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  • P. Barbier Saint Hilaire, A. Warnet, Y. Gimbert, U. M. Hohenester, G. Giorgi, M. - F. Olivier, F. Fenaille, B. Colsch, C. Junot, et J. - C. Tabet, « Mechanistic study of competitive releases of H2O, NH3 and CO2 from deprotonated aspartic and glutamic acids: Role of conformation », Journal of Chromatography B, vol. 1047, p. 64-74.
    Résumé : The aims of this study were to highlight the impact of minor structural differences (e.g. an aminoacid side chain enlargement by one methylene group), on ion dissociation under collision-induced dissociation conditions, and to determine the underlying chemical mechanisms. Therefore, we compared fragmentations of deprotonated aspartic and glutamic acids generated in negative electrospray ionization. Energy-resolved mass spectrometry breakdown curves were recorded and MS3 experiments performed on an Orbitrap Fusion for high-resolution and high-mass accuracy measurements. Activated fragmentations were performed using both the resonant and non-resonant excitation modes (i.e., CID and HCD, respectively) in order to get complementary information on the competitive and consecutive dissociative pathways. These experiments showed a specific loss of ammonia from the activated aspartate but not from the activated glutamate. We mainly focused on this specific observed loss from aspartate. Two different mechanisms based on intramolecular reactions (similar to those occurring in organic chemistry) were proposed, such as intramolecular elimination (i.e. Ei-like) and nucleophilic substitution (i.e. SNi-like) reactions, respectively, yielding anions as fumarate and α lactone from a particular conformation with the lowest steric hindrance (i.e. with antiperiplanar carboxyl groups). The detected deaminated aspartate anion can then release CO2 as observed in the MS3 experimental spectra. However, quantum calculations did not indicate the formation of such a deaminated aspartate product ion without loss of carbon dioxide. Actually, calculations displayed the double neutral (NH3+CO2) loss as a concomitant pathway (from a particular conformation) with relative high activation energy instead of a consecutive process. This disagreement is apparent since the concomitant pathway may be changed into consecutive dissociations according to the collision energy i.e., at higher collision energy and at lower excitation conditions, respectively. The latter takes place by stabilization of the deaminated aspartate solvated with two residual molecules of water (present in the collision cell). This desolvated anion formed is an α lactone substituted by a methylene carboxylate group. The vibrational excitation acquired by [(D−H)−NH3]−during its isolation is enough to allow its prompt decarboxylation with a barrier lower than 8.4 kJ/mol. In addition, study of glutamic acid-like diastereomers constituted by a cyclopropane, hindering any side chain rotation, confirms the impact of the three-dimensional geometry on fragmentation pathways. A significant specific loss of water is only observed for one of these diastereomers. Other experiments, such as stable isotope labeling, need to be performed to elucidate all the observed losses from activated aspartate and glutamate anions. These first mechanistic interpretations enhance understanding of this dissociative pathway and underline the necessity of studying fragmentation of a large number of various compounds to implement properly new algorithms for de novo elucidation of unknown metabolites.
    Mots-clés : CSOB, Electrospray high-resolution mass spectrometry, POLE 3, Regioselective dissociation, Unexpected cleavage of aspartate anion.

  • E. Darii, S. Alves, Y. Gimbert, A. Perret, et J. - C. Tabet, « Meaning and consequence of the coexistence of competitive hydrogen bond/salt forms on the dissociation orientation of non-covalent complexes », Journal of Chromatography B, vol. 1047, p. 45-58.
    Résumé : Non-covalent complexes (NCC) between hexose monophosphates (HexP) and arginine (R) were analyzed using ESI MS and MS/MS in negative mode under different (hard, HC and soft, SC) desolvation conditions. High resolution mass spectrometry (HRMS) revealed the presence of different ionic species, namely, homo- and heteromultimers of R and HexP. Deprotonated heterodimers and corresponding sodiated species were enhanced under HC likely due to a decrease in available charge number associated with the reduction of H+/Na+ exchange. The quantum calculations showed that the formation of covalent systems is very little exothermic, therefore, such systems are disfavored. Desolvation dependent CID spectra of deprotonated [(HexP+R)‒H]− complexes demonstrated that they can exist within the hydrogen bond (HB) and salt bridge (SB) forms, yielding either NCC separation or covalent bond cleavages, respectively. Although HB forms are the main species, they cannot survive under HC; therefore, the minor SB forms became detectable. Energy-resolved mass spectrometry (ERMS) experiments revealed diagnostic fragment ions from both SB and HB forms, providing evidence that these isomeric forms are inconvertible. SB formation should result from the ionic interactions of highly acidic group of HexP with strongly basic guanidine group of arginine and thus requires an arginine zwitterion (ZW) form. This was confirmed by quantum calculations. Ion-ion interactions are significantly affected by the presence of sodium cation as demonstrated by the fragmentation patterns of sodiated complex species. Regarding CID data, only SB between protonated amino group of R and deprotonated phosphate group of HexP could be suggested, but the primary amine is not enough basic then, the SB must be fleeting. Nevertheless, the observation of the covalent bond cleavages suggests the presence of structures with a free negative charge able to induce fragmentations. Indeed, according to quantum calculations, solvated salt (SS) systems involving Na+/COO− salt solvated by neutral phosphate and negative charge on sugar ring are preferentially formed.
    Mots-clés : CSOB, POLE 3.

  • G. A. Garcia, H. Dossmann, L. Nahon, S. Daly, et I. Powis, « Identifying and Understanding Strong Vibronic Interaction Effects Observed in the Asymmetry of Chiral Molecule Photoelectron Angular Distributions », ChemPhysChem, vol. 18, nᵒ 5, p. 500-512.
    Résumé : Electron–ion coincidence imaging is used to study chiral asymmetry in the angular distribution of electrons emitted from randomly-oriented enantiomers of two molecules, methyloxirane and trifluoromethyloxirane, upon ionization by circularly polarized VUV synchrotron radiation. Vibrationally-resolved photoelectron circular dichroism (PECD) measurements of the outermost orbital ionization reveal unanticipated large fluctuations in the magnitude of the forward–backward electron scattering asymmetry, including even a complete reversal of direction. Identification and assignment of the vibrational excitations is supported by Franck–Condon simulations of the photoelectron spectra. A previously proposed quasi-diatomic model for PECD is developed and extended to treat polyatomic systems. The parametric dependence of the electronic dipole matrix elements on nuclear geometry is evaluated in the adiabatic approximation. It provokes vibrational level dependent shifts in amplitude and phase, to which the chiral photoelectron angular distributions are especially sensitive. It is shown that single quantum excitation of those vibrational modes, which experience only a relatively small displacement of the ion equilibrium geometry along the normal coordinate and which are then only weakly excited in the Franck–Condon limit, can be accompanied by big shifts in scattering phase; hence the observed big fluctuations in PECD asymmetry for such modes.
    Mots-clés : circular dichroism, CSOB, photoelectron circular dichroism, photoelectron spectroscopy, photoionization, Photophysics, POLE 3.

  • B. Habchi, S. Alves, D. J. - R. Bouveresse, B. Moslah, A. Paris, Y. Lécluse, P. Gauduchon, P. Lebailly, D. N. Rutledge, et E. Rathahao-Paris, « An innovative chemometric method for processing direct introduction high resolution mass spectrometry metabolomic data: independent component–discriminant analysis (IC–DA) », Metabolomics, vol. 13, nᵒ 4, p. 45.
    Résumé : IntroductionTo perform large scale metabolomic analyses, high throughput approaches are required. The direct introduction mass spectrometry (DIMS) approach appears to be very attractive to achieve this goal. However, processing DIMS data is still very challenging due to the large number of samples and the intrinsic complexity of the mass spectra.ObjectivesThe objective of this study is to develop a computational procedure, based on an innovative chemometric method, i.e. Independent component–discriminant analysis (IC–DA), for processing DIMS data.MethodMetabolomic fingerprints were obtained by direct introduction high resolution mass spectrometry (DI-HRMS) analysis of urine samples of subjects that had been professionally exposed to pesticides. Spectral data were processed using the developed IC–DA procedure. Results obtained from this method were compared to those obtained by the conventional Partial least squares–discriminant analysis (PLS–DA). For both the IC–DA and PLS–DA methods, a validation was performed based on a permutation test.ResultIC–DA results enabled a good detection of discriminant variables and a clear discrimination of control samples and exposure classes whereas a less striking discrimination was obtained with PLS–DA. Putative annotation of these variables was performed using metabolomic databases. Targeted correlation analysis was used for the detection of ions associated with the most discriminant variables, consolidating their identity assignment.ConclusionThis study demonstrated the efficiency of IC–DA to discriminate the different exposure groups. As well the improvement of high throughput metabolomic studies was provided by combining DI–HRMS with this new chemometric tool.
    Mots-clés : CSOB, POLE 3.

  • E. Rathahao-Paris, S. Alves, L. Debrauwer, J. - P. Cravedi, et A. Paris, « An efficient data-filtering strategy for easy metabolite detection from the direct analysis of a biological fluid using Fourier transform mass spectrometry », Rapid Communications in Mass Spectrometry, vol. 31, nᵒ 6, p. 485-494.
    Résumé : Rationale High-throughput analyses require an overall analytical workflow including not only a robust and high-speed technical platform, but also dedicated data-processing tools able to extract the relevant information. This work aimed at evaluating post-acquisition data-mining tools for selective extraction of metabolite species from direct introduction high-resolution mass spectrometry data. Methods Investigations were performed on spectral data in which seven metabolites of vinclozolin, a dicarboximide fungicide containing two chloride atoms, were previously manually identified. The spectral data obtained from direct introduction (DI) and high-resolution mass spectrometry (HRMS) detection were post-processed by plotting the mass defect profiles and applying various data-filtering methods based on accurate mass values. Results Exploration of mass defect profiles highlighted, in a specific plotting region, the presence of compounds containing common chemical elements and pairs of conjugated and non-conjugated metabolites resulting from classical metabolic pathways. Additionally, the judicious application of mass defect and/or isotope pattern filters removed many interfering ions from DI-HRMS data, greatly facilitating the detection of vinclozolin metabolites. Compared with previous results obtained by manual data treatment, three additional metabolites of vinclozolin were detected and putatively annotated. Conclusions Tracking simultaneously several specific species could be efficiently performed using data-mining tools based on accurate mass values. The selectivity of the data extraction was improved when the isotope filter was used for halogenated compounds, facilitating metabolite ion detection even for low-abundance species. Copyright © 2016 John Wiley & Sons, Ltd.
    Mots-clés : CSOB, POLE 3.


