Deuterium

Distribution by Scientific Domains
Distribution within Chemistry

Terms modified by Deuterium

  • deuterium content
  • deuterium enrichment
  • deuterium exchange
  • deuterium incorporation
  • deuterium isotope effect
  • deuterium isotope effects
  • deuterium labeling
  • deuterium labelling
  • deuterium oxide

  • Selected Abstracts


    10th international symposium on the synthesis and applications of isotopes and isotopically labelled compounds,Professor John R. Jones memorial lectures, Monday, June 15, 2009

    JOURNAL OF LABELLED COMPOUNDS AND RADIOPHARMACEUTICALS, Issue 5-6 2010
    David Hesk Session Chair
    Abstract The first Session of the Conference was dedicated to the memory of Professor John R. Jones. Labelling with Deuterium and Tritium was the common theme. William J.S. Lockley, Frank Tang and Shuiyu Lu gave presentations. Copyright © 2010 John Wiley & Sons, Ltd. [source]


    Insights into the mechanisms of flavoprotein oxidases from kinetic isotope effects,

    JOURNAL OF LABELLED COMPOUNDS AND RADIOPHARMACEUTICALS, Issue 11-12 2007
    Paul F. Fitzpatrick
    Abstract Deuterium, solvent, and 15N kinetic isotope effects have been used to probe the mechanisms by which flavoproteins oxidize carbon,oxygen and carbon,nitrogen bonds in amines, hydroxy acids, and alcohols. For the amine oxidases D -amino acid oxidase, N -methyltryptophan oxidase, and tryptophan monooxygenase, D -serine, sarcosine, and alanine are slow substrates for which CH bond cleavage is fully rate limiting. Inverse isotope effects for each of 0.992,0.996 are consistent with a common mechanism involving hydride transfer from the uncharged amine. Computational analyses of possible mechanisms support this conclusion. Deuterium and solvent isotope effects with wild-type and mutant variants of the lactate dehydrogenase flavocytochrome b2 show that OH and CH bond cleavage are not concerted, but become so in the Y254F enzyme. This is consistent with a highly asynchronous reaction in which OH bond cleavage precedes hydride transfer. The results of Hammett analyses and solvent and deuterium isotope effects support a similar mechanism for alcohol oxidase. Copyright © 2007 John Wiley & Sons, Ltd. [source]


    Innentitelbild: Tunneln von Wasserstoffatomen kann zur Bildung von H2 im Weltraum beitragen (Angew. Chem.

    ANGEWANDTE CHEMIE, Issue 40 2010
    40/2010)
    Der quantenmechanische Tunneleffekt von H-Atomen bei der Bildung von H2 im Weltraum wurde untersucht. In der Zuschrift auf Seite,7508,ff. nutzen T.,P.,M. Goumans und J. Kästner eine neue Variante der harmonischen Quantenübergangszustandstheorie, um die Geschwindigkeit der Reaktion von H-Atomen mit Benzol zu untersuchen. Dieses Modell des geschwindigkeitsbestimmenden Schritts der Wasserstoffbildung an kohlenstoffhaltigen Staubpartikeln zeigt, dass H etwa zwei Größenordnungen schneller reagiert als das schwerere Deuterium. Hintergrundbild: NASA/JPL-Caltech/STScI/CXC/UofA/ESA/AURA/JHU. [source]


    ChemInform Abstract: Infrared Spectra of the Novel Ge2H2 and Ge2H4 Species and the Reactive GeH1,2,3 Intermediates in Solid Neon, Deuterium and Argon.

    CHEMINFORM, Issue 37 2002
    Xuefeng Wang
    Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a "Full Text" option. The original article is trackable via the "References" option. [source]


    Location of Disulfide bonds in mature ,- L;-fucosidase from pea

    JOURNAL OF PEPTIDE SCIENCE, Issue 6 2001
    Anna Codina
    Abstract Fuc-9 is the mature form of a vacuolar ,- L;-fucosidase enzyme which seems to play an important role in plant growth regulation. Fuc-9 is a 202-residue protein containing five Cys residues located at positions 64, 109, 127, 162 and 169. In this study, the disulfide structure of Fuc-9 was determined by MALDI-TOF mass spectrometry (MS), with minimal clean-up of the samples and at a nanomolar scale. Two strategies, based on a specific chemical cleavage (with 2-nitro-5-thiocyanobenzoic acid and alkaline conditions) at the Cys residues and modification of Cys residues by acrylamide/deuterium labeled acrylamide alkylation, were used. Using these methods, the disulfide pairings Cys64-Cys109 and Cys162-Cys169 could be established. The advantages and limitations of our experimental approach are discussed. Copyright © 2001 European Peptide Society and John Wiley & Sons, Ltd. [source]


