Nos tutelles

CNRS

Nos partenaires

Rechercher




Accueil

Productions scientifiques

Charles, Laurence.

ACL - Articles dans des revues à comité de lecture

92 références.
2019

  • Amalian, J. - A.; Cavallo, G.; Al Ouahabi, A.; Lutz, J. - F.; Charles, L. Analytical Chemistry 2019, 91 (11), 7266-7272.
    Résumé : The defined sequence of two comonomers in sequence-controlled macromolecules can be used to store binary information which is further decoded by MS/MS sequencing. In order to achieve the full sequence coverage requested for reliable decoding, the structure of these polymers can be optimized to minimize their dissociation extent, as shown for poly(alkoxyamine phosphodiester)s (PAPs) where weak alkoxyamine bonds were introduced in each repeating unit to make all phosphate groups MS/MS silent. However, for secret communications, a too high MS/MS readability could be a drawback. In this context, the design of PAPs was further optimized in this work to also include a decrypting key based on slight variation of a fragment collision cross section. This was achieved by employing two different nitroxides to build the alkoxyamine moiety, each containing a coding alkyl segment of the same mass but different architectures. As a result, the digital sequence determined from primary fragments observed in MS/MS had to be decrypted according to appropriate rules that depend on the drift times measured by ion mobility spectrometry for repeating units released as secondary product ions.

  • Charles, L.; Chendo, C.; Poyer, S. Rapid communications in mass spectrometry : RCM 2019.
    Résumé : This review covers applications of ion mobility spectrometry (IMS) hyphenated to mass spectrometry (MS) in the field of synthetic polymers.

  • Combes, S.; Tran, K. T.; Ayhan, M. M.; Karoui, H.; Rockenbauer, A.; Tonetto, A.; Monnier, V.; Charles, L.; Rosas, R.; Viel, S.; Siri, D.; Tordo, P.; Clair, S.; Wang, R.; Bardelang, D.; Ouari, O. Journal of the American Chemical Society 2019.
    Résumé : Triangular shapes have inspired scientists over time and are common in nature, such as the flower petals of oxalis triangularis, the triangular faces of tetrahedrite crystals, and the icosahedron faces of virus capsids. Supramolecular chemistry has enabled the construction of triangular assemblies, many of which possess functional features. Among these structures, cucurbiturils have been used to build supramolecular triangles, and we recently reported paramagnetic cucurbit[8]uril (CB[8]) triangles, but the reasons for their formation remain unclear. Several parameters have now been identified to explain their formation. At first sight, the radical nature of the guest was of prime importance in obtaining the triangles, and we focused on extending this concept to biradicals to get supramolecular hexaradicals. Two sodium ions were systematically observed by ESI-MS in trimer structures, and the presence of Na+ triggered or strengthened the triangulation of CB[8]/guest 1:1 complexes in solution. X-ray crystallography and molecular modeling have allowed the proposal of two plausible sites of residence for the two sodium cations. We then found that a diamagnetic guest with an H-bond acceptor function is equally good at forming CB[8] triangles. Hence, a guest molecule containing a ketone function has been precisely triangulated thanks to CB[8] and sodium cations as determined by DOSY-NMR and DLS. A binding constant for the triangulation of 1:1 to 3:3 complexes is proposed. This concept has finally been extended to the triangulation of ditopic guests toward network formation by the reticulation of CB[8] triangles using dinitroxide biradicals.

  • Gaudel-Siri, A.; Marchal, C.; Ledentu, V.; Gigmes, D.; Siri, D.; Charles, L. European Journal of Mass Spectrometry 2019, 25 (2), 229-238.
    Résumé : The dissociation behavior of two stable nitroxides, namely 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO center dot) and N-tert-butyl-1-diethylphosphono-2,2-dimethylpropyl nitroxide (SG1(center dot)), subjected as protonated molecules to collisional activation was investigated using a combination of different mass spectrometry experiments and theoretical calculations. Elemental composition of reaction products was derived from accurate mass data measured in high resolution tandem mass spectrometry experiments, primary fragments were distinguished from secondary ions based on both breakdown curves and MS3 data, and H/D exchange experiments were performed to support proposed structures. Postulated fragmentation pathways were then studied in terms of energetic, using the standard B3LYP/6-31G(d) method. While protonation of TEMPO center dot mainly occurred on the oxygen atom of the nitroxyl function, a series of protomers were found for SG1(center dot) with the adducted proton preferentially located onto the P=O group of this phosphorylated species. For both protonated nitroxides, major product ions measured in tandem mass spectrometry arose from reactions occurring at low energy costs via elimination of radical species. Formation of secondary fragments that were detected with low abundance when raising the activation level of both precursor ions could be rationalized with pathways proceeding via high energy transition states.

  • Konig, N. F.; Al Ouahabi, A.; Oswald, L.; Szweda, R.; Charles, L.; Lutz, J. - F. Nature Communications 2019, 10, 3774.
    Résumé : Light-induced alteration of macromolecular information plays a central role in biology and is known to influence health, aging and Darwinian evolution. Here, we report that light can also trigger sequence variations in abiotic information-containing polymers. Sequence-coded poly (phosphodiester)s were synthesized using four phosphoramidite monomers containing either photo-sensitive or photo-inert substituents. These monomers allow different sequence manipulations. For instance, using two light-cleavable monomers containing o-nitrobenzyl ether and o-nitroveratryl ether motifs, photo-erasable digital polymers were prepared. These polymers can be decoded by tandem mass spectrometry but become unreadable after UVA exposure. The opposite behavior, i.e. photo-revealable sequences, was obtained with polymers made of two isobaric monomers containing light-cleavable o-nitrobenzyl ether and light-inert p-nitrobenzyl ether substituents. Furthermore, when the latter two monomers were used in conjunction with a third monomer bearing a light-inert OH group, site-directed photo-mutations were induced in synthetic polymers. This was used herein to change the meaning of binary sequences.

  • Mondal, T.; Greff, V.; Petit, B. E.; Charles, L.; Lutz, J. - F. Acs Macro Letters 2019, 8 (8), 1002-1005.
    Résumé : Sequence-defined poly(N-substituted urethanes) were synthesized via a solid-phase iterative protocol including two successive orthogonal coupling steps: the formation of an activated carbonate and its chemoselective reaction with the secondary amine group of amino alcohol building blocks. This simple method was used to write binary information on the formed polymers using four-coded molecules, 2-(methylamino)ethanol, 2-(ethylamino)ethanol, 2-(propylamino)ethanol, and 2-(butylamino)ethanol, symbolizing binary dyads 00, 01, 10, and 11, respectively. The method is fast and allows synthesis of uniform oligomers and polymers with controlled lengths (4-mer to 28-mer) and digital information sequences. Furthermore, the coded poly(N-substituted urethanes) were easily characterized by electrospray mass spectrometry and decoded by tandem mass spectrometry. Overall, these digital macromolecules offer interesting advantages over conventional sequence-coded polyurethanes, i.e., synthesis of longer chains, reduced synthesis times, and better solubility and processing in common organic solvents.

  • Oswald, L.; Al Ouahabi, A.; Laure, C.; Amalian, J. - A.; Charles, L.; Lutz, J. - F. Journal of Polymer Science Part a-Polymer Chemistry 2019, 57 (3), 403-410.
    Résumé : Soluble supports, with optimal molecular structures for iterative oligomer synthesis, were prepared by atom transfer radical copolymerization of styrene with Fmoc-amino ethyl methacrylate. Size exclusion chromatography and nuclear magnetic resonance indicated formation of copolymers with controlled chain lengths, chain ends, dispersity, and comonomer compositions. These polymers were afterward subjected to two subsequent modifications steps: (a) the debromination of their omega-chain ends via a tributyltin hydride treatment and (b) the removal of the Fmoc-protecting groups in acidic conditions, thus leading to bromine-free copolymers with a precise primary amine loading capacity. These universal amine-containing precursors were then derived into a variety of functional supports. A glycine-loaded Wang-type soluble polystyrene support was prepared in two steps and tested for peptide synthesis as well as for the preparation of digital oligo(alkoxyamine amide)s. In both cases, it was possible to obtain uniform sequence-defined oligomers as evidenced by electrospray ionization tandem mass spectrometry. However, each type of oligomer required specific experimental conditions and therefore soluble supports with an adapted loading capacity for optimal synthesis. Furthermore, the amine-containing universal precursors were also transformed into soluble supports for iterative phosphoramidite chemistry. A support was specifically conceived for the iterative synthesis of abiotic digital oligo(phosphodiester)s and another one was designed for oligonucleotide synthesis. (c) 2018 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2019, 57, 403-410

  • Poyer, S.; Chendo, C.; Laure, C.; Lutz, J. - F.; Siri, D.; Charles, L. International Journal of Mass Spectrometry 2019, 438, 29-35.
    Résumé : Information could be stored in the backbone of sequence-defined oligo(alkoxyamine amide)s based on coded amide moieties, and further retrieved by MS/MS sequencing since their collision-induced dissociation only proceeded via competitive homolysis of alkoxyamine linkages. However, when occurring at chain ends, C-ON bond homolysis did not yield the set of complementary product ions expected from such a charge-remote reaction. The actual role of the adducted proton on the dissociation mechanism was then investigated. Using a set of tri(alkoxyamine amide)s that each contained two C-ON bonds, theoretical calculations first showed that protonation most favorably occurred at nitroxide moieties or at the central amide group compared to terminal amides. This result explained why the fragment at the left-hand side of the first C-ON bond was always released as a radical and never detected as a charged product. These calculations also showed that tri(alkoxyamine amide)s would exist as different protomers that could be experimentally evidenced for some of the studied species by traveling wave ion mobility spectrometry (TWIMS). TWIMS-MS/MS experiments were then performed for individual study of the IMS-resolved protomer. So-obtained data suggested that C-ON bond cleavage did not occur when the nitroxide nitrogen was protonated. However, calculations performed on optimized structures evidenced that, prior to alkoxyamine homolysis, the proton adducted to the nitroxide could be transferred onto the nearby amide oxygen atom, hence permitting to rationalize TWIMS-MS/MS data. (C) 2018 Elsevier B.V. All rights reserved.

  • Yin, H.; Cheng, Q.; Rosas, R.; Viel, S.; Monnier, V.; Charles, L.; Siri, D.; Gigmes, D.; Ouari, O.; Wang, R.; Kermagoret, A.; Bardelang, D. Chemistry-a European Journal 2019, 25 (54), 12552-12559.
    Résumé : The capture of pH-responsive guest molecules by CB[8] macrocycles made it possible to produce 2:2 host:guest complexes, releasing protons initially trapped on the guests, in a manner similar to the proton release observed in biology and operating through cascade supramolecular events. More information can be found in the Full Paper by R. Wang, A. Kermagoret, D. Bardelang, et al. (DOI: 10.1002/chem.201902057).
2018

  • Autissier, L.; Mabrouk, K.; Chendo, C.; Guillaneuf, Y.; Rollet, M.; Charles, L.; Gigmes, D.; Trimaille, T. Chemistry-a European Journal 2018, 24 (15), 3699-3702.
    Résumé : A catalyst/initiator-free radical addition reaction performed under mild conditions (water, 30 degrees C) with high yields is reported for the first time. This reaction implies simple pH-mediated alkoxyamine dissociation followed by addition onto olefinic substrates. The versatility and relevance of this selective reaction for macromolecular conjugation and engineering are shown through the syntheses of block copolymers, as well as hydrogels containing insitu-loaded proteins, which could retain biological activity. This contrasts with standard thermal radical conditions that lead to complete protein inactivation.
    Mots-clés : access, alkoxyamines, block copolymers, click chemistry, copolymers, hydrogels, olefins, polymerization, powerful, radical addition, water solvent.

  • Cavallo, G.; Poyer, S.; Amalian, J. - A.; Dufour, F.; Burel, A.; Carapito, C.; Charles, L.; Lutz, J. - F. Angewandte Chemie-International Edition 2018, 57 (21), 6266-6269.
    Résumé : Digital polymers are uniform macromolecules that store monomer-based binary sequences. Molecularly stored information is usually extracted from the polymer by a tandem mass spectrometry (MS/MS) measurement, in which the coded chains are fragmented to reveal each bit (i.e. basic coded monomer unit) of the sequence. Here, we show that data-extraction can be greatly simplified by favoring the formation of MS/MS fragments containing two bits instead of one. In order to do so, digital poly(alkoxyamine phosphodiester)s, containing binary dyads in each repeat unit, were prepared by an orthogonal solid-phase approach involving successive phosphoramidite and radical-radical coupling steps. Three different sets of monomers were considered to build these polymers. In all cases, four coded building blockstwo hydroxy-nitroxides and two phosphoramidite monomerswere required to build the dyads. Among the three studied monomer sets, one combination allowed synthesis of uniform sequence-coded polymers. The resulting polymers led to clear dyad-containing fragments in MS/MS and could therefore be efficiently decoded. Additionally, an algorithm was created to detect specific dyad fragments, thus enabling automated sequencing.

  • Chendo, C.; Phan, T. N. T.; Rollet, M.; Gigmes, D.; Charles, L. Rapid Communications in Mass Spectrometry 2018, 32 (5), 423-430.
    Résumé : RationaleThe goal of this work was to modify the dissociation pathways of polylactide (PLA) holding benzyl and hydroxyl terminations, in order to circumvent coincidence of product ions generated during collisional activation of sodiated chains, which prevented their reliable characterization. MethodsBenzyl-, hydroxyl-terminated PLAs were ionized as ammonium adducts in positive ion mode electrospray and subjected to collision-induced dissociation (CID). Tandem mass spectrometry (MS/MS) experiments were conducted in a quadrupole time-of-flight (QTOF) instrument for safe assignment of product ions based on their elemental composition derived from accurate mass measurements. ResultsAdduction of ammonium to PLAs was found to induce chain fragmentation via charge-assisted processes, in great contrast to the charge-remote mechanisms experienced by sodiated molecules. The main reaction produced ions containing the termination only, hence allowing straightforward end-group determination. Other minor pathways were studied in detail to establish dissociation rules for ammoniated PLAs. Some reactions were found to be end-group specific, highlighting the higher reactivity of ammonium than alkali ion adducts. ConclusionsChanging the usually employed sodium-cationizing agent to ammonium was shown to induce dramatic changes in the CID behavior of PLAs. This was a simple and efficient approach to address issues encountered for end-group analysis of the particular PLA studied here.
    Mots-clés : electrospray-ionization, fragmentation pathways, liquid-chromatography, oligomers, polymer, tandem mass-spectrometry.