  • M. Barbazanges, E. Caytan, D. Lesage, C. Aubert, L. Fensterbank, V. Gandon, et C. Ollivier, « Chiral Phosphate in Rhodium-Catalyzed Asymmetric [2+2+2] Cycloaddition: Ligand, Counterion, or Both? », Chemistry – A European Journal, vol. 22, nᵒ 25, p. 8553-8558.
    Résumé : Investigations based on NMR spectroscopy, mass spectrometry, and DFT calculations shed light on the metallic species generated in the rhodium-catalyzed asymmetric [2+2+2] cycloaddition reaction between diynes and isocyanates with the chiral phosphate TRIP. The catalytic mixture comprising [{Rh(cod)Cl}2], 1,4-diphenylphosphinobutane (dppb), and Ag(S)-TRIP actually gives rise to two species, both having an effect on the stereoselectivity. One is a rhodium(I) complex in which TRIP is a weakly coordinating counterion, whereas the other is a bimetallic Rh/Ag complex in which TRIP is a strongly coordinating X-type ligand.
    Mots-clés : chirality, CSOB, cycloaddition, homogeneous catalysis, ligand effects, MACO, POLE 1, POLE 3, Rhodium.

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  • T. T. Boukerche, S. Alves, P. Le Faouder, A. Warnet, J. Bertrand-Michel, M. Bouchekara, M. Belbachir, et J. - C. Tabet, « Atypical cleavage of protonated N-fatty acyl amino acids derived from aspartic acid evidenced by sequential MS(3) experiments », Amino Acids, vol. 48, nᵒ 12, p. 2717-2729.
    Résumé : Lipidomics calls for information on detected lipids and conjugates whose structural elucidation by mass spectrometry requires to rationalization of their gas phase dissociations toward collision-induced dissociation (CID) processes. This study focused on activated dissociations of two lipoamino acid (LAA) systems composed of N-palmitoyl acyl coupled with aspartic and glutamic acid mono ethyl esters (as LAA(*D) and LAA(*E)). Although in MS/MS, their CID spectra show similar trends, e.g., release of water and ethanol, the [(LAA(*D/*E)+H)-C2H5OH](+) product ions dissociate via distinct pathways in sequential MS(3) experiments. The formation of all the product ions is rationalized by charge-promoted cleavages often involving stepwise processes with ion isomerization into ion-dipole prior to dissociation. The latter explains the maleic anhydride or ketene neutral losses from N-palmitoyl acyl aspartate and glutamate anhydride fragment ions, respectively. Consequently, protonated palmitoyl acid amide is generated from LAA(*D), whereas LAA(*E) leads to the [*E+H-H2O](+) anhydride. The former releases ammonia to provide acylium, which gives the C n H(2n-1) and C n H(2n-3) carbenium series. This should offer structural information, e.g., to locate either unsaturation(s) or alkyl group branching present on the various fatty acyl moieties of lipo-aspartic acid in further studies based on MS (n) experiments.
    Mots-clés : CSOB, ESI/MS n, Ion–dipole, N-fatty-acyl amino-acid, POLE 3, Regioselectivity.

  • J. E. Boulicault, S. Alves, et R. B. Cole, « Negative Ion MALDI Mass Spectrometry of Polyoxometalates (POMs): Mechanism of Singly Charged Anion Formation and Chemical Properties Evaluation », Journal of The American Society for Mass Spectrometry, vol. 27, nᵒ 8, p. 1301-1313.
    Résumé : MALDI-MS has been developed for the negative ion mode analysis of polyoxometalates (POMs). Matrix optimization was performed using a variety of matrix compounds. A first group of matrixes offers MALDI mass spectra containing abundant intact singly charged anionic adduct ions, as well as abundant in-source fragmentations at elevated laser powers. A relative ranking of the ability to induce POM fragmentation is found to be: DAN > CHCA > CNA > DIT> HABA > DCTB > IAA. Matrixes of a second group provide poorer quality MALDI mass spectra without observable fragments. Sample preparation, including the testing of salt additives, was performed to optimize signals for a model POM, POMc12, the core structure of which bears four negative charges. The matrix 9-cyanoanthracene (CNA) provided the best signals corresponding to singly charged intact POMc12 anions. Decompositions of these intact anionic species were examined in detail, and it was concluded that hydrogen radical-induced mechanisms were not prevalent, but rather that the observed prompt fragments originate from transferred energy derived from initial electronic excitation of the CNA matrix. Moreover, in obtained MALDI mass spectra, clear evidence of electron transfer to analyte POM species was found: a manifestation of the POMs ability to readily capture electrons. The affinity of polyanionic POMc12 toward a variety of cations was evaluated and the following affinity ranking was established: Fe3+ > Al3+ > Li+ > Ga3+ > Co2+ > Cr3+ > Cu2+ > [Mn2+, Mg2+] > [Na+, K+]. Thus, from the available cationic species, specific adducts are preferentially formed, and evidence is given that these higher affinity POM complexes are formed in the gas phase during the early stages of plume expansion.Graphical Abstractᅟ
    Mots-clés : CSOB, POLE 3.

  • M. C. Bridoux, A. Schwarzenberg, S. Schramm, et R. B. Cole, « Combined use of direct analysis in real-time/Orbitrap mass spectrometry and micro-Raman spectroscopy for the comprehensive characterization of real explosive samples », Analytical and Bioanalytical Chemistry, vol. 408, nᵒ 21, p. 5677-5687.
    Résumé : Direct Analysis in Real Time (DART™) high-resolution Orbitrap™ mass spectrometry (HRMS) in combination with Raman microscopy was used for the detailed molecular level characterization of explosives including not only the charge but also the complex matrix of binders, plasticizers, polymers, and other possible organic additives. A total of 15 defused military weapons including grenades, mines, rockets, submunitions, and mortars were examined. Swabs and wipes were used to collect trace (residual) amounts of explosives and their organic constituents from the defused military weapons and micrometer-size explosive particles were transferred using a vacuum suction-impact collection device (vacuum impactor) from wipe and swap samples to an impaction plate made of carbon. The particles deposited on the carbon plate were then characterized using micro-Raman spectroscopy followed by DART-HRMS providing fingerprint signatures of orthogonal nature. The optical microscope of the micro-Raman spectrometer was first used to localize and characterize the explosive charge on the impaction plate which was then targeted for identification by DART-HRMS analysis in both the negative and positive modes. Raman spectra of the explosives TNT, RDX and PETN were acquired from micrometer size particles and characterized by the presence of their characteristic Raman bands obtained directly at the surface of the impaction plate nondestructively without further sample preparation. Negative mode DART-HRMS confirmed the types of charges contained in the weapons (mainly TNT, RDX, HMX, and PETN; either as individual components or as mixtures). These energetic compounds were mainly detected as deprotonated species [M–H]−, or as adduct [M + 35Cl]−, [M + 37Cl]−, or [M + NO3]− anions. Chloride adducts were promoted in the heated DART reagent gas by adding chloroform vapors to the helium stream using an “in-house” delivery method. When the polarity was switched to positive mode, DART-HRMS revealed a very complex distribution of polymeric binders (mainly polyethylene glycols and polypropylene glycols), plasticizers (e.g., dioctyl sebacate, tributyl phosphate), as well as wax-like compounds whose structural features could not be precisely assigned. In positive mode, compounds were identified either as protonated molecules or ammonium adduct species. These results clearly demonstrate the complementarity of micro-Raman microscopy combined with DART-MS. The former technique provides structural information on the type of explosives present at the surface of the sample, whereas the latter provides not only a confirmation of the nature of the explosive charge but also useful additional information regarding the nature of the complex organic matrix of binders, plasticizers, polymers, oils, and potentially other organic additives and contaminants present in the sample. Combining these two techniques provides a powerful tool for the screening, comprehensive characterization, and differentiation of particulate explosive samples for forensic sciences and homeland security applications.Graphical AbstractComprehensive characterization of explosive particles collected from swipe samples by micro-Raman and DART™-HRMS
    Mots-clés : CSOB, POLE 3.

  • Q. Dumont, M. Bárcenas, H. Dossmann, I. Bailloux, C. Buisson, N. Mechin, A. Molina, F. Lasne, N. S. Rannulu, et R. B. Cole, « Improved Steroids Detection and Evidence for Their Regiospecific Decompositions Using Anion Attachment Mass Spectrometry », Analytical Chemistry, vol. 88, nᵒ 7, p. 3585-3591.
    Résumé : Nonpolar anabolic steroids are doping agents that typically do not provide strong signals by electrospray ionization-mass spectrometry (ESI-MS) owing especially to the low polarity of the functional groups present. We have investigated the addition of anions, in ammonium salt form, to anabolic steroid samples as ionization enhancers and have confirmed that lower instrumental limits of detection (as low as 10 ng/mL for fluoxymesterone-M) are obtained by fluoride anion attachment mass spectrometry, as compared to ESI(+)/(−) or atmospheric pressure photoionization (APPI)(+). Moreover, collision-induced decomposition (CID) spectra of precursor fluoride adducts of the bifunctional steroid “reduced pregnenolone” (containing two hydroxyl groups) and its d4-analogue provide evidence of regiospecific decompositions after attachment of fluoride anion to a specific hydroxyl group of the steroid. This type of charting of specific CID reaction pathways can offer value to selected reaction monitoring experiments (SRM) as it may result in a gain in selectivity in detection as well as in improvements in quantification.
    Mots-clés : CSOB, POLE 3.

  • B. Guan et R. B. Cole, « The Background to Electrospray », in The Encyclopedia of Mass Spectrometry, Boston: Elsevier, p. 132-140.
    Résumé : This article traces the development of electrospray back to its earliest beginnings. Many readers may be surprised to learn that descriptions of the electrostatic attraction of liquids to surfaces appear in the scientific literature as early as the year 1600, and that true electrospray experiments are documented to have been performed in the eighteenth century. Progress in the development of electrospray is detailed through these earliest observations and subsequent ingenious applications, mathematical descriptions, and, finally, coupling to mass analyzer instrumentation.
    Mots-clés : CSOB, Electrospray development, Electrospray history, Geoffrey Taylor, Harold Ransburg, Jean-Antoine Nollet, John Ellicott, John William Strutt, John Zeleny, Lord Kelvin, Lord Rayleigh, Malcolm Dole, POLE 3, Sir Thomas Browne, Stephen Gray, W. A. Macky, William Gilbert, William Henley, William Thomson.

