Research interests:
Mass spectrometry: instrumentation, ion chemistry and thermochemistry, ion activation, application in metabolomics, in security and environment and doping.
Current research:
The following works are developed by my old team (S. Alves, H. Dossman, C. Charvy, D. Lesage, H. Nedev, Surrugue M., and P. Colomby and A. Warnet) which is now under the direction of my colleague, R. Cole. The role played by my PhD students, post-docts and visiting professors was undeniable in the described topics:
1. Instrumentation
i) Development of the coupling of Penning source and FT-ICR. (Ii) Optimization by simion program of the coupling of cubic ion trap and linar ion trap and modification of the ETD into EI source. (iii) Optimization of the coupling DESI, DRT and paper spray with the LQT/Orbitrap tandem.
2. Fundamental.
based on the internal energy of ions in ESI, thermochemistry (acidity / basicity in the gas phase), and the RRKM theory (program MassKinetic).
(a) Internal energy of the molecular ion species for: (i) building of MS/MS databases and an algorithm for structural elucidation of unknown compounds. (Ii) direct applications in the fields of metabolomics, environment, homeland security and legal sciences as well as in the doping detection.
(b) Chemical reactivity and catalysis in the gas phase: search for reaction intermediates by using tandem ESI-CAR/CAR ESI-CAR/CID (organometallic reaction in the gas phase).
(c) Prediction of deprotonated heterogeneous dimer formation associated to their competitive dissociations : (i) application for building of the gas phase acidity scales. (ii) Access to both the E° and A terms of the Arrhenius equation with BIRD activation.
(d) Ion activation and determination of biomolecule structures: a tools for generating charge-remote processes by in situ generation of radicals (i) with the transition metals associated to zwitterion formation highlighted in the gas phase, ( ii) electron capture (ECD), (iii) electron detachment (ESD), and (iv) activation by vertical electronic excitation (EID).
(e) Non-covalent biosystems stabilized by hydrogen bonds and salt bridge: (i) peptide/peptide. (Ii) protein/protein, (iii) interaction sites and stability of protein/inhibitor and also (iv) ss(ds)DNA/DNA and active/peptide complexes;
3. Benefits for the structural elucidation and biomolecule analysis.
(a) by the use in metabolomics of : (i) new ionization modes, (ii) accurate mass measurements and elemental compositions, and (iii) ergodic activation modes, (iv) data processing and "universal" MS/MS databases.
(b) Analysis of proteins and toxins to safety issues and environmental application using pyrolysis mode/soft ionization/ FT-MS with different activation modes.
Recent results:
1. Instrumentation
Applications in the chemical agent and explosive detections involve using : (i) coupling of soft ionization to the hQH/FT-ICR tandem. (ii) the cubic trap/linear trap tandem and the modified ETD cell into the EI source to LTQ. (iii) the mode DESI, DART PaperSpray implanted to the tandem LQT / Orbitrap.
2. Fundamental.
(a) Internal energy of the molecular ion species for: (i) inter-laboratory exercises after a strict CID spectrum optimization for the establishment of a MS/MS database in metabolomics and security homeland, (ii) the development of an algorithm for chemical agent structural elucidation. (iii) annotation of metabolomic mass spectra in the detection of doping horses.
(b) Intermediates of catalyzed gas phase reactions involving (i) organometallic, (ii) mechanism modeling of [2 +1] cycloaddition between an alkyne and norbornadiene with Pd (II). (ii) Structure and reactivity of reduced form as XMg(η2-O2C) and (iii) the cyclization reaction of Panson-Khand from which, the E and A° terms of the Arrhenius equation by usin BIRD activation.
(c) Prediction of the protonated or deprotonated heterodimer formation and their competitive dissociations : its use for acidity scales of (i) acidic amino acids, (ii) substituted phenols, and (iii) estrogen steroids.
(d) Ion activation and structural determination of biomolecules by in situ generation of radical reactions : (i) by CID (identification of peptides from gas phase formation of zwitterion; and enantioselective reduction and distinction of chiral amino acid), (ii) by ECD (distinction diastereoisomeric cyclopeptides; gas phase conformational role of lasso peptides in the H• transfer specificity), (iii) by EDD (for DNA and its non-covalent complexes) and (iv) vertical electronic activation (EID) of multideprotonated ss(ds)DNA strands.
(e) Stability of non-covalent biosystem complexes (interaction by hydrogen bonds and salt bridges and the use of the acidity and cation affinity scales on the stability of complexes): (i) case of peptide/ peptides, (ii) localization of interaction sites and stability of non-covalent protein/ inhibitor, (iii) analysis of DNA and dissociations of the ss(ds)DNA/drug and ss(ds)DNA/peptides.
3. Benefits for the structural and analytical biomolecules.
(a) Development in metabolomics: (i) for high-throughput analysis using new soft ionization methods (Penning and supersonic jets), accurate mass measurements, annotation processing, database MS/MS, (ii) evaluation of a Fourier transform mass spectrometer (LTQ / Orbitrap) for the metabolite quantification from cell extracts.
(b) For homeland security, specific and sensitive detections of: (i) proteins and toxins by using pyrolysis/Penning ionization toxins and bacteria, (ii) cobra toxins with FT/MS using various activations mode; and the ricin by coupling of immuno-affinity/MS.
(c) Using ion-pairing for improving, by reduction of the charge state distribution of like-heparine systems allowing sensitive ion chromatographic separation when coupling with ESI.
Scientific career- Post-doctoral studies under the supervision of T. Gaumann at the EPFL - Lausanne (Suisse).
- Ph. D. thesis under the supervision of E.H. Audier .
- Chemistry studies at University ofOrsay – Paris XI.
Selected publications:- Charge state effect on zwitterion influence on stability of non‐covalent interaction of ssDNA with peptides. S. Alves, A. Woods, J.-C. Tabet, J. Mass Spectrom. 42 (2007) 1613.
- Direct Introduction of Biological Samples into a LTQ‐Orbitrap Hybrid Mass spectrometer as a Tool for Fast Metabolome Analysis. G. Madalinski, E. Godat, S. Alves, D. Lesage, E. Genin, P. Levi, J. Labarre, J.-C. Tabet, E. Ezan, C. Junot, Anal. Chem. 80 (2008) 3291.
- DsDNA/drug interaction by ESI/FT ICR: dissociation orientation relates to stabilizing salt bridges. Y. Xu, C. Afonso, R. Wen, J.-C. Tabet., J. Mass Spectrom.; 43 (2008) 1531.
- Internal energy distribution of peptides in electrospray ionization: ESI and collision-induced dissociation spectra calculation, A. Pak, D. Lesage, Y. Gimbert, K. Vékey, J.-C. Tabet, J. Mass Spectrom., 43 (2008) 447.
- Gas‐phase study of phenylacetylene & norbornadiene on a Pd(II) phosphinous acid complex: importance of the introduction order of the organic partners. R. Thota, D. Lesage, Y. Gimbert, L. Giordano, S. Humbel, A. Milet, G. Buono, J.-C. Tabet, Organometallics 28 (2009) 2735.
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