    Mitigation of Electromagnetic Instabilities in Fast Ignition Scenario

    CONTRIBUTIONS TO PLASMA PHYSICS, Issue 3-4 2005
    C. Deutsch
    Abstract We address the issues of collective stopping for intense relativistic electron beams (REB) used to selectively ignite precompressed deuterium + tritium (DT) fuels. We investigate the subtle interplay of electron collisions in target as well as in beam plasmas with quasi-linear electromagnetic growth rates. Intrabeam scattering is found effective in taming those instabilities, in particular for high transverse temperatures. (© 2005 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim) [source]


    Crystal structures and isotope effect on Na5H3(SeO4)4·2H2O and Na5D3(SeO4)4·2D2O crystals

    CRYSTAL RESEARCH AND TECHNOLOGY, Issue 8 2010
    T. Fukami
    Abstract Differential scanning calorimetry (DSC) and X-ray diffraction measurements have been performed on pentasodium trihydrogen tetraselenate dihydrate Na5H3(SeO4)4·2H2O and deuterated Na5D3(SeO4)4·2D2O crystals. Any distinct anomaly around 428 K in the DSC curves for both crystals is suggested to be caused by a chemical reaction of thermal decomposition with hydrolysis at high temperature. The space group symmetry (triclinic P) and the structure parameters are determined at room temperature. The hydrogen atom in the centrosymmetric O-H(D)-O hydrogen bond of both crystals is found to be equally distributed at two equivalent sites in the bond. The expansions of two O-H-O hydrogen bonds by the substitution of deuterium are observed to be 0.016(6) and 0.011(4) Å. The geometric isotope effect on hydrogen bonds is confirmed to be existed in Na5H3(SeO4)4·2H2O. (© 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim) [source]


    Comparative metabolite profiling of carboxylic acids in rat urine by CE-ESI MS/MS through positively pre-charged and 2H-coded derivatization

    ELECTROPHORESIS, Issue 22 2008
    Wen-Chu Yang
    Abstract A new approach to the selective comparative metabolite profiling of carboxylic acids in rat urine was established using CE-MS and a method for positively pre-charged and 2H-coded derivatization. Novel derivatizing reagents, N -alkyl-4-aminomethyl-pyridinum iodide (alkyl=butyl, butyl-d9 or hexyl), containing quaternary amine and stable-isotope atoms (deuterium), were introduced for the derivatization of carboxylic acids. CE separation in positive polarity showed high reproducibility (0.99,1.32% RSD of migration time) and eliminated problems with capillary coating known in CE-MS anion analyses. Essentially complete ionization and increased hydrophobicity after the derivatization also enhanced MS detection sensitivity (e.g. formic acid was detected at 0.5,pg). Simultaneous derivatization of one sample using two structurally similar reagents, N -butyl-4-aminomethyl-pyridinum iodide (BAMP) and N -hexyl-4-aminomethyl-pyridinum iodide, provided additional information for recognizing a carboxylic acid in an unknown sample. Moreover, characteristic fragmentation acquired by online CE-MS/MS allowed for identification and categorization of carboxylic acids. Applying this method on rat urine, we found 59 ions matching the characteristic patterns of carboxylic acids. From these 59, 32 ions were positively identified and confirmed with standards. For comparative analysis, 24 standard carboxylic acids were derivatized by chemically identical but isotopically distinct BAMP and N -butyl-d9-4-aminomethyl-pyridinium iodide, and their derivatization limits and linearity ranges were determined. Comparative analysis was also performed on two individual urine samples derivatized with BAMP and N -butyl-d9-4-aminomethyl-pyridinium iodide. The metabolite profiling variation between these two samples was clearly visualized. [source]


    An Efficient Synthesis of Substituted meta -Halophenols and Their Methyl Ethers: Insight into the Reaction Mechanism

    EUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 15 2010
    Faiz Ahmed Khan
    Abstract An expeditious synthetic methodology leading to substituted meta -halophenols and their corresponding methyl ether derivatives through acid-mediated fragmentation of suitably substituted dihalonorbornyl ketones has been devised. The reaction sequence consists of TBTH-mediated (TBTH is tri- n -butyltin hydride) selective bridgehead halogen reduction of easily accessible Diels,Alder adducts derived from 1,2,3,4-tetrahalo-5,5-dimethoxycyclopentadiene and ,-substituted vinyl acetates, with subsequent conversion into the requisite bicyclic ketones by a two-step hydrolysis/oxidation approach. An extensive mechanistic investigation based on isotope labeling and cross experiments has been carried out and plausible mechanistic pathways based on these results have been proposed. The absence of halogen atoms at the bridgehead positions steers the reaction through a novel pathway involving the incorporation of proton (or deuterium) followed by elimination of HX (or DX), so the described methodology also provides a reliable route to ortho-para dideuteratedphenolic derivatives. [source]


    Hydraulic lift in a neotropical savanna

    FUNCTIONAL ECOLOGY, Issue 5 2003
    M. Z. Moreira
    Summary 1We report hydraulic lift in the savanna vegetation of central Brazil (Cerrado). Both heat-pulse measurements and isotopic (deuterium) labelling were used to determine whether hydraulic lift occurred in two common species, and whether neighbouring small shrubs and trees were utilizing this water. 2Both techniques showed water uptake by tap-roots and reverse flow of water in lateral roots. Roots transferred hydraulically lifted water to the soil, and small shrubs and trees neighbouring the labelled individuals were labelled by deuterated water. 3Isotopic mass-balance equations and sap-flow measurements showed that water taken up by the central tap-root in each individual constituted only a small percentage of total flux of water through the treated plants. Mass-balance equations also indicated that small shrubs and trees neighbouring the treated plants utilized only a few thousandths of a per cent of the label. 4The small proportion of water uptake by the tap-root of these two species may be limiting hydraulic lift in this system, unless sinker roots descending from lateral roots contribute to hydraulic lift. [source]


    Development of Saline Ground Water through Transpiration of Sea Water

    GROUND WATER, Issue 6 2007
    T. Fass
    As vegetation usually excludes salt during water uptake, transpiration will increase the salinity of the residual water. If the source water is sea water, then the residual water may become highly saline. In the unconfined coastal aquifer of the tropical Burdekin River delta, northeastern Australia, areas of highly saline ground water with chloride concentrations up to almost three times that of sea water occur up to 15 km from the present coastline, and are attributed to transpiration by mangrove vegetation during periods of high sea level. Radiogenic (14C) carbon isotope analyses indicate that ground water with chloride concentrations between 15,000 and 35,000 mg/L is mostly between 4000 and 6000 years old, at which time sea level was 2 to 3 m higher than present. Stable isotope analyses of oxygen-18 and deuterium show no evidence for evaporative enrichment of this water. Oxygen-18, deuterium, and stable (,13C) carbon isotope analyses of ground water and soil water point to a recharge environment beneath the mangrove forests during this postglacial sea level high stand. During that period, transpiration of the mangrove forests would have led to high chloride concentrations in the residual ground water, without inducing isotopic fractionation. Due to the higher density, this hypersaline water moved downward through the aquifer by gravity and has formed lenses of highly saline ground water at the bottom of the unconfined aquifer. [source]


    Assessing the impact of mixing assumptions on the estimation of streamwater mean residence time

