mass (b.m.)/day), for 10 weeks (microgram/kilogram b.m./day). (3) The HFD/STZ group fed a high-fat diet (HFD, 40 % fat) for 2 weeks and then received streptozotocin (STZ, 40 mg/kg, i.p.) (i.v.) HFD-STZ-CrPic group treated as the previous group and then were administered CrPic. CrPic administration to HFD/STZ-treated rats increased brain chromium levels and improved all measurements of carbohydrate metabolism and serotonergic properties (P<0.001). CrPic also significantly increased levels of insulin, tryptophan, and serotonin (P<0.001) in the serum and brain, and decreased cortisol levels in the serum (P<0.01). Except chromium levels, no significant effect of CrPic supplementation was detected on the overall measured parameters in the control group. CrPic administration was well tolerated without any adverse events. The results support the use of CrPic supplementation which improves serotonergic properties of brain in diabetes.

  2. Structurally simple pyridine N-oxides as efficient organocatalysts for the enantioselective allylation of aromatic aldehydes.

    PubMed

    Pignataro, Luca; Benaglia, Maurizio; Annunziata, Rita; Cinquini, Mauro; Cozzi, Franco

    2006-02-17

    A series of structurally simple pyridine N-oxides have readily been assembled from inexpensive amino acids and tested as organocatalysts in the allylation of aldehydes with allyl(trichloro)silane to afford homoallylic alcohols. (S)-proline-based catalysts afforded the products derived from aromatic aldehydes in fair to good yields and in up to 84% enantiomeric excess (ee). The allylation of heteroaromatic, unsaturated, and aliphatic aldehydes was less satisfactory. By running the reaction in the presence of achiral and chiral additives and structurally different catalysts, we collected some insights into the relationship between the stereochemical outcome and the catalyst's structural features. Even if the ee's obtained are inferior to the best values observed with other catalysts, this work concurs to show that structurally simple pyridine N-oxides can also promote the allylation reaction with satisfactory stereocontrol.

  3. Chromium picolinate intake and risk of type 2 diabetes: an evidence-based review by the United States Food and Drug Administration.

    PubMed

    Trumbo, Paula R; Ellwood, Kathleen C

    2006-08-01

    The labeling of both health claims that meet significant scientific agreement (SSA) and qualified health claims on conventional foods and dietary supplements requires pre-market approval by the US Food and Drug Administration (FDA). Approval by the FDA involves, in part, a thorough review of the scientific evidence to support an SSA or a qualified health claim. This article discusses FDA's evidence-based review of the scientific evidence on the role of chromium picolinate supplements in reducing the risk of type 2 diabetes. Based on this evidence-based review, FDA issued a letter of enforcement discretion for one qualified health claim on chromium picolinate and risk of insulin resistance, a surrogate endpoint for type 2 diabetes. The agency concluded that the relationship between chromium picolinate intake and insulin resistance is highly uncertain.

  4. Luminescent sensor for carbonate ion based on lanthanide(III) complexes of 1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid (DO3A).

    PubMed

    Vaněk, Jakub; Lubal, Přemysl; Hermann, Petr; Anzenbacher, Pavel

    2013-01-01

    Lanthanide(III) complexes of 1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid (H(3)DO3A) are suggested as sensors for sensitive luminescence-based determination of a carbonate anion. Thermodynamic study of association of [Eu(H(2)O)(2)(DO3A)] with bidentate anionic ligands using luminescence spectroscopy reveals an affinity order CO(3)(2-) > oxalate(2-) > picolinate(-) > phthalate(2-) ≈ citrate(3-); presumably as a consequence of an increasing chelate ring size. The ternary [Eu(DO3A)(picolinate)](-) and [Tb(DO3A)(picolinate)](-) complexes show improved photophysical properties due to the antenna effect of the picolinate anion. High quenching effect of carbonate anion and, to a lesser extent also oxalate, enables construction of a linear calibration plot utilizing optimized experimental conditions (e.g. c(LnL) = 0.1 mM, c(picolinate) = 2-5 mM, pH = 7.4, λ(exc) = 286 nm, etc.) for carbonate determination in solution. Both sensors show a comparable sensitivity and the detection limit of about 0.4 mM. In order to improve the photophysical properties of Ln(III) sensor by shift of excitation wavelength about 40 nm to VIS range, the isoquinoline-3-carboxylic acid (IQCA) as antenna ligand was employed instead of picolinic acid. The analysis of commercial samples of European mineral waters was carried out and they were compared to the results obtained by capillary isotachophoresis to confirm there is no inherent (systematic) error to the present analysis. The Ln(III) sensor with IQCA is recommended since it has a better robustness than that with picolinate. The present analytical method is simple and rapid, and it is useful for sensitive determination of bicarbonate/carbonate concentration in water samples under aerobic conditions.

  5. Determination of fusaric acid in maize using molecularly imprinted SPE clean-up

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A new liquid chromatography method to detect fusaric acid in maize is reported based on molecularly imprinted polymer solid phase extraction clean-up (MISPE) using mimic-templated molecularly-imprinted polymers. Picolinic acid was used as a toxin analog for imprinting polymers during a thermolytic s...

  6. Pyridine N-oxide and pyridine-d5 N-oxide: an electrospray/tandem mass spectrometric study carried out at high mass resolution.

    PubMed

    March, Raymond E; Stadey, Christopher J; Lewars, Errol G

    2005-01-01

    A mass spectrometric study of pyridine N-oxide and pyridine-d5 N-oxide was carried out with a hybrid quadrupole/time-of-flight (TOF) mass spectrometer coupled with an electrospray (ES) source. In addition to the observation of protonated, sodiated, and proton-bound dimers of pyridine N-oxide and pyridine-d5 N-oxide, mass scans revealed the presence of several doubly-charged ion species. Doubly-charged ions of m/z 191 were identified as diprotonated tetramers of pyridine N-oxide; a structure has been proposed for the diprotonated tetramer and its energy relative to that of protonated pyridine N-oxide has been obtained from geometry optimizations. The principal ion species observed were subjected to collision-induced dissociation; accurate mass measurements were made of each fragment ion so as to determine its elemental composition. On the basis of mass spectrometric evidence, it is suggested that dissociation of pyridine N-oxide may occur during the ES process and the resulting fragments become embedded in doubly-charged ions. The proton affinity for both pyridine N-oxide and pyridine-d5 N-oxide was calculated; the difference between these proton affinities was compared with an experimentally determined difference between the proton affinities of pyridine N-oxide and pyridine-d5 N-oxide.

  7. The stability of amitriptyline N-oxide and clozapine N-oxide on treated and untreated dry blood spot cards.

    PubMed

    Temesi, David; Swales, John; Keene, Warren; Dick, Samuel

    2013-03-25

    Procedures for drug monitoring based on Dried Blood Spot (DBS) sampling are gaining acceptance for an increasing number of clinical and preclinical applications, where ease of use, small sample requirement, and improved sample stability have been shown to offer advantages over blood tube sampling. However, to-date, the vast majority of this work has described the analysis of well characterized drugs. Using amitriptyline, clozapine, and their potentially labile N-oxide metabolites as model compounds, we consider the merits of using DBS for discovery pharmacokinetic (PK) studies where the metabolic fate of test compounds are often unknown. Both N-oxide metabolites reverted to parent compound under standard drying (2hr) and extraction conditions. Card type significantly affected the outcome, with 14% and 22% degradation occurring for clozapine-N-oxide and amitriptyline-N-oxide on a brand of untreated DBS cards, compared to 59 and 88% on a brand of treated DBS cards. Enrichment of the parent compound ex vivo leads to overestimation of circulating blood concentration and inaccurate determination of the PK profile.

  8. Photochemical activation of ruthenium(II)-pyridylamine complexes having a pyridine-N-oxide pendant toward oxygenation of organic substrates.

    PubMed

    Kojima, Takahiko; Nakayama, Kazuya; Sakaguchi, Miyuki; Ogura, Takashi; Ohkubo, Kei; Fukuzumi, Shunichi

    2011-11-09

    Ruthenium(II)-acetonitrile complexes having η(3)-tris(2-pyridylmethyl)amine (TPA) with an uncoordinated pyridine ring and diimine such as 2,2'-bipyridine (bpy) and 2,2'-bipyrimidine (bpm), [Ru(II)(η(3)-TPA)(diimine)(CH(3)CN)](2+), reacted with m-chloroperbenzoic acid to afford corresponding Ru(II)-acetonitrile complexes having an uncoordinated pyridine-N-oxide arm, [Ru(II)(η(3)-TPA-O)(diimine)(CH(3)CN)](2+), with retention of the coordination environment. Photoirradiation of the acetonitrile complexes having diimine and the η(3)-TPA with the uncoordinated pyridine-N-oxide arm afforded a mixture of [Ru(II)(TPA)(diimine)](2+), intermediate-spin (S = 1) Ru(IV)-oxo complex with uncoordinated pyridine arm, and intermediate-spin Ru(IV)-oxo complex with uncoordinated pyridine-N-oxide arm. A Ru(II) complex bearing an oxygen-bound pyridine-N-oxide as a ligand and bpm as a diimine ligand was also obtained, and its crystal structure was determined by X-ray crystallography. Femtosecond laser flash photolysis of the isolated O-coordinated Ru(II)-pyridine-N-oxide complex has been investigated to reveal the photodynamics. The Ru(IV)-oxo complex with an uncoordinated pyridine moiety was alternatively prepared by reaction of the corresponding acetonitrile complex with 2,6-dichloropyridine-N-oxide (Cl(2)py-O) to identify the Ru(IV)-oxo species. The formation of Ru(IV)-oxo complexes was concluded to proceed via intermolecular oxygen atom transfer from the uncoordinated pyridine-N-oxide to a Ru(II) center on the basis of the results of the reaction with Cl(2)py-O and the concentration dependence of the consumption of the starting Ru(II) complexes having the uncoordinated pyridine-N-oxide moiety. Oxygenation reactions of organic substrates by [Ru(II)(η(3)-TPA-O)(diimine)(CH(3)CN)](2+) were examined under irradiation (at 420 ± 5 nm) and showed selective allylic oxygenation of cyclohexene to give cyclohexen-1-ol and cyclohexen-1-one and cumene oxygenation to afford cumyl alcohol

  9. A single-chain magnet based on {Co(II)₄} complexes and azido/picolinate ligands.

    PubMed

    Liu, Jiang; Qu, Mei; Rouzières, Mathieu; Zhang, Xian-Ming; Clérac, Rodolphe

    2014-08-04

    A new homonuclear single-chain magnet self-assembles as a one-dimensional coordination network of defective dicubane {Co(II)4} complexes linked by single Co(II) ions with the assistance of azido and picolinate ligands. Dominating intrachain ferromagnetic interactions, intrinsic Ising-like Co(II) anisotropy, and negligible interchain magnetic interactions lead to a thermally activated relaxation time of the magnetization below 8 K. Two thermally activated regimes above and below 3.5 K are observed with the following energy barriers: Δ(τ1)/k(B) = 66 K (τ0 = 3.7 × 10(-11) s) and Δ(τ2)/k(B) = 51 K (τ0 = 2.3 × 10(-9) s), respectively. The difference between the two energy barriers of the relaxation time, 15 K, agrees well with the experimental energy, Δ(ξ), to create a domain wall along the chain.

  10. A Bioorthogonal Reaction of N-Oxide and Boron Reagents.

    PubMed

    Kim, Justin; Bertozzi, Carolyn R

    2015-12-21

    The development of bioorthogonal reactions has classically focused on bond-forming ligation reactions. In this report, we seek to expand the functional repertoire of such transformations by introducing a new bond-cleaving reaction between N-oxide and boron reagents. The reaction features a large dynamic range of reactivity, showcasing second-order rate constants as high as 2.3×10(3)  M(-1)  s(-1) using diboron reaction partners. Diboron reagents display minimal cell toxicity at millimolar concentrations, penetrate cell membranes, and effectively reduce N-oxides inside mammalian cells. This new bioorthogonal process based on miniscule components is thus well-suited for activating molecules within cells under chemical control. Furthermore, we demonstrate that the metabolic diversity of nature enables the use of naturally occurring functional groups that display inherent biocompatibility alongside abiotic components for organism-specific applications.

  11. Synthesis and biological evaluation of unnatural derivatives of narciclasine: 7-aza-nornarciclasine and its N-oxide.

    PubMed

    Vshyvenko, Sergey; Reisenauer, Mary Rose; Rogelj, Snezna; Hudlicky, Tomas

    2014-09-01

    Several unnatural derivatives of narciclasine were prepared in which the C-7 carbon was replaced with nitrogen. The 7-aza derivative and its N-oxide were prepared by the coupling of iodopicolinic acid with a conduramine unit derived chemoenzymatically from bromobenzene. Intramolecular Heck reaction was used to construct the isocarbostyryl ring system. The compounds were submitted to biological screening against cancer cell lines. Full experimental and spectra data are provided for all new compounds.

  12. Synthesis of Nitrogen Heterocycles via Photochemical Ring Opening of Pyridazine N-Oxides.

    PubMed

    Portillo, Maribel; Maxwell, Michael A; Frederich, James H

    2016-10-07

    A photochemical method for the direct synthesis of 1H-pyrazoles from pyridazine N-oxides was developed. This chemistry features a regioselective approach to nonsymmetrically substituted pyridazine N-oxides. Herein, we highlight the first strategic use of photoinduced ring-opening reactions of 1,2-diazine N-oxides for the preparative synthesis of nitrogen heterocycles.

  13. Synthesis, X-Ray crystal structure, photophysical characterization and nonlinear optical properties of the unique manganese complex with picolinate and 1,10 phenantroline: toward the designing of new high NLO response crystal

    NASA Astrophysics Data System (ADS)

    Tamer, Ömer; Avcı, Davut; Atalay, Yusuf

    2016-12-01

    The first manganese complex of picolinic acid (also known as 2-pyridinecarboxylic acid) and 1,10 phenantroline has been synthesized, and its structure has been fully characterized by means of X-Ray diffraction method as well as FT-IR, Raman and UV-vis spectroscopies. In order to provide a deep understanding about the relation among the nonlinear optical properties, structural, spectroscopic and electronic behaviors, density functional theory (DFT) calculations have been performed by using hybrid B3LYP level. The intensive interactions between the bonding orbitals of donor O/N atoms and antibonding orbitals of Mn(II) lone pairs confirm the X-Ray diffraction results. Each of the conditions such as small energy gap between HOMO and LUMO, high energy second order perturbation interaction, elongation of conjugated π system and high spin Mn(II) ion induce the first static hyperpolarizability (β) parameter of investigated complex. The β parameter for [Mn(pic)2(phen)]·H2O complex has been found to be approximately 22 times higher than p-nitroaniline.

  14. Synthesis of amino Derivatives of Dithio Acids as Potential Radiation Protective Agents

    DTIC Science & Technology

    1984-08-01

    ation Management S SI ____ K> AD Synthesis of Amino Derivatives of Dithio Acids as Potential Radiation Protective Agents * 0 Annual Report "TIi: o DTIC...Sftcuntiy Clatuftcatio") Synthesis of Amino Derivatives of Dithio Acids as PotentitI- Radiation Protective Agents 12l PERISONAL. Ak.TI4OR(S) * William...methyl- picoline derivatives was accomplished. Use of N-mthyl-2,6-dimethylpyridine also allowed the synthesis of a bis(dithioacetic acid) function not

  15. Purification and characterization of trimethylamine-N-oxide demethylase from jumbo squid (Dosidicus gigas).

    PubMed

    Fu, Xue-Yan; Xue, Chang-Hu; Miao, Ben-Chun; Liang, Jun-Ni; Li, Zhao-Jie; Cui, Feng-Xia

    2006-02-08

    Trimethylamine-N-oxide demethylase (TMAOase) was purified from Jumbo squid (Dosidicus gigas) and characterized in detail herein. The TMAOase was extracted from squid with 20 mM Tris-acetate buffer (pH 7.0) containing 1.0 M NaCl, followed by acid treatment and heat treatment. Then it was purified by deithylaminoethyl-cellulose and Sephacryl S-300 chromatography, subsequently resulting in an 839-fold purification. The molecular mass of the TMAOase was defined to be 17.5 kDa. The optimum pH of the purified TMAOase was 7.0, and its optimum temperature was confirmed to be 55 degrees C. The TMAOase was stable to heat treatment up to 50 degrees C and stable at pH 7.0-9.0. Reducing agents such as DTT, Na2SO3, and NADH were effective at activating TMAOase, and ethylenediaminetetraacetic acid, as well as Mg2+ and Ca2+, could also enhance the activity of TMAOase remarkably, whereas the TMAOase could be significantly inhibited by tea polyphenol, phytic acid and acetic acid. In addition, the TMAOase converted TMAO to dimethylamine and formaldehyde stoichiometrically with a K(m) of 26.2 mM.

  16. Influence of deuteration and fluorination on the supramolecular architecture of pyridine N-oxide crystals.

    PubMed

    Shishkin, Oleg V; Shishkina, Svitlana V; Maleev, Andrey V; Zubatyuk, Roman I; Vasylyeva, Vera; Merz, Klaus

    2013-03-18

    To understand how deuterium and fluorine substituents influence the supramolecular architecture of pyridine N-oxide crystals, the crystal structure of 3-fluoropyridine N-oxide (PNO-3F) was determined and the crystal packing motives of non-deuterated pyridine-N-oxide (PNO), partial-deuterated pyridine-N-oxide (PNO-D) and PNO-3F were analyzed based on ab initio quantum-chemical calculations of the intermolecular interaction energy, using the MP2/6-311G(d,p) method. The appearance of the weak-directing substituents deuterium and fluorine leads to significant changes in the crystal organization of the isotropic packing of PNO molecules.

  17. The role of steric constraints in the formation of rare aqua bridged coordination polymers: Synthesis, characterization and X-ray structures of polymeric, [Cu(2-chlorobenzoate)2(β-picoline)2(μ-H2O)]n and monomeric, [Cu(2-chlorobenzoate)2(γ-picoline)2(H2O)

    NASA Astrophysics Data System (ADS)

    Kumar, Santosh; Sharma, Raj Pal; Venugopalan, Paloth; Aree, Thammarat; Ferretti, Valeria

    2015-07-01

    Reaction of hydrated copper(II) 2-chloro-benzoate with β-/γ-picoline in methanol: water mixture (4:1 v/v) yielded polymeric [Cu(2-chlorobenzoate)2(β-picoline)2(μ-H2O)]n; 1 and monomeric [Cu(2-chlorobenzoate)2(γ-picoline)2(H2O)]; 2. The newly synthesized complexes have been characterized by elemental analyses, FT-IR spectroscopy, UV-Visible spectroscopy, TGA and single crystal X-ray structure determination. X-ray crystallographic analysis revealed that both complexes crystallize in the monoclinic crystal system with space group and unit cell dimensions: C2/c; a = 51.71 Å, b = 10.58 Å, c = 10.02 Å and β = 100.5° for 1 and P21/c; a = 11.81 Å, b = 16.33 Å, c = 13.79 Å and β = 90.77° for 2. Whereas in 1 the presence of constituent and mediating water molecules running along a-axis gives rise to 1-dimensional zig-zag polymer chains, in complex 2, the presence of square pyramidal arrangement of ligands around copper(II) center results in monomeric structure. Various non-covalent interactions like Osbnd H⋯O, Csbnd H⋯O and Csbnd H⋯л have been observed to play a decisive role in the stabilization of crystal lattices in both complexes.

  18. [A new lupin alkaloid, (-)-leontalbinine N-oxide, in Sophora flavescens var. angustifolia seeds and its synthesis by biomimetic transformation from (+)-matrine N-oxide].

    PubMed

    Sekine, T; Saito, K; Minami, R; Arai, N; Suzuki, H; Koike, Y; Murakoshi, I

    1993-01-01

    The possibility of the biomimetic transformation of (+)-matrine N-oxide, a main alkaloid in Sophora flavescens var. angustifolia, under various oxidative conditions was examined by the use of several metallic ions. When (+)-matrine N-oxide was warmed with FeSO4, or Fe(COOH)2 in MeOH-H2O at 40 degrees C, (-)-7, 11-didehydromatrine [(-)-leontalbinine], a minor alkaloid in the same plant, was obtained along with (+)-matrine. This selective formation of (-)-leontalbinine seems to be specific to the reaction of (+)-matrine N-oxide with ferrous reagents. In addition, the structure of the newly isolated minor lupin alkaloid from the seeds of S. flavescens. was determined as (-)-leontalbinine N-oxide from its spectral comparison with the authentic sample.

  19. Thermotriggered Catalyst-Free Modification of a Glass Surface with an Orthogonal Agent Possessing Nitrile N-Oxide and Masked Ketene Functions.

    PubMed

    Cheawchan, Sumitra; Uchida, Satoshi; Sogawa, Hiromitsu; Koyama, Yasuhito; Takata, Toshikazu

    2016-01-12

    The thermotriggered modification of surfaces was performed under catalyst-free conditions using an orthogonal agent possessing both nitrile N-oxide and Meldrum's acid moieties. The nitrile N-oxide moiety of the orthogonal agent successfully underwent catalyst-free 1,3-dipolar cycloaddition to unsaturated bonds of glass surfaces to produce Meldrum's acid-functionalized surfaces. The subsequent thermal decomposition of Meldrum's acid moiety in the presence of nucleophiles afforded versatile nucleophile-modified surfaces (e.g., wet, waterproof, and photoactive surfaces). Surface characteristics were investigated with the water contact angle, time-of-flight secondary ion mass spectrometry (TOF-SIMS), and X-ray photoelectron spectroscopy (XPS). In addition, the surface modification of silica nanoparticles using the orthogonal agent was also achieved to evaluate the density of the functional group concentration on the surface.

  20. 3-Picoline mediated self-assembly of M(II)-malonate complexes (M = Ni/Co/Mn/Mg/Zn/Cu) assisted by various weak forces involving lone pair-π, π-π, and anion···π-hole interactions.

    PubMed

    Mitra, Monojit; Manna, Prankrishna; Bauzá, Antonio; Ballester, Pablo; Seth, Saikat Kumar; Ray Choudhury, Somnath; Frontera, Antonio; Mukhopadhyay, Subrata

    2014-12-18

    Five M(II)-malonate complexes having a common formula (C(6)H(9)N(2))(4)[M(II)(C(3)H(2)O(4))(2)(H(2)O)(2)](PF(6))(2).(H(2)O)(2) (1-5) [where C(6)H(9)N(2) = protonated 3-picoline, M(II) = Ni/Co/Mn/Mg/Zn, C(3)H(4)O(4) = malonic acid, and PF(6)(-) = hexafluorophospahte], have been synthesized and their crystal structures have been determined. Complexes 1-5 were found to be isostructural and protonated 3-picoline has primarily mediated the self-assembly process. Role of a discrete water dimer in complexes 1-5 was also studied. Weaker π-interactions have also played crucial role in stabilizing 1D chain constructed by discrete [M(II)(C(3)H(2)O(4))(2)(H(2)O)(2)] units. An additional copper complex namely, (C(6)H(9)N(2))(4)[Cu(C(3)H(2)O(4))(2)](PF(6))(2) (6) has been synthesized from the same reagents and was found to have a completely different structure from the others. Structures of all the complexes are fully described and compared here. Moreover, the lone pair-π and π-π noncovalent interactions have been analyzed by means of DFT calculations, mainly focusing our attention to the influence of the coordinating metal on the strength of the interactions and the interplay between hydrogen bonding and π-interactions. We also present here Hirshfeld surface analysis to investigate the close intermolecular contacts.

  1. Chromium picolinate enhances skeletal muscle cellular insulin signaling in vivo in obese, insulin-resistant JCR:LA-cp rats.

    PubMed

    Wang, Zhong Q; Zhang, Xian H; Russell, James C; Hulver, Matthew; Cefalu, William T

    2006-02-01

    Chromium is one of the few trace minerals for which a specific cellular mechanism of action has not been identified. Recent in vitro studies suggest that chromium supplementation may improve insulin sensitivity by enhancing insulin receptor signaling, but this has not been demonstrated in vivo. We investigated the effect of chromium supplementation on insulin receptor signaling in an insulin-resistant rat model, the JCR:LA-corpulent rat. Male JCR:LA-cp rats (4 mo of age) were randomly assigned to receive chromium picolinate (CrPic) (obese n=6, lean n=5) or vehicle (obese n=5, lean n=5) for 3 mo. The CrPic was provided in the water, and based on calculated water intake, rats randomized to CrPic received 80 microg/(kg.d). At the end of the study, skeletal muscle (vastus lateralis) biopsies were obtained at baseline and at 5, 15, and 30 min postinsulin stimulation to assess insulin signaling. Obese rats treated with CrPic had significantly improved glucose disposal rates and demonstrated a significant increase in insulin-stimulated phosphorylation of insulin receptor substrate (IRS)-1 and phosphatidylinositol (PI)-3 kinase activity in skeletal muscle compared with obese controls. The increase in cellular signaling was not associated with increased protein levels of the IRS proteins, PI-3 kinase or Akt. However, protein tyrosine phosphatase 1B (PTP1B) levels were significantly lower in obese rats administered CrPic than obese controls. When corrected for protein content, PTP1B activity was also significantly lower in obese rats administered CrPic than obese controls. Our data suggest that chromium supplementation of obese, insulin-resistant rats may improve insulin action by enhancing intracellular signaling.

  2. Effects of chromium picolinate on vascular reactivity and cardiac ischemia-reperfusion injury in spontaneously hypertensive rats.

    PubMed

    Abebe, Worku; Liu, Jun Yao; Wimborne, Hereward; Mozaffari, Mahmood S

    2010-01-01

    Chromium picolinate [Cr(pic)(3)] is a nutritional supplement widely promoted to exert beneficial metabolic effects in patients with type 2 diabetes/impaired glucose tolerance. Frequent comorbidities in these individuals include systemic hypertension, abnormal vascular function and ischemic heart disease, but information on the effects of the supplement on these aspects is sparse. Utilizing male spontaneously hypertensive rats (SHR), we examined the potential impact of Cr(pic)(3) on blood pressure, vascular reactivity and myocardial ischemia-reperfusion injury (IRI). Dietary Cr(pic)(3) supplementation (as 10 mg chromium/kg diet for six weeks) did not affect blood pressure of the SHR. Also, neither norepinephrine (NE) and potassium chloride (KCl)-induced contractility nor sodium nitroprusside (SNP)-induced relaxation of aortic smooth muscle from the SHR was altered by Cr(pic)(3) treatment. However, Cr(pic)(3) augmented endothelium-dependent relaxation of aortas, produced by acetylcholine (ACh), and this effect was abolished by N-nitro-L-arginine methyl ester (L-NAME), suggesting induction of nitric oxide (NO) production/release. Treatment with Cr(pic)(3) did not affect baseline coronary flow rate and rate-pressure-product (RPP) or infarct size following regional IRI. Nonetheless, Cr(pic)(3) treatment was associated with improved coronary flow and recovery of myocardial contractility and relaxation following ischemia-reperfusion insult. In conclusion, dietary Cr(pic)(3) treatment of SHR alters neither blood pressure nor vascular smooth muscle reactivity but causes enhancement of endothelium-dependent vasorelaxation associated with NO production/release. Additionally, while the treatment does not affect infarct size, it improves functional recovery of the viable portion of the myocardium following IRI.

  3. Heterocyclic N-Oxides – An Emerging Class of Therapeutic Agents

    PubMed Central

    Mfuh, Adelphe M.; Larionov, Oleg V.

    2016-01-01

    Heterocyclic N-oxides have emerged as potent compounds with anticancer, antibacterial, antihypertensive, antiparasitic, anti-HIV, anti-inflammatory, herbicidal, neuroprotective, and procognitive activities. The N-oxide motif has been successfully employed in a number of recent drug development projects. This review surveys the emergence of this scaffold in the mainstream medicinal chemistry with a focus on the discovery of the heterocyclic N-oxide drugs, N-oxide-specific mechanisms of action, drug-receptor interactions and synthetic avenues to these compounds. As the first review on this subject that covers the developments since 1950s to date, it is expected that it will inspire wider implementation of the heterocyclic N-oxide motif in the rational design of new medicinal agents. PMID:26087764

  4. Combination of best promoter and micellar catalyst for chromic acid oxidation of 1-butanol to 1-butanal in aqueous media at room temperature.

    PubMed

    Saha, Rumpa; Ghosh, Aniruddha; Saha, Bidyut

    2014-04-24

    In aqueous acidic media, picolinic acid, 2,2'-bipyridine and 1,10-phenanthroline promoted Cr(VI) oxidation of 1-butanol produces 1-butanal. 1-butanal is separated from mixture by fractional distillation. The anionic surfactant (SDS) and neutral surfactant (TX-100) accelerate the process while the cationic surfactant (CPC) retards the reaction. Combination of bipy and SDS is the best choice for chromic acid oxidation of 1-butanol to 1-butanal in aqueous media.

  5. Experimental and Mechanistic Analysis of the Palladium-Catalyzed Oxidative C8-Selective C–H Homocoupling of Quinoline N-Oxides

    PubMed Central

    Stephens, David E.; Lakey-Beitia, Johant; Chavez, Gabriel; Ilie, Carla; Arman, Hadi D.

    2016-01-01

    A novel site-selective palladium-catalyzed oxidative C8–H homocoupling reaction of quinoline N-oxides has been developed. The reaction affords substituted 8,8'-biquinolyl N,N'-dioxides that can be readily converted to a variety of functionalized 8,8'-biquinolyls. Mechanistic studies point to the crucial role of the oxidant and a non-innocent behavior of acetic acid as a solvent. PMID:25966913

  6. Biocatalytic Dynamic Kinetic Resolution for the Synthesis of Atropisomeric Biaryl N-Oxide Lewis Base Catalysts.

    PubMed

    Staniland, Samantha; Adams, Ralph W; McDouall, Joseph J W; Maffucci, Irene; Contini, Alessandro; Grainger, Damian M; Turner, Nicholas J; Clayden, Jonathan

    2016-08-26

    Atropisomeric biaryl pyridine and isoquinoline N-oxides were synthesized enantioselectively by dynamic kinetic resolution (DKR) of rapidly racemizing precursors exhibiting free bond rotation. The DKR was achieved by ketoreductase (KRED) catalyzed reduction of an aldehyde to form a configurationally stable atropisomeric alcohol, with the substantial increase in rotational barrier arising from the loss of a bonding interaction between the N-oxide and the aldehyde. Use of different KREDs allowed either the M or P enantiomer to be synthesized in excellent enantiopurity. The enantioenriched biaryl N-oxide compounds catalyze the asymmetric allylation of benzaldehyde derivatives with allyltrichlorosilane.

  7. Toxicology of 4-nitroquinoline-N-oxide (4NOO) in the umu and Xenometrix Protox{trademark} assays

    SciTech Connect

    Metosh-Dickey, C.A.; Winston, G.W.

    1995-12-31

    4NQO is a benchmark mutagen often used to initiate carcinogenesis in laboratory animals. The mechanism by which it exerts its mutagenic effect is largely uncharacterized. The authors have studied 4NQO and other structural analogs in the umu mutagenicity assay and the Xenometrix Protox, assay. Four strains of Salmonella typhimurium were used in the umu assay to assess the structure/function relationships in the mutagenicity of 4NQO. In the wild type, 1-nitronaphthalene (INN) gave a maximum of a 2-fold induction while quinoline-N-oxide (ONO) gave a response similar to DMSO values, However, 4-nitropyridine-N-oxide (4NPO) and 4-hydroxyaminoquinoline-N-oxide (4HAQO), a purified metabolite of 4NQO, were strongly mutagenic in the wild type strain (3-fold and 5-fold increase in mutagenicity respectively), although not as strong as 4NQO (7-fold increase in mutagenicity). 4NQO, 4HAQO, 1-NN, and QNO were further tested in the nitroreductase and acetylase deficient strains and an acetylase enriched strain. The mutagenic expression of the compounds was not altered in the deficient strains, however, the mutagenicity of 4NQO and 4HAQO were slightly decreased while 1 NN was somewhat enhanced in the acetylase enriched strain. This indicates an important role for acetylase in the metabolism of these compounds. When 4NQO and 4HAQO were incubated with the wild type strain in the presence of liver microsomes and cytosol from Aroclor-induced rats the mutagenicity of 4NQO was dramatically reduced, while the mutagenicity of 4HAQO was essentially unaffected. Oxygen consumption, as observed in a Clark oxygen electrode, was enhanced upon addition of 4NQO to a system containing either ascorbic acid or microsomal protein and NAD(P)H suggesting that oxygen radicals are produced during 4NQO reduction. When 4NQO was incubated in the presence of superoxide dismutase and catalase with the wild-type strain no reduction of mutagenicity was observed.

  8. The synergism of nucleoside antibiotics combined with guanine 7-N-oxide against a rhabdovirus, infectious hematopoietic necrosis virus (IHNV).

    PubMed

    Hasobe, M; Saneyoshi, M; Isono, K

    1986-09-01

    Guanine 7-N-oxide was shown to have synergistic activity in combination with neplanocin A against a rhabdovirus, infectious hematopoietic necrosis virus (IHNV), as reported previously. We examined further the antiviral activity of guanine 7-N-oxide in combination with other nucleoside antibiotics against IHNV. Synergism was seen between guanine 7-N-oxide and D-eritadenine or cordycepin. It is considered that compounds inhibiting RNA methylation show synergism with guanine 7-N-oxide.

  9. Is N,N-dimethylglycine N-oxide a choline and betaine metabolite?

    PubMed

    Lever, Michael; McEntyre, Christopher J; George, Peter M; Chambers, Stephen T

    2017-01-13

    Choline metabolism is by oxidation to betaine, which is demethylated to N,N-dimethylglycine; dimethylglycine is oxidatively demethylated to sarcosine. This pathway is important for osmoregulation and as a source of methyl groups. We asked whether another metabolite was involved. We synthesized the N-oxide of dimethylglycine (DMGO) by oxidizing dimethylglycine with peracetic acid, and measured DMGO in human plasma and urine by HPLC-MS/MS with positive ion detection, using two chromatography procedures, based on ion exchange and HILIC separations. The molecular ion DMGOH+ (m/z=120) yielded four significant fragments (m/z=103, 102, 58 and 42). The suspected DMGO peak in human body fluids showed all these fragments, and co-chromatographed with added standard DMGO in both HPLC systems. Typical plasma concentrations of DMGO are under 1 μmol/l. They may be lower in metabolic syndrome patients. Urine concentrations are higher, and DMGO has a higher fractional clearance than dimethylglycine, betaine and choline. It was present in all of over 80 human urine and plasma samples assayed. Plasma DMGO concentrations correlate with plasma DMG concentrations, with betaine and choline concentrations, with the osmolyte myo-inositol, and strongly with urinary DMGO excretion. We conclude that DMGO is probably a normal human metabolite.

  10. Trimethylamine N-Oxide: The Good, the Bad and the Unknown

    PubMed Central

    Velasquez, Manuel T.; Ramezani, Ali; Manal, Alotaibi; Raj, Dominic S.

    2016-01-01

    Trimethylamine N-oxide (TMAO) is a small colorless amine oxide generated from choline, betaine, and carnitine by gut microbial metabolism. It accumulates in the tissue of marine animals in high concentrations and protects against the protein-destabilizing effects of urea. Plasma level of TMAO is determined by a number of factors including diet, gut microbial flora and liver flavin monooxygenase activity. In humans, a positive correlation between elevated plasma levels of TMAO and an increased risk for major adverse cardiovascular events and death is reported. The atherogenic effect of TMAO is attributed to alterations in cholesterol and bile acid metabolism, activation of inflammatory pathways and promotion foam cell formation. TMAO levels increase with decreasing levels of kidney function and is associated with mortality in patients with chronic kidney disease. A number of therapeutic strategies are being explored to reduce TMAO levels, including use of oral broad spectrum antibiotics, promoting the growth of bacteria that utilize TMAO as substrate and the development of target-specific molecules with varying level of success. Despite the accumulating evidence, it is questioned whether TMAO is the mediator of a bystander in the disease process. Thus, it is important to undertake studies examining the cellular signaling in physiology and pathological states in order to establish the role of TMAO in health and disease in humans. PMID:27834801

  11. Facile synthesis of planar chiral N-oxides and their use in Lewis base catalysis.

    PubMed

    Fulton, J Robin; Glover, Jean E; Kamara, Lamin; Rowlands, Gareth J

    2011-01-07

    A rapid and versatile method for the preparation of planar chiral [2.2]paracyclophane-derived pyridines and pyridine N-oxides is reported. The potential utility of these compounds in Lewis base catalysis is briefly introduced.

  12. Bulk Gold-Catalyzed Reactions of Isocyanides, Amines, and Amine N-Oxides

    SciTech Connect

    Klobukowski, Erik; Angelici, Robert; Woo, Keith L.

    2012-01-26

    Bulk gold powder (5–50 μm particles) catalyzes the reactions of isocyanides with amines and amine N-oxides to produce ureas. The reaction of n-butyl isocyanide (nBu–N≡C) with di-n-propylamine and N-methylmorpholine N-oxide in acetonitrile, which was studied in the greatest detail, produced 3-butyl-1,1-dipropylurea (O═C(NHnBu)(NnPr2)) in 99% yield at 60 °C within 2 h. Sterically and electronically different isocyanides, amines, and amine N-oxides react successfully under these conditions. Detailed studies support a two-step mechanism that involves a gold-catalyzed reaction of adsorbed isocyanide with the amine N-oxide to form an isocyanate (RN═C═O), which rapidly reacts with the amine to give the urea product. These investigations show that bulk gold, despite its reputation for poor catalytic activity, is capable of catalyzing these reactions.

  13. Voriconazole N-oxide and its UVB photoproduct sensitize keratinocytes to UVA

    PubMed Central

    Ona-Vu, K.; Oh, D.H.

    2015-01-01

    Background The antifungal agent, voriconazole, is associated with phototoxicity and photocarcinogenicity. Prior work has indicated that voriconazole and its hepatic N-oxide metabolite do not sensitize keratinocytes to ultraviolet B (UVB). Clinical observations have suggested ultraviolet A (UVA) may be involved. Objectives To determine the photochemistry and photobiology of voriconazole and its major hepatic metabolite, voriconazole N-oxide. Methods Voriconazole and voriconazole N-oxide were spectrophotometrically monitored following various doses of UVB. Cultured human keratinocytes were treated with parental drugs or with their UVB photoproducts, and survival following UVA irradiation was measured by thiazolyl blue metabolism. Reactive oxygen species and 8-oxoguanine were monitored by fluorescence microscopy. Results Voriconazole and voriconazole N-oxide have varying ultraviolet B (UVB) absorption but do not acutely sensitize cultured human keratinocytes following UVB exposure. However, sustained UVB exposures produced notable dose- and solvent-dependent changes in the absorption spectra of voriconazole N-oxide which in aqueous solution acquires a prominent ultraviolet A (UVA) absorption band, suggesting formation of a discrete photoproduct. Neither the parental drugs nor their photoproducts sensitized cells to UVB though all but voriconazole N-oxide were moderately toxic to cells in the dark. Notably, both voriconazole N-oxide and its UVB photoproduct, but not voriconazole or its photoproduct, additionally sensitized cells to UVA by >3-fold relative to controls in association with UVA-induced reactive oxygen species and 8-oxoguanine levels. Conclusions Voriconazole N-oxide and its UVB-photoproduct act as UVA-sensitizers that generate reactive oxygen species and that produce oxidative DNA damage. These results suggest a mechanism for the phototoxicity and photocarcinogenicity observed with voriconazole treatment. PMID:25919127

  14. Room-temperature amination of deactivated aniline and aryl halide partners with carbonate base using a Pd-PEPPSI-IPentCl-o-picoline catalyst.

    PubMed

    Pompeo, Matthew; Farmer, Jennifer L; Froese, Robert D J; Organ, Michael G

    2014-03-17

    Current state-of-the-art protocols for the coupling of unreactive amines (e.g., electron-poor anilines) with deactivated oxidative-addition partners (e.g., electron-rich and/or hindered aryl chlorides) involve strong heating (usually >100°C) and/or tert-butoxide base, and even then not all couplings are successful. The aggressive base tert-butoxide reacts with and in many instances destroys the typical functional groups that are necessary for the function of most organic molecules, such as carbonyl groups, esters, nitriles, amides, alcohols, and amines. The new catalyst described herein, Pd-PEPPSI-IPentCl-o-picoline, is able to aminate profoundly deactivated coupling partners when using only carbonate base at room temperature.

  15. The effects of chromium picolinate and chromium histidinate administration on NF-κB and Nrf2/HO-1 pathway in the brain of diabetic rats.

    PubMed

    Sahin, Kazim; Tuzcu, Mehmet; Orhan, Cemal; Gencoglu, Hasan; Ulas, Mustafa; Atalay, Mustafa; Sahin, Nurhan; Hayirli, Armagan; Komorowski, James R

    2012-12-01

    The objective of this experiment was to investigate the effects of supplemental chromium picolinate (CrPic) and chromium histidinate (CrHis) on nuclear factor-kappa B (NF-κB p65) and nuclear factor (erythroid-derived 2)-like 2 (Nrf2) signaling pathway in diabetic rat brain. Nondiabetic (n = 45) and diabetic (n = 45) male Wistar rats were either not supplemented or supplemented with CrPic or CrHis via drinking water to consume 8 μg elemental chromium (Cr) per day for 12 weeks. Diabetes was induced by streptozotocin injection (40 mg/kg i.p., for 2 weeks) and maintained by high-fat feeding (40 %). Diabetes was associated with increases in cerebral NF-κB and 4-hydroxynonenal (4-HNE) protein adducts and decreased in cerebral nuclear factor of kappa light polypeptide gene enhancer in B cells inhibitor, alpha (IκBα) and Nrf2 levels. Both Cr chelates were effective to decrease levels of NF-κB and 4-HNE protein adducts and to increase levels of IκBα and Nrf2 in the brain of diabetic rats. However, responses of these increases and decreases were more notable when Cr was supplemented as CrHis than as CrPic. In conclusion, Cr may play a protective role in cerebral antioxidant defense system in diabetic subjects via the Nrf2 pathway by reducing inflammation through NF-κB p65 inhibition. Histidinate form of Cr was superior to picolinate form of Cr in reducing NF-κB expression and increasing Nrf2 expression in the brain of diabetic rats.

  16. Synthesis and f-element ligation properties of NCMPO-decorated pyridine N-oxide platforms

    SciTech Connect

    Ouizem, Sabrina; Rosario-Amorin, Daniel; Dickie, D. A.; Paine, Robert T.; De Bettencourt-Dias, Ana; Hay, Benjamin; Podair, Julien; Delmau, Laetitia Helene

    2014-01-01

    Stepwise syntheses of 2-{[2-(diphenylphosphoryl)acetamido]methyl}pyridine 1-oxide, 2-[Ph2P(O)CH2C(O)N(H)CH2]C5H4NO (6), 2-{[2-(diphenylphosphoryl)acetamido]methyl}-6-[(diphenylphosphoryl)methyl]pyridine 1-oxide, 2-[Ph2P(O)CH2C(O)N(H)CH2]-6-[Ph2P(O)CH2]C5H3NO (7) and 2,6-bis{[2-(diphenylphosphoryl)acetamido]methyl}pyridine 1-oxide, 2,6-[Ph2P(O)CH2C(O)N(H)CH2]2C5H3NO (8), are reported along with spectroscopic characterization data and single crystal X-ray diffraction structure determination for 6 2H2O, 7 and 2,6-[Ph2P(O)CH2C(O)N(H)CH2]2C5H3N MeOH 18 MeOH, the pyridine precursor of 8. Molecular mechanics computations indicate that 6, 7 and 8 should experience minimal steric hindrance to donor group reorganization that would permit tridentate, tetradentate and pentadentate docking structures for the respective ligands on lanthanide cations. However, crystal structure determination for the lanthanide complexes, {[Yb(6)(NO3)3] (MeOH)}n, {[Lu(6)(NO3)3] (MeOH)}n, [Er(6)2(H2O)2](NO3)3 (H2O)4}n, {[La(13)(NO3)3(MeOH)] (MeOH)}n, {[Eu(7)(NO3)2(EtOAc)0.5(H2O)0.5](NO3)}2 MeOH and [Dy3(7)4(NO3)4(H2O)2](NO3)5 (MeOH)5 (H2O)2 reveal solid-state structures with mixed chelating/bridging ligand:Ln(III) interactions that employ lower than the maximal denticity. The binding of 6 and 7 with Eu(III) in the solid state and in MeOH solutions is also accessed by emission spectroscopy. The acid dependence for solvent extractions with 6 and 7 in 1,2-dichloroethane for Eu(III) and Am(III) in nitric acid solutions is described and compared with the behavior of n-octyl(phenyl)-N,N-diisobutylcarbamoylmethylphosphine oxide (OPhDiBCMPO, 1b) and 2-[(diphenyl)phosphinoylmethyl]pyridine N-oxide (DPhNOPO, 4a).

  17. Transition-Metal-Free Regioselective Alkylation of Pyridine N-Oxides Using 1,1-Diborylalkanes as Alkylating Reagents.

    PubMed

    Jo, Woohyun; Kim, Junghoon; Choi, Seoyoung; Cho, Seung Hwan

    2016-08-08

    Reported herein is an unprecedented base-promoted deborylative alkylation of pyridine N-oxides using 1,1-diborylalkanes as alkyl sources. The reaction proceeds efficiently for a wide range of pyridine N-oxides and 1,1-diborylalkanes with excellent regioselectivity. The utility of the developed method is demonstrated by the sequential C-H arylation and methylation of pyridine N-oxides. The reaction also can be applied for the direct introduction of a methyl group to 9-O-methylquinine N-oxide, thus it can serve as a powerful method for late-stage functionalization.

  18. Reactions between Grignard reagents and heterocyclic N-oxides: stereoselective synthesis of substituted pyridines, piperidines, and piperazines.

    PubMed

    Andersson, Hans; Olsson, Roger; Almqvist, Fredrik

    2011-01-21

    In this perspective we discuss the recent developments of stereoselective synthesis of substituted pyridines, piperidines, and piperazines from cheap and commercially readily available starting materials. Pyridine N-oxides and pyrazine N-oxides are reacted with alkyl, aryl, alkynyl and vinyl Grignard reagents to give a diverse set of heterocycles in high yields. Optically active substituted piperazines are obtained by an asymmetric reaction from pyrazine N-oxides using sparteine as chiral ligand. In addition, a stereoselective synthesis of dienal-oximes from the reaction between pyridine N-oxides and Grignard reagents is presented, which results in a useful intermediate for the synthesis of a diverse set of compounds.

  19. Association of FMO3 Variants and Trimethylamine N-Oxide Concentration, Disease Progression, and Mortality in CKD Patients

    PubMed Central

    Robinson-Cohen, Cassianne; Newitt, Richard; Shen, Danny D.; Rettie, Allan E.; Kestenbaum, Bryan R.; Himmelfarb, Jonathan; Yeung, Catherine K.

    2016-01-01

    Elevated levels of circulating pro-atherogenic uremic solutes, particularly trimethylamine N-oxide (TMAO), have been implicated in cardiovascular disease development in patients with chronic kidney disease (CKD). TMAO is generated from trimethylamine (TMA) via metabolism by hepatic flavin-containing monooxygenase isoform 3 (FMO3). We determined the functional effects of three common FMO3 variants at amino acids 158, 308, and 257 on TMAO concentrations in a prospective cohort study and evaluated associations of polymorphisms with CKD progression and mortality. Each additional minor allele at amino acid 158 was associated with a 0.38 μg/mL higher circulating TMAO (p = 0.01) and with faster rates of annualized relative eGFR decline. Participants with 0, 1 and 2 variant alleles averaged an eGFR loss of 8%, 12%, and 14% per year, respectively (p-for trend = 0.05). Compared to participants with the homozygous reference allele, heterozygous and homozygous variant participants had a 2.0-fold (95% CI: 0.85, 4.6) and 2.2-fold (95% CI: 0.89, 5.48) higher risk of mortality, respectively (p-for-trend = 0.04). No associations with clinical outcomes were observed for allelic variants at amino acids 257 or 308. Understanding the contribution of genetic variation of FMO3 to disease progression and all-cause mortality can guide recommendations for diet modification or pharmacotherapy in CKD patients at increased risk of adverse outcomes. PMID:27513517

  20. Combination of best promoter and micellar catalyst for more than kilo-fold rate acceleration in favor of chromic acid oxidation of D-galactose to D-galactonic acid in aqueous media at room temperature

    NASA Astrophysics Data System (ADS)

    Saha, Rumpa; Ghosh, Aniruddha; Sar, Pintu; Saha, Indrajit; Ghosh, Sumanta K.; Mukherjee, Kakali; Saha, Bidyut

    2013-12-01

    Picolinic acid, 2,2‧-bipyridine and 1,10-phenanthroline promoted Cr(VI) oxidation of D-galactose to D-galactonic acid in three representative aqueous micellar media has been studied. The anionic surfactant (SDS) accelerated the rate of reaction while the cationic surfactant (CPC) and neutral surfactant (TX-100) retarded the reaction rate. Combination of bipy and SDS is the best choice for chromic acid oxidation of D-galactose to D-galactonic acid in aqueous media although 1,10-phenanthroline is best promoter in absence of micellar catalyst.

  1. Prophylactic use of polyvinylpyridine-N-oxide (PVNO) in baboons exposed to quartz dust

    SciTech Connect

    Goldstein, B.; Rendall, R.E.G.

    1987-04-01

    Twelve baboons were exposed to a quartz dust cloud. Four of these were also given polyvinylpyridine-N-oxide (PVNO) by aerosol and four received PVNO by aerosol and injection. A prophylactic effect was demonstrated during the course of treatment, but when treatment stopped the silicosis progressed to the same degree of severity as in the untreated animals.

  2. Metachelins, mannosylated and N-oxidized coprogen-type siderophores from Metarhizium robertsii

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Under iron-depleted culture conditions, the entomopathogenic fungus Metarhizium robertsii (Bischoff, Humber, and Rehner) (= M. anisopliae) produces a complex of extracellular siderophores including novel O-glycosylated and/or N-oxidized coprogen-type compounds as well as the known fungal siderophore...

  3. Helical chiral pyridine N-oxides: a new family of asymmetric catalysts.

    PubMed

    Chen, Jinshui; Takenaka, Norito

    2009-07-27

    Optically active chiral alkyl chlorides are valuable compounds because of their bioactivity and versatile synthetic utility. Accordingly, the ring opening of epoxides with a chloride nucleophile stands as an important goal in asymmetric catalysis. We describe herein recent advances in the design and development of chiral pyridine N-oxide catalysts for the enantioselective synthesis of chlorohydrins.

  4. Catalytic enantioselective [2,3]-rearrangements of amine N-oxides.

    PubMed

    Bao, Hongli; Qi, Xiangbing; Tambar, Uttam K

    2011-02-09

    The first Pd-catalyzed enantioselective [2,3]-rearrangement of allylic amine N-oxides is described, which formally represents an asymmetric Meisenheimer rearrangement. The mild reaction conditions enable the synthesis of chiral nonracemic aliphatic allylic alcohol derivatives with reactive functional groups. On the basis of preliminary studies, a cyclization-mediated mechanism is proposed.

  5. N-oxide 1,2,4,5-tetrazine-based high-performance energetic materials.

    PubMed

    Wei, Hao; Gao, Haixiang; Shreeve, Jean'ne M

    2014-12-15

    One route to high density and high performance energetic materials based on 1,2,4,5-tetrazine is the introduction of 2,4-di-N-oxide functionalities. Based on several examples and through theoretical analysis, the strategy of regioselective introduction of these moieties into 1,2,4,5-tetrazines has been developed. Using this methodology, various new tetrazine structures containing the N-oxide functionality were synthesized and fully characterized using IR, NMR, and mass spectroscopy, elemental analysis, and single-crystal X-ray analysis. Hydrogen peroxide (50 %) was used very effectively in lieu of the usual 90 % peroxide in this system to generate N-oxide tetrazine compounds successfully. Comparison of the experimental densities of N-oxide 1,2,4,5-tetrazine compounds with their 1,2,4,5-tetrazine precursors shows that introducing the N-oxide functionality is a highly effective and feasible method to enhance the density of these materials. The heats of formation for all compounds were calculated with Gaussian 03 (revision D.01) and these values were combined with measured densities to calculate detonation pressures (P) and velocities (νD ) of these energetic materials (Explo 5.0 v. 6.01). The new oxygen-containing tetrazines exhibit high density, good thermal stability, acceptable oxygen balance, positive heat of formation, and excellent detonation properties, which, in some cases, are superior to those of 1,3,5-tritnitrotoluene (TNT), 1,3,5-trinitrotriazacyclohexane (RDX), and octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine (HMX).

  6. N-demethylation and N-oxidation of imipramine in rat thoracic aortic endothelial cells.

    PubMed

    Ueda, Yukari; Yaginuma, Toshihiko; Sakurai, Eiko; Sakurai, Eiichi

    2014-06-01

    The aim of this study was to examine whether cultured rat thoracic aortic endothelial cells (TAECs) have the ability to metabolize the tertiary amine, imipramine. In rat TAECs, imipramine was biotransformed into N-demethylate and N-oxide by cytochrome P450 (CYP) and flavin-containing monooxygenase (FMO), respectively. The intrinsic clearance (V max/K m) for the N-oxide formation was approximately five times as high as that for the N-demethylate formation, indicating that oxidation by CYP was much higher than that by FMO. Moreover, we suggest that CYP2C11 and CYP3A2 are key players in the metabolism to N-demethylate in rat TAECs using the respective anti-rat CYP antibodies (anti-CYP2C11 and anti-CYP3A2). The presence of CYP2C11 and CYP3A2 proteins was also confirmed in cultured rat TAECs using a polyclonal anti-CYP antibody and immunofluorescence microscopy. In contrast, the formation rate of N-oxide at pH 8.4 was higher than that at pH 7.4. Inhibition of N-oxide formation by methimazole was found to be the best model of competitive inhibition yielding an apparent K i value of 0.80 μmol/L, demonstrating that N-oxidation was catalyzed by FMO in rat TAECs. These results suggest that rat TAEC enzymes can convert substrates of exogenous origin such as imipramine, indicating that TAECs have an important function for metabolic products, besides hepatic cells.

  7. Oral chromium picolinate impedes hyperglycemia-induced atherosclerosis and inhibits proatherogenic protein TSP-1 expression in STZ-induced type 1 diabetic ApoE−/− mice

    PubMed Central

    Ganguly, Rituparna; Sahu, Soumyadip; Ohanyan, Vahagn; Haney, Rebecca; Chavez, Ronaldo J.; Shah, Shivani; Yalamanchili, Siri; Raman, Priya

    2017-01-01

    Increasing evidence suggests thrombospondin-1 (TSP-1), a potent proatherogenic matricellular protein, as a putative link between hyperglycemia and atherosclerotic complications in diabetes. We previously reported that the micronutrient chromium picolinate (CrP), with long-standing cardiovascular benefits, inhibits TSP-1 expression in glucose-stimulated human aortic smooth muscle cells in vitro. Here, we investigated the atheroprotective action of orally administered CrP in type 1 diabetic apolipoprotein E-deficient (ApoE−/−) mice and elucidated the role of TSP-1 in this process. CrP decreased lipid burden and neointimal thickness in aortic root lesions of hyperglycemic ApoE−/− mice; also, smooth muscle cell (SMC), macrophage and leukocyte abundance was prevented coupled with reduced cell proliferation. Attenuated lesion progression was accompanied with inhibition of hyperglycemia-induced TSP-1 expression and reduced protein O-glycosylation following CrP treatment; also, PCNA and vimentin (SMC synthetic marker) expression were reduced while SM-MHC (SMC contractile marker) levels were increased. To confirm a direct role of TSP-1 in diabetic atherosclerosis, hyperglycemic TSP-1−/−/ApoE−/− double knockout mice were compared with age-matched hyperglycemic ApoE−/− littermates. Lack of TSP-1 prevented lesion formation in hyperglycemic ApoE−/− mice, mimicking the atheroprotective phenotype of CrP-treated mice. These results suggest that therapeutic TSP-1 inhibition may have important atheroprotective potential in diabetic vascular disease. PMID:28345659

  8. Effects of dietary chromium (III) picolinate on growth performance, respiratory rate, plasma variables, and carcass traits of pigs fed high-fat diets.

    PubMed

    Kim, Beob G; Lindemann, Merlin D; Cromwell, Gary L

    2010-02-01

    We investigated the effects of supplemental chromium (Cr) as Cr (III) picolinate on pigs fed high-fat diets (HFD) in a 56-day experiment. Thirty-two crossbred pigs (9.6 kg) were allotted to four treatments with four blocks and two pigs/pen. Treatments included: (1) low-fat diet (fat < 3.5%; LFD) with no Cr, (2) HFD (fat > 30%) with no Cr, (3) HFD with 1,000 ppb Cr, and (4) HFD with 2,000 ppb Cr. Pigs fed HFD gained weight faster, consumed less, and had lower feed:gain (p < 0.05). Pigs fed HFD had higher respiration rates than pigs fed LFD on d 41 (p < 0.05). Plasma insulin on d 14 linearly decreased with Cr (p = 0.05). Plasma cholesterol concentrations were higher in the pigs fed HFD than those fed LFD, but were largely unaffected by supplemental Cr. Consumption of HFD resulted in greater carcass weight, perirenal fat, and backfat measures (p < 0.01) compared with the LFD group. Cr resulted in linear reductions of hot carcass weight (p = 0.08) and average backfat (p < 0.05). The effects of Cr on carcass fat measures were more pronounced in castrated males than in females. These results indicate that Cr attenuates some effects of a HFD, mainly body fat accretion of pigs, and especially in castrated pigs.

  9. Complexation facilitated reduction of aromatic N-oxides by aqueous Fe(II)-tiron complex: reaction kinetics and mechanisms.