  • Karamessini, D.; Simon-Yarza, T.; Poyer, S.; Konishcheva, E.; Charles, L.; Letourneur, D.; Lutz, J. - F. Angewandte Chemie-International Edition 2018, 57 (33), 10574-10578.
    Résumé : Sequence-defined oligourethanes were tested as invivo taggants for implant identification. The oligomers were prepared in an orthogonal solid-phase iterative approach and thus contained a coded monomer sequence that can be unequivocally identified by tandem mass spectrometry (MS/MS). The oligomers were then included in small amounts (1wt%) in square-centimeter-sized crosslinked poly(vinyl alcohol) (PVA) model films, which were intramuscularly and subcutaneously implanted in the abdomen of rats. After one week, one month, or three months of implantation, the PVA films were explanted. The rat tissues exposed to the implants did not exhibit any adverse reactions, which suggested that the taggants are not harmful and probably not leaching out from the films. Furthermore, the explanted films were immersed in methanol, as a solvent for oligourethanes, and the liquid extract was analyzed by mass spectrometry. In all cases, the oligourethane taggant was detected, and its sequence was identified by MS/MS.

  • Poyer, S.; Fouquet, T.; Sato, H.; Lutz, J. - F.; Charles, L. Macromolecular Chemistry and Physics 2018, 219 (16), 1800173.
    Résumé : Kendrick mass defect (KMD) analysis is shown here to be a convenient method to read binary messages encoded in the structure of two types of sequence-defined synthetic polymers, namely, polyurethanes and poly(alkoxyamine phosphodiester)s. KMD analysis allows graphical ranking of mass data obtained for species containing repeating units. This is performed on MS/MS data in which distribution of fragments reveals the comonomer sequence of digital macromolecules. Choosing one coding monomer as the base unit, KMD computation of MS/MS data leads to stair-like plots where flat steps correspond to that monomer selected as the base unit while oblique steps reveal the other monomer. To correct for any point misalignments resulting from slight inaccuracy of fragment mass measurement, fractional base units are used to perform resolution-enhanced KMD (RE-KMD) analysis. As the length of the chain increased, a procedure aiming at correct aliased points is also implemented to achieve continuous, more convenient, stair-like plots.
2017

  • Al Ouahabi, A.; Amalian, J. - A.; Charles, L.; Lutz, J. - F. Nature Communications 2017, 8, 967.
    Résumé : In the context of data storage miniaturization, it was recently shown that digital information can be stored in the monomer sequences of non-natural macromolecules. However, the sequencing of such digital polymers is currently limited to short chains. Here, we report that intact multi-byte digital polymers can be sequenced in a moderate resolution mass spectrometer and that full sequence coverage can be attained without requiring pre-analysis digestion or the help of sequence databases. In order to do so, the polymers are designed to undergo controlled fragmentations in collision-induced dissociation conditions. Each byte of the sequence is labeled by an identification tag and a weak alkoxyamine group is placed between 2 bytes. As a consequence of this design, the NO-C bonds break first upon collisional activation, thus leading to a pattern of mass tag-shifted intact bytes. Afterwards, each byte is individually sequenced in pseudo-MS3 conditions and the whole sequence is found.
    Mots-clés : chemistry, defined polymers, DNA, efficient, information-storage, macromolecules, oligonucleotides, phosphoramidite, robust.

  • Amalian, J. - A.; Poyer, S.; Petit, B. E.; Telitel, S.; Monnier, V.; Karamessini, D.; Gigmes, D.; Lutz, J. - F.; Charles, L. International Journal of Mass Spectrometry 2017, 421, 271–278.
    Résumé : MS/MS sequencing is an unrivaled technique to decipher binary information chemically encoded in the backbone of sequence-controlled synthetic polymers constructed with two co-monomers of different mass, arbitrarily designated as the 0- and 1-bit of the ASCII alphabet. Efficiency of this "reading" step relies however on the simplicity of MS/MS patterns, which depends on both polymer chemistry and chain length. In this context, polyurethanes (PUs) were very promising candidates as dissociation of small deprotonated oligomers (n \textless 8) yielded a single fragment series. The carbamate bond cleavage reaction was hence studied in details to tentatively anticipate the CID behavior of longer chains prior to optimizing their synthesis. In spite of the simplicity of MS/MS spectra, three different mechanisms were evidenced; however, they were not expected to induce MS/MS complexity when activating longer chains, as verified for sequence-controlled PUs containing up to two bytes of information (i.e., 16 co-monomers). In contrast, the ionization step appeared to be an issue: deprotonation yield of the end-group in negative ion mode electrospray was observed to strongly decrease as PU chain length increases. This sensitivity issue was addressed by introducing a second acidic end-group to allow doubly deprotonated oligomers with no impact on their CID behavior. (C) 2017 Elsevier B.V. All rights reserved.
    Mots-clés : Carbamate bond cleavage, collision-induced dissociation, containing macromolecules, Digital polymers, DNA, mass-spectrometry, MS/MS sequencing, phosphoramidite, polymers, Polyurethanes, sequence-controlled polymers, storage.

  • Burel, A.; Carapito, C.; Lutz, J. - F.; Charles, L. Macromolecules 2017, 50 (20), 8290–8296.
    Mots-clés : DNA, information, macromolecules, phosphoramidite, poly(alkoxyamine amide)s, synthetic-polymers, tandem mass-spectrometry.

  • Charles, L.; Cavallo, G.; Monnier, V.; Oswald, L.; Szweda, R.; Lutz, J. - F. Journal of the American Society for Mass Spectrometry 2017, 28 (6), 1149–1159.
    Résumé : In order to improve their MS/MS sequencing, structure of sequence-controlled synthetic polymers can be optimized based on considerations regarding their fragmentation behavior in collision-induced dissociation conditions, as demonstrated here for two digitally encoded polymer families. In poly(triazole amide)s, the main dissociation route proceeded via cleavage of the amide bond in each monomer, hence allowing the chains to be safely sequenced. However, a competitive cleavage of an ether bond in a tri(ethylene glycol) spacer placed between each coding moiety complicated MS/MS spectra while not bringing new structural information. Changing the tri(ethylene glycol) spacer to an alkyl group of the same size allowed this unwanted fragmentation pathway to be avoided, hence greatly simplifying the MS/MS reading step for such undecyl-based poly(triazole amide)s. In poly(alkoxyamine phosphodiester)s, a single dissociation pathway was achieved with repeating units containing an alkoxyamine linkage, which, by very low dissociation energy, made any other chemical bonds MS/MS-silent. Structure of these polymers was further tailored to enhance the stability of those precursor ions with a negatively charged phosphate group per monomer in order to improve their MS/MS readability. Increasing the size of both the alkyl coding moiety and the nitroxide spacer allowed sufficient distance between phosphate groups for all of them to be deprotonated simultaneously. Because the charge state of product ions increased with their polymerization degree, MS/MS spectra typically exhibited groups of fragments at one or the other side of the precursor ion depending on the original alpha or omega end-group they contain, allowing sequence reconstruction in a straightforward manner.
    Mots-clés : Coded monomer sequence, collision-induced dissociation, containing macromolecules, copolymers, fragmentation, information-containing macromolecules, kinetic-energy spectrometry, ms/ms, nomenclature, phosphoramidite, poly(alkoxyamine amide)s, Polymer sequencing, sequence-controlled polymers, tandem mass-spectrometry, time-of-flight.

  • Karamessini, D.; Poyer, S.; Charles, L.; Lutz, J. - F. Macromolecular Rapid Communications 2017, 38 (24), 1700426.
    Résumé : Mixtures of uniform sequence-defined oligourethanes are evaluated as 2D molecular barcodes for labeling three different commodity polymers, namely polystyrene, polyvinylchloride and polyethylene terephthalate. Six different oligourethanes are synthesized by solid-phase iterative synthesis and are coded using a binary monomer alphabet. High-resolution mass spectrometry studies indicate that all oligomers are uniform and sequence-defined. However, instead of using them as individual coded chains, oligomers with different chain-length, mass and sequence are mixed into intentionally polydispersed libraries. In particular, a three-component library and a four-component library are created to encode a 2-bytes model binary sequence. These 2D-coded libraries are incorporated in all commodity plastics via a simple solvent casting procedure. Furthermore, in all cases, the oligomer mixtures can be extracted from the host polymer films and deciphered by mass spectrometry, thus opening interesting avenues for anti-counterfeiting and traceability applications.
    Mots-clés : anti-counterfeiting technologies, building-blocks, design, Digital polymers, encoded polymers, information, information-containing macromolecules, macromolecules, oligomers, phase synthesis, phosphoramidite, sequence-controlled polymers, sequencing.

  • Konig, N. F.; Al Ouahabi, A.; Poyer, S.; Charles, L.; Lutz, J. - F. Angewandte Chemie-International Edition 2017, 56 (25), 7297–7301.
    Résumé : A three-step post-polymerization modification method was developed for the design of digitally encoded poly(phosphodiester)s with controllable side groups. Sequence-defined precursors were synthesized, either manually on polystyrene resins or automatically on controlled pore glass supports, using two phosphoramidite monomers containing either terminal alkynes or triisopropylsilyl (TIPS) protected alkyne side groups. Afterwards, these polymers were modified by stepwise copper-catalyzed azide-alkyne cycloaddition (CuAAC). The terminal alkynes were first reacted with a model azide compound, and after removal of the TIPS groups, the remaining alkynes were reacted with another organic azide. This simple method allows for quantitative side-chain modification, thus opening up interesting avenues for the preparation of a wide variety of digital polymers.
    Mots-clés : chemistry, containing macromolecules, cycloaddition, digitally encoded polymers, DNA, efficient, encoded oligomers, information-containing macromolecules, phosphoramidite, polymer modification, sequence-controlled polymers, sequence-defined oligomers, single, solid-phase synthesis, storage.

  • Konig, N. F.; Telitel, S.; Poyer, S.; Charles, L.; Lutz, J. - F. Macromolecular Rapid Communications 2017, 38 (24), 1700651.
    Résumé : A photoregulated phosphoramidite iterative process is studied for the synthesis of non-natural, digitally encoded oligo(phosphodiester)s. The oligomers are prepared using two reactive phosphoramidite monomers containing a 2-(2-nitrophenyl)propoxycarbonyl (NPPOC) protected OH group. The stepwise synthesis is performed on an OH-functional soluble polystyrene support, which allows recycling by precipitation in a nonsolvent. Repeating cycles involving phosphoramidite coupling, oxidation of phosphite to phosphate, and NPPOC deprotection by light irradiation at lambda = 365 nm are performed in order to prepare oligomers with different lengths and sequences. Synthesis is conducted on a micromolar scale and good recycling yields are obtained in all cases. The use of a soluble polymer support allows an in-depth characterization of the NPPOC photo-deprotection step by H-1 NMR, UV spectroscopy, and size exclusion chromatography, and thus identification of optimal synthesis conditions. After cleavage from the support, the oligo(phosphodiester)s are characterized by tandem mass spectrometry, which confirms preparation of uniform sequence-coded oligomers.
    Mots-clés : Digital polymers, encoded polymers, gene synthesis, information, macromolecules, microarrays, phosphoramidite chemistry, Photochemistry, protecting groups, sequence-controlled polymers, sequencing, soluble polymer support, soluble polymer supports.

  • Lescic, S.; Karoui, H.; Hardy, M.; Charles, L.; Tordo, P.; Ouari, O.; Gaudel-Siri, A.; Siri, D. Journal of Physical Organic Chemistry 2017, 30 (10), e3677.
    Résumé : Spin trapping coupled with electron paramagnetic resonance spectroscopy is the most direct method for detection of very low concentrations of free radicals, and it has been intensively used to detect superoxide or alkylperoxyl radicals in biological systems, using cyclic nitrones as spin traps. The half-life time of the ensuing spin adducts depends dramatically on the spin trap structure; however, their mechanism of decay has never been definitely established. We investigated at the MRMP2/CASSCF (MultiReference second-order Moller-Plesset perturbation theory/Complete Active Set Self Consistent Field) level of theory the mechanism of decay of methylperoxyl and tert-butylperoxyl spin adducts formed with various cyclic nitrones. We showed that no transition state can be located for the O-O homolytic cleavage, which yields an intermediate biradical with the following sequence O-center dot-N-C-O-center dot. Then, homolytic cleavage of the N-C bond yields a nitrosoaldehyde, through an early transition state with a very low activation energy. For each nitrone used as spin trap, electrospray ionization mass spectrometry analysis of the spin trapping mixture allowed to detect the presence of the expected nitrosoaldehyde. We generated tert-butylperoxyl spin adducts in toluene, and we found a good correlation between their half-life time and the bond dissociation energy of their peroxidic O-O bond. The theoretical method was then extended to hydroperoxyl spin adducts in water and provided promising results.
    Mots-clés : 2nd-order perturbation-theory, alkylperoxyl spin adducts, biradical, centered radicals, cyclic nitrones, depmpo, dft, dmpo, epr, half-life time, mrmp2/casscf, radical-anion adduct, spin trapping, superoxide, trapping properties.

  • Szweda, R.; Chendo, C.; Charles, L.; Baxter, P. N. W.; Lutz, J. - F. Chemical Communications 2017, 53 (59), 8312–8315.
    Résumé : Due to their strong tendency to self-aggregate, unfunctionalized oligoarylacetylenes are difficult to synthesize. Here, tailored polystyrene soluble supports, prepared by atom transfer radical polymerization and post-polymerization modification, were tested for preparing sequence-defined oligoarylacetylenes. Controlled aromatic sequences were obtained by iterative Sonogarisha coupling, using phenyl- and pyridine-based building-blocks.
    Mots-clés : block-copolymers, encoded polymers, hydrolysis, liquid-phase synthesis, macromolecules, nanoarchitectures, oligomers, organic-synthesis, phosphoramidite chemistry, transfer radical polymerization.