  • B. Habchi, S. Alves, A. Paris, D. N. Rutledge, et E. Rathahao-Paris, « How to really perform high throughput metabolomic analyses efficiently? », TrAC Trends in Analytical Chemistry, vol. 85, Part C, p. 128-139.
    Résumé : High-throughput analyses are based on technologies characterized by their rapidity, simplicity, sensitivity, robustness, low cost and high efficiency. They offer the potential for screening a large number of samples per day, which cannot be done using classical methods. High-throughput analyses have shown their feasibility and efficiency in multidisciplinary fields such as drug screening, bioassays of compound against mycobacteria. Another successful application is based on direct introduction mass spectrometry for the analysis of very complex organic materials in petroleomics. High-throughput analyses appear to be very attractive in metabolomics, which aims to study the interface between the chemical universe and biology, to detect general metabolic disruptions induced by external factors through a metabolite profiling approach. In this review, we focus on high-throughput metabolomics using high resolution mass spectrometry (HRMS). Specifically, performances and limits of available analytical techniques dedicated to high-throughput analyses, including sample introduction methods, HRMS and data processing tools are discussed.
    Mots-clés : CSOB, Data processing, DIMS, FTMS, High-throughput analyses, metabolomics, POLE 3.

  • E. Rathahao-Paris, S. Alves, C. Junot, et J. - C. Tabet, « High resolution mass spectrometry for structural identification of metabolites in metabolomics », Metabolomics, vol. 12, nᵒ 1, p. 10.
    Résumé : High resolution mass spectrometry (HRMS) is increasingly used to produce metabolomics data. Thanks to its high mass resolution and mass measurement accuracy, it is also very useful for metabolite identification. Nevertheless, a rigorous methodology is required. This manuscript describes different steps involved in the structural elucidation of metabolites and demonstrates the utility of HRMS for such purpose. After a brief overview of HRMS performances in terms of mass measurement accuracy, peak resolution, isotopic clusters/patterns and the instrumentation used, the first section is devoted to the data processing generally performed to reduce the data set size. Based on the mass accuracy measurements, different post-acquisition data processing procedures have been developed for complex mixture analysis and can be used in metabolomics. The second section describes protocols used to process putative metabolite annotations or identifications with HRMS data, based on elemental composition determined from accurately measured m/z value and mass spectral databases. Non-classical approaches are also proposed for tentative structure elucidation of unknown metabolites. Finally, limitations of the proposed workflow for metabolite structure elucidation are discussed and possible improvements are proposed.
    Mots-clés : CSOB, POLE 3.

  • S. Sladkevich, A. - L. Dupont, M. Sablier, D. Seghouane, et R. B. Cole, « Understanding paper degradation: identification of products of cellulosic paper decomposition at the wet-dry “tideline” interface using GC-MS », Analytical and Bioanalytical Chemistry, vol. 408, nᵒ 28, p. 8133-8147.
    Résumé : Cellulose paper degradation products forming in the “tideline” area at the wet-dry interface of pure cellulose paper were analyzed using gas chromatography-electron ionization-mass spectrometry (GC-EI-MS) and high-resolution electrospray ionization-mass spectrometry (ESI-MS, LTQ Orbitrap) techniques. Different extraction protocols were employed in order to solubilize the products of oxidative cellulose decomposition, i.e., a direct solvent extraction or a more laborious chromophore release and identification (CRI) technique aiming to reveal products responsible for paper discoloration in the tideline area. Several groups of low molecular weight compounds were identified, suggesting a complex pathway of cellulose decomposition in the tidelines formed at the cellulose-water-oxygen interface. Our findings, namely the appearance of a wide range of linear saturated carboxylic acids (from formic to nonanoic), support the oxidative autocatalytic mechanism of decomposition. In addition, the identification of several furanic compounds (which can be, in part, responsible for paper discoloration) plus anhydro carbohydrate derivatives sheds more light on the pathways of cellulose decomposition. Most notably, the mechanisms of tideline formation in the presence of molecular oxygen appear surprisingly similar to pathways of pyrolytic cellulose degradation. More complex chromophore compounds were not detected in this study, thereby revealing a difference between this short-term tideline experiment and longer-term cellulose aging.
    Mots-clés : CSOB, POLE 3.


  • A. M. Debela, M. Ortiz, V. Beni, S. Thorimbert, D. Lesage, R. B. Cole, C. K. O'Sullivan, et B. Hasenknopf, « Biofunctionalization of Polyoxometalates with DNA Primers, Their Use in the Polymerase Chain Reaction (PCR) and Electrochemical Detection of PCR Products », Chemistry – A European Journal, vol. 21, nᵒ 49, p. 17721-17727.
    Résumé : The bioconjugation of polyoxometalates (POMs), which are inorganic metal oxido clusters, to DNA strands to obtain functional labeled DNA primers and their potential use in electrochemical detection have been investigated. Activated monooxoacylated polyoxotungstates [SiW11O39{Sn(CH2)2CO}]8− and [P2W17O61{Sn(CH2)2CO}]6− have been used to link to a 5′-NH2 terminated 21-mer DNA forward primer through amide coupling. The functionalized primer was characterized by using a battery of techniques, including electrophoresis, mass spectrometry, as well as IR and Raman spectroscopy. The functionality of the POM-labeled primers was demonstrated through hybridization with a surface-immobilized probe. Finally, the labeled primers were successfully used in the polymerase chain reaction (PCR) and the PCR products were characterized by using electrophoresis.
    Mots-clés : CHEMBIO, CSOB, DNA, DNA Primers, Electrochemistry, GOBS, Nucleic Acid Hybridization, POLE 3, polymerase chain reaction, Polyoxometalates, Redox chemistry, Tungsten Compounds.

  • K. Jeanne Dit Fouque, H. Lavanant, S. Zirah, J. Lemoine, S. Rebuffat, J. - C. Tabet, A. Kulesza, C. Afonso, P. Dugourd, et F. Chirot, « Gas-phase conformations of capistruin – comparison of lasso, branched-cyclic and linear topologies », Rapid Communications in Mass Spectrometry, vol. 29, nᵒ 15, p. 1411-1419.
    Résumé : Rationale Capistruin is a peptide synthesized by Burkholderia thailandensis E264, which displays a lasso topology. This knot-like structure confers interesting properties to peptides (e.g. antibacterial). Therefore, it is important to evaluate the sensitivity of structural characterization methods to such topological constraints. Methods Ion mobility mass spectrometry (IMS-MS) experiments, using both drift tube and travelling wave instruments, were performed on lasso capistruin and on peptides with the same sequence, but displaying a branched-cyclic (un-threaded) or linear topology. Molecular dynamics (MD) simulations were then performed to further interpret the IMS results in terms of conformation. Results The collision cross sections (CCSs) measured via IMS for the different forms of capistruin were found to be similar, despite their different topologies for the doubly charged species, but significant differences arise as the charge state is increased. MD simulations for the doubly charged linear peptide were consistent with the hypothesis that salt bridges are present in the gas phase. Moreover, through CCS measurements for peptides with site-specific mutations, the arginine residue at position 11 was found to play a major role in the stabilization of compact structures for the linear peptide. Conclusions Differences in peptide topologies did not yield marked signatures in their respective IMS spectra. Such signatures were only visible for relatively high charge states, that allow Coulomb repulsion to force unfolding. At low charge states, the topologically unconstrained linear form of capistruin was found to adopt charge solvation-constrained structures, possibly including salt bridges, with CCSs comparable to those measured for the topologically constrained lasso form. Copyright © 2015 John Wiley & Sons, Ltd.
    Mots-clés : CSOB, POLE 3.

  • Y. Jiang, J. A. Madsen, V. Farutin, J. C. Lansing, et R. B. Cole, « High fidelity approach for proteomic scale enrichment and identification of N-termini », International Journal of Mass Spectrometry, vol. 391, p. 115-122.
    Résumé : A novel workflow was designed for the large-scale identification of protein N-terminal sequences. The workflow started with converting lysine to homoarginine, followed by reaction with sulfonation of N-termini by 4-sulfophenyl isothiocyanate (SPITC). Upon trypsin digestion, the SPITC modified N-terminal peptides were enriched by electrostatic repulsion hydrophilic interaction (ERLIC) chromatography in which the internal and C-terminal peptides eluted at the void volume, and the SPITC peptides were retained in the column due to the hydrophilicity and electrostatic attraction of the sulfonyl group to the stationary phase. Upon higher-energy collisional induced dissociation (HCD) SPITC peptides in ESI generated predominately y-type ion series; such simplification of spectra enables the identification of N-termini with high confidence. The appearance of b1 + SPITC product ions upon HCD further boosts the confidence for N-terminal identifications. This method was applied to an Escherichia coli cell lysate, thus allowing the identification of 358 high confidence N-terminal peptides representing 274 distinct E. coli proteins as certain proteins were found to have multiple N-terminal peptides due to cleavage from various cellular enzymes. Confidence in N-terminal assignments is further heightened since 224 of the unique proteins identified from N-terminal peptides were also identified in the analysis of flow-through fractions.
    Mots-clés : CSOB, ERLIC enrichment, N-termini proteomics, POLE 3, SPITC modification.

  • D. Lesage, G. Barozzino-Consiglio, R. Duwald, C. Fressigné, A. Harrison-Marchand, K. F. Faull, J. Maddaluno, et Y. Gimbert, « A Lithium Amide Protected Against Protonation in the Gas Phase: Unexpected Effect of LiCl », The Journal of Organic Chemistry, vol. 80, nᵒ 12, p. 6441-6446.
    Résumé : In cold THF and in the presence of LiCl, a lithium pyrrolidinylamide forms a 1:1 mixed aggregate, which is observed directly by ESI-MS. Gas-phase protonation of this species leads to selective transfer of H+ to the chlorine, suggesting that LiCl shields the amide nitrogen and prevents its direct protonation.
    Mots-clés : CSOB, POLE 3.