    PubMed

    Chen, Yiling; Zhang, Huichun

    2013-10-01

    Rapid reduction of carbadox (CDX), olaquindox and several other aromatic N-oxides were investigated in aqueous solution containing Fe(II) and tiron. Consistent with previous work, the 1:2 Fe(II)-tiron complex, FeL2(6-), is the dominant reactive species as its concentration linearly correlates with the observed rate constant kobs under various conditions. The N-oxides without any side chains were much less reactive, suggesting direct reduction of the N-oxides is slow. UV-vis spectra suggest FeL2(6-) likely forms 5- or 7-membered rings with CDX and olaquindox through the N and O atoms on the side chain. The formed inner-sphere complexes significantly facilitated electron transfer from FeL2(6-) to the N-oxides. Reduction products of the N-oxides were identified by HPLC/QToF-MS to be the deoxygenated analogs. QSAR analysis indicated neither the first electron transfer nor N-O bond cleavage is the rate-limiting step. Calculations of the atomic spin densities of the anionic N-oxides confirmed the extensive delocalization between the aromatic ring and the side chain, suggesting complex formation can significantly affect the reduction kinetics. Our results suggest the complexation facilitated N-oxide reduction by Fe(II)-tiron involves a free radical mechanism, and the subsequent deoxygenation might also benefit from the weak complexation of Fe(II) with the N-oxide O atom.

  10. Selective activity against Mycobacteriumtuberculosis of new quinoxaline 1,4-di-N-oxides.

    PubMed

    Vicente, Esther; Pérez-Silanes, Silvia; Lima, Lidia M; Ancizu, Saioa; Burguete, Asunción; Solano, Beatriz; Villar, Raquel; Aldana, Ignacio; Monge, Antonio

    2009-01-01

    New series of 3-phenylquinoxaline 1,4-di-N-oxide with selective activity against Mycobacterium tuberculosis have been prepared and evaluated. Thirty-four of the seventy tested compounds showed an MIC value less than 0.2 microg/mL, a value on the order of the MIC of rifampicin. Furthermore, 45% of the evaluated derivatives showed a good in vitro activity/toxicity ratio. The most active and selective compounds carry a fluorine atom in the quinoxaline 7-position or in the phenyl substituent para-position. In conclusion, the potency, low cytotoxicity and selectivity of these compounds make them valid lead compounds for synthesizing new analogues, particularly compound 7-methyl-3-(4'-fluoro)phenylquinoxaline-2-carbonitrile 1,4-di-N-oxide (MIC <0.2 microg/mL and SI > 500).

  11. Synthesis and NMR characterization of seven new substituted pyridine N-oxides

    NASA Astrophysics Data System (ADS)

    Laihia, K.; Puszko, A.; Kolehmainen, E.; Lorenc, J.

    2008-10-01

    Seven 3-substituted (alkylamino, alkylnitramino and alkylnitrosoamino) derivatives of pyridine N-oxide have been prepared and their 1H, 13C and 15N NMR chemical shifts assigned based on PFG 1H, 13C HMQC and PFG 1H, X (X = 13C or 15N) HMBC experiments. In the sterically most crowded congener, 3-ethylnitramino-4-nitropyridine N-oxide, chemical non-equivalence or diastereotopicity of the N-CH 2 protons was observed probably due to the chirality of the adjacent amino nitrogen caused by its restricted inversion. The coalescence temperature for the 1H NMR chemical shifts of these geminal protons has been determined and the corresponding Δ G∗ for the energy barrier of the dynamic process has been estimated.

  12. Synthesis and lanthanide coordination chemistry of trifluoromethyl derivatives of phosphinoylmethyl pyridine N-oxides

    SciTech Connect

    Pailloux, Sylvie; Shirima, Cornel Edicome; Duesler, Eileen N.; Smith, Karen Ann; Paine, Robert T.; Klaehn, John D.; McIlwain, Michael E; Hay, Benjamin

    2009-01-01

    A synthetic route for the formation of 2-[bis-(2-trifluoromethyl-phenyl)-phosphinoylmethyl]-pyridine N-oxide (1c) and 2-[bis-(3,5-trifluoromethyl-phenyl)-phosphinoylmethyl]-pyridine N-oxide (1d) was developed and the new ligands characterized by spectroscopic methods and single crystal X-ray diffraction analyses. The coordination chemistry of the ligands was examined with early and late lanthanide ions. The molecular structure of one complex, [Yb(1c)(NO3)3(DMF)](DMF)(H2O)0.5, was determined by single crystal X-ray diffraction methods and the ligand found to coordinate in a bidentate fashion. This coordination chemistry is compared against lanthanide coordination chemistry observed for the related ligand, [Ph2P(O)CH2] C5H4NO.

  13. Geissoschizine methyl ether N-oxide, a new alkaloid with antiacetylcholinesterase activity from Uncaria rhynchophylla.

    PubMed

    Jiang, Wei-Wei; Su, Jia; Wu, Xing-De; He, Juan; Peng, Li-Yan; Cheng, Xiao; Zhao, Qin-Shi

    2015-01-01

    Geissoschizine methyl ether N-oxide, a new oxindole alkaloid, along with 14 known alkaloids, was isolated from the aerial part of Uncaria rhynchophylla. Their structures were identified by comprehensive spectral methods, including 2D NMR experiments, and confirmed by comparing with the literature data. In vitro acetylcholinesterase (AChE) inhibitory activity assay showed that the new compound exhibited anti-AChE activity with IC₅₀ value of 23.4 μM.

  14. Efficacy of quinoxaline-2-carboxylate 1,4-di-N-oxide derivatives in experimental tuberculosis.

    PubMed

    Vicente, Esther; Villar, Raquel; Burguete, Asunción; Solano, Beatriz; Pérez-Silanes, Silvia; Aldana, Ignacio; Maddry, Joseph A; Lenaerts, Anne J; Franzblau, Scott G; Cho, Sang-Hyun; Monge, Antonio; Goldman, Robert C

    2008-09-01

    This study extends earlier reports regarding the in vitro efficacies of the 1,4-di-N-oxide quinoxaline derivatives against Mycobacterium tuberculosis and has led to the discovery of a derivative with in vivo efficacy in the mouse model of tuberculosis. Quinoxaline-2-carboxylate 1,4-di-N-oxide derivatives were tested in vitro against a broad panel of single-drug-resistant M. tuberculosis strains. The susceptibilities of these strains to some compounds were comparable to those of strain H(37)Rv, as indicated by the ratios of MICs for resistant and nonresistant strains, supporting the premise that 1,4-di-N-oxide quinoxaline derivatives have a novel mode of action unrelated to those of the currently used antitubercular drugs. Specific derivatives were further evaluated in a series of in vivo assays, including evaluations of the maximum tolerated doses, the levels of oral bioavailability, and the efficacies in a low-dose aerosol model of tuberculosis in mice. One compound, ethyl 7-chloro-3-methylquinoxaline-2-carboxylate 1,4-dioxide, was found to be (i) active in reducing CFU counts in both the lungs and spleens of infected mice following oral administration, (ii) active against PA-824-resistant Mycobacterium bovis, indicating that the pathway of bioreduction/activation is different from that of PA-824 (a bioreduced nitroimidazole that is in clinical trials), and (iii) very active against nonreplicating bacteria adapted to low-oxygen conditions. These data indicate that 1,4-di-N-oxide quinoxalines hold promise for the treatment of tuberculosis.

  15. Dehydrogenative N-incorporation: a direct approach to quinoxaline N-oxides under mild conditions.

    PubMed

    Chen, Feng; Huang, Xiaoqiang; Li, Xinyao; Shen, Tao; Zou, Miancheng; Jiao, Ning

    2014-09-22

    An efficient method for the synthesis of quinoxaline N-oxides proceeds by the dehydrogenative N-incorporation of simple imines by C(sp(2))-H and C(sp(3))-H bond functionalization. The overall transformation involves the cleavage of three C-H bonds. The reaction is easily handled and proceeds under mild conditions. Simple and readily available tert-butyl nitrite (TBN) was employed as the NO source.

  16. Octanol-water partition coefficients of substituted alpha, N-diphenylnitrones and benzonitrile N-oxides

    SciTech Connect

    Kirchner, J.J.; Acree, W.E. Jr.; Leo, A.J.; Gelli, G.

    1985-10-01

    Experimental octanol-water partition coefficients are reported for substituted alpha, N-diphenylnitrones and benzonitrile N-oxides. The results of these measurements are used to calculate the aromatic fragment constants pi HC = N(O)C6H5, pi C = N----O, fHC = N(O), and fC = N----O for the group contribution methods of Hansch and Leo.

  17. Substitutions of fluorine atoms and phenoxy groups in the synthesis of quinoxaline 1,4-di-N-oxide derivatives.

    PubMed

    Vicente, Esther; Villar, Raquel; Burguete, Asunción; Solano, Beatriz; Ancizu, Saioa; Pérez-Silanes, Silvia; Aldana, Ignacio; Monge, Antonio

    2008-01-18

    The unexpected substitution of fluorine atoms and phenoxy groups attached to quinoxaline or benzofuroxan rings is described. The synthesis of 2-benzyl- and 2-phenoxy-3-methylquinoxaline 1,4-di-N-oxide derivatives was based on the classical Beirut reaction. The tendency of fluorine atoms linked to quinoxaline or benzofuroxan rings to be replaced by a methoxy group when dissolved in an ammonia saturated solution of methanol was clearly demonstrated. In addition, 2-phenoxyquinoxaline 1,4-di-N-oxide derivatives became 2-aminoquinoxaline 1,4-di-N-oxide derivatives in the presence of gaseous ammonia.

  18. A Double-blind, Randomized Pilot Trial of Chromium Picolinate for Binge Eating Disorder: Results of the Binge Eating and Chromium (BEACh) Study

    PubMed Central

    Brownley, Kimberly A.; Holle, Ann Von; Hamer, Robert M.; Via, Maria La; Bulik, Cynthia M.

    2015-01-01

    Objective Chromium treatment has been shown to improve mood, appetite, and glucose regulation in various psychiatric and medical patient populations. The authors propose that chromium may be useful in the treatment of binge eating disorder (BED). Method Twenty-four overweight adults with BED were enrolled in a 6-month double-blind placebo-controlled trial and randomly assigned to receive either 1000mcg chromium/day (“high dose”; n=8) or 600mcg chromium/day (“moderate dose”; n=9) as chromium picolinate or placebo (n=7). Mixed linear regression models were used to estimate mean change in binge frequency and related psychopathology, weight, symptoms of depression, and fasting glucose. Results Fasting glucose was significantly reduced in both chromium groups compared to the placebo group; similarly, numerically, but not significantly, greater reductions in binge frequency, weight, and symptoms of depression were observed in those treated with chromium versus placebo, although statistical power was limited in this pilot trial. For fasting glucose, the findings suggest a dose response with larger effects in the high dose compared to moderate dose group. Conclusion These initial findings support further larger trials to determine chromium’s efficacy in maintaining normal glucose regulation, reducing binge eating and related psychopathology, promoting modest weight loss, and reducing symptoms of depression in individuals with BED. Studies designed to link the clinical effects of chromium with changes in underlying insulin, serotonin, and dopamine pathways may be especially informative. If efficacious, chromium supplementation may provide a useful, low-cost alternative to or augmentation strategy for selective serotonin reuptake inhibitors, which have partial efficacy in BED. ClinicalTrials.gov NCT00904306. PMID:23751236

  19. Effects of dietary chromium picolinate and peppermint essential oil on growth performance and blood biochemical parameters of broiler chicks reared under heat stress conditions.

    PubMed

    Akbari, Mohsen; Torki, Mehran

    2014-08-01

    A study was conducted using 240 female day-old broiler chicks to evaluate the effects of dietary chromium picolinate (CrPic), peppermint essential oil (P.mint), or their combination on growth performance and blood biochemical parameters of female broiler chicks raised under heat stress conditions (HS, 23.9 to 38 °C cycling). Average daily gain (ADG), average daily feed intake (ADFI), and feed conversion ratio (FCR) were obtained from 1 to 42 days of age. Furthermore, at the end of the experiment (day 42), birds were bled to determine some blood biochemical parameters and weighed for final body weight (BW). ADFI, ADG, and BW were not influenced significantly by dietary CrPic and P.mint (P>0.05). A significant interaction between dietary CrPic and P.mint on FCR (P=0.012) was detected. FCR significantly decreased in chicks fed the diet including both CrPic and P.mint compared with the CrPic group. Significant interaction between dietary P.mint and CrPic on serum concentrations of triglycerides, glucose, and albumin were observed (P<0.05), but the other measured blood biochemical parameters were not statistically affected by dietary treatments (P>0.05). The serum concentrations of glucose, triglycerides were decreased (P<0.05) in broilers fed the diet including both CrPic and P.mint. Plasma chromium (Cr) content increased significantly (P<0.05) in birds fed the CrPic-included diet compared with the control group (P<0.05). From the results of the present experiment it can be concluded that dietary supplementation with combined P.mint and CrPic could have beneficial effects on some blood biochemical parameters of female chicks reared under heat stress conditions.

  20. Effects of dietary chromium picolinate and peppermint essential oil on growth performance and blood biochemical parameters of broiler chicks reared under heat stress conditions

    NASA Astrophysics Data System (ADS)

    Akbari, Mohsen; Torki, Mehran

    2014-08-01

    A study was conducted using 240 female day-old broiler chicks to evaluate the effects of dietary chromium picolinate (CrPic), peppermint essential oil (P.mint), or their combination on growth performance and blood biochemical parameters of female broiler chicks raised under heat stress conditions (HS, 23.9 to 38 °C cycling). Average daily gain (ADG), average daily feed intake (ADFI), and feed conversion ratio (FCR) were obtained from 1 to 42 days of age. Furthermore, at the end of the experiment (day 42), birds were bled to determine some blood biochemical parameters and weighed for final body weight (BW). ADFI, ADG, and BW were not influenced significantly by dietary CrPic and P.mint ( P > 0.05). A significant interaction between dietary CrPic and P.mint on FCR ( P = 0.012) was detected. FCR significantly decreased in chicks fed the diet including both CrPic and P.mint compared with the CrPic group. Significant interaction between dietary P.mint and CrPic on serum concentrations of triglycerides, glucose, and albumin were observed ( P < 0.05), but the other measured blood biochemical parameters were not statistically affected by dietary treatments ( P > 0.05). The serum concentrations of glucose, triglycerides were decreased ( P < 0.05) in broilers fed the diet including both CrPic and P.mint. Plasma chromium (Cr) content increased significantly ( P < 0.05) in birds fed the CrPic-included diet compared with the control group ( P < 0.05). From the results of the present experiment it can be concluded that dietary supplementation with combined P.mint and CrPic could have beneficial effects on some blood biochemical parameters of female chicks reared under heat stress conditions.

  1. Oral chromium picolinate improves carbohydrate and lipid metabolism and enhances skeletal muscle Glut-4 translocation in obese, hyperinsulinemic (JCR-LA corpulent) rats.

    PubMed

    Cefalu, William T; Wang, Zhong Q; Zhang, Xian H; Baldor, Linda C; Russell, James C

    2002-06-01

    Human studies suggest that chromium picolinate (CrPic) decreases insulin levels and improves glucose disposal in obese and type 2 diabetic populations. To evaluate whether CrPic may aid in treatment of the insulin resistance syndrome, we assessed its effects in JCR:LA-corpulent rats, a model of this syndrome. Male lean and obese hyperinsulinemic rats were randomly assigned to receive oral CrPic [80 microg/(kg. d); n = 5 or 6, respectively) in water or to control conditions (water, n = 5). After 3 mo, a 120-min intraperitoneal glucose tolerance test (IPGTT) and a 30-min insulin tolerance test were performed. Obese rats administered CrPic had significantly lower fasting insulin levels (1848 +/- 102 vs. 2688 +/- 234 pmol/L; P < 0.001; mean +/- SEM) and significantly improved glucose disappearance (P < 0.001) compared with obese controls. Glucose and insulin areas under the curve for IPGTT were significantly less for obese CrPic-treated rats than in obese controls (P < 0.001). Obese CrPic-treated rats had lower plasma total cholesterol (3.57 +/- 0.28 vs. 4.11 +/- 0.47 mmol/L, P < 0.05) and higher HDL cholesterol levels (1.92 +/- 0.09 vs. 1.37 +/- 0.36 mmol/L, P < 0.01) than obese controls. CrPic did not alter plasma glucose or cholesterol levels in lean rats. Total skeletal muscle glucose transporter (Glut)-4 did not differ among groups; however, CrPic significantly enhanced membrane-associated Glut-4 in obese rats after insulin stimulation. Thus, CrPic supplementation enhances insulin sensitivity and glucose disappearance, and improves lipids in male obese hyperinsulinemic JCR:LA-corpulent rats.

  2. Performance, egg quality traits, and serum metabolite concentrations of laying hens affected by dietary supplemental chromium picolinate and vitamin C under a heat-stress condition.

    PubMed

    Torki, Mehran; Zangeneh, Samira; Habibian, Mahmood

    2014-02-01

    A 3 × 2 factorial experiment consisting three levels (0, 200, and 400 μg/kg) of chromium (chromium picolinate) and two levels (0 and 250 mg/kg) of vitamin C was employed to evaluate the effects of these dietary supplements on performance, egg quality traits, and serum biochemical parameters of heat-stressed laying hens (Lohmann LSL-Lite) from 66 to 74 weeks of age. Feed intake increased when birds were given either 400 μg/kg chromium or 250 mg/kg vitamin C (P < 0.05), but the birds that received both chromium and vitamin C consumed feed similar to those that received only chromium. Dietary treatments had no effect on egg production, egg mass, egg volume, feed conversion ratio, and body mass (P > 0.05). The birds that fed on diet with chromium or vitamin C produced eggs with higher shell mass and thickness compared to the control. Both eggshell mass and thickness decreased when vitamin C and chromium were supplemented simultaneously, and birds given the diet supplemented with 400 μg/kg chromium and 250 mg/kg vitamin C had eggshell mass and thickness similar to those of the control group. The serum concentration of chromium increased due to increasing level of dietary chromium (P < 0.05). The birds that received diet with chromium and vitamin C had higher serum concentrations of chromium compared to those that received only chromium (P < 0.05). Similarly, the hens that received chromium and vitamin C had higher serum concentrations of calcium and phosphorus compared to the hens fed with other treatments (P < 0.05). The birds given with supplemental chromium exhibited lower serum glucose, total cholesterol, and triglycerides concentrations but higher serum albumin and total protein concentrations compared to the other groups (P < 0.05).

  3. Anti-diabetic activity of chromium picolinate and biotin in rats with type 2 diabetes induced by high-fat diet and streptozotocin.

    PubMed

    Sahin, Kazim; Tuzcu, Mehmet; Orhan, Cemal; Sahin, Nurhan; Kucuk, Osman; Ozercan, Ibrahim H; Juturu, Vijaya; Komorowski, James R

    2013-07-28

    The objective of the present study was to evaluate anti-diabetic effects of chromium picolinate (CrPic) and biotin supplementations in type 2 diabetic rats. The type 2 diabetic rat model was induced by high-fat diet (HFD) and low-dose streptozotocin. The rats were divided into five groups as follows: (1) non-diabetic rats fed a regular diet; (2) diabetic rats fed a HFD; (3) diabetic rats fed a HFD and supplemented with CrPic (80 μg/kg body weight (BW) per d); (4) diabetic rats fed a HFD and supplemented with biotin (300 μg/kg BW per d); (5) diabetic rats fed a HFD and supplemented with both CrPic and biotin. Circulating glucose, cortisol, total cholesterol, TAG, NEFA and malondialdehyde concentrations decreased (P< 0·05), but serum insulin concentrations increased (P< 0·05) in diabetic rats treated with biotin and CrPic, particularly with a combination of the supplements. Feeding a HFD to diabetic rats decreased PPAR-γ expression in adipose tissue and phosphorylated insulin receptor substrate 1 (p-IRS-1) expression of liver, kidney and muscle tissues, while the supplements increased (P< 0·001) PPAR-γ and p-IRS-1 expressions in relevant tissues. Expression of NF-κB in the liver and kidney was greater in diabetic rats fed a HFD, as compared with rats fed a regular diet (P< 0·01). The supplements decreased the expression of NF-κB in diabetic rats (P< 0·05). Results of the present study revealed that supplementing CrPic and biotin alone or in a combination exerts anti-diabetic activities, probably through modulation of PPAR-γ, IRS-1 and NF-κB proteins.

  4. Effect of chromium picolinate and melatonin either in single or in a combination in high carbohydrate diet-fed male Wistar rats.

    PubMed

    Doddigarla, Zephy; Ahmad, Jamal; Parwez, Iqbal

    2016-01-01

    This study is designed to know the effects of chromium picolinate (CrPic) and melatonin (Mel) each alone and in a combination on high carbohydrate diet-fed (HCD-fed) male Wistar rats that exhibit insulin resistance (IR), hyperglycemia, and oxidative stress. Wistar rats have been categorized into five groups. Each group consisted of six male Wistar rats, control rats (group I), HCD (group II), HCD + CrPic (group III), HCD + Mel (group IV), and HCD + CrPic + Mel (group V). Insignificant differences were observed in serum levels of superoxide dismutase, nitric oxide, and zinc in group III, group IV, and group V when each group was compared with group II rats respectively. Significant differences were observed in group III, group IV, and group V when each group was compared with group II in homeostasis model assessment-estimated IR (P < 0.05, <0.0.05, <0.05), and in the levels of blood glucose (P < 0.05, <0.0.05, <0.05), total cholesterol (P < 0.05, <0.001, <0.001), triacylglycerols (<0.05, <0.001, <0.001), high density lipoprotein cholesterol (P < 0.05, <0.001, <0.001), malondialdehyde (P < 0.05, <0.05, <0.001), catalase (P <0.05, <0.05, <0.05), glutathione (P < 0.05, <0.05, <0.05), Mel (P < 0.05, <0.05, <0.001), and copper (P < 0.05, <0.05, < 0.001). In view of these results, HCD-fed male Wistar rats that are destined to attain IR and T2DM through diet can be prevented by giving CrPic and Mel administration in alone or in a combination.

  5. Synthesis of meta-substituted [(18)F]3-fluoro-4-aminopyridine via direct radiofluorination of pyridine N-oxides.

    PubMed

    Brugarolas, P; Freifelder, R; Cheng, S-H; DeJesus, O

    2016-06-04

    Due to their electron-rich aromatic structure, nucleophilic (radio)fluorination of pyridines is challenging, especially at the meta position. In this paper, we describe the first example of direct fluorination of a pyridine N-oxide to produce a meta fluorinated pyridine. Specifically, fluorination of 3-bromo-4-nitropyridine N-oxide produced in several minutes 3-fluoro-4-nitropyridine N-oxide in moderate yield at room temperature. This intermediate compound was later converted to 3-fluoro-4-aminopyridine easily by catalytic hydrogenation. Furthermore, this approach was successfully applied for labeling with fluorine-18. The use of pyridine N-oxides for the preparation of fluoropyridines is unprecedented in the chemical literature and has the potential to offer a new way for the synthesis of these important structures in pharmaceuticals and radiopharmaceuticals.

  6. "Marking" the nitrogen atoms of phenyl-(2-pyridyl)-(3-pyridyl)-(4-pyridyl)-methane. Synthesis and absolute configuration of the corresponding tris(pyridine N-oxide).

    PubMed

    Matsumoto, Kouzou; Miki, Kaori; Inagaki, Takuya; Nehira, Tatsuo; Pescitelli, Gennaro; Hirao, Yasukazu; Kurata, Hiroyuki; Kawase, Takeshi; Kubo, Takashi

    2011-08-01

    To "mark" the nitrogen atoms in phenyl-(2-pyridyl)-(3-pyridyl)-(4-pyridyl)methane (1), we have synthesized the corresponding tris(pyridine N-oxide) 2 by oxidation of 1 with m-chloroperbenzoic acid. The nitrogen atoms of 2 are unequivocally determined by the X-ray crystal analysis of a single crystal of rac-2 whereas the nitrogen atoms cannot be assigned at all in the case of rac-1. N-Oxide 2 can be resolved by chiral high-performance liquid chromatography under similar conditions to those used for the resolution of 1. The calculated circular dichroism (CD) curve for (R)-2 on the basis of time-dependent density functional theory reproduces the experimental spectra very well to suggest that the second-eluted fraction ([CD(+)283]-2) is the R isomer, namely (R)-[CD(+)283]-2. The independent absolute configuration determinations for 1 and 2 are in keeping with the chemical correlation between the two compounds by oxidation of (R)-1 into (R)-2.

  7. Isothermal and isochoric crystallization of highly hygroscopic pyridine N-oxide of aqueous solution.

    PubMed

    Patyk, Ewa; Marciniak, Jedrzej; Tomkowiak, Hanna; Katrusiak, Andrzej; Merz, Klaus

    2014-06-01

    Highly hygroscopic pyridine N-oxide, C5H5NO, dissolves in water absorbed from atmospheric air, but it crystallizes in the neat form of the aqueous solution under high pressure. The crystals grown at high-pressure isochoric conditions are of the same phase as that obtained from anhydrous crystallization at ambient pressure. This feature can be employed for retrieving compounds highly soluble in water from their aqueous solutions. The crystal structure is strongly stabilized by CH...O contacts. The crystal compression and thermal expansion as well as three shortest H...O distances comply with the inverse-relationship rule of pressure and temperature changes.

  8. Structure of the Molybdenum Site of EEcherichia Coli Trimethylamine N-Oxide Reductase

    SciTech Connect

    Zhang, L.; Nelson, K.Johnson; Rajagopalan, K.V.; George, G.N.

    2009-05-28

    We report a structural characterization of the molybdenum site of recombinant Escherichia coli trimethylamine N-oxide (TMAO) reductase using X-ray absorption spectroscopy. The enzyme active site shows considerable similarity to that of dimethyl sulfoxide (DMSO) reductase, in that, like DMSO reductase, the TMAO reductase active site can exist in multiple forms. Examination of the published crystal structure of TMAO oxidase from Shewanella massilia indicates that the postulated Mo coordination structure is chemically impossible. The presence of multiple active site structures provides a potential explanation for the anomalous features reported from the crystal structure.

  9. Structures and spectroscopic properties of Ni(II) and Mn(II) complexes based on 5-(3‧, 5‧-dicarboxylphenyl) picolinic acid ligand

    NASA Astrophysics Data System (ADS)

    Ma, Qi; Song, Jin-Ping; Su, Feng; Guo, Jun-Mei; Guo, Yong; Dong, Chuan

    2016-05-01

    Two novel complexes including [Ni(Hdcppa)(H2O)4] (1) and {[Mn3(dcppa)2(H2O)6]·2H2O}n (2) have been synthesized and characterized by single crystal X-ray structure analysis and elemental analysis. Results show that 1 is a mononuclear nickel(II) compound with octahedron coordination geometry, while 2 is a stairs-like 2D layer structure consisting of the trinuclear MnII units linked through dcppa3-. Spectroscopic and electrochemical properties of the complexes 1-2 have also been studied in dimethyl sulfoxide solution at room temperature.

  10. Protonation of trimethylamine N-oxide (TMAO) is required for stabilization of RNA tertiary structure.

    PubMed

    Denning, Elizabeth J; Thirumalai, D; MacKerell, Alexander D

    2013-12-31

    The osmolyte trimethylamine N-oxide (TMAO) stabilizes the tertiary but not the secondary structures of RNA. However, molecular dynamics simulations performed on the PreQ1 riboswitch showed that TMAO destabilizes the tertiary riboswitch structure, leading us to hypothesize that the presence of RNA could result in enhanced population of the protonated form, TMAOP. Constant pH replica exchange simulations showed that a percentage of TMAO is indeed protonated, thus contributing to the stability of the tertiary but not the secondary structure of PreQ1. TMAOP results in an unfavorable dehydration of phosphodiester backbone, which is compensated by electrostatic attraction between TMAOP and the phosphate groups. In addition, TMAOP interacts with specific sites in the tertiary RNA structure, mimicking the behavior of positively charged ions and of the PreQ1 ligand in stabilizing RNA. Finally, we predict that TMAO-induced stabilization of RNA tertiary structures should be strongly pH dependent.

  11. Restored mutant receptor:Corticoid binding in chaperone complexes by trimethylamine N-oxide

    PubMed Central

    Miller, Aaron L.; Elam, W. Austin; Johnson, Betty H.; Khan, Shagufta H.; Kumar, Raj; Thompson, E. Brad

    2017-01-01

    Without a glucocorticoid (GC) ligand, the transcription factor glucocorticoid receptor (GR) is largely cytoplasmic, with its GC-binding domain held in high affinity conformation by a cluster of chaperones. Binding a GC causes serial dis- and re-associations with chaperones, translocation of the GR to the nucleus, where it binds to DNA sites and associates with coregulatory proteins and basic transcription complexes. Herein, we describe the effects of a potent protective osmolyte, trimethylamine N-oxide (TMAO), on a conditions-dependent “activation-labile” mutant GR (GRact/l), which under GR-activating conditions cannot bind GCs in cells or in cell cytosols. In both cells and cytosols, TMAO restores binding to GRact/l by stabilizing it in complex with chaperones. Cells bathed in much lower concentrations of TMAO than those required in vitro show restoration of GC binding, presumably due to intracellular molecular crowding effects. PMID:28301576

  12. Crystal structure of 3,5-di­methyl­pyridine N-oxide dihydrate

    PubMed Central

    Merino García, Rosario; Ríos-Merino, Francisco Javier; Bernès, Sylvain; Reyes-Ortega, Yasmi

    2016-01-01

    In the title compound, also known as 3,5-lutidine N-oxide dihydrate, C7H9NO·2H2O, the N—O bond is weakened due to the involvement of the O atom as an acceptor of hydrogen bonds from the two water mol­ecules of crystallization present in the asymmetric unit. Fused R 3 5(10) ring motifs based on O—H⋯O hydrogen bonds form chains in the [010] direction, which are further connected by weak C—H⋯O inter­molecular contacts. As a result, the lutidine mol­ecules are stacked in an efficient manner, with π–π contacts characterized by a short separation of 3.569 (1) Å between the benzene rings. PMID:27980810

  13. Effects of trimethylamine N-oxide and urea on DNA duplex and G-quadruplex

    PubMed Central

    Ueda, Yu-mi; Zouzumi, Yu-ki; Maruyama, Atsushi; Nakano, Shu-ichi; Sugimoto, Naoki; Miyoshi, Daisuke

    2016-01-01

    Abstract We systematically investigated effects of molecular crowding with trimethylamine N-oxide (TMAO) as a zwitterionic and protective osmolyte and urea as a nonionic denaturing osmolyte on conformation and thermodynamics of the canonical DNA duplex and the non-canonical DNA G-quadruplex. It was found that TMAO and urea stabilized and destabilized, respectively, the G-quadruplex. On the other hand, these osmolytes generally destabilize the duplex; however, it was observed that osmolytes having the trimethylamine group stabilized the duplex at the lower concentrations because of a direct binding to a groove of the duplex. These results are useful not only to predict DNA structures and their thermodynamics under physiological environments in living cells, but also design of polymers and materials to regulate structure and stability of DNA sequences. PMID:27933115

  14. Protonation of Trimethylamine N-Oxide (TMAO) is required for stabilization of RNA tertiary structure

    PubMed Central

    Denning, Elizabeth J.; Thirumalai, D.; MacKerell, Alexander D.

    2013-01-01

    The osmolyte trimethylamine N-oxide (TMAO) stabilizes the tertiary but not the secondary structures of RNA. However, molecular dynamics simulations performed on the PreQl riboswitch showed that TMAO destabilizes the tertiary riboswitch structure, leading us to hypothesize that the presence of RNA could result in enhanced population of the protonated form, TMAOP. Constant pH replica exchange simulations showed that a percentage of TMAO is indeed protonated, thus contributing to the stability of the tertiary but not the secondary structure of PreQl. TMAOP results in an unfavorable dehydration of phosphodiester backbone, which is compensated by electrostatic attraction between TMAOP and the phosphate groups. In addition, TMAOP interacts with specific sites in the tertiary RNA structure, mimicking the behavior of positively charged ions and of the PreQl ligand in stabilizing RNA. Finally, we predict that TMAO-induced stabilization of RNA tertiary structures should be strongly pH dependent. PMID:24012912

  15. Comparative studies on the cumene hydroperoxide- and NADPH-supported N-oxidation of 4-chloroaniline by cytochrome P-450.

    PubMed

    Hlavica, P; Golly, I; Mietaschk, J

    1983-06-15

    The present study confirms that cytochrome P-450 can act as a catalyst in the cumene hydroperoxide-supported N-oxidation of 4-chloroaniline. Analogous to the NADPH/O2-driven N-oxidation process, product dissociation is likely to limit the overall rate of cytochrome P-450 cycling also in the peroxidatic pathway. The oxy complexes involved in either metabolic route differ with respect to stability, spectral properties and need for thiolate-mediated resonance stabilization. With the organic hydroperoxide, the metabolic profile is shifted from the preponderant production of N-(4-chlorophenyl)hydroxylamine to the formation of 1-chloro-4-nitrobenzene. This finding suggests that the peroxide-sustained N-oxidation mechanism differs in several ways from that functional in the NADPH/O2-dependent oxenoid reaction. Thus one-electron oxidation, triggered by homolytic cleavage of the oxygen donor, is proposed as the mechanism of peroxidatic transformation of 4-chloroaniline.

  16. Radical Chemistry and Cytotoxicity of Bioreductive 3-Substituted Quinoxaline Di-N-Oxides.

    PubMed

    Anderson, Robert F; Yadav, Pooja; Shinde, Sujata S; Hong, Cho R; Pullen, Susan M; Reynisson, Jóhannes; Wilson, William R; Hay, Michael P

    2016-08-15

    The radical chemistry and cytotoxicity of a series of quinoxaline di-N-oxide (QDO) compounds has been investigated to explore the mechanism of action of this class of bioreductive drugs. A series of water-soluble 3-trifluoromethyl (4-10), 3-phenyl (11-19), and 3-methyl (20-21) substituted QDO compounds were designed to span a range of electron affinities consistent with bioreduction. The stoichiometry of loss of QDOs by steady-state radiolysis of anaerobic aqueous formate buffer indicated that one-electron reduction of QDOs generates radicals able to initiate chain reactions by oxidation of formate. The 3-trifluoromethyl analogues exhibited long chain reactions consistent with the release of the HO(•), as identified in EPR spin trapping experiments. Several carbon-centered radical intermediates, produced by anaerobic incubation of the QDO compounds with N-terminal truncated cytochrome P450 reductase (POR), were characterized using N-tert-butyl-α-phenylnitrone (PBN) and 5-(diethoxyphosphoryl)-5-methyl-1-pyrroline-N-oxide (DEPMPO) spin traps and were observed by EPR. Experimental data were well simulated for the production of strongly oxidizing radicals, capable of H atom abstraction from methyl groups. The kinetics of formation and decay of the radicals produced following one-electron reduction of the parent compounds, both in oxic and anoxic solutions, were determined using pulse radiolysis. Back oxidation of the initially formed radical anions by molecular oxygen did not compete effectively with the breakdown of the radical anions to form oxidizing radicals. The QDO compounds displayed low hypoxic selectivity when tested against oxic and hypoxic cancer cell lines in vitro. The results from this study form a kinetic description and explanation of the low hypoxia-selective cytotoxicity of QDOs against cancer cells compared to the related benzotriazine 1,4-dioxide (BTO) class of compounds.

  17. Ultra-performance liquid chromatography-tandem mass spectrometric assay for the simultaneous determination of brucine, strychnine and brucine N-oxide in rat plasma: application to a pharmacokinetic study.

    PubMed

    Gu, Wei; Wang, Dongyue; Pan, Zihao; Liu, Xiao; Cai, Baochang; Chen, Jun

    2016-07-01

    A rapid, simple and sensitive UHPLC-MS/MS method was developed and validated for the simultaneous determination of brucine, strychnine and brucine N-oxide in rat plasma using huperzine A as an internal standard (IS) after protein precipitation with methanol. The analytes were separated on a Purospher® STAR RP18 UHPLC column (2 µm, 2.1 × 100 mm) by gradient elution using a mobile phase composed of methanol and water (containing 0.1% formic acid) at a flow rate of 0.3 mL/min. Brucine, strychnine, brucine N-oxide and IS were detected in positive ion multiple reaction monitoring mode by means of an electrospray ionization interface (m/z 395.2 → 324.1, m/z 335.2 → 184.1, m/z 411.2 → 394.2, m/z 243.1 → 226.1). The calibration curve was linear over the range of 1-500 ng/mL for brucine and strychnine and 0.2-50 ng/mL for brucine N-oxide. The intra- and inter-day precisions of these analytes were all within 15% and the accuracy ranged from 85 to 115%. The stability experiment indicated that the plasma samples at three concentration levels were stable under different conditions. The developed method was successfully applied for the first time to pharmacokinetic studies of brucine, strychnine and brucine N-oxide following a single oral and intravenous administration of modified total alkaloid fraction in rats. Copyright © 2016 John Wiley & Sons, Ltd.

  18. Biotransformation of prochiral 2-phenyl-1,3-di(4-pyridyl)-2-propanol to a chiral N-oxide metabolite.

    PubMed

    Schwartz, M A; Williams, T H; Kolis, S J; Postma, E; Sasso, G J

    1978-01-01

    The prochiral compound, 2-phenyl-1,3-di(4-pyridyl)-2-propanol (PPP) labeled with 3H in the phenyl ring, was administered to rats, dogs, and a human subject. Paper chromatography of the urine indicated that a major metabolite common to all three species was excreted. This metabolite was isolated from the urine of chronically dosed dogs and was identified by mass, nuclear magnetic resonance (NMR), and infrared spectrometry as the N-oxide, 2-phenyl-1-(4-pyridyl)-3-(4-pyridyl-1-oxide)-2-propanol. In addition, polarimetry indicated that this metabolite was levorotatory. Examination of the enantiomeric purity of a crystallized sample of the metabolite by NMR spectroscopy of resolvable diastereomeric salts formed with lasalocid revealed the presence of only the levorotatory enantiomer. Accordingly, this metabolic N-oxide formation in the dog was at least stereoselective, and perhaps stereospecific. The N-oxidation of PPP was also demonstrated in vitro with 9000 g supernatant fraction of rat liver fortified with an NADPH generating system, and this reaction was inducible by phenobarbital, indicating that it is mediated by the cytochrome P-450 mixed-function oxidase system. This study, in addition to providing another example of the pyridyl N-oxidation pathway, illustrates the necessity of considering the stereochemical aspects of the metabolism of prochiral drugs.

  19. Determination of Methylamines and Trimethylamine-N-oxide in particulate matter by non-suppressed ion chromatography

    Technology Transfer Automated Retrieval System (TEKTRAN)

    An ion chromatography method with non-suppressed conductivity detection was developed for the simultaneous determination of methylamines (methylamine, dimethylamine, trimethylamine) and trimethylamine-N-oxide in particulate matter air samples. The analytes were well separated by means of cation-exch...

  20. Rapid screening of N-oxides of chemical warfare agents degradation products by ESI-tandem mass spectrometry.

    PubMed

    Sridhar, L; Karthikraj, R; Lakshmi, V V S; Raju, N Prasada; Prabhakar, S

    2014-08-01

    Rapid detection and identification of chemical warfare agents and related precursors/degradation products in various environmental matrices is of paramount importance for verification of standards set by the chemical weapons convention (CWC). Nitrogen mustards, N,N-dialkylaminoethyl-2-chlorides, N,N-dialkylaminoethanols, N-alkyldiethanolamines, and triethanolamine, which are listed CWC scheduled chemicals, are prone to undergo N-oxidation in environmental matrices or during decontamination process. Thus, screening of the oxidized products of these compounds is also an important task in the verification process because the presence of these products reveals alleged use of nitrogen mustards or precursors of VX compounds. The N-oxides of aminoethanols and aminoethylchlorides easily produce [M + H](+) ions under electrospray ionization conditions, and their collision-induced dissociation spectra include a specific neutral loss of 48 u (OH + CH2OH) and 66 u (OH + CH2Cl), respectively. Based on this specific fragmentation, a rapid screening method was developed for screening of the N-oxides by applying neutral loss scan technique. The method was validated and the applicability of the method was demonstrated by analyzing positive and negative samples. The method was useful in the detection of N-oxides of aminoethanols and aminoethylchlorides in environmental matrices at trace levels (LOD, up to 500 ppb), even in the presence of complex masking agents, without the use of time-consuming sample preparation methods and chromatographic steps. This method is advantageous for the off-site verification program and also for participation in official proficiency tests conducted by the Organization for the Prohibition of Chemical Weapons (OPCW), the Netherlands. The structure of N-oxides can be confirmed by the MS/MS experiments on the detected peaks. A liquid chromatography-mass spectrometry (LC-MS) method was developed for the separation of isomeric N-oxides of aminoethanols and

  1. Roflumilast n-oxide associated with PGE2 prevents the neutrophil elastase-induced production of chemokines by epithelial cells.

    PubMed

    Victoni, Tatiana; Gicquel, Thomas; Bodin, Aude; Daude, Marion; Tenor, Hermann; Valença, Samuel; Devillier, Philippe; Porto, Luis Cristovão; Lagente, Vincent; Boichot, Elisabeth

    2016-01-01

    Neutrophil chemotaxis is involved in the lung inflammatory process in conditions such as chronic obstructive pulmonary disease (COPD). Neutrophil elastase (NE), one of the main proteases produced by neutrophils, has an important role in the inflammatory process via the release of chemokines from airway epithelial cells. It was recently shown that roflumilast N-oxide has therapeutic potential in COPD. The aim of the present study was to investigate roflumilast N-oxide's effect on NE-induced chemokine production and signaling pathways in A549 epithelial cells. A549 cells were incubated with NE for 30min, washed with PBS and then cultured for 2h (for measurement of mRNA expression) and 24h (for chemokine release) or for 5 to 30min (for protein phosphorylation assays). Prior to the addition of NE, cells were also pre-incubated with prostaglandin E2 (PGE2), alone and in combination with roflumilast N-oxide. Addition of NE was associated with elevated chemokine production by A549 cells and induction of the p38α pathway. In contrast when combined with PGE2, the roflumilast N-oxide had an additive effect on the inhibition of NE-induced chemokine release and p38α and other kinases activation. In conclusion, we demonstrated that NE is able to increase the release of chemokines from epithelial cells via the activation of p38α MAP-kinase and that roflumilast N-oxide when combined with PGE2 lowers NE-induced kinase activation and chemokine production.

  2. Destruction of hydrogen bonds of poly(N-isopropylacrylamide) aqueous solution by trimethylamine N-oxide

    NASA Astrophysics Data System (ADS)

    Reddy, P. Madhusudhana; Taha, Mohamed; Venkatesu, Pannuru; Kumar, Awanish; Lee, Ming-Jer

    2012-06-01

    Trimethylamine N-oxide (TMAO) is a compatible or protective osmolyte that stabilizes the protein native structure through non-bonding mechanism between TMAO and hydration surface of protein. However, we have shown here first time the direct binding mechanism for naturally occurring osmolyte TMAO with hydration structure of poly(N-isopropylacrylamide) (PNIPAM), an isomer of polyleucine, and subsequent aggregation of PNIPAM. The influence of TMAO on lower critical solution temperature (LCST) of PNIPAM was investigated as a function of TMAO concentration at different temperatures by fluorescence spectroscopy, viscosity (η), multi angle dynamic light scattering, zeta potential, and Fourier transform infrared (FTIR) spectroscopy measurements. To address some of the basis for further analysis of FTIR spectra of PNIPAM, we have also measured FTIR spectra for the monomer of N-isopropylacrylamide (NIPAM) in deuterium oxide (D2O) as a function of TMAO concentration. Our experimental results purportedly elucidate that the LCST values decrease with increasing TMAO concentration, which is mainly contributing to the direct hydrogen bonding of TMAO with the water molecules that are bound to the amide (-CONH) functional groups of the PNIPAM. We believed that the present work may act as a ladder to reach the heights of understanding of molecular mechanism between TMAO and macromolecule.

  3. Effects of the osmolyte TMAO (Trimethylamine-N-oxide) on aqueous hydrophobic contact-pair interactions.

    PubMed

    Macdonald, Ryan D; Khajehpour, Mazdak

    2013-12-31

    Osmolytes are small, soluble organic molecules produced by living organisms for maintaining cell volume. These molecules have also been shown to have significant effects on the stability of proteins. Perhaps one of the most studied osmolytes is Trimethylamine-N-oxide (TMAO). Thermodynamic studies of the effects of TMAO on proteins have shown that this molecule is a strong stabilizer of the protein folded state, thus being able to counteract the effects of protein denaturants such as urea and guanidine hydrochloride. Most studies of TMAO effects on bio-molecular stability have until now been focused on how the osmolyte reduces the solubility of polypeptide backbones, while the effects of TMAO on hydrophobic interactions are still not well understood. In fact, there are few experimental data measuring the effect of TMAO on hydrophobic interactions. This work studies phenyl and alkyl contact pairs as model hydrophobic contact pairs. The formation of these contact pairs is monitored using fluorescence, i.e., through the quenching of phenol fluorescence by carboxylate ions; and a methodology is developed to isolate hydrophobic contributions from other interactions. The data demonstrate that the addition of TMAO to the aqueous solvent destabilizes hydrophobic contact pairs formed between alkyl and phenyl moieties. In other words, TMAO acts as a "denaturant" for hydrophobic interactions.

  4. Trypanocidal Activity of Quinoxaline 1,4 Di-N-oxide Derivatives as Trypanothione Reductase Inhibitors.

    PubMed

    Chacón-Vargas, Karla Fabiola; Nogueda-Torres, Benjamin; Sánchez-Torres, Luvia E; Suarez-Contreras, Erick; Villalobos-Rocha, Juan Carlos; Torres-Martinez, Yuridia; Lara-Ramirez, Edgar E; Fiorani, Giulia; Krauth-Siegel, R Luise; Bolognesi, Maria Laura; Monge, Antonio; Rivera, Gildardo

    2017-02-01

    Chagas disease or American trypanosomiasis is a worldwide public health problem. In this work, we evaluated 26 new propyl and isopropyl quinoxaline-7-carboxylate 1,4-di-N-oxide derivatives as potential trypanocidal agents. Additionally, molecular docking and enzymatic assays on trypanothione reductase (TR) were performed to provide a basis for their potential mechanism of action. Seven compounds showed better trypanocidal activity on epimastigotes than the reference drugs, and only four displayed activity on trypomastigotes; T-085 was the lead compound with an IC50 = 59.9 and 73.02 µM on NINOA and INC-5 strain, respectively. An in silico analysis proposed compound T-085 as a potential TR inhibitor with better affinity than the natural substrate. Enzymatic analysis revealed that T-085 inhibits parasite TR non-competitively. Compound T-085 carries a carbonyl, a CF3, and an isopropyl carboxylate group at 2-, 3- and 7-position, respectively. These results suggest the chemical structure of this compound as a good starting point for the design and synthesis of novel trypanocidal derivatives with higher TR inhibitory potency and lower toxicity.

  5. Trimethylamine N-oxide as a media supplement for cartilage tissue engineering.

    PubMed

    O'Connell, Grace D; Fong, Jason V; Dunleavy, Neil; Joffe, Avrum; Ateshian, Gerard A; Hung, Clark T

    2012-12-01

    Supplements added to the culture media (e.g., growth factors and dexamethasone) have been successful in improving mechanical and biochemical properties of engineered cartilage towards native values. Trimethylamine N-oxide (TMAO), a natural osmolyte found in shark cartilage, is thought to induce protein folding, and counteracts the destabilizing effect of the high concentrations of urea stored by sharks. The objective of this study was to investigate the use of TMAO as a media supplement for promoting growth of functional engineered cartilage in culture. In the first study, TMAO was added to the culture media for the first 14 days in culture and concentrations of 0-200 mM were evaluated. In the second study, TMAO was supplemented to the culture media following chondroitinase ABC digestion, which has been previously shown to mediate an increased collagen content in engineered cartilage. A dose-dependent response was observed with improved mechanical and biochemical properties for engineered constructs cultured with TMAO at concentrations of 5-100 mM. The Young's modulus of digested constructs cultured in TMAO was 2× greater than digested constructs cultured in the control medium and recovered to undigested control levels by day 42. In conclusion, these initial studies with TMAO as a media supplement show promise for improving the compressive mechanical properties, increasing extracellular matrix production, and increasing the recovery time following chABC digestion.

  6. Quinoxaline 1,4-di-N-Oxides: Biological Activities and Mechanisms of Actions

    PubMed Central

    Cheng, Guyue; Sa, Wei; Cao, Chen; Guo, Liangliang; Hao, Haihong; Liu, Zhenli; Wang, Xu; Yuan, Zonghui

    2016-01-01

    Quinoxaline 1,4-di-N-oxides (QdNOs) have manifold biological properties, including antimicrobial, antitumoral, antitrypanosomal and antiinflammatory/antioxidant activities. These diverse activities endow them broad applications and prospects in human and veterinary medicines. As QdNOs arouse widespread interest, the evaluation of their medicinal chemistry is still in progress. In the meantime, adverse effects have been reported in some of the QdNO derivatives. For example, genotoxicity and bacterial resistance have been found in QdNO antibacterial growth promoters, conferring urgent need for discovery of new QdNO drugs. However, the modes of actions of QdNOs are not fully understood, hindering the development and innovation of these promising compounds. Here, QdNOs are categorized based on the activities and usages, among which the antimicrobial activities are consist of antibacterial, antimycobacterial and anticandida activities, and the antiprotozoal activities include antitrypanosomal, antimalarial, antitrichomonas, and antiamoebic activities. The structure-activity relationship and the mode of actions of each type of activity of QdNOs are summarized, and the toxicity and the underlying mechanisms are also discussed, providing insight for the future research and development of these fascinating compounds. PMID:27047380

  7. Dietary trimethylamine N-oxide exacerbates impaired glucose tolerance in mice fed a high fat diet.

    PubMed

    Gao, Xiang; Liu, Xiaofang; Xu, Jie; Xue, Changhu; Xue, Yong; Wang, Yuming

    2014-10-01

    Trimethylamine N-oxide (TMAO) is an oxidation product of trimethylamine (TMA) and is present in many aquatic foods. Here, we investigated the effects of TMAO on glucose tolerance in high fat diet (HFD)-fed mice. Male C57BL/6 mice were randomly assigned to the control, high fat (HF), and TMAO groups. The HF group was fed a diet containing 25% fat, and the TMAO group was fed the HFD plus 0.2% TMAO for 4 weeks. After 3 weeks of feeding, oral glucose tolerance tests were performed. Dietary TMAO increased fasting insulin levels and homeostasis model assessment-estimated insulin resistance (HOMA-IR) and exacerbated the impaired glucose tolerance in HFD-fed mice. These effects were associated with the expression of genes related to the insulin signal pathway, glycogen synthesis, gluconeogenesis and glucose transport in liver. mRNA levels of the pro-inflammatory cytokine MCP-1 increased significantly and of the anti-inflammatory cytokine IL-10 greatly decreased in adipose tissue. Our results suggest that dietary TMAO exacerbates impaired glucose tolerance, obstructs the hepatic insulin signaling pathway, and causes adipose tissue inflammation in mice fed a high fat diet.

  8. Measurement of trimethylamine-N-oxide by stable isotope dilution liquid chromatography tandem mass spectrometry

    PubMed Central

    Wang, Zeneng; Levison, Bruce S.; Hazen, Jennie E.; Donahue, Lillian; Li, Xin-Min; Hazen, Stanley L.

    2014-01-01

    Trimethylamine-N-oxide (TMAO) levels in blood predict future risk for major adverse cardiac events including myocardial infarction, stroke and death. Thus, the rapid determination of circulating TMAO concentration is of clinical interest. Here we report a method to measure TMAO in biological matrices by stable isotope dilution liquid chromatography tandem mass spectrometry (LC/MS/MS) with lower and upper limits of quantification of 0.05 and >200 µM, respectively. Spike and recovery studies demonstrate an accuracy at low (0.5 µM), mid (5 µM) and high (100 µM) levels of 98.2%, 97.3% and 101.6%, respectively. Additional assay performance metrics include intra-day and inter-day coefficients of variance of < 6.4% and < 9.9%, respectively, across the range of TMAO levels. Stability studies reveal TMAO in plasma is stable both during storage at −80 °C for 5 years and to multiple freeze thaw cycles. Fasting plasma normal range studies among apparently healthy subjects (n=349) shows a range of 0.73 – 126 µM, median (interquartile range) levels of 3.45 (2.25–5.79) µM, and increasing values with age. The LC/MS/MS based assay reported should be of value for further studies evaluating TMAO as a risk marker and for examining the effect of dietary, pharmacologic and environmental factors on TMAO levels. PMID:24704102

  9. Further investigations into the genotoxicity of quinoxaline-di-N-oxides and their primary metabolites.

    PubMed

    Liu, Qianying; Zhang, Jianwu; Luo, Xun; Ihsan, Awais; Liu, Xianglian; Dai, Menghong; Cheng, Guyue; Hao, Haihong; Wang, Xu; Yuan, Zonghui

    2016-07-01

    Quinoxaline-di-N-oxides (QdNOs) are potential antibacterial agents with a wide range of biological properties. Quinocetone (QCT), carbadox (CBX), olaquindox (OLA), mequindox (MEQ) and cyadox (CYA) are classical QdNOs. Though the genotoxicity of parent drugs has been evaluated, the genotoxicity of their primary N → O reduced metabolites remains unclear. In the present study, a battery of four different short-term tests, mouse lymphoma assay (MLA), Ames test, chromosomal aberration assay in vitro and bone marrow erythrocyte micronucleus assay in vivo was carried out to investigate the genotoxicity of the six primary N → O reduced metabolites. Additionally, the genotoxicity of five parent drugs was evaluated by the MLA. Strong genotoxicity of N1-MEQ, B-MEQ and B-CBX was found in three of the assays but not in the Ames assay, and the rank order was N1-MEQ>B-MEQ>B-CBX that is consistent with prototype QdNOs. Negative results for the five QdNOs were noted in the MLA. We present for the first time a comparison of the genotoxicity of primary N → O reduced metabolites, and evaluate the ability of five QdNOs to cause mutations in the MLA. The present study demonstrates that metabolites are involved in genetic toxicity mediated by QdNOs, and improve the prudent use of QdNOs for public health.

  10. Mechanistic investigation of trimethylamine-N-oxide reduction catalysed by biomimetic molybdenum enzyme models.

    PubMed

    Fortino, M; Marino, T; Russo, N; Sicilia, E

    2016-03-28

    In this paper, we report a theoretical investigation of the reduction reaction mechanism of Me3NO using molybdenum containing systems that are functional and structural analogues of trimethylamine N-oxide reductase mononuclear molybdenum enzyme. The reactivity of the monooxomolybdenum(IV) benzenedithiolato complex and its derivatives to carbamoyl (t-BuNHCO) and acylamino (t-BuCONH) substituents on the benzene rings in both cis and trans arrangements was explored. The calculated energy profiles describing the steps of two mechanisms of attack considered viable (named cis- and trans-attack) by the Me3NO substrate at cis and trans positions with respect to the oxo ligand show that the attack on cis is energetically more favourable than the attack on trans. Along the pathway for the cis-attack the first step of the reaction, that is rate-determining for all the studied compounds, is the approach of the substrate to the Mo centre in cis to the oxo ligand that causes a distortion of the initial square-pyramidal geometry of the complex. The reaction steps involved in the trans position attack were also explored. Calculations confirm that, as previously suggested, the introduction of ligands able to form intramolecular NH···S hydrogen bonds accelerates the reduction of the Me3NO substrate and contributes to the tuning of the reactivity of molybdoenzyme models.

  11. Structural mechanism for bacterial oxidation of oceanic trimethylamine into trimethylamine N-oxide.

    PubMed

    Li, Chun-Yang; Chen, Xiu-Lan; Zhang, Dian; Wang, Peng; Sheng, Qi; Peng, Ming; Xie, Bin-Bin; Qin, Qi-Long; Li, Ping-Yi; Zhang, Xi-Ying; Su, Hai-Nan; Song, Xiao-Yan; Shi, Mei; Zhou, Bai-Cheng; Xun, Lu-Ying; Chen, Yin; Zhang, Yu-Zhong

    2017-03-01

    Trimethylamine (TMA) and trimethylamine N-oxide (TMAO) are widespread in the ocean and are important nitrogen source for bacteria. TMA monooxygenase (Tmm), a bacterial flavin-containing monooxygenase (FMO), is found widespread in marine bacteria and is responsible for converting TMA to TMAO. However, the molecular mechanism of TMA oxygenation by Tmm has not been explained. Here, we determined the crystal structures of two reaction intermediates of a marine bacterial Tmm (RnTmm) and elucidated the catalytic mechanism of TMA oxidation by RnTmm. The catalytic process of Tmm consists of a reductive half-reaction and an oxidative half-reaction. In the reductive half-reaction, FAD is reduced and a C4a-hydroperoxyflavin intermediate forms. In the oxidative half-reaction, this intermediate attracts TMA through electronic interactions. After TMA binding, NADP(+) bends and interacts with D317, shutting off the entrance to create a protected micro-environment for catalysis and exposing C4a-hydroperoxyflavin to TMA for oxidation. Sequence analysis suggests that the proposed catalytic mechanism is common for bacterial Tmms. These findings reveal the catalytic process of TMA oxidation by marine bacterial Tmm and first show that NADP(+) undergoes a conformational change in the oxidative half-reaction of FMOs.

  12. Direct preparation of N-quaternized and N-oxidized polycyclic azines by palladium-catalyzed cross-coupling. An unequivocal isomer synthesis

    SciTech Connect

    Zoltewicz, J.A.; Cruskie, M.P. Jr.; Dill, C.D.