  • Telitel, S.; Petit, B. E.; Poyer, S.; Charles, L.; Lutz, J. - F. Polymer Chemistry 2017, 8 (34), 4988–4991.
    Résumé : Sequence-coded oligourethanes were tested as macroinitiators for the atom transfer radical polymerization (ATRP) of styrene. These oligomers were synthesized by solid-phase orthogonal iterative chemistry and transformed into ATRP initiators using a three-step modification procedure. A controlled radical polymerization behavior was observed with these macroinitiators, thus opening interesting opportunies for the synthesis of macromolecular architectures containing sequence-defined segments.
    Mots-clés : block-copolymers, initiators, phosphoramidite, polymers, transfer radical polymerization.
2016

  • Amalian, J. - A.; Trinh, T. T.; Lutz, J. - F.; Charles, L. Analytical Chemistry 2016, 88 (7), 3715-3722.
    Résumé : Tandem mass spectrometry was evaluated as a reliable sequencing methodology to read codes encrypted in monodisperse sequence-coded oligo(triazole amide)s. The studied oligomers were composed of monomers containing a triazole ring, a short ethylene oxide segment, and an amide group as well as a short alkyl chain (propyl or isobutyl) which defined the 0/1 molecular binary code. Using electrospray ionization, oligo(triazole amide)s were best ionized as protonated molecules and were observed to adopt a single charge state, suggesting that adducted protons were located on every other monomer unit. Upon collisional activation, cleavages of the amide bond and of one ether bond were observed to proceed in each monomer, yielding two sets of complementary product ions. Distribution of protons over the precursor structure was found to remain unchanged upon activation, allowing charge state to be anticipated for product ions in the four series and hence facilitating their assignment for a straightforward characterization of any encoded oligo(triazole amide)s.
    Mots-clés : collision-induced dissociation, containing macromolecules, defined oligomers, electrospray-ionization mass, fragmentation pathways, lithium-attachment ions, poly(alkoxyamine amide)s, synthetic-polymers, tandem mass-spectrometry, time-of-flight.

  • Cavallo, G.; Al Ouahabi, A.; Oswald, L.; Charles, L.; Lutz, J. - F. Journal of the American Chemical Society 2016, 138 (30), 9417-9420.
    Résumé : A new orthogonal solid-phase iterative strategy is proposed for the synthesis of sequence-coded polymers. This approach relies on the use of two successive chemoselective steps: (i) phosphoramidite coupling, and (ii) radical radical coupling. These repeated steps can be performed using two different types of building blocks, i.e. a phosphoramidite monomer that also contains an alkyl bromide and a hydroxy-functionalized nitroxide. The phosphoramidite and the hydroxy group are reacted in step (i), thus leading to a phosphite that is oxidized in situ into a phosphate bond. The alkyl bromide is activated by copper bromide in step (ii) to afford a carbon-centered radical that is spin-trapped in situ by the nitroxide. The iterative repetition of these steps allow synthesis of uniform polymers, as evidenced by high resolution electrospray mass spectrometry. Moreover, binary information could be easily implemented in the polymers using different types of phosphoramidite monomers in step (i). Interestingly, it was found that the formed information-containing polymers are very easy to sequence by tandem mass spectrometry due to the presence of easily cleavable alkoxyamine bonds formed in step (ii).
    Mots-clés : block, chemistry, DNA, efficient, encoded polymers, macromolecules, sequence-defined oligomers, solid-phase synthesis.

  • Charles, L.; Laure, C.; Lutz, J. - F.; Roy, R. K. Rapid Communications in Mass Spectrometry 2016, 30 (1), 22-28.
    Résumé : RationaleDigitally encoded oligomers composed of two distinct amide coding units spaced by a nitroxide moiety were recently decrypted using a tandem mass spectrometry (MS/MS) sequencing approach developed for protonated oligomers. Here, the MS/MS behavior of deprotonated oligomers was explored in the negative ion mode to provide both structural and mechanistic complementary information. MethodsBinary-encoded oligo(alkoxyamine)amides, containing coding 0/1 amide units spaced by a TEMPO nitroxide moiety, were ionized in negative ion mode electrospray thanks to their end-group containing a carboxylic acid function. Deprotonated molecules were subjected to collision-induced dissociation in MS/MS and MS3 experiments, combined with accurate mass measurements, for a thorough investigation of their dissociation behavior. ResultsDeprotonated oligomers readily dissociated upon collisional activation via competitive homolytic cleavages of all fragile alkoxyamine linkages between any coding 0 or 1 monomers and a nitroxide moiety. As expected, only product ions holding the deprotonated end-group were detected while complementary moieties containing the termination were released as radicals. The so-formed distonic radical anions were observed to further depolymerize according to a radical-induced process, as evidenced by MS3 experiments. ConclusionsMessages encoded in oligo(alkoxyamine)amides were readily decrypted by MS/MS sequencing performed in the negative ion mode. When compared with results obtained in positive ion mode ESI-MS/MS, these data provided further evidence regarding the influence of adducted proton on the charge-remote homolytic cleavage of alkoxyamine linkages. Copyright (c) 2015 John Wiley & Sons, Ltd.

  • Chendo, C.; Le, D.; Phan, T. N. T.; Gigmes, D.; Charles, L. Journal of Polymer Science Part a-Polymer Chemistry 2016, 54 (20), 3388-3397.
    Résumé : An analytical workflow involving high resolution mass analysis, collision-induced dissociation and ion mobility was implemented to structurally characterize polymeric by-products detected in lieu of intact species when performing matrix-assisted laser desorption/ionization (MALDI) of polystyrenes with fragile end groups. Studied samples were prepared by atom transfer radical polymerization, reversible addition-fragmentation transfer polymerization and nitroxide-mediated polymerization. Spectral resolution enabled by orthogonal injection of MALDI ions into a reflectron time-of-flight mass analyzer allowed a thorough inventory of species, including some with the same nominal m/z value but different elemental composition. Individual end-group mass determination was achieved in MS/MS experiments, implementing an additional separative dimension based on ion mobility prior to CID to assist precursor ion selection in case of interferences. Besides validating commonly reported polystyrene chains terminated with either endo- or exo-double bond, this multidimensional approach permitted to show that initiating moiety could also be affected by the MALDI process. (c) 2016 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2016, 54, 3388-3397
    Mots-clés : atrp, capped polystyrene, Controlled radical polymerization, easy access, end-groups, initiators, ion mobility, liquid-chromatography, maldi-ms, mo(iii)/mo(iv), oxide)/polystyrene block-copolymer, Polystyrene, styrene, synthetic-polymers, tandem mass spectrometry.

  • Chendo, C.; Phan, T. N. T.; Marque, S. R. A.; Gigmes, D.; Charles, L. International Journal of Mass Spectrometry 2016, 405, 50-58.
    Résumé : Reactive MALDI was evidenced to occur when using acidic matrices to assist ionization of poly(4-vinylpyridine) (P4VP) prepared by nitroxide mediated polymerization (NMP). The high accessibility of nitrogen atoms in each 4VP units would allow strong hydrogen bonding with acidic matrix molecules, which was shown to further weaken the fragile C-ON linkage between the last monomeric unit and the nitroxide end-group. As a result, release of the nitroxide upon laser irradiation of the MALDI sample would lead to radical chains capable of reacting with the matrix molecule in interaction with the last 4VP unit, yielding a new polymeric by-product where one matrix molecule is incorporated in the chain termination. The mechanism proposed for this reaction was supported by accurate mass measurements, MS/MS data as well as electron paramagnetic resonance (EPR) experiments. Interestingly, such matrix/polymer covalent adducts were no longer observed when using MALDI source operated at high vacuum. (C) 2016 Elsevier B.V. All rights reserved.
    Mots-clés : assisted-laser-desorption/ionization, Covalent matrix adduct, dynamics model, free sample preparation, ionization, labile end-groups, Mass spectrometry, matrix, mechanism, on bond homolysis, P4VP, Poly(4-vinylpyridine), Reactive MALDI, sinapinic acid, Synthetic polymer, tof ms.

  • Fouquet, T.; Ziarelli, F.; Sato, H.; Charles, L. International Journal of Mass Spectrometry 2016, 402, 42-48.
    Résumé : Poly(methoxymethylsiloxane)s (PMMS) are silicon-based polymers usually prepared according to a poorly controlled synthesis route, yielding samples of high structural dispersity. Collision induced dissociation of PMMS was hence studied in detail in order to propose MS/MS rules to be usefully employed for end-group characterization. Lithium adduction did not provide meaningful insights through charge remote dissociation while ammonium adduction allowed PMMS to readily dissociate according to two main information-rich charge driven routes. On one hand, after precursor ions have eliminated methanol together with ammonia, a series of 46 Da (CH2O + CH4) losses was observed, the number of which could be used to decipher the polymerization degree of the dissociating precursor. On the other hand, cleavage of Si-O bonds in the polymer backbone generated two series of product ions of low m/z values, each containing one or the other end-group found to be methoxy and tetramethyltetramethoxycyclotetrasiloxy terminations. Proposed mechanisms were all supported by accurate mass measurements and MS3 experiments. Based on these two highly complementary routes, the three main species of a PMMS sample were thoroughly characterized, allowing unique insights on the synthesis mechanism. (C) 2016 Elsevier B.V. All rights reserved.
    Mots-clés : adducts, dissociation, gas-phase, improvement, ions, oligomers, polymer, Polymethoxymethylsiloxane, Silicone, Siloxane, state, Structural characterization, tandem mass spectrometry.

  • Gunay, U. S.; Petit, B. E.; Karamessini, D.; Al Ouahabi, A.; Amalian, J. - A.; Chendo, C.; Bouquey, M.; Gigmes, D.; Charles, L.; Lutz, J. - F. Chem 2016, 1 (1), 114-126.
    Résumé : Polyurethanes (PUs) constitute a popular class of plastic materials with a wide range of applications in construction, coatings, and the automotive industry. PUs are usually synthesized by step-growth polymerization and, therefore, exhibit non-uniform molecular structures. Here, we show that uniform PUs can be prepared by a facile chemoselective multistep-growth approach. This strategy permits precise control of the chain lengths of the PUs formed and their primary structure, thus making the preparation of coded monomer sequences possible. Furthermore, it was found that these polymers are remarkably easy to analyze by tandem mass spectrometry sequencing. Thus, these precision polymers can potentially be used as molecular barcodes in various applications. As a proof of concept, their use as anti-counterfeiting tags for identification of materials is reported here.
    Mots-clés : block, chemistry, design, encoded poly(alkoxyamine amide)s, information-containing macromolecules, oligomers, phase synthesis, polymers.

  • Laure, C.; Karamessini, D.; Milenkovic, O.; Charles, L.; Lutz, J. - F. Angewandte Chemie-International Edition 2016, 55 (36), 10722-10725.
    Résumé : A 2D approach was studied for the design of polymer-based molecular barcodes. Uniform oligo(alkoxyamine amide)s, containing a monomer-coded binary message, were synthesized by orthogonal solid-phase chemistry. Sets of oligomers with different chain-lengths were prepared. The physical mixture of these uniform oligomers leads to an intentional dispersity (1st dimension fingerprint), which is measured by electrospray mass spectrometry. Furthermore, the monomer sequence of each component of the mass distribution can be analyzed by tandem mass spectrometry (2nd dimension sequencing). By summing the sequence information of all components, a binary message can be read. A 4-bytes extended ASCII-coded message was written on a set of six uniform oligomers. Alternatively, a 3-bytes sequence was written on a set of five oligomers. In both cases, the coded binary information was recovered.
    Mots-clés : barcodes, containing macromolecules, data storage, electrospray-ionization, encoded poly(alkoxyamine amide)s, ions, ms/ms, oligomers, peptides, sequence-controlled polymers, solid-phase synthesis, tandem mass spectrometry.

  • Le, D.; Phan, T. N. T.; Autissier, L.; Charles, L.; Gigmes, D. Polymer Chemistry 2016, 7 (8), 1659-1667.
    Résumé : A series of carboxylic acid-based alkoxyamines associated with SnBr4, a Lewis acid, have been used as protonic acids of a binary initiating system to control the cationic polymerization of vinyl ether. The living character of the homopolymerization of isobutyl vinyl ether was investigated under various conditions (solvent, amount of catalyst, initiator structure etc.). Among the different studied dual initiators, TEMPO based-alkoxyamine showed high efficiency to lead the polymerization of isobutyl vinyl ether (IBVE) in a controlled manner. The prepared polymers exhibited high TEMPO functionality (> 0.85) and low dispersity (1.2) which is essential for the synthesis of well-defined block copolymers thereafter. TEMPO-functionalized PIBVE was used as a macro-initiator controller in the nitroxide-mediated polymerization (NMP) of styrene at 130 degrees C leading successfully to well-defined block copolymers of poly(isobutyl vinyl ether)-b-polystyrene (PIBVE-b-PS) with a narrow dispersity (1.2).

  • Liu, X.; Wang, Y.; Chen, C.; Tintaru, A.; Cao, Y.; Liu, J.; Ziarelli, F.; Tang, J.; Guo, H.; Rosas, R.; Giorgio, S.; Charles, L.; Rocchi, P.; Peng, L. Advanced Functional Materials 2016, 26 (47), 8594-8603.
    Résumé : Functional materials capable of responding to stimuli intrinsic to diseases are extremely important for specific drug delivery at the disease site. However, developing on-demand stimulus-responsive vectors for targeted delivery is highly challenging. Here, a stimulus-responsive fluorinated bola-amphiphilic dendrimer is reported for on-demand delivery of small interfering RNA (siRNA) in response to the characteristic high level of reactive oxygen species (ROS) in cancer cells. This dendrimer bears a ROS-sensitive thioacetal in the hydrophobic core and positively charged poly(amidoamine) dendrons at the terminals, capable of interacting and compacting the negatively charged siRNA into nanoparticles to protect the siRNA and promote cellular uptake. The ROS-sensitive feature of this dendrimer boosts specific and efficient disassembly of the siRNA/vector complexes in ROS-rich cancer cells for effective siRNA delivery and gene silencing. Moreover, the fluorine tags in the vector enable F-19-NMR analysis of the ROS-responsive delivery process. In addition, this ingenious and distinct bola-amphiphilic dendrimer is also able to combine the advantageous delivery features of both lipid and dendrimer vectors. Therefore, it represents an innovative on-demand stimulus-responsive delivery platform.
    Mots-clés : androgen ablation, cells, drug-delivery, efficient, in-vivo, nanomedicine, nanoparticles, prostate-cancer, rnai, therapeutics.