    HYDROLOGICAL PROCESSES, Issue 12 2010
    Fabrizio Fenicia
    Abstract Catchment streamwater mean residence time (Tmr) is an important descriptor of hydrological systems, reflecting their storage and flow pathway properties. Tmr is typically inferred from the composition of stable water isotopes (oxygen-18 and deuterium) in observed rainfall and discharge. Currently, lumped parameter models based on convolution and sinewave functions are usually used for tracer simulation. These traditional models are based on simplistic assumptions that are often known to be unrealistic, in particular, steady flow conditions, linearity, complete mixing and others. However, the effect of these assumptions on Tmr estimation is seldom evaluated. In this article, we build a conceptual model that overcomes several assumptions made in traditional mixing models. Using data from the experimental Maimai catchment (New Zealand), we compare a complete-mixing (CM) model, where rainfall water is assumed to mix completely and instantaneously with the total catchment storage, with a partial-mixing (PM) model, where the tracer input is divided between an ,active' and a ,dead' storage compartment. We show that the inferred distribution of Tmr is strongly dependent on the treatment of mixing processes and flow pathways. The CM model returns estimates of Tmr that are well identifiable and are in general agreement with previous studies of the Maimai catchment. On the other hand, the PM model,motivated by a priori catchment insights,provides Tmr estimates that appear exceedingly large and highly uncertain. This suggests that water isotope composition measurements in rainfall and discharge alone may be insufficient for inferring Tmr. Given our model hypothesis, we also analysed the effect of different controls on Tmr. It was found that Tmr is controlled primarily by the storage properties of the catchment, rather than by the speed of streamflow response. This provides guidance on the type of information necessary to improve Tmr estimation. Copyright © 2010 John Wiley & Sons, Ltd. [source]


    Hydrological versus biogeochemical controls on catchment nitrate export: a test of the flushing mechanism

    HYDROLOGICAL PROCESSES, Issue 20 2006
    Carlos J. Ocampo
    Abstract Deciphering the connection between streamflows and nitrate (NO,3) discharge requires identification of the various water flow pathways within a catchment, and the different time-scales at which hydrological and biogeochemical processes occur. Despite the complexity of the processes involved, many catchments around the world present a characteristic flushing response of NO,3 export. Yet the controls on the flushing response, and how they vary across space and time, are still not clearly understood. In this paper, the ,flushing response' of NO,3 export from a rural catchment in Western Australia was investigated using isotopic (deuterium), chemical (chloride, NO,3), and hydrometric data across different antecedent conditions and time-scales. The catchment streamflow was at all time-scales dominated by a pre-event water source, and the NO,3 discharge was correlated with the magnitude of areas contributing to saturation overland flow. The NO,3 discharge also appeared related to the shallow groundwater dynamics. Thus, the antecedent moisture condition of the catchment at seasonal and interannual time-scales had a major impact on the NO,3 flushing response. In particular, the dynamics of the shallow ephemeral perched aquifer drove a shift from hydrological controls on NO,3 discharge during the ,early flushing' stage to an apparent biogeochemical control on NO,3 discharge during the ,steady decline' stage of the flushing response. This temporally variable control hypothesis provides a new and alternative description of the mechanisms behind the commonly seen flushing response. Copyright © 2006 John Wiley & Sons, Ltd. [source]


    ,Distribution of oxygen-18 and deuterium in river waters across the United States

    HYDROLOGICAL PROCESSES, Issue 7 2001
    Carol Kendall
    Abstract Reconstruction of continental palaeoclimate and palaeohydrology is currently hampered by limited information about isotopic patterns in the modern hydrologic cycle. To remedy this situation and to provide baseline data for other isotope hydrology studies, more than 4800, depth- and width-integrated, stream samples from 391 selected sites within the USGS National Stream Quality Accounting Network (NASQAN) and Hydrologic Benchmark Network (HBN) were analysed for ,18O and ,2H (http://water.usgs.gov/pubs/ofr/ofr00-160/pdf/ofr00-160.pdf). Each site was sampled bimonthly or quarterly for 2·5 to 3 years between 1984 and 1987. The ability of this dataset to serve as a proxy for the isotopic composition of modern precipitation in the USA is supported by the excellent agreement between the river dataset and the isotopic compositions of adjacent precipitation monitoring sites, the strong spatial coherence of the distributions of ,18O and ,2H, the good correlations of the isotopic compositions with climatic parameters, and the good agreement between the ,national' meteoric water line (MWL) generated from unweighted analyses of samples from the 48 contiguous states of ,2H=8·11,18O+8·99 (r2=0·98) and the unweighted global MWL of sites from the Global Network for Isotopes in Precipitation (GNIP) of the International Atomic Energy Agency and the World Meteorological Organization (WMO) of ,2H=8·17,18O+10·35. The national MWL is composed of water samples that arise in diverse local conditions where the local meteoric water lines (LMWLs) usually have much lower slopes. Adjacent sites often have similar LMWLs, allowing the datasets to be combined into regional MWLs. The slopes of regional MWLs probably reflect the humidity of the local air mass, which imparts a distinctive evaporative isotopic signature to rainfall and hence to stream samples. Deuterium excess values range from 6 to 15, in the eastern half of the USA, along the northwest coast and on the Colorado Plateau. In the rest of the USA, these values range from ,2 to 6,, with strong spatial correlations with regional aridity. The river samples have successfully integrated the spatial variability in the meteorological cycle and provide the best available dataset on the spatial distributions of ,18O and ,2H values of meteoric waters in the USA. Published in 2001 by John Wiley & Sons, Ltd. [source]