    1995-01-13

    The authors report several examples of unequivocal isomer preparations using palladium-catalyzed cross-coupling to yield N-oxides and N-quaternized polycyclic azines. This approach serves as a model for such syntheses where selective N-quaternization, N-oxidation, or other types of N-functionalization of several rings is now possible in a regioncontrolled manner.

  13. Design and construction of two rare aqua bridged copper (II) coordination polymers through mixed ligand strategy: Synthesis, characterization and single crystal X-ray structure determination of [Cu(2-iodobenzoate)2(β/γ-picoline)2(μ-H2O)]n

    NASA Astrophysics Data System (ADS)

    Kumar, Santosh; Sharma, Raj Pal; Saini, Anju; Venugopalan, Paloth; Ferretti, Valeria

    2015-03-01

    Reaction of hydrated copper (II) 2-iodobenzoate with β/γ-picoline in methanol:water mixture (4:1, v/v) yielded two rare aqua bridged zig-zag polymers [Cu(2-iodobenzoate)2(β-picoline)2(μ-H2O)]n; 1 and [Cu(2-iodobenzoate)2(γ-picoline)2(μ-H2O)]n; 2. The newly synthesized complexes have been characterized by elemental analysis, FT-IR spectroscopy, UV-Vis spectroscopy and single crystal X-ray structure determination. Complex 1 crystallized in monoclinic crystal system with C2/c space group, and complex 2 crystallized in triclinic crystal system with P 1 ‾ space group. X-ray structure determination revealed the presence of 1-dimensional chains of constituent molecules running along a-axis in both complexes. Water molecules act as bridges between constituent molecules and hence play a crucial role in 1-dimensional chain propagation in zig-zag manner. Empty channels have been observed between the zig-zag chains of complexes. Non-covalent interactions interactions such as O-H⋯O, C-H⋯O and C-H⋯π have been observed, which play a decisive role in the stabilization of crystal lattices in both complexes 1 and 2.

  14. Effect of trimethylamine-N-oxide on pressure-induced dissolution of hydrophobic solute

    NASA Astrophysics Data System (ADS)

    Sarma, Rahul; Paul, Sandip

    2012-09-01

    Molecular dynamics simulations are performed to study the effects of increasing trimethylamine-N-oxide (TMAO) concentration on the pressure-induced dissolution of hydrophobic solutes immersed in water. Such systems are of interest mainly because pressure increases the dissolution of hydrophobic protein interior causing protein denaturation and TMAO acts to offset the protein denaturing effect of high hydrostatic pressures. In view of this, in this study, methane molecules are considered as model hydrophobic molecules and simulations are performed for four independent TMAO solutions each at four different pressures ranging from 2 to 8 kbar. From potentials of mean force calculations, it is found that application of pressure reduces the free energy difference between contact minimum (CM) and solvent-separated (SSM) minimum of hydrophobic solute, suggesting dissolution at high pressures. TMAO, on the other hand, increases the relative stability of CM state of methane molecules relative to its SSM state. High packing efficiency of water molecules around the hydrophobic solute at high pressure is observed. Also observed are TMAO-induced enhancement of water structure and direct hydrogen-bonding interaction between TMAO and water and the correlated dehydration of hydrophobic solute. From hydrogen bond properties and dynamics calculations, it is observed that pressure increases average number of water-water hydrogen bonds while reduces their life-times. In contrast, TMAO reduces water-water hydrogen bonding but enhances their life-times. These results suggest that TMAO can reduce water penetration into the protein interior by enhancing water structure and also forming hydrogen bonds with water and hence counteracts protein unfolding.

  15. O2 -independent demethylation of trimethylamine N-oxide by Tdm of Methylocella silvestris.

    PubMed

    Zhu, Yijun; Ksibe, Amira Z; Schäfer, Hendrik; Blindauer, Claudia A; Bugg, Timothy D H; Chen, Yin

    2016-11-01

    Bacterial trimethylamine N-oxide (TMAO) demethylase, Tdm, carries out an unusual oxygen-independent demethylation reaction, resulting in the formation of dimethylamine and formaldehyde. In this study, site-directed mutagenesis, homology modelling and metal analyses by inorganic mass spectrometry have been applied to gain insight into metal stoichiometry and underlying catalytic mechanism of Tdm of Methylocella silvestris BL2. Herein, we demonstrate that active Tdm has 1 molar equivalent of Zn(2+) and 1 molar equivalent of non-haem Fe(2+) . We further investigated Zn(2+) - and Fe(2+) -binding sites through homology modelling and site-directed mutagenesis and found that Zn(2+) is coordinated by a 3-sulfur-1-O motif. An aspartate residue (D198) likely bridges Fe(2+) and Zn(2+) centres, either directly or indirectly via H-bonding through a neighbouring H2 O molecule. H276 contributes to Fe(2+) binding, mutation of which results in an inactive enzyme, and the loss of iron, but not zinc. Site-directed mutagenesis of Tdm also led to the identification of three hydrophobic aromatic residues likely involved in substrate coordination (F259, Y305, W321), potentially through a cation-π interaction. Furthermore, a crossover experiment using a substrate analogue gave direct evidence that a trimethylamine-alike intermediate was produced during the Tdm catalytic cycle, suggesting TMAO has a dual role of being both a substrate and an oxygen donor for formaldehyde formation. Together, our results provide novel insight into the role of Zn(2+) and Fe(2+) in the catalysis of TMAO demethylation by this unique oxygen-independent enzyme.

  16. Relationship of Serum Trimethylamine N-Oxide (TMAO) Levels with early Atherosclerosis in Humans

    PubMed Central

    Randrianarisoa, Elko; Lehn-Stefan, Angela; Wang, Xiaolin; Hoene, Miriam; Peter, Andreas; Heinzmann, Silke S; Zhao, Xinjie; Königsrainer, Ingmar; Königsrainer, Alfred; Balletshofer, Bernd; Machann, Jürgen; Schick, Fritz; Fritsche, Andreas; Häring, Hans-Ulrich; Xu, Guowang; Lehmann, Rainer; Stefan, Norbert

    2016-01-01

    Circulating trimethylamine N-Oxide (TMAO) levels predict cardiovascular disease (CVD), possibly by impacting on cholesterol metabolism and oxidative stress. Because hepatic TMAO production is regulated by insulin signalling and it is unclear whether and to what extent circulating TMAO levels associate with CVD risk, independently of insulin resistance and its important determinants fatty liver and visceral obesity, we have now addressed this question in 220 subjects who participated in the Tübingen Lifestyle Intervention Program. Visceral fat mass (r = 0.40, p < 0.0001), liver fat content (r = 0.23, p = 0.0005) and TMAO levels (r = 0.26, p < 0.0001) associated positively, and insulin sensitivity associated negatively (r = −0.18, p = 0.009) with carotid intima-media thickness (cIMT). Higher TMAO levels (std.−Beta 0.11, p = 0.03) predicted increased cIMT, independently of age, sex and visceral fat mass. While during the lifestyle intervention most cardiovascular risk parameters improved, mean TMAO levels did not change (p = 0.18). However, cIMT decreased significantly (p = 0.0056) only in subjects in the tertile with the largest decrease of TMAO levels (>20%). We provide novel information that increased serum TMAO levels associate with increased cIMT, independently of established cardiovascular risk markers, including insulin resistance, visceral obesity and fatty liver. Furthermore, the decrease of cIMT during a lifestyle intervention may be related to the decrease of TMAO levels. PMID:27228955

  17. Short-term high-fat diet increases postprandial trimethylamine-N-oxide in humans.

    PubMed

    Boutagy, Nabil E; Neilson, Andrew P; Osterberg, Kristin L; Smithson, Andrew T; Englund, Tessa R; Davy, Brenda M; Hulver, Matthew W; Davy, Kevin P

    2015-10-01

    The gut microbiota plays an obligatory role in the metabolism of nutrients containing trimethylamine moieties, such as L-carnitine and choline, leading to the production of the proatherogenic trimethylamine-N-oxide (TMAO). We hypothesized that a short-term, high-fat diet would increase fasting and postprandial plasma concentrations of TMAO in response to a high-fat meal challenge. Following a 2-week eucaloric control diet, 10 nonobese men (18-30 years) consumed a eucaloric, high-fat diet (55% fat) for 5 days. Plasma TMAO was measured after a 12-hour fast and each hour after for 4 hours following a high-fat meal (63% fat) at baseline and after the high-fat diet using ultraperformance liquid chromatography/ tandem mass spectrometry. Fasting plasma TMAO did not increase significantly following the high-fat diet (1.83 ± 0.21 vs 1.6 ± 0.24 μmol/L). However, plasma TMAO was higher at hour 1 (2.15 ± 0.28 vs 1.7 ± 0.30 μmol/L), hour 2 (2.3 ± 0.29 vs 1.8 ± 0.32 μmol/L), hour 3 (2.4 ± 0.34 vs 1.58 ± 0.19 μmol/L), and hour 4 (2.51 ± 0.33 vs 1.5 ± 0.12 μmol/L) (all P < .05) following the high-fat diet as compared with the baseline postprandial response. In conclusion, a short-term, high-fat diet does not increase fasting plasma TMAO concentrations but appears to increase postprandial TMAO concentrations in healthy, nonobese, young men. Future studies are needed to determine the mechanisms responsible for these observations.

  18. Activation of cholera toxin production by anaerobic respiration of trimethylamine N-oxide in Vibrio cholerae.

    PubMed

    Lee, Kang-Mu; Park, Yongjin; Bari, Wasimul; Yoon, Mi Young; Go, Junhyeok; Kim, Sang Cheol; Lee, Hyung-Il; Yoon, Sang Sun

    2012-11-16

    Vibrio cholerae is a gram-negative bacterium that causes cholera. Although the pathogenesis caused by this deadly pathogen takes place in the intestine, commonly thought to be anaerobic, anaerobiosis-induced virulence regulations are not fully elucidated. Anerobic growth of the V. cholerae strain, N16961, was promoted when trimethylamine N-oxide (TMAO) was used as an alternative electron acceptor. Strikingly, cholera toxin (CT) production was markedly induced during anaerobic TMAO respiration. N16961 mutants unable to metabolize TMAO were incapable of producing CT, suggesting a mechanistic link between anaerobic TMAO respiration and CT production. TMAO reductase is transported to the periplasm via the twin arginine transport (TAT) system. A similar defect in both anaerobic TMAO respiration and CT production was also observed in a N16961 TAT mutant. In contrast, the abilities to grow on TMAO and to produce CT were not affected in a mutant of the general secretion pathway. This suggests that V. cholerae may utilize the TAT system to secrete CT during TMAO respiration. During anaerobic growth with TMAO, N16961 cells exhibit green fluorescence when stained with 2',7'-dichlorofluorescein diacetate, a specific dye for reactive oxygen species (ROS). Furthermore, CT production was decreased in the presence of an ROS scavenger suggesting a positive role of ROS in regulating CT production. When TMAO was co-administered to infant mice infected with N16961, the mice exhibited more severe pathogenic symptoms. Together, our results reveal a novel anaerobic growth condition that stimulates V. cholerae to produce its major virulence factor.

  19. Effect of trimethylamine-N-oxide on pressure-induced dissolution of hydrophobic solute.

    PubMed

    Sarma, Rahul; Paul, Sandip

    2012-09-21

    Molecular dynamics simulations are performed to study the effects of increasing trimethylamine-N-oxide (TMAO) concentration on the pressure-induced dissolution of hydrophobic solutes immersed in water. Such systems are of interest mainly because pressure increases the dissolution of hydrophobic protein interior causing protein denaturation and TMAO acts to offset the protein denaturing effect of high hydrostatic pressures. In view of this, in this study, methane molecules are considered as model hydrophobic molecules and simulations are performed for four independent TMAO solutions each at four different pressures ranging from 2 to 8 kbar. From potentials of mean force calculations, it is found that application of pressure reduces the free energy difference between contact minimum (CM) and solvent-separated (SSM) minimum of hydrophobic solute, suggesting dissolution at high pressures. TMAO, on the other hand, increases the relative stability of CM state of methane molecules relative to its SSM state. High packing efficiency of water molecules around the hydrophobic solute at high pressure is observed. Also observed are TMAO-induced enhancement of water structure and direct hydrogen-bonding interaction between TMAO and water and the correlated dehydration of hydrophobic solute. From hydrogen bond properties and dynamics calculations, it is observed that pressure increases average number of water-water hydrogen bonds while reduces their life-times. In contrast, TMAO reduces water-water hydrogen bonding but enhances their life-times. These results suggest that TMAO can reduce water penetration into the protein interior by enhancing water structure and also forming hydrogen bonds with water and hence counteracts protein unfolding.

  20. Synthesis and structure-activity relationship of 3-phenylquinoxaline 1,4-di-N-oxide derivatives as antimalarial agents.

    PubMed

    Vicente, Esther; Lima, Lidia M; Bongard, Emily; Charnaud, Sarah; Villar, Raquel; Solano, Beatriz; Burguete, Asunción; Perez-Silanes, Silvia; Aldana, Ignacio; Vivas, Livia; Monge, Antonio

    2008-09-01

    As a continuation of our research and with the aim of obtaining new antimalarial agents, new series of 3-phenylquinoxaline 1,4-di-N-oxide derivatives have been synthesized following the classical Beirut reaction. Antiplasmodial activity was evaluated in vitro against Plasmodium falciparum by the incorporation of [3H]-hypoxanthine. Cytotoxicity was tested in KB cells by AlamarBlue assay. Twenty-one of the 60 compounds that were assayed against 3D7 (CQ-sensitive) showed enough activity to be also evaluated against K1 (CQ-resistant) strain. Ten of them were shown to be more active than chloroquine in the resistant strain. The most interesting compounds are 7-(methyl or methoxy)-3-(4'-fluoro or chloro)phenylquinoxaline-2-carbonitrile 1,4-di-N-oxides because of their low IC50 and their high SI shown for the K1 strain, making them valid new leads.

  1. New 3-methylquinoxaline-2-carboxamide 1,4-di-N-oxide derivatives as anti-Mycobacterium tuberculosis agents.

    PubMed

    Ancizu, Saioa; Moreno, Elsa; Solano, Beatriz; Villar, Raquel; Burguete, Asunción; Torres, Enrique; Pérez-Silanes, Silvia; Aldana, Ignacio; Monge, Antonio

    2010-04-01

    Mycobacterium tuberculosis (M.Tb) is a bacillus capable of causing a chronic and fatal condition in humans known as tuberculosis (TB). It is estimated that there are 8 million new cases of TB per year and 3.1 million infected people die annually. Thirty-six new amide quinoxaline 1,4-di-N-oxide derivatives have been synthesized and evaluated as potential anti-tubercular agents, obtaining biological values similar to the reference compound, Rifampin (RIF).

  2. Efficacy of Quinoxaline-2-Carboxylate 1,4-Di-N-Oxide Derivatives in Experimental Tuberculosis ▿

    PubMed Central

    Vicente, Esther; Villar, Raquel; Burguete, Asunción; Solano, Beatriz; Pérez-Silanes, Silvia; Aldana, Ignacio; Maddry, Joseph A.; Lenaerts, Anne J.; Franzblau, Scott G.; Cho, Sang-hyun; Monge, Antonio; Goldman, Robert C.

    2008-01-01

    This study extends earlier reports regarding the in vitro efficacies of the 1,4-di-N-oxide quinoxaline derivatives against Mycobacterium tuberculosis and has led to the discovery of a derivative with in vivo efficacy in the mouse model of tuberculosis. Quinoxaline-2-carboxylate 1,4-di-N-oxide derivatives were tested in vitro against a broad panel of single-drug-resistant M. tuberculosis strains. The susceptibilities of these strains to some compounds were comparable to those of strain H37Rv, as indicated by the ratios of MICs for resistant and nonresistant strains, supporting the premise that 1,4-di-N-oxide quinoxaline derivatives have a novel mode of action unrelated to those of the currently used antitubercular drugs. Specific derivatives were further evaluated in a series of in vivo assays, including evaluations of the maximum tolerated doses, the levels of oral bioavailability, and the efficacies in a low-dose aerosol model of tuberculosis in mice. One compound, ethyl 7-chloro-3-methylquinoxaline-2-carboxylate 1,4-dioxide, was found to be (i) active in reducing CFU counts in both the lungs and spleens of infected mice following oral administration, (ii) active against PA-824-resistant Mycobacterium bovis, indicating that the pathway of bioreduction/activation is different from that of PA-824 (a bioreduced nitroimidazole that is in clinical trials), and (iii) very active against nonreplicating bacteria adapted to low-oxygen conditions. These data indicate that 1,4-di-N-oxide quinoxalines hold promise for the treatment of tuberculosis. PMID:18625764

  3. Prenatal exposure to integerrimine N-oxide impaired the maternal care and the physical and behavioral development of offspring rats.

    PubMed

    Sandini, Thaísa M; Udo, Mariana S B; Reis-Silva, Thiago M; Bernardi, Maria Martha; Spinosa, Helenice de S

    2014-08-01

    Plants that contain pyrrolizidine alkaloids (PAs) have been reported as contaminants of pastures and food, as well as being used in herbal medicine. PAs are responsible for poisoning events in livestock and human beings. The aim of this present study was to evaluate effects of prenatal exposure to integerrimine N-oxide, the main PA found in the butanolic residue (BR) of Senecio brasiliensis, on both physical and behavioral parameters of Wistar rat offspring. The toxicity and maternal behavior were also evaluated. For this, pregnant Wistar rats received integerrimine N-oxide from the BR of Senecio brasiliensis, by gavage, on gestational days 6-20 (during organogenesis and fetal development period) at doses of 3, 6 and 9 mg/kg. During treatment, maternal body weight gain, and food and water intake were evaluated. After parturition, maternal behavior and aggressive maternal behavior were analyzed. In addition, physical development and behavioral assessments were observed in both male and female pups. Results showed that prenatal exposure to integerrimine N-oxide of S. brasiliensis induced maternal toxicity, impairment in maternal behavior and aggressive maternal behavior, mainly in the highest dose group. Between sexes comparison of pups showed loss of body weight, delayed physical development such as pinna detachment, hair growth, eruption of incisor teeth, eye and vaginal openings. These pups also showed a delay of palmar grasp, surface righting reflex, negative geotaxis and auditory startle reflexes. Thus, prenatal exposure to integerrimine N-oxide induces maternal toxicity, impairment of maternal care and delayed in physical and behavioral development of the offspring.

  4. Lanthanide dinuclear complexes constructed from mixed oxygen-donor ligands: the effect of substituent positions of the neutral ligand on the magnetic dynamics in Dy analogues.

    PubMed

    Zhu, Wen-Hua; Li, Shan; Gao, Chen; Xiong, Xia; Zhang, Yan; Liu, Li; Powell, Annie K; Gao, Song

    2016-03-21

    Two series of lanthanide dinuclear complexes with the general formulae, [Ln(n-PNO)(Bza)3(H2O)] {Bza = benzoic acid; n = 3, n-PNO = 3-picoline N-oxide, Dy(1) and Er(2); and n = 4, n-PNO = 4-picoline N-oxide, Nd(3), Eu(4), Gd(5), Tb(6), Dy(7), Er(8) and Y(9)} have been successfully synthesized by the hydrothermal method. Single-crystal X-ray diffraction experiments illustrate that the two series of compounds possess similar carboxylic ligand-bridged dinuclear structure and coordination geometry around the lanthanide ions despite the different methyl-substituent positions on the neutral ligand. Comparative studies of the Dy analogues in the static-field measurements reveal only a little difference with a small butterfly-shaped opening for complex 1 and a close hysteresis loop for 7 at 2.0 K. However, systematic investigations of the alternating-current (ac) measurements indicate that the different substituent positions of the picoline N-oxide ligand have a significant effect on the magnetic relaxation dynamics. A more substantial suppression of the quantum tunnelling of magnetization (QTM) effect and pronounced slow magnetic relaxation were observed in complex 7 as compared to 1 under both zero and a 1 kOe static field.

  5. Monitoring Serum Levels of Sorafenib and Its N-Oxide Is Essential for Long-Term Sorafenib Treatment of Patients with Hepatocellular Carcinoma.

    PubMed

    Shimada, Miki; Okawa, Hoshimi; Kondo, Yasuteru; Maejima, Takahiro; Kataoka, Yuta; Hisamichi, Kanehiko; Maekawa, Masamitsu; Matsuura, Masaki; Jin, Yuko; Mori, Masaru; Suzuki, Hiroyuki; Shimosegawa, Tooru; Mano, Nariyasu

    2015-01-01

    Sorafenib, an oral multi-kinase inhibitor, is the final therapy prior to palliative care for advanced hepatocellular carcinoma (HCC). However, due to its adverse effects, 20% of patients must discontinue sorafenib within 1 month after first administration. To identify ways to predict the adverse effects and administer the drug for longer periods, we explored the relationship between the duration of sorafenib treatment and the pharmacokinetics of sorafenib and its major metabolite, sorafenib N-oxide. Twenty-five subjects enrolled in the study were divided into two groups: patients with dosage reduced or withdrawn due to adverse effects (n = 8), and patients with dosage maintained for 1 month after initial administration (n = 17). We evaluated early sorafenib accumulation as the area under the curve of sorafenib and sorafenib N-oxide concentrations during days 1-7 (AUC(sorafenib) and AUC(N-oxide), respectively). Inter-group comparison revealed that AUC(N-oxide) and AUC ratio (AUC(N-oxide)/AUC(sorafenib)) were significantly higher in the dosage reduction/withdrawal group (P = 0.031 and P = 0.0022, respectively). Receiver operating characteristic analysis indicated that AUC(N-oxide) and AUC ratio were reliable predictors of adverse effects. When patients were classified by cut-off points (AUC(N-oxide:) 2.0 μg ∙ day/mL, AUC ratio: 0.13), progression-free survival was significantly longer in patients with AUC(N-oxide) ≤ 2.0 μg ∙ day/mL (P = 0.0048, log-rank test). In conclusion, we recommend to simultaneously monitor serum levels of sorafenib and its N-oxide during the early stage after the first administration, which enables us to provide safe and long-term therapy for each HCC patient with sorafenib.

  6. Long-Term Supplementation with Chromium Malate Improves Short Chain Fatty Acid Content in Sprague-Dawley Rats.

    PubMed

    Wu, Huiyu; Feng, Weiwei; Mao, Guanghua; Zhao, Ting; Wu, Xiangyang; Wang, Songmei; Zou, Yanmin; Yang, Liuqing; Wang, Liang

    2016-11-01

    Our previous study showed that chromium malate improved the composition of intestinal flora, glycometabolism, glycometabolism-related enzymes, and lipid metabolism in type 2 diabetes mellitus (T2DM) rats. The present study was designed to evaluate the effect of chromium malate with long-term supplementation on short chain fatty acid (SCFA) content in Sprague-Dawley rats. The samples were analyzed by gas chromatography with high linearity (R (2) ≥ 0.9995), low quantification limit (0.011-0.070 mM), and satisfactory recoveries. The method was simple and environmentally friendly. The acetic content in cecum of 3-month control group was significantly higher than that of 1-year control group. When compared with 1-year control group, chromium malate (at a dose of 20.0 μg Cr/kg bw) could significantly increase acetic, propionic, i-butyric butyric, butyric, i-valeric, valeric, and n-caproic levels. The acetic, propionic, i-butyric, valeric, and n-caproic contents of 1-year chromium malate group (at a dose of 20.0 μg Cr/kg bw) had a significant improvement when compared with 1-year chromium picolinate group. Acetic, propionic, and butyric contained approximately 91.65 % of the total SCFAs in 1-year group. The results indicated that the improvement of chromium malate on short chain fatty acid content change was better than that of chromium picolinate.

  7. Di-μ-chlorido-bis-{aqua-chlorido[2,2'-thio-bis(pyridine N-oxide)-κO]copper(II)}.

    PubMed

    Seidel, Rüdiger W; Oppel, Iris M

    2009-03-28

    The crystal structure of the title compound, [Cu(2)Cl(4)(C(10)H(8)N(2)O(2)S)(2)(H(2)O)(2)], comprises neutral centrosymmetric μ-chloride-bridged dinuclear units. Each Cu(II) ion is penta-coordinated by three chloride ligands, a pyridine N-oxide O atom and a water mol-ecule. Intra- and inter-molecular O-H⋯O hydrogen bonds occur between the coordinated water mol-ecules and the uncoordinated and coordinated pyridine N-oxide groups of the 2,2'-thio-bis(pyridine N-oxide) ligands, respectively.

  8. Di-μ-chlorido-bis­{aqua­chlorido[2,2′-thio­bis(pyridine N-oxide)-κO]copper(II)}

    PubMed Central

    Seidel, Rüdiger W.; Oppel, Iris M.

    2009-01-01

    The crystal structure of the title compound, [Cu2Cl4(C10H8N2O2S)2(H2O)2], comprises neutral centrosymmetric μ-chloride-bridged dinuclear units. Each CuII ion is penta­coordinated by three chloride ligands, a pyridine N-oxide O atom and a water mol­ecule. Intra- and inter­molecular O—H⋯O hydrogen bonds occur between the coordinated water mol­ecules and the uncoordinated and coordinated pyridine N-oxide groups of the 2,2′-thio­bis(pyridine N-oxide) ligands, respectively. PMID:21582393

  9. Hepatic microsomal N-oxidation and N-demethylation of N,N-dimethylaniline in red-winged blackbird compared with rat and other birds

    USGS Publications Warehouse

    Pan, H.P.; Fouts, J.R.; Devereux, T.R.

    1975-01-01

    Hepatic microsomes prepared from red-winged blackbirds and albino rats were incubated with N,N-dimethylaniline (DMA)_in complete incubation mixtures at pH 7.9 and 37?C for 10 min. Formaldehyde and N,N-dimethylaniline--oxide produced from DMA were measured. Redwings were found to have significantly lower N-demethylation activities than rats, and redwings had only marginal or no N-oxidation activities. Hepatic microsomes from redwings did not further metabolize the N-oxide. The N-oxidation and N-demethylation activities of brown-headed cowbirds, common grackles, and starlings were similar to those of redwings.

  10. Decreasing urea∶trimethylamine N-oxide ratios with depth in chondrichthyes: a physiological depth limit?

    PubMed

    Laxson, Carrie J; Condon, Nicole E; Drazen, Jeffrey C; Yancey, Paul H

    2011-01-01

    In marine osmoconformers, cells use organic osmolytes to maintain osmotic balance with seawater. High levels of urea are utilized in chondrichthyans (sharks, rays, skates, and chimaeras) for this purpose. Because of urea's perturbing nature, cells also accumulate counteracting methylamines, such as trimethylamine N-oxide (TMAO), at about a 2∶1 urea∶methylamine ratio, the most thermodynamically favorable mixture for protein stabilization, in shallow species. However, previous work on deep-sea teleosts (15 species) and chondrichthyans (three species) found an increase in muscle TMAO content and a decrease in urea content in chondrichthyans with depth. We hypothesized that TMAO counteracts protein destabilization resulting from hydrostatic pressure, as is demonstrated in vitro. Chondrichthyans are almost absent below 3,000 m, and we hypothesized that a limitation in urea excretion and/or TMAO retention might play a role. To test this, we measured the content of major organic osmolytes in white muscle of 13 chondrichthyan species caught with along-contour trawls at depths of 50-3,000 m; the deepest species caught was from 2,165 m. Urea and TMAO contents changed significantly with depth, with urea∶TMAO declining from 2.96 in the shallowest (50-90 m) groups to 0.67 in the deepest (1,911-2,165 m) groups. Urea content was 291-371 mmol/kg in the shallowest group and 170-189 mmol/kg in the deepest group, declining linearly with depth and showing no plateau. TMAO content was 85-168 mmol/kg in the shallowest group and 250-289 mmol/kg in the deepest groups. With data from a previous study for a skate at 2,850 m included, a second-order polynomial fit suggested a plateau at the greatest depths. When data for skates (Rajidae) were analyzed separately, a sigmoidal fit was suggested. Thus, the deepest chondrichthyans may be unable to accumulate sufficient TMAO to counteract pressure; however, deeper-living specimens are needed to fully test this hypothesis.

  11. Direct tandem mass spectrometric analysis of amino acids in plasma using fluorous derivatization and monolithic solid-phase purification.

    PubMed

    Tamashima, Erina; Hayama, Tadashi; Yoshida, Hideyuki; Imakyure, Osamu; Yamaguchi, Masatoshi; Nohta, Hitoshi

    2015-11-10

    In this study, we developed a novel direct tandem mass spectrometric method for rapid and accurate analysis of amino acids utilizing a fluorous derivatization and purification technique. Amino acids were perfluoroalkylated with 2H,2H,3H,3H-perfluoroundecan-1-al in the presence of 2-picoline borane via reductive amination. The derivatives were purified by perfluoroalkyl-modified silica-based monolithic solid-phase extraction (monolithic F-SPE), and directly analyzed by tandem mass spectrometry using electrospray ionization without liquid chromatographic separation. The perfluoroalkyl derivatives could be sufficiently distinguished from non-fluorous compounds, i.e. the biological matrix, due to their fluorous interaction. Thus, rapid and accurate determination of amino acids was accomplished. The method was validated with human plasma samples and applied to the analysis of amino acids in the plasma of mice with maple syrup urine disease or phenylketonuria.

  12. A Phospholipid-Protein Complex from Antarctic Krill Reduced Plasma Homocysteine Levels and Increased Plasma Trimethylamine-N-Oxide (TMAO) and Carnitine Levels in Male Wistar Rats

    PubMed Central

    Bjørndal, Bodil; Ramsvik, Marie S.; Lindquist, Carine; Nordrehaug, Jan E.; Bruheim, Inge; Svardal, Asbjørn; Nygård, Ottar; Berge, Rolf K.

    2015-01-01

    Seafood is assumed to be beneficial for cardiovascular health, mainly based on plasma lipid lowering and anti-inflammatory effects of n-3 polyunsaturated fatty acids. However, other plasma risk factors linked to cardiovascular disease are less studied. This study aimed to penetrate the effect of a phospholipid-protein complex (PPC) from Antarctic krill on one-carbon metabolism and production of trimethylamine-N-oxide (TMAO) in rats. Male Wistar rats were fed isoenergetic control, 6%, or 11% PPC diets for four weeks. Rats fed PPC had reduced total homocysteine plasma level and increased levels of choline, dimethylglycine and cysteine, whereas the plasma level of methionine was unchanged compared to control. PPC feeding increased the plasma level of TMAO, carnitine, its precursors trimethyllysine and γ-butyrobetaine. There was a close correlation between plasma TMAO and carnitine, trimethyllysine, and γ-butyrobetaine, but not between TMAO and choline. The present data suggest that PPC has a homocysteine lowering effect and is associated with altered plasma concentrations of metabolites related to one-carbon metabolism and B-vitamin status in rats. Moreover, the present study reveals a non-obligatory role of gut microbiota in the increased plasma TMAO level as it can be explained by the PPC’s content of TMAO. The increased level of carnitine and carnitine precursors is interpreted to reflect increased carnitine biosynthesis. PMID:26371012

  13. A Phospholipid-Protein Complex from Antarctic Krill Reduced Plasma Homocysteine Levels and Increased Plasma Trimethylamine-N-Oxide (TMAO) and Carnitine Levels in Male Wistar Rats.

    PubMed

    Bjørndal, Bodil; Ramsvik, Marie S; Lindquist, Carine; Nordrehaug, Jan E; Bruheim, Inge; Svardal, Asbjørn; Nygård, Ottar; Berge, Rolf K

    2015-09-08

    Seafood is assumed to be beneficial for cardiovascular health, mainly based on plasma lipid lowering and anti-inflammatory effects of n-3 polyunsaturated fatty acids. However, other plasma risk factors linked to cardiovascular disease are less studied. This study aimed to penetrate the effect of a phospholipid-protein complex (PPC) from Antarctic krill on one-carbon metabolism and production of trimethylamine-N-oxide (TMAO) in rats. Male Wistar rats were fed isoenergetic control, 6%, or 11% PPC diets for four weeks. Rats fed PPC had reduced total homocysteine plasma level and increased levels of choline, dimethylglycine and cysteine, whereas the plasma level of methionine was unchanged compared to control. PPC feeding increased the plasma level of TMAO, carnitine, its precursors trimethyllysine and γ-butyrobetaine. There was a close correlation between plasma TMAO and carnitine, trimethyllysine, and γ-butyrobetaine, but not between TMAO and choline. The present data suggest that PPC has a homocysteine lowering effect and is associated with altered plasma concentrations of metabolites related to one-carbon metabolism and B-vitamin status in rats. Moreover, the present study reveals a non-obligatory role of gut microbiota in the increased plasma TMAO level as it can be explained by the PPC's content of TMAO. The increased level of carnitine and carnitine precursors is interpreted to reflect increased carnitine biosynthesis.

  14. Hydrogen-bonded supra­molecular motifs in pyrimethaminium 4-methyl­benzoate, pyrimethaminium 3-hydroxy­picolinate and pyri­meth­aminium 2,4-di­chloro­benzoate

    PubMed Central

    Thanigaimani, Kaliyaperumal; Muthiah, Packianathan Thomas

    2010-01-01

    In 2,4-diamino-5-(4-chloro­phenyl)-6-ethyl­pyrimidin-1-ium (pyri­methaminium, PMNH) 4-methyl­benzoate, C12H14ClN4 +·C8H7O2 −, (I), pyrimethaminium 3-hydroxy­picolinate, C12H14ClN4 +·C6H4NO3 −, (II), and pyrimethaminium 2,4-dichloro­benzoate, C12H14ClN4 +·C7H3Cl2O2 −, (III), the PMNH cations inter­act with the carboxyl­ate groups of the corresponding anion via nearly parallel N—H⋯O hydrogen bonds, forming R 2 2(8) ring motifs. A description of the observed arrays of quadruple hydrogen bonds in (I) and (II) in terms of hydrogen donors and acceptors (the DA model), their graph-set motifs and the resulting supra­molecular ladder is given. In (III), supra­molecular chains along the b axis and helical chains along the a axis are formed via N—H⋯O hydrogen bonds involving the 2-amino and 4-amino groups of the PMNH cation, respectively. Weak Cl⋯Cl inter­actions are also found in (III). PMID:20203404

  15. Simultaneous determination of trimethylamine and trimethylamine N-oxide in mouse plasma samples by hydrophilic interaction liquid chromatography coupled to tandem mass spectrometry.

    PubMed

    Mi, Si; Zhao, Yuan-Yuan; Jacobs, René L; Curtis, Jonathan M

    2017-02-01

    A method was developed that applies hydrophilic interaction liquid chromatography with tandem mass spectrometry in the multiple reaction monitoring mode to separate and accurately quantify trimethylamine and trimethylamine N-oxide in a single chromatographic run. This was achieved by converting trimethylamine to ethyl betaine, which is less volatile and hence results in greatly improved quantitation. Ethyl betaine also gives a similar response to trimethylamine N-oxide using positive-ion electrospray ionization mass spectrometry. It is readily separated from trimethylamine N-oxide by hydrophilic liquid chromatography in a 5 min run and with improved peak shape compared to underivatized trimethylamine. Validation of the method yielded a limit of detection (S/N ≥ 3) of 0.5 ng/mL for trimethylamine and 0.25 ng/mL for trimethylamine N-oxide. Method accuracies of 91.4-105.3% with precisions of 0.4-5.5% were obtained for standard mixtures over the range of 2.5-500 ng/mL. Recoveries measured for the extraction of trimethylamine and trimethylamine N-oxide spikes into mouse plasma were both >90%. The method, which simultaneously measures trimethylamine and trimethylamine N-oxide, was successfully applied to mouse plasma samples and could be adapted for use with other biological fluids.

  16. Mode of action of nifurtimox and N-oxide-containing heterocycles against Trypanosoma cruzi: is oxidative stress involved?

    PubMed

    Boiani, Mariana; Piacenza, Lucia; Hernández, Paola; Boiani, Lucia; Cerecetto, Hugo; González, Mercedes; Denicola, Ana

    2010-06-15

    Chagas disease is caused by the trypanosomatid parasite Trypanosoma cruzi and threatens millions of lives in South America. As other neglected diseases there is almost no research and development effort by the pharmaceutical industry and the treatment relies on two drugs, Nifurtimox and Benznidazole, discovered empirically more than three decades ago. Nifurtimox, a nitrofurane derivative, is believed to exert its biological activity through the bioreduction of the nitro-group to a nitro-anion radical which undergoes redox-cycling with molecular oxygen. This hypothesis is generally accepted, although arguments against it have been presented. In the present work we studied the ability of Nifurtimox and five N-oxide-containing heterocycles to induce oxidative stress in T. cruzi. N-Oxide-containing heterocycles represent a promising group of new trypanosomicidal agents and their mode of action is not completely elucidated. The results here obtained argue against the oxidative stress hypothesis almost for all the studied compounds, including Nifurtimox. A significant reduction in the level of parasitic low-molecular-weight thiols was observed after Nifurtimox treatment; however, it was not linked to the production of reactive oxidant species. Besides, redox-cycling is only observed at high Nifurtimox concentrations (>400microM), two orders of magnitude higher than the concentration required for anti-proliferative activity (5microM). Our results indicate that an increase in oxidative stress is not the main mechanism of action of Nifurtimox. Among the studied N-oxide-containing heterocycles, benzofuroxan derivatives strongly inhibited parasite dehydrogenase activity and affected mitochondrial membrane potential. The indazole derivative raised intracellular oxidants production, but it was the least effective as anti-T. cruzi.

  17. Synthesis and antiplasmodial activity of 3-furyl and 3-thienylquinoxaline-2-carbonitrile 1,4-di-N-oxide derivatives.

    PubMed

    Vicente, Esther; Charnaud, Sarah; Bongard, Emily; Villar, Raquel; Burguete, Asunción; Solano, Beatriz; Ancizu, Saioa; Pérez-Silanes, Silvia; Aldana, Ignacio; Vivas, Livia; Monge, Antonio

    2008-01-17

    The aim of this study was to identify new compounds active against Plasmodium falciparum based on our previous research carried out on 3-phenyl-quinoxaline-2-carbonitrile 1,4-di-N-oxide derivatives. Twelve compounds were synthesized and evaluated for antimalarial activity. Eight of them showed an IC(50) less than 1 microM against the 3D7 strain. Derivative 1 demonstrated high potency (IC(50)= 0.63 microM) and good selectivity (SI=10.35), thereby becoming a new lead-compound.

  18. Mechanistic dichotomy in the asymmetric allylation of aldehydes with allyltrichlorosilanes catalyzed by chiral pyridine N-oxides.

    PubMed

    Malkov, Andrei V; Stončius, Sigitas; Bell, Mark; Castelluzzo, Fabiomassimo; Ramírez-López, Pedro; Biedermannová, Lada; Langer, Vratislav; Rulíšek, Lubomír; Kočovský, Pavel

    2013-07-08

    Detailed kinetic and computational investigation of the enantio- and diastereoselective allylation of aldehydes 1 with allyltrichlorosilanes 5, employing the pyridine N-oxides METHOX (9) and QUINOX (10) as chiral organocatalysts, indicate that the reaction can proceed through a dissociative (cationic) or associative (neutral) mechanism: METHOX apparently favors a pentacoordinate cationic transition state, while the less sterically demanding QUINOX is likely to operate via a hexacoordinate neutral complex. In both pathways, only one molecule of the catalyst is involved in the rate- and selectivity-determining step, which is supported by both experimental and computational data.

  19. An Ion Chromatographic Method to Determine Methylamines and Amine-N-Oxides in Particulate Matter

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Several studies have indicated the presence of amines in the particulate phase, believed to result from atmospheric reactions of volatile amines emitted from sources including agriculture. The resulting particulate amines are a combination of cationized (from acid-base reactions) and free base forms...

  20. Bonding situation and N-O-bond strengths in amine-N-oxides--a combined experimental and theoretical study.

    PubMed

    Rogachev, Andrey Yu; Burger, Peter

    2012-02-14

    The bonding situation and energetics of the N-O bond in a series of amine-N-oxides, Ph(x)(CH(3))(3-x)N-O, where x = 0-3, were analyzed experimentally and theoretically. There is a notable nearly linear decrease of the N-O bond dissociation energies (BDEs) for this series with an increasing number of phenyl groups x. This was investigated experimentally by X-ray high angle multipole refinement techniques in combination with subsequent topological analysis of the electron density for the representative (CH(3))(2)PhN-O, 2, and complementary theoretical calculations at the DFT and multireference CASSCF and MR-perturbation theory (MCQDPT2) levels. Both the theoretical and experimental results unambiguously revealed a polar covalent σ-bond for the N-O bond with an essentially identical bonding situation for all amine-N-oxides studied. This apparent disparity between the bonding situation and the trend of BDEs is attributed to the large differences of the relaxation energies of the corresponding amines Ph(x)(CH(3))(3-x)N, (x = 0-3), respectively, the required preparation energies (ΔE(prep)) for the reverse N-O bond forming process. The detailed theoretical analysis of the amines allowed us to trace the trend of larger values of ΔE(prep) for a higher number of phenyl groups x to an increase of n(N) → π*(C-C) delocalization interactions.

  1. Discovery of syn-/anti-cocaine-N-oxide diastereomers in unwashed postmortem hair via LC-MS-MS.

    PubMed

    Marsh, Christine M; Crawley, Lindsey R; Himes, Sarah K; Aranda, Roman; Miller, Mark L

    2014-01-01

    The discovery of two cocaine-N-oxide (CNO) diastereomers, syn- and anti-CNO, is reported for the first time. Prior to this study, only one structural form of CNO was known to exist and has not been analyzed in hair before. CNO is a metabolite of cocaine (COC) and may be considered as an additional biomarker of COC use, along with other known COC metabolites. The analysis of COC in hair for forensic applications is under scrutiny due to the possibility of external contamination. A qualitative liquid chromatography-tandem mass spectrometry method was developed, validated and applied to unwashed postmortem hair samples from drug users. The limit of detection in hair was 8 pg/mg (using 10 mg of unwashed hair) for each CNO diastereomer. The presence of both syn- and anti-forms of CNO was verified in vivo using hair samples collected from known COC-using individuals. Due to the low levels of CNO, it will not always be detectable in COC user hair. In the hair samples analyzed, syn-CNO was detected in more samples than anti-CNO. The stereoselective N-oxidation of COC which favors syn-CNO could have a diagnostic value for COC ingestion determination in hair analysis.

  2. Effect of Chromium Niacinate and Chromium Picolinate Supplementation on Lipid Peroxidation, TNF-α, IL-6, CRP, Glycated Hemoglobin, Triglycerides and Cholesterol Levels in blood of Streptozotocin-treated Diabetic Rats

    PubMed Central

    Jain, Sushil K.; Rains, Justin L.; Croad, Jennifer L.

    2013-01-01

    SUMMARY Chromium (Cr3+) supplementation facilitate normal protein, fat and carbohydrate metabolism, and is widely used by public in many countries. This study examined the effect of chromium niacinate (Cr-N) or chromium picolinate (Cr-P) supplementation on lipid peroxidation (LP), TNF-α, IL-6, CRP, glycosylated hemoglobin (HbA1), cholesterol and triglycerides (TG) in diabetic rats. Diabetes (D) was induced in Sprague Dawley rats by streptozotocin (STZ) (ip, 65 mg/kg BW). Control buffer, Cr-N or Cr-P (400 µg Cr/Kg BW) was administered by gavages daily for 7 wks. Blood was collected by heart puncture using light anesthesia. Diabetes caused a significant increase in blood levels of TNF-α, IL-6, glucose, HbA1, cholesterol, TG and LP. Compared with D, Cr-N supplementation lowered the blood levels of TNF-α (p=0.04), IL-6 (p=0.02), CRP (p=0.02) LP (p=0.01), HbA1 (p=0.02), TG (p=0.04) and cholesterol (p=0.04). Compared with D, Cr-P supplementation showed a decrease in TNF-α (p=0.02), IL-6 (p=0.02) and LP (p=0.01). Chromium niacinate lowers blood levels of pro-inflammatory cytokines (TNF-α, IL-6, CRP), oxidative stress and lipids levels in diabetic rats, and appears to be more effective form of Cr3+-supplementation. This study suggests that Cr3+-supplementation can lower risk of vascular inflammation in diabetes. PMID:17854708

  3. Effect of chromium niacinate and chromium picolinate supplementation on lipid peroxidation, TNF-alpha, IL-6, CRP, glycated hemoglobin, triglycerides, and cholesterol levels in blood of streptozotocin-treated diabetic rats.

    PubMed

    Jain, Sushil K; Rains, Justin L; Croad, Jennifer L

    2007-10-15

    Chromium (Cr(3+)) supplementation facilitates normal protein, fat, and carbohydrate metabolism, and is widely used by the public in many countries. This study examined the effect of chromium niacinate (Cr-N) or chromium picolinate (Cr-P) supplementation on lipid peroxidation (LP), TNF-alpha, IL-6, C-reactive protein (CRP), glycosylated hemoglobin (HbA(1)), cholesterol, and triglycerides (TG) in diabetic rats. Diabetes (D) was induced in Sprague-Dawley rats by streptozotocin (STZ) (ip, 65 mg/kg BW). Control buffer, Cr-N, or Cr-P (400 microg Cr/kg BW) was administered by gavages daily for 7 weeks. Blood was collected by heart puncture using light anesthesia. Diabetes caused a significant increase in blood levels of TNF-alpha, IL-6, glucose, HbA(1), cholesterol, TG, and LP. Compared with D, Cr-N supplementation lowered the blood levels of TNF-alpha (P=0.04), IL-6 (P=0.02), CRP (P=0.02), LP (P=0.01), HbA(1) (P=0.02), TG (P=0.04), and cholesterol (P=0.04). Compared with D, Cr-P supplementation showed a decrease in TNF-alpha (P=0.02), IL-6 (P=0.02), and LP (P=0.01). Chromium niacinate lowers blood levels of proinflammatory cytokines (TNF-alpha, IL-6, CRP), oxidative stress, and lipids levels in diabetic rats, and appears to be a more effective form of Cr(3+) supplementation. This study suggests that Cr(3+) supplementation can lower the risk of vascular inflammation in diabetes.

  4. Characterization of inhibitory effects of the potential therapeutic inhibitors, benzoic acid and pyridine derivatives, on the monophenolase and diphenolase activities of tyrosinase

    PubMed Central

    Gheibi, Nematollah; Taherkhani, Negar; Ahmadi, Abolfazl; Haghbeen, Kamahldin; Ilghari, Dariush

    2015-01-01

    Objective(s): Involvement of tyrosinase in the synthesis of melanin and cell signaling pathway has made it an attractive target in the search for therapeutic inhibitors for treatment of different skin hyperpigmentation disorders and melanoma cancers. Materials and Methods: In the present study, we conducted a comprehensive kinetic analysis to understand the mechanisms of inhibition imposed by 2-amino benzoic acid, 4-amino benzoic acid, nicotinic acid, and picolinic acid on the monophenolase and diphenolase activities of the mushroom tyrosinase, and then MTT assay was exploited to evaluate their toxicity on the melanoma cells. Results: Kinetic analysis revealed that nicotinic acid and picolinic acid competitively restricted the monophenolase activity with inhibition constants (Ki) of 1.21 mM and 1.97 mM and the diphenolase activity with Kis of 2.4 mM and 2.93 mM, respectively. 2-aminobenzoic acid and 4-aminobenzoic acid inhibited the monophenolase activity in a non-competitive fashion with Kis of 5.15 µM and 3.8 µM and the diphenolase activity with Kis of 4.72 µM and 20 µM, respectively. Conclusion: Our cell-based data revealed that only the pyridine derivatives imposed cytotoxicity in melanoma cells. Importantly, the concentrations of the inhibitors leading to 50% decrease in the cell density (IC50) were comparable to those causing 50% drop in the enzyme activity, implying that the observed cytotoxicity is highly likely due to the tyrosinase inhibition. Moreover, our cell-based data exhibited that the pyridine derivatives acted as anti-proliferative agents, perhaps inducing cytotoxicity in the melanoma cells through inhibition of the tyrosinase activities. PMID:25810885

  5. The mitochondrial amidoxime reducing component (mARC): involvement in metabolic reduction of N-oxides, oximes and N-hydroxyamidinohydrazones.

    PubMed

    Jakobs, Heyka H; Froriep, Danilo; Havemeyer, Antje; Mendel, Ralf R; Bittner, Florian; Clement, Bernd

    2014-10-01

    The mitochondrial amidoxime reducing component (mARC) is a molybdenum-containing enzyme and capable of reducing N-hydroxylated structures such as amidoxime prodrugs. In this study, we tested the involvement of mARC in the reduction of N-oxides (amitriptyline-N-oxide, nicotinamide-N-oxide), oximes ((E)-/(Z)-2,4,6-trimethylacetophenonoxime) and a N-hydroxyamidinohydrazone (guanoxabenz). All groups are reduced by mARC proteins, and the enzymes are therefore involved in the interconversion of N-oxygenated metabolites originating from cytochrome P450s and flavin-containing monooxygenases. In addition, these structures open up further options for serving as prodrugs. Thus, with respect to these reactions, testing of candidates with N-oxygenated structures should not solely be carried out in microsomal enzyme sources but as well in mitochondria. However, differences in the reduction of oximes and N-oxides between the two isoforms, namely mARC1 and mARC2, were detectable; N-oxides are exclusively reduced by mARC1. We therefore assume differences between the so far unknown 3D structures of the two proteins.

  6. Improvement of enzymatic hydrolysis and ethanol production from corn stalk by alkali and N-methylmorpholine-N-oxide pretreatments.

    PubMed

    Cai, Ling-Yan; Ma, Yu-Long; Ma, Xiao-Xia; Lv, Jun-Min

    2016-07-01

    A combinative technology of alkali and N-methylmorpholine-N-oxide (NMMO) was used to pretreat corn stalk (CS) for improving the efficiencies of subsequent enzymatic hydrolysis and ethanol fermentation. The results showed that this strategy could not only remove hemicellulose and lignin but also decrease the crystallinity of cellulose. About 98.0% of enzymatic hydrolysis yield was obtained from the pretreated CS as compared with 46.9% from the untreated sample. The yield for corresponding ethanol yield was 64.6% while untreated CS was only 18.8%. Besides, xylose yield obtained from the untreated CS was only 11.1%, while this value was 93.8% for alkali with NMMO pretreated sample. These results suggest that a combination of alkali with 50% (wt/wt) NMMO solution may be a promising alternative for pretreatment of lignocellulose, which can increase the productions of subsequent enzymatic hydrolysis and ethanol fermentation.

  7. Simultaneous targeted analysis of trimethylamine-N-oxide, choline, betaine, and carnitine by high performance liquid chromatography tandem mass spectrometry.

    PubMed

    Liu, Jia; Zhao, Mingming; Zhou, Juntuo; Liu, Changjie; Zheng, Lemin; Yin, Yuxin

    2016-11-01

    Trimethylamine-N-oxide (TMAO) is a metabolite generated from choline, betaine and carnitine in a gut microbiota-dependent way. This molecule is associated with development of atherosclerosis and cardiovascular events. A sensitive liquid chromatographic electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) has been developed and validated for the simultaneous determination of TMAO related molecules including TMAO, betaine, choline, and carnitine in mouse plasma. Analytes are extracted after protein precipitation by methanol and subjected to LC-ESI-MS/MS without preliminary derivatization. Separation of analytes was achieved on an amide column with acetonitrile-water as the mobile phase. This method has been fully validated in this study in terms of selectivity, linearity, sensitivity, precision, accuracy, and carryover effect, and the stability of the analyte under various conditions has been confirmed. This developed method has successfully been applied to plasma samples of our mouse model.

  8. Antagonistic activity of poly (4-vinylpyridine-N-oxide) to the inhibition of viral interferon induction by asbestos fibres.

    PubMed Central

    Hahon, N; Booth, J A; Eckert, H L

    1977-01-01

    The depressive activity of both serpentine (Canadian and Rhodesian chrysotiles) and amphibole (amosite, crocidolite, and anthophyllite) asbestos fibres on interferon induction by influenza virus was significantly diminished or abolished completely when either asbestos fibres or LLC-MK2 cell monolayers were pretreated with poly(4-vinylpyridine-N-oxide). Maximal antagonistic activity of the polymer was time and concentration dependent. Pretreating asbestos fibres with the polymer was more rapid and effective in encouraging viral interferon synthesis than pretreating cell monolayers. Virus multiplication in the presence of asbestos fibre-treated cell monolayers attained a twofold higher level than that noted in normal cell monolayers or those containing polymer-pretreated asbestos fibres. These findings were related to the suppression of interferon production. PMID:871442

  9. Quantitative Characterization of the Compensating Effects of Trimethylamine-N-oxide and Guanidine Hydrochloride on the Dissociation of Human Cyanmethmoglobin

    PubMed Central

    Wu, Di; Minton, Allen P.

    2015-01-01

    Dynamic light scattering was used to measure the extent of dissociation of human cyanmethemoglobin (HbCN) α2β2 tetramers into αβ dimers as a function of HbCN concentration in the presence of varying concentrations of guanidine hydrochloride (GuHCl) and trimethylamine-N-oxide (TMAO). It was found that increasing concentrations of GuHCl enhance the dissociation of HbCN, and that GuHCl-induced dissociation is progressively inhibited with increasing concentrations of TMAO. The effects of both cosolutes upon the free energy of HbCN dissociation are shown to be additive. The effect of TMAO on Hb dissociation is largely attributed to steric volume exclusion but is partially compensated by a small attractive interaction between TMAO and the protein. PMID:23863125

  10. Radiolabeling of equine platelets in plasma with /sup 111/In-(2-mercaptopyridine-N-oxide) and their in vivo survival

    SciTech Connect

    Coyne, C.P.; Kelly, A.B.; Hornof, W.J.; O'Brien, T.R.; Philp, M.S.; Lamb, J.F.

    1987-03-01

    A method is presented for the in vitro isolation and radiolabeling of equine platelets with the isotope indium /sup 111/ (/sup 111/In: half-life = 2.8 days, gamma = 173 keV, 89%; 247 keV, 94%). The technique described involves complexing /sup 111/In with the lipid-soluble chelating agent, 2-mercaptopyridine-N-oxide (merc), in an aqueous medium. /sup 111/In-merc platelet-labeling efficiencies in autologous plasma pretreated with or without ferric citrate reagent were 82 +/- 7% and 24 +/- 12%, respectively. Mean intravascular survivals of /sup 111/In-merc-radiolabeled platelets in 8 healthy horses according to simple linear, exponential, mean, weighted-mean residual sum of squares analysis, and multiple-hit model were 5.5 +/- 0.49, 3.5 +/- 0.53, 4.5 +/- 0.18, 4.3 +/- 0.65, and 3.6 +/- 0.97 days, respectively.

  11. The electronic states of pyridine-N-oxide studied by VUV photoabsorption and ab initio configuration interaction computations.

    PubMed

    Palmer, Michael H; Hoffmann, Søren Vrønning; Jones, Nykola C; Smith, Elliott R; Lichtenberger, Dennis L

    2013-06-07

    The first vacuum-ultraviolet absorption spectrum of pyridine-N-oxide has been obtained, and has led to the identification of nearly 30 Rydberg states. These states were identified by use of the vibrational envelope ("footprint") of the UV-photoelectron spectrum, and are based on the first to the third ionization energies (IE). The adiabatic IE order, central to the Rydberg state symmetry identification, is confirmed by multi-configuration SCF calculations as: 1(2)B1 < 1(2)B2 < 1(2)A2 < 2(2)B1. Several excited valence state equilibrium structures were determined by multi-configuration SCF and coupled cluster procedures. Multi-reference multi-root CI was used to calculate both Rydberg and valence state vertical excitation energies and oscillator strengths, which were correlated with the experimental measurements.

  12. Effect of Water Content in N-Methylmorpholine N-Oxide/Cellulose Solutions on Thermodynamics, Structure, and Hydrogen Bonding.

    PubMed

    Rabideau, Brooks D; Ismail, Ahmed E

    2015-12-03

    Native crystalline cellulose is notoriously difficult to dissolve due to its dense hydrogen bond network between chains and weaker hydrophobic forces between cellulose sheets. N-Methylmorpholine N-oxide (NMMO), the solvent behind the Lyocell process, is one of the most successful commercial solvents for the nonderivatized dissolution of cellulose. In this process, water plays a very important role. Its presence at low concentrations allows NMMO to dissolve substantial amounts of cellulose, while at much higher concentrations it precipitates the crystalline fibers. Using all-atom molecular dynamics, we study the thermodynamic and structural properties of ternary solutions of cellulose, NMMO, and water. Using the two-phase thermodynamic method to calculate solvent entropy, we estimate the free energy of dissolution of cellulose as a function of the water concentration and find a transition of spontaneity that is in excellent agreement with experiment. In pure water, we find that cellulose dissolution is nonspontaneous, a result that is due entirely to strong decreases in water entropy. Although the combined effect of enthalpy on dissolution in water is negligible, we observe a net loss of hydrogen bonds, resulting in a change in hydrogen bond energy that opposes dissolution. At lower water concentrations, cellulose dissolution is spontaneous and largely driven by decreases in enthalpy, with solvent entropy playing only a very minor role. When searching for the root causes of this enthalpy decrease, a complex picture emerges in which not one but many different factors contribute to NMMO's good solvent behavior. The reduction in enthalpy is led by the formation of strong hydrogen bonds between cellulose and NMMO's N-oxide, intensified through van der Waals interactions between NMMO's nonpolar body and the nonpolar surfaces of cellulose and unhindered by water at low concentrations due to the formation of efficient hydrogen bonds between water and cellulose.

  13. AQ4N: an alkylaminoanthraquinone N-oxide showing bioreductive potential and positive interaction with radiation in vivo.