  • J. - C. Martin, M. Maillot, G. Mazerolles, A. Verdu, B. Lyan, C. Migné, C. Defoort, C. Canlet, C. Junot, C. Guillou, C. Manach, D. Jabob, D. J. - R. Bouveresse, E. Paris, E. Pujos-Guillot, F. Jourdan, F. Giacomoni, F. Courant, G. Favé, G. L. Gall, H. Chassaigne, J. - C. Tabet, J. - F. Martin, J. - P. Antignac, L. Shintu, M. Defernez, M. Philo, M. - C. Alexandre-Gouaubau, M. - J. Amiot-Carlin, M. Bossis, M. N. Triba, N. Stojilkovic, N. Banzet, R. Molinié, R. Bott, S. Goulitquer, S. Caldarelli, et D. N. Rutledge, « Can we trust untargeted metabolomics? Results of the metabo-ring initiative, a large-scale, multi-instrument inter-laboratory study », Metabolomics, vol. 11, nᵒ 4, p. 807-821.
    Résumé : The metabo-ring initiative brought together five nuclear magnetic resonance instruments (NMR) and 11 different mass spectrometers with the objective of assessing the reliability of untargeted metabolomics approaches in obtaining comparable metabolomics profiles. This was estimated by measuring the proportion of common spectral information extracted from the different LCMS and NMR platforms. Biological samples obtained from 2 different conditions were analysed by the partners using their own in-house protocols. Test #1 examined urine samples from adult volunteers either spiked or not spiked with 32 metabolite standards. Test #2 involved a low biological contrast situation comparing the plasma of rats fed a diet either supplemented or not with vitamin D. The spectral information from each instrument was assembled into separate statistical blocks. Correlations between blocks (e.g., instruments) were examined (RV coefficients) along with the structure of the common spectral information (common components and specific weights analysis). In addition, in Test #1, an outlier individual was blindly introduced, and its identification by the various platforms was evaluated. Despite large differences in the number of spectral features produced after post-processing and the heterogeneity of the analytical conditions and the data treatment, the spectral information both within (NMR and LCMS) and across methods (NMR vs. LCMS) was highly convergent (from 64 to 91 % on average). No effect of the LCMS instrumentation (TOF, QTOF, LTQ-Orbitrap) was noted. The outlier individual was best detected and characterised by LCMS instruments. In conclusion, untargeted metabolomics analyses report consistent information within and across instruments of various technologies, even without prior standardisation.
    Mots-clés : CSOB, POLE 3.

  • J. - P. Mbakidi, F. Brégier, T. - S. Ouk, R. Granet, S. Alves, E. Rivière, S. Chevreux, G. Lemercier, et V. Sol, « Magnetic Dextran Nanoparticles That Bear Hydrophilic Porphyrin Derivatives: Bimodal Agents for Potential Application in Photodynamic Therapy », ChemPlusChem, vol. 80, nᵒ 9, p. 1416-1426.
    Résumé : This study reports the chemical synthesis of a class of dextran superparamagnetic nanoparticles that bear hydrophilic porphyrin units covalently grafted by a click chemistry reaction in aqueous solution. Magnetic nanoparticles are used in magnetic resonance imaging (MRI) and hyperthermia, and the grafting of hydrophilic photosensitizers (PS) leads to elaborate new multifunctional platforms for potential diagnostic and targeted photodynamic therapy (PDT). The therapeutic potential for PDT of these nanoparticles is evaluated in vitro against the HaCaT cell line. The results show that these new multicharged nanomagnets—in particular, those that bear cationic porphyrins—show a significant uptake and an interesting photocytotoxic activity toward HaCaT cells. The whole series of these synthesized PS are massively incorporated inside HaCat cells and associated with mitochondria.
    Mots-clés : click chemistry, CSOB, Magnetic properties, nanoparticles, photodynamic therapy, POLE 3, porphyrinoids.

  • M. Pérot-Taillandier, C. Afonso, Q. Enjalbert, R. Antoine, P. Dugourd, R. B. Cole, J. - C. Tabet, S. Rebuffat, et S. Zirah, « Electron detachment/photodetachment dissociation of lasso peptides », International Journal of Mass Spectrometry, vol. 390, p. 91-100.
    Résumé : Lasso peptides are bioactive peptides produced by bacteria, characterized by a mechanically interlocked topology where the C-terminal tail of the peptide is threaded through and trapped within an N-terminal macrolactam ring. The structural characterization of lasso peptides and differentiation from their unthreaded topoisomers by mass spectrometry are challenging tasks. We previously explored the fragmentation mechanisms of lasso peptides in positive ion mode and showed several signatures of the lasso topology under collision induced dissociation (CID) and electron capture dissociation. Here we analyzed the dissociation of the multiply-deprotonated microcin J25 (MccJ25), a 21-residue lasso peptide produced by Escherichia coli, together with its non-lasso topoisomer and several variants generated by site-directed mutagenesis, under different modes of activation. The fragmentation patterns obtained by CID for the threaded and unthreaded structures were very similar. By contrast, electron detachment dissociation (EDD) as well as activated-electron photodetachment dissociation (a-EPD) revealed very different dissociation pathways for the two topoisomers. The doubly deprotonated topoisomers showed a different deprotonation pattern, Tyr20 residue being deprotonated for MccJ25 only, yielding the singly charged [c19−C2H4O] product ion. MccJ25 also triggered several two-peptide product ions diagnostic of the lasso topology, including the [(c8)*(z2)] species, which could be maintained by either a covalent or a non-covalent linkage.
    Mots-clés : CSOB, Electron detachment dissociation, Electron photodetachment dissociation, Lasso peptides, POLE 3.

  • B. P. Pozniak et R. B. Cole, « Perspective on Electrospray Ionization and Its Relation to Electrochemistry », Journal of The American Society for Mass Spectrometry, vol. 26, nᵒ 3, p. 369-385.
    Résumé : The phenomenon of electrospraying of liquids is presented from the perspective of the electrochemistry involved. Basics of current and liquid flow in the capillary and spray tip are discussed, followed by specifics of charging and discharging of the sprayed liquid surface. Fundamental theories and numerical modeling relating electrospray current to solution and spray parameters are described and then compared with our own experimentally obtained data. The method of mapping potentials and currents inside the electrospray capillary by using an inserted electrically-isolated small wire probe electrode is discussed in detail with illustrations from new and published data. Based on these experimentally obtained results, a new mathematical model is derived. The introduced “nonlinear resistor electrospray capillary model” divides the electrospray capillary into small sections, adds their contributions, and then, by transition to infinitely small section thickness, produces analytical formulas that relate current and potential maps to other properties of the electrospraying liquid: primarily conductivity and current density. The presentation of the model is undertaken from an elementary standpoint, and it offers the possibility to obtain quantitative information regarding operating parameters from typical analytical systems subjected to electrospray. The model stresses simplicity and ease of use; examples applying experimental data are shown and some predictions of the model are also presented. The developed nonlinear resistor electrospray capillary model is intended to provide a new quantitative basis for improving the understanding of electrochemical transformations occurring in the electrospray emitter. A supplemental material section gives full derivation of the model and discusses other consequences.Graphical Abstractᅟ
    Mots-clés : CSOB, POLE 3.

  • B. Quéméner, J. Vigouroux, E. Rathahao, J. C. Tabet, A. Dimitrijevic, et M. Lahaye, « Negative electrospray ionization mass spectrometry: a method for sequencing and determining linkage position in oligosaccharides from branched hemicelluloses », Journal of Mass Spectrometry, vol. 50, nᵒ 1, p. 247-264.
    Résumé : Xyloglucans of apple, tomato, bilberry and tamarind were hydrolyzed by commercial endo β-1-4-D-endoglucanase. The xylo-gluco-oligosaccharides (XylGos) released were separated on CarboPac PA 200 column in less than 15 min, and, after purification, they were structurally characterized by negative electrospray ionization mass spectrometry using a quadrupole time-of-flight (ESI-Q-TOF), a hybrid linear ion trap (LTQ)/Orbitrap and a hybrid quadrupole Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometers. In order to corroborate the fragmentation routes observed on XylGos, some commercial galacto-manno-oligosaccharides (GalMOs) and glucurono-xylo-oligosaccharides were also studied. The fragmentation pathways of the ionized GalMos were similar to those of XylGos ones. The product ion spectra were mainly characterized by prominent double cleavage (D) ions corresponding to the entire inner side chains. The directed fragmentation from the reducing end to the other end was observed for the main glycosylated backbone but also for the side-chains, allowing their complete sequencing. Relevant cross-ring cleavage ions from 0,2Xj -type revealed to be diagnostic of the 1-2-linked- glycosyl units from XylGos together with the 1-2-linked glucuronic acid unit from glucuronoxylans. Resonant activation in the LTQ Orbitrap allowed not only determining the type of all linkages but also the O-acetyl group location on fucosylated side-chains. Moreover, the fragmentation of the different side chains using the MSn capabilities of the LTQ/Orbitrap analyzer also allowed differentiating terminal arabinosyl and xylosyl substituents inside S and U side-chains of XylGos, respectively. The CID spectra obtained were very informative for distinction of isomeric structures differing only in their substitution pattern. These features together makes the fragmentation in negative ionization mode a relevant and powerful technique useful to highlight the subtle structural changes generally observed during the development of plant organs such as during fruit ripening and for the screening of cell wall mutants with altered hemicellulose structure. Copyright © 2015 John Wiley & Sons, Ltd.
    Mots-clés : CSOB, endo β-1-4 endoglucanase, hemicellulose, HPAEC, negative ESI-MS, POLE 3, xyloglucans.