    Theoretical study of NMR chemical shift induced by H/D isotope effect

    INTERNATIONAL JOURNAL OF QUANTUM CHEMISTRY, Issue 15 2010
    Kimikazu Sugimori
    Abstract The isotope effect induced by deuterium substituted species is observed in molecular properties, such as geometry, kinetics, and electronic state, of the molecules through nuclear-electron interaction. Theoretical considerations and experimental alignments have been studied by ab initio molecular orbital, density functional theory, and other empirical strategies. The Born-Oppenheimer approximation with nuclear vibrational wavefunction can treat isotope effect because nuclear mass effect account for the average distance of vibrational motion. In this study, we introduce Morse anharmonic oscillator model to calculate average internuclear distance of diatomic molecules having X-H bonding and X-D bonding. Morse parameters are determined by fitting to potential energy surface of molecular orbital and/or density functional calculations, and then the average distance are obtained as the expectation value of the analytical Morse vibrational wavefunction. Nuclear magnetic resonance shielding constants of the H/D isotopomer are calculated again on the average distance by using GIAO with B3LYP and CCSD calculation. © 2010 Wiley Periodicals, Inc. Int J Quantum Chem, 2010 [source]


    Headspace Evaluation of Methanethiol and Dimethyl Trisulfide in Aqueous Solutions of Soy-protein Isolates

    JOURNAL OF FOOD SCIENCE, Issue 5 2000
    W.L. Boatright
    ABSTRACT Volatile compounds from 2 samples of aqueous soy-protein isolates (SPI) (7%) were analyzed using both static and dynamic headspace methods. Based on dynamic headspace analyses, the most powerful odorants were (1) dimethyl trisulfide, (2) methanethiol, (3) hexanal, (4) an unidentified charred, sweaty feet-like odor, (5) 2-pentyl furan, (6) 2,3-butadione, and (7) an unknown burnt-like odor. The most powerful odorants by static headspace analyses were (1) dimethyl trisulfide, (2) hexanal, (3) methanethiol, and (4) 2-pentyl furan. Using deuterium labeled DMTS as an internal standard, DMTS was quantified at 60.1 and 45.5 ppb in the SPIs. This corresponds to odor values of 6014 and 4554, respectively. Using a cool, on-column technique, direct injection of concentrated-headspace volatiles and solvent-recovered volatiles with an internal standard of d6 -DMTS detected both methanethiol and DMTS at similar levels as with the traditional injection methods. [source]


    Photochemistry of 4- and 5- phenyl substituted isoxazoles

    JOURNAL OF HETEROCYCLIC CHEMISTRY, Issue 2 2005
    James W. Pavlik
    5-Phenylisoxazole (4) and 4-phenylisoxazole (22) underwent phototransposition to 5-phenyloxazole (5) and 4-phenyloxazole (24) respectively. Labeling with deuterium or methyl confirmed that these phototranspositions occurred via the P4 pathway which involves only interchange of the N2 and C3 ring position. Thus, 4-deuterio-5-phenylisoxazole (4-4d), 4-methyl-5-phenylisoxazole (10), and 5-methyl-4-phenylisoxazole (23) phototransposed to 4-deuterio-5-phenyloxazole (5-4d), 4-methyl-5-phenyloxazole (11), and 5-methyl-4-phenyloxazole (25) respectively. In addition to phototransposition, isoxazoles 4, 10, and 23 also underwent photo-ring cleavage to yield benzoylacetonitrile (9), ,-benzoylpropionitrile (15), and aceto-,-phenylacetonitrile (26) respectively. Irradiation of 5-phenyl-3-(trifluoromethyl)isoxazole (16) in acetonitrile led to 5-phenyl-2-(trifluoromethyl)oxazole (17), the P4 phototransposition product. Irradiation of 16 in methanol led to a substantial decrease in the yield of 17 and to the formation of a mixture of (E) and (Z)-2-methoxy-2-(trifluoromethyl)-3-benzoylaziridines 18a and 18b. [source]