    PubMed Central

    McKeown, S. R.; Hejmadi, M. V.; McIntyre, I. A.; McAleer, J. J.; Patterson, L. H.

    1995-01-01

    AQ4N (1,4-bis([2-(dimethylamino-N-oxide)ethyl]amino)5,8-dihydroxy- anthracene-9,10-dione) is a novel alkylaminoanthraquinone N-oxide which, on reduction, forms a stable DNA affinic cytotoxic compound AQ4. The in vivo anti-tumour efficacy of AQ4N was investigated in B6D2F1 mice bearing the T50/80 mammary carcinoma. The effect of the drug was evaluated in combination with hypobaric hypoxia and with radiation (single and multiple fractions). Systemic toxicity was assessed by weight loss post treatment. This was low for AQ4N and was less than that obtained with the bioreductive drugs, RSU 1069 (1-[3-aziridinyl-2-hydroxypropyl]-2-nitroimidazole) and SR 4233 (Tirapazamine, 3-amino-1,2,4-benzotriazine-1,4-dioxide). The anti-tumour effect of AQ4N was potentiated in vivo by combination with hypobaric hypoxia with a dose enhancement ratio of 5.1. This is consistent with the proposal that AQ4N was reduced in vivo to AQ4, resulting in enhanced anti-tumour toxicity. When AQ4N (200 mg kg-1) was combined with single dose radiation (12 Gy) the drug was shown to have an additive interaction with radiation. This was obtained even if the drug was administered from 4 days before to 6 h after radiation treatment. Equivalent anti-tumour activity was also shown when both AQ4N (200 mg kg-1) and radiation (5 x 3 Gy) were administered in fractionated schedules. In conclusion, AQ4N shows significant potential as a bioreductive drug for combination with fractionated radiotherapy. PMID:7599069

  14. Complexation of heteroaromatic N-oxides with rhodium(II) tetracarboxylates in solution: DFT and NMR investigations

    NASA Astrophysics Data System (ADS)

    Głaszczka, Rafał; Jaźwiński, Jarosław

    2014-03-01

    Complexation of rhodium(II) tetraacetate and rhodium(II) tetrakistrifluoroacetate with a set of heteroaromatic N-oxides containing additional functional groups was investigated by means of density functional theory (DFT) calculations, and 1H, 13C and 15N nuclear magnetic resonance (NMR) spectroscopy in CDCl3 solutions. Chemical shifts for five N-oxides and their 1:1 adducts with rhodium tetraacetate were computed at the B3PW91/[6-311++G(2d,p), Stuttgart ECP)//B3LYP/[6-31G(2d), LANL2DZ] theory level applying IEF PCM (CHCl3) solvation model and taking into account various complexation modes and conformational variety. Calculated values were used for the estimation of complexation shifts Δδ (Δδ = δadduct - δligand). The largest negative complexation shift were estimated for heteroatoms bonded to Rh, from -37 to -70 ppm (N), from -100 to -160 ppm (O in NO group), from -13 to -23 ppm (O in OCH3 group), and from -12 to -22 ppm (Cl). For the remaining heteroatoms in adducts, the corresponding Δδ values ranged from -22 to +8.2 ppm (N), from +3 to +58 ppm (O) and from +6 to +51 ppm (Cl). The Δδ(1H) usually did not exceed 1 ppm, whereas Δδ(13C) varied from ca. -1 to +7 ppm. Some trends useful for the determination of the complexation site were extracted from calculated data sets. Theoretical findings were applied to analyse experimental NMR data.

  15. Potentiometric titration of heterocyclic nitrogen bases in non-aqueous media.

    PubMed

    Rao, K C; Naidu, P R

    1972-11-01

    Pyridine, quinoline, isoquinoline, acridine, alpha-picoline, beta-picoline, gamma-picoline and 2,6-lutidine have been titrated potentio-metrically (calomel and glass electrodes), with chlorosulphonic acid in methyl ethyl ketone-acetic acid (1:1) medium, with an error of less than 1%.

  16. The two facies of pyrrolizidine alkaloids: the role of the tertiary amine and its N-oxide in chemical defense of insects with acquired plant alkaloids.

    PubMed

    Lindigkeit, R; Biller, A; Buch, M; Schiebel, H M; Boppré, M; Hartmann, T

    1997-05-01

    Larvae of Creatonotos transiens (Lepidoptera, Arctiidae) and Zonocerus variegatus (Orthoptera, Pyrgomorphidae) ingest 14C-labeled senecionine and its N-oxide with the same efficiency but sequester the two tracers exclusively as N-oxide. Larvae of the non-sequestering Spodoptera littoralis eliminate efficiently the ingested alkaloids. During feeding on the two alkaloidal forms transient levels of senecionine (but not of the N-oxide) are built up in the haemolymph of S. littoralis larvae. Based on these results, senecionine [18O]N-oxide was fed to C. transiens larvae and Z. variegatus adults. The senecionine N-oxide recovered from the haemolymph of the two insects shows an almost complete loss of 18O label, indicating reduction of the orally fed N-oxide in the guts, uptake of the tertiary alkaloid and its re-N-oxidation in the haemolymph. The enzyme responsible for N-oxidation is a soluble mixed function monooxygenase. It was isolated from the haemolymph of the sequestering arctiid Tyria jacobaeae and purified to electrophoretic homogeneity. The enzyme is a flavoprotein with a native Mr of 200000 and a subunit Mr of 51000. It shows a pH optimum at 7.0, has its maximal activity at a temperature of 40-45 degrees C and an isoelectric point at pH 4.9. The reaction is strictly NADPH-dependent (Km 1.3 microM). From 20 pyrrolizidine alkaloids so far tested as substrates, the enyzme N-oxidizes only alkaloids with structural elements which are essential for hepatotoxic and genotoxic pyrrolizidine alkaloids (i.e. 1,2-double bond, esterification of the allylic hydroxyl group, presence of a second free or esterified hydroxyl group at carbon 7). A great variety of related alkaloids and xenobiotics were tested as substrate, none was accepted. The Km values of senecionine, monocrotaline and heliotrine, representing the three main types of pyrrolizidine alkaloids, are 1.3 microM, 12.5 microM and 290 microM, respectively. The novel enzyme was named senecionine N-oxygenase (SNO). The

  17. Rh(III)- and Zn(II)-Catalyzed Synthesis of Quinazoline N-Oxides via C-H Amidation-Cyclization of Oximes.

    PubMed

    Wang, Qiang; Wang, Fen; Yang, Xifa; Zhou, Xukai; Li, Xingwei

    2016-12-02

    Quinazoline N-oxides have been prepared from simple ketoximes and 1,4,2-dioxazol-5-ones via Rh(III)-catalyzed C-H activation-amidation of the ketoximes and subsequent Zn(II)-catalyzed cyclization. The substrate scope and functional group compatibility were examined. The reaction features relay catalysis by Rh(III) and Zn(II).

  18. Synthesis and biological evaluation of new 2-arylcarbonyl-3-trifluoromethylquinoxaline 1,4-di-N-oxide derivatives and their reduced analogues.

    PubMed

    Solano, Beatriz; Junnotula, Venkatraman; Marín, Adoración; Villar, Raquel; Burguete, Asunción; Vicente, Esther; Pérez-Silanes, Silvia; Aldana, Ignacio; Monge, Antonio; Dutta, Sanjay; Sarkar, Ujjal; Gates, Kent S

    2007-11-01

    As a continuation of our research in the quinoxaline 1,4-di-N-oxide new series of 2-arylcarbonyl-3-trifluoromethylquinoxaline, 1,4-di-N-oxide derivatives have been synthesized and evaluated in a full panel of 60 human tumor cell lines. Selective reductions were carried out on two compounds which allowed us to determine the compound structures by comparison of the 1H NMR spectra. In general, all the di-N-oxidized compounds showed good cytotoxic parameters. The best activity was observed in derivatives with electron-withdrawing groups in position 6 or 7 on the quinoxaline ring and in the unsubstituted analogues, whereas loss of one or two oxygens reduced the cytotoxicity. The best five compounds were selected for evaluation for the in vivo hollow fiber assays. In vitro studies reveal that compound 5h efficiently generates reactive oxygen species via redox cycling in the presence of the NADPH/cytochrome P450 enzyme system, providing a plausible molecular mechanism for the observed aerobic cytotoxicity of these quinoxaline N-oxides.

  19. Analysis of swainsonine and swainsonine N-oxide as trimethylsilyl derivatives by Liquid Chromatography-Mass Spectrometry and their relative occurrence in plants toxic to livestock

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A liquid chromatography-mass spectrometry method was developed for the analysis of the indolizidine alkaloid swainsonine and its N-oxide. The method is based on a one step solvent partitioning extraction procedure followed by trimethylsilylation of the dried extract and subsequent detection and qua...

  20. Trimethylamine-N-oxide switches from stabilizing nature: A mechanistic outlook through experimental techniques and molecular dynamics simulation

    NASA Astrophysics Data System (ADS)

    Rani, Anjeeta; Jayaraj, Abhilash; Jayaram, B.; Pannuru, Venkatesu

    2016-03-01

    In adaptation biology of the discovery of the intracellular osmolytes, the osmolytes are found to play a central role in cellular homeostasis and stress response. A number of models using these molecules are now poised to address a wide range of problems in biology. Here, a combination of biophysical measurements and molecular dynamics (MD) simulation method is used to examine the effect of trimethylamine-N-oxide (TMAO) on stem bromelain (BM) structure, stability and function. From the analysis of our results, we found that TMAO destabilizes BM hydrophobic pockets and active site as a result of concerted polar and non-polar interactions which is strongly evidenced by MD simulation carried out for 250 ns. This destabilization is enthalpically favourable at higher concentrations of TMAO while entropically unfavourable. However, to the best of our knowledge, the results constitute first detailed unambiguous proof of destabilizing effect of most commonly addressed TMAO on the interactions governing stability of BM and present plausible mechanism of protein unfolding by TMAO.

  1. Discovery and Optimization of Benzotriazine Di-N-Oxides Targeting Replicating and Non-replicating Mycobacterium tuberculosis

    PubMed Central

    Chopra, Sidharth; Koolpe, Gary A.; Tambo-ong, Arlyn A.; Matsuyama, Karen N.; Ryan, Kenneth J.; Tran, Tran B.; Doppalapudi, Rupa S.; Riccio, Edward S.; Iyer, Lalitha V.; Green, Carol E.; Wan, Baojie; Franzblau, Scott G.; Madrid, Peter B.

    2012-01-01

    Compounds bactericidal against both replicating and non-replicating Mtb may shorten the length of TB treatment regimens by eliminating infections more rapidly. Screening of a panel of antimicrobial and anticancer drug classes that are bioreduced into cytotoxic species revealed that 1,2,4-benzotriazine di-N-oxides (BTOs) are potently bactericidal against replicating and non-replicating Mtb. Medicinal chemistry optimization, guided by semi-empirical molecular orbital calculations, identified a new lead compound (20q) from this series with an MIC of 0.31 μg/mL against H37Rv and a cytotoxicity (CC50) against Vero cells of 25 μg/mL. 20q also had equivalent potency against a panel of single-drug resistant strains of Mtb and remarkably selective activity for Mtb over a panel of other pathogenic bacterial strains. 20q was also negative in a L5178Y MOLY assay, indicating low potential for genetic toxicity. These data along with measurements of the physiochemical properties and pharmacokinetic profile demonstrate that BTOs have the potential to be developed into a new class of antitubercular drugs. PMID:22691154

  2. Aqueous solvation of amphiphilic molecules by extended depolarized light scattering: the case of trimethylamine-N-oxide.

    PubMed

    Comez, L; Paolantoni, M; Corezzi, S; Lupi, L; Sassi, P; Morresi, A; Fioretto, D

    2016-04-07

    Hydrophilic and hydrophobic interactions strongly affect the solvation dynamics of biomolecules. To understand their role, small model systems are generally employed to simplify the investigations. In this study the amphiphile trimethylamine N-oxide (TMAO) is chosen as an exemplar, and studied by means of extended frequency range depolarized light scattering (EDLS) experiments as a function of solute concentration. This technique proves to be a suitable tool for investigating different aspects of aqueous solvation, being able at the same time to provide information about relaxation processes and vibrational modes of solvent and solute. In the case study of TMAO, we find that the relaxation dynamics of hydration water is moderately retarded compared to the bulk, and the perturbation induced by the solute on surrounding water is confined to the first hydration shell. The results highlight the hydrophobic character of TMAO in its interaction with water. The number of molecules taking part in the solvation process decreases as the solute concentration increases, following a trend consistent with the hydration water-sharing model, and suggesting that aggregation between solute molecules is negligible. Finally, the analysis of the resonant modes in the THz region and the comparison with the corresponding results obtained for the isosteric molecule tert-butyl alcohol (TBA) allow us to provide new insights into the different solvating properties of these two biologically relevant molecules.

  3. Trimethylamine-N-oxide switches from stabilizing nature: A mechanistic outlook through experimental techniques and molecular dynamics simulation

    PubMed Central

    Rani, Anjeeta; Jayaraj, Abhilash; Jayaram, B.; Pannuru, Venkatesu

    2016-01-01

    In adaptation biology of the discovery of the intracellular osmolytes, the osmolytes are found to play a central role in cellular homeostasis and stress response. A number of models using these molecules are now poised to address a wide range of problems in biology. Here, a combination of biophysical measurements and molecular dynamics (MD) simulation method is used to examine the effect of trimethylamine-N-oxide (TMAO) on stem bromelain (BM) structure, stability and function. From the analysis of our results, we found that TMAO destabilizes BM hydrophobic pockets and active site as a result of concerted polar and non-polar interactions which is strongly evidenced by MD simulation carried out for 250 ns. This destabilization is enthalpically favourable at higher concentrations of TMAO while entropically unfavourable. However, to the best of our knowledge, the results constitute first detailed unambiguous proof of destabilizing effect of most commonly addressed TMAO on the interactions governing stability of BM and present plausible mechanism of protein unfolding by TMAO. PMID:27025561

  4. Furoxans (1,2,5-Oxadiazole-N-Oxides) as Novel NO Mimetic Neuroprotective and Procognitive Agents

    SciTech Connect

    Schiefer, Isaac T.; VandeVrede, Lawren; Fa; , Mauro; Arancio, Ottavio; Thatcher, Gregory R.J.

    2012-08-31

    Furoxans (1,2,5-oxadiazole-N-oxides) are thiol-bioactivated NO-mimetics that have not hitherto been studied in the CNS. Incorporation of varied substituents adjacent to the furoxan ring system led to modulation of reactivity toward bioactivation, studied by HPLC-MS/MS analysis of reaction products. Attenuated reactivity unmasked the cytoprotective actions of NO in contrast to the cytotoxic actions of higher NO fluxes reported previously for furoxans. Neuroprotection was observed in primary neuronal cell cultures following oxygen glucose deprivation (OGD). Neuroprotective activity was observed to correlate with thiol-dependent bioactivation to produce NO{sub 2}{sup -}, but not with depletion of free thiol itself. Neuroprotection was abrogated upon cotreatment with a sGC inhibitor, ODQ, thus supporting activation of the NO/sGC/CREB signaling cascade by furoxans. Long-term potentiation (LTP), essential for learning and memory, has been shown to be potentiated by NO signaling, therefore, a peptidomimetic furoxan was tested in hippocampal slices treated with oligomeric amyloid-{beta} peptide (A{beta}) and was shown to restore synaptic function. The novel observation of furoxan activity of potential therapeutic use in the CNS warrants further studies.

  5. Quantification of glycine betaine, choline and trimethylamine N-oxide in seawater particulates: Minimisation of seawater associated ion suppression.

    PubMed

    Beale, Rachael; Airs, Ruth

    2016-09-28

    A liquid chromatography/mass spectrometry (LC/MS, electrospray ionisation) method has been developed for the quantification of nitrogenous osmolytes (N-osmolytes) in the particulate fraction of natural water samples. Full method validation demonstrates the validity of the method for measuring glycine betaine (GBT), choline and trimethylamine N-oxide (TMAO) in particulates from seawater. Limits of detection were calculated as 3.5, 1.2 and 5.9 pg injected onto column (equivalent to 1.5, 0.6 and 3.9 nmol per litre) for GBT, choline and TMAO respectively. Precision of the method was typically 3% for both GBT and choline and 6% for TMAO. Collection of the particulate fraction of natural samples was achieved via in-line filtration. Resulting chromatography and method sensitivity was assessed and compared for the use of both glass fibre and polycarbonate filters during sample collection. Ion suppression was shown to be a significant cause of reduced instrument response to N-osmolytes and was associated with the presence of seawater in the sample matrix.

  6. Advanced chronic kidney disease populations have elevated trimethylamine N-oxide levels associated with increased cardiovascular events.

    PubMed

    Kim, Richard B; Morse, Bridget L; Djurdjev, Ognjenka; Tang, Mila; Muirhead, Norman; Barrett, Brendan; Holmes, Daniel T; Madore, Francois; Clase, Catherine M; Rigatto, Claudio; Levin, Adeera

    2016-05-01

    Cardiovascular disease is more common in patients with chronic kidney disease (CKD), and traditional risk factors do not adequately predict those at risk for cardiovascular (CV) events. Recent evidence suggests elevated trimethylamine N-oxide (TMAO), created by gut microflora from dietary L-carnitine and choline, is associated with CV events. We investigated the relationship of TMAO levels in patients with stages 3b and 4 CKD to ischemic CV events using the CanPREDDICT cohort, a Canada-wide observational study with prospective 3-year follow-up of adjudicated CV events. Baseline samples were obtained for 2529 CKD patients. TMAO, choline, and L-carnitine levels were measured using tandem mass spectrometry. Baseline median TMAO level was high for the whole cohort (20.41 μM; interquartile range [IQR]: 12.82-32.70 μM). TMAO was independently associated with CV events (hazard ratio 1.23; 95% confidence interval: 1.06-1.42 / 1 SD lnTMAO) after adjusting for all potential CV risk factors. Those in the highest TMAO quartile had significantly higher risk of CV events (adjusted hazard ratio 1.59; 95% confidence interval: 1.04-2.43; P = 0.0351) in the analysis of recurring ischemic events. Among those with stage 3b CKD (hazard ratio 1.45; 95% confidence interval: 1.12-1.87 / 1 SD lnTMAO), independent of kidney function, TMAO levels identified those at highest risk for events. Our results suggest that TMAO may represent a new potentially modifiable CV risk factor for CKD patients. Further studies are needed to determine sources of variability and if lowering of TMAO reduces CV risk in CKD.

  7. Choline Diet and Its Gut Microbe Derived Metabolite, Trimethylamine N-Oxide (TMAO), Exacerbate Pressure Overload-Induced Heart Failure

    PubMed Central

    Organ, Chelsea L.; Otsuka, Hiroyuki; Bhushan, Shashi; Wang, Zeneng; Bradley, Jessica; Trivedi, Rishi; Polhemus, David J.; Tang, W. H. Wilson; Wu, Yuping; Hazen, Stanley L.; Lefer, David J.

    2015-01-01

    Background Trimethylamine N-oxide (TMAO), a gut microbe dependent metabolite of dietary choline and other trimethylamine containing nutrients, is both elevated in the circulation of patients suffering from heart failure (HF) and heralds worse overall prognosis. In animal studies, dietary choline or TMAO significantly accelerate atherosclerotic lesion development in ApoE deficient mice, and reduction in TMAO levels inhibits atherosclerosis development in the LDL receptor knockout mouse. Methods and Results C57BL6/J mice were fed either a control diet, a diet containing choline (1.2%) or a diet containing TMAO (0.12%) starting 3 weeks prior to surgical TAC. Mice were studied for 12 weeks following TAC. Cardiac function and left ventricular structure were monitored at 3-week intervals using echocardiography. Twelve weeks post-TAC myocardial tissues were collected to evaluate cardiac and vascular fibrosis, and blood samples were evaluated for cardiac BNP, choline, and TMAO levels. Pulmonary edema, cardiac enlargement, and left ventricular ejection fraction (LVEF) were significantly (p < 0.05, each) worse in mice fed either TMAO or choline supplemented diets compared to the control diet. In addition, myocardial fibrosis was also significantly greater (p < 0.01, each) in the TMAO and choline groups relative to controls. Conclusions Heart failure severity is significantly enhanced in mice fed diets supplemented in either choline or the gut microbe-dependent metabolite TMAO. The present results suggest that further studies are warranted examining whether gut microbiota and the dietary choline -> TMAO pathway contribute to increased heart failure susceptibility. PMID:26699388

  8. Gut Microbiota-Dependent Metabolite Trimethylamine N-Oxide Contributes to Cardiac Dysfunction in Western Diet-Induced Obese Mice

    PubMed Central

    Chen, Kui; Zheng, Xiaoqian; Feng, Mingchen; Li, Dongliang; Zhang, Hongqi

    2017-01-01

    Excessive consumption of diets high in sugars and saturated fat, frequently known as western diet (WD), may lead to obesity and metabolic syndrome. Recent evidence shows that WD-induced obesity impairs cardiac function, but the underlying mechanisms are not fully understood. Trimethylamine N-oxide (TMAO), a gut microbiota-dependent metabolite of specific dietary nutrients, has emerged as a key contributor to cardiovascular disease pathogenesis. We tested the hypothesis that elevated circulating TMAO levels contribute to cardiac dysfunction in WD-induced obesity. CD1 mice were fed a normal diet (ND) or a WD, without or with 1.0% 3,3-Dimethyl-1-butanol (DMB, an inhibitor of trimethylamine formation) in drinking water for 8 weeks. Compared with mice fed a ND, mice fed a WD showed a significant increase in body weight and dyslipidemia, and had markedly higher plasma TMAO levels at the end of the feeding protocol. Echocardiography revealed that cardiac systolic and diastolic function was impaired in mice fed a WD. DMB treatment had no effects on body weight and dyslipidemia, but significantly reduced plasma TMAO levels and prevented cardiac dysfunction in mice fed a WD. In addition, mice fed a WD had elevated expression of pro-inflammatory cytokines tumor necrosis factor-α and interleukin IL-1β, decreased expression of anti-inflammatory cytokine IL-10, and increased interstitial fibrosis in the hearts, all of which were prevented by DMB treatment. Notably, DMB treatment also reduced plasma TMAO levels in mice fed a ND but did not alter other parameters. These results suggest that consumption of a WD increases circulating TMAO levels, which lead to cardiac inflammation and fibrosis, contributing to cardiac dysfunction. Interventions that reduce circulating TMAO levels may be a novel therapeutic strategy for prevention and treatment of WD-induced cardiac dysfunction. PMID:28377725

  9. Mechanisms of Antibacterial Action of Quinoxaline 1,4-di-N-oxides against Clostridium perfringens and Brachyspira hyodysenteriae

    PubMed Central

    Xu, Fanfan; Cheng, Guyue; Hao, Haihong; Wang, Yulian; Wang, Xu; Chen, Dongmei; Peng, Dapeng; Liu, Zhenli; Yuan, Zonghui; Dai, Menghong

    2016-01-01

    Quinoxaline 1,4-di-N-oxides (QdNOs) are a class of bioreductive compounds, however, their antibacterial mechanisms are still unclarified. The aim of this study was to assess the ability of two representative QdNO drugs, cyadox (CYA) and olaquindox (OLA), to produce reactive oxide species (ROS) in Gram-positive anaerobe Clostridium perfringens CVCC1125 and Gram-negative anaerobe Brachyspira hyodysenteriae B204. In addition, the effects of QdNOs on the integrity of bacterial cell walls and membranes as well as the morphological alterations and DNA oxidative damage in C. perfringens and B. hyodysenteriae were analyzed. It was demonstrated that under anaerobic conditions, QdNOs were metabolized into the reduced products which did not show any antibacterial activity. A significant dose-related increase of intracellular ROS level and intracellular hydroxyl radicals were evident in bacteria exposed to QdNOs. The result of biochemical assay showed that the cell walls and membranes of the bacteria treated with QdNOs were damaged. After exposure to 1/2MIC to 4MIC of CYA and OLA, C. perfringens and B. hyodysenteriae became elongated and filamentous. Morphological observation with scanning and transmission electron microscopes revealed rupture, loss of cytoplasmic material and cell lysis in QdNO-treated bacteria, indicating serious damage of cells. There was an increase of 8-OHdG in the two strains treated by QdNOs, but it was lower in C. perfringens CVCC1125 than in B. hyodysenteriae B204. Agarose gel electrophoresis showed the degradation of chromosomal DNA in both of the two anaerobes treated by QdNOs. The results suggest that QdNOs may kill C. perfringens and B. hyodysenteriae via the generation of ROS and hydroxyl radicals from the bacterial metabolism of QdNOs, which cause oxidative damage in bacteria under anaerobic conditions. PMID:28018297

  10. Blood Trimethylamine-N-Oxide Originates from Microbiota Mediated Breakdown of Phosphatidylcholine and Absorption from Small Intestine

    PubMed Central

    Stremmel, Wolfgang; Schmidt, Kathrin V.; Schuhmann, Vera; Kratzer, Frank; Garbade, Sven F.; Langhans, Claus-Dieter; Fricker, Gert; Okun, Jürgen G.

    2017-01-01

    Elevated serum trimethylamine-N-oxide (TMAO) was previously reported to be associated with an elevated risk for cardiovascular events. TMAO originates from the microbiota-dependent breakdown of food-derived phosphatidylcholine (PC) to trimethylamine (TMA), which is oxidized by hepatic flavin-containing monooxygenases to TMAO. Our aim was to investigate the predominant site of absorption of the bacterial PC-breakdown product TMA. A healthy human proband was exposed to 6.9 g native phosphatidylcholine, either without concomitant treatment or during application with the topical antibiotic rifaximin, or exposed only to 6.9 g of a delayed-release PC formulation. Plasma and urine concentrations of TMA and TMAO were determined by electrospray ionization tandem mass spectrometry (plasma) and gas chromatography-mass spectrometry (urine). Native PC administration without concomitant treatment resulted in peak plasma TMAO levels of 43 ± 8 μM at 12 h post-ingestion, which was reduced by concomitant rifaximin treatment to 22 ± 8 μM (p < 0.05). TMAO levels observed after delayed-release PC administration were 20 ± 3 μM (p < 0.001). Accordingly, the peak urinary concentration at 24 h post-exposure dropped from 252 ± 33 to 185 ± 31 mmol/mmol creatinine after rifaximin treatment. In contrast, delayed-release PC resulted in even more suppressed urinary TMAO levels after the initial 12-h observation period (143 ± 18 mmol/mmol creatinine) and thereafter remained within the control range (24 h: 97 ± 9 mmol/mmol creatinine, p < 0.001 24 h vs. 12 h), indicating a lack of substrate absorption in distal intestine and large bowel. Our results showed that the microbiota in the small intestine generated the PC breakdown product TMA. The resulting TMAO, as a cardiovascular risk factor, was suppressed by topical-acting antibiotics or when PC was presented in an intestinally delayed release preparation. PMID:28129384

  11. Cholera toxin production during anaerobic trimethylamine N-oxide respiration is mediated by stringent response in Vibrio cholerae.

    PubMed

    Oh, Young Taek; Park, Yongjin; Yoon, Mi Young; Bari, Wasimul; Go, Junhyeok; Min, Kyung Bae; Raskin, David M; Lee, Kang-Mu; Yoon, Sang Sun

    2014-05-09

    As a facultative anaerobe, Vibrio cholerae can grow by anaerobic respiration. Production of cholera toxin (CT), a major virulence factor of V. cholerae, is highly promoted during anaerobic growth using trimethylamine N-oxide (TMAO) as an alternative electron acceptor. Here, we investigated the molecular mechanisms of TMAO-stimulated CT production and uncovered the crucial involvement of stringent response in this process. V. cholerae 7th pandemic strain N16961 produced a significantly elevated level of ppGpp, the bacterial stringent response alarmone, during anaerobic TMAO respiration. Bacterial viability was impaired, and DNA replication was also affected under the same growth condition, further suggesting that stringent response is induced. A ΔrelA ΔspoT ppGpp overproducer strain produced an enhanced level of CT, whereas anaerobic growth via TMAO respiration was severely inhibited. In contrast, a ppGpp-null strain (ΔrelA ΔspoT ΔrelV) grew substantially better, but produced no CT, suggesting that CT production and bacterial growth are inversely regulated in response to ppGpp accumulation. Bacterial capability to produce CT was completely lost when the dksA gene, which encodes a protein that works cooperatively with ppGpp, was deleted. In the ΔdksA mutant, stringent response growth inhibition was alleviated, further supporting the inverse regulation of CT production and anaerobic growth. In vivo virulence of ΔrelA ΔspoT ΔrelV or ΔdksA mutants was significantly attenuated. The ΔrelA ΔspoT mutant maintained virulence when infected with exogenous TMAO despite its defective growth. Together, our results reveal that stringent response is activated under TMAO-stimulated anaerobic growth, and it regulates CT production in a growth-dependent manner in V. cholerae.

  12. Osmolyte trimethylamine-N-oxide does not affect the strength of hydrophobic interactions: origin of osmolyte compatibility.

    PubMed

    Athawale, Manoj V; Dordick, Jonathan S; Garde, Shekhar

    2005-08-01

    Osmolytes are small organic solutes accumulated at high concentrations by cells/tissues in response to osmotic stress. Osmolytes increase thermodynamic stability of folded proteins and provide protection against denaturing stresses. The mechanism of osmolyte compatibility and osmolyte-induced stability has, therefore, attracted considerable attention in recent years. However, to our knowledge, no quantitative study of osmolyte effects on the strength of hydrophobic interactions has been reported. Here, we present a detailed molecular dynamics simulation study of the effect of the osmolyte trimethylamine-N-oxide (TMAO) on hydrophobic phenomena at molecular and nanoscopic length scales. Specifically, we investigate the effects of TMAO on the thermodynamics of hydrophobic hydration and interactions of small solutes as well as on the folding-unfolding conformational equilibrium of a hydrophobic polymer in water. The major conclusion of our study is that TMAO has almost no effect either on the thermodynamics of hydration of small nonpolar solutes or on the hydrophobic interactions at the pair and many-body level. We propose that this neutrality of TMAO toward hydrophobic interactions-one of the primary driving forces in protein folding-is at least partially responsible for making TMAO a "compatible" osmolyte. That is, TMAO can be tolerated at high concentrations in organisms without affecting nonspecific hydrophobic effects. Our study implies that protein stabilization by TMAO occurs through other mechanisms, such as unfavorable water-mediated interaction of TMAO with the protein backbone, as suggested by recent experimental studies. We complement the above calculations with analysis of TMAO hydration and changes in water structure in the presence of TMAO molecules. TMAO is an amphiphilic molecule containing both hydrophobic and hydrophilic parts. The precise balance of the effects of hydrophobic and hydrophilic segments of the molecule appears to explain the virtual

  13. Serum Trimethylamine-N-Oxide Is Strongly Related to Renal Function and Predicts Outcome in Chronic Kidney Disease

    PubMed Central

    Missailidis, Catharina; Hällqvist, Jenny; Qureshi, Abdel Rashid; Barany, Peter; Heimbürger, Olof; Lindholm, Bengt

    2016-01-01

    Background The microbial metabolite Trimethylamine-N-oxide (TMAO) has been linked to adverse cardiovascular outcome and mortality in the general population. Objective To assess the contribution of TMAO to inflammation and mortality in chronic kidney disease (CKD) patients ranging from mild-moderate to end-stage disease and 1) associations with glomerular filtration rate (GFR) 2) effect of dialysis and renal transplantation (Rtx) 3) association with inflammatory biomarkers and 4) its predictive value for all-cause mortality. Methods Levels of metabolites were quantified by a novel liquid chromatography/tandem mass spectrometry-based method in fasting plasma samples from 80 controls and 179 CKD 3–5 patients. Comorbidities, nutritional status, biomarkers of inflammation and GFR were assessed. Results GFR was the dominant variable affecting TMAO (β = -0.41; p<0.001), choline (β = -0.38; p<0.001), and betaine (β = 0.45; p<0.001) levels. A longitudinal study of 74 CKD 5 patients starting renal replacement therapy demonstrated that whereas dialysis treatment did not affect TMAO, Rtx reduced levels of TMAO to that of controls (p<0.001). Following Rtx choline and betaine levels continued to increase. In CKD 3–5, TMAO levels were associated with IL-6 (Rho = 0.42; p<0.0001), fibrinogen (Rho = 0.43; p<0.0001) and hsCRP (Rho = 0.17; p = 0.022). Higher TMAO levels were associated with an increased risk for all-cause mortality that remained significant after multivariate adjustment (HR 4.32, 95% CI 1.32–14.2; p = 0.016). Conclusion Elevated TMAO levels are strongly associated with degree of renal function in CKD and normalize after renal transplantation. TMAO levels correlates with increased systemic inflammation and is an independent predictor of mortality in CKD 3–5 patients. PMID:26751065

  14. Clozapine N-Oxide Administration Produces Behavioral Effects in Long–Evans Rats: Implications for Designing DREADD Experiments

    PubMed Central

    MacLaren, Duncan A. A.; Browne, Richard W.; Krishnan Radhakrishnan, Sandhya; Khare, Prachi; España, Rodrigo A.

    2016-01-01

    Abstract Clozapine N-oxide (CNO) is a ligand for a powerful chemogenetic system that can selectively inhibit or activate neurons; the so-called Designer Receptors Exclusively Activated by Designer Drugs (DREADD) system. This system consists of synthetic G-protein-coupled receptors, which are not believed to be activated by any endogenous ligand, but are activated by the otherwise inert CNO. However, it has previously been shown that the administration of CNO in humans and rats leads to detectable levels of the bioactive compounds clozapine and N-desmethylclozapine (N-Des). As a follow-up, experiments were conducted to investigate the effects of CNO in male Long–Evans rats. It was found that 1 mg/kg CNO reduced the acoustic startle reflex but had no effect on prepulse inhibition (PPI; a measure of sensorimotor gating). CNO (2 and 5 mg/kg) had no effect on the disruption to PPI induced by the NMDA antagonist phencyclidine or the muscarinic antagonist scopolamine. In locomotor studies, CNO alone (at 1, 2, and 5 mg/kg) had no effect on spontaneous locomotion, but 5 mg/kg CNO pretreatment significantly attenuated d-amphetamine-induced hyperlocomotion. In line with the behavioral results, fast-scan cyclic voltammetry found that 5 mg/kg CNO significantly attenuated the d-amphetamine-induced increase in evoked dopamine. However, the effects seen after CNO administration cannot be definitively ascribed to CNO because biologically relevant levels of clozapine and N-Des were found in plasma after CNO injection. Our results show that CNO has multiple dose-dependent effects in vivo and is converted to clozapine and N-Des emphasizing the need for a CNO-only DREADD-free control group when designing DREADD-based experiments. PMID:27822508

  15. Effect of egg ingestion on trimethylamine-N-oxide production in humans: a randomized, controlled, dose-response study1234

    PubMed Central

    Miller, Carolyn A; Corbin, Karen D; da Costa, Kerry-Ann; Zhang, Shucha; Zhao, Xueqing; Galanko, Joseph A; Blevins, Tondra; Bennett, Brian J; O'Connor, Annalouise; Zeisel, Steven H

    2014-01-01

    Background: It is important to understand whether eating eggs, which are a major source of dietary choline, results in increased exposure to trimethylamine-N-oxide (TMAO), which is purported to be a risk factor for developing heart disease. Objective: We determined whether humans eating eggs generate TMAO and, if so, whether there is an associated increase in a marker for inflammation [ie, high-sensitivity C-reactive protein (hsCRP)] or increased oxidation of low-density lipoprotein (LDL). Design: In a longitudinal, double-blind, randomized dietary intervention, 6 volunteers were fed breakfast doses of 0, 1, 2, 4, or 6 egg yolks. Diets were otherwise controlled on the day before and day of each egg dose with a standardized low-choline menu. Plasma TMAO at timed intervals (immediately before and 1, 2, 4, 8, and 24 h after each dose), 24-h urine TMAO, predose and 24-h postdose serum hsCRP, and plasma oxidized LDL were measured. Volunteers received all 5 doses with each dose separated by >2-wk washout periods. Results: The consumption of eggs was associated with increased plasma and urine TMAO concentrations (P < 0.01), with ∼14% of the total choline in eggs having been converted to TMAO. There was considerable variation between individuals in the TMAO response. There was no difference in hsCRP or oxidized LDL concentrations after egg doses. Conclusions: The consumption of ≥2 eggs results in an increased formation of TMAO. Choline is an essential nutrient that is required for normal human liver and muscle functions and important for normal fetal development. Additional study is needed to both confirm the association between TMAO and atherosclerosis and identify factors, microbiota and genetic, that influence the generation of TMAO before policy and medical recommendations are made that suggest reduced dietary choline intake. This trial was registered at clinicaltrials.gov as NCT01906554. PMID:24944063

  16. Highly Diastereo- and Enantioselective Michael Addition of Nitroalkanes to 2-Enoyl-Pyridine N-Oxides Catalyzed by Scandium(III)/Copper(II) Complexes.

    PubMed

    Li, Lijun; Zhang, Sheng; Hu, Yanbin; Li, Yanan; Li, Chong; Zha, Zhenggen; Wang, Zhiyong

    2015-09-07

    A C2 -symmetric Schiff-base ligand, derived from tridentate-Schiff-base, was developed and successfully applied to the asymmetric Michael addition of nitroalkanes to 2-enoyl-pyridine N-oxides. With this newly catalytic system, an unprecedented diastereoselectivity was obtained in the asymmetric Michael addition of nitroalkanes to 2-enoyl-pyridine N-oxides. In addition, a switch in enantioselectivity was achieved by using this newly catalytic system and our previous catalyst. After a facile reduction, the optically active adduct was converted to a biologically active dihydro-2H-pyrrol 4 a. Furthermore, a connection of two tridentate-Schiff-base subunits proved to be an effective strategy in ligand design.

  17. A Car-Parrinello and path integral molecular dynamics study of the intramolecular lithium bond in the lithium 2-pyridyl-N-oxide acetate

    NASA Astrophysics Data System (ADS)

    Durlak, Piotr; Latajka, Zdzisław; Berski, Sławomir

    2009-07-01

    Lithium bonding in lithium 2-pyridyl-N-oxide acetate has been investigated using classic Car-Parrinello molecular dynamics (CPMD) and the path integral approach [path integrals molecular dynamics (PIMD)]. The simulations have been performed in 300 K. Structures, energies, and lithium trajectories have been determined. The CPMD results show that the lithium atom is generally equidistant between heavy atoms in the (O⋯Li⋯O) bridge. Applying quantum effects through the PIMD leads to similar conclusion. The theoretical lithium 2-pyridyl-N-oxide acetate infrared spectrum has also been determined using the CPMD calculations. This shows very good agreement with available experimental results and reproduces well the broad low-frequency band observed experimentally. In order to gain deeper understanding of the nature of the lithium bonding topological analysis of the electron localization function has been applied.

  18. Site-specific indolation of proline-based peptides via copper(II)-catalyzed oxidative coupling of tertiary amine N-oxides.

    PubMed

    Wu, Xiaowei; Zhang, Dengyou; Zhou, Shengbin; Gao, Feng; Liu, Hong

    2015-08-14

    The first site-specific and purely chemical method for modifying proline-based peptides was developed via a convenient, copper-catalyzed oxidative coupling of tertiary amine N-oxides with indoles. This novel approach features high regioselectivity and diastereoselectivity, mild conditions, and compatibility with various functional groups. In addition, a simplified process was realized in one pot and two steps via in situ oxidative coupling of tertiary amine and indoles.

  19. Simultaneous determination of diphenhydramine, its N-oxide metabolite and their deuterium-labeled analogues in ovine plasma and urine using liquid chromatography/electrospray tandem mass spectrometry.

    PubMed

    Kumar, S; Rurak, D W; Riggs, K W

    1998-12-01

    Our studies on drug disposition in chronically instrumented pregnant sheep involve simultaneous administration of the antihistamine diphenhydramine (DPHM), its deuterated analogue ([2H10]DPHM) and their metabolites to the mother or the fetus via various routes. Such studies require sensitive and selective mass spectrometric methods for quantitation of these labeled and unlabeled compounds in order to assess comparative maternal and fetal drug metabolism. The objective of this study was to develop and validate a liquid chromatographic/tandem mass spectrometric (LC/MS/MS) method for the simultaneous quantitation of DPHM, its N-oxide metabolite and their deuterium-labeled analogues in ovine plasma and urine. Samples spiked with the analytes and the internal standard, orphenadrine, were processed using liquid-liquid extraction. The extract was chromatographed on a propylamino LC column and MS/MS detection was performed in the positive ion electrospray mode using multiple reaction monitoring. The linear concentration ranges of the calibration curves for the N-oxides and the parent amines were 0.4-100.0 and 0.2-250.0 ng ml-1, respectively. In validation tests, the assay exhibited acceptable variability (< or = 15% at analyte concentrations below 2.0 ng ml-1 and < 10% at all other concentrations) and bias (< 15% at all concentrations), and the analytes were stable under a variety of sample handling conditions. Using this method, the labeled and unlabeled N-oxide metabolite was identified in fetal plasma after DPHM and [2H10]DPHM administration. This method will be used further to examine the comparative metabolism of diphenhydramine to its N-oxide metabolite in the mother and the fetus.

  20. Enantioselective Mukaiyama-Michael with 2-enoyl pyridine N-oxides catalyzed by PYBOX-DIPH-Zn(II)-complexes at ambient temperature.

    PubMed

    Rout, Subhrajit; Ray, Sumit K; Singh, Vinod K

    2013-07-21

    A chiral PYBOX-DIPH-Zn(II) catalyzed enantioselective Mukaiyama-Michael reaction of acyclic silyl enol ethers with 2-enoylpyridine N-oxides has been studied in external additive free conditions at ambient temperature. The methodology offers straightforward access to a variety of functionalized chiral 1,5-dicarbonyl compounds, which could easily be elaborated into synthetically viable pyrones via hydrolysis followed by cyclization. A transition state model has been proposed to explain the stereochemical outcome.

  1. In vitro and in vivo antimycobacterial activities of ketone and amide derivatives of quinoxaline 1,4-di-N-oxide

    PubMed Central

    Villar, Raquel; Vicente, Esther; Solano, Beatriz; Pérez-Silanes, Silvia; Aldana, Ignacio; Maddry, Joseph A.; Lenaerts, Anne J.; Franzblau, Scott G.; Cho, Sang-Hyun; Monge, Antonio; Goldman, Robert C.

    2008-01-01

    Objectives To evaluate a novel series of quinoxaline 1,4-di-N-oxides for in vitro activity against Mycobacterium tuberculosis and for efficacy in a mouse model of tuberculosis (TB). Methods Ketone and amide derivatives of quinoxaline 1,4-di-N-oxide were evaluated in in vitro and in vivo tests including: (i) activity against M. tuberculosis resistant to currently used antitubercular drugs including multidrug-resistant strains (MDR-TB resistant to isoniazid and rifampicin); (ii) activity against non-replicating persistent (NRP) bacteria; (iii) MBC; (iv) maximum tolerated dose, oral bioavailability and in vivo efficacy in mice; and (v) potential for cross-resistance with another bioreduced drug, PA-824. Results Ten compounds were tested on single drug-resistant M. tuberculosis. In general, all compounds were active with ratios of MICs against resistant and non-resistant strains of ≤4.00. One compound, 5, was orally active in a murine model of TB, bactericidal, active against NRP bacteria and active on MDR-TB and poly drug-resistant clinical isolates (resistant to 3–5 antitubercular drugs). Conclusions Quinoxaline 1,4-di-N-oxides represent a new class of orally active antitubercular drugs. They are likely bioreduced to an active metabolite, but the pathway of bacterial activation was different from PA-824, a bioreducible nitroimidazole in clinical trials. Compound 5 was bactericidal and active on NRP organisms indicating that activation occurred in both growing and non-replicating bacteria leading to cell death. The presence of NRP bacteria is believed to be a major factor responsible for the prolonged nature of antitubercular therapy. If the bactericidal activity and activity on non-replicating bacteria in vitro translate to in vivo conditions, quinoxaline 1,4-di-N-oxides may offer a path to shortened therapy. PMID:18502817

  2. 1-(2-biphenyl)-3-methyltriazenide-N-oxide as a template for intramolecular copper(II)⋯arene-π interactions

    NASA Astrophysics Data System (ADS)

    Paraginski, Gustavo Luiz; Hörner, Manfredo; Back, Davi Fernando; Wohlmuth Alves dos Santos, Aline Joana Rolina; Beck, Johannes

    2016-01-01

    Deprotonated triazene N-oxides are able to chelate metal ions resulting in five-membered rings without carbon atoms. A new ligand 1-(2-biphenyl)-3-methyltriazenide-N-oxide (1) and its mononuclear Cu(II) complex (2) were synthesized to verify the capability of this ligand to promote Cu(II)⋯arene-π interactions. Ligand 1 and complex 2 have been characterized by elemental analysis, mass spectrometry (ESI(+)-TOF), IR, and UV-Vis spectroscopy. In addition, ligand 1 was characterized by 1H and 13C NMR and complex 2 by X-ray diffraction on single crystal. The crystal structure of complex 2 reveals a distorted tetrahedral geometry of Cu(II) in the first coordination sphere, which expands to a distorted octahedral environment by two symmetrically independent intramolecular metal⋯arene-π interactions. These interactions are provided by ortho-phenyl rings of both triazene N-oxide ligands 1. The aim of this work was to contribute to the architecture of new Cu(II)⋯arene-π complexes based on the synthesis of appropriated ligand for intramolecular interactions

  3. Profiling of Dehydropyrrolizidine Alkaloids and their N-Oxides in Herbarium-Preserved Specimens of Amsinckia Species Using HPLC-esi(+)MS

    PubMed Central

    2015-01-01

    Species of the Amsinckia genus (Boraginaceae) are known to produce potentially hepato-, pneumo-, and/or genotoxic dehydropyrrolizidine alkaloids. However, the taxonomic differentiation of Amsinckia species can be very subtle and there seems to be marked differences in toxicity toward grazing livestock. Methanol extracts of mass-limited leaf samples from herbarium specimens (collected from 1899 to 2013) of 10 Amsinckia species and one variety were analyzed using HPLC-esi(+)MS and MS/MS for the presence of potentially toxic dehydropyrrolizidine alkaloids and/or their N-oxides. Dehydropyrrolizidine alkaloids were detected in all specimens examined ranging from about 1 to 4000 μg/g of plant. Usually occurring mainly as their N-oxides, the predominant alkaloids were the epimeric lycopsamine and intermedine. Also sometimes observed in higher concentrations were the 3′- and 7-acetyl derivatives of lycopsamine/intermedine and their N-oxides. Within a designated species, an inconsistent profile was often observed that may be due to natural variation, taxonomic misassignment, or nonuniform degradation due to plant collection and storage differences. PMID:24655304

  4. Coordinatively polymeric and monomeric bismuth(III) complexes with pyridine carboxylic acids.

    PubMed

    Anjaneyulu, O; Prasad, T K; Swamy, K C Kumara

    2010-02-28

    Three crystalline compounds, [Bi(2-O(2)C-C(5)H(4)N)(3)](n) (), {Bi[(2,6-O(2)C)(2)C(5)H(3)N)][(2-HO(2)C-6-O(2)C)C(5)H(3)N].H(2)O}(n) (3) and Bi(O(2)CC(9)H(6)N)(2)(O(3)N)(O(2)CC(9)H(6)NH).2H(2)O () have been prepared by simple reactions in aqueous medium using the readily available bismuth nitrate and the corresponding acids, picolinic acid, dipicolinic acid and quinaldic acid. While and are coordination polymers with bismuth in tricapped trigonal prismatic and dodecahedral environments, compound is a monomeric species with dodecahedral geometry at bismuth. Compound represents a second crystalline form of a recently reported structure with subtle differences in bond parameters, and highlights the flexibility in structural motifs during crystallization. Compound involves skeletons with dimeric [Bi(2)O(2)] and trimeric [BiOCOBiOBiOCO] moieties. In , while the N-protonated carboxylate forms a four-membered chelate ring with bismuth, the other two carboxylates form five-membered ring chelates with the nitrate accounting for the remaining two sites again as a chelate. TGA studies are consistent with the presence of non-coordinated water in and . Compounds and , although insoluble in most of the organic solvents and water, are readily soluble in dilute hydrochloric acid.

  5. Metal-free functionalization of N,N-dialkylanilines via temporary oxidation to N,N-dialkylaniline N-oxides and group transfer.

    PubMed

    Lewis, Robert S; Wisthoff, Michael F; Grissmerson, J; Chain, William J

    2014-07-18

    A simple set of protocols for the controlled elaboration of anilines is reported allowing access to a diverse array of aminophenols, aminoarylsulfonates, alkylated anilines, and aminoanilines in 29-95% yield in a single laboratory operation from easily isolable, bench-stable N,N-dialkylaniline N-oxides. The introduction of new C-O, C-C, and C-N bonds on the aromatic ring is made possible by a temporary increase in oxidation level and excision of a weak N-O bond.

  6. Determination of trimethylamine-N-oxide in combination with L-carnitine and γ-butyrobetaine in human plasma by UPLC/MS/MS.

    PubMed

    Grinberga, Solveiga; Dambrova, Maija; Latkovskis, Gustavs; Strele, Ieva; Konrade, Ilze; Hartmane, Dace; Sevostjanovs, Eduards; Liepinsh, Edgars; Pugovics, Osvalds

    2015-11-01

    An ultra-high-performance liquid chromatography-mass spectrometry (UPLC/MS/MS) method was developed and validated for the quantification of trimethylamine-N-oxide (TMAO) simultaneously with TMAO-related molecules L-carnitine and γ-butyrobetaine (GBB) in human blood plasma. The separation of analytes was achieved using a Hydrophilic interaction liquid chromatography (HILIC)-type column with ammonium acetate-acetonitrile as the mobile phase. TMAO determination was validated according to valid US Food and Drug Administration guidelines. The developed method was successfully applied to plasma samples from healthy volunteers.

  7. Optical microinterferometry method for evaluation of phase state and diffusion in ternary systems: phase separation in cellulose/N-Methylmorpholine-N-oxide/non-solvent mixtures

    NASA Astrophysics Data System (ADS)

    Makarova, V. V.; Antonov, S. V.; Anokhina, T. A.; Volkov, V. V.

    2016-09-01

    Microinterferometry technique was used to evaluate the phase state and diffusion of cellulose solutions N-Methylmorpholine-N-oxide upon contact with non-solvents (water and aqueous solutions of isopropyl alcohol). The method was helpful in visualization of the structure of the forming cellulose film in connection with the diffusivity of the components of the systems. The interdiffusion coefficient were determined. Isopropyl alcohol addition to water slows down the diffusion of the coagulant into the cellulose solution thus delaying cellulose precipitation. Increase of temperature leads to formation of less dense cellulose film morphology with large vacuoles.

  8. Theoretical studies on the structure, thermochemical and detonation properties of amino and nitroso substituted 1,2,4-triazol-5-one-N-oxides.

    PubMed

    Ravi, P; Venkatesan, V; Tewari, Surya P

    2013-11-01

    DFT calculations at the B3LYP/aug-cc-pVDZ level have been carried out to explore the structure, stability, electron density, heat of formation, detonation velocity and detonation pressure of substituted amino- and nitroso-1,2,4-triazol-5-one-N-oxides. Heats of formation of substituted triazol-5-one-N-oxides have been computed at the B3LYP/aug-cc-pVDZ level via isodesmic reaction procedure. Materials Studio 4.1 package was used to predict the crystal density of model compounds. Kamlet-Jacob equations were used to calculate detonation properties based on the calculated heat of explosion and crystal density. The designed compounds 4, 6, 7 and 8 have shown higher performance compared with those of 2,4,6,8,10,12-hexanitro-2,4,6,8,10,12-hexaazaisowurtzitane and octanitrocubane. Atoms-in-molecule (AIM) analyses have also been carried out to understand the nature of intramolecular interactions in the designed molecules.

  9. Structural and spectroscopic characterization of methyl isocyanate, methyl cyanate, methyl fulminate, and acetonitrile N-oxide using highly correlated ab initio methods

    NASA Astrophysics Data System (ADS)

    Dalbouha, S.; Senent, M. L.; Komiha, N.; Domínguez-Gómez, R.

    2016-09-01

    Various astrophysical relevant molecules obeying the empirical formula C2H3NO are characterized using explicitly correlated coupled cluster methods (CCSD(T)-F12). Rotational and rovibrational parameters are provided for four isomers: methyl isocyanate (CH3NCO), methyl cyanate (CH3OCN), methyl fulminate (CH3ONC), and acetonitrile N-oxide (CH3CNO). A CH3CON transition state is inspected. A variational procedure is employed to explore the far infrared region because some species present non-rigidity. Second order perturbation theory is used for the determination of anharmonic frequencies, rovibrational constants, and to predict Fermi resonances. Three species, methyl cyanate, methyl fulminate, and CH3CON, show a unique methyl torsion hindered by energy barriers. In methyl isocyanate, the methyl group barrier is so low that the internal top can be considered a free rotor. On the other hand, acetonitrile N-oxide presents a linear skeleton, C3v symmetry, and free internal rotation. Its equilibrium geometry depends strongly on electron correlation. The remaining isomers present a bend skeleton. Divergences between theoretical rotational constants and previous parameters fitted from observed lines for methyl isocyanate are discussed on the basis of the relevant rovibrational interaction and the quasi-linearity of the molecular skeleton.

  10. Structural and spectroscopic characterization of methyl isocyanate, methyl cyanate, methyl fulminate, and acetonitrile N-oxide using highly correlated ab initio methods.

    PubMed

    Dalbouha, S; Senent, M L; Komiha, N; Domínguez-Gómez, R

    2016-09-28

    Various astrophysical relevant molecules obeying the empirical formula C2H3NO are characterized using explicitly correlated coupled cluster methods (CCSD(T)-F12). Rotational and rovibrational parameters are provided for four isomers: methyl isocyanate (CH3NCO), methyl cyanate (CH3OCN), methyl fulminate (CH3ONC), and acetonitrile N-oxide (CH3CNO). A CH3CON transition state is inspected. A variational procedure is employed to explore the far infrared region because some species present non-rigidity. Second order perturbation theory is used for the determination of anharmonic frequencies, rovibrational constants, and to predict Fermi resonances. Three species, methyl cyanate, methyl fulminate, and CH3CON, show a unique methyl torsion hindered by energy barriers. In methyl isocyanate, the methyl group barrier is so low that the internal top can be considered a free rotor. On the other hand, acetonitrile N-oxide presents a linear skeleton, C3v symmetry, and free internal rotation. Its equilibrium geometry depends strongly on electron correlation. The remaining isomers present a bend skeleton. Divergences between theoretical rotational constants and previous parameters fitted from observed lines for methyl isocyanate are discussed on the basis of the relevant rovibrational interaction and the quasi-linearity of the molecular skeleton.

  11. In vitro metabolism of α7 neuronal nicotinic receptor agonist AZD0328 and enzyme identification for its N-oxide metabolite.

    PubMed

    Zhou, Diansong; Zhang, Minli; Ye, Xiaomei; Gu, Chungang; Piser, Timothy M; Lanoue, Bernard A; Schock, Sara A; Cheng, Yi-Fang; Grimm, Scott W

    2011-03-01

    1. AZD0328 was pharmacologically characterized as a α7 neuronal nicotinic receptor agonist intended for treatment of Alzheimer's disease. In vitro AZD0328 cross species metabolite profile and enzyme identification for its N-oxide metabolite were evaluated in this study. 2. AZD0328 was very stable in the human hepatocyte incubation, whereas extensively metabolized in rat, dog and guinea pig hepatocyte incubations. The N-oxidation metabolite (M6) was the only metabolite detected in human hepatocyte incubations, and it also appeared to be the major in vitro metabolic pathway in a number of preclinical species. In addition, N-glucuronide metabolite of AZD0328 was observed in human liver microsomes. 3. Other metabolic pathways in the preclinical species include hydroxylation in azabicyclo octane or furopyridine part of the molecule. Pyridine N-methylation of AZD0328 (M2) was identified as a dog specific metabolite, not observed in human or other preclinical species. 4. Multiple enzymes including CYP2D6, CYP3A4/5, FMO1 and FMO3 catalyzed AZD0328 metabolism. The potential for AZD0328 to be inhibited clinically by co-administered drugs or genetic polymorphism is relative low.

  12. Inhibition of Tapeworm Thioredoxin and Glutathione Pathways by an Oxadiazole N-Oxide Leads to Reduced Mesocestoides vogae Infection Burden in Mice.

    PubMed

    Pasquet, Vivian; Bisio, Hugo; López, Gloria V; Romanelli-Cedrez, Laura; Bonilla, Mariana; Saldaña, Jenny; Salinas, Gustavo

    2015-06-26

    Parasitic flatworms cause serious infectious diseases that affect humans and livestock in vast regions of the world, yet there are few effective drugs to treat them. Thioredoxin glutathione reductase (TGR) is an essential enzyme for redox homeostasis in flatworm parasites and a promising pharmacological target. We purified to homogeneity and characterized the TGR from the tapeworm Mesocestoides vogae (syn. M. corti). This purification revealed absence of conventional TR and GR. The glutathione reductase activity of the purified TGR exhibits a hysteretic behavior typical of flatworm TGRs. Consistently, M. vogae genome analysis revealed the presence of a selenocysteine-containing TGR and absence of conventional TR and GR. M. vogae thioredoxin and glutathione reductase activities were inhibited by 3,4-bis(phenylsulfonyl)-1,2,5-oxadiazole N2-oxide (VL16E), an oxadiazole N-oxide previously identified as an inhibitor of fluke and tapeworm TGRs. Finally, we show that mice experimentally infected with M. vogae tetrathyridia and treated with either praziquantel, the reference drug for flatworm infections, or VL16E exhibited a 28% reduction of intraperitoneal larvae numbers compared to vehicle treated mice. Our results show that oxadiazole N-oxide is a promising chemotype in vivo and highlights the convenience of M. vogae as a model for rapid assessment of tapeworm infections in vivo.