  • A. Schwarzenberg, J. - C. Tabet, R. B. Cole, X. Machuron-Mandard, et H. Dossmann, « New insights into dissociation of deprotonated 2,4-dinitrotoluene by combined high-resolution mass spectrometry and density functional theory calculations », Rapid Communications in Mass Spectrometry, vol. 29, nᵒ 1, p. 29-34.
    Résumé : RATIONALE 2,4-Dinitrotoluene (2,4-DNT) is a nitroaromatic explosive which is commonly found in environmental samples close to training points, firing places, and manufacturers. Mass spectrometry analysis of this compound shows one main product ion that distinguishes it from the other isomers of DNT. We present here a detailed mechanistic study on the formation of this ion. METHODS 2,4-DNT was analyzed using negative electrospray ionization high-resolution mass spectrometry (ESI-HRMS) using a linear ion trap quadrupole LTQ-Orbitrap XL mass spectrometer. Collision-induced dissociation (CID) experiments were performed on the [M–H]– ion obtained. Density functional theory (DFT) calculations were used to support experimental observations. RESULTS Fragmentation of deprotonated 2,4-DNT [M–H]– (m/z 181) yields a main product ion at m/z 116. The mechanism of formation of this diagnostic product ion is not obvious and it has never been rationalized. Calculations were performed to probe different mechanistic variants, which are discussed in this work. CONCLUSIONS Analysis of possible pathways to form the m/z 116 ion from the m/z 181 precursor shows that its formation is likely to proceed first via NO• loss, followed by eliminations of H2O and then HO•. Copyright © 2014 John Wiley & Sons, Ltd.
    Mots-clés : CSOB, POLE 3.

  • J. Shraberg, S. W. Rick, N. Rannulu, et R. B. Cole, « A study of procyanidin binding to Histatin 5 using Electrospray Ionization Tandem Mass Spectrometry (ESI-MS/MS) and molecular simulations », Physical Chemistry Chemical Physics, vol. 17, nᵒ 18, p. 12247-12258.
    Résumé : Tannins act as antioxidants, anticarcinogens, cardio-protectants, anti-inflammatory and anti-microbial agents and bind to salivary peptides by hydrophilic and hydrophobic mechanisms. Electrospray Ionization Mass Spectrometry (ESI-MS) has been used to assess both hydrophilic and hydrophobic components of noncovalent binding in protein complexes. In the present study, direct infusion Electrospray-Fourier Transform Ion Cyclotron Resonance Mass Spectrometry (ES-FTICR MS) is used to assess relative binding affinities of procyanidin tannin stereoisomers for salivary peptides arising from aqueous solutions. The condensed tannins procyanidin B1, B2, B3, and B4 demonstrate significantly different binding affinities for the salivary peptide Histatin 5. Rigid docking combined with molecular dynamics optimization is used to investigate procyanidin–Histatin 5 binding mechanisms and as a basis to rationalize trends found in the corresponding ES-FTICR MS experiments. The relative binding affinities of the four procyanidin rotamers are different in the gas and liquid phases. The simulation results indicate that many of the same contact points are made in both phases, but there is a increase in strong electrostatic interactions and an decrease in π–π contacts upon transfer from the liquid to the gas phase. The simulations reveal that the tannin interactions can make close contacts with a variety of amino acid residues on the peptide.
    Mots-clés : CSOB, POLE 3.

  • V. P. Stankov-Jovanović, M. D. Ilić, V. D. Mitić, T. M. Mihajilov-Krstev, S. R. Simonović, S. D. Nikolić Mandić, J. C. Tabet, et R. B. Cole, « Secondary metabolites of Seseli rigidum: Chemical composition plus antioxidant, antimicrobial and cholinesterase inhibition activity », Journal of Pharmaceutical and Biomedical Analysis, vol. 111, p. 78-90.
    Résumé : Extracts of different polarity obtained from various plant parts (root, leaf, flower and fruit) of Seseli rigidum were studied by different antioxidant assays: DPPH and ABTS radical scavenging activity, by total reducing power method as well as via total content of flavonoids and polyphenols. Essential oils of all plant parts showed weak antioxidant characteristics. The inhibitory concentration range of the tested extracts, against bacteria Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Bacillus cereus, and fungi Candida albicans and Aspergillus niger was 0.01–1.50 mg/mL and of a microbicidal 0.02–3.00 mg/mL. In the interaction with cholinesterase, all essential oils proved effective as inhibitors. The highest percentage of inhibition versus human and horse cholinesterase was shown by root essential oil (38.20% and 48.30%, respectively) among oils, and root hexane extract (40.56% and 50.65% respectively). Essential oils and volatile components of all plant parts were identified by GC, GC–MS and headspace/GC–MS. Statistical analysis of the ensemble of results showed that the root essential oil composition differed significantly from essential oils of other parts of the plant. Taking into account all of the studied activities, the root hexane extract showed the best overall properties. By means of high performance liquid chromatography coupled to high resolution mass spectrometry, the 30 most abundant constituents were identified in extracts of different polarity. The presence of identified constituents was linked to observed specific biological activities, thus designating compounds potentially responsible for each exhibited activity.
    Mots-clés : Antimicrobial activity, antioxidant activity, Cholinesterase inhibition, CSOB, POLE 3, Secondary metabolites, Seseli rigidum.

  • T. Tripković, C. Charvy, S. Alves, A. D. Lolić, R. M. Baosić, S. N. Nikolić-Mandic, et J. C. Tabet, « Electrospray ionization linear trap quadrupole Orbitrap in analysis of old tempera paintings: application to nineteenth-century Orthodox icons », European Journal of Mass Spectrometry, vol. 21, nᵒ 4, p. 679-692.

  • A. Warnet, N. Auzeil, et J. - C. Tabet, « Unusual Post-Spray Proton Transfer to Protein Using Acetone Spray in Desorption Electrospray Ionization », Journal of Analytical & Bioanalytical Techniques, vol. 6, nᵒ 6.
    Résumé : Although acetone, in DESI ionisation generally leads to protein aggregation, in this study we report unexpected multi-proton transfers to lysozyme using this aprotic solvent as a charged spray. The DESI/acetone mass spectrum of lysozyme displays (i) a significant increase in the average charge state (Zav) and (ii) an incomplete H+/Ca2+ exchange, even though the overall contribution of cationised species is high, relative to those from spraying with a methanol/water solvent. This behavior is contrary to that expected from gas phase basicity, because GBacetone >GBmethanol. Decreasing the amount of sample deposited on the target (from 50 to 0.050 pmole) leads to a charge state increase, as seen in ESI, but not in the extent of cationisation. Moreover, the DESI signal duration is extended with sprayed acetone even though the total ionic current is significantly lowered. With a d6-acetone spray, no incorporation of a deuteron occurs, and the ionization yield is strongly decreased for multi-protonated lysoi+ lysozyme. This is in contrast to that observed with a d4-methanol spray, which displays a distribution of 48 deuterons in the lyso9+ ion as shown in high resolution with a LTQ/Orbitrap instrument. This unexpected behavior of the (CD3)2CO spray suggests that protons do not originate from acetone. Furthermore, dry argon post-flow on the target surface results in the lysozyme signal suppression, whereas with a humid argon flow, the signal is regenerated. On the other hand, an argon stream bubbling in heavy water, yields incorporation of several deuterons. The interpretation of this behavior is explained by considering the acetone radical ions at the surface of the primary droplets (and/or offspring droplets and/or at the wet sample surface), being able to react with ambient moisture (or with traces of water adsorbed at liquid phase). Under these conditions, enough protons are produced to generate multi-charged solvated lysozyme aggregates which then become desolvated in the reduced pressure in the skimmer area.
    Mots-clés : CSOB, POLE 3.

  • Z. Zendong, P. McCarron, C. Herrenknecht, M. Sibat, Z. Amzil, R. B. Cole, et P. Hess, « High resolution mass spectrometry for quantitative analysis and untargeted screening of algal toxins in mussels and passive samplers », Journal of Chromatography A, vol. 1416, p. 10-21.

    Résumé : Measurement of marine algal toxins has traditionally focussed on shellfish monitoring while, over the last decade, passive sampling has been introduced as a complementary tool for exploratory studies. Since 2011, liquid chromatography–tandem mass spectrometry (LC–MS/MS) has been adopted as the EU reference method (No. 15/2011) for detection and quantitation of lipophilic toxins. Traditional LC–MS approaches have been based on low-resolution mass spectrometry (LRMS), however, advances in instrument platforms have led to a heightened interest in the use of high-resolution mass spectrometry (HRMS) for toxin detection. This work describes the use of HRMS in combination with passive sampling as a progressive approach to marine algal toxin surveys. Experiments focused on comparison of LRMS and HRMS for determination of a broad range of toxins in shellfish and passive samplers. Matrix effects are an important issue to address in LC–MS; therefore, this phenomenon was evaluated for mussels (Mytilus galloprovincialis) and passive samplers using LRMS (triple quadrupole) and HRMS (quadrupole time-of-flight and Orbitrap) instruments. Matrix-matched calibration solutions containing okadaic acid and dinophysistoxins, pectenotoxin, azaspiracids, yessotoxins, domoic acid, pinnatoxins, gymnodimine A and 13-desmethyl spirolide C were prepared. Similar matrix effects were observed on all instruments types. Most notably, there was ion enhancement for pectenotoxins, okadaic acid/dinophysistoxins on one hand, and ion suppression for yessotoxins on the other. Interestingly, the ion selected for quantitation of PTX2 also influenced the magnitude of matrix effects, with the sodium adduct typically exhibiting less susceptibility to matrix effects than the ammonium adduct. As expected, mussel as a biological matrix, quantitatively produced significantly more matrix effects than passive sampler extracts, irrespective of toxin. Sample dilution was demonstrated as an effective measure to reduce matrix effects for all compounds, and was found to be particularly useful for the non-targeted approach. Limits of detection and method accuracy were comparable between the systems tested, demonstrating the applicability of HRMS as an effective tool for screening and quantitative analysis. HRMS offers the advantage of untargeted analysis, meaning that datasets can be retrospectively analyzed. HRMS (full scan) chromatograms of passive samplers yielded significantly less complex data sets than mussels, and were thus more easily screened for unknowns. Consequently, we recommend the use of HRMS in combination with passive sampling for studies investigating emerging or hitherto uncharacterized toxins.
    Mots-clés : CSOB, Marine toxins, Matrix effects, Monitoring, Passive sampling, POLE 3, SPATT.