    Influence of [2H]-labelled acetic acid as solvent in the synthesis of [2H]-labelled perhexiline

    JOURNAL OF LABELLED COMPOUNDS AND RADIOPHARMACEUTICALS, Issue 1 2010
    Søren Christian Schou
    Abstract Preparation of deuterium-labelled perhexiline from an unsaturated analogue was performed via reduction with deuterium gas and PtO2 in acetic acid. Low incorporation was observed when using acetic acid as solvent (most abundant mass peak was M), but when changing the solvent to deuterium-labelled acetic acid, e.g. acetic acid-OD or acetic acid- d4, a higher incorporation was observed (most abundant mass peak was M). Using hydrogen gas instead of deuterium gas with deuterium-labelled acetic acid, high levels of deuterium incorporation were observed (most abundant mass peak was M). An attempt to reduce a precursor with a fully deuterated pyridine to obtain perhexiline with a higher content of deuterium failed. Copyright © 2009 John Wiley & Sons, Ltd. [source]


    Synthesis of deuterium labelled diclofenac with improved isotopic enrichment

    JOURNAL OF LABELLED COMPOUNDS AND RADIOPHARMACEUTICALS, Issue 13 2009
    Keying Wu
    Abstract A five-step synthesis of deuterium-labelled diclofenac starting from 2-phenyl[2H5] acetic acid is described. The synthesis prevents deuterium from scrambling during the reaction. It offers the labelled compound with over 99% isotopic enrichment. It also provides a possible alternative route for the synthesis of deuterium-labelled 4,-hydroxydiclofenac, which is the principal human metabolite of diclofenac. Copyright © 2009 John Wiley & Sons, Ltd. [source]


    Synthesis and elucidation of deuterated vanillylamine hydrochloride and capsaicin

    JOURNAL OF LABELLED COMPOUNDS AND RADIOPHARMACEUTICALS, Issue 13 2009
    Sang Wook Kim
    Abstract Capsaicin is the major pungent component of hot peppers, which belong to the plant genus Capsicum. Although the biosynthesis of capsaicin is known to involve the condensation of vanillylamine and 8-methylnonenoic acid by capsaicin synthase, the mechanism of biosynthesis is still not fully understood. In this study, deuterium labelled versions of capsaicin and the precursor vanillylamine were synthesized in order to investigate the biosynthesis of capsaicin in hot peppers. Copyright © 2009 John Wiley & Sons, Ltd. [source]


    Easy preparative scale syntheses of labelled xanthines: caffeine, theophylline and theobromine

    JOURNAL OF LABELLED COMPOUNDS AND RADIOPHARMACEUTICALS, Issue 1 2007
    Frédéric Balssa
    Abstract Several easy preparative scale (0.5,1.5 g) syntheses of deuterium labelled caffeine, theophylline and theobromine are described. Some new selective syntheses of theophylline and theobromine have been developed. Labelled xanthines are of great interest in qualitative or quantitative isotope dilution-mass spectrometry, coupled with gas or liquid chromatography, currently performed in anti-doping and forensic laboratories. Copyright © 2007 John Wiley & Sons, Ltd. [source]


    Investigations into the C -deuteriation of silyl enol ethers derived from aryl alkyl ketones

    JOURNAL OF LABELLED COMPOUNDS AND RADIOPHARMACEUTICALS, Issue 9 2006
    Svitlana Buksha
    Abstract Results are reported on the regioselective C -deuteriation of a series of silyl enol ethers derived from aryl alkyl ketones using deuterium (D2) gas as the deuterium source and palladium-on-barium sulfate as the mediator. These results highlight the numerous reaction pathways and different product types available from simple deuteriation of substituted enol precursors. Copyright © 2006 John Wiley & Sons, Ltd. [source]