  13. Precious-Metal-Free Heteroarylation of Azlactones: Direct Synthesis of α-Pyridyl, α-Substituted Amino Acid Derivatives.

    PubMed

    Johnson, Tarn C; Marsden, Stephen P

    2016-10-21

    A one-pot, three-component synthesis of α-pyridyl, α-substituted amino acid derivatives is described. The key transformation is a direct, precious-metal-free heteroarylation of readily available, amino acid derived azlactones with electrophilically activated pyridine N-oxides. The resulting intermediates can be used directly as efficient acylating agents for a range of nucleophiles, leading to the heteroarylated amino acid derivatives in a single vessel.

  14. Gold Catalysed Redox Synthesis of Imidazo[1,2-a]pyridine using Pyridine N-Oxide and Alkynes

    PubMed Central

    Talbot, Eric P. A.; Richardson, Melodie; McKenna, Jeffrey M.; Toste, F. Dean

    2014-01-01

    A mild, catalytic, atom economical synthesis of imidazo[1,2-a]pyridines has been developed: catalytic PicAuCl2 in the presence of an acid produces a range imidazo[1,2-a]pyridines in good yield. This strategy is mild and forseen to be of particular use for the installation of stereogenic centers adjacent to the imidazo[1,2-a]pyridine ring without loss of enantiomeric excess. PMID:24839436

  15. Aromatic N-oxides in construction of different carboxylate coordination polymers of zinc(II), cadmium(II) and mercury(II)

    NASA Astrophysics Data System (ADS)

    Sarma, Rupam; Baruah, Jubaraj B.

    2011-09-01

    The coordination polymers [Zn(C 6H 5COO) 2(PNO)] n ( 1), [Zn 2(C 6H 5COO) 4(4,4'-BPNO)] n ( 2), [Zn 4(C 6H 4C 2O 4) 4(4,4'-BPNO) 2(H 2O) 5] n· nH 2O ( 3), [Cd(C 6H 5COO) 2(PNO)] n ( 4), [Cd 3(C 6H 5COO) 6(4,4'-BPNO) 2] n·2 nH 2O ( 5), [Cd(C 6H 4C 2O 4)(4,4'-BPNO)(H 2O)] n ( 6) and [Hg(C 6H 5COO) 2(4,4'-BPNO) 2] n ( 7), (where PNO = pyridine N-oxide, 4,4'-BPNO = 4,4'-bipyridyl- N,N'-dioxide) are synthesized and structurally characterized. The structures of these coordination polymers exhibit mononuclear to trinuclear nodes built by ligation of carboxylate to metal ions connected by N-oxide ligands. Pyridine N-oxide interconnects metal nodes by acting as μ 2-bridging ligand in complexes 1, and 4. In the linear coordination polymer 2, the paddle wheel structure of zinc(II) benzoate units are interconnected by 4,4'-bipyridyl- N,N'-dioxide which acts as a bidentate spacer ligand adopting a trans μ 2-η 1 : η 1 coordination mode. The polymeric structure of 3 formed by terephthalate and 4,4'-bipyridyl- N,N'-dioxide with zinc(II) contains self-assembled dinuclear Zn 2O 2 type of carboxylate cores, with 4,4'-bipyridyl- N,N'-dioxide coordinating through cis μ 2-η 1 : η 1 coordination mode. The cadmium coordination polymer 5, comprising of 4,4'-bipyridyl- N,N'-dioxide and benzoate, has trinuclear cadmium benzoate cores wherein the terminal cadmium ions are interconnected by monodentate 4,4'-bipyridyl- N,N'-dioxide bridges. The coordination polymer 6 comprises of mononuclear cadmium nodes independently bridged by terephthalate and 4,4'-bipyridyl- N,N'-dioxide thereby leading to a 3-fold interpenetrated three dimensional network. Double helical polymeric structure is observed in the coordination polymer 7 derived from mononuclear mercury(II) benzoate nodes bridged by 4,4'-bipyridyl- N,N'-dioxide with cis μ 2-η 1 : η 1 coordination mode.

  16. Reduction of carbadox mediated by reaction of Mn(III) with oxalic acid.

    PubMed

    Chen, Wan-Ru; Liu, Cun; Boyd, Stephen A; Teppen, Brian J; Li, Hui

    2013-02-05

    Manganese(III) geocomponents are commonly found in the soil environment, yet their roles in many biogeochemical processes remain unknown. In this study, we demonstrated that Mn(III) generated from the reaction of MnO(2) and oxalic acid caused rapid and extensive decompositions of a quinoxaline-di-N-oxide antibiotics, viz carbadox. The reaction occurred primarily at the quinoxaline-di-N-oxide moiety resulting in the removal of one -O from N1-oxide and formation of desoxycarbadox. The reaction rate was accelerated by increasing amounts of Mn(III), carbadox and oxalate. The critical step in the overall reaction was the formation of a quinoxaline-di-N-oxide/Mn(III)/oxalate ternary complex in which Mn(III) functioned as the central complexing cation and electron conduit in which the arrangement of ligands facilitated electron transfer from oxalate to carbadox. In the complex, the C-C bond in oxalate was cleaved to create CO(2)(-•) radicals, followed by electron transfer to carbadox through the Mn(III) center. This proposed reaction mechanism is supported by the reaction products formed, reaction kinetics, and quantum mechanical calculations. The results obtained from this study suggest that naturally occurring Mn(III)-oxalic acid complexes could reductively decompose certain organic compounds in the environment such as the antibiotic quinoxaline-di-N-oxide.

  17. Vibrational characteristics and structure of the six- and eight-coordinate praseodymium(III) complexes with 2,6-lutidine N-oxide derivatives

    NASA Astrophysics Data System (ADS)

    Ban-Oganowska, H.; Godlewska, P.; Macalik, L.; Hanuza, J.; Oganowski, W.; van der Maas, J. H.

    2002-03-01

    New praseodymium complexes of 2,6-lutidine, 4-methoxy-2,6-lutidine and 3-halo-2,6-lutidine N-oxides (LuO) have been synthesised and chemically characterised. The Fourier transform IR and Raman spectra have been measured in the range 50-4000 and 80-4000 cm -1, respectively, and discussed in terms of possible structure and composition of compounds studied. The frequencies of the stretching N-O, Pr-O and Pr-Cl vibrations have been assigned and related to the possible molecular structures of the Pr(LuO) 8, Pr(LuO) 7O', Pr(LuO) 5O' 2O″, Pr(LuO) 6, PrCl 3(LuO) 3 and PrCl 3(LuO) 2O' complexes (O' and O″ denotes the H 2O and C 2H 5OH ligands).

  18. The use of trimethylamine N-oxide as a primary precipitating agent and related methylamine osmolytes as cryoprotective agents for macromolecular crystallography

    SciTech Connect

    Marshall, Haley; Venkat, Murugappan; Hti Lar Seng, Nang San; Cahn, Jackson; Juers, Douglas H.

    2012-01-01

    The stabilizing osmolyte trimethylamine N-oxide (TMAO) is shown to be an efficient primary precipitant for protein crystal growth. In addition to TMAO, two other methylamine osmolytes, sarcosine and betaine, are shown to be effective cryoprotective agents for protein crystal cooling. Both crystallization and cryoprotection are often bottlenecks for high-resolution X-ray structure determination of macromolecules. Methylamine osmolytes are known stabilizers of protein structure. One such osmolyte, trimethylamine N-oxide (TMAO), has seen occasional use as an additive to improve macromolecular crystal quality and has recently been shown to be an effective cryoprotective agent for low-temperature data collection. Here, TMAO and the related osmolytes sarcosine and betaine are investigated as primary precipitating agents for protein crystal growth. Crystallization experiments were undertaken with 14 proteins. Using TMAO, seven proteins crystallized in a total of 13 crystal forms, including a new tetragonal crystal form of trypsin. The crystals diffracted well, and eight of the 13 crystal forms could be effectively cryocooled as grown with TMAO as an in situ cryoprotective agent. Sarcosine and betaine produced crystals of four and two of the 14 proteins, respectively. In addition to TMAO, sarcosine and betaine were effective post-crystallization cryoprotective agents for two different crystal forms of thermolysin. Precipitation reactions of TMAO with several transition-metal ions (Fe{sup 3+}, Co{sup 2+}, Cu{sup 2+} and Zn{sup 2+}) did not occur with sarcosine or betaine and were inhibited for TMAO at lower pH. Structures of proteins from TMAO-grown crystals and from crystals soaked in TMAO, sarcosine or betaine were determined, showing osmolyte binding in five of the 12 crystals tested. When an osmolyte was shown to bind, it did so near the protein surface, interacting with water molecules, side chains and backbone atoms, often at crystal contacts.

  19. A sensitive capillary LC-UV method for the simultaneous analysis of olanzapine, chlorpromazine and their FMO-mediated N-oxidation products in brain microdialysates.

    PubMed

    Hendrickx, Stijn; Uğur, Duygu Yeniceli; Yilmaz, Işil Tan; Şener, Erol; Van Schepdael, Ann; Adams, Erwin; Broeckhoven, Ken; Cabooter, Deirdre

    2017-01-01

    A specific and sensitive capillary liquid chromatography-ultraviolet detection (cap-LC-UV) method in combination with a micro-extraction by packed sorbent (MEPS) sample clean-up procedure has been developed and validated for the simultaneous analysis of chlorpromazine, olanzapine and their flavin-containing monooxygenase (FMO) mediated N-oxides in rat brain microdialysates. Chromatographic separation was obtained on an Acclaim Pepmap RP C18 column with an ID of 300µm. An injection volume of 20µL was used to inject the largely aqueous samples and was shown to have no influence on the obtained peak shape of the compounds of interest. Optimal conditions for MEPS extraction were obtained on a mixed-mode M1 (80% C8, 20% SCX) cartridge after diluting microdialysate samples with phosphate buffer pH 2.5 (1:3 v/v). The method was validated and lower limits of quantification (LLOQ) were determined at 0.5nM for all compounds. Linearity was demonstrated between the LLOQ and 1µM for all compounds (R(2)>0.995). MEPS recoveries were between 92% and 98%, with intra- and interday variabilities below 15%. The applicability of the developed method was successfully demonstrated by analysing rat brain microdialysates. The capillary LC-UV method in combination with MEPS sample treatment provides a simple, sensitive method to quantify all compounds of interest in 45min and can be applied for routine therapeutic monitoring and pharmacokinetic studies of olanzapine, chlorpromazine and their respective N-oxides.

  20. Modification of agarose: 6-aminoagarose mediated syntheses of fluorogenic pyridine carboxylic acid amides.

    PubMed

    Kondaveeti, Stalin; Mehta, Gaurav K; Siddhanta, A K

    2014-06-15

    A facile 6-aminoagarose (AA) mediated synthesis of new fluorogenic amides of agarose with nicotinic (AA-NA) and picolinic acids (AA-PA) employing carbodiimide chemistry have been described. 6-Amino agarose (AA) was synthesized in a facile Mitsunobu-inspired microwave mediated method involving the reaction of agarose with phthalimide in presence of diisopropyl azodicarboxylate and triphenylphosphene (DIAD/TPP) followed by hydrazinolysis. All compounds were characterized by GPC, UV spectrophotometry, fluorescence spectroscopy, FT-IR, (1)H and (13)C NMR spectra. The fluorescence emissions (λmax 430 and 412 nm) of 1 × 10(-3)M solutions of AA-NA and AA-PA in water were significantly higher (ca. 82% and ca. 90%) than those of the molar equivalents (0.2mg) of NA and PA present in the 1 × 10(-3)M solutions of the amides, respectively. These fluorogenic pyridine carboxylic acid amides of agarose may find applications as sensors in biomedical and pharmaceutical industries.

  1. Heterocyclic-2-carboxylic acid (3-cyano-1,4-di-N-oxidequinoxalin-2-yl)amide derivatives as hits for the development of neglected disease drugs.

    PubMed

    Ancizu, Saioa; Moreno, Elsa; Torres, Enrique; Burguete, Asunción; Pérez-Silanes, Silvia; Benítez, Diego; Villar, Raquel; Solano, Beatriz; Marín, Adoración; Aldana, Ignacio; Cerecetto, Hugo; González, Mercedes; Monge, Antonio

    2009-06-22

    Neglected diseases represent a major health problem. It is estimated that one third of the world population is infected with tuberculosis (TB). Besides TB, Chagas disease, affects approximately 20 million people. Quinoxalines display great activities against TB and Chagas. Forty new quinoxaline 1,4-di-N-oxide derivatives have been prepared and tested against M. tuberculosis and T. cruzi. Carboxylic acid quinoxaline 1,4-di-N-oxides (CAQDOs) 5 and 17 showed MIC values on the same order as the reference antituberculosis drug, rifampicin. Meanwhile, CAQDOs 12 and 22 presented IC(50) values in the same order as the anti-chagasic drug, nifurtimox.

  2. Asymmetric synthesis of α-amino acids via homologation of Ni(II) complexes of glycine Schiff bases; Part 1: alkyl halide alkylations.

    PubMed

    Sorochinsky, Alexander E; Aceña, José Luis; Moriwaki, Hiroki; Sato, Tatsunori; Soloshonok, Vadim A

    2013-10-01

    Alkylations of chiral or achiral Ni(II) complexes of glycine Schiff bases constitute a landmark in the development of practical methodology for asymmetric synthesis of α-amino acids. Straightforward, easy preparation as well as high reactivity of these Ni(II) complexes render them ready available and inexpensive glycine equivalents for preparing a wide variety of α-amino acids, in particular on a relatively large scale. In the case of Ni(II) complexes containing benzylproline moiety as a chiral auxiliary, their alkylation proceeds with high thermodynamically controlled diastereoselectivity. Similar type of Ni(II) complexes derived from alanine can also be used for alkylation providing convenient access to quaternary, α,α-disubstituted α-amino acids. Achiral type of Ni(II) complexes can be prepared from picolinic acid or via recently developed modular approach using simple secondary or primary amines. These Ni(II) complexes can be easily mono/bis-alkylated under homogeneous or phase-transfer catalysis conditions. Origin of diastereo-/enantioselectivity in the alkylations reactions, aspects of practicality, generality and limitations of this methodology is critically discussed.

  3. The Mechanism of N-O Bond Cleavage in Rhodium-Catalyzed C-H Bond Functionalization of Quinoline N-oxides with Alkynes: A Computational Study.

    PubMed

    Li, Yingzi; Liu, Song; Qi, Zisong; Qi, Xiaotian; Li, Xingwei; Lan, Yu

    2015-07-06

    Metal-catalyzed C-H activation not only offers important strategies to construct new bonds, it also allows the merge of important research areas. When quinoline N-oxide is used as an arene source in C-H activation studies, the N-O bond can act as a directing group as well as an O-atom donor. The newly reported density functional theory method, M11L, has been used to elucidate the mechanistic details of the coupling between quinoline N-O bond and alkynes, which results in C-H activation and O-atom transfer. The computational results indicated that the most favorable pathway involves an electrophilic deprotonation, an insertion of an acetylene group into a Rh-C bond, a reductive elimination to form an oxazinoquinolinium-coordinated Rh(I) intermediate, an oxidative addition to break the N-O bond, and a protonation reaction to regenerate the active catalyst. The regioselectivity of the reaction has also been studied by using prop-1-yn-1-ylbenzene as a model unsymmetrical substrate. Theoretical calculations suggested that 1-phenyl-2-quinolinylpropanone would be the major product because of better conjugation between the phenyl group and enolate moiety in the corresponding transition state of the regioselectivity-determining step. These calculated data are consistent with the experimental observations.

  4. Mechanism of the autocatalytic formation of ferrihemoglobin by N,N-dimethylaniline-N-oxide. Structure and ferrihemoglobin forming activity of the purple dye.

    PubMed

    Kiese, M; Renner, G

    1976-03-01

    The structure of the leuco compound of the purple dye which is formed in mixtrues of N,N-dimethylaniline-N-oxide (DANO) and ferrihemoglobin or ferricytochrome c was elucidated. IR, NMR, mass spectroscopy, and synthesis by oxidation of mixtures of N-methylaniline and 2-dimethylaminophenol showed that the leuco compound is produced by condensation of these two compounds. But only X-ray analysis proved the structure: 2-dimethylamino-4-(N-methylanilino)-phenol. The purple dye was produced from the leuco compound by withdrawal of two electrons and may be considered as resonance hybrid of the p-quinonimine and the o-quinonimine. When DANO was incubated with ferrihemoglobin or ferricytochrome c the oxygen of DANO was used for the production of the dye by oxidation of N-methylaniline and 2-dimethylaminophenol. The amount of N,N-dimethylaniline found in the incubation mixtures corresponded with the amount of purple dye produced. In the absence of molecular oxygen from incubation mixtures of DANO with cytochrome c the purple dye was formed at the same rate as under air. In blood in vitro the purple dye catalytically transferred electrons from ferrohemoglobin to molecuar oxygen. Its ferrihemoglobin-forming activity was lower than that of 4-dimethylaminophenol but higher than that of 2-dimethylaminophenol. The chemical mechanism of the autocatalytic formation of ferrihemoglobin by DANO is described.

  5. Development and validation of a simple UHPLC-MS/MS method for the simultaneous determination of trimethylamine N-oxide, choline, and betaine in human plasma and urine.

    PubMed

    Ocque, Andrew J; Stubbs, Jason R; Nolin, Thomas D

    2015-05-10

    A simple, sensitive, and precise ultra-high performance liquid chromatography-tandem mass spectrometry method was developed and validated for the simultaneous determination of trimethylamine N-oxide, choline, and betaine in human plasma and urine. Sample preparation involved protein precipitation with methanol containing internal standards. Chromatographic separation was achieved using an Acquity BEH Amide (2.1mm×50mm, 1.7μm) analytical column with gradient elution of solvent A (10mM ammonium formate, pH 3.5) and solvent B (acetonitrile). The flow rate was 0.4mL/min and the total run time was 5min. Detection of analytes was performed using heated electrospray ionization (positive mode) and selected reaction monitoring. Excellent linearity was observed over the standard curve concentration ranges of 0.010-5.00μg/mL (plasma) and 1.00-150μg/mL (urine) for all analytes. The intra- and inter-day accuracy and precision for all quality controls were within ±10%. Excellent recovery was observed. The method is rapid, accurate and reproducible, and was successfully applied to a pilot study of markers of atherosclerosis in patients with kidney disease who underwent successful kidney transplantation.

  6. N-tert-butylmethanimine N-oxide is an efficient spin-trapping probe for EPR analysis of glutathione thiyl radical

    PubMed Central

    Scott, Melanie J.; Billiar, Timothy R.; Stoyanovsky, Detcho A.

    2016-01-01

    The electron spin resonance (EPR) spin-trapping technique allows detection of radical species with nanosecond half-lives. This technique is based on the high rates of addition of radicals to nitrones or nitroso compounds (spin traps; STs). The paramagnetic nitroxides (spin-adducts) formed as a result of reactions between STs and radical species are relatively stable compounds whose EPR spectra represent “structural fingerprints” of the parent radical species. Herein we report a novel protocol for the synthesis of N-tert-butylmethanimine N-oxide (EBN), which is the simplest nitrone containing an α-H and a tertiary α′-C atom. We present EPR spin-trapping proof that: (i) EBN is an efficient probe for the analysis of glutathione thiyl radical (GS•); (ii) β-cyclodextrins increase the kinetic stability of the spin-adduct EBN/•SG; and (iii) in aqueous solutions, EBN does not react with superoxide anion radical (O2−•) to form EBN/•OOH to any significant extent. The data presented complement previous studies within the context of synthetic accessibility to EBN and efficient spin-trapping analysis of GS•. PMID:27941944

  7. Trimethylamine and trimethylamine N-oxide are supplementary energy sources for a marine heterotrophic bacterium: implications for marine carbon and nitrogen cycling.

    PubMed

    Lidbury, Ian D E A; Murrell, J Colin; Chen, Yin

    2015-03-01

    Bacteria of the marine Roseobacter clade are characterised by their ability to utilise a wide range of organic and inorganic compounds to support growth. Trimethylamine (TMA) and trimethylamine N-oxide (TMAO) are methylated amines (MA) and form part of the dissolved organic nitrogen pool, the second largest source of nitrogen after N2 gas, in the oceans. We investigated if the marine heterotrophic bacterium, Ruegeria pomeroyi DSS-3, could utilise TMA and TMAO as a supplementary energy source and whether this trait had any beneficial effect on growth. In R. pomeroyi, catabolism of TMA and TMAO resulted in the production of intracellular ATP which in turn helped to enhance growth rate and growth yield as well as enhancing cell survival during prolonged energy starvation. Furthermore, the simultaneous use of two different exogenous energy sources led to a greater enhancement of chemoorganoheterotrophic growth. The use of TMA and TMAO primarily as an energy source resulted in the remineralisation of nitrogen in the form of ammonium, which could cross feed into another bacterium. This study provides greater insight into the microbial metabolism of MAs in the marine environment and how it may affect both nutrient flow within marine surface waters and the flux of these climatically important compounds into the atmosphere.

  8. Associations of gut-flora-dependent metabolite trimethylamine-N-oxide, betaine and choline with non-alcoholic fatty liver disease in adults.

    PubMed

    Chen, Yu-ming; Liu, Yan; Zhou, Rui-fen; Chen, Xiao-ling; Wang, Cheng; Tan, Xu-ying; Wang, Li-jun; Zheng, Rui-dan; Zhang, Hong-wei; Ling, Wen-hua; Zhu, Hui-lian

    2016-01-08

    Many studies suggest that trimethylamine-N-oxide (TMAO), a gut-flora-dependent metabolite of choline, contributes to the risk of cardiovascular diseases, but little is known for non-alcoholic fatty liver disease (NAFLD). We examined the association of circulating TMAO, choline and betaine with the presence and severity of NAFLD in Chinese adults. We performed a hospital-based case-control study (CCS) and a cross-sectional study (CSS). In the CCS, we recruited 60 biopsy-proven NAFLD cases and 35 controls (18-60 years) and determined serum concentrations of TMAO, choline and betaine by HPLC-MS/MS. For the CSS, 1,628 community-based adults (40-75 years) completed the blood tests and ultrasonographic NAFLD evaluation. In the CCS, analyses of covariance showed adverse associations of ln-transformed serum levels of TMAO, choline and betaine/choline ratio with the scores of steatosis and total NAFLD activity (NAS) (all P-trend <0.05). The CSS revealed that a greater severity of NAFLD was independently correlated with higher TMAO but lower betaine and betaine/choline ratio (all P-trend <0.05). No significant choline-NAFLD association was observed. Our findings showed adverse associations between the circulating TMAO level and the presence and severity of NAFLD in hospital- and community-based Chinese adults, and a favorable betaine-NAFLD relationship in the community-based participants.

  9. Associations of gut-flora-dependent metabolite trimethylamine-N-oxide, betaine and choline with non-alcoholic fatty liver disease in adults

    PubMed Central

    Chen, Yu-ming; Liu, Yan; Zhou, Rui-fen; Chen, Xiao-ling; Wang, Cheng; Tan, Xu-ying; Wang, Li-jun; Zheng, Rui-dan; Zhang, Hong-wei; Ling, Wen-hua; Zhu, Hui-lian

    2016-01-01

    Many studies suggest that trimethylamine-N-oxide (TMAO), a gut-flora-dependent metabolite of choline, contributes to the risk of cardiovascular diseases, but little is known for non-alcoholic fatty liver disease (NAFLD). We examined the association of circulating TMAO, choline and betaine with the presence and severity of NAFLD in Chinese adults. We performed a hospital-based case-control study (CCS) and a cross-sectional study (CSS). In the CCS, we recruited 60 biopsy-proven NAFLD cases and 35 controls (18–60 years) and determined serum concentrations of TMAO, choline and betaine by HPLC-MS/MS. For the CSS, 1,628 community-based adults (40-75 years) completed the blood tests and ultrasonographic NAFLD evaluation. In the CCS, analyses of covariance showed adverse associations of ln-transformed serum levels of TMAO, choline and betaine/choline ratio with the scores of steatosis and total NAFLD activity (NAS) (all P-trend <0.05). The CSS revealed that a greater severity of NAFLD was independently correlated with higher TMAO but lower betaine and betaine/choline ratio (all P-trend <0.05). No significant choline-NAFLD association was observed. Our findings showed adverse associations between the circulating TMAO level and the presence and severity of NAFLD in hospital- and community-based Chinese adults, and a favorable betaine-NAFLD relationship in the community-based participants. PMID:26743949

  10. Anaerobic respiratory growth of Vibrio harveyi, Vibrio fischeri and Photobacterium leiognathi with trimethylamine N-oxide, nitrate and fumarate: ecological implications.

    PubMed

    Proctor, L M; Gunsalus, R P

    2000-08-01

    Two symbiotic species, Photobacterium leiognathi and Vibrio fischeri, and one non-symbiotic species, Vibrio harveyi, of the Vibrionaceae were tested for their ability to grow by anaerobic respiration on various electron acceptors, including trimethylamine N-oxide (TMAO) and dimethylsulphoxide (DMSO), compounds common in the marine environment. Each species was able to grow anaerobically with TMAO, nitrate or fumarate, but not with DMSO, as an electron acceptor. Cell growth under microaerophilic growth conditions resulted in elevated levels of TMAO reductase, nitrate reductase and fumarate reductase activity in each strain, whereas growth in the presence of the respective substrate for each enzyme further elevated enzyme activity. TMAO reductase specific activity was the highest of all the reductases. Interestingly, the bacteria-colonized light organs from the two squids, Euprymna scolopes and Euprymna morsei, and the light organ of the ponyfish, Leiognathus equus, also had high levels of TMAO reductase enzyme activity, in contrast to non-symbiotic tissues. The ability of these bacterial symbionts to support cell growth by respiration with TMAO may conceivably eliminate the competition for oxygen needed for both bioluminescence and metabolism.

  11. Kinetics of reduction of sulfur dioxide by hydrogen sulfide in the presence of sulfoxides, pyridine N-oxide, trioctylphosphine oxide and tributyl phosphate

    SciTech Connect

    Bikbaeva, G.G.; Baranovskaya, E.M.; Nikitin, Yu.E.

    1989-01-01

    The kinetic regularities were studied of the reduction of SO/sub 2/ by hydrogen sulfide in m-xylene containing 0.025 M of aliphatic sulfoxides, (C/sub 1/-C/sub 8/alkyl), diphenyl-, dibenzyl sulfoxides, tributyl phosphate (TBP), trioctylphosphine oxide (TOPO) at 25/degree/C, and 0.001-0.003 M pyridine N-oxide (PyO) at 21-60/degree/C. It was shown that the reaction proceeds with the participation of an SO/sub 2/ complex having the composition of R/sub n/XO...SO/sub 2/ (where X = S, P, N). The kinetic regularities for the reaction taking place in the presence of aromatic sulfoxides are explainable by the contribution to the reaction of intermediate SO/sub 2/ complexes. The equilibrium constants of the complexation of SO/sub 2/ with aliphatic sulfoxides, PyO, TOPO, and TBP and the rate constant of the limiting stage of the reaction were calculated.

  12. Quantitative analysis of zopiclone, N-desmethylzopiclone, zopiclone N-oxide and 2-amino-5-chloropyridine in urine using LC-MS-MS.

    PubMed

    Nilsson, Gunnel H; Kugelberg, Fredrik C; Ahlner, Johan; Kronstrand, Robert

    2014-01-01

    A simple liquid chromatography-tandem mass spectrometry method was validated to allow determination of zopiclone (ZOP), N-desmethylzopiclone (NDZOP), zopiclone N-oxide (ZOPNO) and 2-amino-5-chloropyridine (ACP) in urine at concentrations up to 3,000 ng/mL within 3.5 min. This method was used for quantitative analysis of the analytes in authentic urine samples obtained 10 h after oral administration of zopiclone (Imovane(®)) and in aliquots of the same urine samples after different storage conditions. In addition, pH of each studied urine sample was measured over time. The results showed that formation of ACP occurred at elevated pH and/or temperature by degradation of ZOP, NDZOP and ZOPNO. This method was also applied to samples obtained from two female victims of drug-facilitated assault. One sample had been exposed to long-term storage conditions at different temperatures and at pH >8.2, which resulted in high concentrations of ACP. The other sample, which was exposed to pH <6.5, showed no formation of ACP. ACP is formed both from ZOP and from its metabolites NDZOP and ZOPNO depending on the pH of the urine, time of storage and/or the temperature conditions. For correct interpretation in forensic cases, ZOP, its major metabolites and ACP should be analyzed. When ACP is identified in urine, the concentrations of ZOP, NDZOP and ZOPNO should be interpreted with great caution.

  13. Prevention of polymerization of M and Z alpha1-Antitrypsin (alpha1-AT) with trimethylamine N-oxide. Implications for the treatment of alpha1-at deficiency.

    PubMed

    Devlin, G L; Parfrey, H; Tew, D J; Lomas, D A; Bottomley, S P

    2001-06-01

    alpha1-Antitrypsin (alpha1-AT) is the most abundant circulating proteinase inhibitor. The Z variant results in profound plasma deficiency as the mutant polymerizes within hepatocytes. The retained polymers are associated with cirrhosis, and the lack of circulating protein predisposes to early onset emphysema. We have investigated the role of the naturally occurring solute trimethylamine N-oxide (TMAO) in modulating the polymerization of normal M and disease-associated Z alpha1-AT. TMAO stabilized both M and Z alpha1-AT in an active conformation against heat-induced polymerization. Spectroscopic analysis demonstrated that this was due to inhibition of the conversion of the native state to a polymerogenic intermediate. However, TMAO did not aid the refolding of denatured alpha1-AT to a native conformation; instead, it enhanced polymerization. These data show that TMAO can be used to control the conformational transitions of folded alpha1-AT but that it is ineffective in promoting folding of the polypeptide chain within the secretory pathway.

  14. Pretreatment of oil palm empty fruit bunch (OPEFB) by N-methylmorpholine-N-oxide (NMMO) for biogas production: structural changes and digestion improvement.

    PubMed

    Purwandari, Fiametta Ayu; Sanjaya, Adhitya Pitara; Millati, Ria; Cahyanto, Muhammad Nur; Horváth, Ilona Sárvári; Niklasson, Claes; Taherzadeh, Mohammad J

    2013-01-01

    Pretreatment of OPEFB (oil palm empty fruit bunch) by NMMO (N-methylmorpholine-N-oxide) on its subsequent digestions was investigated. The pretreatments were carried out at 90 and 120 °C for 1, 3, and 5h in three different modes of dissolution (by 85% NMMO solution), ballooning (79% NMMO solution), and swelling (73% NMMO solution). The total solid recovery after the pretreatment was 89-94%. The pretreatment process did not have a major impact on the composition of OPEFB, other than a reduction of ash from 5.4% up to 1.3%. The best improvement in biogas production was achieved by a dissolution mode pretreatment of OPEFB, using conditions of 85% NMMO, 3h, and 120 °C. It resulted in 0.408 Nm(3)/kg VS methane yield and 0.032 Nm(3)CH(4)/kg VS/day initial methane production rate, which correspond in improving by 48% and 167% compared to the untreated OPEFB, respectively.

  15. Spectroscopic (NMR, UV, FT-IR and FT-Raman) analysis and theoretical investigation of nicotinamide N-oxide with density functional theory.

    PubMed

    Atac, Ahmet; Karabacak, Mehmet; Kose, Etem; Karaca, Caglar

    2011-12-01

    The spectroscopic properties of the nicotinamide N-oxide (abbreviated as NANO, C(6)H(6)N(2)O(2)) were examined by FT-IR, FT-Raman, NMR and UV techniques. FT-IR and FT-Raman spectra in solid state were observed in the region 4000-400 cm(-1) and 3500-50 cm(-1), respectively. The (1)H and (13)C NMR spectra were recorded in DMSO. The UV absorption spectrum of the compound that dissolved in water was recorded in the range of 200-800 nm. The structural and spectroscopic data of the molecule in the ground state were calculated by using Density Functional Theory (DFT) employing B3LYP methods with the 6-311++G(d,p) basis set. The geometry of the molecule was fully optimized, vibrational spectra were calculated and fundamental vibrations were assigned on the basis of the total energy distribution (TED) of the vibrational modes, calculated with scaled quantum mechanics (SQM) method and PQS program. The optimized structure of compound was interpreted and compared with the reported experimental values. The observed vibrational wavenumbers, absorption wavelengths and chemical shifts were compared with calculated values. As a result, the optimized geometry and calculated spectroscopic data show a good agreement with the experimental results.

  16. Separation of transition metals on a poly-iminodiacetic acid grafted polymeric resin column with post-column reaction detection utilising a paired emitter-detector diode system.

    PubMed

    Barron, Leon; O'Toole, Martina; Diamond, Dermot; Nesterenko, Pavel N; Paull, Brett

    2008-12-05

    The selectivity, retention and separation of transition metals on a short (2 mm x 50 mm) column packed with a poly-iminodiacetic acid functionalised polymer 10 microm resin (Dionex ProPac IMAC-10) are presented. This stationary phase, typically used for the separation of proteins, is composed of long chain poly-iminodiacetic acid groups grafted to a hydrophilic layer surrounding a 10 microm polymeric bead. Through the use of a combination of a multi-step pH and picolinic acid gradient, the separation of magnesium, iron, cobalt, cadmium, zinc, lead and copper was possible, followed by post-column reaction with 4-(2-pyridylazo) resorcinol (PAR) and absorbance detection at 510 nm using a novel and inexpensive optical detector, comprised of two light emitting diodes with one acting as a light source and the other as a detector. Column efficiency for selective transition metals was in excess of N=10,000, with the baseline separation of seven metal cations in <3 min possible under optimised conditions. Detection limits of between 5 and 81 microg/L were possible based upon a 50 microL injection volume.

  17. Simultaneous determination of morinidazole, its N-oxide, sulfate, and diastereoisomeric N(+)-glucuronides in human plasma by liquid chromatography-tandem mass spectrometry.

    PubMed

    Gao, Ruina; Zhong, Dafang; Liu, Ke; Xia, Yu; Shi, Rongwei; Li, Hua; Chen, Xiaoyan

    2012-11-01

    Morinidazole is a new third-generation 5-nitroimidazole antimicrobial drug. To investigate the pharmacokinetic profiles of morinidazole and its major metabolites in humans, a liquid chromatography-tandem mass spectrometry method was developed and validated for simultaneous determination of morinidazole, its N-oxide metabolite (M4-1), a sulfate conjugate (M7), and two diastereoisomeric N(+)-glucuronides (M8-1 and M8-2) in human plasma. A simple acetonitrile-induced protein precipitation was employed to extract five analytes and internal standard metronidazole from 50μL human plasma. To avoid the interference from the in-source dissociation of the sulfate and achieve the baseline-separation of diastereoisomeric N(+)-glucuronides, all the analytes were separated from each other with the mobile phase consisting of 10mM ammonium formate and acetonitrile using gradient elution on a Hydro-RP C(18) column (50mm×2mm, 4μm) with a total run time of 5min. The API 4000 triple quadrupole mass spectrometer was operated under the multiple reaction-monitoring mode using the electrospray ionization technique. The developed method was linear in the concentration ranges of 10.0-12,000ng/mL for morinidazole, 1.00-200ng/mL for M4-1, 2.50-500ng/mL for M7, 3.00-600ng/mL for M8-1, and 10.0-3000ng/mL for M8-2. The intra- and inter-day precisions for each analyte met the accepted value. Results of the stability of morinidazole and its metabolites in human plasma were also presented. The method was successfully applied to the clinical pharmacokinetic studies of morinidazole injection in healthy subjects, patients with moderate hepatic insufficiency, and patients with severe renal insufficiency, respectively.

  18. Intake of up to 3 Eggs/Day Increases HDL Cholesterol and Plasma Choline While Plasma Trimethylamine-N-oxide is Unchanged in a Healthy Population.

    PubMed

    DiMarco, Diana M; Missimer, Amanda; Murillo, Ana Gabriela; Lemos, Bruno S; Malysheva, Olga V; Caudill, Marie A; Blesso, Christopher N; Fernandez, Maria Luz

    2017-03-01

    Eggs are a source of cholesterol and choline and may impact plasma lipids and trimethylamine-N-oxide (TMAO) concentrations, which are biomarkers for cardiovascular disease (CVD) risk. Therefore, the effects of increasing egg intake (0, 1, 2, and 3 eggs/day) on these and other CVD risk biomarkers were evaluated in a young, healthy population. Thirty-eight subjects [19 men/19 women, 24.1 ± 2.2 years, body mass index (BMI) 24.3 ± 2.5 kg/m(2)] participated in this 14-week crossover intervention. Participants underwent a 2-week washout with no egg consumption, followed by intake of 1, 2, and 3 eggs/day for 4 weeks each. Anthropometric data, blood pressure (BP), dietary records, and plasma biomarkers (lipids, glucose, choline, and TMAO) were measured during each intervention phase. BMI, waist circumference, systolic BP, plasma glucose, and plasma triacylglycerol did not change throughout the intervention. Diastolic BP decreased with egg intake (P < 0.05). Compared to 0 eggs/day, intake of 1 egg/day increased HDL cholesterol (HDL-c) (P < 0.05), and decreased LDL cholesterol (LDL-c) (P < 0.05) and the LDL-c/HDL-c ratio (P < 0.01). With intake of 2-3 eggs/day, these changes were maintained. Plasma choline increased dose-dependently with egg intake (P < 0.0001) while fasting plasma TMAO was unchanged. These results indicate that in a healthy population, consuming up to 3 eggs/day results in an overall beneficial effect on biomarkers associated with CVD risk, as documented by increased HDL-c, a reduced LDL-c/HDL-c ratio, and increased plasma choline in combination with no change in plasma LDL-c or TMAO concentrations.

  19. Trimethylamine and Trimethylamine N-Oxide, a Flavin-Containing Monooxygenase 3 (FMO3)-Mediated Host-Microbiome Metabolic Axis Implicated in Health and Disease

    PubMed Central

    Fennema, Diede; Phillips, Ian R.

    2016-01-01

    Flavin-containing monooxygenase 3 (FMO3) is known primarily as an enzyme involved in the metabolism of therapeutic drugs. On a daily basis, however, we are exposed to one of the most abundant substrates of the enzyme trimethylamine (TMA), which is released from various dietary components by the action of gut bacteria. FMO3 converts the odorous TMA to nonodorous TMA N-oxide (TMAO), which is excreted in urine. Impaired FMO3 activity gives rise to the inherited disorder primary trimethylaminuria (TMAU). Affected individuals cannot produce TMAO and, consequently, excrete large amounts of TMA. A dysbiosis in gut bacteria can give rise to secondary TMAU. Recently, there has been much interest in FMO3 and its catalytic product, TMAO, because TMAO has been implicated in various conditions affecting health, including cardiovascular disease, reverse cholesterol transport, and glucose and lipid homeostasis. In this review, we consider the dietary components that can give rise to TMA, the gut bacteria involved in the production of TMA from dietary precursors, the metabolic reactions by which bacteria produce and use TMA, and the enzymes that catalyze the reactions. Also included is information on bacteria that produce TMA in the oral cavity and vagina, two key microbiome niches that can influence health. Finally, we discuss the importance of the TMA/TMAO microbiome-host axis in health and disease, considering factors that affect bacterial production and host metabolism of TMA, the involvement of TMAO and FMO3 in disease, and the implications of the host-microbiome axis for management of TMAU. PMID:27190056

  20. The effect of trimethylamine N-oxide on Helicobacter pylori-induced changes of immunoinflammatory genes expression in gastric epithelial cells.

    PubMed

    Wu, Daoyan; Cao, Mei; Peng, Jingshan; Li, Ningzhe; Yi, Sijun; Song, Liju; Wang, Xuege; Zhang, Mao; Zhao, Jian

    2017-02-01

    Colonization of Helicobacter pylori (H. pylori) induces immune and inflammatory response in gastric mucosa. Trimethylamine N-oxide (TMAO), from diet and metabolite through the action of gut microbiota, has been linked to inflammatory diseases. To investigate the effects of TMAO and H. pylori infection on gene expression in gastric epithelial cells, Human gene chip Affymetrix HTA 2.0 was used in this study. 1312 genes were identified as differentially expressed genes in GES-1 cells with H. pylori and TMAO co-treatment compared to the control. GO and KEGG analyses indicated that the functions of these differentially expressed genes were related closely with immune inflammation. GO-network showed that Toll-like receptor signaling pathway was the most important biological processes and 49 up-regulated genes related to immune inflammation were obtained. The synergistic effects of H. pylori and TMAO enhanced the genes expression of IL-6, CXCL1, CXCL2, FOS and C3 related to immune inflammation in comparison with those of non-infected control cells, H. pylori-infected cells, and TMAO-stimulated cells. RT-PCR verified the expression levels of IL-6, CXCL1. Additionally, expression levels of 2053 genes were altered and 52 immunoinflammatory genes were upregulated in comparison with H. pylori-infected cells. This study suggested that TMAO altered the expression levels of immunoinflammatory genes induced by H. pylori infection, and the synergistic effects of H. pylori and TMAO provided novel insights into the development of chronic gastritis, gastric ulcer and gastric cancer.

  1. Sonochemical synthesis and characterization of three nano zinc(II) coordination polymers; Precursors for preparation of zinc(II) oxide nanoparticles.

    PubMed

    Marandi, Farzin; Hashemi, Lida; Morsali, Ali; Krautscheid, Harald

    2016-09-01

    Nanostructures of three Zinc(II) coordination polymers, [Zn(NNO)2(H2O)4]n (1), [Zn(PNNO)2(H2O)2]n (2) and [Zn(H2O)6]·(INNO)2 (3) {NNO: Nicotinic acid N-oxide, PNNO: Picolinic acid N-oxide and INNO: Isonicotinic acid N-oxide}, have been synthesized by a sonochemical process and reaction of ligands with Zn(CH3COO)2. The Zinc(II) oxide nano-particles have been synthesized from thermolysis of [Zn(NNO)2(H2O)4]n (1), [Zn(PNNO)2(H2O)2]n (2) and [Zn(H2O)6]·(INNO)2 (3) at two different methods (with surfactant and without surfactant) and two temperatures (200 and 600°C). The ZnO nanoparticles were characterized by X-ray diffraction (XRD) and scanning electron microscopy (SEM). Comparison of the SEM images of ZnO nano-particles at two different methods and temperatures shows that higher temperature results in an increasing of agglomeration and thus small and spherical ZnO particles with good separation were produced by thermolysis of compounds at 200°C and by use of surfactant.

  2. Generation of Free Oxygen Atoms O(3P) in Solution by Photolysis of 4-Benzoylpyridine N-Oxide

    SciTech Connect

    Carraher, Jack M.; Bakac, Andreja

    2014-08-04

    Laser flash photolysis of 4-benzoylpyridine N-oxide (BPyO) at 308 nm in aqueous solutions generates a triplet excited state 3BPyO* that absorbs strongly in the visible, λmax 490 and 380 nm. 3BPyO* decays with the rate law kdecay/s-1 = (3.3 ± 0.9) × 104 + (1.5 ± 0.2) × 109 [BPyO] to generate a mixture of isomeric hydroxylated benzoylpyridines, BPy(OH), in addition to small amounts of oxygen atoms, O(3P). Molecular oxygen quenches 3BPyO*, kQ = 1.4 × 109 M-1 s-1, but the yields of O(3P) increase in O2-saturated solutions to 36%. Other triplet quenchers have a similar effect, which rules out the observed 3BPyO* as a source of O(3P). It is concluded that O(3P) is produced from either 1BPyO* or a short-lived, unobserved, higher energy triplet generated directly from 1BPyO*. 3BPyO* is reduced by Fe2+ and by ABTS2- to the radical anion BPyO.- which exhibits a maximum at 510 nm, ε = 2200 M-1 cm-1. The anion engages in back electron transfer with ABTS.- with k = 1.7 × 109 M-1 s-1. The same species can be generated by reducing ground state BPyO with .C(CH3)2OH. The photochemistry of BPyO in acetonitrile is similar to that in aqueous solutions.

  3. Effect of detergent concentration on the thermal stability of a membrane protein: The case study of bacterial reaction center solubilized by N,N-dimethyldodecylamine-N-oxide.

    PubMed

    Palazzo, Gerardo; Lopez, Francesco; Mallardi, Antonia

    2010-01-01

    We report on the response of reaction center (RC) from Rhodobacter sphaeroides (an archetype of membrane proteins) to the exposure at high temperature. The RCs have been solubilized in aqueous solution of the detergent N,N-dimethyldodecylamine-N-oxide (LDAO). Changes in the protein conformation have been probed by monitoring the variation in the absorbance of the bacteriochlorine cofactors and modification in the efficiency of energy transfer from tryptophans to cofactors and among the cofactors (through fluorescence measurements). The RC aggregation taking place at high temperature has been investigated by means of dynamic light scattering. Two experimental protocols have been used: (i) isothermal kinetics, in which the time evolution of RC after a sudden increase of the temperature is probed, and (ii) T-scans, in which the RCs are heated at constant rate. The analysis of the results coming from both the experiments indicates that the minimal kinetic scheme requires an equilibrium step and an irreversible process. The irreversible step is characterized by a activation energy of 205+/-14 kJ/mol and is independent from the detergent concentration. Since the temperature dependence of the aggregation rate was found to obey to the same law, the aggregation process is unfolding-limited. On the other hand, the equilibrium process between the native and a partially unfolded conformations was found to be strongly dependent on the detergent concentration. Increasing the LDAO content from 0.025 to 0.5 wt.% decreases the melting temperature from 49 to 42 degrees C. This corresponds to a sizeable (22 kJ/mol at 25 degrees C) destabilization of the native conformation induced by the detergent. The nature of the aggregates formed by the denatured RCs depends on the temperature. For temperature below 60 degrees C compact aggregates are formed while at 60 degrees C the clusters are less dense with a scaling relation between mass and size close to that expected for diffusion

  4. Roflumilast N-oxide prevents cytokine secretion induced by cigarette smoke combined with LPS through JAK/STAT and ERK1/2 inhibition in airway epithelial cells.

    PubMed

    Victoni, Tatiana; Gleonnec, Florence; Lanzetti, Manuella; Tenor, Hermann; Valença, Samuel; Porto, Luis Cristovão; Lagente, Vincent; Boichot, Elisabeth

    2014-01-01

    Cigarette smoke is a major cause of chronic obstructive pulmonary disease (COPD). Airway epithelial cells and macrophages are the first defense cells against cigarette smoke and these cells are an important source of pro-inflammatory cytokines. These cytokines play a role in progressive airflow limitation and chronic airways inflammation. Furthermore, the chronic colonization of airways by Gram-negative bacteria, contributes to the persistent airways inflammation and progression of COPD. The current study addressed the effects of cigarette smoke along with lipolysaccharide (LPS) in airway epithelial cells as a representative in vitro model of COPD exacerbations. Furthermore, we evaluated the effects of PDE4 inhibitor, the roflumilast N-oxide (RNO), in this experimental model. A549 cells were stimulated with cigarette smoke extract (CSE) alone (0.4% to 10%) or in combination with a low concentration of LPS (0.1 µg/ml) for 2 h or 24 h for measurement of chemokine protein and mRNAs and 5-120 min for protein phosphorylation. Cells were also pre-incubated with MAP kinases inhibitors and Prostaglandin E2 alone or combined with RNO, before the addition of CSE+LPS. Production of cytokines was determined by ELISA and protein phosphorylation by western blotting and phospho-kinase array. CSE did not induce production of IL-8/CXCL8 and Gro-α/CXCL1 from A549 cells, but increase production of CCL2/MCP-1. However the combination of LPS 0.1 µg/ml with CSE 2% or 4% induced an important production of these chemokines, that appears to be dependent of ERK1/2 and JAK/STAT pathways but did not require JNK and p38 pathways. Moreover, RNO associated with PGE2 reduced CSE+LPS-induced cytokine release, which can happen by occur through of ERK1/2 and JAK/STAT pathways. We report here an in vitro model that can reflect what happen in airway epithelial cells in COPD exacerbation. We also showed a new pathway where CSE+LPS can induce cytokine release from A549 cells, which is reduced by RNO.

  5. The Study of NADPH-Dependent Flavoenzyme-Catalyzed Reduction of Benzo[1,2-c]1,2,5-oxadiazole N-Oxides (Benzofuroxans)

    PubMed Central

    Šarlauskas, Jonas; Misevičienė, Lina; Marozienė, Audronė; Karvelis, Laimonas; Stankevičiūtė, Jonita; Krikštopaitis, Kastis; Čėnas, Narimantas; Yantsevich, Aleksey; Laurynėnas, Audrius; Anusevičius, Žilvinas

    2014-01-01

    The enzymatic reactivity of a series of benzo[1,2-c]1,2,5-oxadiazole N-oxides (benzofuroxans; BFXs) towards mammalian single-electron transferring NADPH:cytochrome P-450 reductase (P-450R) and two-electron (hydride) transferring NAD(P)H:quinone oxidoreductase (NQO1) was examined in this work. Since the =N+ (→O)O− moiety of furoxan fragments of BFXs bears some similarity to the aromatic nitro-group, the reactivity of BFXs was compared to that of nitro-aromatic compounds (NACs) whose reduction mechanisms by these and other related flavoenzymes have been extensively investigated. The reduction of BFXs by both P-450R and NQO1 was accompanied by O2 uptake, which was much lower than the NADPH oxidation rate; except for annelated BFXs, whose reduction was followed by the production of peroxide. In order to analyze the possible quantitative structure-activity relationships (QSARs) of the enzymatic reactivity of the compounds, their electron-accepting potency and other reactivity indices were assessed by quantum mechanical methods. In P-450R-catalyzed reactions, both BFXs and NACs showed the same reactivity dependence on their electron-accepting potency which might be consistent with an “outer sphere” electron transfer mechanism. In NQO1-catalyzed two-electron (hydride) transferring reactions, BFXs acted as more efficient substrates than NACs, and the reduction efficacy of BFXs by NQO1 was in general higher than by single-electron transferring P-450R. In NQO1-catalyzed reactions, QSARs obtained showed that the reduction efficacy of BFXs, as well as that of NACs, was determined by their electron-accepting potency and could be influenced by their binding mode in the active center of NQO1 and by their global softness as their electronic characteristic. The reductive conversion of benzofuroxan by both flavoenzymes yielded the same reduction product of benzofuroxan, 2,3-diaminophenazine, with the formation of o-benzoquinone dioxime as a putative primary reductive

  6. Effects of N,N-dimethyl-N-alkylamine-N-oxides on DOPC bilayers in unilamellar vesicles: small-angle neutron scattering study.

    PubMed

    Belička, Michal; Kučerka, Norbert; Uhríková, Daniela; Islamov, Akhmed Kh; Kuklin, Alexander I; Devínsky, Ferdinand; Balgavý, Pavol

    2014-05-01

    Small-angle neutron scattering data were collected from aqueous dispersions of unilamellar vesicles (ULVs) consisting of mixtures of 1,2-dioleoyl-sn-glycero-3-phosphatidylcholine and a homologous series of N,N-dimethyl-N-alkylamine-N-oxides (CnNO, n = 12, 14, 16, and 18, where n is the number of carbon atoms in the alkyl chain). A modeling approach was applied to the neutron scattering curves to obtain the bilayer structural parameters. Particularly, the external (2)H2O/H2O contrast variation technique was carried out on pure dioleoylphosphatidylcholine (DOPC) ULVs to determine the hydrophilic region thickness [Formula: see text] = 9.8 ± 0.6 Å. Consequently, the hydrocarbon region thickness [Formula: see text], the lateral bilayer area per one lipid molecule [Formula: see text], and the number of water molecules located in the hydrophilic region per one lipid molecule [Formula: see text] were obtained from single-contrast neutron scattering curves using the previously determined [Formula: see text]. The structural parameters were extracted as functions of [Formula: see text] (the CnNO:DOPC molar ratio) and n. The dependences [Formula: see text] provided the partial lateral areas of CnNOs ([Formula: see text]) and DOPC ([Formula: see text]) in bilayers. It was observed that the [Formula: see text]'s were constant in the investigated interval of [Formula: see text] and for n = 12, 14, and 16 equal to 36.6 ± 0.4 Å(2), while [Formula: see text] increased to 39.4 ± 0.4 Å(2). The bilayer hydrocarbon region thickness [Formula: see text] decreased with intercalation of each CnNO. This effect increased with [Formula: see text] and decreased with increasing CnNO alkyl chain length. The intercalation of C18NO changed the [Formula: see text] only slightly. To quantify the effect of CnNO intercalation into DOPC bilayers we fit the [Formula: see text] dependences with weighted linear approximations and acquired their slopes [Formula: see text].

  7. Aspartic acid

    MedlinePlus

    ... also called asparaginic acid. Aspartic acid helps every cell in the body work. It plays a role in: Hormone production and release Normal nervous system function Plant sources of aspartic acid include: Legumes such as ...

  8. Folic Acid

    MedlinePlus

    Folic acid is a B vitamin. It helps the body make healthy new cells. Everyone needs folic acid. For women who may get pregnant, it is really important. Getting enough folic acid before and during pregnancy can prevent major birth ...

  9. Folic Acid

    MedlinePlus

    Folic acid is used to treat or prevent folic acid deficiency. It is a B-complex vitamin needed by ... Folic acid comes in tablets. It usually is taken once a day. Follow the directions on your prescription label ...

  10. Cu-Catalyzed Cyanation of Arylboronic Acids with Acetonitrile: A Dual Role of TEMPO.

    PubMed

    Zhu, Yamin; Li, Linyi; Shen, Zengming

    2015-09-14

    The cyanation of arylboronic acids by using acetonitrile as the "CN" source has been achieved under a Cu(cat.)/TEMPO system (TEMPO=2,2,6,6-tetramethylpiperidine N-oxide). The broad substrate scope includes a variety of electron-rich and electron-poor arylboronic acids, which react well to give the cyanated products in high to excellent yields. Mechanistic studies reveal that TEMPO-CH2 CN, generated in situ, is an active cyanating reagent, and shows high reactivity for the formation of the CN(-) moiety. Moreover, TEMPO acts as a cheap oxidant to enable the reaction to be catalytic in copper.

  11. Development of multicomponent hybrid density functional theory with polarizable continuum model for the analysis of nuclear quantum effect and solvent effect on NMR chemical shift

    SciTech Connect

    Kanematsu, Yusuke; Tachikawa, Masanori

    2014-04-28

    We have developed the multicomponent hybrid density functional theory [MC-(HF+DFT)] method with polarizable continuum model (PCM) for the analysis of molecular properties including both nuclear quantum effect and solvent effect. The chemical shifts and H/D isotope shifts of the picolinic acid N-oxide (PANO) molecule in chloroform and acetonitrile solvents are applied by B3LYP electron exchange-correlation functional for our MC-(HF+DFT) method with PCM (MC-B3LYP/PCM). Our MC-B3LYP/PCM results for PANO are in reasonable agreement with the corresponding experimental chemical shifts and isotope shifts. We further investigated the applicability of our method for acetylacetone in several solvents.

  12. Sonochemical synthesis of two new nano lead(II) coordination polymers: Evaluation of structural transformation via mechanochemical approach.

    PubMed

    Aboutorabi, Leila; Morsali, Ali

    2016-09-01

    Two new lead(II) mixed-ligand coordination polymers, [Pb(PNO)(SCN)]n (1) and [Pb(PNO)(N3)]n (2), (HPNO=picolinic acid N-oxide) were synthesized by a sonochemical method and characterized by scanning electron microscopy, X-ray powder diffraction, IR spectroscopy and elemental analysis. Compounds 1 and 2 were structurally characterized by single crystal X-ray diffraction. The thermal behavior of 1 and 2 were studied by thermal gravimetric analysis. Structural transformations of compounds 1 and 2 were evaluated through anion-replacement processes by mechanochemical method. Moreover, the effect of sonication conditions including time, concentrations of initial reagents and power of irradiation were evaluated on size and morphology of compounds 1 and 2.

  13. Acid Rain

    USGS Publications Warehouse

    Bricker, Owen P.; Rice, Karen C.

    1995-01-01

    Although acid rain is fading as a political issue in the United States and funds for research in this area have largely disappeared, the acidity of rain in the Eastern United States has not changed significantly over the last decade, and it continues to be a serious environmental problem. Acid deposition (commonly called acid rain) is a term applied to all forms of atmospheric deposition of acidic substances - rain, snow, fog, acidic dry particulates, aerosols, and acid-forming gases. Water in the atmosphere reacts with certain atmospheric gases to become acidic. For example, water reacts with carbon dioxide in the atmosphere to produce a solution with a pH of about 5.6. Gases that produce acids in the presence of water in the atmosphere include carbon dioxide (which converts to carbonic acid), oxides of sulfur and nitrogen (which convert to sulfuric and nitric acids}, and hydrogen chloride (which converts to hydrochloric acid). These acid-producing gases are released to the atmosphere through natural processes, such as volcanic emissions, lightning, forest fires, and decay of organic matter. Accordingly, precipitation is slightly acidic, with a pH of 5.0 to 5.7 even in undeveloped areas. In industrialized areas, most of the acid-producing gases are released to the atmosphere from burning fossil fuels. Major emitters of acid-producing gases include power plants, industrial operations, and motor vehicles. Acid-producing gases can be transported through the atmosphere for hundreds of miles before being converted to acids and deposited as acid rain. Because acids tend to build up in the atmosphere between storms, the most acidic rain falls at the beginning of a storm, and as the rain continues, the acids "wash out" of the atmosphere.