  • Oswald, L.; Al Ouahabi, A.; Charles, L.; Lutz, J. - F. Chemistry-a European Journal 2016, 22 (10), 3462-3469.
    Résumé : Soluble polystyrene supports with optimal molecular structures for iterative phosphoramidite chemistry were prepared by atom-transfer radical polymerization (ATRP) and subsequent chain-end modification steps. The controlled radical polymerization of styrene was first performed in the presence of an 9-fluorenylmethoxycarbonyl (Fmoc)-protected amino-functional ATRP initiator. Soluble supports of different molecular weight were prepared. Size-exclusion chromatography and NMR analysis indicated formation of well-defined polymers with controlled chain lengths and narrow dispersity. After synthesis, the bromo end group of the ATRP polymer was removed by dehalogenation in the presence of tributyltin hydride, and the Fmoc protecting group of the moiety was subsequently cleaved with piperidine. The resulting -primary amine was afterwards treated with a linker containing a carboxyl group, a cleavable ester site, and a dimethoxytrityl-protected hydroxyl group to afford ideal soluble supports for phosphoramidite chemistry. NMR analysis indicated that these chain-end modifications were quantitative. The supports were tested for the synthesis of a non-natural sequence-defined oligophosphates. High-resolution ESI-MS analysis of the cleaved oligomers indicated formation of uniform species, and thus confirmed the efficiency of the ATRP-made soluble polymer supports. In addition, the synthesis of a thymidine-loaded soluble support was achieved.
    Mots-clés : deoxyribooligonucleotide synthesis, design, encoded polymers, information-containing macromolecules, information-containing oligomers, iterative synthesis, liquid-phase synthesis, peptide-synthesis, Polymerization, polymers, soluble supports, transfer radical polymerization.

  • Toure, M.; Charles, L.; Chendo, C.; Viel, S.; Chuzel, O.; Parrain, J. - L. Chemistry-a European Journal 2016, 22 (26), 8937-8942.
    Résumé : A straightforward synthesis of air- and water-stable bis-cationic macrocyclic imidazolylboronium anion receptors is described herein. By taking advantage of the bulky and rigid 9-borabicyclo[3.3.1]-nonane (9-BBN) attaching point and a well-designed bis-imidazolylaryl, highly stable dimeric imidazolylboronium macrocycles were synthesized. Additionally, NMR spectroscopy (H-1, DOSY, and HOESY), mass spectrometry (MS), and X-ray diffraction studies revealed that these macrocyclic scaffolds can bind several monoanions with high association constants in DMSO, and are particularly sensitive for the MS detection of anions (with concentrations in the nm range). This anion/receptor interaction involves eight C-H binding sites, which include C-sp2-H and unusual C-sp3-H hydrogen-bonding donors.
    Mots-clés : anion receptors, binding, boronium cations, chemistry highlights, complexes, dot-center-dot, driven, fluorescent, hydrogen bonds, macrocycles, NMR spectroscopy, preorganization, reactivity, recognition, special-issue.

  • Viode, A.; Dagany, X.; Kerleroux, M.; Dugourd, P.; Doussineau, T.; Charles, L.; Antoine, R. Rapid Communications in Mass Spectrometry 2016, 30 (1), 132-136.
    Résumé : RationaleCoupling size-exclusion chromatography (SEC) with mass spectrometry (MS) allowed generation of a SEC calibration curve based on the analyte itself, which is more reliable than calibration based on non-related standards and faster than the use of the multiple detection mode. However, such SEC/MS couplings were limited to rather small synthetic polymers. MethodsBased on the concept of image current detection, charge-detection mass spectrometry (CDMS) coupled to electrospray ionization (ESI) is a useful method for weighing macro-ions from compounds with masses higher than one megadalton (MDa). Using columns designed to allow analysis of synthetic polymers of over 15 million Dalton in mass, performance of the SEC/ESI-CDMS coupling was evaluated for polyacrylamide (PAM, 5-6 MDa) and a poly(2-acrylamido-2-methyl-1-propanesulfonic acid) (PAMPS, 2 MDa). ResultsThe SEC/ESI-CDMS profiles were first compared with SEC-UV profiles: the systematic shift in retention time was assigned to the slightly different geometries of the two instrumental systems. The SEC/ESI-CDMS data were then compared with results obtained after the direct infusion of each sample into the ESI source. Both the shape of the molecular weight distribution and the mass values were similar with or without separation prior to ESI, and these values were consistent with data provided by the sample supplier. ConclusionsSEC/MS incorporating an online ESI-CDMS coupling was shown to be a rapid and efficient technique for the analysis of water-soluble synthetic polymers with ultra-high molecular mass in the megadalton range. The coupling also afforded an attractive solution for SEC calibration without the use of external standards. Copyright (c) 2015 John Wiley & Sons, Ltd.
2015

  • Al Ouahabi, A.; Charles, L.; Lutz, J. - F. Journal of the American Chemical Society 2015, 137 (16), 5629-5635.
    Résumé : Sequence-defined non-natural polyphosphates were prepared using iterative phosphoramidite protocols on a polystyrene solid support. Three monomers were used in this work: 2-cyanoethyl (3-dimethoxytrityloxy-propyl) diisopropylphosphoramidite (0), 2-cyanoethyl (3-dimethoxytrityloxy-2,2-dimethyl-propyl) diisopropylphosphoramidite (1), and 2-cyanoethyl (3-dimethoxytrityloxy-2,2-dipropargyl-propyl) diisopropylphosphoramidite (1'). Phosphoramidite coupling steps allowed rapid synthesis of homopolymers and copolymers. In particular, the comonomers (0, 1), (0, 1'), and (1, 1') were used to synthesize sequence-encoded copolymers. It was found that long encoded sequences could be easily built using phosphoramidite chemistry. ESI-HRMS, MALDI-HRMS, NMR, and size exclusion chromatography analyses indicated the formation of monodisperse polymers with controlled comonomer sequences. The polymers obtained with the comonomers (0, 1') and (1, 1') were also modified by copper-catalyzed azide alkyne cycloaddition with a model azide compound, namely 11-azido-3,6,9-trioxaundecan-1-amine. H-1 and C-13 NMR analysis evidenced quantitative modification of the alkyne side-chains of the monodisperse copolymers. Thus, the molecular structure of the coding monomer units can be easily varied after polymerization. Altogether, the present results open up interesting avenues for the design of information-containing macromolecules.

  • Al Ouahabi, A.; Kotera, M.; Charles, L.; Lutz, J. - F. Acs Macro Letters 2015, 4 (10), 1077-1080.
    Résumé : Non-natural, sequence-encoded polyphosphates were prepared using the phosphoramidite approach on a DNA synthesizer. Two phosphoramidite monomers, namely, 2-cyanoethyl (3-dimethoxytrityloxy-propyl) diisopropylphosphoramidite (0) and 2-cyanoethyl (3-dimethoxytrityloxy-2,2-dimethyl-propyl) diisopropylphosphoramidite (1), were used in this approach to form binary-coded sequences. Using 1000 A controlled pore glass as a support and a large excess of monomers at each step, it was possible to synthesize homopolymers and sequence-coded copolymers of high chain-length. For instance, monodisperse polymers containing 16, 24, 56, and 104 coded monomer units were synthesized and characterized in this work. These results indicate that highly efficient phosphoramidite steps are suitable for the synthesis of long non-natural information-containing macromolecules.

  • Ayhan, M. M.; Karoui, H.; Hardy, M.; Rockenbauer, A.; Charles, L.; Rosas, R.; Udachin, K.; Tordo, P.; Bardelang, D.; Ouari, O. Journal of the American Chemical Society 2015, 137 (32), 10238-10245.
    Résumé : We describe a photochemical method to introduce a single alcohol function directly on cucurbit[n]urils (n = 5, 6, 7, 8) with conversions of the order 95-100% using hydrogen peroxide and UV light. The reaction was easily scaled up to 1 g for CB[6] and CB[7]. Spin trapping of cucurbituril radicals combined with MS experiments allowed us to get insights about the reaction mechanism and characterize CB [5], CB[6], CB[7], and C13[8] monofunctional compounds. Experiments involving O-18 isotopically labeled water indicated that the mechanism was complex and showed signs of both radical and ionic intermediates. DFT calculations allowed estimating the Bond Dissociation Energies (BDEs) of each hydrogen atom type in the CB series, providing an explanation of the higher reactivity of the "equatorial" C-H position of CB[n] compounds. These results also showed that, for CB [8], direct functionalization on the cucurbituril skeleton is more difficult because one of the methylene hydrogen atoms (H-b) has its BDE lowering within the series and coming close to that of H-c, thus opening the way to other types of free radicals generated on the CB[8] skeleton leading to several side products. Yet CB[5]-(OH)(1) and CB[8]-(OH)(1), the first CB[8] derivative, were obtained in excellent yields thanks to the soft method presented here.

  • Charles, L.; Laure, C.; Lutz, J. - F.; Roy, R. K. Macromolecules 2015, 48 (13), 4319-4328.
    Résumé : Monodisperse sequence-coded oligo(alkoxyamine amide)s were thoroughly investigated by tandem mass spectrometry to evaluate the robustness of this analytical approach as a reliable sequencing methodology. Studied samples were synthesized by orthogonal iterative chemistry on a solid support, and the 0/1 coding system was based on the mass of two amide synthons that alternate with a nitroxide moiety. The major fragmentation pathway experienced by these co-oligomers proceeded via homolysis of all fragile C-ON bonds between a coding unit and a nitroxide moiety. The relative rate of competing C-ON bond cleavages was observed to be sequence-dependent, offering an additional means to validate the sequences reconstructed from the MS/MS fragments. The same fragmentation rules applied for all studied samples, varying in terms of chain length, charge state, encoded sequence, end-groups, and nitroxide moiety. Ion mobility separation was coupled to MS/MS to sequence some more complex co-oligomers composed of both different nitroxides and coding units.

  • Chendo, C.; Moreira, G.; Tintaru, A.; Posocco, P.; Laurini, E.; Lefay, C.; Gigmes, D.; Viel, S.; Pricl, S.; Charles, L. Journal of the American Society for Mass Spectrometry 2015, 26 (9), 1483-1493.
    Résumé : Anomerization of simple sugars in the liquid phase is known as an acid- and base-catalyzed process, which highly depends on solvent polarity. This reaction is reported here to occur in the gas phase, during traveling wave ion mobility spectrometry (TWIMS) experiments aimed at separating alpha- and beta-anomers of penta-acrylated glucose generated as ammonium adducts in electrospray ionization. This compound was available in two samples prepared from glucose dissolved in solvents of different polarity, namely tetrahydrofuran (THF) and N,N-dimethylacetamide (DMAC), and analyzed by electrospray tandem mass spectrometry (ESI-MS/MS) as well as traveling wave ion mobility (ESI-TWIMS-MS). In MS/MS, an anchimerically-assisted process was found to be unique to the electrosprayed alpha-anomer, and was only observed for the THF sample. In ESI-TWIMS-MS, a signal was measured at the drift time expected for the alpha-anomer for both the THF and DMAC samples, in apparent contradiction to the MS/MS results, which indicated that the alpha-anomer was not present in the DMAC sample. However, MS/MS experiments performed after TWIMS separation revealed that ammonium adducts of the alpha-anomer produced from each sample, although exhibiting the same collision cross section, were clearly different. Indeed, while the alpha-anomer actually present in the THF sample was electrosprayed with the ammonium adducted at the C2 acrylate, its homologue only observed when the DMAC sample was subjected to TWIMS hold the adducted ammonium at the C1 acrylate. These findings were explained by a beta/alpha inter-conversion upon injection in the TWIMS cell, as supported by theoretical calculation and dynamic molecular modeling.


  • Chendo, C.; Rollet, M.; Phan, T. N. T.; Viel, S.; Gigmes, D.; Charles, L. International Journal of Mass Spectrometry 2015, 376, 90-96.
    Résumé : The position of nitrogen atoms in poly(4-vinylpyridine) (P4VP), compared to their poly(2-vinylpyridine) (P2VP) isomers, explains most difficulties faced when determining their molecular weight parameters by size exclusion chromatography, due to oligomers strongly adsorbing onto stationary phases. The high accessibility of these nitrogen atoms is shown here to be challenging also in matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS), probably accounting for the lack of mass data reported for P4VP in the literature. Using a “bottom-up” strategy starting from small oligomers prior to consider high molecular weight polymers, P4VP species were observed here to strongly interact with acidic matrix molecules such as 2,5-DHB when preparing MALDI sample using the traditional dried-droplet procedure. In contrast, MALDI best performed when using a solvent-free sample preparation involving a non-acidic matrix such as DCTB. Accordingly, reliable MS determination of molecular weight parameters could be achieved for P4VP up to about 40 kDa, as validated by diffusion NMR experiments.
    Mots-clés : MALDI, Mass spectrometry, P4VP, Poly(4-vinylpyridine), Solvent-free preparation, Synthetic polymer.

  • Moreira, G.; Fedeli, E.; Ziarelli, F.; Capitani, D.; Mannina, L.; Charles, L.; Viel, S.; Gigmes, D.; Lefay, C. Polymer Chemistry 2015, 6 (29), 5244-5253.
    Résumé : Cellulose acetate-g-polystyrene (CA-g-PS) grafted copolymers have been synthesized by nitroxide-mediated polymerization (NMP) under homogeneous conditions by using the 1,2-intermolecular radical addition (1,2-IRA) methodology to introduce the SG1-based alkoxyamine BlocBuilder MA (BB) on the polysaccharide backbone. A preliminary study conducted on model sugar-based alkoxyamines proved that whatever the position of the alkoxyamine on the sugar unit, the number of sugar units and the presence of OH groups, one could expect a controlled/living polymerization process. This was confirmed by the graft polymerization of styrene from the BB-modified cellulose acetate backbone with two different grafting ratios (3 and 20%) and different grafted chain lengths (40 000 and 80 000 g mol(-1) targeted M-n). The grafted copolymers were carefully analyzed, in particular, by DOSY NMR to confirm their grafted structure.

  • Pereira, B. de F. A.; Tardy, A.; Monnier, V.; Guillaneuf, Y.; Gigmes, D.; Charles, L. Rapid Communications in Mass Spectrometry 2015, 29 (23), 2302-2308.
    Résumé : RATIONALE: In order to prevent side reactions while developing new polymerization processes, their mechanism has to be understood and one first key insight is the structure of the end-groups in polymeric by-products. The synthetic method scrutinized here is the nitroxide-mediated polymerization (NMP) of a cyclic ketene acetal, a promising alternative process to the production of polyesters. METHODS: Polymer end-group characterization was performed by mass spectrometry (MS), combining elemental composition information derived from accurate mass data in the MS mode with fragmentation features recorded in the MS/MS mode. Electrospray was used as the ionization method to ensure the integrity of original chain terminations and a quadrupole time-of-flight (QTOF) instrument was employed for high-resolution mass measurements in both MS and tandem mass spectrometry (MS/MS) modes. RESULTS: Occurrence of side reactions in the studied polymerization method, first evidenced by an unusual increase in dispersity with conversion, was confirmed in MS with the detection of two polymeric impurities in addition to the expected species. Fragmentation rules were first established for this new polyester family in order to derive useful structural information from MS/MS data. In addition to a usual NMP by-product, the initiating group of the second polymeric impurities revealed the degradation of the nitroxide moiety. CONCLUSIONS: Unambiguous MS/MS identification of end-groups in by-products sampled from the polymerization medium allowed an unusual side reaction to be identified during the NMP preparation of polyesters. On-going optimization of the polymerization method aims at preventing this undesired process. Copyright (C) 2015 John Wiley & Sons, Ltd.