    Syntheses of [2H3, 15N], [14C]NexavarÔ and its labeled metabolites

    JOURNAL OF LABELLED COMPOUNDS AND RADIOPHARMACEUTICALS, Issue 7 2006
    U. Pleiss
    Abstract NexavarÔ, Sorafenib tosylate (BAY 43-9006 tosylate) is a potent small molecule Raf kinase inhibitor for the treatment of hyperproliferative disorders such as cancer. Both radiolabeled and stable isotope labeled compounds were required for drug absorption, distribution, metabolism and excretion (ADME) and quantitative mass spectrometry bio-analytical studies. NexavarÔ labeled with carbon-14 in the carboxamide group was prepared in two steps in an overall radiochemical yield of 42% starting from 4-chloro- N -methyl-2-pyridine-[14C]carboxamide. The [2H3,15N] version of NexavarÔ was prepared in 75% yield based on 4-chloro- N -[2H3]methyl-2-pyridine-[15N]carboxamide. The pyridine N -oxide metabolite labeled with carbon-14 as well as with deuterium and nitrogen-15 and was synthesized by oxidation in yields of 59% and 87%, respectively. Starting from [2H2, 13C]formaldehyde the N -hydroxymethyl metabolite was labeled with carbon-13 and deuterium in one step in a 45% overall yield. Copyright © 2006 John Wiley & Sons, Ltd. [source]


    Synthesis of ,3 adrenergic receptor agonist LY377604 and its metabolite 4-hydroxycarbazole, labeled with carbon-14 and deuterium

    JOURNAL OF LABELLED COMPOUNDS AND RADIOPHARMACEUTICALS, Issue 6 2005
    Boris A. Czeskis
    Abstract Synthesis of 14C-radiolabeled 4-hydroxycarbazole was accomplished starting from aniline-[U- 14C], based on zinc chloride initiated Fischer cyclization of the phenylhydrazone prepared from phenylhydrazine-[U- 14C] and cyclohexane-1,3-dione. The resulting tetrahydrooxocarbazole was subjected to dehydrogenation,aromatization using palladium on carbon. The aromatized 4-hydroxycarbazole-[4b,5,6,7,8,8a- 14C] was then used for the synthesis of 14C-labeled ,3 adrenergic receptor agonist LY377604. The introduction of four deuteria in the carbazole fragment of LY377604 accomplished by its initial bromination and subsequent catalytic deuteration of the resulting tetrabromide. A similar approach was used for the conversion of 4-hydroxycarbazole into its tetradeutero-isotopomer. Copyright © 2005 John Wiley & Sons, Ltd. [source]


    Synthesis of deuterium labelled 2-bromobenzylamine by directed ortho -metalation chemistry

    JOURNAL OF LABELLED COMPOUNDS AND RADIOPHARMACEUTICALS, Issue 3 2005
    Jens Atzrodt
    Abstract Directed ortho -metalation (DoM) strategy has been applied for the development of a short procedure for the regiospecific synthesis of [phenyl - 2H4]-2-bromo-benzylamine 6 starting from commercially available [phenyl - 2H5]-benzoyl chloride 1. A strong isotope effect was observed during the ortho -substitution. Copyright © 2005 John Wiley & Sons, Ltd. [source]


    Synthesis of deuterium, tritium, and carbon-14 labeled BIRB 796, a p38 MAP kinase inhibitor

    JOURNAL OF LABELLED COMPOUNDS AND RADIOPHARMACEUTICALS, Issue 12 2004
    Bachir Latli
    Abstract 1-(5- tert -Butyl-2- p -tolyl-2H-pyrazol-3-yl)-3-[4-(2-morpholin-4-yl-ethoxy)naphthalen-1-yl]urea (BIRB 796), currently in clinical trials for the treatment of inflammatory diseases, is a potent inhibitor of p38 MAP kinase. Labeled BIRB 796 with stable and radioactive isotopes was required for metabolism, distribution, and absorption studies. We first report the synthesis of carbon-14 labeled BIRB 796 with a specific activity of 2 GBq/mmol (54.2 mCi/mmol), using [14C]-phosgene under modified Schotten,Baumann conditions; second the preparation of tritium-labeled BIRB 796 with a specific activity of 659 GBq/mmol (17.81 Ci/mmol) by reductive dehalogenation of iodo-BIRB 796 with tritium gas; and finally, the synthesis of 2H8 -BIRB 796 using morpholine-2,2,3,3,5,5,6,6- 2H8 with isotopic enrichment of 98.9 at% 2H. Copyright © 2004 John Wiley & Sons, Ltd. [source]