  • S. Boudah, M. - F. Olivier, S. Aros-Calt, L. Oliveira, F. Fenaille, J. - C. Tabet, et C. Junot, « Annotation of the human serum metabolome by coupling three liquid chromatography methods to high-resolution mass spectrometry », Journal of Chromatography B-Analytical Technologies in the Biomedical and Life Sciences, vol. 966, p. 34-47.
    Résumé : This work aims at evaluating the relevance and versatility of liquid chromatography coupled to high resolution mass spectrometry (LC/HRMS) for performing a qualitative and comprehensive study of the human serum metabolome. To this end, three different chromatographic systems based on a reversed phase (RP), hydrophilic interaction chromatography (HILIC) and a pentafluorophenylpropyl (PFPP) stationary phase were used, with detection in both positive and negative electrospray modes. LC/HRMS platforms were first assessed for their ability to detect, retain and separate 657 metabolite standards representative of the chemical families occurring in biological fluids. More than 75% were efficiently retained in either one LC-condition and less than 5% were exclusively retained by the RP column. These three LC/HRMS systems were then evaluated for their coverage of serum metabolome. The combination of RP, HILIC and PFPP based LC/HRMS methods resulted in the annotation of about 1328 features in the negative ionization mode, and 1358 in the positive ionization mode on the basis of their accurate mass and precise retention time in at least one chromatographic condition. Less than 12% of these annotations were shared by the three LC systems, which highlights their complementarity. HILIC column ensured the greatest metabolome coverage in the negative ionization mode, whereas PFPP column was the most effective in the positive ionization mode. Altogether, 192 annotations were confirmed using our spectral database and 74 others by performing MS/MS experiments. This resulted in the formal or putative identification of 266 metabolites, among which 59 are reported for the first time in human serum. (C) 2014 Elsevier B.V. All rights reserved.
    Mots-clés : CSOB, database, extraction, fragmentation trees, high resolution mass spectrometry, identification, liquid chromatography, Metabolite identification, Metabolome annotation, metabolomics, ms, performance, phase stationary phases, POLE 3, reversed-phase, serum, strategy, Structure elucidation, Tandem mass spectrometry.

  • J. Cotton, F. Leroux, S. Broudin, M. Marie, B. Corman, J. - C. Tabet, C. Ducruix, et C. Junot, « High-Resolution Mass Spectrometry Associated with Data Mining Tools for the Detection of Pollutants and Chemical Characterization of Honey Samples », Journal of Agricultural and Food Chemistry, vol. 62, nᵒ 46, p. 11335-11345.
    Résumé : Analytical methods for food control are mainly focused on restricted lists of well-known contaminants. This paper shows that liquid chromatography high-resolution mass spectrometry (LC/ESI-HRMS) associated with the data mining tools developed for metabolomics can address this issue by enabling (i) targeted analyses of pollutants, (ii) detection of untargeted and unknown xenobiotics, and (iii) detection of metabolites useful for the characterization of food matrices. A proof-of-concept study was performed on 76 honey samples. Targeted analysis indicated that 35 of 83 targeted molecules were detected in the 76 honey samples at concentrations below regulatory limits. Furthermore, untargeted metabolomic-like analyses highlighted 12 chlorinated xenobiotics, 1 of which was detected in lavender honey samples and identified as 2,6-dichlorobenzamide, a metabolite of dichlobenil, a pesticide banned in France since 2010. Lastly, multivariate statistical analyses discriminated honey samples according to their floral origin, and six discriminating metabolites were characterized thanks to the MS/MS experiments.
    Mots-clés : bees, contaminants, CSOB, data mining, Electrospray, food analysis, gas, high-resolution mass spectrometry, honey, liquid chromatography, Metabolite, metabolite identification, metabolomics, multi-residue analysis, multiresidue, performance liquid-chromatography, pesticides, POLE 3, pollutants, vegetables, veterinary drugs, waste-water, water samples, xenobiotics.

  • E. Darii, G. Saravanamuthu, I. G. Gut, et J. - C. Tabet, « Structural studies of the sBBI/trypsin non-covalent complex using covalent modification and mass spectrometry », Rapid Communications in Mass Spectrometry, vol. 28, nᵒ 5, p. 413-429.
    Résumé : RATIONALEThe study of protein recognition sites is crucial for understanding the mechanisms of protein interaction. Mass spectrometry can be a method of choice for the investigation of the contact surface within the protein non-covalent complexes. METHODSProbing the reactivity of essential amino acid residues of soybean Bowman-Birk inhibitor (sBBI) within the non-covalent sBBI/bovine trypsin complex was performed using covalent labeling by the BS3 cross-linker and charge tag with a quaternary ammonium group in combination with matrix-assisted laser desorption/ionization (MALDI) mass spectrometry (MS) and tandem mass spectrometry (MS/MS) analysis. RESULTSSignificant modulation of the reactivity of essential K16 and S17 residues in the sBBI molecule upon binding to trypsin was established. The studies of sBBI proteolytic peptides with the same structure but carrying different labels using metastable dissociation in LIFT mode demonstrated that fragmentation pathways were oriented by used modification (BS3 cross-linker or charge tag). CONCLUSIONSThe effectiveness of the mass spectrometric approach including covalent modification for exploring protein-protein interaction sites has been demonstrated. The alteration of the reactivity of functionally important amino acid residues in the sBBI molecule is most likely related to changes in their microenvironment. It has been suggested that in the presence of charge tags fragmentation in LIFT mode proceeds through the formation of salt bridges between quaternary ammonium groups and acidic residues due to the occurrence of zwitterions (including basic and acidic residues). Despite the presence of one or several charge tags, fragmentation takes place yielding modulated b(i)/y(j) ion series depending on the positions of the tags. Copyright (c) 2014 John Wiley & Sons, Ltd.
    Mots-clés : bowman-birk inhibitor, charge-remote fragmentation, chemical cross-linking, collision-induced dissociation, crystal-structure, CSOB, ionizable groups, n-hydroxysuccinimide esters, POLE 3, protein-protein interactions, protonated peptides, soybean trypsin-inhibitors.

  • H. Dossmann, A. Schwarzenberg, D. Lesage, M. Perot-Taillandier, C. Afonso, B. C. de Miranda, et G. A. Garcia, « Vacuum Ultraviolet Photoionization Study of Gas Phase Vitamins A and B1 Using Aerosol Thermodesorption and Synchrotron Radiation », Journal of Physical Chemistry A, vol. 118, nᵒ 47, p. 11185-11192.
    Résumé : Gas-phase studies of biomolecules are often difficult to initiate because of the thermolability of these systems. Such studies are nevertheless important to determine fundamental intrinsic properties of the molecules. Here we present the valence shell photoionization of gas-phase vitamins A and B1 close to their ionization threshold. The study was performed by means of an aerosol thermodesorption source coupled to an electron/ion coincidence spectrometer and synchrotron radiation (SOLEIL facility, France). Ion yield curves were recorded for both molecules over a few electronvolt energy range and the threshold photoelectron spectrum was also obtained for vitamin A. Some fundamental properties were extracted for both ions such as adiabatic and the three first vertical ionization energies of retinol (IEad = 6.8 +/- 0.2 eV and IEvert = 7.4, 8.3, and 9.2 eV) and dissociation appearance energies for the main fragment ions of vitamin B1. Analysis of the data was supported by ab initio calculations which show a very good agreement with the experimental observations.
    Mots-clés : approximate, atoms, basis-sets, CSOB, energies, high-resolution, mass-spectrometry, POLE 3, retinoic acid, spectra, spin.

  • Q. Dumont et R. B. Cole, « Jean-Antoine Nollet: The Father of Experimental Electrospray », Mass Spectrometry Reviews, vol. 33, nᵒ 6, p. 418-423.
    Résumé : The development of electrospray ionization mass spectrometry (ESI-MS) was a 20th century occurrence that underwent rapid acceleration especially in the 1990's. However, long prior to its coupling with mass spectrometry, the electrification of liquids had been studied in a variety of contexts. Although initial reports describing cone formation upon electrification of water drops came out of England, the first true experiments investigating the electrospray phenomenon were performed in the middle of the 18th century by Abbe Jean-Antoine Nollet. The current report, associated with the French Regional Issue of Mass Spectrometry Reviews, examines the contributions of Abbe Nollet to the earliest understanding of the electrospray phenomenon. A description of his accomplishments is placed in the context of the societal and scientific developments of the Age of Enlightenment out of which Jean-Antoine Nollet arose. (c) 2013 Wiley Periodicals, Inc. Mass Spec Rev 33: 418-423, 2014.
    Mots-clés : CSOB, POLE 3.

  • G. A. Garcia, H. Dossmann, L. Nahon, S. Daly, et I. Powis, « Photoelectron circular dichroism and spectroscopy of trifluoromethyl- and methyl-oxirane: a comparative study », Physical Chemistry Chemical Physics, vol. 16, nᵒ 30, p. 16214-16224.
    Résumé : Photoelectron circular dichroism (PECD), a forward-backward asymmetry along the light propagation direction observed in the angular distribution of photoelectrons formed in the ionization of a chiral gas phase target with circularly polarized light, is becoming an established technique for chiral differentiation. In this work some of the fundamental and analytical properties of PECD are confirmed and explored further through a comparative study of the valence shell photoionization of enantiomerically pure trifluoromethyl-oxirane and methyloxirane, namely the sensitivity of PECD to the initial orbital and to chemical substitution. The recorded PECD experimental data and corresponding continuum multiple scattering calculations for the outermost orbitals obtained at various photon energies reveal the dramatic effect of substituting the CF3 and CH3 groups attached at the asymmetric chiral center. The previously unknown trifluoromethyl-oxirane ion spectroscopy and the fragmentation pattern measured by threshold electron/ion coincidence techniques over the first four eVs above the ionization threshold are also presented in this work and assigned through the use of ab initio calculations. The state-selected photochemistry and threshold electron spectroscopy of methyl-oxirane have additionally been recorded to complement previous spectroscopic studies.
    Mots-clés : angular-distribution, asymmetry, camphor, chiral molecules, co molecule, CSOB, enantiomers, gas-phase, photoionization, POLE 3, synchrotron-radiation, variable-polarization.

  • C. Hubert, A. Schwarzenberg, H

    . Dossmann, R. B. Cole, X. Machuron-Mandard, et J. - C. Tabet, « Clarification of the 30 Da releases from the [M-H](-) and M-. ions of trinitrotoluene by electrospray high resolution mass spectrometry », Journal of Mass Spectrometry, vol. 49, nᵒ 4, p. 327-330.
    Mots-clés : ch2o, CSOB, esi, explosives, high resolution, mass spectrometry, POLE 3, tnt.