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

    PubMed

    Burguete, Asunción; Estevez, Yannick; Castillo, Denis; González, Germán; Villar, Raquel; Solano, Beatriz; Vicente, Esther; Silanes, Silvia Pérez; Aldana, Ignacio; Monge, Antonio; Sauvain, Michel; Deharo, Eric

    2008-12-01

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

  15. Acid Rain.

    ERIC Educational Resources Information Center

    Openshaw, Peter

    1987-01-01

    Provides some background information on acid deposition. Includes a historical perspective, describes some effects of acid precipitation, and discusses acid rain in the United Kingdom. Contains several experiments that deal with the effects of acid rain on water quality and soil. (TW)

  16. Lanthanide complexes based on a diazapyridinophane platform containing picolinate pendants.

    PubMed

    Roca-Sabio, Adrián; Bonnet, Célia S; Mato-Iglesias, Marta; Esteban-Gómez, David; Tóth, Éva; de Blas, Andrés; Rodríguez-Blas, Teresa; Platas-Iglesias, Carlos

    2012-10-15

    A new macrocyclic ligand, N,N'-bis[(6-carboxy-2-pyridyl)methyl]-2,11-diaza[3.3](2,6)pyridinophane (H(2)BPDPA), was prepared, and its coordination properties toward the Ln(III) ions were investigated. The hydration numbers (q) obtained from luminescence lifetime measurements in aqueous solution of the Eu(III) and Tb(III) complexes indicate that they contain one inner-sphere water molecule. The structure of the complexes in solution has been investigated by (1)H and (13)C NMR spectroscopy, as well as by theoretical calculations performed at the density functional theory (B3LYP) level. The minimum-energy conformation calculated for the Yb(III) complex is in excellent agreement with the experimental structure in solution, as demonstrated by analysis of the Yb(III)-induced paramagnetic (1)H shifts. Nuclear magnetic relaxation dispersion (NMRD) profiles and (17)O NMR measurements recorded on solutions of the Gd(III) complex were used to determine the parameters governing the relaxivity. The results show that this system is endowed with a relatively fast water-exchange rate k(ex)(298) = 63 × 10(6) s(-1). Thermodynamic stability constants were determined by pH-potentiometric titration at 25 °C in 0.1 M KCl. The stability constants, which fall within the range logK(LnL) = 12.5-14.2, point to a relatively low stability of the complexes primarily as a consequence of the low basicity of the ligand.

  17. Characterization and screening of pyrrolizidine alkaloids and N-oxides from various parts of many botanicals and dietary supplements using liquid chromatography high resolution mass spectrometry

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The UHPLC-QToF-MS analysis of pyrrolizidine alkaloids from various parts of 37 botanicals and 7 dietary supplements was performed. A separation by LC was achieved using a reversed-phase column and a gradient of water/acetonitrile each containing formic acid as the mobile phase. MS-MS detection was u...

  18. Synthesis and biological activity of novel amino acid-(N'-benzoyl) hydrazide and amino acid-(N'-nicotinoyl) hydrazide derivatives.

    PubMed

    Khattab, Sherine N

    2005-09-30

    The coupling reaction of benzoic acid and nicotinic acid hydrazides with N- protected L-amino acids including valine, leucine, phenylalanine, glutamic acid and tyrosine is reported. The target compounds, N-Boc-amino acid-(N;-benzoyl)- and N- Boc-amino acid-(N;-nicotinoyl) hydrazides 5a-5e and 6a-6e were prepared in very high yields and purity using N-[(dimethylamino)-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl- methylene]-N-methyl-methanaminium hexafluorophosphate N-oxide (HATU) as coupling reagent. The antimicrobial activity of the Cu and Cd complexes of the designed compounds was tested. The products were deprotected affording the corresponding amino acid-(N;-benzoyl) hydrazide hydrochloride salts (7a-7e) and amino acid-(N;- nicotinoyl) hydrazide hydrochloride salts (8a-8e). These compounds and their Cu and Cd complexes were also tested for their antimicrobial activity. Several compounds showed comparable activity to that of ampicillin against S. aureus and E. coli.

  19. A study of dinitro-bis-1,2,4-triazole-1,1'-diol and derivatives: design of high-performance insensitive energetic materials by the introduction of N-oxides.

    PubMed

    Dippold, Alexander A; Klapötke, Thomas M

    2013-07-03

    In this contribution we report on the synthesis and full structural as well as spectroscopic characterization of 3,3'-dinitro-5,5'-bis-1,2,4-triazole-1,1'-diol and nitrogen-rich salts thereof. The first synthesis and characterization of an energetic 1-hydroxy-bistriazole in excellent yields and high purity is presented. This simple and straightforward method of N-oxide introduction in triazole compounds using commercially available oxone improves the energetic properties and reveals a straightforward synthetic pathway toward novel energetic 1,2,4-triazole derivatives. X-ray crystallographic measurements were performed and deliver insight into structural characteristics and strong intermolecular interactions. The standard enthalpies of formation were calculated for all compounds at the CBS-4 M level of theory, revealing highly positive heats of formation for all compounds. The energetic properties of all compounds (detonation velocity, pressure, etc.) were calculated using the EXPLO5.05 program, and the ionic derivatives show superior performance in comparison to the corresponding compounds bearing no N-oxide. All substances were characterized in terms of sensitivities (impact, friction, electrostatic) and thermal stabilities, and the ionic derivatives were found to be high thermally stable, insensitive compounds that are exceedingly powerful but safe to handle and prepare.

  20. Obeticholic Acid

    MedlinePlus

    Obeticholic acid is used alone or in combination with ursodiol (Actigall, Urso) to treat primary biliary cholangitis (PBC; a ... were not treated successfully with ursodiol alone. Obeticholic acid is in a class of medications called farnesoid ...

  1. Aminocaproic Acid

    MedlinePlus

    Aminocaproic acid is used to control bleeding that occurs when blood clots are broken down too quickly. This type ... the baby is ready to be born). Aminocaproic acid is also used to control bleeding in the ...

  2. Acid mucopolysaccharides

    MedlinePlus

    ... this page: //medlineplus.gov/ency/article/003368.htm Acid mucopolysaccharides To use the sharing features on this page, please enable JavaScript. Acid mucopolysaccharides is a test that measures the amount ...

  3. Aristolochic Acids

    MedlinePlus

    ... Sciences NIH-HHS www.niehs.nih.gov Aristolochic Acids Key Points Report on Carcinogens Status Known to be human carcinogens Aristolochia Clematitis Aristolochic Acids n Known human carcinogens n Found in certain ...

  4. Ascorbic Acid

    MedlinePlus

    Ascorbic acid is used to prevent and treat scurvy, a disease caused by a lack of vitamin C in ... Ascorbic acid comes in extended-release (long-acting) capsules and tablets, lozenges, syrup, chewable tablets, and liquid drops to ...

  5. Ethacrynic Acid

    MedlinePlus

    Ethacrynic acid, a 'water pill,' is used to treat swelling and fluid retention caused by various medical problems. It ... Ethacrynic acid comes as a tablet to take by mouth. It is usually taken once or twice a day ...

  6. Amino acids

    MedlinePlus

    ... page: //medlineplus.gov/ency/article/002222.htm Amino acids To use the sharing features on this page, please enable JavaScript. Amino acids are organic compounds that combine to form proteins . ...

  7. Valproic Acid

    MedlinePlus

    Valproic acid is used alone or with other medications to treat certain types of seizures. Valproic acid is also used to treat mania (episodes of ... to relieve headaches that have already begun. Valproic acid is in a class of medications called anticonvulsants. ...

  8. Fatty acids - trans fatty acids

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The data supporting a negative effect of dietary trans fatty acids on cardiovascular disease risk is consistent. The primary dietary sources of trans fatty acids include partially hydrogenated fat and rudiment fat. The adverse effect of trans fatty acids on plasma lipoprotein profiles is consisten...

  9. Benzo[1,2-c]1,2,5-oxadiazole N-oxide derivatives as potential antitrypanosomal drugs. Part 3: Substituents-clustering methodology in the search for new active compounds.

    PubMed

    Aguirre, Gabriela; Boiani, Lucía; Cerecetto, Hugo; Di Maio, Rossanna; González, Mercedes; Porcal, Williams; Denicola, Ana; Möller, Matías; Thomson, Leonor; Tórtora, Verónica

    2005-12-01

    The results of a study on the use of Hansch's series design, cluster methodology, for the generation of new benzo[1,2-c]1,2,5-oxadiazole N-oxide derivatives as antitrypanosomal compounds are described. In vitro activity of these compounds was tested against Tulahuen 2 strain of Trypanosoma cruzi. Clearly, the Hansch methodology allowed identifying two cluster-substituents suitable for further structural modifications. The most effective drugs, derivatives 11, 18, and 21, with 50% inhibitory concentration (IC(50)) of the same order as that of the reference drug, represent an excellent structural point of chemical modifications for the design of future drugs. Preliminary results from the study of the mechanism of action of these benzofuroxans point to perturbation of the mitochondrial electron chain, inhibiting parasite respiration.

  10. Generation of hydroxyl radicals from metal-loaded humic acids

    SciTech Connect

    Paciolla, M.D.; Jansen, S.A.; Davies, G.

    1999-06-01

    Humic acids (HAs) are naturally occurring biopolymers that are ubiquitous in the environment. They are most commonly found in the soil, drinking water, and a variety of plants. Pharmacological and therapeutic studies involving humic acids have been reported to some extent. However, when certain transition metals are bound to humic acids, e.g., iron and copper, they can be harmful to biological organisms. For this study, humic acids were extracted from German, Irish, and New Hampshire soils that were selectively chosen because of their reich abundance in humic material. Each sample was treated at room temperature with 0.1 M ferric and cupric solutions for 48 h. The amount of iron and copper adsorbed by humic acid was accurately quantitated using atomic absorption spectroscopy. The authors further demonstrate that these metal-loaded humic acids can produce deleterious oxidizing species such as the hydroxyl radical (HO*) through the metal-driven Fenton reaction. Electron paramagnetic resonance (EPR) employing spin trapping techniques with 5,5-dimethylpyrroline N-oxide (DMPO) is used to confirm the generation of hydroxyl radicals. The DMPO-OH adduct with hyperfine splitting constants A{sub N} = A{sub H} = 14.9 G is observed upon the addition of exogenous hydrogen peroxide. The concentration of hydroxyl radical was determined using 4-hydroxytempo (TEMPO-OH) as a spin standard. The presence of another oxidizing species, Fe{double_bond}O{sup 2+}, is also proposed in the absence of hydrogen peroxide.

  11. Acid rain

    SciTech Connect

    Elsworth, S.

    1985-01-01

    This book was written in a concise and readable style for the lay public. It's purpose was to make the public aware of the damage caused by acid rain and to mobilize public opinion to favor the elimination of the causes of acid rain.

  12. Asparagusic acid.

    PubMed

    Mitchell, Stephen C; Waring, Rosemary H

    2014-01-01

    Asparagusic acid (1,2-dithiolane-4-carboxylic acid) is a simple sulphur-containing 5-membered heterocyclic compound that appears unique to asparagus, though other dithiolane derivatives have been identified in non-food species. This molecule, apparently innocuous toxicologically to man, is the most probable culprit responsible for the curious excretion of odorous urine following asparagus ingestion. The presence of the two adjacent sulphur atoms leads to an enhanced chemical reactivity, endowing it with biological properties including the ability to substitute potentially for α-lipoic acid in α-keto-acid oxidation systems. This brief review collects the scattered data available in the literature concerning asparagusic acid and highlights its properties, intermediary metabolism and exploratory applications.

  13. Acid rain

    SciTech Connect

    Sweet, W.

    1980-06-20

    Acid precipitation includes not only rain but also acidified snow, hail and frost, as well as sulfur and nitrogen dust. The principal source of acid precipitation is pollution emitted by power plants and smelters. Sulfur and nitrogen compounds contained in the emissions combine with moisture to form droplets with a high acid content - sometimes as acidic as vinegar. When sufficiently concentrated, these acids can kill fish and damage material structures. Under certain circumstances they may reduce crop and forest yields and cause or aggravate respiratory diseases in humans. During the summer, especially, pollutants tend to collect over the Great Lakes in high pressure systems. Since winds typically are westerly and rotate clockwise around high pressure systems, the pollutants gradually are dispersed throughout the eastern part of the continent.

  14. Acid fog

    SciTech Connect

    Hileman, B.

    1983-03-01

    Fog in areas of southern California previously thought to be pollution-free has been shown to have a pH as low as 1.69. It has been found to be most acidic after smoggy days, suggesting that it forms on the aerosol associated with the previously exiting smog. Studies on Whiteface Mountain in the Adirondacks show that fog water is often 10 times as acidic as rainwater. As a result of their studies, California plans to spend $4 million on acid deposition research in the coming year. (JMT)

  15. NMR and DFT study on media effects on proton transfer in hydrogen bonding: concept of molecular probe with an application to ionic and super-polar liquids.

    PubMed

    Balevicius, Vytautas; Gdaniec, Zofia; Aidas, Kestutis

    2009-10-14

    Media effects of ionic and super-polar liquids on the state of H-bonding were studied by NMR and DFT methods. The proton sharing (positioning) in the H-bond was monitored following the chemical shifts of picolinic acid N-oxide (PANO) used as the molecular probe. The relationships between PANO 1H and 13C chemical shifts and proton position in the O-H...O bridge were calibrated using traditional organic solvents and other H-bond complexes of pyridine N-oxide with acids to increase the H-bond strength. A reliable parameter for H-bond monitoring was proposed. The state of the H-bond in ionic liquid media is largely governed by the dielectric properties of the bulk media. A drastic fall-out of PANO/[BuMePyr][TfO] from the general dielectric scheme built using solvents with increasing dielectric constant (from chloroform to water and culminating with formamide) was observed. On a molecular level this effect indicates that the ionic liquid [BuMePyr][TfO] can act on H-bonded systems as a stimulant of proton transfer. In 'super-polar' media (formamide) the intramolecular H-bond system converts into an intermolecular one forming a neutral H-bond complex of PANO with the formamide molecule.

  16. Mefenamic Acid

    MedlinePlus

    ... as mefenamic acid may cause ulcers, bleeding, or holes in the stomach or intestine. These problems may ... like coffee grounds, blood in the stool, or black and tarry stools.Keep all appointments with your ...

  17. Acid Rain

    MedlinePlus

    ... EPA Is Doing Acid Rain Program Cross-State Air Pollution Rule Progress Reports Educational Resources Kid's Site for ... Monitoring National Atmospheric Deposition Program (NADP) Exit Interstate Air Pollution Transport Contact Us to ask a question, provide ...

  18. Folic Acid

    MedlinePlus

    ... folic acid can hide signs that you lack vitamin B12, which can cause nerve damage. 10 Do I ... Rosenberg, I.H., et al. (2007). Folate and vitamin B12 status in relation to anemia, macrocytosis and cognitive ...

  19. Acid Precipitation

    ERIC Educational Resources Information Center

    Likens, Gene E.

    1976-01-01

    Discusses the fact that the acidity of rain and snow falling on parts of the U.S. and Europe has been rising. The reasons are still not entirely clear and the consequences have yet to be well evaluated. (MLH)

  20. Acidic precipitation

    SciTech Connect

    Martin, H.C.

    1987-01-01

    At the International Symposium on Acidic Precipitation, over 400 papers were presented, and nearly 200 of them are included here. They provide an overview of the present state of the art of acid rain research. The Conference focused on atmospheric science (monitoring, source-receptor relationships), aquatic effects (marine eutrophication, lake acidification, impacts on plant and fish populations), and terrestrial effects (forest decline, soil acidification, etc.).

  1. The three-component cocrystal 1,3,5-trifluoro-2,4,6-triiodobenzene-pyridine N-oxide-water (1/2/1) built up by halogen bonds, hydrogen bonds and π-π interactions.

    PubMed

    Raffo, Pablo A; Cukiernik, Fabio D; Baggio, Ricardo F

    2015-02-01

    The title three-component cocrystal, C6F3I3·2C5H5NO·H2O, has been prepared as a strong candidate for multiple I...O interactions. Its crystal structure is compared with its 1:1 close relative, C6F3I3·C5H5NO [Aakeröy et al. (2014a). CrystEngComm, 16, 28-31]. The 1,3,5-trifluoro-2,4,6-triiodobenzene and water species both have crystallographic twofold axial symmetry. The main synthon in both structures is the π-π stacking of benzene rings, complemented by a number of O-H...O, C-F...π and, fundamentally, C-I...O interactions. As expected, the latter are among the strongest and more directional interactions of the sort reported in the literature, confirming that pyridine N-oxide is an eager acceptor. On the other hand, the structure presents only two of these contacts per 1,3,5-trifluoro-2,4,6-triiodobenzene molecule instead of the expected three. Possible reasons for this limitation are analyzed.

  2. Acid Rain

    USGS Publications Warehouse

    Bricker, Owen P.; Rice, Karen C.

    1993-01-01

    Acid deposition, or acid rain as it is more commonly referred to, has become a widely publicized environmental issue in the U.S. over the past decade. The term usually conjures up images of fish kills, dying forests, "dead" lakes, and damage to monuments and other historic artifacts. The primary cause of acid deposition is emission of S02 and NOx to the atmosphere during the combustion of fossil fuels. Oxidation of these compounds in the atmosphere forms strong acids - H2SO4 and HNO3 - which are returned to the Earth in rain, snow, fog, cloud water, and as dry deposition.Although acid deposition has only recently been recognized as an environmental problem in the U.S., it is not a new phenomenon (Cogbill & Likens 1974). As early as the middle of the 17th century in England, the deleterious effects of industrial emissions on plants, animals, and humans, and the atmospheric transport of pollutants between England and France had become issues of concern (Evelyn 1661, Graunt 1662). It is interesting that well over three hundred years ago in England, recommendations were made to move industry outside of towns and build higher chimneys to spread the pollution into "distant parts." Increasing the height of smokestacks has helped alleviate local problems, but has exacerbated others. In the U.S. the height of the tallest smokestack has more than doubled, and the average height of smokestacks has tripled since the 1950s (Patrick et al 1981). This trend occurred in most industrialized nations during the 20th century and has had the effect of transforming acid rain from a local urban problem into a problem of global scale.

  3. Acid Rain

    USGS Publications Warehouse

    Bricker, Owen P.; Rice, Karen C.; Dietrich, W.E.; Sposito, Garrison

    1997-01-01

    Acid deposition, or acid rain as it is more commonly referred to, has become a widely publicized environmental issue in the U.S. over the past decade. The term usually conjures up images of fish kills, dying forests, "dead" lakes, and damage to monuments and other historic artifacts. The primary cause of acid deposition is emission of S02 and NOx to the atmosphere during the combustion of fossil fuels. Oxidation of these compounds in the atmosphere forms strong acids - H2SO4 and HNO3 - which are returned to the Earth in rain, snow, fog, cloud water, and as dry deposition.Although acid deposition has only recently been recognized as an environmental problem in the U.S., it is not a new phenomenon (Cogbill & Likens 1974). As early as the middle of the 17th century in England, the deleterious effects of industrial emissions on plants, animals, and humans, and the atmospheric transport of pollutants between England and France had become issues of concern (Evelyn 1661, Graunt 1662). It is interesting that well over three hundred years ago in England, recommendations were made to move industry outside of towns and build higher chimneys to spread the pollution into "distant parts." Increasing the height of smokestacks has helped alleviate local problems, but has exacerbated others. In the U.S. the height of the tallest smokestack has more than doubled, and the average height of smokestacks has tripled since the 1950s (Patrick et al 1981). This trend occurred in most industrialized nations during the 20th century and has had the effect of transforming acid rain from a local urban problem into a problem of global scale.

  4. Salicylic acids

    PubMed Central

    Hayat, Shamsul; Irfan, Mohd; Wani, Arif; Nasser, Alyemeni; Ahmad, Aqil

    2012-01-01

    Salicylic acid is well known phytohormone, emerging recently as a new paradigm of an array of manifestations of growth regulators. The area unleashed yet encompassed the applied agriculture sector to find the roles to strengthen the crops against plethora of abiotic and biotic stresses. The skipped part of integrated picture, however, was the evolutionary insight of salicylic acid to either allow or discard the microbial invasion depending upon various internal factors of two interactants under the prevailing external conditions. The metabolic status that allows the host invasion either as pathogenesis or symbiosis with possible intermediary stages in close systems has been tried to underpin here. PMID:22301975

  5. Selenious acid

    Integrated Risk Information System (IRIS)

    Selenious acid ; CASRN 7783 - 00 - 8 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments for Noncarcinogenic E

  6. Dichloroacetic acid

    Integrated Risk Information System (IRIS)

    EPA 635 / R - 03 / 007 www.epa.gov / iris TOXICOLOGICAL REVIEW OF DICHLOROACETIC ACID ( CAS No . 79 - 43 - 6 ) In Support of Summary Information on the Integrated Risk Information System ( IRIS ) August 2003 U.S . Environmental Protection Agency Washington , DC DISCLAIMER This document has been revi

  7. Trichloroacetic acid

    Integrated Risk Information System (IRIS)

    EPA / 635 / R - 09 / 003F www.epa.gov / iris TOXICOLOGICAL REVIEW OF TRICHLOROACETIC ACID ( CAS No . 76 - 03 - 9 ) In Support of Summary Information on the Integrated Risk Information System ( IRIS ) September 2011 U.S . Environmental Protection Agency Washington , DC ii DISCLAIMER This document has

  8. Acid rain

    SciTech Connect

    Not Available

    1984-06-01

    An overview is presented of acid rain and the problems it causes to the environment worldwide. The acidification of lakes and streams is having a dramatic effect on aquatic life. Aluminum, present in virtually all forest soils, leaches out readily under acid conditions and interferes with the gills of all fish, some more seriously than others. There is evidence of major damage to forests in European countries. In the US, the most severe forest damage appears to be in New England, New York's Adirondacks, and the central Appalachians. This small region is part of a larger area of the Northeast and Canada that appears to have more acid rainfall than the rest of the country. It is downwind from major coal burning states, which produce about one quarter of US SO/sub 2/ emissions and one sixth of nitrogen oxide emissions. Uncertainties exist over the causes of forest damage and more research is needed before advocating expensive programs to reduce rain acidity. The President's current budget seeks an expansion of research funds from the current $30 million per year to $120 million.

  9. Benzoic acid

    Integrated Risk Information System (IRIS)

    Benzoic acid ; CASRN 65 - 85 - 0 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments for Noncarcinogenic Effec

  10. Formic acid

    Integrated Risk Information System (IRIS)

    Formic acid ; CASRN 64 - 18 - 6 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments for Noncarcinogenic Effect

  11. Acrylic acid

    Integrated Risk Information System (IRIS)

    Acrylic acid ( CASRN 79 - 10 - 7 ) Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments for Noncarcinogenic Eff

  12. Phosphoric acid

    Integrated Risk Information System (IRIS)

    Phosphoric acid ; CASRN 7664 - 38 - 2 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments for Noncarcinogenic

  13. Cacodylic acid

    Integrated Risk Information System (IRIS)

    Cacodylic acid ; CASRN 75 - 60 - 5 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments for Noncarcinogenic Eff

  14. Azelaic acid.

    PubMed

    Nazzaro-Porro, M

    1987-12-01

    This review is an update on the literature accumulated over the past 10 years following the original observation that azelaic acid, a naturally occurring and nontoxic C9 dicarboxylic acid, possesses significant biologic properties and a potential as a therapeutic agent. These studies have shown that azelaic acid is a reversible inhibitor of tyrosinase and other oxidoreductases in vitro and that it inhibits mitochondrial respiration. It can also inhibit anaerobic glycolysis. Both in vitro and in vivo it has an antimicrobial effect on both aerobic and anaerobic (Propionibacterium acnes) microorganisms. In tissue culture it exerts a dose- and time-dependent cytotoxic effect on malignant melanocytes, associated with mitochondrial damage and inhibition of deoxyribonucleic acid (DNA) synthesis. Tumoral cell lines not containing tyrosinase are equally affected. Normal cells in culture exposed to the same concentrations of the diacid that are toxic for tumoral cells are in general not damaged. Radioactive azelaic acid has been shown to penetrate tumoral cells at a higher level than normal cells of the corresponding line. Topically applied (a 20% cream), it has been shown to be of therapeutic value in skin disorders of different etiologies. Its beneficial effect on various forms of acne (comedogenic, papulopustular, nodulocystic) has been clearly demonstrated. Particularly important is its action on abnormal melanocytes, which has led to the possibility of obtaining good results on melasma and highly durable therapeutic responses on lentigo maligna. It is also capable of causing regression of cutaneous malignant melanoma, but its role in melanoma therapy remains to be investigated.(ABSTRACT TRUNCATED AT 250 WORDS)

  15. Mutagenic activity of 4-nitroquinoline-N-oxide in upper aerodigestive tissue in lacZ mice (MutaMouse) and the effects of 1, 4-phenylenebis(methylene)selenocyanate.

    PubMed

    von Pressentin, M M; El-Bayoumy, K; Guttenplan, J B

    2000-03-03

    4-Nitroquinoline-N-oxide (4-NQO) was administered to lacZ mice at a concentration of 20 microg/ml in drinking water for 2 weeks, and the mutagenic fractions in a number of organs were assayed. The mutant fractions in tongue, esophagus and other pooled oral tissues were, respectively, 117+/-26, 73+/-15, and 48+/-15 mutants/10(5) plaque-forming units (pfu) (ca. 15-40xbackground). 4-NQO was not mutagenic in lung, liver or colon at conditions used here. We had previously demonstrated that the synthetic organoselenium compound, 1,4-phenylenebis(methylene)selenocyanate (p-XSC), an established chemopreventive agent, greatly reduced carcinogenicity in 4-NQO in rat tongue, and we observed here that administration of p-XSC (10 ppm se) in the diet for 6 weeks (2 weeks before, during, and 2 weeks after 4-NQO) resulted in a 33% decrease in mutagenesis in oral tissue, a 17% decrease in esophagus, and a slight increase in tongue. Only the decrease in oral tissue reached statistical significance (p<0.04). The results reported here demonstrate that 4-NQO was extremely mutagenic in lacZ mouse tongue, with lower, but highly significant activities in esophagus and other pooled oral tissues. The high activity of 4-NQO in lacZ mouse tongue is consistent with the organ specificity of 4-NQO in the rat. Inhibition of 4-NQO-induced mutagenesis by p-XSC was observed mainly in pooled oral tissues, other than tongue. Possible reasons for the difference between inhibition of mutagenesis and carcinogenesis in tongue are discussed, as well as advantages and disadvantages of in vivo mutagenesis assays as surrogates for carcinogenicity assays in chemoprevention studies.

  16. Hydroxycarboxylic acids and salts

    DOEpatents

    Kiely, Donald E; Hash, Kirk R; Kramer-Presta, Kylie; Smith, Tyler N

    2015-02-24

    Compositions which inhibit corrosion and alter the physical properties of concrete (admixtures) are prepared from salt mixtures of hydroxycarboxylic acids, carboxylic acids, and nitric acid. The salt mixtures are prepared by neutralizing acid product mixtures from the oxidation of polyols using nitric acid and oxygen as the oxidizing agents. Nitric acid is removed from the hydroxycarboxylic acids by evaporation and diffusion dialysis.

  17. Acidic domains around nucleic acids.

    PubMed Central

    Lamm, G; Pack, G R

    1990-01-01

    The hydrogen ion concentration in the vicinity of DNA was mapped out within the Poisson-Boltzmann approximation. Experimental conditions were modeled by assuming Na-DNA to be solvated in a buffer solution containing 45 mM Tris and 3 mM Mg cations at pH 7.5. Three regions of high H+ concentration (greater than 10 microM) are predicted: one throughout the minor groove of DNA and two localized in the major groove near N7 of guanine and C5 of cytosine for a G.C base pair. These acidic domains correlate well with the observed covalent binding sites of benzo[a]pyrene epoxide (N2 of guanine) and of aflatoxin B1 epoxide (N7 of guanine), chemical carcinogens that presumably undergo acid catalysis to form highly reactive carbocations that ultimately bind to DNA. It is suggested that these regions of high H+ concentration may also be of concern in understanding interactions involving proteins and noncarcinogenic molecules with or near nucleic acids. PMID:2123348

  18. Factors that Affect Oxygen Activation and Coupling of the Two Redox Cycles in the Aromatization Reaction Catalyzed by NikD, an Unusual Amino Acid Oxidase†‡

    PubMed Central

    Kommoju, Phaneeswara-Rao; Bruckner, Robert C.; Ferreira, Patricia; Carrell, Christopher J.; Mathews, F. Scott; Jorns, Marilyn Schuman

    2009-01-01

    NikD is a flavoprotein oxidase that catalyzes the oxidation of piperideine-2-carboxylate (P2C) to picolinate in a remarkable aromatization reaction comprising two redox cycles and at least one isomerization step. Tyr258 forms part of an "aromatic cage" that surrounds the ring in picolinate and its precursors. Mutation of Tyr258 to Phe does not perturb the structure of nikD but does affect the coupling of the two redox cycles and causes a 10-fold decrease in turnover rate. Tyr258Phe catalyzes a quantitative 2-electron oxidation of P2C but only 60% of the resulting dihydropicolinate intermediate undergoes a second redox cycle to produce picolinate. The mutation does not affect product yield with an alternate substrate (3,4-dehydro-L-proline) that is aromatized in a single 2-electron oxidation step. Wild-type and mutant enzyme exhibit identical rate constants for P2C oxidation to dihydropicolinate and isomerization of a reduced enzyme•dihydropicolinate complex. The observed rates are 200- and 10-fold faster, respectively, than the mutant turnover rate. Picolinate release from Tyr258Phe is 100-fold faster than turnover. The presence of bound substrate or product is a key factor in oxygen activation by wild-type nikD, as judged by the 10- to 75-fold faster rates observed for complexes of the reduced enzyme with picolinate, benzoate or 1-cyclohexenoate, a 1-deaza P2C analog. The reduced Tyr258Phe•1-cyclohexenoate complex is 25-fold less reactive with oxygen than the wild-type complex. We postulate that mutation of Tyr258 causes subtle changes in active site dynamics that promote release of the reactive dihydropicolinate intermediate and disrupt the efficient synchronization of oxygen activation observed with wild-type nikD. PMID:19702312

  19. Folic Acid and Pregnancy

    MedlinePlus

    ... Feeding Your 1- to 2-Year-Old Folic Acid and Pregnancy KidsHealth > For Parents > Folic Acid and ... before conception and during early pregnancy . About Folic Acid Folic acid, sometimes called folate, is a B ...

  20. Multiplex Ultra-Performance Liquid Chromatography-Tandem Mass Spectrometry Method for Simultaneous Quantification in Human Plasma of Fluconazole, Itraconazole, Hydroxyitraconazole, Posaconazole, Voriconazole, Voriconazole-N-Oxide, Anidulafungin, and Caspofungin▿ †

    PubMed Central

    Decosterd, Laurent Arthur; Rochat, Bertrand; Pesse, Benoît; Mercier, Thomas; Tissot, Frédéric; Widmer, Nicolas; Bille, Jacques; Calandra, Thierry; Zanolari, Boris; Marchetti, Oscar

    2010-01-01

    Therapeutic drug monitoring (TDM) may contribute to optimizing the efficacy and safety of antifungal therapy because of the large variability in drug pharmacokinetics. Rapid, sensitive, and selective laboratory methods are needed for efficient TDM. Quantification of several antifungals in a single analytical run may best fulfill these requirements. We therefore developed a multiplex ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method requiring 100 μl of plasma for simultaneous quantification within 7 min of fluconazole, itraconazole, hydroxyitraconazole, posaconazole, voriconazole, voriconazole-N-oxide, caspofungin, and anidulafungin. Protein precipitation with acetonitrile was used in a single extraction procedure for eight analytes. After reverse-phase chromatographic separation, antifungals were quantified by electrospray ionization-triple-quadrupole mass spectrometry by selected reaction monitoring detection using the positive mode. Deuterated isotopic compounds of azole antifungals were used as internal standards. The method was validated based on FDA recommendations, including assessment of extraction yields, matrix effect variability (<9.2%), and analytical recovery (80.1 to 107%). The method is sensitive (lower limits of azole quantification, 0.01 to 0.1 μg/ml; those of echinocandin quantification, 0.06 to 0.1 μg/ml), accurate (intra- and interassay biases of −9.9 to +5% and −4.0 to +8.8%, respectively), and precise (intra- and interassay coefficients of variation of 1.2 to 11.1% and 1.2 to 8.9%, respectively) over clinical concentration ranges (upper limits of quantification, 5 to 50 μg/ml). Thus, we developed a simple, rapid, and robust multiplex UPLC-MS/MS assay for simultaneous quantification of plasma concentrations of six antifungals and two metabolites. This offers, by optimized and cost-effective lab resource utilization, an efficient tool for daily routine TDM aimed at maximizing the real-time efficacy and

  1. Mass Spectrometric Characterization of Human Serum Albumin Adducts Formed with N-Oxidized Metabolites of 2-Amino-1-methyl-phenylimidazo[4,5-b]pyridine in Human Plasma and Hepatocytes

    PubMed Central

    Wang, Yi; Peng, Lijuan; Bellamri, Medjda; Langoueët, Sophie; Turesky, Robert J.

    2015-01-01

    2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), a carcinogenic heterocyclic aromatic amine formed in cooked meats, is metabolically activated to electrophilic intermediates that form covalent adducts with DNA and protein. We previously identified an adduct of PhIP formed at the Cys34 residue of human serum albumin following reaction of albumin with the genotoxic metabolite 2-hydroxyamino-1-methyl-6-phenylimidazo[4,5-b]pyridine (HONH-PhIP). The major adducted peptide recovered from a tryptic/chymotryptic digest was identified as the missed-cleavage peptide LQQC*[SO2PhIP]PFEDHVK, a [Cysteine-S-yl-PhIP]-S-dioxide linked adduct. In this investigation, we have characterized the albumin adduction products of N-sulfooxy-2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (N-sulfooxy-PhIP), which is thought to be a major genotoxic metabolite of PhIP formed in vivo. Targeted and data-dependent scanning methods showed that N-sulfooxy-PhIP adducted to the Cys34 of albumin in human plasma to form LQQC*[SO2PhIP]PFEDHVK at levels that were 8 to 10-fold greater than the adduct levels formed with N-(acetyloxy)-2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (N-acetoxy-PhIP) or HONH-PhIP. We also discovered that N-sulfooxy-PhIP forms an adduct at the sole tryptophan (Trp214) residue of albumin in the sequence AW*[PhIP]AVAR. However, stable adducts of PhIP with albumin were not detected in human hepatocytes. Instead, PhIP and 2-amino-1-methyl-6-(5-hydroxy)-phenylimidazo[4,5-b]pyridine (5-HO-PhIP), a solvolysis product of the proposed nitrenium ion of PhIP, were recovered during the proteolysis, suggesting a labile sulfenamide linkage had formed between an N-oxidized intermediate of PhIP and Cys34 of albumin. A stable adduct was formed at the Tyr411 residue of albumin in hepatocytes, and identified as a deaminated product of PhIP, Y*[desaminoPhIP]TK, where the 4-HO-tyrosine group bound to the C-2 imidazole atom of PhIP. PMID:25815793

  2. Effects of 1,4-phenylenebis(methylene)selenocyanate on mutagenesis and p53 protein expression in the tongue of lacI rats treated with 4-nitroquinoline-N-oxide

    PubMed Central

    Guttenplan, Joseph; Chen, Kun-Ming; Khmelnitsky, Michael; Kosinska, Wieslawa; Hennessy, Jeanine; Bruggeman, Richard; Desai, Dhimant; Amin, Shantu; Sun, Yuan-Wan; Spratt, Tomas; El-Bayoumy, Karam

    2009-01-01

    Previously we showed that the organoselenium compound, 1,4-phenylenebis(methylene)selenocyanate (p-XSC)1 inhibits 4-nitroquinoline-N-oxide (4-NQO)-induced tongue tumorigenesis in Fisher rats. Here we investigate possible mechanisms of this inhibition by monitoring mutagenesis and p53 protein levels in lacI and conventional Fisher rats treated with: 1) a carcinogenic dose of 4-NQO for 10 weeks in drinking water, 2) 4-NQO + p-XSC (15 ppm as selenium), and 3) 4-NQO followed by p-XSC. For mutagenesis studies, rats were euthanized at 7, 12 or 23 wks after the start of 4-NQO. For studies on p53 levels, rats were euthanized at 11, 15 and 23 wks. Appropriate controls were also monitored. In the 4-NQO-alone groups, the mutant fraction (MF) in the cII gene in tongue increased at least 50 × background level. The MF (in units of mutants/105 plaque forming units) for the 7, 12 and 23 week 4-NQO groups were respectively, 184 ± 88, 237 ± 105, 329 ± 110. Thus, mutagenesis increased with length of exposure and post-treatment time. p-XSC modestly (ca. 15 - 30%) inhibited mutagenesis under all conditions. The inhibition reached significance at the last time point. When p-XSC was administered after 4-NQO, the MF was also modestly reduced. In 4-NQO-alone animals, levels of p53 in tongue (determined by Western blotting) were 1, 1.5 and 2.4 control levels at 10, 15 and 23 weeks respectively. In the p-XSC + 4-NQO group, the enhancement in p53 levels by 4-NQO treatment was decreased about 90% at 15 weeks and 45% (P < 0.05) at 23 weeks, and by slightly smaller percentages in corresponding post-treatment groups. p-XSC alone did not alter p53 levels. As p53 levels generally increase in response to DNA damage, these results suggest that p-XSC reduces 4-NQO-induced DNA damage, resulting in reduced 4-NQO-induced mutagenesis and carcinogenesis. However, the fact that p-XSC is also effective when administered after 4-NQO, suggests additional mechanisms of inhibition exist. PMID:17720616

  3. Understanding Acid Rain

    ERIC Educational Resources Information Center

    Damonte, Kathleen

    2004-01-01

    The term acid rain describes rain, snow, or fog that is more acidic than normal precipitation. To understand what acid rain is, it is first necessary to know what an acid is. Acids can be defined as substances that produce hydrogen ions (H+), when dissolved in water. Scientists indicate how acidic a substance is by a set of numbers called the pH…

  4. New Bioactive Fatty Acids

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Many oxygenated fatty acids are bioactive compounds. Nocardia cholesterolicum and Flavobacterium DS5 convert oleic acid to 10 hydroxy stearic acid and linoleic acid to 10-hydroxy-12(Z)-octadecanoic acid. Pseudomonas aeruginosa PR3 converts oleic acid to new compounds, 7,10-dihydroxy-8(E)-octadecen...

  5. New bioactive fatty acids

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Many oxygenated fatty acids are bioactive compounds. Nocardia cholesterolicum and Flavobacterium DS5 convert oleic acid to 10 hydroxy stearic acid and linoleic acid to 10-hydroxy-12(Z)-octadecanoic acid. Pseudomonas aeruginosa PR3 converts oleic acid to the new compounds, 7,10-dihydroxy-8(E)-octad...

  6. Gold-Catalyzed Highly Regioselective Oxidation of C-C Triple Bonds Without Acid Additives: Propargyl Moieties as Masked α,β-Unsaturated Carbonyls

    PubMed Central

    Lu, Biao; Li, Chaoqun; Zhang, Liming

    2010-01-01

    Gold-catalyzed intermolecular oxidations of internal alkynes have been achieved with high regioselectivities using 8-alkylqinoline N-oxides as oxidants and in the absence of acid additives. Synthetically versatile α,β-unsaturated carbonyls are obtained in good to excellent yields and with excellent E-selectivities. A range of functional groups such as THP, MOMO, N3, OTBS, and N-Boc are tolerated. This reaction allows to mask α,β-unsaturated carbonyls as propargyl moieties, thus offering a practical solution to issues of functional group compatibility with α,β-unsaturated carbonyls, likely encountered in syntheses of complex structures. PMID:20853846

  7. Acid rain

    SciTech Connect

    Boyle, R.H.; Boyle, R.A.

    1983-01-01

    Acid rain, says Boyle is a chemical leprosy eating into the face of North America and Europe, perhaps the major ecological problem of our time. Boyle describes the causes and scope of the phenomenon; the effects on man, wildlife, water, and our cultural heritage. He probes the delays of politicians and the frequent self-serving arguments advanced by industry in the face of what scientists have proved. The solutions he offers are to strengthen the Clean Air Act and require emission reductions that can be accomplished by establishing emission standards on a regional or bubble basis, burn low-sulfur coal, install scrubbers at critical plants, and invest in alternative energy sources. 73 references, 1 figure.

  8. Combined Dilute Acid and Solvent Based Pretreatment of Agricultural Wastes for Efficient Lignocellulosic Fractionation and Biofuels Production

    SciTech Connect

    Brodeur, G.; Ramakrishnan, S.; Wilson, C.; Telotte, J.; Collier, J.; Stickel, J.

    2013-01-01

    A true biorefinery for processing lignocellulosic biomass should achieve maximum utilization of all major constituents (cellulose, hemicellulose, & lignin) within the feedstock. In this work a combined pretreatment process of dilute acid (DA) and N-methyl morpholine N-oxide (NMMO) is described that allows for both fractionation and subsequent complete hydrolysis of the feedstocks (corn stover and sugarcane bagasse). During this multi-step processing, the dilute acid pretreatment solubilizes the majority (>90%) of the hemicellulosic fraction, while the NMMO treatment yields a cellulosic fraction that is completely digestible within 48 hours at low enzyme loadings. With both the cellulosic and hemicellulosic fractions being converted into separate, dissolved sugar fractions, the remaining portion is nearly pure lignin. When used independently, DA and NMMO pretreatments are only able to achieve ~80% and ~45% cellulosic conversion, respectively. Mass balance calculations along with experimental results are used to illustrate the feasibility of separation and recycling of NMMO.

  9. [Teichoic acids from lactic acid bacteria].

    PubMed

    Livins'ka, O P; Harmasheva, I L; Kovalenko, N K

    2012-01-01

    The current view of the structural diversity of teichoic acids and their involvement in the biological activity of lactobacilli has been reviewed. The mechanisms of effects of probiotic lactic acid bacteria, in particular adhesive and immunostimulating functions have been described. The prospects of the use of structure data of teichoic acid in the assessment of intraspecific diversity of lactic acid bacteria have been also reflected.

  10. Two-stage dilute-acid and organic-solvent lignocellulosic pretreatment for enhanced bioprocessing

    DOE PAGES

    Brodeur, G.; Telotte, J.; Stickel, J. J.; ...

    2016-08-26

    A two stage pretreatment approach for biomass is developed in the current work in which dilute acid (DA) pretreatment is followed by a solvent based pretreatment (N-methyl morpholine N oxide -- NMMO). When the combined pretreatment (DAWNT) is applied to sugarcane bagasse and corn stover, the rates of hydrolysis and overall yields (>90%) are seen to dramatically improve and under certain conditions 48 h can be taken off the time of hydrolysis with the additional NMMO step to reach similar conversions. DAWNT shows a 2-fold increase in characteristic rates and also fractionates different components of biomass -- DA treatment removesmore » the hemicellulose while the remaining cellulose is broken down by enzymatic hydrolysis after NMMO treatment to simple sugars. The remaining residual solid is high purity lignin. Lastly, future work will focus on developing a full scale economic analysis of DAWNT for use in biomass fractionation.« less

  11. Two-stage dilute-acid and organic-solvent lignocellulosic pretreatment for enhanced bioprocessing

    SciTech Connect

    Brodeur, G.; Telotte, J.; Stickel, J. J.; Ramakrishnan, S.

    2016-08-26

    A two stage pretreatment approach for biomass is developed in the current work in which dilute acid (DA) pretreatment is followed by a solvent based pretreatment (N-methyl morpholine N oxide -- NMMO). When the combined pretreatment (DAWNT) is applied to sugarcane bagasse and corn stover, the rates of hydrolysis and overall yields (>90%) are seen to dramatically improve and under certain conditions 48 h can be taken off the time of hydrolysis with the additional NMMO step to reach similar conversions. DAWNT shows a 2-fold increase in characteristic rates and also fractionates different components of biomass -- DA treatment removes the hemicellulose while the remaining cellulose is broken down by enzymatic hydrolysis after NMMO treatment to simple sugars. The remaining residual solid is high purity lignin. Lastly, future work will focus on developing a full scale economic analysis of DAWNT for use in biomass fractionation.

  12. Two-stage dilute-acid and organic-solvent lignocellulosic pretreatment for enhanced bioprocessing.

    PubMed

    Brodeur, G; Telotte, J; Stickel, J J; Ramakrishnan, S

    2016-11-01

    A two stage pretreatment approach for biomass is developed in the current work in which dilute acid (DA) pretreatment is followed by a solvent based pretreatment (N-methyl morpholine N oxide - NMMO). When the combined pretreatment (DAWNT) is applied to sugarcane bagasse and corn stover, the rates of hydrolysis and overall yields (>90%) are seen to dramatically improve and under certain conditions 48h can be taken off the time of hydrolysis with the additional NMMO step to reach similar conversions. DAWNT shows a 2-fold increase in characteristic rates and also fractionates different components of biomass - DA treatment removes the hemicellulose while the remaining cellulose is broken down by enzymatic hydrolysis after NMMO treatment to simple sugars. The remaining residual solid is high purity lignin. Future work will focus on developing a full scale economic analysis of DAWNT for use in biomass fractionation.

  13. Synthesis and anti-inflammatory/antioxidant activities of some new ring substituted 3-phenyl-1-(1,4-di-N-oxide quinoxalin-2-yl)-2-propen-1-one derivatives and of their 4,5-dihydro-(1H)-pyrazole analogues.

    PubMed

    Burguete, Asunción; Pontiki, Eleni; Hadjipavlou-Litina, Dimitra; Villar, Raquel; Vicente, Esther; Solano, Beatriz; Ancizu, Saioa; Pérez-Silanes, Silvia; Aldana, Ignacio; Monge, Antonio

    2007-12-01

    We report the synthesis, anti-inflammatory and antioxidant activities of novel ring substituted 3-phenyl-1-(1,4-di-N-oxide quinoxalin-2-yl)-2-propen-1-one derivatives and of their 4,5-dihydro-(1H)-pyrazole analogues. The tested compounds inhibit the carrageenin-induced rat paw edema (4.5-56.1%) and present important scavenging activities. Compound 2a is the most potent (56.1%) in the in vivo experiment and exhibits promising in vitro inhibition of soybean lipoxygenase (IC(50)<1microM).

  14. Organic acids tunably catalyze carbonic acid decomposition.

    PubMed

    Kumar, Manoj; Busch, Daryle H; Subramaniam, Bala; Thompson, Ward H

    2014-07-10

    Density functional theory calculations predict that the gas-phase decomposition of carbonic acid, a high-energy, 1,3-hydrogen atom transfer reaction, can be catalyzed by a monocarboxylic acid or a dicarboxylic acid, including carbonic acid itself. Carboxylic acids are found to be more effective catalysts than water. Among the carboxylic acids, the monocarboxylic acids outperform the dicarboxylic ones wherein the presence of an intramolecular hydrogen bond hampers the hydrogen transfer. Further, the calculations reveal a direct correlation between the catalytic activity of a monocarboxylic acid and its pKa, in contrast to prior assumptions about carboxylic-acid-catalyzed hydrogen-transfer reactions. The catalytic efficacy of a dicarboxylic acid, on the other hand, is significantly affected by the strength of an intramolecular hydrogen bond. Transition-state theory estimates indicate that effective rate constants for the acid-catalyzed decomposition are four orders-of-magnitude larger than those for the water-catalyzed reaction. These results offer new insights into the determinants of general acid catalysis with potentially broad implications.

  15. Plasma amino acids

    MedlinePlus

    Amino acids blood test ... types of methods used to determine the individual amino acid levels in the blood. ... test is done to measure the level of amino acids in the blood. An increased level of a ...

  16. Uric acid - urine

    MedlinePlus

    ... page: //medlineplus.gov/ency/article/003616.htm Uric acid urine test To use the sharing features on this page, please enable JavaScript. The uric acid urine test measures the level of uric acid ...

  17. Facts about Folic Acid

    MedlinePlus

    ... Information For... Media Policy Makers Facts About Folic Acid Language: English Español (Spanish) Recommend on Facebook Tweet ... of the baby's brain and spine. About folic acid Folic acid is a B vitamin. Our bodies ...

  18. Stomach acid test

    MedlinePlus

    Gastric acid secretion test ... of the cells in the stomach to release acid. The stomach contents are then removed and analyzed. ... 3.5). These numbers are converted to actual acid production in units of milliequivalents per hour in ...

  19. Methylmalonic acid blood test

    MedlinePlus

    ... page: //medlineplus.gov/ency/article/003565.htm Methylmalonic acid blood test To use the sharing features on this page, please enable JavaScript. The methylmalonic acid blood test measures the amount of methylmalonic acid ...

  20. Uric acid test (image)

    MedlinePlus

    Uric acid urine test is performed to check for the amount of uric acid in urine. Urine is collected over a 24 ... testing. The most common reason for measuring uric acid levels is in the diagnosis or treatment of ...

  1. Fatty Acid Oxidation Disorders

    MedlinePlus

    ... other health conditions > Fatty acid oxidation disorders Fatty acid oxidation disorders E-mail to a friend Please ... these disorders, go to genetests.org . What fatty acid oxidation disorders are tested for in newborn screening? ...

  2. Acid distribution in phosphoric acid fuel cells

    SciTech Connect

    Okae, I.; Seya, A.; Umemoto, M.

    1996-12-31

    Electrolyte acid distribution among each component of a cell is determined by capillary force when the cell is not in operation, but the distribution under the current load conditions had not been clear so far. Since the loss of electrolyte acid during operation is inevitable, it is necessary to store enough amount of acid in every cell. But it must be under the level of which the acid disturbs the diffusion of reactive gases. Accordingly to know the actual acid distribution during operation in a cell is very important. In this report, we carried out experiments to clarify the distribution using small single cells.

  3. Comparing metabolic effects of six different commercial trivalent chromium compounds.

    PubMed

    Preuss, Harry G; Echard, Bobby; Perricone, Nicholas V; Bagchi, Debasis; Yasmin, Taharat; Stohs, Sidney J

    2008-11-01

    Recent reports provide cogent evidence that the average individual becomes chromium deficient with age. Unfortunately, chromium deficiency is strongly associated with many aspects of the Metabolic Syndrome, including insulin resistance and type 2 diabetes. Since replacement of chromium, per os, often ameliorates many deleterious manifestations associated with insulin resistance and diabetes, it is not surprising that many different, commercial trivalent chromium compounds are available on the market. However, previous reports have shown that the form of trivalent chromium (negative charges) can influence effectiveness markedly. We compared various commercial forms of trivalent chromium commonly used alone or in formulations, to examine whether they are equally effective and non-toxic. In the first study, five different chromium products were examined - citrate, amino acid chelate (AAC), chelavite, polynicotinate (NBC), and nicotinate. In the second study, effects of NBC and picolinate were assessed. Results demonstrated that only chelavite and NBC improved insulin sensitivity, and only NBC decreased systolic blood pressure (SBP) significantly. In the second study, both picolinate and NBC significantly decreased SBP compared to control. NBC and picolinate decreased malonyldialdehyde concentrations (free radical formation) and DNA fragmentation in hepatic and renal tissues. No evidence of adverse effects was noted with any of the compounds tested. In conclusion, while all the trivalent chromium compounds tested seem safe, only three enhanced insulin sensitivity (NBC, chelavite, and picolinate) and only two decreased SBP significantly (NBC and picolinate). Furthermore, both NBC and picolinate were protective in lessening free radical formation and DNA damage in the liver and kidneys.

  4. Leachability of decontamination reagents from cement waste forms

    SciTech Connect

    Piciulo, P.L.; Davis, M.S.; Adams, J.W.

    1984-11-26

    Brookhaven National Laboratory, in order to provide technical information needed by the US Nuclear Regulatory Commission to evaluate the adequacy of near-surface disposal of decontamination wstes, has begun to study the leachability of organic reagents from solidified simulated decontamination wastes. Laboratory-scale cement waste forms containing EDTA, picolinic acid or simulated LOMI decontamination reagent were leach tested. Samples containing an organic reagent on either mixed bed ion-exchange resins or anion exchange resins were tested. A fixed interval leach procedure was used, as well as the standard procedure ANS 16.1. The leachability indices measured for the release of the acid from resin/cement composites are: 10.1 for EDTA on mixed bed resins; 9.1 for picolinic acid on mixed bed resins; 9.2 for picolinic acid on anion exchange resins; 8.8 for picolinic acid in forms containing simulated low oxidation metallic ion (LOMI) reagent on mixed bed resins and 8.7 for picolinic acid in forms containing simulated LOMI reagent on anion exchange resins. The leachability indices measured varied with leach time and the data indicate that the release mechanism may not be simply diffusion controlled. 5 references, 2 tables.

  5. Pulmonary inflammation in rats after intratracheal instillation of quartz, amorphous SiO2, carbon black, and coal dust and the influence of poly-2-vinylpyridine-N-oxide (PVNO).

    PubMed

    Ernst, Heinrich; Rittinghausen, Susanne; Bartsch, Wilfried; Creutzenberg, Otto; Dasenbrock, Clemens; Görlitz, Bernd-Detlef; Hecht, Matthias; Kairies, Ulf; Muhle, Hartwig; Müller, Meike; Heinrich, Uwe; Pott, Friedrich

    2002-08-01

    Effects of poly-2-vinylpyridine-N-oxide (PVNO) were investigated in numerous in vivo and in vitro studies published in the nineteen sixties and seventies. These studies showed that PVNO inhibited development of fibrosis from quartz dust and improved lung clearance of quartz after inhalation exposure. Ameliorating effects of PVNO were observed also for pulmonary damage from colloidal SiO2 and organic substances, and the fibrogenic inflammation caused by carrageenan. Although it is not proven that silicosis is a precondition for quartz-induced lung tumours, we investigated the hypothesis that PVNO could reduce the lung tumour risk from quartz in rats. A carcinogenicity study was therefore started in rats with the main focus on the quantitative relationships among pulmonary inflammation, fibrosis and neoplasia caused by intratracheal instillation of 3 mg quartz DQ 12 with or without additional subcutaneous PVNO treatment. Other study groups were treated with multiple dust instillations, i.e. 30 instillations of 0.5 mg amorphous SiO2 at intervals of 2 weeks, 10 instillations of 0.5 mg of ultrafine carbon black or 1 mg coal at weekly intervals. The analyses of the bronchoalveolar lavage fluid (BALF) 9 months after start of the life-time study showed that the aim of producing similar levels of increased enzyme concentrations in the four groups treated with quartz/PVNO, amorphous SiO2, carbon black and coal was achieved. A 2.5- to 7.7-fold increase for lactate dehydrogenase (LDH), total protein, alkaline phosphatase and gamma-glutamyl transferase (gamma-GT) was found in these groups as compared to the control. In contrast, quartz treatment without PVNO increased the LDH level up to 24-fold and of total protein to 13-fold. However, the cell counts in the BALF were not so much different in all five groups, i.e. quartz without PVNO (leukocytes: 480.000, PMN: 190.000), quartz with PVNO (leukocytes: 300.000, PMN: 100.000), amorphous SiO2 (leukocytes: 570.000, PMN: 315

  6. Acid tolerance in amphibians

    SciTech Connect

    Pierce, B.A.

    1985-04-01

    Studies of amphibian acid tolerance provide information about the potential effects of acid deposition on amphibian communities. Amphibians as a group appear to be relatively acid tolerant, with many species suffering increased mortality only below pH 4. However, amphibians exhibit much intraspecific variation in acid tolerance, and some species are sensitive to even low levels of acidity. Furthermore, nonlethal effects, including depression of growth rates and increases in developmental abnormalities, can occur at higher pH.

  7. Metabolic stability of new anticonvulsants in body fluids and organ homogenates.

    PubMed

    Marszałek, Dorota; Goldnik, Anna; Pluciński, Franciszek; Mazurek, Aleksander P; Jakubiak, Anna; Lis, Ewa; Tazbir, Piotr; Koziorowska, Agnieszka

    2012-01-01

    The stability as a function of time of compounds with established anticonvulsant activity: picolinic acid benzylamide (Pic-BZA), picolinic acid 2-fluorobenzylamide (Pic-2-F-BZA), picolinic acid 3-fluorobenzylamide (Pic-3-F-BZA), picolinic acid 4-fluorobenzylamide (Pic-4-F-BZA) and picolinic acid 2-methylbenzylamide (Pic-2-Me-BZA) in body fluids and homogenates of body organs were determined after incubation. It was found that they decompose relatively rapidly in liver and kidney and are stable against enzymes present in body fluids and some organs. These results are consistent with the bond strength expressed as total energy of amide bonds (calculated by quantum chemical methods) in the studied anticonvulsants. The calculated values of the amide bond energy are: 199.4 kcal/mol, 200.2 kcal/mol, 207.5 kcal/mol, 208.4 kcal/mol and 198.2 kcal/mol, respectively. The strength of the amide bonds in the studied anticonvulsants correctly reflects their stability in liver or kidney.

  8. Gas-phase acidities of aspartic acid, glutamic acid, and their amino acid amides

    NASA Astrophysics Data System (ADS)

    Li, Zhong; Matus, Myrna H.; Velazquez, Hector Adam; Dixon, David A.; Cassady, Carolyn J.