    Uncatalyzed microwave deuterium exchange labeling of bleomycin A2

    JOURNAL OF LABELLED COMPOUNDS AND RADIOPHARMACEUTICALS, Issue 11 2004
    Steve A. de Keczer
    Abstract Bleomycin sulfate in D2O was deuterated using microwave irradiation under catalyst free conditions. Following the removal of labile deuterium and purification, bleomycin A2 with mass M + 1 to M + 7 was obtained. Successful selective uncatalyzed microwave deuterium exchange reactions on examples from the following classes of heterocycles are also described: imidazole, thiazole, indole, purine, and quinazoline. The described method was used as a test for non-labile active protons. Copyright © 2004 John Wiley & Sons, Ltd. [source]


    Enzymatic synthesis of l-tryptophan and 5prime-hydroxy-l-tryptophan labeled with deuterium and tritium at the alpha-carbon position

    JOURNAL OF LABELLED COMPOUNDS AND RADIOPHARMACEUTICALS, Issue 8 2003
    E. Boroda
    Abstract The enzymatic synthesis of l-tryptophan and its derivative 5,-hydroxy-l-tryptophan labeled with deuterium and tritium at the ,-carbon position is reported. The mixture containing S -methyl-l-cysteine, indole or 5-hydroxyindole dissolved in deuteriated or tritiated water has been converted to [2- 2H]-l-tryptophan, [2- 3H]-l-tryptophan, 5,-hydroxy-[2- 2H]-l-tryptophan, and 5,-hydroxy-[2- 3H]-l-tryptophan, respectively, in a one-pot reaction using the enzyme tryptophanase. The same reaction carried out in heavy water with THO added yielded either doubly labeled [2- 2H/3H]-l-tryptophan or 5,-hydroxy-[2- 2H/3H]-l-tryptophan. Copyright © 2003 John Wiley & Sons, Ltd. [source]


    Isotopic labeling of 2-desoxoparaherquamide A (PNU-141962) with deuterium

    JOURNAL OF LABELLED COMPOUNDS AND RADIOPHARMACEUTICALS, Issue 14 2002
    Byung H. Lee
    Abstract Modifications of marcfortine A and paraherquamide A led to the discovery of 2-desoxoparaherquamide A (PNU-141962, 3) which is as active as paraherquamide A and has an improved safety profile. In order to do preclinical studies, we wished to synthesize isotope-labeled PNU-141962. This account will describe the synthesis of [CD3]-2-desoxoparaherquamide A (4). The deuterium product was prepared in anticipation of using a similar synthesis for the preparation of the corresponding 14C- and 3H-labeled products. Copyright © 2002 John Wiley & Sons, Ltd. [source]


    Proton and metal-ion activation of C,H exchange in five-membered azoles

    JOURNAL OF LABELLED COMPOUNDS AND RADIOPHARMACEUTICALS, Issue 4 2002
    Erwin Buncel
    Abstract Factors influencing C,H isotopic exchange rates in five-membered azoles, that is imidazoles and thiazoles, under catalysis by H+ and Mn+, especially transition metals, Pt(II) and Co(III) are discussed. Hydrogen ion catalysis through N(3) protonation of azoles 1,3 is generally the most efficient, with rate enhancements in the range 102,109 over the neutral process being attained. Metal-ion coordination also results in effective catalysis, though less so than catalysis by protons. Catalysis of C,H exchange by Mn+ can be studied through addition of the metal salts to a buffered solution of the heterocycle in which labile complexes exist, or on synthesized complexes such as 4,13 which are substitution-inert thus precluding complications from unknown dissociation equilibria. A delicate balance of factors influence the ease of C,H exchange, including: (1) the magnitude of the fractional charge located at N(3) of the heterocycle through Mn+,N(3) , bond polarization; (2) metal-to-ligand , back-bonding; (3) the electronic structure of the metal ions. These considerations have obvious consequences for deuterium- and tritium-labelling of a number of biomolecules, e.g. proteins, enzymes, nucleic acids, some vitamins, as well as drugs which incorporate five-membered azoles in their structures. Copyright © 2002 John Wiley & Sons, Ltd. [source]