  • Roy, R. K.; Laure, C.; Fischer-Krauser, D.; Charles, L.; Lutz, J. - F. Chemical Communications 2015, 51 (86), 15677-15680.
    Résumé : Binary-encoded poly(alkoxyamine amide)s were prepared by oligomer ligation. These polymers contain digital sequences based on two monomers defined as 0 and 1 bits. A library of oligomers containing all possible dyads 00, 01, 10 and 11 was prepared and used to construct long coded sequences.

  • Roy, R. K.; Meszynska, A.; Laure, C.; Charles, L.; Verchin, C.; Lutz, J. - F. Nature Communications 2015, 6, 7237.
    Résumé : Biopolymers such as DNA store information in their chains using controlled sequences of monomers. Here we describe a non-natural information-containing macromolecule that can store and retrieve digital information. Monodisperse sequence-encoded poly(alkoxyamine amide)s were synthesized using an iterative strategy employing two chemoselective steps: the reaction of a primary amine with an acid anhydride and the radical coupling of a carbon-centred radical with a nitroxide. A binary code was implemented in the polymer chains using three monomers: one nitroxide spacer and two interchangeable anhydrides defined as 0-bit and 1-bit. This methodology allows encryption of any desired sequence in the chains. Moreover, the formed sequences are easy to decode using tandem mass spectrometry. Indeed, these polymers follow predictable fragmentation pathways that can be easily deciphered. Moreover, poly(alkoxyamine amide) s are thermolabile. Thus, the digital information encrypted in the chains can be erased by heating the polymers in the solid state or in solution.

  • Tintaru, A.; Ungaro, R.; Liu, X.; Chen, C.; Giordano, L.; Peng, L.; Charles, L. Analytica Chimica Acta 2015, 853, 451-459.
    Résumé : A new side-reaction occurring during divergent synthesis of PAMAM dendrimers (generations G(0)-G(2)) was revealed by mass spectrometric detection of defective molecules with a net gain of a single carbon atom as compared to expected compounds. Combining MS/MS experiments performed on different electrosprayed precursor ions (protonated molecules and lithiated adducts) with NMR analyses allowed the origin of these by-products to be elucidated. Modification of one ethylenediamine end-group of perfect dendrimers into a cyclic imidazolidine moiety was induced by formaldehyde present at trace level in the methanol solvent used as the synthesis medium. Dendrimers studied here were purposely constructed from a triethanolamine core to make them more flexible, as compared to NH3- or ethylenediamine-core PAMAM, and hence improve their interaction with DNA. Occurrence of this side-reaction would be favored by the particular flexibility of the dendrimer branches. (C) 2014 Elsevier B.V. All rights reserved.

  • Trinh, T. T.; Oswald, L.; Chan-Seng, D.; Charles, L.; Lutz, J. - F. Chemistry-a European Journal 2015, 21 (34), 11961-11965.
    Résumé : A simplified strategy for preparing non-natural information-containing polymers is reported. The concept relies on the successive ligation of oligomers that contain minimal sequence motifs. It was applied here to the synthesis of digitally-encoded poly(triazole amide)s, in which propyl and 2-methyl propyl motifs are used to code 0 and 1, respectively. A library of four oligo(triazole amide)s containing the information dyads 00, 01, 10, and 11 was prepared. These oligomers contain two reactive functions, that is, an alkyne and a carboxylic acid. Thus, they can be linked to another with the help of a reactive spacer containing azide and amine functions. Using two successive chemoselective steps, that is, azide-alkyne Huisgen cycloaddition and carboxylic acid-amine coupling, monodisperse polymers can be obtained. In particular, the library of dyads permits the implementation of any desired sequence using a small number of steps. As a proof-of-concept, the synthesis of molecular bytes 00000000 and 00000110 is described.
2014

  • Charles, L. Mass Spectrometry Reviews 2014, 33 (6), 523-543.
    Résumé : Mass spectrometry is increasingly used in the field of synthetic polymers as a fast and accurate technique for end-group analysis. More particularly, matrix-assisted laser desorption/ionization (MALDI) has gained much popularity because it allows quite simple mass spectra to be obtained, displaying a single distribution for each polymeric species present in the sample, in contrast to electrospray ionization (ESI) which readily promotes multiple charging for most polymers. A soft ionization process, ensuring the integrity of the species upon transfer into gas phase ions, is however mandatory for polymer end-group analysis since information about the chain terminations mainly rely on the m/z values measured for polymer adducts. As compared to ESI, MALDI is sometimes suspected to be a quite hard ionization technique, leading to spontaneous dissociation of ionized species either in the source or during their flight time. This issue is of particular concern for polymers carrying so-called fragile end-groups arising from their mode of synthesis. In particular, controlled radical polymerization (CRP) processes, one of the most important advances in the field of polymer science during the last 20 years, allow the production of polymers with well-defined molecular distribution and low polydispersities, but they are all based on the low dissociation energy of the chemical bond between the last monomer and the terminating group. As a result, if macromolecules are activated while being ionized, this end-group is prone to fragmentation and ions measured in the mass spectra do no longer reflect the original chain composition. However, different results are reported in the literature about the ability of MALDI to generate intact ions from CRP synthetic polymers. This article reviews MALDI MS data reported for synthetic polymers produced by atom transfer radical polymerization (ATRP), reversible addition-fragmentation transfer polymerization (RAFT), and nitroxide-mediated polymerization (NMP), the three most studied CRP techniques. The general principle of each polymerization process, which defines the structure of the end-groups in both targeted macromolecules and species arising from eventual side-reactions, is first briefly presented. An overview of MALDI data reported for samples obtained upon polymerization of different monomers are then commented for each polymerization techniques with regards to the success of the ionization method to generate intact cationic adducts and its propensity to distinguish in-source fragments from polymerization side-products. (c) 2013 Wiley Periodicals, Inc. Mass Spec Rev 33: 523-543, 2014.

  • Mayeux, C.; Massi, L.; Gal, J. - F.; Charles, L.; Burk, P. Chemistry-a European Journal 2014, 20 (3), 815-823.
    Résumé : The effect of Cs+ ligation on the decarboxylation of malonic acids (unsubstituted and methyl-, dimethyl-, ethyl-, and phenyl-substituted) in their carboxylate form was studied in the gas phase using tandem mass spectrometry. The study is based on the comparison of the decarboxylation of the bare monoanion (hydrogen malonates) and of the cesium adduct of the cesium salt (Cs+[cesium hydrogen malonates]) under collisional activation. Energy-resolved dissociation curves of the negative and positive ions exhibit major differences. Decarboxylation of the cationic adducts of substituted malonic acid salts occurs at significantly lower collisional activation than for the corresponding bare hydrogen malonate anions. The conclusions from these experiments are supported by DFT calculations. The calculated activation parameters (enthalpy and Gibbs energy) confirm that the cesium cation coordination assists the decarboxylation of the carboxylate form.

  • Tintaru, A.; Chendo, C.; Wang, Q.; Viel, S.; Quelever, G.; Peng, L.; Posocco, P.; Pricl, S.; Charles, L. Analytica Chimica Acta 2014, 808, 163-174.
    Résumé : Tandem mass spectrometry and ion mobility spectrometry experiments were performed on multiply charged molecules formed upon conjugation of a poly(amidoamine) (PAMAM) dendrimer with a poly(ethylene oxide) (PEO) linear polymer to evidence any conformational modification as a function of their charge state (2+ to 4+) and of the adducted cation (H+ vs Li+). Experimental findings were rationalized by molecular dynamics simulations. The G0 PAMAM head-group could accommodate up to three protons, with protonated terminal amine group enclosed in a pseudo 18-crown-6 ring formed by the PEO segment. This particular conformation enabled a hydrogen bond network which allowed long-range proton transfer to occur during collisionally activated dissociation. In contrast, lithium adduction was found to mainly occur onto oxygen atoms of the polyether, each Li+ cation being coordinated by a 12-crown-4 pseudo structure. As a result, for the studied polymeric segment (M-n = 1500 g mol(-1)), PEO-PAMAM hybrid molecules exhibited a more expanded shape when adducted to lithium as compared to proton. (C) 2013 Elsevier B. V. All rights reserved.
2013


  • Astolfi, P.; Charles, L.; Gigmes, D.; Greci, L.; Rizzoli, C.; Sorana, F.; Stipa, P. Organic & Biomolecular Chemistry 2013, 11 (8), 1399-1406.
    Résumé : The formation of a di-tert-alkyl nitroxide has been observed by Electron Spin Resonance during the exposure of coenzyme CoQ10, in both the oxidized and reduced forms, to nitrogen dioxide (˙NO2) or to nitric oxide (˙NO) in the presence of oxygen. The same kind of nitroxide has been observed also with CoQ1, CoQ3 or with 1-phenyl-3-methyl-2-butene, chosen as model compounds. In all cases, the formation of the nitroxide may be justified only by admitting the involvement of the isoprenic chain of the coenzymes and in particular the addition of ˙NO2 to the double bond. A mechanism which accounts for the formation of the nitroxide as well as the other compounds observed in the reactions is proposed and confirmed by a spectroscopic investigation (FT-IR, 1H NMR, X-ray analysis) and by ESI-MS.

  • Fouquet, T.; Chendo, C.; Toniazzo, V.; Ruch, D.; Charles, L. Rapid Communications in Mass Spectrometry 2013, 27 (1), 88-96.
    Résumé : RATIONALE When substituting one methyl moiety by a hydrogen atom in each end-group of a trimethylsilyl-terminated poly(dimethylsiloxane) (PDMS), dissociation reactions of oligomers adducted with ammonium were observed to proceed at a much higher rate, evidencing the high reactivity of hydride groups. Polymeric molecules containing methylhydrosiloxane (MHS) units could thus be expected to exhibit a different tandem mass spectrometric (MS/MS) behavior from PDMS. METHODS Trimethylsilyl-terminated PMHS and trimethylsilyl-terminated poly(MHS)-co-(DMS) were electrosprayed in the gas phase either as ammonium adducts or lithium adducts. Product ions generated upon collision-induced dissociation (CID) were accurately mass measured in an orthogonal acceleration time-of-flight mass analyzer. RESULTS In contrast to PDMS adducted with lithium, useful structural features could be obtained from product ions generated upon CID of lithium adducts of PMHS. The presence of multiple hydride groups in PMHS induced numerous rearrangements when activating ammonium adducts of these oligomers. MS/MS reactions observed for cationic adducts of MHS-DMS co-oligomers were clearly a combination of major dissociation routes established for the corresponding homopolymers. However, the concerted loss of H2 and ammonia typically observed from ammonium adducts of PMHS was always shown to generate a quite abundant product ion even from co-oligomers enriched with DMS units. CONCLUSIONS The high reactivity of hydride moieties, previously evidenced when these groups were at the end of PDMS chains, is also at work in PMHS, where each monomer contains a Si-H function. The presence of these hydride groups would increase the nucleophilic character of the oxygen atoms, favoring a tight bonding of lithium, and hence allowing in-chain cleavages to occur. In PMHS ammonium adducts, the particular reactivity of hydride moieties was illustrated by multiple hydride transfers but also by a dehydrogenation reaction systematically observed to proceed, together with the loss of ammonia, from all precursor ions. This latter reaction remained a very competitive process even from MHS/DMS co-oligomers with a low relative number of MHS units. Copyright (c) 2012 John Wiley & Sons, Ltd.

  • Fouquet, T.; Petersen, J.; Ziarelli, F.; Bour, J.; Toniazzo, V.; Ruch, D.; Charles, L. Plasma Processes and Polymers 2013, 10 (3), 271-284.
    Résumé : Thin films obtained upon plasma polymerization of D4 and HMDSO precursors at atmospheric pressure are submitted to controlled ethanolysis to produce oligomers amenable to electrospray mass spectrometry. When using high resolution mass spectrometry to assess their elemental composition and tandem mass spectrometry to characterize their end-groups, a whole set of ethanolysis products is identified, from which the network connectivity in the original film can be reconstructed. Ethanolysis products of ppD4 and ppHMDSO exhibit the same structural features composed of linear and cross-linked PDMS moieties, the extent of cross-linking reflecting the inorganic character of the film. Oligomers originally embedded in the solid network and released as intact species upon its dissolution are also observed. [GRAPHICS] .

  • Fouquet, T.; Toniazzo, V.; Ruch, D.; Charles, L. Journal of the American Society for Mass Spectrometry 2013, 24 (7), 1123-1129.
    Résumé : Collision-induced dissociation of doubly charged poly(dimethylsiloxane) (PDMS) molecules was investigated to provide experimental evidence for fragmentation reactions proposed to occur upon activation of singly charged oligomers. This study focuses on two PDMS species holding trimethylsilyl or methoxy end-groups and cationized with ammonium. In both cases, introduction of the additional charge did not induce significant differences in dissociation behavior, and the use of doubly charged precursors enabled the occurrence of charge-separation reactions, allowing molecules always eliminated as neutrals upon activation of singly charged oligomers to be detected as cationized species. In the case of trimethylsilyl-terminated oligomers, random location of the adducted charge combined with rapid consecutive reactions proposed to occur from singly charged precursors could be validated based on MS/MS data of doubly charged oligomers. In the case of methoxy-terminated PDMS, favored interaction of the adducted ammonium with both end-groups, proposed to rationalize the dissociation behavior of singly charged molecules, was also supported by MS/MS data obtained for molecules adducted with two ammonium cations.