    2007-09-01

    Gas-phase acidities (GA or [Delta]Gacid) for the two most acidic common amino acids, aspartic acid and glutamic acid, have been determined for the first time. Because of the amide linkage's importance in peptides and as an aid in studying side chain versus main chain deprotonation, aspartic acid amide and glutamic acid amide were also studied. Experimental GA values were measured by proton transfer reactions in an electrospray ionization/Fourier transform ion cyclotron resonance mass spectrometer. Calculated GAs were obtained by density functional and molecular orbital theory approaches. The best agreement with experiment was found at the G3MP2 level; the MP2/CBS and B3LYP/aug-cc-pVDZ results are 3-4 kcal/mol more acidic than the G3MP2 results. Experiment shows that aspartic acid is more acidic than glutamic acid by ca. 3 kcal/mol whereas the G3MP2 results show a smaller acidity difference of 0.2 kcal/mol. Similarly, aspartic acid amide is experimentally observed to be ca. 2 kcal/mol more acidic than glutamic acid amide whereas the G3MP2 results show a correspondingly smaller energy difference of 0.7 kcal/mol. The computational results clearly show that the anions are all ring-like structures with strong hydrogen bonds between the OH or NH2 groups and the CO2- group from which the proton is removed. The two amino acids are main-chain deprotonated. In addition, use of the COSMO model for the prediction of the free energy differences in aqueous solution gave values in excellent agreement with the most recent experimental values for pKa. Glutamic acid is predicted to be more acidic than aspartic acid in aqueous solution due to differential solvation effects.

  9. Toxicity of adipic acid.

    PubMed

    Kennedy, Gerald L

    2002-05-01

    Adipic acid has very low acute toxicity in rats with an LD50 > 5000 mg/kg. Adipic acid produced mild to no skin irritation on intact guinea pig skin as a 50% concentration in propylene glycol; it was not a skin sensitizer. Adipic acid caused mild conjunctival irritation in washed rabbit eyes; in unwashed rabbit eyes, there was mild conjunctival irritation, minimal iritis, but no corneal effects. Adipic acid dust may irritate the mucous membranes of the lungs and nose. In a 2-year feeding study, rats fed adipic acid at concentrations up to 5% in the diet exhibited only weight loss. Adipic acid is not genetically active in a wide variety of assay systems. Adipic acid caused no developmental toxicity in mice, rats, rabbits, or hamsters when administered orally. Adipic acid is partially metabolized in humans; the balance is eliminated unchanged in the urine. Adipic acid is slightly to moderately toxic to fish, daphnia, and algae in acute tests.

  10. Quantity of acid in acid fog

    SciTech Connect

    Deal, W.J.

    1983-07-01

    This communication notes the actual magnitude of the acidity in acidic fog particles and suggests a possible line of inquiry into the health effects of such fog so that it can be determined whether a typical fog is detrimental or beneficial relative to dry air.

  11. Acid Thunder: Acid Rain and Ancient Mesoamerica

    ERIC Educational Resources Information Center

    Kahl, Jonathan D. W.; Berg, Craig A.

    2006-01-01

    Much of Mesoamerica's rich cultural heritage is slowly eroding because of acid rain. Just as water dissolves an Alka-Seltzer tablet, acid rain erodes the limestone surfaces of Mexican archaeological sites at a rate of about one-half millimeter per century (Bravo et al. 2003). A half-millimeter may not seem like much, but at this pace, a few…

  12. Fatty acid analogs

    DOEpatents

    Elmaleh, David R.; Livni, Eli

    1985-01-01

    In one aspect, a radioactively labeled analog of a fatty acid which is capable of being taken up by mammalian tissue and which exhibits an in vivo beta-oxidation rate below that with a corresponding radioactively labeled fatty acid.

  13. Omega-3 fatty acids

    PubMed Central

    Schwalfenberg, Gerry

    2006-01-01

    OBJECTIVE To examine evidence for the role of omega-3 fatty acids in cardiovascular disease. QUALITY OF EVIDENCE PubMed was searched for articles on the role of omega-3 fatty acids in cardiovascular disease. Level I and II evidence indicates that omega-3 fatty acids are beneficial in improving cardiovascular outcomes. MAIN MESSAGE Dietary intake of omega-3 fatty acids has declined by 80% during the last 100 years, while intake of omega-6 fatty acids has greatly increased. Omega-3 fatty acids are cardioprotective mainly due to beneficial effects on arrhythmias, atherosclerosis, inflammation, and thrombosis. There is also evidence that they improve endothelial function, lower blood pressure, and significantly lower triglycerides. CONCLUSION There is good evidence in the literature that increasing intake of omega-3 fatty acids improves cardiac outcomes. Physicians need to integrate dietary recommendations for consumption of omega-3 fatty acids into their usual cardiovascular care. PMID:16812965

  14. Sulfuric acid poisoning

    MedlinePlus

    Sulfuric acid is a very strong chemical that is corrosive. Corrosive means it can cause severe burns and ... or mucous membranes. This article discusses poisoning from sulfuric acid. This article is for information only. Do NOT ...

  15. Lactic acid test

    MedlinePlus

    Lactate test ... test. Exercise can cause a temporary increase in lactic acid levels. ... not getting enough oxygen. Conditions that can increase lactic acid levels include: Heart failure Liver disease Lung disease ...

  16. Folic Acid Quiz

    MedlinePlus

    ... About Us Information For... Media Policy Makers Folic Acid Quiz Language: English Español (Spanish) Recommend on Facebook ... button beside the question. Good Luck! 1. Folic acid is: A a B vitamin B a form ...

  17. Hydrochloric acid poisoning

    MedlinePlus

    Hydrochloric acid is a clear, poisonous liquid. It is highly corrosive, which means it immediately causes severe damage, such ... poisoning due to swallowing or breathing in hydrochloric acid. This article is for information only. Do NOT ...

  18. Azelaic Acid Topical

    MedlinePlus

    Azelaic acid gel and foam is used to clear the bumps, lesions, and swelling caused by rosacea (a skin ... redness, flushing, and pimples on the face). Azelaic acid cream is used to treat the pimples and ...

  19. Zoledronic Acid Injection

    MedlinePlus

    Zoledronic acid (Reclast) is used to prevent or treat osteoporosis (condition in which the bones become thin and weak ... of life,' end of regular menstrual periods). Zoledronic acid (Reclast) is also used to treat osteoporosis in ...

  20. Alpha Hydroxy Acids

    MedlinePlus

    ... Cosmetics Home Cosmetics Products & Ingredients Ingredients Alpha Hydroxy Acids Share Tweet Linkedin Pin it More sharing options ... for Industry: Labeling for Cosmetics Containing Alpha Hydroxy Acids The following information is intended to answer questions ...

  1. Uric Acid Test

    MedlinePlus

    ... products and services. Advertising & Sponsorship: Policy | Opportunities Uric Acid Share this page: Was this page helpful? Also known as: Serum Urate; UA Formal name: Uric Acid Related tests: Synovial Fluid Analysis , Kidney Stone Analysis , ...

  2. Amino Acid Metabolism Disorders

    MedlinePlus

    ... breaks the food parts down into sugars and acids, your body's fuel. Your body can use this ... process. One group of these disorders is amino acid metabolism disorders. They include phenylketonuria (PKU) and maple ...

  3. Valproic Acid and Pregnancy

    MedlinePlus

    ... live chat Live Help Fact Sheets Share Valproic Acid and Pregnancy Wednesday, 01 July 2015 In every ... This sheet talks about whether exposure to valproic acid may increase the risk for birth defects over ...

  4. Aminocaproic Acid Injection

    MedlinePlus

    Aminocaproic acid injection is used to control bleeding that occurs when blood clots are broken down too quickly. This ... the baby is ready to be born). Aminocaproic acid injection is also used to control bleeding in ...

  5. Omega-6 Fatty Acids

    MedlinePlus

    Omega-6 fatty acids are types of fats. Some types are found in vegetable oils, including corn, evening primrose seed, safflower, and soybean oils. Other types of omega-6 fatty acids are found in black currant seed, borage seed, ...

  6. Deoxycholic Acid Injection

    MedlinePlus

    Deoxycholic acid injection is used to improve the appearance and profile of moderate to severe submental fat ('double chin'; fatty tissue located under the chin). Deoxycholic acid injection is in a class of medications called ...

  7. A New Structural Family of Gas-Sorbing Coordination Polymers Derived from Phenolic Carboxylic Acids.

    PubMed

    White, Keith F; Abrahams, Brendan F; Babarao, Ravichandar; Dharma, A David; Hudson, Timothy A; Maynard-Casely, Helen E; Robson, Richard

    2015-12-07

    The structure of Li(inox)⋅2/3 DMF (inox(-) =the N-oxide of the isonicotinate anion) consists of a 3D framework with solvent-filled, square cross-section channels of approximate dimensions 5.5×5.5 Å. Unfortunately, the Li(inox) framework is unstable upon removal of DMF from the channels. When the structurally related 4-hydroxybenzoic acid (H2 hba) was used in place of Hinox, and Zn(2+) in place of the Li(+) , a structurally similar but more robust network, Zn(hba), was obtained; the isostructural compound, Co(hba), may also be prepared. Longer ligands with phenolate and carboxylate functional groups at opposite ends, such as the dianions of 4-coumaric acid (H2 cma) and 4'-hydroxy-4-biphenylcarboxylic acid (H2 hbpc), in combination with Zn(2+) yield Zn(cma) and Zn(hbpc) frameworks, respectively, with the same PtS topology but with larger channels. The coordination polymers remain intact after desolvation and exhibit microporosity, showing the ability to sorb significant quantities of CO2 , CH4 , and H2 .

  8. PRODUCTION OF TRIFLUOROACETIC ACID

    DOEpatents

    Haworth, W.N.; Stacey, M.

    1949-07-19

    A method is given for the production of improved yields of trifluoroacetic acid. The compound is prepared by oxidizing m-aminobenzotrifluoride with an alkali metal or alkaline earth metal permanganate at a temperature in the range of 80 deg C to 100 deg C while dissolved ln a mixture of water with glacial acetic acid and/or trifluoroacetic acid. Preferably a mixture of water and trifluoroacetic acid ls used as the solvent.

  9. Refining Lurgi tar acids

    SciTech Connect

    Greco, N.P.

    1984-04-17

    There is disclosed a process for removing tar bases and neutral oils from the Lurgi tar acids by treating the tar acids with aqueous sodium bisulfate to change the tar bases to salts and to hydrolyze the neutral oils to hydrolysis products and distilling the tar acids to obtain refined tar acid as the distillate while the tar base salts and neutral oil hydrolysis products remain as residue.

  10. Plant fatty acid hydroxylases

    DOEpatents

    Somerville, Chris; Broun, Pierre; van de Loo, Frank

    2001-01-01

    This invention relates to plant fatty acyl hydroxylases. Methods to use conserved amino acid or nucleotide sequences to obtain plant fatty acyl hydroxylases are described. Also described is the use of cDNA clones encoding a plant hydroxylase to produce a family of hydroxylated fatty acids in transgenic plants. In addition, the use of genes encoding fatty acid hydroxylases or desaturases to alter the level of lipid fatty acid unsaturation in transgenic plants is described.

  11. 78 FR 20029 - Castor Oil, Polymer With Adipic Acid, Linoleic Acid, Oleic Acid and Ricinoleic Acid; Tolerance...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-03

    ... AGENCY 40 CFR Part 180 Castor Oil, Polymer With Adipic Acid, Linoleic Acid, Oleic Acid and Ricinoleic..., polymer with adipic acid, linoleic acid, oleic acid and ricinoleic acid (CAS Reg. No. 1357486-09- 9) when used as an inert ingredient in a pesticide formulation. Advance Polymer Technology submitted a...

  12. Quantity of acid in acid fog

    SciTech Connect

    Deal, W.J.

    1983-07-01

    The chemical composition of fog particles has become of considerable interest, because of both the possibility of interpreting atmospheric- chemistry processes in fog particles in terms of the principles of aqueous chemistry and the potential health effects of species present in fog particles. The acidity of fog particles has received wide attention. This communication noted the actual magnitude of the excess acidity in acidic fog particles and suggested a possible line of inquiry into the health effects of such fog so that it can be determined whether a typical fog is detrimental or beneficial relative to dry air. (DP)

  13. What Is Acid Rain?

    ERIC Educational Resources Information Center

    Likens, Gene E.

    2004-01-01

    Acid rain is the collective term for any type of acidified precipitation: rain, snow, sleet, and hail, as well as the presence of acidifying gases, particles, cloud water, and fog in the atmosphere. The increased acidity, primarily from sulfuric and nitric acids, is generated as a by-product of the combustion of fossil fuels such as coal and oil.…

  14. The Acid Rain Reader.

    ERIC Educational Resources Information Center

    Stubbs, Harriett S.; And Others

    A topic which is often not sufficiently dealt with in elementary school textbooks is acid rain. This student text is designed to supplement classroom materials on the topic. Discussed are: (1) "Rain"; (2) "Water Cycle"; (3) "Fossil Fuels"; (4) "Air Pollution"; (5) "Superstacks"; (6) "Acid/Neutral/Bases"; (7) "pH Scale"; (8) "Acid Rain"; (9)…

  15. Acid Rain Study Guide.

    ERIC Educational Resources Information Center

    Hunger, Carolyn; And Others

    Acid rain is a complex, worldwide environmental problem. This study guide is intended to aid teachers of grades 4-12 to help their students understand what acid rain is, why it is a problem, and what possible solutions exist. The document contains specific sections on: (1) the various terms used in conjunction with acid rain (such as acid…

  16. Acid Lipase Disease

    MedlinePlus

    ... Page You are here Home » Disorders » All Disorders Acid Lipase Disease Information Page Acid Lipase Disease Information Page What research is being ... research to understand lipid storage diseases such as acid lipase deficiency. Additional research studies hope to identify ...

  17. [alpha]-Oxocarboxylic Acids

    ERIC Educational Resources Information Center

    Kerber, Robert C.; Fernando, Marian S.

    2010-01-01

    Several [alpha]-oxocarboxylic acids play key roles in metabolism in plants and animals. However, there are inconsistencies between the structures as commonly portrayed and the reported acid ionization constants, which result because the acids are predominantly hydrated in aqueous solution; that is, the predominant form is RC(OH)[subscript 2]COOH…

  18. Vibrational and excited electronic states of six-coordinate rare earth complexes with 2,6-lutidine n-oxide: [Ln(C 7H 9NO) 6](ClO 4) 3·H 2O (Ln=Pr,Nd,Sm,Eu,Gd,Dy)

    NASA Astrophysics Data System (ADS)

    Ban-Oganowska, H.; Godlewska, P.; Macalik, L.; Hanuza, J.; Oganowski, W.; Hermanowicz, K.

    2002-09-01

    A series of six-coordinate complexes of 2,6-lutidine N-oxide (C 7H 9NO) with praseodymium, neodymium, samarium, europium, gadolinium and dysprosium has been synthesised and chemically characterised. FT-IR and FT-Raman spectra in the range 80-4000 cm -1 as well as electronic absorption and emission spectra in the range 4000-50,000 cm -1 have been measured. The Lorenzian deconvolution of the vibrational contour in the 100-300 cm -1 region has been used in the discussion of the molecular and site symmetries of the Ln 3+ ion situated in the oxygen polyhedron. The sequence of the electronic levels for all RE ions has been obtained and assigned to the respective transitions.

  19. Effects of dicyandiamide and dolomite application on N2O emission from an acidic soil.

    PubMed

    Shaaban, Muhammad; Wu, Yupeng; Peng, Qi-an; Lin, Shan; Mo, Yongliang; Wu, Lei; Hu, Ronggui; Zhou, Wei

    2016-04-01

    Soil acidification is a major problem for sustainable agriculture since it limits productivity of several crops. Liming is usually adopted to ameliorate soil acidity that can trigger soil processes such as nitrification, denitrification, and loss of nitrogen (N) as nitrous oxide (N2O) emissions. The loss of N following liming of acidic soils can be controlled by nitrification inhibitors (such as dicyandiamide). However, effects of nitrification inhibitors following liming of acidic soils are not well understood so far. Here, we conducted a laboratory study using an acidic soil to examine the effects of dolomite and dicyandiamide (DCD) application on N2O emissions. Three levels of DCD (0, 10, and 20 mg kg(-1); DCD0, DCD10, and DCD20, respectively) were applied to the acidic soil under two levels of dolomite (0 and 1 g kg(-1)) which were further treated with two levels of N fertilizer (0 and 200 mg N kg(-1)). Results showed that N2O emissions were highest at low soil pH levels in fertilizer-treated soil without application of DCD and dolomite. Application of DCD and dolomite significantly (P ≤ 0.001) reduced N2O emissions through decreasing rates of NH4 (+)-N oxidation and increasing soil pH, respectively. Total N2O emissions were reduced by 44 and 13% in DCD20 and dolomite alone treatments, respectively, while DCD20 + dolomite reduced N2O emissions by 54% when compared with DCD0 treatment. The present study suggests that application of DCD and dolomite to acidic soils can mitigate N2O emissions.

  20. Cleavage of nucleic acids

    DOEpatents

    Prudent, James R.; Hall, Jeff G.; Lyamichev, Victor I.; Brow; Mary Ann D.; Dahlberg, James E.

    2010-11-09

    The present invention relates to means for the detection and characterization of nucleic acid sequences, as well as variations in nucleic acid sequences. The present invention also relates to methods for forming a nucleic acid cleavage structure on a target sequence and cleaving the nucleic acid cleavage structure in a site-specific manner. The structure-specific nuclease activity of a variety of enzymes is used to cleave the target-dependent cleavage structure, thereby indicating the presence of specific nucleic acid sequences or specific variations thereof.

  1. Amino acid analysis

    NASA Technical Reports Server (NTRS)

    Winitz, M.; Graff, J. (Inventor)

    1974-01-01

    The process and apparatus for qualitative and quantitative analysis of the amino acid content of a biological sample are presented. The sample is deposited on a cation exchange resin and then is washed with suitable solvents. The amino acids and various cations and organic material with a basic function remain on the resin. The resin is eluted with an acid eluant, and the eluate containing the amino acids is transferred to a reaction vessel where the eluant is removed. Final analysis of the purified acylated amino acid esters is accomplished by gas-liquid chromatographic techniques.

  2. Editorial: Acid precipitation

    SciTech Connect

    1995-09-01

    This editorial focuses on acid rain and the history of public and governmental response to acid rain. Comments on a book by Gwineth Howell `Acid Rain and Acid Waters` are included. The editor feels that Howells has provide a service to the environmental scientific community, with a textbook useful to a range of people, as well as a call for decision makers to learn from the acid rain issue and use it as a model for more sweeping global environmental issues. A balance is needed among several parameters such as level of evidence, probability that the evidence will lead to a specific direction and the cost to the global community. 1 tab.

  3. Nucleic acid detection compositions

    DOEpatents

    Prudent, James R.; Hall, Jeff G.; Lyamichev, Victor I.; Brow, Mary Ann; Dahlberg, James L.

    2008-08-05

    The present invention relates to means for the detection and characterization of nucleic acid sequences, as well as variations in nucleic acid sequences. The present invention also relates to methods for forming a nucleic acid cleavage structure on a target sequence and cleaving the nucleic acid cleavage structure in a site-specific manner. The structure-specific nuclease activity of a variety of enzymes is used to cleave the target-dependent cleavage structure, thereby indicating the presence of specific nucleic acid sequences or specific variations thereof.

  4. Nucleic acid detection assays

    DOEpatents

    Prudent, James R.; Hall, Jeff G.; Lyamichev, Victor I.; Brow, Mary Ann; Dahlberg, James E.

    2005-04-05

    The present invention relates to means for the detection and characterization of nucleic acid sequences, as well as variations in nucleic acid sequences. The present invention also relates to methods for forming a nucleic acid cleavage structure on a target sequence and cleaving the nucleic acid cleavage structure in a site-specific manner. The structure-specific nuclease activity of a variety of enzymes is used to cleave the target-dependent cleavage structure, thereby indicating the presence of specific nucleic acid sequences or specific variations thereof.

  5. Cleavage of nucleic acids

    DOEpatents

    Prudent, James R.; Hall, Jeff G.; Lyamichev, Victor L.; Brow, Mary Ann D.; Dahlberg, James E.

    2007-12-11

    The present invention relates to means for the detection and characterization of nucleic acid sequences, as well as variations in nucleic acid sequences. The present invention also relates to methods for forming a nucleic acid cleavage structure on a target sequence and cleaving the nucleic acid cleavage structure in a site-specific manner. The structure-specific nuclease activity of a variety of enzymes is used to cleave the target-dependent cleavage structure, thereby indicating the presence of specific nucleic acid sequences or specific variations thereof.

  6. Designing and characterization of Fe(III) complexes of oxydiacetate containing α-diimine as auxiliary ligand: 57Fe-Mössbauer and cyclic voltammetric studies

    NASA Astrophysics Data System (ADS)

    Shahid, M.; Sharma, Prashant K.; Siddiqi, Zafar A.; Sama, Farasha; Ansari, Istikhar A.; Khalid, Mohd.

    2014-04-01

    The newly prepared complexes with stoichiometries [Fe(oda)(phen)Cl] (1), [Fe(oda)(4-picNO)(H2O)Cl)] (2) and [Fe2(oda)2(H2O)2Cl2] (3) [H2oda = oxydiacetic acid, phen = 1,10‧-phenantroline and 4-picNO = 4-picoline-N-oxide] were synthesized under varying experimental conditions. The complexes were characterized by spectral (IR, FAB-MS and Mössbauer), electrochemical and thermal studies. 57Fe-Mössbauer spectral data for complexes exhibit a quadrupole splitting confirming the presence of iron nuclei in asymmetric environment. The relevant parameters like isomer shift (δ), quadruple splitting (ΔEQ), line widths and peak height ratio (HWh/HWl) are consistent with high spin state of Fe(III) centre with the presence of Kramer’s double degeneracy in distorted octahedral environment. The electrochemical studies indicate existence of quasi-reversible redox couples (FeII/III) in solution.

  7. Nucleic acid detection kits

    DOEpatents

    Hall, Jeff G.; Lyamichev, Victor I.; Mast, Andrea L.; Brow, Mary Ann; Kwiatkowski, Robert W.; Vavra, Stephanie H.

    2005-03-29

    The present invention relates to means for the detection and characterization of nucleic acid sequences, as well as variations in nucleic acid sequences. The present invention also relates to methods for forming a nucleic acid cleavage structure on a target sequence and cleaving the nucleic acid cleavage structure in a site-specific manner. The structure-specific nuclease activity of a variety of enzymes is used to cleave the target-dependent cleavage structure, thereby indicating the presence of specific nucleic acid sequences or specific variations thereof. The present invention further relates to methods and devices for the separation of nucleic acid molecules based on charge. The present invention also provides methods for the detection of non-target cleavage products via the formation of a complete and activated protein binding region. The invention further provides sensitive and specific methods for the detection of nucleic acid from various viruses in a sample.

  8. [Biosynthesis of adipic acid].

    PubMed

    Han, Li; Chen, Wujiu; Yuan, Fei; Zhang, Yuanyuan; Wang, Qinhong; Ma, Yanhe

    2013-10-01

    Adipic acid is a six-carbon dicarboxylic acid, mainly for the production of polymers such as nylon, chemical fiber and engineering plastics. Its annual demand is close to 3 million tons worldwide. Currently, the industrial production of adipic acid is based on the oxidation of aromatics from non-renewable petroleum resources by chemo-catalytic processes. It is heavily polluted and unsustainable, and the possible alternative method for adipic acid production should be developed. In the past years, with the development of synthetic biology and metabolic engineering, green and clean biotechnological methods for adipic acid production attracted more attention. In this study, the research advances of adipic acid and its precursor production are reviewed, followed by addressing the perspective of the possible new pathways for adipic acid production.

  9. Acidic Ionic Liquids.

    PubMed

    Amarasekara, Ananda S

    2016-05-25

    Ionic liquid with acidic properties is an important branch in the wide ionic liquid field and the aim of this article is to cover all aspects of these acidic ionic liquids, especially focusing on the developments in the last four years. The structural diversity and synthesis of acidic ionic liquids are discussed in the introduction sections of this review. In addition, an unambiguous classification system for various types of acidic ionic liquids is presented in the introduction. The physical properties including acidity, thermo-physical properties, ionic conductivity, spectroscopy, and computational studies on acidic ionic liquids are covered in the next sections. The final section provides a comprehensive review on applications of acidic ionic liquids in a wide array of fields including catalysis, CO2 fixation, ionogel, electrolyte, fuel-cell, membrane, biomass processing, biodiesel synthesis, desulfurization of gasoline/diesel, metal processing, and metal electrodeposition.

  10. Boric acid and boronic acids inhibition of pigeonpea urease.

    PubMed

    Reddy, K Ravi Charan; Kayastha, Arvind M

    2006-08-01

    Urease from the seeds of pigeonpea was competitively inhibited by boric acid, butylboronic acid, phenylboronic acid, and 4-bromophenylboronic acid; 4-bromophenylboronic acid being the strongest inhibitor, followed by boric acid > butylboronic acid > phenylboronic acid, respectively. Urease inhibition by boric acid is maximal at acidic pH (5.0) and minimal at alkaline pH (10.0), i.e., the trigonal planar B(OH)3 form is a more effective inhibitor than the tetrahedral B(OH)4 -anionic form. Similarly, the anionic form of phenylboronic acid was least inhibiting in nature.

  11. Biotransformation of cinnamic acid, p-coumaric acid, caffeic acid, and ferulic acid by plant cell cultures of Eucalyptus perriniana.

    PubMed

    Katsuragi, Hisashi; Shimoda, Kei; Kubota, Naoji; Nakajima, Nobuyoshi; Hamada, Hatsuyuki; Hamada, Hiroki

    2010-01-01

    Biotransformations of phenylpropanoids such as cinnamic acid, p-coumaric acid, caffeic acid, and ferulic acid were investigated with plant-cultured cells of Eucalyptus perriniana. The plant-cultured cells of E. perriniana converted cinnamic acid into cinnamic acid β-D-glucopyranosyl ester, p-coumaric acid, and 4-O-β-D-glucopyranosylcoumaric acid. p-Coumaric acid was converted into 4-O-β-D-glucopyranosylcoumaric acid, p-coumaric acid β-D-glucopyranosyl ester, 4-O-β-D-glucopyranosylcoumaric acid β-D-glucopyranosyl ester, a new compound, caffeic acid, and 3-O-β-D-glucopyranosylcaffeic acid. On the other hand, incubation of caffeic acid with cultured E. perriniana cells gave 3-O-β-D-glucopyranosylcaffeic acid, 3-O-(6-O-β-D-glucopyranosyl)-β-D-glucopyranosylcaffeic acid, a new compound, 3-O-β-D-glucopyranosylcaffeic acid β-D-glucopyranosyl ester, 4-O-β-D-glucopyranosylcaffeic acid, 4-O-β-D-glucopyranosylcaffeic acid β-D-glucopyranosyl ester, ferulic acid, and 4-O-β-D-glucopyranosylferulic acid. 4-O-β-D-Glucopyranosylferulic acid, ferulic acid β-D-glucopyranosyl ester, and 4-O-β-D-glucopyranosylferulic acid β-D-glucopyranosyl ester were isolated from E. perriniana cells treated with ferulic acid.

  12. Process for the preparation of lactic acid and glyceric acid

    DOEpatents

    Jackson, James E [Haslett, MI; Miller, Dennis J [Okemos, MI; Marincean, Simona [Dewitt, MI

    2008-12-02

    Hexose and pentose monosaccharides are degraded to lactic acid and glyceric acid in an aqueous solution in the presence of an excess of a strongly anionic exchange resin, such as AMBERLITE IRN78 and AMBERLITE IRA400. The glyceric acid and lactic acid can be separated from the aqueous solution. Lactic acid and glyceric acid are staple articles of commerce.

  13. Microorganisms for producing organic acids

    DOEpatents

    Pfleger, Brian Frederick; Begemann, Matthew Brett

    2014-09-30

    Organic acid-producing microorganisms and methods of using same. The organic acid-producing microorganisms comprise modifications that reduce or ablate AcsA activity or AcsA homolog activity. The modifications increase tolerance of the microorganisms to such organic acids as 3-hydroxypropionic acid, acrylic acid, propionic acid, lactic acid, and others. Further modifications to the microorganisms increase production of such organic acids as 3-hydroxypropionic acid, lactate, and others. Methods of producing such organic acids as 3-hydroxypropionic acid, lactate, and others with the modified microorganisms are provided. Methods of using acsA or homologs thereof as counter-selectable markers are also provided.

  14. Citric Acid Alternative to Nitric Acid Passivation

    NASA Technical Reports Server (NTRS)

    Lewis, Pattie L. (Compiler)

    2013-01-01

    The Ground Systems Development and Operations GSDO) Program at NASA John F. Kennedy Space Center (KSC) has the primary objective of modernizing and transforming the launch and range complex at KSC to benefit current and future NASA programs along with other emerging users. Described as the launch support and infrastructure modernization program in the NASA Authorization Act of 2010, the GSDO Program will develop and implement shared infrastructure and process improvements to provide more flexible, affordable, and responsive capabilities to a multi-user community. In support of the GSDO Program, the purpose of this project is to demonstratevalidate citric acid as a passivation agent for stainless steel. Successful completion of this project will result in citric acid being qualified for use as an environmentally preferable alternative to nitric acid for passivation of stainless steel alloys in NASA and DoD applications.

  15. Recovery of organic acids

    DOEpatents

    Verser, Dan W.; Eggeman, Timothy J.

    2009-10-13

    A method is disclosed for the recovery of an organic acid from a dilute salt solution in which the cation of the salt forms an insoluble carbonate salt. A tertiary amine and CO.sub.2 are introduced to the solution to form the insoluble carbonate salt and a complex between the acid and an amine. A water immiscible solvent, such as an alcohol, is added to extract the acid/amine complex from the dilute salt solution to a reaction phase. The reaction phase is continuously dried and a product between the acid and the solvent, such as an ester, is formed.

  16. Recovery of organic acids

    DOEpatents

    Verser, Dan W [Menlo Park, CA; Eggeman, Timothy J [Lakewood, CO

    2011-11-01

    A method is disclosed for the recovery of an organic acid from a dilute salt solution in which the cation of the salt forms an insoluble carbonate salt. A tertiary amine and CO.sub.2 are introduced to the solution to form the insoluble carbonate salt and a complex between the acid and an amine. A water immiscible solvent, such as an alcohol, is added to extract the acid/amine complex from the dilute salt solution to a reaction phase. The reaction phase is continuously dried and a product between the acid and the solvent, such as an ester, is formed.

  17. USGS Tracks Acid Rain

    USGS Publications Warehouse

    Gordon, John D.; Nilles, Mark A.; Schroder, LeRoy J.

    1995-01-01

    The U.S. Geological Survey (USGS) has been actively studying acid rain for the past 15 years. When scientists learned that acid rain could harm fish, fear of damage to our natural environment from acid rain concerned the American public. Research by USGS scientists and other groups began to show that the processes resulting in acid rain are very complex. Scientists were puzzled by the fact that in some cases it was difficult to demonstrate that the pollution from automobiles and factories was causing streams or lakes to become more acidic. Further experiments showed how the natural ability of many soils to neutralize acids would reduce the effects of acid rain in some locations--at least as long as the neutralizing ability lasted (Young, 1991). The USGS has played a key role in establishing and maintaining the only nationwide network of acid rain monitoring stations. This program is called the National Atmospheric Deposition Program/National Trends Network (NADP/NTN). Each week, at approximately 220 NADP/NTN sites across the country, rain and snow samples are collected for analysis. NADP/NTN site in Montana. The USGS supports about 72 of these sites. The information gained from monitoring the chemistry of our nation's rain and snow is important for testing the results of pollution control laws on acid rain.

  18. Parenteral Nutrition: Amino Acids.

    PubMed

    Hoffer, Leonard John

    2017-03-10

    There is growing interest in nutrition therapies that deliver a generous amount of protein, but not a toxic amount of energy, to protein-catabolic critically ill patients. Parenteral amino acids can achieve this goal. This article summarizes the biochemical and nutritional principles that guide parenteral amino acid therapy, explains how parenteral amino acid solutions are formulated, and compares the advantages and disadvantages of different parenteral amino acid products with enterally-delivered whole protein products in the context of protein-catabolic critical illness.

  19. Parenteral Nutrition: Amino Acids

    PubMed Central

    Hoffer, Leonard John

    2017-01-01

    There is growing interest in nutrition therapies that deliver a generous amount of protein, but not a toxic amount of energy, to protein-catabolic critically ill patients. Parenteral amino acids can achieve this goal. This article summarizes the biochemical and nutritional principles that guide parenteral amino acid therapy, explains how parenteral amino acid solutions are formulated, and compares the advantages and disadvantages of different parenteral amino acid products with enterally-delivered whole protein products in the context of protein-catabolic critical illness. PMID:28287411

  20. Method for one-to-one polishing of silicon nitride and silicon oxide

    NASA Technical Reports Server (NTRS)

    Babu, Suryadevara V. (Inventor); Natarajan, Anita (Inventor)

    2009-01-01

    The present invention provides a method of removing silicon nitride at about the same removal rate as silicon dioxide by CMP. The method utilizes a polishing slurry that includes colloidal silica abrasive particles dispersed in water and additives that modulate the silicon dioxide and silicon nitride removal rates such that they are about the same. In one embodiment of the invention, the additive is lysine or lysine mono hydrochloride in combination with picolinic acid, which is effective at a pH of about 8. In another embodiment of the invention, the additive is arginine in combination with picolinic acid, which is effective at a pH of about 10.

  1. Diterpenoid acids from Grindelia nana.

    PubMed

    Mahmoud, A A; Ahmed, A A; Tanaka, T; Iinuma, M

    2000-03-01

    Two new norditerpenoid acids of the labdane-type (norgrindelic acids), 4,5-dehydro-6-oxo-18-norgrindelic acid (1) and 4beta-hydroxy-6-oxo-19-norgrindelic acid (2), as well as a new grindelic acid derivative, 18-hydroxy-6-oxogrindelic acid (3), were isolated from the aerial parts of Grindelia nana. In addition, the known compounds, 6-oxogrindelic acid, grindelic acid, methyl grindeloate, 7alpha,8alpha-epoxygrindelic acid, and 4alpha-carboxygrindelic acid were also isolated. The structures of the new compounds were characterized on the basis of spectroscopic analysis.

  2. An NMR-Based Metabolomic Approach to Investigate the Effects of Supplementation with Glutamic Acid in Piglets Challenged with Deoxynivalenol

    PubMed Central

    Ren, Wenkai; Yin, Jie; Hu, Jiayu; Duan, Jielin; Liu, Gang; Tan, Bie; Xiong, Xia; Oso, Abimbola Oladele; Adeola, Olayiwola; Yao, Kang; Yin, Yulong; Li, Tiejun

    2014-01-01

    Deoxynivalenol (DON) has various toxicological effects in humans and pigs that result from the ingestion of contaminated cereal products. This study was conducted to investigate the protective effects of dietary supplementation with glutamic acid on piglets challenged with DON. A total of 20 piglets weaned at 28 d of age were randomly assigned to receive 1 of 4 treatments (5 piglets/treatment): 1) basal diet, negative control (NC); 2) basal diet +4 mg/kg DON (DON); 3) basal diet +2% (g/g) glutamic acid (GLU); 4) basal diet +4 mg/kg DON +2% glutamic acid (DG). A 7-d adaptation period was followed by 30 days of treatment. A metabolite analysis using nuclear magnetic resonance spectroscopy (1H-NMR)-based metabolomic technology and the determination of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities for plasma, as well as the activity of Caspase-3 and the proliferation of epithelial cells were conducted. The results showed that contents of low-density lipoprotein, alanine, arginine, acetate, glycoprotein, trimethylamine-N-oxide (TMAO), glycine, lactate, and urea, as well as the glutamate/creatinine ratio were higher but high-density lipoprotein, proline, citrate, choline, unsaturated lipids and fumarate were lower in piglets of DON treatment than that of NC treatment (P<0.05). Compared with DON treatment, dietary supplementation with glutamic acid increased the plasma concentrations of proline, citrate, creatinine, unsaturated lipids, and fumarate, and decreased the concentrations of alanine, glycoprotein, TMAO, glycine, and lactate, as well as the glutamate/creatinine ratio (P<0.05). Addition glutamic acid to DON treatment increased the plasma activities of SOD and GSH-Px and the proliferating cell nuclear antigen (PCNA) labeling indexes for the jejunum and ileum (P<0.05). These novel findings indicate that glutamic acid has the potential to repair the injuries associated with oxidative stress as well as the disturbances of energy and amino

  3. An NMR-based metabolomic approach to investigate the effects of supplementation with glutamic acid in piglets challenged with deoxynivalenol.

    PubMed

    Wu, Miaomiao; Xiao, Hao; Ren, Wenkai; Yin, Jie; Hu, Jiayu; Duan, Jielin; Liu, Gang; Tan, Bie; Xiong, Xia; Oso, Abimbola Oladele; Adeola, Olayiwola; Yao, Kang; Yin, Yulong; Li, Tiejun

    2014-01-01

    Deoxynivalenol (DON) has various toxicological effects in humans and pigs that result from the ingestion of contaminated cereal products. This study was conducted to investigate the protective effects of dietary supplementation with glutamic acid on piglets challenged with DON. A total of 20 piglets weaned at 28 d of age were randomly assigned to receive 1 of 4 treatments (5 piglets/treatment): 1) basal diet, negative control (NC); 2) basal diet +4 mg/kg DON (DON); 3) basal diet +2% (g/g) glutamic acid (GLU); 4) basal diet +4 mg/kg DON +2% glutamic acid (DG). A 7-d adaptation period was followed by 30 days of treatment. A metabolite analysis using nuclear magnetic resonance spectroscopy (1H-NMR)-based metabolomic technology and the determination of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities for plasma, as well as the activity of Caspase-3 and the proliferation of epithelial cells were conducted. The results showed that contents of low-density lipoprotein, alanine, arginine, acetate, glycoprotein, trimethylamine-N-oxide (TMAO), glycine, lactate, and urea, as well as the glutamate/creatinine ratio were higher but high-density lipoprotein, proline, citrate, choline, unsaturated lipids and fumarate were lower in piglets of DON treatment than that of NC treatment (P<0.05). Compared with DON treatment, dietary supplementation with glutamic acid increased the plasma concentrations of proline, citrate, creatinine, unsaturated lipids, and fumarate, and decreased the concentrations of alanine, glycoprotein, TMAO, glycine, and lactate, as well as the glutamate/creatinine ratio (P<0.05). Addition glutamic acid to DON treatment increased the plasma activities of SOD and GSH-Px and the proliferating cell nuclear antigen (PCNA) labeling indexes for the jejunum and ileum (P<0.05). These novel findings indicate that glutamic acid has the potential to repair the injuries associated with oxidative stress as well as the disturbances of energy and amino

  4. Structure of Acid phosphatases.

    PubMed

    Araujo, César L; Vihko, Pirkko T

    2013-01-01

    Acid phosphatases are enzymes that have been studied extensively due to the fact that their dysregulation is associated with pathophysiological conditions. This characteristic has been exploited for the development of diagnostic and therapeutic methods. As an example, prostatic acid phosphatase was the first marker for metastatic prostate cancer diagnosis and the dysregulation of tartrate resistant acid phosphatase is associated with abnormal bone resorption linked to osteoporosis. The pioneering crystallization studies on prostatic acid phosphatase and mammalian tartrate-resistant acid phosphatase conformed significant milestones towards the elucidation of the mechanisms followed by these enzymes (Schneider et al., EMBO J 12:2609-2615, 1993). Acid phosphatases are also found in nonmammalian species such as bacteria, fungi, parasites, and plants, and most of them share structural similarities with mammalian acid phosphatase enzymes. Acid phosphatase (EC 3.1.3.2) enzymes catalyze the hydrolysis of phosphate monoesters following the general equation. Phosphate monoester + H2O -->/<-- alcohol + phosphate. The general classification "acid phosphatase" relies only on the optimum acidic pH for the enzymatic activity in assay conditions using non-physiological substrates. These enzymes accept a wide range of substrates in vitro, ranging from small organic molecules to phosphoproteins, constituting a heterogeneous group of enzymes from the structural point of view. These structural differences account for the divergence in cofactor dependences and behavior against substrates, inhibitors, and activators. In this group only the tartrate-resistant acid phosphatase is a metallo-enzyme whereas the other members do not require metal-ion binding for their catalytic activity. In addition, tartrate-resistant acid phosphatase and erythrocytic acid phosphatase are not inhibited by L-(+)-tartrate ion while the prostatic acid phosphatase is tartrate-sensitive. This is an important

  5. Folic Acid and Pregnancy

    MedlinePlus

    ... Lessons? Visit KidsHealth in the Classroom What Other Parents Are Reading Your Child's Development (Birth to 3 Years) Feeding Your 1- to 3-Month-Old Feeding Your 4- to 7-Month-Old Feeding Your 8- to 12-Month-Old Feeding Your 1- to 2-Year-Old Folic Acid ... > For Parents > Folic Acid and Pregnancy A A A What's ...

  6. Bile acid transporters

    PubMed Central

    Dawson, Paul A.; Lan, Tian; Rao, Anuradha

    2009-01-01

    In liver and intestine, transporters play a critical role in maintaining the enterohepatic circulation and bile acid homeostasis. Over the past two decades, there has been significant progress toward identifying the individual membrane transporters and unraveling their complex regulation. In the liver, bile acids are efficiently transported across the sinusoidal membrane by the Na+ taurocholate cotransporting polypeptide with assistance by members of the organic anion transporting polypeptide family. The bile acids are then secreted in an ATP-dependent fashion across the canalicular membrane by the bile salt export pump. Following their movement with bile into the lumen of the small intestine, bile acids are almost quantitatively reclaimed in the ileum by the apical sodium-dependent bile acid transporter. The bile acids are shuttled across the enterocyte to the basolateral membrane and effluxed into the portal circulation by the recently indentified heteromeric organic solute transporter, OSTα-OSTβ. In addition to the hepatocyte and enterocyte, subgroups of these bile acid transporters are expressed by the biliary, renal, and colonic epithelium where they contribute to maintaining bile acid homeostasis and play important cytoprotective roles. This article will review our current understanding of the physiological role and regulation of these important carriers. PMID:19498215

  7. Analysis of Organic Acids.

    ERIC Educational Resources Information Center

    Griswold, John R.; Rauner, Richard A.

    1990-01-01

    Presented are the procedures and a discussion of the results for an experiment in which students select unknown carboxylic acids, determine their melting points, and investigate their solubility behavior in water and ethanol. A table of selected carboxylic acids is included. (CW)

  8. Salicylic Acid Topical

    MedlinePlus

    Propa pH® Peel-Off Acne Mask ... pimples and skin blemishes in people who have acne. Topical salicylic acid is also used to treat ... medications called keratolytic agents. Topical salicylic acid treats acne by reducing swelling and redness and unplugging blocked ...

  9. Toxicology of Perfluoroalkyl Acids*

    EPA Science Inventory

    The perfluoroalkyl acids (PFAAs) are a family of organic chemicals consisting of a perfluorinated carbon backbone (4-12 in length) and an acidic functional moiety (carboxylate or sulfonate). These compounds are chemically stable, have excellent surface-tension reducing properties...

  10. Mutant fatty acid desaturase

    DOEpatents

    Shanklin, John; Cahoon, Edgar B.

    2004-02-03

    The present invention relates to a method for producing mutants of a fatty acid desaturase having a substantially increased activity towards fatty acid substrates with chains containing fewer than 18 carbons relative to an unmutagenized precursor desaturase having an 18 carbon atom chain length substrate specificity. The method involves inducing one or more mutations in the nucleic acid sequence encoding the precursor desaturase, transforming the mutated sequence into an unsaturated fatty acid auxotroph cell such as MH13 E. coli, culturing the cells in the absence of supplemental unsaturated fatty acids, thereby selecting for recipient cells which have received and which express a mutant fatty acid desaturase with an elevated specificity for fatty acid substrates having chain lengths of less than 18 carbon atoms. A variety of mutants having 16 or fewer carbon atom chain length substrate specificities are produced by this method. Mutant desaturases produced by this method can be introduced via expression vectors into prokaryotic and eukaryotic cells and can also be used in the production of transgenic plants which may be used to produce specific fatty acid products.

  11. Omega-3 Fatty Acids

    MedlinePlus

    Omega-3 fatty acids are used together with lifestyle changes (diet, weight-loss, exercise) to reduce the amount of triglycerides (a fat-like ... people with very high triglycerides. Omega-3 fatty acids are in a class of medications called antilipemic ...

  12. Amino Acid Crossword Puzzle

    ERIC Educational Resources Information Center

    Sims, Paul A.

    2011-01-01

    Learning the 20 standard amino acids is an essential component of an introductory course in biochemistry. Later in the course, the students study metabolism and learn about various catabolic and anabolic pathways involving amino acids. Learning new material or concepts often is easier if one can connect the new material to what one already knows;…

  13. Production of shikimic acid.

    PubMed

    Ghosh, Saptarshi; Chisti, Yusuf; Banerjee, Uttam C

    2012-01-01

    Shikimic acid is a key intermediate for the synthesis of the antiviral drug oseltamivir (Tamiflu®). Shikimic acid can be produced via chemical synthesis, microbial fermentation and extraction from certain plants. An alternative production route is via biotransformation of the more readily available quinic acid. Much of the current supply of shikimic acid is sourced from the seeds of Chinese star anise (Illicium verum). Supply from star anise seeds has experienced difficulties and is susceptible to vagaries of weather. Star anise tree takes around six-years from planting to bear fruit, but remains productive for long. Extraction and purification from seeds are expensive. Production via fermentation is increasing. Other production methods are too expensive, or insufficiently developed. In the future, production in recombinant microorganisms via fermentation may become established as the preferred route. Methods for producing shikimic acid are reviewed.

  14. Fatty acid production from amino acids and alpha-keto acids by Brevibacterium linens BL2.

    PubMed

    Ganesan, Balasubramanian; Seefeldt, Kimberly; Weimer, Bart C

    2004-11-01

    Low concentrations of branched-chain fatty acids, such as isobutyric and isovaleric acids, develop during the ripening of hard cheeses and contribute to the beneficial flavor profile. Catabolism of amino acids, such as branched-chain amino acids, by bacteria via aminotransferase reactions and alpha-keto acids is one mechanism to generate these flavorful compounds; however, metabolism of alpha-keto acids to flavor-associated compounds is controversial. The objective of this study was to determine the ability of Brevibacterium linens BL2 to produce fatty acids from amino acids and alpha-keto acids and determine the occurrence of the likely genes in the draft genome sequence. BL2 catabolized amino acids to fatty acids only under carbohydrate starvation conditions. The primary fatty acid end products from leucine were isovaleric acid, acetic acid, and propionic acid. In contrast, logarithmic-phase cells of BL2 produced fatty acids from alpha-keto acids only. BL2 also converted alpha-keto acids to branched-chain fatty acids after carbohydrate starvation was achieved. At least 100 genes are potentially involved in five different metabolic pathways. The genome of B. linens ATCC 9174 contained these genes for production and degradation of fatty acids. These data indicate that brevibacteria have the ability to produce fatty acids from amino and alpha-keto acids and that carbon metabolism is important in regulating this event.

  15. Total syntheses of cis-cyclopropane fatty acids: dihydromalvalic acid, dihydrosterculic acid, lactobacillic acid, and 9,10-methylenehexadecanoic acid.

    PubMed

    Shah, Sayali; White, Jonathan M; Williams, Spencer J

    2014-12-14

    cis-Cyclopropane fatty acids (cis-CFAs) are widespread constituents of the seed oils of subtropical plants, membrane components of bacteria and protozoa, and the fats and phospholipids of animals. We describe a systematic approach to the synthesis of enantiomeric pairs of four cis-CFAs: cis-9,10-methylenehexadecanoic acid, lactobacillic acid, dihydromalvalic acid, and dihydrosterculic acid. The approach commences with Rh2(OAc)4-catalyzed cyclopropenation of 1-octyne and 1-decyne, and hinges on the preparative scale chromatographic resolution of racemic 2-alkylcycloprop-2-ene-1-carboxylic acids using a homochiral Evan's auxiliary. Saturation of the individual diastereomeric N-cycloprop-2-ene-1-carbonylacyloxazolidines, followed by elaboration to alkylcyclopropylmethylsulfones, allowed Julia-Kocienski olefination with various ω-aldehyde-esters. Finally, saponification and diimide reduction afforded the individual cis-CFA enantiomers.

  16. Sulfuric Acid on Europa

    NASA Technical Reports Server (NTRS)

    1999-01-01

    Frozen sulfuric acid on Jupiter's moon Europa is depicted in this image produced from data gathered by NASA's Galileo spacecraft. The brightest areas, where the yellow is most intense, represent regions of high frozen sulfuric acid concentration. Sulfuric acid is found in battery acid and in Earth's acid rain.

    This image is based on data gathered by Galileo's near infrared mapping spectrometer.

    Europa's leading hemisphere is toward the bottom right, and there are enhanced concentrations of sulfuric acid in the trailing side of Europa (the upper left side of the image). This is the face of Europa that is struck by sulfur ions coming from Jupiter's innermost moon, Io. The long, narrow features that crisscross Europa also show sulfuric acid that may be from sulfurous material extruded in cracks.

    Galileo, launched in 1989, has been orbiting Jupiter and its moons since December 1995. JPL manages the Galileo mission for NASA's Office of Space Science, Washington DC. JPL is a division of the California Institute of Technology, Pasadena, CA.

  17. Trans Fatty Acids

    NASA Astrophysics Data System (ADS)

    Doyle, Ellin

    1997-09-01

    Fats and their various fatty acid components seem to be a perennial concern of nutritionists and persons concerned with healthful diets. Advice on the consumption of saturated, polyunsaturated, monounsaturated, and total fat bombards us from magazines and newspapers. One of the newer players in this field is the group of trans fatty acids found predominantly in partially hydrogenated fats such as margarines and cooking fats. The controversy concerning dietary trans fatty acids was recently addressed in an American Heart Association (AHA) science advisory (1) and in a position paper from the American Society of Clinical Nutrition/American Institute of Nutrition (ASCN/AIN) (2). Both reports emphasize that the best preventive strategy for reducing risk for cardiovascular disease and some types of cancer is a reduction in total and saturated fats in the diet, but a reduction in the intake of trans fatty acids was also recommended. Although the actual health effects of trans fatty acids remain uncertain, experimental evidence indicates that consumption of trans fatty acids adversely affects serum lipid levels. Since elevated levels of serum cholesterol and triacylglycerols are associated with increased risk of cardiovascular disease, it follows that intake of trans fatty acids should be minimized.

  18. Gluconic acid production.

    PubMed

    Anastassiadis, Savas; Morgunov, Igor G

    2007-01-01

    Gluconic acid, the oxidation product of glucose, is a mild neither caustic nor corrosive, non toxic and readily biodegradable organic acid of great interest for many applications. As a multifunctional carbonic acid belonging to the bulk chemicals and due to its physiological and chemical characteristics, gluconic acid itself, its salts (e.g. alkali metal salts, in especially sodium gluconate) and the gluconolactone form have found extensively versatile uses in the chemical, pharmaceutical, food, construction and other industries. Present review article presents the comprehensive information of patent bibliography for the production of gluconic acid and compares the advantages and disadvantages of known processes. Numerous manufacturing processes are described in the international bibliography and patent literature of the last 100 years for the production of gluconic acid from glucose, including chemical and electrochemical catalysis, enzymatic biocatalysis by free or immobilized enzymes in specialized enzyme bioreactors as well as discontinuous and continuous fermentation processes using free growing or immobilized cells of various microorganisms, including bacteria, yeast-like fungi and fungi. Alternatively, new superior fermentation processes have been developed and extensively described for the continuous and discontinuous production of gluconic acid by isolated strains of yeast-like mold Aureobasidium pullulans, offering numerous advantages over the traditional discontinuous fungi processes.

  19. Effects of iron and phytic acid on production of extracellular radicals by Enterococcus faecalis.

    PubMed

    Moore, Danny R; Kotake, Yashige; Huycke, Mark M

    2004-12-01

    Enterococcus faecalis is a human intestinal commensal that produces extracellular superoxide, hydrogen peroxide, and hydroxyl radical while colonizing the intestinal tract. To determine whether dietary factors implicated in colorectal cancer affect oxidant production by E. faecalis, radicals were measured in rats colonized with this microorganism while on diets supplemented with iron or phytic acid. Hydroxyl radical activity was measured by assaying for aromatic hydroxylation products of D-phenylalanine using reverse-phase high-performance liquid chromatography and electrochemical detection. In vitro, as expected, iron enhanced, and phytic acid decreased, hydroxyl radical formation by E. faecalis. For rats colonized with E. faecalis given supplemental dietary iron (740 mg elemental iron as ferric phosphate per kg diet) or phytic acid (1.2% w/w), no differences were found in concentrations of urinary ortho- or meta- isomers of D-phenylalanine compared to rats on a basal diet. Aqueous radicals in colonic contents were further assessed ex vivo by electron spin resonance using 5,5-dimethyl-1-pyrroline-N-oxide as a spin trap. Mixtures of thiyl (sulfur-centered) and oxygen-centered radicals were detected across all diets. In vitro, similar spectra were observed when E. faecalis was incubated with hydrogen sulfide, air-oxidized cysteine, or an alkylsulfide, as typical sulfur-containing compounds that might occur in colonic contents. In conclusion, intestinal colonization with E. faecalis in a rat model generates both thiyl and oxygen-centered radicals in colonic contents. Radical formation, however, was not significantly altered by short-term dietary supplementation with iron or phytic acid.

  20. Strongly Acidic Auxin Indole-3-Methanesulfonic Acid

    PubMed Central

    Cohen, Jerry D.; Baldi, Bruce G.; Bialek, Krystyna

    1985-01-01

    A radiochemical synthesis is described for [14C]indole-3-methanesulfonic acid (IMS), a strongly acidic auxin analog. Techniques were developed for fractionation and purification of IMS using normal and reverse phase chromatography. In addition, the utility of both Fourier transform infrared spectrometry and fast atom bombardment mass spectrometry for analysis of IMS has been demonstrated. IMS was shown to be an active auxin, stimulating soybean hypocotyl elongation, bean first internode curvature, and ethylene production. IMS uptake by thin sections of soybean hypocotyl was essentially independent of solution pH and, when applied at a 100 micromolar concentration, IMS exhibited a basipetal polarity in its transport in both corn coleoptile and soybean hypocotyl sections. [14C]IMS should, therefore, be a useful compound to study fundamental processes related to the movement of auxins in plant tissues and organelles. PMID:16664007

  1. Aminolevulinic Acid Topical

    MedlinePlus

    ... under the skin that result from exposure to sunlight and can develop into skin cancer) of the ... acid will make your skin very sensitive to sunlight (likely to get sunburn). Avoid exposure of treated ...

  2. Difficult Decisions: Acid Rain.

    ERIC Educational Resources Information Center

    Miller, John A.; Slesnick, Irwin L.

    1989-01-01

    Discusses some of the contributing factors and chemical reactions involved in the production of acid rain, its effects, and political issues pertaining to who should pay for the clean up. Supplies questions for consideration and discussion. (RT)

  3. Folic acid - test

    MedlinePlus

    ... folic acid before and during pregnancy helps prevent neural tube defects, such as spina bifida. Women who ... take more if they have a history of neural tube defects in earlier pregnancies. Ask your provider ...

  4. Acid soldering flux poisoning

    MedlinePlus

    The harmful substances in soldering fluxes are called hydrocarbons. They include: Ammonium chloride Rosin Hydrochloric acid Zinc ... Lee DC. Hydrocarbons. In: Marx JA, Hockberger RS, Walls RM, et ... Rosen's Emergency Medicine: Concepts and Clinical Practice . 8th ...

  5. Amoxicillin and Clavulanic Acid

    MedlinePlus

    ... Amoxicillin is in a class of medications called penicillin-like antibiotics. It works by stopping the growth ... allergic to amoxicillin (Amoxil, Trimox, Wymox), clavulanic acid, penicillin, cephalosporins, or any other medications.tell your doctor ...

  6. Amino Acid Metabolism Disorders

    MedlinePlus

    ... acidemia? In ASA, the body can’t remove ammonia or a substance called argininosuccinic acid from the ... and children include: Breathing problems High levels of ammonia in the bloodIntense headache, especially after a high- ...

  7. [Hydrofluoric acid burns].

    PubMed

    Holla, Robin; Gorter, Ramon R; Tenhagen, Mark; Vloemans, A F P M Jos; Breederveld, Roelf S

    2016-01-01

    Hydrofluoric acid is increasingly used as a rust remover and detergent. Dermal contact with hydrofluoric acid results in a chemical burn characterized by severe pain and deep tissue necrosis. It may cause electrolyte imbalances with lethal consequences. It is important to identify high-risk patients. 'High risk' is defined as a total affected body area > 3% or exposure to hydrofluoric acid in a concentration > 50%. We present the cases of three male patients (26, 31, and 39 years old) with hydrofluoric acid burns of varying severity and describe the subsequent treatments. The application of calcium gluconate 2.5% gel to the skin is the cornerstone of the treatment, reducing pain as well as improving wound healing. Nails should be thoroughly inspected and possibly removed if the nail is involved, to ensure proper healing. In high-risk patients, plasma calcium levels should be evaluated and cardiac monitoring is indicated.

  8. Citric acid urine test

    MedlinePlus

    ... used to diagnose renal tubular acidosis and evaluate kidney stone disease. Normal Results The normal range is 320 ... tubular acidosis and a tendency to form calcium kidney stones. The following may decrease urine citric acid levels: ...

  9. Lead/acid batteries

    NASA Astrophysics Data System (ADS)

    Bullock, Kathryn R.

    Lead/acid batteries are produced in sizes from less than 1 to 3000 Ah for a wide variety of portable, industrial and automotive applications. Designs include Planté, Fauré or pasted, and tubular electrodes. In addition to the traditional designs which are flooded with sulfuric acid, newer 'valve-regulated" designs have the acid immolibized in a silica gel or absorbed in a porous glass separator. Development is ongoing worldwide to increase the specific power, energy and deep discharge cycle life of this commercially successful system to meet the needs of new applications such as electric vehicles, load leveling, and solar energy storage. The operating principles, current status, technical challenges and commercial impact of the lead/acid battery are reviewed.