  • F. Ichou, A. Schwarzenberg, D. Lesage, S. Alves, C. Junot, X. Machuron-Mandard, et J. - C. Tabet, « Comparison of the activation time effects and the internal energy distributions for the CID, PQD and HCD excitation modes », Journal of Mass Spectrometry, vol. 49, nᵒ 6, p. 498-508.
    Résumé : Reproducibility among different types of excitation modes is a major bottleneck in the field of tandem mass spectrometry library development in metabolomics. In this study, we specifically evaluated the influence of collision voltage and activation time parameters on tandem mass spectrometry spectra for various excitation modes [collision-induced dissociation (CID), pulsed Q dissociation (PQD) and higher-energy collision dissociation (HCD)] of Orbitrap-based instruments. For this purpose, internal energy deposition was probed using an approach based on Rice-Rampserger-Kassel-Marcus modeling with three thermometer compounds of different degree of freedom (69, 228 and 420) and a thermal model. This model treats consecutively the activation and decomposition steps, and the survival precursor ion populations are characterized by truncated Maxwell-Boltzmann internal energy distributions. This study demonstrates that the activation time has a significant impact on MS/MS spectra using the CID and PQD modes. The proposed model seems suitable to describe the multiple collision regime in the PQD and HCD modes. Linear relationships between mean internal energy and collision voltage are shown for the latter modes and the three thermometer molecules. These results suggest that a calibration based on the collision voltage should provide reproducible for PQD, HCD to be compared with CID in tandem in space instruments. However, an important signal loss is observed in PQD excitation mode whatever the mass of the studied compounds, which may affect not only parent ions but also fragment ions depending on the fragmentation parameters. A calibration approach for the CID mode based on the variation of activation time parameter is more appropriate than one based on collision voltage. In fact, the activation time parameter in CID induces a modification of the collisional regime and thus helps control the orientation of the fragmentation pathways (competitive or consecutive dissociations). Copyright (c) 2014 John Wiley & Sons, Ltd.
    Mots-clés : activation time, cid, collisional activation, CSOB, electrospray-ionization, fragmentation, gas reactions, hcd, induced dissociation spectra, internal energy distribution, metabolomics, POLE 3, pqd, protonated leucine-enkephalin, quadrupole ion-trap, RRKM modeling, surface-induced dissociation, tandem mass-spectrometry, Temperature.

  • C. Le Vot, C. Afonso, C. Beaugrand, et J. - C. Tabet, « Penning ionization-FT-ICR: Application to diesel fuel analysis », International Journal of Mass Spectrometry, vol. 367, p. 35-42.
    Résumé : The Penning ionization (Pel) source uses atoms of rare gases or molecules (N-2) excited to give a flux of metastable atoms or molecules (A*) able by collision to ionize a target molecule (M) on the condition that the process is exothermic (i.e., IE(M)< EE(A)). As electron ionization, PeI allows the ionization of apolar species such as saturated hydrocarbons yielding molecular ions. In this work we present the application of vacuum PeI source coupled with a FT-ICR instrument for the characterization of a diesel fuel. Argon and krypton, as metastable gas, allow reducing significantly the fragmentation extent compared to electron ionization. Unlike with an atmospheric pressure source, the use of a vacuum source allows a good control of the ionization conditions with the absence of oxygen or other reactant such as water. (c) 2014 Elsevier B.V. All rights reserved.
    Mots-clés : aromatic-compounds, benzothiophene, CSOB, Diesel fuel, elemental composition, ft-icr, hydrocarbons, identification, Metastable, oil, Penning ionization, POLE 3, pressure chemical-ionization, refinery streams, resolution, resonance mass-spectrometry.

  • D. Lesage, A. Milet, A. Memboeuf, J. Blu, A. E. Greene, J. - C. Tabet, et Y. Gimbert, « The Pauson-Khand Mechanism Revisited: Origin of CO in the Final Product », Angewandte Chemie-International Edition, vol. 53, nᵒ 7, p. 1939-1942.
    Résumé : The mechanism of the Pauson-Khand reaction has been studied by mass spectrometry and it has been found, through ion-molecule reaction with (CO)-C-13, that the carbon monoxide incorporated into the product cyclopentenone is one that has been retained within the complex. Theoretical and kinetic calculations support this finding, which provides a complementary explanation for the effect of Pauson-Khand promoters.
    Mots-clés : cobalt, CSOB, cyclizations, density functional calculations, gas-phase reactions, ionization mass-spectrometry, mass spectrometry, n-oxide, POLE 3, Reaction mechanisms.

  • X. Liu et R. B. Cole, « "Best Match" Model and Effect of Na+/H+ Exchange on Anion Attachment to Peptides and Stability of Formed Adducts in Negative Ion Electrospray Mass Spectrometry », Journal of the American Society for Mass Spectrometry, vol. 25, nᵒ 2, p. 204-213.
    Résumé : The "Best Match" model has been extended to account for the role that Na+/H+ exchange plays on anion attachment in negative ion electrospray. Without any Na+/H+ exchange on (Glu) fibrinopeptide B, the higher basicity anions F- and CH3COO- can hardly form observable adducts; however, after multiple Na+/H+ exchanges, adduct formation is enabled. Moreover, dissociation pathways of CF3COO- adducts with singly deprotonated peptides that have undergone 0 to 3 Na+/H+ exchanges exhibit a shift in CID product ions from losing predominately CF3COOH (case of 0 Na+/H+ exchanges) to losing predominately CF3COO- (case of 3 Na+/H+ exchanges). These phenomena can be rationalized by considering that Na+ cations exchange at, and serve to "block", the most acidic sites, thereby forcing implicated anions to attach to lower acidity protons. In addition to forming ion pairs with carboxylate groups, Na+ also participates in formation of tri-atomic ions of the form ANaA(-) during adduct dissociation. The fact that low gas-phase basicity (GB) anions preferentially form ANaA(-) species, even though high GB anions form more stable tri-atomic species, indicates that the monatomic ions were not in close contact in the initial adduct. The propensity for formation of stable anionic adducts is dependent on the degree of matching between anion GBs and GB(app) of deprotonated sites on the peptide. The GB(app) is raised dramatically as the charge state of the peptide increases via a through-space effect. The presence of Na+ on carboxylate sites substantially decreases the GB(app) by neutralizing these sites, while slightly increasing the intrinsic GBs by an inductive effect.
    Mots-clés : absence, Anion attachment, Anionic adducts, Best Match model, charge-state, CSOB, Gas-phase acidity, Gas-phase basicity, ionization, Negative ion, Peptide adducts, POLE 3, protein ions, solvent.

  • X. Liu, J. - C. Tabet, et R. B. Cole, « Evidence for ion-ion interactions between peptides and anions (HSO4- or ClO4-) derived from high-acidity acids », Journal of Mass Spectrometry, vol. 49, nᵒ 6, p. 490-497.
    Résumé : The existence of gas-phase electrostatic ion-ion interactions between protonated sites on peptides ([Glu] Fibrinopeptide B, Angiotensin I and [Asn1, Val5]-Angiotensin II) and attaching anions (ClO4- and HSO4-) derived from strong inorganic acids has been confirmed by CID MS/MS. Evidence for ion-ion interactions comes especially from the product ions formed during the first dissociation step, where, in addition to the expected loss of the anion or neutral acid, other product ions are also observed that require covalent bond cleavage (i.e. H2O loss when several carboxylate groups are present, or NH3 loss when only one carboxylate group is present). For [[Glu] Fibrinopeptide B+HSO4]-, under CID, H2O water loss was found to require less energy than H2SO4 departure. This indicates that the interaction between HSO4- and the peptide is stronger than the covalent bond holding the hydroxyl group, and must be an ion-ion interaction. The strength and stability of this type of ion-pairing interaction are highly dependent on the accessibility of additional mobile charges to the site. Positive mobile charges such as protons from the peptide can be transferred to the attaching anion to possibly form a neutral that may depart from the complex. Alternatively, an ion-ion interaction can be disrupted by a competing proximal additional negatively charged site of the peptide that can potentially form a salt bridge with the positively charged site and thereby facilitate the attaching anion's departure. Copyright (c) 2014 John Wiley & Sons, Ltd.
    Mots-clés : adduct, Anion attachment, best match model, bronsted acids, cations, complexes, CSOB, gas-phase acidity, mass-spectrometry, POLE 3, protein ions, salt bridge, salt-bridge interactions, Stability.

  • A. Martelet, G. L'Hostis, P. Tavares, S. Brasiles, F. Fenaille, C. Rozand, A. Theretz, G. Gervasi, J. - C. Tabet, E. Ezan, C. Junot, B. H. Muller, et F. Becher, « Bacterial Detection Using Unlabeled Phage Amplification and Mass Spectrometry through Structural and Nonstructural Phage Markers », Journal of Proteome Research, vol. 13, nᵒ 3, p. 1450-1465.
    Résumé : According to the World Health Organization, food safety is an essential public health priority. In this context, we report a relevant proof of feasibility for the indirect specific detection of bacteria in food samples using unlabeled phage amplification coupled to ESI mass spectrometry analysis and illustrated with the model phage systems T4 and SPP1. High-resolving power mass spectrometry analysis (including bottom-up and top-down protein analysis) was used for the discovery of specific markers of phage infection. Structural components of the viral particle and nonstructural proteins encoded by the phage genome were identified. Then, targeted detection of these markers was performed on a triple quadrupole mass spectrometer operating in the selected reaction monitoring mode. E. coli at 1 X 10(5), 5 X 10(5), and 1 X 10(6) CFU/mL concentrations was successfully detected after only a 2 h infection time by monitoring phage T4 structural markers in Luria-Bertani broth, orange juice, and French bean stew ("cassoulet") matrices. Reproducible detection of nonstructural markers was also demonstrated, particularly when a high titer of input phages was required to achieve successful amplification. This strategy provides a highly time-effective and sensitive assay for bacterial detection.
    Mots-clés : assay, bacillus-subtilis, bacterial detection, bacteriophage spp1, CSOB, gene, high-resolving power mass spectrometry, identification, ionization, marker discovery, nonstructural protein, pathogen detection, POLE 3, protein-synthesis, proteomics, quantification, srm, unlabeled phage.