  • Girod, M.; Antoine, R.; Lemoine, J.; Dugourd, P.; Charles, L. International Journal of Mass Spectrometry 2013, 333, 27-33.
    Résumé : Tandem mass spectrometry of co-oligomers composed of methacrylic acid (MAA) and methyl methacrylate (MMA) units was performed after activated electron photo-detachment dissociation (activated EPD). In this technique, doubly charged MAA/MMA co-oligomers were first produced in negative mode electrospray ionization. Species produced upon electron photo-detachment (220 nm) of these doubly charged co-oligomers were observed to spontaneously eliminate a carbon dioxide molecule. The so-formed radical anions were then activated by collision. In contrast to CID of negatively charged MAA/MMA co-oligomers, which does not provide informative data with regards to the end-groups, activated EPD is shown here to promote efficient radical-induced dissociation reactions thanks to the oxidation of a carboxylate pendant group upon laser irradiation. Product ions generated after backbone bond cleavages only contained the anionic initiating group. Combining these MS/MS results with the sum of the end-group masses determined from MS data allowed the terminating group to be characterized. As compared to activated EPD data obtained for a PMAA homopolymer holding the same end-groups, an additional product ion series was generated in the case of MAA/MMA copolymers, strongly suggesting that the hydrogen bond network established between neighboring MAA monomers is disrupted when M


  • Lefay, C.; Guillaneuf, Y.; Moreira, G.; Thevarajah, J. J.; Castignolles, P.; Ziarelli, F.; Bloch, E.; Major, M.; Charles, L.; Gaborieau, M.; Bertin, D.; Gigmes, D. Polymer Chemistry 2013, 4 (2), 322-328.
    Résumé : Chitosan (CS) was modified by SG1-based nitroxide-mediated polymerization under heterogeneous conditions. After introduction of acrylamide and/or acrylate functions onto the CS backbone followed by intermolecular 1,2 radical addition of the BlocBuilder alkoxyamine (CS–BB), methyl methacrylate (MMA) in the presence of a small amount of acrylonitrile (AN) or sodium 4-styrenesulfonate (SS) was polymerized by nitroxide-mediated polymerization (NMP). ESR and free-solution capillary electrophoresis confirmed the synthesis of CS–BB. The successful synthesis of CS-g-P(MMA-co-AN) and CS-g-PSS grafted copolymers was proved by TGA and solid-state NMR spectroscopy with ca. 20 to 30 wt% of grafted synthetic polymer in the final product.

  • Moreira, G.; Charles, L.; Major, M.; Vacandio, F.; Guillaneuf, Y.; Lefay, C.; Gigmes, D. Beilstein Journal of Organic Chemistry 2013, 9, 1589-1600.
    Résumé : The range of applications of cellulose, a glucose-based polysaccharide, is limited by its inherently poor mechanical properties. The grafting of synthetic polymer chains by, for example, a "grafting from" process may provide the means to broaden the range of applications. The nitroxide-mediated polymerization (NMP) method is a technique of choice to control the length, the composition and the architecture of the grafted copolymers. Nevertheless, cellulose is difficult to solubilize in organic media because of inter and intramolecular hydrogen bonds. One possibility to circumvent this limitation is to solubilize cellulose in N,N-dimethyl-formamide (DMF) or N,N-dimethylacetamide (DMA) with 5 to 10 wt % of lithium salts (LiCl or LiBr), and carry out grafted polymerization in this medium. The stability of nitroxides such as SG1 has not been studied under these conditions yet, even though these parameters are of crucial importance to perform the graft modification of polysaccharide by NMP. The aim of this work is to offer a model study of the stability of the SG1 nitroxide in organic media in the presence of unprotected glucose or cellobiose (used as a model of cellulose) and in the presence of lithium salts (LiBr or LiCl) in DMF or DMA. Contrary to TEMPO, SG1 proved to be stable in the presence of unprotected sugar, even with an excess of 100 molar equivalents of glucose. On the other hand, lithium salts in DMF or DMA clearly degrade SG1 nitroxide as proven by electron-spin resonance measurements. The instability of SG1 in these lithium-containing solvents may be explained by the acidification of the medium by the hydrolysis of DMA in the presence of LiCl. This, in turn, enables the disproportionation of the SG1 nitroxide into an unstable hydroxylamine and an oxoammonium ion. Once the conditions to perform an SG1-based nitroxide-mediated graft polymerization from cellobiose have been established, the next stage of this work will be the modification of cellulose and cellulose derivatives by NMP.

  • Nawaz, F.; Mohanan, K.; Charles, L.; Rajzmann, M.; Bonne, D.; Chuzel, O.; Rodriguez, J.; Coquerel, Y. Chemistry-a European Journal 2013, 19 (51), 17578-17583.
    Résumé : Nucleophilic addition of pyridines to benzyne generates zwitterionic adducts that evolve by a rapid intramolecular proton shift to produce the corresponding pyridine carbenes, N-phenyl pyrid-2-ylidenes. In the presence of electrophilic ketones (isatin derivatives), the pyridylidenes can further react by an original bis-arylation reaction of the carbonyl compounds involving a formal pyridine CH bond functionalisation. The overall transformation is an unprecedented three-component reaction featuring a carbene intermediate. The mechanism of this transformation was examined in detail by using both experimental and theoretical approaches. It was found that the generation of N-phenyl pyrid-2-ylidene from pyridine and benzyne is energetically favoured, and that the corresponding carbene dimer can also form easily. Under the three-component reaction conditions, the pyridylidene preferentially adds to the ketone group of the isatin derivative to produce a zwitterionic adduct amenable to an intramolecular aryl transfer reaction by a concerted nucleophilic aromatic substitution. This peculiar reactivity for a carbene was compared to possibly competitive known reactions of stable carbenes with carbonyl compounds, and the reaction was found to be under thermodynamic control. The reported method of generation of N-phenyl pyrid-2-ylidenes and their reactivity with carbonyl compounds unlock new perspectives in organic synthesis.


  • Tardy, A.; Delplace, V.; Siri, D.; Lefay, C.; Harrisson, S.; Pereira, B. de F. A.; Charles, L.; Gigmes, D.; Nicolas, J.; Guillaneuf, Y. Polymer Chemistry 2013, 4 (17), 4776-4787.
    Résumé : The ring-opening polymerization of cyclic ketene acetals (CKAs) by controlled radical mechanisms represents an alternative route for the synthesis of aliphatic polyesters. For the first time, 5,6-benzo-2-methylene-1,3-dioxepane (BMDO) and 2-methylene-4-phenyl-1,3-dioxolane (MPDL) were homopolymerized by nitroxide mediated polymerization (NMP), from the commercially available SG1-based BlocBuilder MA alkoxyamine. Various experimental conditions (i.e., reaction temperature, nature of solvent, and nature of the alkyl initiating radical) were varied to determine the optimized conditions in terms of polymerization kinetics and living character of the final polymer. Chain-end extensions from either PS-SG1 or PBMDO-SG1 were also performed in order to furnish PS-b-PBMDO and PBMDO-b-PS, respectively, thus demonstrating the synthesis of block copolymers comprising a CKA block. In order to have a better insight into the polymerization mechanism, the occurrence of side reactions was analyzed by 31P NMR spectroscopy and ESI-MS. It was supposed that the ketal-based macroradical could be irreversibly trapped by nitroxide and thus the corresponding macroalkoxyamine decomposed by CO–N bond dissociation. DFT calculations as well as PREDICI modeling were also undertaken in order to support this hypothesis.


  • Tintaru, A.; Chendo, C.; Phan, T. N. T.; Rollet, M.; Giordano, L.; Viel, S.; Gigmes, D.; Charles, L. Analytical Chemistry 2013, 85 (11), 5454-5462.
    Résumé : Cleavage of the labile halide termination upon matrix-assisted laser desorption/ionization (MALDI) has always been reported as a major concern in mass analysis of polystyrene prepared by atom transfer radical polymerization (ATRP). By studying this issue using nuclear magnetic resonance (NMR) and electrospray ionization?mass spectrometry, we evidence here that the ionization step is not involved in this deleterious process. Instead, removal of the halogen was shown to readily occur upon interaction of the silver salt (AgTFA) used as the cationizing agent in mass spectrometry, either in solution or in the solid-state when performing solvent-free sample preparation. In solution, this silver-induced reaction mostly consists of a nucleophilic substitution, leading to polystyrene molecules holding different terminations, depending on relative nucleophilicity of species present in the liquid-phase solution composition. In chloroform supplemented with AgTFA, trifluoroacetate-terminated PS were evidenced in ESI-MS spectra but experienced end-group cleavage in MALDI. In contrast, the major methoxy-terminated PS macromolecules formed when the silver-catalyzed nucleophilic substitution was performed in methanol were generated as intact gas-phase ions using both ionization techniques. This controlled and fast modification could hence be advantageously used as a rapid sample pretreatment for safe MALDI mass analysis of ATRP-made polystyrene.

  • Tintaru, A.; Pricl, S.; Denbigh, L.; Liu, X.; Peng, L.; Charles, L. International Journal of Mass Spectrometry 2013, 354, 235-241.
    Résumé : Mass spectrometry was used in conjunction with ion mobility experiments and molecular modeling to study any conformational changes of two PAMAM dendrimers of different structure as a function of their protonation degree. Changes of molecular conformation conjectured from peculiar charge state distribution in the electrospray mass spectra were confirmed by collision cross section values derived from ion mobilograms and supported by theoretical calculations. Shape extension was significant for triply charged molecules of both dendrimers, but the extent of this swelling phenomenon was shown to strongly depend on the PAMAM dendrimers architecture. (C) 2013 Elsevier B.V. All rights reserved.
2012

  • Barrere, C.; Chendo, C.; Phan, T. N. T.; Monnier, V.; Trimaille, T.; Humbel, S.; Viel, S.; Gigmes, D.; Charles, L. Chemistry-a European Journal 2012, 18 (25), 7916-7924.
    Résumé : A sample pretreatment was evaluated to enable the production of intact cationic species of synthetic polymers holding a labile end-group using matrix-assisted laser desorption/ionization (MALDI) mass spectrometry. More specifically, polymers obtained by nitroxide-mediated polymerization involving the MAMA-SG1 alkoxyamine were stirred for a few hours in trifluoroacetic acid (TFA) to induce the substitution of a tert-butyl group on the nitrogen of nitroxide end-group by a hydrogen atom. Nuclear magnetic resonance, electrospray ionization tandem mass spectrometry, and theoretical calculations were combined to scrutinize this sample pretreatment from both mechanistic and energetic points of view. The substitution reaction was found to increase the dissociation energy of the fragile C?ON bond to a sufficient extent to prevent this bond to be spontaneously cleaved during MALDI analysis. This TFA treatment is shown to be very efficient regardless of the nature of the polymer, as evidenced by reliable MALDI mass spectrometric data obtained for poly(ethylene oxide), polystyrene and poly(butylacrylate).

  • Charles, L.; Lejars, M.; Margaillan, A.; Bressy, C. International Journal of Mass Spectrometry 2012, 311, 31-39.
    Résumé : Fragmentation pathways of methacrylic polymers containing labile silyl ester pendant groups were characterized upon collisional activation of electrosprayed oligomer adducts. Dissociation of lithiated oligomers mainly generated low mass product ions containing the a end-group and arising from backbone bond homolytic cleavages, as typically observed for poly(alkylmethacrylate)s. Combined with the sum of the end-group masses as determined from MS data, this main reaction allowed both end-groups to be validated. In contrast, loss of HCOOR (with R = triisopropylsilyl) or elimination of alkene species from alkylsilyl groups, such as reported from poly(butylmethacrylate), was not observed here, probably due to steric hindrance of the pendant moieties. Activation of ammonium oligomer adducts was found to provide highly complementary information, since they exhibited a similar behavior as compared to poly(methacrylic acid), with serial eliminations of a triisopropylsilanol neutral conducting to the determination of the polymerization degree of the dissociating precursor ion. It should be noted however that this useful pathway was not always observed to efficiently compete with dissociation of reactive omega end-groups. Based on these fragmentation rules, five poly(triisopropylsilyl methacrylate)s were identified in a sample obtained via reversible addition-fragmentation chain transfer (RAFT) polymerization using cyanoisopropyl dithiobenzoate as the chain transfer agent. Their structure could be rationalized with regards to RAFT processes: (i) dormant chains initiated by a cyanoisopropyl group and terminated by a dithiobenzoate group, as the main species: (ii) proton- and (iii) vinyl-terminated dead chains produced by disproportionation termination events: (iv) alpha,omega-cyanoisopropyl-terminated polymer chains arising from a combination termination between two macromolecular propagating radicals, and (v) dormant chains containing methacrylic acid monomer units within the chain. (C) 2011 Elsevier B.V. All rights reserved.

  • Choteau, F.; Tuccio, B.; Villamena, F. A.; Charles, L.; Pucci, B.; Durand, G. Journal of Organic Chemistry 2012, 77 (2), 938-948.
    Résumé : A novel series of a-phenyl-N-tert-butyl nitrone derivatives, bearing a hydrophobic chain on the aromatic ring and three hydroxyl functions on the tert-butyl group, was synthesized through a short and convenient synthetic route based on a one-pot reduction/condensation of tris(hydroxymethyl)nitromethane with a benzaldehyde derivative. Because of the presence of hydroxyl functions on the tert-butyl group, an intramolecular Forrester-Hepburn reaction leading to the formation of an oxazolidine-N-oxyl compound was observed by electron paramagnetic resonance (EPR). The mechanism of cyclization was further studied by computational methods showing that intramolecular hydrogen bonding and high positive charge on the nitronyl carbon could facilitate the nucleophilic addition of a hydroxyl group onto the nitronyl carbon. At high nitrone concentrations, a second paramagnetic species, very likely formed by intermolecular nucleophilic addition of two nitrone molecules, was also observed but to a lesser extent. In addition, theoretical data confirmed that the intramolecular reaction is much more favored than the intermolecular one. These nitrones were also found to efficiently trap carbon-centered radicals, but complex spectra were observed due to the presence of oxazolidine-N-oxyl derivatives.

  • Fouquet, T.; Bour, J.; Toniazzo, V.; Ruch, D.; Charles, L. Rapid Communications in Mass Spectrometry 2012, 26 (17), 2057-2067.
    Résumé : RATIONALE The partial and controlled degradation of insoluble cross-linked silicon-based polymers is a promising approach to enable their characterization by mass spectrometry. Providing that the chemolysis reaction specifically proceeds at cross-linking sites, the size of linear poly(dimethylsiloxane)s (PDMS) produced during the treatment should reflect the length of linear segments between branching points in the original network. In this context, the specificity of ethanol to act as a nucleophilic agent towards tri-functional silicon atoms in a D3TDnTD3 model was evaluated. METHODS Tandem mass spectrometry (MS/MS) combined with accurate mass measurements, MS3 experiments and collision-induced dissociation of authentic compounds was used for structural characterization of D3TDnTD3 ethanolysis products. All MS/MS data were obtained from electrosprayed ammonium adducts, previously reported to provide the most informative data for silicon-based polymers. RESULTS Since the expected ethanolysis products were hydroxy- and ethoxy-terminated PDMS, the dissociation behavior of such polymeric species was established, using electrosprayed ammonium adducts as the precursor ions. Diagnostic product ions were identified, allowing four main D3TDnTD3 ethanolysis products to be structurally characterized. End-group analysis of these polymeric distributions clearly indicated that ethanolysis was mostly occurring on tri-functional silicon atoms but also, to a lesser extent, on those D atoms close to T silicons. CONCLUSIONS The size of the linear skeleton located between two tri-functional silicon atoms could be accurately determined by mass spectrometric analyses of a polymeric model submitted to ethanolysis. This soft and rapid pre-treatment is thus a promising approach for determining the length of linear segments between branching points in the original network of cross-linked silicon-based polymers. Copyright (C) 2012 John Wiley & Sons, Ltd.