  10. Amino Acids and Chirality

    NASA Technical Reports Server (NTRS)

    Cook, Jamie E.

    2012-01-01

    Amino acids are among the most heavily studied organic compound class in carbonaceous chondrites. The abundance, distributions, enantiomeric compositions, and stable isotopic ratios of amino acids have been determined in carbonaceous chondrites fi'om a range of classes and petrographic types, with interesting correlations observed between these properties and the class and typc of the chondritcs. In particular, isomeric distributions appear to correlate with parent bodies (chondrite class). In addition, certain chiral amino acids are found in enantiomeric excess in some chondrites. The delivery of these enantiomeric excesses to the early Earth may have contributed to the origin of the homochirality that is central to life on Earth today. This talk will explore the amino acids in carbonaceous chondritcs and their relevance to the origin of life.

  11. The linoleic acid and trans fatty acids of margarines.

    PubMed

    Beare-Rogers, J L; Gray, L M; Hollywood, R

    1979-09-01

    Fifty brands of margarine were analysed for cis-polyunsaturated acids by lipoxidase, for trans fatty acid by infared spectroscopy, and for fatty acid composition by gas-liquid chromatography. High concentrations of trans fatty acids tended to be associated with low concentrations of linoleic acid. Later analyses on eight of the brands, respresenting various proportions of linoleic to trans fatty acids, indicated that two of them contained still higher levels of trans fatty acids (greater than 60%) and negligible amounts of linoleic acid. It is proposed that margarine could be a vehicle for the distribution of some dietary linoleic acid and that the level of linoleic acid and the summation of the saturated plus trans fatty acids be known to ascertain nutritional characteristics.

  12. Method for isolating nucleic acids

    SciTech Connect

    Hurt, Jr., Richard Ashley; Elias, Dwayne A.

    2015-09-29

    The current disclosure provides methods and kits for isolating nucleic acid from an environmental sample. The current methods and compositions further provide methods for isolating nucleic acids by reducing adsorption of nucleic acids by charged ions and particles within an environmental sample. The methods of the current disclosure provide methods for isolating nucleic acids by releasing adsorbed nucleic acids from charged particles during the nucleic acid isolation process. The current disclosure facilitates the isolation of nucleic acids of sufficient quality and quantity to enable one of ordinary skill in the art to utilize or analyze the isolated nucleic acids for a wide variety of applications including, sequencing or species population analysis.

  13. [Acids in coffee. XI. The proportion of individual acids in the total titratable acid].

    PubMed

    Engelhardt, U H; Maier, H G

    1985-07-01

    22 acids in ground roast coffees and instant coffees were determined by GLC of their silyl derivatives (after preseparation by gel electrophoresis) or isotachophoresis. The contribution to the total acidity (which was estimated by titration to pH 8 after cation exchange of the coffee solutions) was calculated for each individual acid. The mentioned acids contribute with 67% (roast coffee) and 72% (instant coffee) to the total acidity. In the first place citric acid (12.2% in roast coffee/10.7% in instant coffee), acetic acid (11.2%/8.8%) and the high molecular weight acids (8%/9%) contribute to the total acidity. Also to be mentioned are the shares of chlorogenic acids (9%/4.8%), formic acid (5.3%/4.6%), quinic acid (4.7%/5.9%), malic acid (3.9%/3%) and phosphoric acid (2.5%/5.2%). A notable difference in the contribution to total acidity between roast and instant coffee was found for phosphoric acid and pyrrolidonecarboxylic acid (0.7%/1.9%). It can be concluded that those two acids are formed or released from e.g. their esters in higher amounts than other acids during the production of instant coffee.

  14. Acidification and Acid Rain

    NASA Astrophysics Data System (ADS)

    Norton, S. A.; Veselã½, J.

    2003-12-01

    Air pollution by acids has been known as a problem for centuries (Ducros, 1845; Smith, 1872; Camuffo, 1992; Brimblecombe, 1992). Only in the mid-1900s did it become clear that it was a problem for more than just industrially developed areas, and that precipitation quality can affect aquatic resources ( Gorham, 1955). The last three decades of the twentieth century saw tremendous progress in the documentation of the chemistry of the atmosphere, precipitation, and the systems impacted by acid atmospheric deposition. Chronic acidification of ecosystems results in chemical changes to soil and to surface waters and groundwater as a result of reduction of base cation supply or an increase in acid (H+) supply, or both. The most fundamental changes during chronic acidification are an increase in exchangeable H+ or Al3+ (aluminum) in soils, an increase in H+ activity (˜concentration) in water in contact with soil, and a decrease in alkalinity in waters draining watersheds. Water draining from the soil is acidified and has a lower pH (=-log [H+]). As systems acidify, their biotic community changes.Acidic surface waters occur in many parts of the world as a consequence of natural processes and also due to atmospheric deposition of strong acid (e.g., Canada, Jeffries et al. (1986); the United Kingdom, Evans and Monteith (2001); Sweden, Swedish Environmental Protection Board (1986); Finland, Forsius et al. (1990); Norway, Henriksen et al. (1988a); and the United States (USA), Brakke et al. (1988)). Concern over acidification in the temperate regions of the northern hemisphere has been driven by the potential for accelerating natural acidification by pollution of the atmosphere with acidic or acidifying compounds. Atmospheric pollution ( Figure 1) has resulted in an increased flux of acid to and through ecosystems. Depending on the ability of an ecosystem to neutralize the increased flux of acidity, acidification may increase only imperceptibly or be accelerated at a rate that

  15. The second acidic constant of salicylic acid.

    PubMed

    Porto, Raffaella; De Tommaso, Gaetano; Furia, Emilia

    2005-01-01

    The second dissociation constant of salicylic acid (H2L) has been determined, at 25 degrees C, in NaCl ionic media by UV spectrophotometric measurements. The investigated ionic strength values were 0.16, 0.25, 0.50, 1.0, 2.0 and 3.0 M. The protolysis constants calculated at the different ionic strengths yielded, with the Specific Interaction Theory, the infinite dilution constant, log beta1(0) = 13.62 +/- 0.03, for the equilibrium L2- + H+ <==> HL-. The interaction coefficient between Na+ and L2-, b(Na+, L2-) = 0.02 +/- 0.07, has been also calculated.

  16. Differential activation of pregnane X receptor by carnosic acid, carnosol, ursolic acid, and rosmarinic acid.

    PubMed

    Seow, Chun Ling; Lau, Aik Jiang

    2017-03-10

    Pregnane X receptor (PXR) regulates the expression of many genes, including those involved in drug metabolism and transport, and has been linked to various diseases, including inflammatory bowel disease. In the present study, we determined whether carnosic acid and other chemicals in rosemary extract (carnosol, ursolic acid, and rosmarinic acid) are PXR activators. As assessed in dual-luciferase reporter gene assays, carnosic acid, carnosol, and ursolic acid, but not rosmarinic acid, activated human PXR (hPXR) and mouse PXR (mPXR), whereas carnosol and ursolic acid, but not carnosic acid or rosmarinic acid, activated rat PXR (rPXR). Dose-response experiments indicated that carnosic acid, carnosol, and ursolic acid activated hPXR with EC50 values of 0.79, 2.22, and 10.77μM, respectively. Carnosic acid, carnosol, and ursolic acid, but not rosmarinic acid, transactivated the ligand-binding domain of hPXR and recruited steroid receptor coactivator-1 (SRC-1), SRC-2, and SRC-3 to the ligand-binding domain of hPXR. Carnosic acid, carnosol, and ursolic acid, but not rosmarinic acid, increased hPXR target gene expression, as shown by an increase in CYP3A4, UGT1A3, and ABCB1 mRNA expression in LS180 human colon adenocarcinoma cells. Rosmarinic acid did not attenuate the extent of hPXR activation by rifampicin, suggesting it is not an antagonist of hPXR. Overall, carnosic acid, carnosol, and ursolic acid, but not rosmarinic acid, are hPXR agonists, and carnosic acid shows species-dependent activation of hPXR and mPXR, but not rPXR. The findings provide new mechanistic insight on the effects of carnosic acid, carnosol, and ursolic acid on PXR-mediated biological effects.

  17. Discovery of essential fatty acids

    PubMed Central

    Spector, Arthur A.; Kim, Hee-Yong

    2015-01-01

    Dietary fat was recognized as a good source of energy and fat-soluble vitamins by the first part of the 20th century, but fatty acids were not considered to be essential nutrients because they could be synthesized from dietary carbohydrate. This well-established view was challenged in 1929 by George and Mildred Burr who reported that dietary fatty acid was required to prevent a deficiency disease that occurred in rats fed a fat-free diet. They concluded that fatty acids were essential nutrients and showed that linoleic acid prevented the disease and is an essential fatty acid. The Burrs surmised that other unsaturated fatty acids were essential and subsequently demonstrated that linolenic acid, the omega-3 fatty acid analog of linoleic acid, is also an essential fatty acid. The discovery of essential fatty acids was a paradigm-changing finding, and it is now considered to be one of the landmark discoveries in lipid research. PMID:25339684

  18. Acid Rain, pH & Acidity: A Common Misinterpretation.

    ERIC Educational Resources Information Center

    Clark, David B.; Thompson, Ronald E.

    1989-01-01

    Illustrates the basis for misleading statements about the relationship between pH and acid content in acid rain. Explains why pH cannot be used as a measure of acidity for rain or any other solution. Suggests that teachers present acidity and pH as two separate and distinct concepts. (RT)

  19. [Lipid synthesis by an acidic acid tolerant Rhodotorula glutinis].

    PubMed

    Lin, Zhangnan; Liu, Hongjuan; Zhang, Jian'an; Wang, Gehua

    2016-03-01

    Acetic acid, as a main by-product generated in the pretreatment process of lignocellulose hydrolysis, significantly affects cell growth and lipid synthesis of oleaginous microorganisms. Therefore, we studied the tolerance of Rhodotorula glutinis to acetic acid and its lipid synthesis from substrate containing acetic acid. In the mixed sugar medium containing 6 g/L glucose and 44 g/L xylose, and supplemented with acetic acid, the cell growth was not:inhibited when the acetic acid concentration was below 10 g/L. Compared with the control, the biomass, lipid concentration and lipid content of R. glutinis increased 21.5%, 171% and 122% respectively when acetic acid concentration was 10 g/L. Furthermore, R. glutinis could accumulate lipid with acetate as the sole carbon source. Lipid concentration and lipid yield reached 3.20 g/L and 13% respectively with the initial acetic acid concentration of 25 g/L. The lipid composition was analyzed by gas chromatograph. The main composition of lipid produced with acetic acid was palmitic acid, stearic acid, oleic acid, linoleic acid and linolenic acid, including 40.9% saturated fatty acids and 59.1% unsaturated fatty acids. The lipid composition was similar to that of plant oil, indicating that lipid from oleaginous yeast R. glutinis had potential as the feedstock of biodiesel production. These results demonstrated that a certain concentration of acetic acid need not to be removed in the detoxification process when using lignocelluloses hydrolysate to produce microbial lipid by R. glutinis.

  20. Amino-acid contamination of aqueous hydrochloric acid.

    NASA Technical Reports Server (NTRS)

    Wolman, Y.; Miller, S. L.

    1971-01-01

    Considerable amino-acid contamination in commercially available analytical grade hydrochloric acid (37% HCl) was found. One bottle contained 8,300 nmol of amino-acids per liter. A bottle from another supplier contained 6,700 nmol per liter. The contaminants were mostly protein amino-acids and several unknowns. Data on the volatility of the amino-acids during HCl distillation were also obtained.

  1. Computational analysis of azine-N-oxides as energetic materials

    SciTech Connect

    Ritchie, J.P.

    1994-05-01

    A BKW equation of state in a 1-dimensional hydrodynamic simulation of the cylinder test can be used to estimate the performance of explosives. Using this approach, the novel explosive 1,4-diamino-2,3,5,6-tetrazine-2,5-dioxide (TZX) was analyzed. Despite a high detonation velocity and a predicted CJ pressure comparable to that of RDX, TZX performs relatively poorly in the cylinder test. Theoretical and computational analysis shows this to be the result of a low heat of detonation. A conceptual strategy is proposed to remedy this problem. In order to predict the required heats of formation, new ab initio group equivalents were developed. Crystal structure calculations are also described that show hydrogen-bonding is important in determining the density of TZX and related compounds.

  2. Luminescent lanthanide complexes with macrocyclic N-oxides

    NASA Astrophysics Data System (ADS)

    Pietraszkiewicz, Marek; Karpiuk, Jerzy; Pietraszkiewicz, Oksana

    1998-11-01

    Bicyclic ligand incorporating 3,3‧-biisoquinoline-2,2‧-dioxide unit fused with 1,10-diaza-18-crown-6 and 6,6‧-dicarboxy-2,2‧-bipyridine forms luminescent mononuclear and binuclear europium(III) complexes, respectively, that are stable in water solution. The presence of interfering ions, such as phosphate and Ca(II), caused a slight increase in the quantum yield of Eu(III) emission in the case of bicyclic ligand, and some loss of luminescence efficiency in the case of acyclic Eu(III) complex upon UV irradiation. This feature makes the bicyclic complex very attractive for practical applications in time-resolved fluorimetric immunoassays.

  3. Recurrent uric acid stones.

    PubMed

    Kamel, K S; Cheema-Dhadli, S; Shafiee, M A; Davids, M R; Halperin, M L

    2005-01-01

    A 46-year-old female had a history of recurrent uric acid stone formation, but the reason why uric acid precipitated in her urine was not obvious, because the rate of urate excretion was not high, urine volume was not low, and the pH in her 24-h urine was not low enough. In his discussion of the case, Professor McCance provided new insights into the pathophysiology of uric acid stone formation. He illustrated that measuring the pH in a 24-h urine might obscure the fact that the urine pH was low enough to cause uric acid to precipitate during most of the day. Because he found a low rate of excretion of NH(4)(+) relative to that of sulphate anions, as well as a high rate of citrate excretion, he speculated that the low urine pH would be due to a more alkaline pH in proximal convoluted tubule cells. He went on to suspect that there was a problem in our understanding of the function of renal medullary NH(3) shunt pathway, and he suggested that its major function might be to ensure a urine pH close to 6.0 throughout the day, to minimize the likelihood of forming uric acid kidney stones.

  4. Hydrogen production by fermentation using acetic acid and lactic acid.

    PubMed

    Matsumoto, Mitsufumi; Nishimura, Yasuhiko

    2007-03-01

    Microbial hydrogen production from sho-chu post-distillation slurry solution (slurry solution) containing large amounts of organic acids was investigated. The highest hydrogen producer, Clostridium diolis JPCC H-3, was isolated from natural environment and produced hydrogen at 6.03+/-0.15 ml from 5 ml slurry solution in 30 h. Interestingly, the concentration of acetic acid and lactic acid in the slurry solution decreased during hydrogen production. The substrates for hydrogen production by C. diolis JPCC H-3, in particular organic acids, were investigated in an artificial medium. No hydrogen was produced from acetic acid, propionic acid, succinic acid, or citric acid on their own. Hydrogen and butyric acid were produced from a mixture of acetic acid and lactic acid, showing that C. diolis. JPCC H-3 could produce hydrogen from acetic acid and lactic acid. Furthermore, calculation of the Gibbs free energy strongly suggests that this reaction would proceed. In this paper, we describe for the first time microbial hydrogen production from acetic acid and lactic acid by fermentation.

  5. A Demonstration of Acid Rain

    ERIC Educational Resources Information Center

    Fong, Man Wai

    2004-01-01

    A demonstration showing acid rain formation is described. Oxides of sulfur and nitrogen that result from the burning of fossil fuels are the major pollutants of acid rain. In this demonstration, SO[subscript 2] gas is produced by the burning of matches. An acid-base indicator will show that the dissolved gas turns an aqueous solution acidic.

  6. Kinetic and thermodynamic origins of osmolyte-influenced nucleic acid folding.

    PubMed

    Holmstrom, Erik D; Dupuis, Nicholas F; Nesbitt, David J

    2015-03-05

    The influential role of monovalent and divalent metal cations in facilitating conformational transitions in both RNA and DNA has been a target of intense biophysical research efforts. However, organic neutrally charged cosolutes can also significantly alter nucleic acid conformational transitions. For example, highly soluble small molecules such as trimethylamine N-oxide (TMAO) and urea are occasionally utilized by organisms to regulate cellular osmotic pressure. Ensemble studies have revealed that these so-called osmolytes can substantially influence the thermodynamics of nucleic acid conformational transitions. In the present work, we exploit single-molecule FRET (smFRET) techniques to measure, for first time, the kinetic origins of these osmolyte-induced changes to the folding free energy. In particular, we focus on smFRET RNA and DNA constructs designed as model systems for secondary and tertiary structure formation. These findings reveal that TMAO preferentially stabilizes both secondary and tertiary interactions by increasing kfold and decreasing kunfold, whereas urea destabilizes both conformational transitions, resulting in the exact opposite shift in kinetic rate constants (i.e., decreasing kfold and increasing kunfold). Complementary temperature-dependent smFRET experiments highlight a thermodynamic distinction between the two different mechanisms responsible for TMAO-facilitated conformational transitions, while only a single mechanism is seen for the destabilizing osmolyte urea. Finally, these results are interpreted in the context of preferential interactions between osmolytes, and the solvent accessible surface area (SASA) associated with the (i) nucleobase, (ii) sugar, and (iii) phosphate groups of nucleic acids in order to map out structural changes that occur during the conformational transitions.

  7. Biodegradation of Cyanuric Acid

    PubMed Central

    Saldick, Jerome

    1974-01-01

    Cyanuric acid biodegrades readily under a wide variety of natural conditions, and particularly well in systems of either low or zero dissolved-oxygen level, such as anaerobic activated sludge and sewage, soils, muds, and muddy streams and river waters, as well as ordinary aerated activated sludge systems with typically low (1 to 3 ppm) dissolved-oxygen levels. Degradation also proceeds in 3.5% sodium chloride solution. Consequently, there are degradation pathways widely available for breaking down cyanuric acid discharged in domestic effluents. The overall degradation reaction is merely a hydrolysis; CO2 and ammonia are the initial hydrolytic breakdown products. Since no net oxidation occurs during this breakdown, biodegradation of cyanuric acid exerts no primary biological oxygen demand. However, eventual nitrification of the ammonia released will exert its usual biological oxygen demand. PMID:4451360

  8. [Aristolochic acid nephropathy].

    PubMed

    Witkowicz, Joanna

    2009-01-01

    Aristolochic acid nephropathy is a chronic, fibrosing, interstitial nephritis caused by aristolochic acid (AA), which is a component of the plants of Aristolochiacae family. It was first reported in 1993, in Belgium as a Chinese herb nephropathy, in patients who received a slimming regimen containing AA. The term aristolochic acid nephropathy also includes Balcan endemic nephropathy and other endemic tubulointerstitial fibrosis. Moreover, AA is a human carcinogen which induces urothelial cancer. The AA-containing herbs are banned in many countries and FDA published the warnings concerning the safety of AA-containing botanical remedies in 2000. Regarding the increasing interest in herbal medicines, uncontrolled access to botanical remedies and replacement of one herb by another AA-containing compounds makes thousands of people all around the world at risk of this grave disease.

  9. Calorimetry of Nucleic Acids.

    PubMed

    Rozners, Eriks; Pilch, Daniel S; Egli, Martin

    2015-12-01

    This unit describes the application of calorimetry to characterize the thermodynamics of nucleic acids, specifically, the two major calorimetric methodologies that are currently employed: differential scanning (DSC) and isothermal titration calorimetry (ITC). DSC is used to study thermally induced order-disorder transitions in nucleic acids. A DSC instrument measures, as a function of temperature (T), the excess heat capacity (C(p)(ex)) of a nucleic acid solution relative to the same amount of buffer solution. From a single curve of C(p)(ex) versus T, one can derive the following information: the transition enthalpy (ΔH), entropy (ΔS), free energy (ΔG), and heat capacity (ΔCp); the state of the transition (two-state versus multistate); and the average size of the molecule that melts as a single thermodynamic entity (e.g., the duplex). ITC is used to study the hybridization of nucleic acid molecules at constant temperature. In an ITC experiment, small aliquots of a titrant nucleic acid solution (strand 1) are added to an analyte nucleic acid solution (strand 2), and the released heat is monitored. ITC yields the stoichiometry of the association reaction (n), the enthalpy of association (ΔH), the equilibrium association constant (K), and thus the free energy of association (ΔG). Once ΔH and ΔG are known, ΔS can also be derived. Repetition of the ITC experiment at a number of different temperatures yields the ΔCp for the association reaction from the temperature dependence of ΔH.

  10. Acid rain in Asia

    NASA Astrophysics Data System (ADS)

    Bhatti, Neeloo; Streets, David G.; Foell, Wesley K.

    1992-07-01

    Acid rain has been an issue of great concern in North America and Europe during the past several decades. However, due to the passage of a number of recent regulations, most notably the Clean Air Act in the United States in 1990, there is an emerging perception that the problem in these Western nations is nearing solution. The situation in the developing world, particularly in Asia, is much bleaker. Given the policies of many Asian nations to achieve levels of development comparable with the industrialized world—which necessitate a significant expansion of energy consumption (most derived from indigenous coal reserves)—the potential for the formation of, and damage from, acid deposition in these developing countries is very high. This article delineates and assesses the emissions patterns, meteorology, physical geology, and biological and cultural resources present in various Asian nations. Based on this analysis and the risk factors to acidification, it is concluded that a number of areas in Asia are currently vulnerable to acid rain. These regions include Japan, North and South Korea, southern China, and the mountainous portions of Southeast Asia and southwestern India. Furthermore, with accelerated development (and its attendant increase in energy use and production of emissions of acid deposition precursors) in many nations of Asia, it is likely that other regions will also be affected by acidification in the near future. Based on the results of this overview, it is clear that acid deposition has significant potential to impact the Asian region. However, empirical evidence is urgently needed to confirm this and to provide early warning of increases in the magnitude and spread of acid deposition and its effects throughout this part of the world.

  11. Ethylenediaminetetraacetic acid in endodontics.

    PubMed

    Mohammadi, Zahed; Shalavi, Sousan; Jafarzadeh, Hamid

    2013-09-01

    Ethylenediaminetetraacetic acid (EDTA) is a chelating agent can bind to metals via four carboxylate and two amine groups. It is a polyamino carboxylic acid and a colorless, water-soluble solid, which is widely used to dissolve lime scale. It is produced as several salts, notably disodium EDTA and calcium disodium EDTA. EDTA reacts with the calcium ions in dentine and forms soluble calcium chelates. A review of the literature and a discussion of the different indications and considerations for its usage are presented.

  12. Ethylenediaminetetraacetic acid in endodontics

    PubMed Central

    Mohammadi, Zahed; Shalavi, Sousan; Jafarzadeh, Hamid

    2013-01-01

    Ethylenediaminetetraacetic acid (EDTA) is a chelating agent can bind to metals via four carboxylate and two amine groups. It is a polyamino carboxylic acid and a colorless, water-soluble solid, which is widely used to dissolve lime scale. It is produced as several salts, notably disodium EDTA and calcium disodium EDTA. EDTA reacts with the calcium ions in dentine and forms soluble calcium chelates. A review of the literature and a discussion of the different indications and considerations for its usage are presented. PMID:24966721

  13. The Acid-Base Titration of a Very Weak Acid: Boric Acid

    ERIC Educational Resources Information Center

    Celeste, M.; Azevedo, C.; Cavaleiro, Ana M. V.

    2012-01-01

    A laboratory experiment based on the titration of boric acid with strong base in the presence of d-mannitol is described. Boric acid is a very weak acid and direct titration with NaOH is not possible. An auxiliary reagent that contributes to the release of protons in a known stoichiometry facilitates the acid-base titration. Students obtain the…

  14. Comparison of Buffer Effect of Different Acids During Sandstone Acidizing

    NASA Astrophysics Data System (ADS)

    Umer Shafiq, Mian; Khaled Ben Mahmud, Hisham; Hamid, Mohamed Ali

    2015-04-01

    The most important concern of sandstone matrix acidizing is to increase the formation permeability by removing the silica particles. To accomplish this, the mud acid (HF: HCl) has been utilized successfully for many years to stimulate the sandstone formations, but still it has many complexities. This paper presents the results of laboratory investigations of different acid combinations (HF: HCl, HF: H3PO4 and HF: HCOOH). Hydrofluoric acid and fluoboric acid are used to dissolve clays and feldspar. Phosphoric and formic acids are added as a buffer to maintain the pH of the solution; also it allows the maximum penetration of acid into the core sample. Different tests have been performed on the core samples before and after the acidizing to do the comparative study on the buffer effect of these acids. The analysis consists of permeability, porosity, color change and pH value tests. There is more increase in permeability and porosity while less change in pH when phosphoric and formic acids were used compared to mud acid. From these results it has been found that the buffer effect of phosphoric acid and formic acid is better than hydrochloric acid.

  15. Oxalic acid excretion after intravenous ascorbic acid administration.

    PubMed

    Robitaille, Line; Mamer, Orval A; Miller, Wilson H; Levine, Mark; Assouline, Sarit; Melnychuk, David; Rousseau, Caroline; Hoffer, L John

    2009-02-01

    Ascorbic acid is frequently administered intravenously by alternative health practitioners and, occasionally, by mainstream physicians. Intravenous administration can greatly increase the amount of ascorbic acid that reaches the circulation, potentially increasing the risk of oxalate crystallization in the urinary space. To investigate this possibility, we developed gas chromatography mass spectrometry methodology and sampling and storage procedures for oxalic acid analysis without interference from ascorbic acid and measured urinary oxalic acid excretion in people administered intravenous ascorbic acid in doses ranging from 0.2 to 1.5 g/kg body weight. In vitro oxidation of ascorbic acid to oxalic acid did not occur when urine samples were brought immediately to pH less than 2 and stored at -30 degrees C within 6 hours. Even very high ascorbic acid concentrations did not interfere with the analysis when oxalic acid extraction was carried out at pH 1. As measured during and over the 6 hours after ascorbic acid infusions, urinary oxalic acid excretion increased with increasing doses, reaching approximately 80 mg at a dose of approximately 100 g. We conclude that, when studied using correct procedures for sample handling, storage, and analysis, less than 0.5% of a very large intravenous dose of ascorbic acid is recovered as urinary oxalic acid in people with normal renal function.

  16. Chromate enhanced visible light driven TiO₂ photocatalytic mechanism on Acid Orange 7 photodegradation.

    PubMed

    Wang, Yeoung-Sheng; Shen, Jyun-Hong; Horng, Jao-Jia

    2014-06-15

    When hexavalent chromium (Cr(VI)) is added to a TiO2 photocatalytic reaction, the decolorization and mineralization efficiencies of azo dyes Acid Orange 7 (AO7) are enhanced even though the mechanism is unclear. This study used 5,5-dimethyl-l-pyrroline-N-oxide (DMPO) as the scavenger and the analysis of Electron Spin Resonance (ESR) to investigate this enhancement effect by observing the hydroxyl radical (OH) generation of the Cr(VI)/TiO2 system under UV and visible light (Vis) irradiation. With Cr(VI), the decolorization efficiencies were approximately 95% and 62% under UV and Vis, and those efficiencies were 25% less in the absence of Cr(VI). The phenomena of the DMPO-OH signals during the ESR analysis under Vis 405 and 550 nm irradiation were obviously the enhancement effects of Cr(VI) in aerobic conditions. In anoxic conditions, the catalytic effects of Cr(VI) could not be achieved due to the lack of a redox reaction between Cr(VI) and the adsorbed oxygen at the oxygen vacancy sites on the TiO2 surfaces. The results suggest that by introducing the agents of redox reactions such as chromate ions, we could lower the photoenergy of TiO2 needed and allow Vis irradiation to activate photocatalysis.

  17. [Studies on interaction of acid-treated nanotube titanic acid and amino acids].

    PubMed

    Zhang, Huqin; Chen, Xuemei; Jin, Zhensheng; Liao, Guangxi; Wu, Xiaoming; Du, Jianqiang; Cao, Xiang

    2010-06-01

    Nanotube titanic acid (NTA) has distinct optical and electrical character, and has photocatalysis character. In accordance with these qualities, NTA was treated with acid so as to enhance its surface activity. Surface structures and surface groups of acid-treated NTA were characterized and analyzed by Transmission Electron Microscope (TEM) and Fourier Transform Infrared Spectrometry (FT-IR). The interaction between acid-treated NTA and amino acids was investigated. Analysis results showed that the lengths of acid-treated NTA became obviously shorter. The diameters of nanotube bundles did not change obviously with acid-treating. Meanwhile, the surface of acid-treated NTA was cross-linked with carboxyl or esterfunction. In addition, acid-treated NTA can catch amino acid residues easily, and then form close combination.

  18. Alkyl phosphonic acids and sulfonic acids in the Murchison meteorite

    NASA Technical Reports Server (NTRS)

    Cooper, George W.; Onwo, Wilfred M.; Cronin, John R.

    1992-01-01

    Homologous series of alkyl phosphonic acids and alkyl sulfonic acids, along with inorganic orthophosphate and sulfate, are identified in water extracts of the Murchison meteorite after conversion to their t-butyl dimethylsilyl derivatives. The methyl, ethyl, propyl, and butyl compounds are observed in both series. Five of the eight possible alkyl phosphonic acids and seven of the eight possible alkyl sulfonic acids through C4 are identified. Abundances decrease with increasing carbon number as observed of other homologous series indigenous to Murchison. Concentrations range downward from approximately 380 nmol/gram in the alkyl sulfonic acid series, and from 9 nmol/gram in the alkyl phosphonic acid series.

  19. Effect of domoic acid on brain amino acid levels.

    PubMed

    Durán, R; Arufe, M C; Arias, B; Alfonso, M

    1995-03-01

    The administration of Domoic Acid (Dom) in a 0.2 mg/kg i.p. dose induces changes in the levels of amino acids of neurochemical interest (Asp, Glu, Gly, Tau, Ala, GABA) in different rat brain regions (hypothalamus, hippocampus, amygdala, striatum, cortex and midbrain). The most affected amino acid is the GABA, the main inhibitory amino acid neurotransmitter, whereas glutamate, the main excitatory amino acid, is not affected. The rat brain regions that seem to be the main target of the Dom action belong to the limbic system (hippocampus, amygdala). The possible implication of the amino acids in the actions of Dom is also discussed.

  20. Hydrofluoric acid poisoning

    MedlinePlus

    Chemical Emergencies: Case Definition: Hydrofluoric Acid . Centers for Disease Control and Prevention, U.S. Dept of Health and Human Services; 2005. Goldfrank LR, ed. Goldfrank's Toxicologic Emergencies . 8th ed. New York, NY: McGraw Hill; 2006. Wax PM, Young A. ...

  1. Plant fatty acid hydroxylase

    DOEpatents

    Somerville, Chris; van de Loo, Frank

    2000-01-01

    The present invention relates to the identification of nucleic acid sequences and constructs, and methods related thereto, and the use of these sequences and constructs to produce genetically modified plants for the purpose of altering the composition of plant oils, waxes and related compounds.

  2. The Acid Rain Debate.

    ERIC Educational Resources Information Center

    Oates-Bockenstedt, Catherine

    1997-01-01

    Details an activity designed to motivate students by incorporating science-related issues into a classroom debate. Includes "The Acid Rain Bill" and "Position Guides" for student roles as committee members, consumers, governors, industry owners, tourism professionals, senators, and debate directors. (DKM)

  3. Acid Rain Investigations.

    ERIC Educational Resources Information Center

    Hugo, John C.

    1992-01-01

    Presents an activity in which students investigate the formation of solid ammonium chloride aerosol particles to help students better understand the concept of acid rain. Provides activity objectives, procedures, sample data, clean-up instructions, and questions and answers to help interpret the data. (MDH)

  4. The Acid Rain Game.

    ERIC Educational Resources Information Center

    Rakow, Steven J.; Glenn, Allen

    1982-01-01

    Provides rationale for and description of an acid rain game (designed for two players), a problem-solving model for elementary students. Although complete instructions are provided, including a copy of the game board, the game is also available for Apple II microcomputers. Information for the computer program is available from the author.…

  5. Acid Rain Classroom Projects.

    ERIC Educational Resources Information Center

    Demchik, Michael J.

    2000-01-01

    Describes a curriculum plan in which students learn about acid rain through instructional media, research and class presentations, lab activities, simulations, design, and design implementation. Describes the simulation activity in detail and includes materials, procedures, instructions, examples, results, and discussion sections. (SAH)

  6. The Acid Rain Debate.

    ERIC Educational Resources Information Center

    Bybee, Rodger; And Others

    1984-01-01

    Describes an activity which provides opportunities for role-playing as industrialists, ecologists, and government officials. The activity involves forming an international commission on acid rain, taking testimony, and, based on the testimony, making recommendations to governments on specific ways to solve the problem. Includes suggestions for…

  7. Acid rain bibliography

    SciTech Connect

    Sayers, C.S.

    1983-09-01

    This bibliography identifies 900 citations on various aspects of Acid Rain, covering published bibliographies, books, reports, conference and symposium proceedings, audio visual materials, pamphlets and newsletters. It includes five sections: citations index (complete record of author, title, source, order number); KWIC index; title index; author index; and source index. 900 references.

  8. Docosahexaenoic acid and lactation

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Docosahexaenoic acid (DHA) is an important component of membrane phospholipids in the retina, and brain, and accumulates rapidly in these tissues during early infancy. DHA is present in human milk, but the amount varies considerably and is largely dependent on maternal diet. This article reviews dat...

  9. Spermatotoxicity of dichloroacetic acid

    EPA Science Inventory

    The testicular toxicity of dichloroacetic acid (DCA), a disinfection byproduct of drinking water, was evaluated in adult male rats given both single and multiple (up to 14 d) oral doses. Delayed spermiation and altered resorption of residual bodies were observed in rats given sin...

  10. Water surface is acidic

    PubMed Central

    Buch, Victoria; Milet, Anne; Vácha, Robert; Jungwirth, Pavel; Devlin, J. Paul

    2007-01-01

    Water autoionization reaction 2H2O → H3O− + OH− is a textbook process of basic importance, resulting in pH = 7 for pure water. However, pH of pure water surface is shown to be significantly lower, the reduction being caused by proton stabilization at the surface. The evidence presented here includes ab initio and classical molecular dynamics simulations of water slabs with solvated H3O+ and OH− ions, density functional studies of (H2O)48H+ clusters, and spectroscopic isotopic-exchange data for D2O substitutional impurities at the surface and in the interior of ice nanocrystals. Because H3O+ does, but OH− does not, display preference for surface sites, the H2O surface is predicted to be acidic with pH < 4.8. For similar reasons, the strength of some weak acids, such as carbonic acid, is expected to increase at the surface. Enhanced surface acidity can have a significant impact on aqueous surface chemistry, e.g., in the atmosphere. PMID:17452650

  11. Acid rain sourcebook

    SciTech Connect

    Elliott, T.C.; Schwieger, R.G.

    1984-01-01

    Discusses the problem of acid rain and how it can be controlled. The book is divided into seven key sections: the problem and the legislative solutions; international mitigation programs; planning the US program; emissions reduction-before combustion; emissions/reduction-during combustion; emissions reduction-after combustion and engineering solutions under development. 13 papers have been abstracted separately.

  12. The acid rain sourcebook

    SciTech Connect

    Elliott, T.C.; Schwieger, R.G.

    1985-01-01

    A reference collection of specialized information discussions on areas critical to the acid rain issue: problem definition, impact of legislation, emissions standards, international perspective, cost scenarios, and engineering solutions. The text is reinforced with 130 illustrations and about 50 tables. Contents: International mitigation programs. Emissions reduction: before combustion; during combustion; after combustion. Engineering solutions under development.

  13. A Direct, Biomass-Based Synthesis of Benzoic Acid: Formic Acid-Mediated Deoxygenation of the Glucose-Derived Materials Quinic Acid and Shikimic Acid

    SciTech Connect

    Arceo, Elena; Ellman, Jonathan; Bergman, Robert

    2010-05-03

    An alternative biomass-based route to benzoic acid from the renewable starting materials quinic acid and shikimic acid is described. Benzoic acid is obtained selectively using a highly efficient, one-step formic acid-mediated deoxygenation method.

  14. Synthesis of acid addition salt of delta-aminolevulinic acid from 5-bromo levulinic acid esters

    DOEpatents

    Moens, Luc

    2003-06-24

    A process of preparing an acid addition salt of delta-aminolevulinc acid comprising: a) dissolving a lower alkyl 5-bromolevulinate and hexamethylenetetramine in a solvent selected from the group consisting of water, ethyl acetate, chloroform, acetone, ethanol, tetrahydrofuran and acetonitrile, to form a quaternary ammonium salt of the lower alkyl 5-bromolevulinate; and b) hydrolyzing the quaternary ammonium salt with an inorganic acid to form an acid addition salt of delta-aminolevulinic acid.

  15. Control of adhesion force between ceria particles and polishing pad in shallow trench isolation chemical mechanical planarization.

    PubMed

    Seo, Jihoon; Moon, Jinok; Bae, Jae-Young; Yoon, Kwang Seob; Sigmund, Wolfgang; Paik, Ungyu

    2014-06-01

    The adhesion force between ceria and polyurethane (PU) pad was controlled to remove the step height from cell region to peripheral region during Shallow Trench Isolation Chemical Mechanical Planarization (STI-CMP) for NAND flash. Picolinic acid was found to be adsorbed on ceria particles at pH 4.5 following a Langmuir isotherm with the maximum adsorbed amount of 0.36 mg/m2. The ceria suspension with full surface coverage of picolinic acid showed a threefold increase in the number of adhered ceria particles on the PU pad over non-coated ceria particles. It was shown that the coverage percent of picolinic acid on ceria corresponds well with the amount percent of adsorbed ceria on PU pad. The change in adsorbed particles was directly reflected in the CMP polishing process where significant improvements were achieved. Particularly, convex areas on the chip experienced higher friction force from the attached abrasives on the PU pad than concave areas. As a result, the convex areas have increased removal rate of step height compared to the ceria suspension without picolinic acid. The changing profiles of convex areas are reported during the step height reduction as a function of polishing time.

  16. Cu-catalyzed arylation of phenols: synthesis of sterically hindered and heteroaryl diaryl ethers.

    PubMed

    Maiti, Debabrata; Buchwald, Stephen L

    2010-03-05

    Cu-catalyzed O-arylation of phenols with aryl iodides and bromides can be performed under mild condition in DMSO/K(3)PO(4) with use of picolinic acid as the ligand for copper. This method tolerates a variety of functional groups and is effective in the synthesis of hindered diaryl ethers and heteroaryl ethers.

  17. Photostabilization of ascorbic acid with citric acid, tartaric acid and boric acid in cream formulations.

    PubMed

    Ahmad, I; Ali Sheraz, M; Ahmed, S; Shad, Z; Vaid, F H M

    2012-06-01

    This study involves the evaluation of the effect of certain stabilizers, that is, citric acid (CT), tartaric acid (TA) and boric acid (BA) on the degradation of ascorbic acid (AH(2) ) in oil-in-water cream formulations exposed to the UV light and stored in the dark. The apparent first-order rate constants (0.34-0.95 × 10(-3) min(-1) in light, 0.38-1.24 × 10(-2) day(-1) in dark) for the degradation reactions in the presence of the stabilizers have been determined. These rate constants have been used to derive the second-order rate constants (0.26-1.45 × 10(-2) M(-1) min(-1) in light, 3.75-8.50 × 10(-3) M(-1) day(-1) in dark) for the interaction of AH(2) and the individual stabilizers. These stabilizers are effective in causing the inhibition of the rate of degradation of AH(2) both in the light and in the dark. The inhibitory effect of the stabilizers is in the order of CT > TA > BA. The rate of degradation of AH(2) in the presence of these stabilizers in the light is about 120 times higher than that in the dark. This could be explained on the basis of the deactivation of AH(2) -excited triplet state by CT and TA and by the inhibition of AH(2) degradation through complex formation with BA. AH(2) leads to the formation of dehydroascorbic acid (A) by chemical and photooxidation in cream formulations.

  18. Specific bile acids inhibit hepatic fatty acid uptake

    PubMed Central

    Nie, Biao; Park, Hyo Min; Kazantzis, Melissa; Lin, Min; Henkin, Amy; Ng, Stephanie; Song, Sujin; Chen, Yuli; Tran, Heather; Lai, Robin; Her, Chris; Maher, Jacquelyn J.; Forman, Barry M.; Stahl, Andreas

    2012-01-01

    Bile acids are known to play important roles as detergents in the absorption of hydrophobic nutrients and as signaling molecules in the regulation of metabolism. Here we tested the novel hypothesis that naturally occurring bile acids interfere with protein-mediated hepatic long chain free fatty acid (LCFA) uptake. To this end stable cell lines expressing fatty acid transporters as well as primary hepatocytes from mouse and human livers were incubated with primary and secondary bile acids to determine their effects on LCFA uptake rates. We identified ursodeoxycholic acid (UDCA) and deoxycholic acid (DCA) as the two most potent inhibitors of the liver-specific fatty acid transport protein 5 (FATP5). Both UDCA and DCA were able to inhibit LCFA uptake by primary hepatocytes in a FATP5-dependent manner. Subsequently, mice were treated with these secondary bile acids in vivo to assess their ability to inhibit diet-induced hepatic triglyceride accumulation. Administration of DCA in vivo via injection or as part of a high-fat diet significantly inhibited hepatic fatty acid uptake and reduced liver triglycerides by more than 50%. In summary, the data demonstrate a novel role for specific bile acids, and the secondary bile acid DCA in particular, in the regulation of hepatic LCFA uptake. The results illuminate a previously unappreciated means by which specific bile acids, such as UDCA and DCA, can impact hepatic triglyceride metabolism and may lead to novel approaches to combat obesity-associated fatty liver disease. PMID:22531947

  19. N{sub 2}O production pathways in the subtropical acid forest soils in China

    SciTech Connect

    Zhang Jinbo; Cai Zucong; Zhu Tongbin

    2011-07-15

    To date, N{sub 2}O production pathways are poorly understood in the humid subtropical and tropical forest soils. A {sup 15}N-tracing experiment was carried out under controlled laboratory conditions to investigate the processes responsible for N{sub 2}O production in four subtropical acid forest soils (pH<4.5) in China. The results showed that denitrification was the main source of N{sub 2}O emission in the subtropical acid forest soils, being responsible for 56.1%, 53.5%, 54.4%, and 55.2% of N{sub 2}O production, in the GC, GS, GB, and TC soils, respectively, under aerobic conditions (40%-52%WFPS). The heterotrophic nitrification (recalcitrant organic N oxidation) accounted for 27.3%-41.8% of N{sub 2}O production, while the contribution of autotrophic nitrification was little in the studied subtropical acid forest soils. The ratios of N{sub 2}O-N emission from total nitrification (heterotrophic+autotrophic nitrification) were higher than those in most previous references. The soil with the lowest pH and highest organic-C content (GB) had the highest ratio (1.63%), suggesting that soil pH-organic matter interactions may exist and affect N{sub 2}O product ratios from nitrification. The ratio of N{sub 2}O-N emission from heterotrophic nitrification varied from 0.02% to 25.4% due to soil pH and organic matter. Results are valuable in the accurate modeling of N2O production in the subtropical acid forest soils and global budget. - Highlights: {yields} We studied N{sub 2}O production pathways in subtropical acid forest soil under aerobic conditions. {yields} Denitrification was the main source of N{sub 2}O production in subtropical acid forest soils. {yields} Heterotrophic nitrification accounted for 27.3%-41.8% of N{sub 2}O production. {yields} While, contribution of autotrophic nitrification to N{sub 2}O production was little. {yields} Ratios of N{sub 2}O-N emission from nitrification were higher than those in most previous references.

  20. Acid diffusion through polyaniline membranes

    SciTech Connect

    Su, T.M.; Huang, S.C.; Conklin, J.A.

    1995-12-01

    Polyaniline membranes in the undoped (base) and doped (acid) forms are studied for their utility as pervaporation membranes. The separation of water from mixtures of propionic acid, acetic acid and formic acid have been demonstrated from various feed compositions. Doped polyaniline displays an enhanced selectivity of water over these organic acids as compared with undoped polyaniline. For as-cast polyaniline membranes a diffusion coefficient (D) on the order of 10{sup -9} cm{sup 2}/sec has been determined for the flux of protons through the membranes using hydrochloric acid.

  1. Fatty acid-producing hosts

    DOEpatents

    Pfleger, Brian F; Lennen, Rebecca M

    2013-12-31

    Described are hosts for overproducing a fatty acid product such as a fatty acid. The hosts include an exogenous nucleic acid encoding a thioesterase and, optionally, an exogenous nucleic acid encoding an acetyl-CoA carboxylase, wherein an acyl-CoA synthetase in the hosts are functionally delected. The hosts prefereably include the nucleic acid encoding the thioesterase at an intermediate copy number. The hosts are preferably recominantly stable and growth-competent at 37.degree. C. Methods of producing a fatty acid product comprising culturing such hosts at 37.degree. C. are also described.

  2. Radioenzymatic assay for quinolinic acid

    SciTech Connect

    Foster, A.C.; Okuno, E.; Brougher, D.S.; Schwarcz, R.

    1986-10-01

    A new and rapid method for the determination of the excitotoxic tryptophan metabolite quinolinic acid is based on its enzymatic conversion to nicotinic acid mononucleotide and, in a second step utilizing (/sup 3/H)ATP, further to (/sup 3/H) deamido-NAD. Specificity of the assay is assured by using a highly purified preparation of the specific quinolinic acid-catabolizing enzyme, quinolinic acid phosphoribosyltransferase, in the initial step. The limit of sensitivity was found to be 2.5 pmol of quinolinic acid, sufficient to conveniently determine quinolinic acid levels in small volumes of human urine and blood plasma.

  3. Progress in engineering acid stress resistance of lactic acid bacteria.

    PubMed

    Wu, Chongde; Huang, Jun; Zhou, Rongqing

    2014-02-01

    Lactic acid bacteria (LAB) are widely used for the production of a variety of fermented foods, and are considered as probiotic due to their health-promoting effect. However, LAB encounter various environmental stresses both in industrial fermentation and application, among which acid stress is one of the most important survival challenges. Improving the acid stress resistance may contribute to the application and function of probiotic action to the host. Recently, the advent of genomics, functional genomics and high-throughput technologies have allowed for the understanding of acid tolerance mechanisms at a systems level, and many method to improve acid tolerance have been developed. This review describes the current progress in engineering acid stress resistance of LAB. Special emphasis is placed on engineering cellular microenvironment (engineering amino acid metabolism, introduction of exogenous biosynthetic capacity, and overproduction of stress response proteins) and maintaining cell membrane functionality. Moreover, strategies to improve acid tolerance and the related physiological mechanisms are also discussed.

  4. Effect of phenolic acids on glucose and organic acid metabolism by lactic acid bacteria from wine.

    PubMed

    Campos, Francisco M; Figueiredo, Ana R; Hogg, Tim A; Couto, José A

    2009-06-01

    The influence of phenolic (p-coumaric, caffeic, ferulic, gallic and protocatechuic) acids on glucose and organic acid metabolism by two strains of wine lactic acid bacteria (Oenococcus oeni VF and Lactobacillus hilgardii 5) was investigated. Cultures were grown in modified MRS medium supplemented with different phenolic acids. Cellular growth was monitored and metabolite concentrations were determined by HPLC-RI. Despite the strong inhibitory effect of most tested phenolic acids on the growth of O. oeni VF, the malolactic activity of this strain was not considerably affected by these compounds. While less affected in its growth, the capacity of L. hilgardii 5 to degrade malic acid was clearly diminished. Except for gallic acid, the addition of phenolic acids delayed the metabolism of glucose and citric acid in both strains tested. It was also found that the presence of hydroxycinnamic acids (p-coumaric, caffeic and ferulic) increased the yield of lactic and acetic acid production from glucose by O. oeni VF and not by L. hilgardii 5. The results show that important oenological characteristics of wine lactic acid bacteria, such as the malolactic activity and the production of volatile organic acids, may be differently affected by the presence of phenolic acids, depending on the bacterial species or strain.

  5. NAPAP (National Acid Precipitation Assessment Program) results on acid rain

    SciTech Connect

    Not Available

    1990-06-01

    The National Acid Precipitation Assessment Program (NAPAP) was mandated by Congress in 1980 to study the effects of acid rain. The results of 10 years of research on the effect of acid deposition and ozone on forests, particularly high elevation spruce and fir, southern pines, eastern hardwoods and western conifers, will be published this year.

  6. Acid Earth--The Global Threat of Acid Pollution.

    ERIC Educational Resources Information Center

    McCormick, John

    Acid pollution is a major international problem, but the debate it has elicited has often clouded the distinction between myth and facts. This publication attempts to concerning the acid pollution situation. This publication attempts to identify available facts. It is the first global review of the problem of acid pollution and the first to…

  7. Boric/sulfuric acid anodize - Alternative to chromic acid anodize

    NASA Astrophysics Data System (ADS)

    Koop, Rodney; Moji, Yukimori

    1992-04-01

    The suitability of boric acid/sulfuric acid anodizing (BSAA) solution as a more environmentally acceptable replacement of the chromic acid anodizing (CAA) solution was investigated. Results include data on the BSAA process optimization, the corrosion protection performance, and the compatibility with aircraft finishing. It is shown that the BSSA implementation as a substitude for CAA was successful.

  8. Circulating folic acid in plasma: relation to folic acid fortification

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The implementation of folic acid fortification in the United States has resulted in unprecedented amounts of this synthetic form of folate in the American diet. Folic acid in circulation may be a useful measure of physiologic exposure to synthetic folic acid, and there is a potential for elevated co...

  9. College Chemistry Students' Mental Models of Acids and Acid Strength

    ERIC Educational Resources Information Center

    McClary, LaKeisha; Talanquer, Vicente

    2011-01-01

    The central goal of this study was to characterize the mental models of acids and acid strength expressed by advanced college chemistry students when engaged in prediction, explanation, and justification tasks that asked them to rank chemical compounds based on their relative acid strength. For that purpose we completed a qualitative research…

  10. Eucomic acid methanol monosolvate

    PubMed Central

    Li, Guo-Qiang; Li, Yao-Lan; Wang, Guo-Cai; Liang, Zhi-Hong; Jiang, Ren-Wang

    2011-01-01

    In the crystal structure of the title compound [systematic name: 2-hy­droxy-2-(4-hy­droxy­benz­yl)butane­dioic acid methanol monosolvate], C11H12O6·CH3OH, the dihedral angles between the planes of the carboxyl groups and the benzene ring are 51.23 (9) and 87.97 (9)°. Inter­molecular O—H⋯O hydrogen-bonding inter­actions involving the hy­droxy and carb­oxy­lic acid groups and the methanol solvent mol­ecule give a three-dimensional structure. PMID:22091200

  11. Autohydrolysis of phytic acid.

    PubMed

    Hull, S R; Gray, J S; Montgomery, R

    1999-09-10

    The autohydrolysis of phytic acid at 120 degrees C resulted in the formation of most of the phosphate esters of myo-inositol in varying amounts depending upon the reaction time. Eighteen of the 39 chromatographically distinct myo-inositol mono-, bis-, tris-, tetrakis-, pentakis-, and hexakisphosphates have been characterized using two different HPLC systems. These myo-inositol phosphates were partially purified by preparative anion-exchange chromatography under acidic and alkaline elution conditions. The combination of these two methods provides a two-tiered chromatographic approach to the rapid and sensitive identification of inositol phosphates in complex mixtures. Identification of the products was confirmed by 1D and 2D (1)H NMR analysis. The analytical procedure was applied to the autohydrolysis of the mixture of inositol phosphates from corn steep water.

  12. Optimize acid gas removal

    SciTech Connect

    Nicholas, D.M.; Wilkins, J.T.

    1983-09-01

    Innovative design of physical solvent plants for acid gas removal can materially reduce both installation and operating costs. A review of the design considerations for one physical solvent process (Selexol) points to numerous arrangements for potential improvement. These are evaluated for a specific case in four combinations that identify an optimum for the case in question but, more importantly, illustrate the mechanism for use for such optimization elsewhere.

  13. Perfluorooctanoic acid and environmental risks

    EPA Science Inventory

    Perfluorooctanoic acid (PFOA) is a member of the perfluoroalkyl acids (PFAA) family of chemicals, which consist of a carbon backbone typically four to fourteen carbons in length and a charged functional moiety.

  14. Ideas about Acids and Alkalis.

    ERIC Educational Resources Information Center

    Toplis, Rob

    1998-01-01

    Investigates students' ideas, conceptions, and misconceptions about acids and alkalis before and after a teaching sequence in a small-scale research project. Concludes that student understanding of acids and alkalis is lacking. (DDR)

  15. Pantothenic acid (Vitamin B5)

    MedlinePlus

    Pantothenic acid is a vitamin, also known as vitamin B5. It is widely found in both plants and animals ... Vitamin B5 is commercially available as D-pantothenic acid, as well as dexpanthenol and calcium pantothenate, which ...

  16. Folic Acid Questions and Answers

    MedlinePlus

    ... Controls NCBDDD Cancel Submit Search The CDC Folic Acid Note: Javascript is disabled or is not supported ... please visit this page: About CDC.gov . Folic Acid Homepage Facts Quiz Frequently Asked Questions General Information ...

  17. Omega-3 fatty acids (image)

    MedlinePlus

    Omega-3 fatty acids are a form of polyunsaturated fat that the body derives from food. Omega-3s (and omega-6s) are known as essential fatty acids (EFAs) because they are important for good health. ...

  18. Immunomodulatory spherical nucleic acids.

    PubMed

    Radovic-Moreno, Aleksandar F; Chernyak, Natalia; Mader, Christopher C; Nallagatla, Subbarao; Kang, Richard S; Hao, Liangliang; Walker, David A; Halo, Tiffany L; Merkel, Timothy J; Rische, Clayton H; Anantatmula, Sagar; Burkhart, Merideth; Mirkin, Chad A; Gryaznov, Sergei M

    2015-03-31

    Immunomodulatory nucleic acids have extraordinary promise for treating disease, yet clinical progress has been limited by a lack of tools to safely increase activity in patients. Immunomodulatory nucleic acids act by agonizing or antagonizing endosomal toll-like receptors (TLR3, TLR7/8, and TLR9), proteins involved in innate immune signaling. Immunomodulatory spherical nucleic acids (SNAs) that stimulate (immunostimulatory, IS-SNA) or regulate (immunoregulatory, IR-SNA) immunity by engaging TLRs have been designed, synthesized, and characterized. Compared with free oligonucleotides, IS-SNAs exhibit up to 80-fold increases in potency, 700-fold higher antibody titers, 400-fold higher cellular responses to a model antigen, and improved treatment of mice with lymphomas. IR-SNAs exhibit up to eightfold increases in potency and 30% greater reduction in fibrosis score in mice with nonalcoholic steatohepatitis (NASH). Given the clinical potential of SNAs due to their potency, defined chemical nature, and good tolerability, SNAs are attractive new modalities for developing immunotherapies.

  19. Immunomodulatory spherical nucleic acids

    PubMed Central

    Radovic-Moreno, Aleksandar F.; Chernyak, Natalia; Mader, Christopher C.; Nallagatla, Subbarao; Kang, Richard S.; Hao, Liangliang; Walker, David A.; Halo, Tiffany L.; Merkel, Timothy J.; Rische, Clayton H.; Anantatmula, Sagar; Burkhart, Merideth; Mirkin, Chad A.; Gryaznov, Sergei M.

    2015-01-01

    Immunomodulatory nucleic acids have extraordinary promise for treating disease, yet clinical progress has been limited by a lack of tools to safely increase activity in patients. Immunomodulatory nucleic acids act by agonizing or antagonizing endosomal toll-like receptors (TLR3, TLR7/8, and TLR9), proteins involved in innate immune signaling. Immunomodulatory spherical nucleic acids (SNAs) that stimulate (immunostimulatory, IS-SNA) or regulate (immunoregulatory, IR-SNA) immunity by engaging TLRs have been designed, synthesized, and characterized. Compared with free oligonucleotides, IS-SNAs exhibit up to 80-fold increases in potency, 700-fold higher antibody titers, 400-fold higher cellular responses to a model antigen, and improved treatment of mice with lymphomas. IR-SNAs exhibit up to eightfold increases in potency and 30% greater reduction in fibrosis score in mice with nonalcoholic steatohepatitis (NASH). Given the clinical potential of SNAs due to their potency, defined chemical nature, and good tolerability, SNAs are attractive new modalities for developing immunotherapies. PMID:25775582

  20. Microbial naphthenic Acid degradation.

    PubMed

    Whitby, Corinne

    2010-01-01

    Naphthenic acids (NAs) are an important group of trace organic pollutants predominantly comprising saturated aliphatic and alicyclic carboxylic acids. NAs are ubiquitous; occurring naturally in hydrocarbon deposits (petroleum, oil sands, bitumen, and crude oils) and also have widespread industrial uses. Consequently, NAs can enter the environment from both natural and anthropogenic processes. NAs are highly toxic, recalcitrant compounds that persist in the environment for many years, and it is important to develop efficient bioremediation strategies to decrease both their abundance and toxicity in the environment. However, the diversity of microbial communities involved in NA-degradation, and the mechanisms by which NAs are biodegraded, are poorly understood. This lack of knowledge is mainly due to the difficulties in identifying and purifying individual carboxylic acid compounds from complex NA mixtures found in the environment, for microbial biodegradation studies. This paper will present an overview of NAs, their origin and fate in the environment, and their toxicity to the biota. The review describes the microbial degradation of both naturally occurring and chemically synthesized NAs. Proposed pathways for aerobic NA biodegradation, factors affecting NA biodegradation rates, and possible bioremediation strategies are also discussed.