  • J. - C. Martin, M. Maillot, G. Mazerolles, A. Verdu, B. Lyan, C. Migné, C. Defoort, C. Canlet, C. Junot, C. Guillou, C. Manach, D. Jabob, D. J. - R. Bouveresse, E. Paris, E. Pujos-Guillot, F. Jourdan, F. Giacomoni, F. Courant, G. Favé, G. L. Gall, H. Chassaigne, J. - C. Tabet, J. - F. Martin, J. - P. Antignac, L. Shintu, M. Defernez, M. Philo, M. - C. Alexandre-Gouaubau, M. - J. Amiot-Carlin, M. Bossis, M. N. Triba, N. Stojilkovic, N. Banzet, R. Molinié, R. Bott, S. Goulitquer, S. Caldarelli, et D. N. Rutledge, « Can we trust untargeted metabolomics? Results of the metabo-ring initiative, a large-scale, multi-instrument inter-laboratory study », Metabolomics, p. 1-15.
    Mots-clés : Biochemistry, general, Biomedicine general, Cell Biology, CSOB, Developmental Biology, Inter-laboratory, mass spectrometry, Metabolic fingerprinting, Molecular Medicine, Nuclear magnetic resonance, POLE 3, Untargeted metabolomics.

  • F. Mauger, J. - C. Tabet, et I. G. Gut, « A revisit of high collision energy effects on collision-induced dissociation spectra using matrix-assisted laser desorption/ionization tandem time-of-flight mass spectrometry (MALDI-LIFT-TOF/TOF): application to the sequencing of RNA/DNA chimeras », Rapid Communications in Mass Spectrometry, vol. 28, nᵒ 13, p. 1433-1443.
    Résumé : RATIONALEHigh-energy collision-induced dissociation (CID) spectra of isomeric RNA/DNA chimeras using matrix-assisted laser desorption/ionization time-of-flight LIFT mass spectrometry (MALDI-LIFT-TOF/TOF) can potentially be applied for an exhaustive fragment characterization in a nucleic acid sequencing scheme. These chimeras contain deoxynucleotides and at the 3'-end a ribonucleotide with a 3'-phosphate group. METHODSDeprotonated RNA/DNA chimeras of 4-, 5-, 7- and 10-mers are analyzed by CID. This enhances consecutive dissociations from both the precursor and prompt product anions generated by MALDI and metastable fragmentations prior to entering the LIFT cell. RESULTSGas-phase fragmentations of 4- and 5-mers produced many fragment ions, from base release prior to consecutive cleavage of the nucleotide phosphate bond linkage phosphate. The unusual a4- product ion is a specific and diagnostic dissociation of the 4-mer if the ribonucleotide contains cytosine. As the size of RNA/DNA chimeras increase, several abundant product ions are generated mainly from zwitterionic forms (deprotonated phosphate ester and protonated base sites): [(M-H)-BiH]-, [ai-BiH]-, wj-, [wj, (ai-BiH)]- (if BiT) as internal product ion, and more rarely [wj-BiH]-. The absence of the majority of the [ai-BiH]- series although the wj- series suggested that the higher critical energy processes with a loose transition state are favored yielding the wj- series. A large number of abundant fragment ions are detected which enable each isomer to be sequenced. CONCLUSIONSThis sequencing method is high-throughput, accurate and could be used to sequence isomers of up to 10-mers and also oligonucleotides of unknown sequence. However, RNA/DNA chimeras without thymine must be sufficiently concentrated to reach desorption of deprotonated molecular species to be selected in LIFT to produce all fragment ions within measurable abundances. Copyright (c) 2014 John Wiley & Sons, Ltd.
    Mots-clés : alkali cleavage, CSOB, DNA, in-source fragmentation, metastable decay, modified oligonucleotides, nucleic-acids, oligodeoxynucleotides, POLE 3, post-source-decay, rna fragmentation, tof-ms.

  • S. S. Quadri, R. E. Stratford, S. M. Boue, et R. B. Cole, « Identification of Glyceollin Metabolites Derived from Conjugation with Glutathione and Glucuronic Acid in Male ZDSD Rats by Online Liquid Chromatography-Electrospray Ionization Tandem Mass Spectrometry », Journal of Agricultural and Food Chemistry, vol. 62, nᵒ 12, p. 2692-2700.
    Résumé : Glyceollin-related metabolites produced in rats following oral glyceollin administration were screened in plasma, feces, and urine, and these metabolites were identified by precursor and product ion scanning using liquid chromatography coupled online with electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS). Precursor ion scanning in the negative ion (NI) mode was used to identify all glyceollin metabolites based on production of a diagnostic radical product ion (m/z 148) upon decomposition. Using this approach, precursor peaks of interest were found at m/z 474 and 531. Tandem mass spectra of these two peaks allowed us to characterize them as byproducts of glutathione conjugation. The peak at m/z 474 was identified as the deprotonated cysteinyl conjugate of glyceollins with an addition of an oxygen atom, whereas m/z 531 was identified as the deprotonated cysteinylglyceine glyceollin conjugate plus an oxygen. These results were confirmed by positive ion (PI) mode analyses. Mercapturic acid conjugates of glyceollins were also identified in NI mode. In addition, glucuronidation of glyceollins was observed, giving a peak at m/z 513 corresponding to the deprotonated conjugate. Production of glucuronic acid conjugates of glyceollins was confirmed in vitro in rat liver microsomes. Neither glutathione conjugation byproducts nor glucuronic acid conjugates of glyceollins have been previously reported.
    Mots-clés : cancer, CSOB, flavonoids, genistein, in-vitro, isoflavones, model, Pharmacokinetics, phase I metabolism, phase II metabolism, phytoalexins, phytochemicals, phytoestrogens, POLE 3, reactive oxygen species, soy, soybean glyceollins, women.

  • E. Rathahao-Paris, A. Paris, J. Bursztyka, J. - P. Jaeg, J. - P. Cravedi, et L. Debrauwer, « Identification of xenobiotic metabolites from biological fluids using flow injection analysis high-resolution mass spectrometry and post-acquisition data filtering », Rapid Communications in Mass Spectrometry, vol. 28, nᵒ 24, p. 2713-2722.
    Résumé : RATIONALE Concern for public health entails the need to evaluate the degree of exposure of population to toxicants. To do this, robust high-throughput approaches are required to be able to perform a large number of analyses in cohort studies. In this study, a data-filtering procedure was applied to mass spectral data acquired by direct analysis of biological fluids leading to rapid detection of metabolites in a model xenobiotic system. METHODS Flow injection analysis (FIA) coupled to negative electrospray ionization (ESI)-LTQ Orbitrap Fourier transform mass spectrometry was used to directly analyze urine of rats treated with vinclozolin. Tandem mass spectrometry (MS/MS) experiments were subsequently performed for confirmation of a new metabolite structure. The isotope filtering based on the difference between accurate masses of 35Cl and 37Cl was applied to the raw data for the specific detection of ions containing at least one chlorine atom. RESULTS Seven metabolites of vinclozolin were manually identified thanks to the characteristic isotope pattern of dichlorinated compounds. A new metabolite of vinclozolin was detected for the first time and identified as a sulfate conjugate. The application of an isotope-filtering procedure allowed the selective extraction of pertinent signals from the data. The processed mass spectrum was greatly simplified, significantly facilitating the detection of the seven metabolites previously identified. CONCLUSIONS The use of FIA-HRMS in combination with dedicated bio-informatics data processing is shown to be an efficient approach for the rapid detection of metabolites in biological fluids. This is a very promising high-throughput approach for rapid characterization of the exposure status to xenobiotics. Copyright © 2014 John Wiley & Sons, Ltd.
    Mots-clés : CSOB, POLE 3.

  • A. Schwarzenberg, H. Dossmann, R. B. Cole, X. Machuron-Mandard, et J. - C. Tabet, « Differentiation of isomeric dinitrotoluenes and aminodinitrotoluenes using electrospray high resolution mass spectrometry », Journal of Mass Spectrometry, vol. 49, nᵒ 12, p. 1330-1337.
    Résumé : Explosive detection and identification play an important role in the environmental and forensic sciences. However, accurate identification of isomeric compounds remains a challenging task for current analytical methods. The combination of electrospray multistage mass spectrometry (ESI-MSn) and high resolution mass spectrometry (HRMS) is a powerful tool for the structure characterization of isomeric compounds. We show herein that resonant ion activation performed in a linear quadrupole ion trap allows the differentiation of dinitrotoluene isomers as well as aminodinitrotoluene isomers. The explosive-related compounds: 2,4-dinitrotoluene (2,4-DNT), 2,6-dinitrotoluene (2,6-DNT), 2-amino-4,6-dinitrotoluene (2A-4,6-DNT) and 4-amino-2,6-dinitrotoluene (4A-2,6-DNT) were analyzed by ESI-MS in the negative ion mode; they produced mainly deprotonated molecules [M-H](-). Subsequent low resolution MSn experiments provided support for fragment ion assignments and determination of consecutive dissociation pathways. Resonant activation of deprotonated dinitrotoluene isomers gave different fragment ions according to the position of the nitro and amino groups on the toluene backbone. Fragment ion identification was bolstered by accurate mass measurements performed using Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR/MS). Notably, unexpected results were found from accurate mass measurements performed at high resolution for 2,6-DNT where a 30-Da loss was observed that corresponds to CH2O departure instead of the expected isobaric NO center dot loss. Moreover, 2,4-DNT showed a diagnostic fragment ion at m/z 116, allowing the unambiguous distinction between 2,4- and 2,6-DNT isomers. Here, CH2O loss is hindered by the presence of an amino group in both 2A-4,6-DNT and 4A-2,6-DNT isomers, but nevertheless, these isomers showed significant differences in their fragmentation sequences, thus allowing their differentiation. DFT calculations were also performed to support experimental observations. Copyright (c) 2014 John Wiley & Sons, Ltd.
    Mots-clés : aminodinitrotoluenes, CSOB, dinitrotoluenes, esi-hrms, explosives, gas-chromatography, high resolution mass spectrometry, ionization, ions, isomer differentiation, liquid-chromatography, nitramine, nitrate ester explosives, POLE 3, spectra, trace analysis, trinitrotoluene, water.


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