  • Fouquet, T.; Petersen, J.; Bomfim, J. A. S.; Bour, J.; Ziarelli, F.; Ruch, D.; Charles, L. International Journal of Mass Spectrometry 2012, 313, 58-67.
    Résumé : Electrospray tandem mass spectrometry was used here to study the soluble part of a thin film prepared by plasma polymerization of octamethylcyclotetrasiloxane (D4). Accurate mass measurements and Si-29 nuclear magnetic resonance (NMR) spectroscopy, as well as synthesis of authentic compounds used as models to understand the MS/MS behavior of plasma polymers, were combined to structurally investigate oligomers present in this extract. All precursor ions were protonated or ammoniated molecules, known to provide more useful information for dimethylsiloxane (DMS)-based polymers as compared to alkali adducts. Apart from a major compound consisting of two D4 units connected via an oxygen bridge, it was found that the soluble part of this plasma polymer was mainly composed of cyclolinear polysiloxanes, in which cyclic units composed of four DMS were covalently connected by linear DMS segments. As the size of precursor ions increases, discrepancies observed between MS/MS data of synthesized molecules and of plasma oligomers would reveal the presence of branched isomers in the soluble part of the film, consistently with the expected propensity of the plasma polymerization process to favor random branching. (C) 2012 Elsevier B.V. All rights reserved.

  • Fouquet, T.; Phan, T. N. T.; Charles, L. Rapid Communications in Mass Spectrometry 2012, 26 (7), 765-774.
    Résumé : RATIONALE: Polyhedral oligomeric silsesquioxanes (POSSs), defined as [RSiO3/2](n) with R designating an organic substituent, were considered here as models of highly cross-linked polysiloxanes, to be further used as references in tandem mass spectrometric characterization of plasma polymers of hexamethyldisiloxane, expected to be composed of organic polydimethylsiloxane (PDMS) and inorganic (SiOx) silica-based parts. The collision-induced dissociation (CID) behavior of [RSiO3/2](8) compounds was then studied as a function of the R substituent. METHODS: POSS compounds were produced in the gas phase as ammonium adducts and the product ions generated upon CID, amongst which was the protonated precursor, were accurately mass measured in an orthogonal acceleration time-of-flight mass analyzer. RESULTS: The presence of eight propylamine substituents was shown to induce sequential dehydration of the protonated precursor, ultimately leading to a complete unfolding of the POSS cage. Similar opening of the octahedron structure in the protonated molecule substituted with OSi(CH3)(3), OSiH(CH3)(2) or OH (formed upon methanolysis of dimethylsiloxy substituents) was proposed to account for the product ions generated during their CID. Sequential charge-remote transfers of amethyl group (and of H in the case of dimethylsiloxy substituents) fromone substituent group to a neighboring onewas shown to lead to a linear co-oligomeric chain composed of randomly distributed siloxy-based monomers. CONCLUSIONS: All the peaks observed in CID could be accounted for by applying dissociation reactions typically occurring in protonated polysiloxane-like oligomers. The large number of product ions observed in MS/ MS was found to result from the variety of possible structural rearrangements, producing numerous linear isomeric forms of the dissociating species. Copyright (C)2012 John Wiley & Sons, Ltd.

  • Gal, J. - F.; Mayeux, C.; Massi, L.; Major, M.; Charles, L.; Haljasorg, T. Journal of Chemical Education 2012, 89 (11), 1476-1478.
    Résumé : The determination of the gas-phase basicity of organic bases (ligands) toward the lithium cation may be achieved by mass spectrometry, as described for protonic gas-phase basicity by Sunderlin et al. (J. Chem. Educ. 2005, 82, 1071-1073). The lithium cation-bound dimers, generated by electrospray ionization, are dissociated by collision-induced dissociation in a tandem mass spectrometer such as triple quadrupole or quadrupole-time-of-flight instruments. An ion trap instrument is not recommended because of solvent adduct formation from Li+ containing fragments. The relative intensities of the ionic fragments are treated along the kinetic method. This experiment is another illustration of the possibilities offered by mass spectrometry for the determination of thermochemical data on gas-phase species. In this experiment, students have the opportunity to identify and manipulate metal-cation adducts which are frequently observed spectrometry. Additional pedagogical interest may arise from discussion of the bonding with Li+ the structural effects on Li+ basicity, and the specific applications of the lithium ion, in particular its role in energy storage. in mass

  • Girod, M.; Brunet, C.; Antoine, R.; Lemoine, J.; Dugourd, P.; Charles, L. Journal of the American Society for Mass Spectrometry 2012, 23 (1), 7-11.
    Résumé : Characterization of end-groups in poly(methacrylic acid) (PMAA) was achieved using tandem mass spectrometry after activated-electron photodetachment dissociation (activated-EPD). In this technique, multiply deprotonated PMAA oligomers produced in the negative-ion mode of electrospray ionization were oxidized into radical anions upon electron photodetachment using a 220 nm laser wavelength, and further activated by collision. In contrast to conventional collision induced dissociation of negatively charged PMAA, which mainly consists of multiple dehydration steps, fragmentation of odd-electron species is shown to proceed via a radical-induced decarboxylation, followed by reactions involving backbone bond cleavages, giving rise to product ions containing one or the other oligomer termination. A single radical-induced mechanism accounts for the four main fragment series observed in MS/MS. The relative position of the radical and of the anionic center in distonic precursor ions determines the nature of the reaction products. Experiments performed using PMAA sodium salts allowed us to account for relative abundances of product ions in series obtained from PMAA, revealing that ion stability is ensured by hydrogen bonds within pairs of MAA units.

  • Major, Y.; Pizzala, H.; Ziarelli, F.; Phan, T. N. T.; Mollica, G.; Charles, L. Analytical Methods 2012, 4 (10), 3118-3126.
    Résumé : Molecular organization of MALDI samples is suspected to play a major role in the ionization process. Using solvent-free conditions to prepare polymer samples to be mass analyzed, we show here that the grinding time influenced not only the quality of MALDI data but also the nature of detected adducts. In this context, molecular organization of these MALDI samples was studied by solid-state NMR, due to the ability of this technique to reveal changes in the local nuclear environment in solids. The model system investigated here was composed of 2,5-DHB as the matrix, a small poly(ethylene oxide) (PEG) as the analyte and cesium chloride as the cationizing agent, allowing H-1, C-13 and Cs-133 sites to be directly probed using NMR. To ensure reproducible data, the vortex method was chosen to grind the sample components in the solid state. Three different phases within the MALDI samples were evidenced through NMR. After grinding the three sample components for short times (ca. 2 min), the solid was composed of two phases, a crystalline 2,5-DHB phase and a matrix-PEG co-crystal. In spite of the addition of a cesium salt in the ternary mixture, laser irradiation of these samples only produced polymer sodium adducts. In contrast, longer grinding times (ca. 16 min), shown to promote the formation of a third phase composed of a matrix-salt co-crystal, allowed optimal production of PEG cesium adducts. Water molecules were evidenced for the first time to be part of the MALDI sample. Water could only be observed in the 2,5-DHB-CsCl crystalline complex and its presence in the grinding atmosphere was shown to be necessary for this complex to form. The variety of structural information obtained by solid-state NMR on the investigated model sample showed how this technique can be successfully employed to gain new insights into the MALDI mechanism.
2011

  • Fouquet, T.; Humbel, S.; Charles, L. Journal of the American Society for Mass Spectrometry 2011, 22 (4), 649-658.
    Résumé : Ammonium adducts of trimethylsilyl-terminated poly(dimethylsiloxane) (CH(3)-PDMS) produced by electrospray ionization were submitted to collision induced dissociation and revealed a particular MS/MS behavior: the same three main product ions at m/z 221, 295, and 369 were always generated in very similar relative abundances regardless of the size of the precursor ion. Combining accurate mass measurements and ab initio calculation allowed very stable cyclic geometries to be obtained for these ionic species. Dissociation mechanisms were proposed to account for the three targeted ions to be readily generated in a two-step or a three-step reaction from any CH(3)-PDMS ammonium adducts. A second set of three product ions was also observed with low abundance at m/z 207, 281, and 355, which were shown in MS(3) experiments to be formed in secondary reactions. An alternative dissociation process was shown to consist of a concerted elimination of ammonia and methane and the need for a methyl of an end-group to be involved in the released methane molecule would account for this reaction to mainly proceed from the smallest precursor ions.

  • Fouquet, T.; Humbel, S.; Charles, L. International Journal of Mass Spectrometry 2011, 306 (1), 70-76.
    Résumé : Dissociation behavior of ammonium adducts of alpha,omega-dihydride poly(dimethylsiloxane) (H-PDMS) produced by electrospray ionization was studied in collisional activation conditions. In contrast to MS/MS spectra of synthetic polymers usually displaying fragment series on the whole m/z range, ammonium adducts of H-PDMS were shown to always generate the same product ions regardless of the size of the precursor ion. Based on accurate mass measurement and ab initio calculation, mechanisms could be proposed to account for this MS/MS pattern. A primary reaction consisting of release of ammonia and hydrogen from activated oligomer adducts would be rapidly followed by elimination of a three dimethylsiloxane-containing cyclic species to generate the three main product ions at m/z 207, 281 and 355. Further dissociation of these three species would explain additional signals in MS/MS spectra. Although a similar behavior was previously observed for PDMS bearing methyl terminations (CH(3)-PDMS), strong variations in product ion relative abundance were measured as the size of oligomeric precursor increased in the case of H-PDMS. Perfect similarity of MS/MS spectra is shown to occur once hydride end-groups are no longer involved in primary dissociation reactions. Measuring the degree of similarity between MS/MS spectra of consecutive oligomers within PDMS distribution indicates a much higher reactivity of hydride terminations towards the adducted ammonium cation, as compared to methyl end-groups. (C) 2011 Elsevier B.V. All rights reserved.

  • Girod, M.; Antoine, R.; Lemoine, J.; Dugourd, P.; Charles, L. Rapid Communications in Mass Spectrometry 2011, 25 (21), 3259-3266.
    Résumé : Tandem mass spectrometry of poly(styrene sulfonate sodium salt) (PSS) was performed after activated electron photo-detachment dissociation (activated EPD). In this technique, doubly charged PSS oligomers were first produced in negative mode electrospray ionization, then oxidized into radical anions upon electron photo-detachment using a 220 nm laser wavelength, and further activated by collision. In contrast to the collision-induced dissociation (CID) of negatively charged PSS oligomers, which does not provide informative data with regard to the end-groups, activated-EPD is shown here to promote radical-induced dissociation reactions thanks to the oxidation of a sulfonate group upon laser irradiation. Major product ions generated after backbone bond cleavages contained one or the other chain terminations and could be accounted for by two main mechanisms. Moreover, each of the proposed dissociation reactions was shown to generate two distinct fragments, depending on the location of the oxidized monomer near one or the other chain terminal moieties. As a result, a combination of these two fragments allowed a straightforward mass characterization of each end-group. Copyright (C) 2011 John Wiley & Sons, Ltd.

  • Major, M.; Fouquet, T.; Charles, L. Journal of the American Society for Mass Spectrometry 2011, 22 (7), 1252-1259.
    Résumé : Isomeric distinction of di- and tri-saccharides could be efficiently achieved by using data previously obtained while performing experiments aimed at discriminating monosaccharides using trimeric ion dissociation with data analysis by the kinetic method. This study shows that effects observed for lower homologues when one of the partners is changed in the metal/reference system (typically a transition metal divalent cation associated to amino acids) can be extrapolated to upper homologues, at least for the tested analyte series. Systems allowing galactose, glucose, and fructose distinction were used as starting conditions to resolve cellobiose, lactose, maltose, and saccharose disaccharides. When a unique dissociation reaction was observed from the trimeric clusters, a new reference was selected based on its propensity to favor the analyte or the reference release, as revealed from monosaccharide experiments, depending on the desired effect. The same approach could be implemented from data obtained for disaccharides to select efficient metal/reference systems to distinguish cellotriose, isomaltotriose, maltotriose, and panose trisaccharides. As a result, method optimization is greatly improved due to an enhanced rationalization of the search for discriminant systems. While 40 systems had to be tested for monosaccharides, by screening five transition metals and eight amino acids, the proposed approach allowed efficient metal/reference systems to be found for disaccharides after testing 18 combinations; then, only four systems had to be scrutinized to achieve trisaccharide distinction. Accurate quantitative analyses could be performed in binary mixtures using three-point calibration curves to correct for competition effects between analytes for the formation of the trimeric clusters.

  • Tintaru, A.; Chendo, C.; Monnier, V.; Bouillon, C.; Quelever, G.; Peng, L.; Charles, L. International Journal of Mass Spectrometry 2011, 308 (1), 56-64.
    Résumé : A poly(amino)ester dendrimer, bearing tert-butyl ester terminations and used as the precursor of an acid-terminating poly(amino)ester dendrimer, was studied by electrospray ionization tandem mass spectrometry to establish its fragmentation rules upon collision-induced dissociation. Mechanisms for dissociation reactions experienced by protonated molecules were proposed and supported by accurate mass measurements. The release of 2-methylprop-1-ene was observed as many times as tert-butyl groups were available. Each of these steps was followed by elimination of carbon dioxide and ethylene within the so-deprotected branches. Detachment of an entire arm, released as a neutral or as a protonated molecule, was found to be a useful complementary process but it mainly proceeded from the singly charged precursor. Three targeted dendritic impurities were structurally characterized by monitoring the occurrence of these reactions together with any deviation from the reference behavior. Detection of these compounds in the precursor sample could account for the presence of defective molecules previously characterized in the acid-terminating poly(amino)ester dendrimer sample. (C) 2011 Elsevier B.V. All rights reserved.

  • Triquigneaux, M.; Charles, L.; Tuccio, B. Analytical Methods 2011, 3 (7), 1582-1586.
    Résumé : Continuous wave X-band EPR spectroscopy was used as an analytical tool to follow the formation of nitroxide radicals after the reaction between various nucleophiles and 2-methyl-2-nitrosopropane (MNP). The addition of amines or of trihalogeno-acetic acids onto the nitroso moiety was found to depend on experimental parameters such as exposure to white light or the nature of the solvent, while no nitroxide adducts were ever detected when alcohols or weak carboxylic acids were used. In contrast to results previously obtained with cysteine, the reaction of ten standard amino acids (Gly, Lys, Arg, His, Trp, Ser, Thr, Tyr, Asp and Glu) on MNP never led to an EPR observable adduct, further confirming the particular reactivity of this nitroso compound towards thiols.
2010

  • Bouillon, C.; Tintaru, A.; Monnier, V.; Charles, L.; Quelever, G.; Peng, L. Journal of Organic Chemistry 2010, 75 (24), 8685-8688.
    Résumé : A novel strategy for the synthesis of poly(amino)ester dendrimers was developed on the basis of active cyanomethyl ester intermediates and an iteration of four consecutive steps of deprotection, activation, transesterification, and scavenging.

  • Bour, J.; Charles, L.; Petersen, J.; Michel, M.; Bardon, J.; Ruch, D. Plasma Processes and Polymers 2010, 7 (8), 687-694.
    Résumé : Most of polymers resulting from plasma polymerization exhibit a structure, which is very complex and different from those synthesized by conventional polymerization methods. The molecular structure of such plasma polymers is difficult to assess, but its characterization is a crucial issue. Mass spectrometry (MS) seems to be a promising analytical approach to get this molecular information. The chemical structure of a ppHMDSO (plasma polymer HexaMethylDiSiloxane) film, deposited by means of atmospheric pressure dielectric barrier discharge process, has first been characterized by means of FTIR spectroscopy. Additional insights in the polymer structure were provided by mass spectrometric techniques. MALDI-TOF-MS and ESI-Q-TOF-MS analyses were carried out to obtain information on high molecular weight oligomers and/or small polymers col lected in the THF soluble fraction of a ppHMDSO film. Although uncertainty still remains about the detected species, it could be concluded they were copolymers such as poly(dimethylsiloxane-co-methylsiloxane) or poly(dimethylsiloxane-co-SiO(2)) with a number of monomers up to 20, and some structures could be proposed for the end groups.

  • Fouquet, T.; Charles, L. Journal of the American Society for Mass Spectrometry 2010, 21 (1), 60-67.
    Résumé : Quantitative isomeric analysis of fructose, galactose, and glucose was achieved using electrospray ionization and trimeric ion dissociation with data analysis by the kinetic method. Several L-amino acids and divalent metal cations were tested to select the best systems for isomeric distinction and quantitation of each monosaccharide. High discrimination could be achieved for most tested systems, and serine/Cu(2+) and aspartic acid/Mn(2+) were selected for quantitative analysis due to their ability to strongly distinguish the three analytes and to allow long-term reproducible measuring conditions. Accurate quantitative results were obtained for all isomers using three-point corrected calibration curves, which account for the competition effects evidenced to occur between sugars for the formation of the trimeric complexes. As a result, the relative proportion of one isomer in the liquid and in the gas phase depends on the sugar mixture composition. However, for a given reference/metal system, the extent of competition effects was shown to be constant within a given pair of sugars. The correction factors could thus be established based on data obtained from binary mixtures and successfully used for ternary sample analysis. (J Am Soc Mass Spectrom 2010, 21, 60-67) (C) 2010 American Society for Mass Spectrometry

  • Giordanengo, R.; Viel, S.; Hidalgo, M.; Allard-Breton, B.; Thevand, A.; Charles, L. Journal of the American Society for Mass Spectrometry 2010, 21 (6), 1075-1085.
    Résumé : Molecular weight characterization of random amphiphilic copolymers currently represents an analytical challenge. In particular, molecules composed of methacrylic acid (MAA) and methyl methacrylate (MMA) as the repeat units raise issues in commonly used techniques. The present study shows that when random copolymers cannot be properly ionized by MALDI, and hence detected and measured in MS, one possible analytical strategy is to transform them into homopolymers, which are more amenable to this ionization technique. Then, by combining the molecular weight of the so-obtained homopolymers, as measured by MS, with the relative molar proportion of the MMA and MMA units, as given by (1)H NMR spectrum, one can straightforwardly estimate the molecular weight of the initial copolymer. A methylation reaction was performed to transform MAA-MMA copolymer samples into PMMA homopolymers, using trimethylsilyldiazomethane as a derivatization agent. Weight average molecular weight (M(w)) parameters of the MAA-MMA copolymers could then be derived from My, values obtained for the methylated MAA-MMA molecules by MALDI, which were also validated by pulsed gradient spin echo (PGSE) NMR. An alkene function in one of the studied copolymer end-groups was also shown to react with the methylation agent, giving rise to MMA-like polymeric by-products characterized by tandem mass spectrometry and which could be avoided by adjusting the amount of the trimethylsilyldiazomethane in the reaction medium. (J Am Soc Mass Spectrom 2010, 21, 1075-1085) (C) 2010 American Society for Mass Spectrometry

  • Giordanengo, R.; Viel, S.; Hidalgo, M.; Allard-Breton, B.; Thevand, A.; Charles, L. Rapid Communications in Mass Spectrometry 2010, 24 (14), 1941-1947.
    Résumé : The complete structural characterization of a copolymer composed of methacrylic acid (MAA) and methyl methacrylate (MMA) units was achieved using tandem mass spectrometry. In a first step, collision-induced dissociation (CID) of sodiated MAA-MMA co-oligomers allowed us to determine the co-monomeric composition, the random nature of the copolymer and the sum of the end-group masses. However, dissociation reactions of MAA-based molecules mainly involve the acidic pendant groups, precluding individual characterization of the end groups. Therefore, methylation of all the acrylic acid moieties was performed to transform the MAA-MMA copolymer into a PMMA homopolymer, for which CID mainly proceeds via backbone cleavages. Using trimethylsilyldiazomethane as a derivatization agent, this methylation reaction was shown to be complete without affecting the end groups. Using fragmentation rules established for PMMA polymers together with accurate mass measurements of the product ions and knowledge of reagents used for the studied copolymer synthesis, a structure could be proposed for both end groups and it was found to be consistent with signals obtained in nuclear magnetic resonance spectra. Copyright (C) 2010 John Wiley & Sons, Ltd.

  • Lauricella, R.; Triquigneaux, M.; Andre-Barres, C.; Charles, L.; Tuccio, B. Chemical Communications 2010, 46 (21), 3675-3677.
    Résumé : The title compound behaves as an efficient cheletropic trap for both NO and NO(2) radicals in the presence of oxygen, yielding EPR observable nitroxide and alkoxynitroxide, respectively.

  • Leclaire, J.; Husson, G.; Devaux, N.; Delorme, V.; Charles, L.; Ziarelli, F.; Desbois, P.; Chaumonnot, A.; Jacquin, M.; Fotiadu, F.; Buono, G. Journal of the American Chemical Society 2010, 132 (10), 3582-3593.
    Résumé : We now report that a dynamic combinatorial selection approach can quantitatively provide, from trivial building blocks, an architecturally complex organic material, in which carbon dioxide is reversibly but covalently incorporated as a guest with a mass content of 20%. Solid-state analyses combined with covalent disconnection and quantization of the liberated components allowed identification of a three-component monomeric unit repeated within a range of assembled oligomeric adducts whose repartition and binding capacity can be finely tuned through the starting stoichiometries. The self-assembly of these architectures occurs through the simultaneous creation of more than 25 covalent bonds per molecular entity. It appears that the thermodynamic selection is directed by the packing efficiency of these adducts, explaining the spectacular building block discrimination between homologues differing by one carbon unit. This selectivity, combined with the reversible nature of the system, provided pure molecular building blocks after a simple chemical disconnection, promoting CO2 as a green auxiliary to purify polyaldehyde or polyamine from mixtures of homologous structures. Moreover, the gas template could be expelled as a pure compound under thermodynamic control. This cooperative desorption process yielded back the initial libraries of high molecular diversity with a promising reduction of the energetic costs of capture and recycling.

  • Mayeux, C.; Gal, J. - F.; Charles, L.; Massi, L.; Maria, P. - C.; Tammiku-Taul, J.; Lohu, E. - L.; Burk, P. Journal of Mass Spectrometry 2010, 45 (5), 520-527.
    Résumé : Collision-induced dissociation (CID) of the Cs(+) heterodimer adducts of the nitrate anion (NO(3)(-)) and a variety of substituted benzoates (XBenz(-)) [(XBenz-)(Cs(+))(NO(3)(-))](-) produces essentially nitrate and benzoate ions. A plot of the natural logarithm of their intensity ratio, In(I(NO(3)(-)/I(XBenz(-))], versus the calculated cesium cation affinity (OFT B3LYP) of the substituted benzoate ions (equivalent to the enthalpy of heterolytic dissociation of the salt) is reasonably linear. This suggests that the kinetic method can be used as a source of data on the intrinsic interaction between the anionic and the cationic moieties in a salt. Copyright (C) 2010 John Wiley & Sons, Ltd.

  • Tintaru, A.; Labed, V.; Charles, L. European Journal of Mass Spectrometry 2010, 16 (5), 595-603.
    Résumé : Structural characterisation of 15 degradation products, formed upon di-n-butyl phthalate (DBP) radiolysis, has been achieved using a high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) coupling. The dissociation behaviour of protonated DBP was first established to be further used to characterise structural deviation in the degradation products. Based on accurate mass measurements, compounds shown by H PLC-MS analysis were all found to be DBP oxidation products, amongst which various sets of isomers could be distinguished. Collision-induced dissociation experiments performed on each electrosprayed molecule first allowed unambiguous definition of the location of the additional oxygen atoms; that is, in the alkyl branch or on the aromatic ring. Although location of the oxygen atom in the alkyl branches could not always be precisely determined, relative abundances of some product ions allowed oxygenated functions to be identified

  • Tintaru, A.; Monnier, V.; Bouillon, C.; Giordanengo, R.; Quelever, G.; Peng, L.; Charles, L. Rapid Communications in Mass Spectrometry 2010, 24 (15), 2207-2216.
    Résumé : An acid-terminated poly(amino)ester dendrimer was studied by electrospray ionization tandem mass spectrometry to establish its fragmentation pathways, with the aim of using them to investigate the structure of any defective molecules generated during the dendrimer synthesis. This poly(amino)ester dendrimer could be ionized in both polarities but the most structurally relevant dissociation pathways were found from the deprotonated molecule in negative ion mode. The dissociation pattern of this dendrimer is fully described and supported by accurate mass measurements. The main dissociation reactions of the negatively charged polyacidic dendrimer were shown to consist of (i) the release of carbon dioxide and ethene within a branch, which proceeds as many times as intact neutral branches are available; and (ii) the elimination of an entire dendrimer arm. Monitoring the occurrence of these reactions together with any deviation from these two main routes allowed six major dendritic impurities to be structurally characterized. Copyright (C) 2010 John Wiley & Sons, Ltd.


  • Trimaille, T.; Mabrouk, K.; Monnier, V.; Charles, L.; Bertin, D.; Gigmes, D. Macromolecules 2010, 43 (11), 4864-4870.
    Résumé : We report here a straightforward route to polymer?peptide conjugates via the convenient synthesis of SG1-functionalized peptides able to initiate nitroxide-mediated polymerization (NMP). The NMP initiator SG1-functionalized peptide (SG1-GGGWIKVAV) was prepared by solid-phase peptide synthesis (SPPS) using an automated synthesizer, with a last step consisting of reaction between the carboxylic acid function of the MAMA-SG1 (BlocBuilder) alkoxyamine with the peptide terminal amine in the presence of benzotriazol-1-yl-oxytripyrrolidinophosphonium hexafluorophosphate (PyBOP) as coupling agent. The resulting SG1-functionalized resin-attached peptide was used to perform the controlled NMP of styrene, leading after trifluoroacetic acid cleavage to the corresponding polystyrene?peptide conjugate. The latter was thoroughly characterized by UV spectrometry, gel permeation chromatography (GPC), 1H NMR, and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS).

  • Triquigneaux, M.; Charles, L.; Andre-Barres, C.; Tuccio, B. Organic & Biomolecular Chemistry 2010, 8 (6), 1361-1367.
    Résumé : The spontaneous addition of air oxygen to a dienolic compound, yielding a cyclic peroxide, was followed by spin trapping (ST) combined with EPR spectroscopy and mass spectrometry (MS). Using two different nitrones, the ST/EPR study allowed the detection of the spin adduct of a radical intermediate, and the radical centre in the addend was identified after similar experiments performed with two different (13)C-labelled analogues of the substrate. The media were also submitted to electrospray ionisation, in both positive and negative modes, for structural characterisation of the spin adducts by tandem mass spectrometry. This allowed the structure of the hydroxylamine derivatives of the nitroxides formed to be identified. Following these results, a mechanism pathway was proposed for this autoxidation.

  • Triquigneaux, M.; Charles, L.; Andre-Barres, C.; Tuccio, B. Tetrahedron Letters 2010, 51 (48), 6220-6223.
    Résumé : The combination of electron paramagnetic resonance (EPR) and mass spectrometry (MS) was used as an efficient tool to elucidate the mechanism of an ene-reaction between a dienol compound and 2-methyl-2-nitrosopropane. (C) 2010 Elsevier Ltd. All rights reserved.

  • Triquigneaux, M.; Tuccio, B.; Charles, L. Analytical Methods 2010, 2 (6), 694-700.
    Résumé : An approach combining EPR spectroscopy and electrospray ionisation mass spectrometry was employed to study the reactivity of two alkylthiols and of cysteine towards 2-methyl-2-narosopropane (MNP) in the presence of H(2)O(2) Depending on the experimental conditions, various nitroxides could be EPR-detected, while their diamagnetic derivatives were structurally characterised after tandem mass spectrometry experiments Sample dilution in methanol before electrospray ionisation was also found to generate methyl-hydroxylamine derivatives and could thus constitute a simple derivatisation process to stabilise hardly MS-detectable radical species Upon white light irradiation, the three thiols tested led to alkoxynitroxides according to an inverted spin trapping process On the other hand, only the reduced form of cysteine was found to react with MNP in the dark, yielding an alkylthionitroxide adduct via a Forrester-Hepburn mechanism Besides a better understanding of the reactivity of thiols towards nitroso compounds, the results obtained underlined the particular behaviour of cysteine, suggesting that the use of a molecule as simple as MNP could allow a nitroxide moiety to be linked to a cysteinyl residue