Christophe Chendo

Collision-induced dissociation of synthetic polymers containing hydride groups: the case of poly(methylhydrosiloxane) homopolymers and poly(methylhydrosiloxane)-co-(dimethylsiloxane) copolymers.

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 H(2) 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.

Straightforward and Controlled Shape Access to Efficient Macrocyclic Imidazolylboronium Anion Receptors.

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 ((1) H, 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 Csp2 -H and unusual Csp3 -H hydrogen-bonding donors.

Successful MALDI‐MS Analysis of Synthetic Polymers with Labile End‐Groups: The Case of Nitroxide‐Mediated Polymerization Using the MAMA‐SG1 Alkoxyamine

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).

Conformational sensitivity of conjugated poly(ethylene oxide)-poly(amidoamine) molecules to cations adducted upon electrospray ionization – A mass spectrometry, ion mobility and molecular modeling study

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 (Mn=1500gmol(-1)), PEO-PAMAM hybrid molecules exhibited a more expanded shape when adducted to lithium as compared to proton.

End-group cleavage in MALDI of ATRP-made polystyrene: a silver-catalyzed reaction during sample preparation.

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.

Microwave-Mediated Synthesis of Bulky Lanthanide Porphyrin–Phthalocyanine Triple-Deckers: Electrochemical and Magnetic Properties

Five heteroleptic lanthanide porphyrin-bis-phthalocyanine triple-decker complexes with bulky peripheral groups were prepared via microwave-assisted synthesis and characterized in terms of their spectroscopic, electrochemical, and magnetic properties. These compounds, which were easily obtained under our preparative conditions, would normally not be accessible in large quantities using conventional synthetic methods, as a result of the low yield resulting from steric congestion of bulky groups on the periphery of the phthalocyanine and porphyrin ligands. The electrochemically investigated triple-decker derivatives undergo four reversible one-electron oxidations and three reversible one-electron reductions. The sites of oxidation and reduction were assigned on the basis of redox potentials and UV-vis spectral changes during electron-transfer processes monitored by thin-layer spectroelectrochemistry, in conjunction with assignments of electronic absorption bands of the neutral compounds. Magnetic susceptibility measurements on two derivatives containing TbIII and DyIII metal ions reveal the presence of ferromagnetic interactions, probably resulting from magnetic dipolar interactions. The TbIII derivative shows SMM behavior under an applied field of 0.1 T, where the direct and Orbach process can be determined, resulting in an energy barrier of Ueff = 132.0 K. However, Cole-Cole plots reveal the presence of two relaxation processes, the second of which takes place at higher frequencies, with the data conforming to a 1/t ∝ T7 relation, thus suggesting that it can be assigned to a Raman process. Attempts were made to form two-dimensional (2D) self-assembled networks on a highly oriented pyrolytic graphite (HOPG) surface but were unsuccessful due to bulky peripheral groups on the two Pc macrocycles.

Adduction of ammonium to polylactides to modify their dissociation behavior in collision-induced dissociation

RATIONALE The 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. METHODS Benzyl-, 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. RESULTS Adduction 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 ω 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. CONCLUSIONS Changing 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.

Catalyst- and Initiator-Free Radical Addition under Mild Conditions: A Macromolecular Conjugation Tool

A catalyst/initiator-free radical addition reaction performed under mild conditions (water, 30 °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 in situ-loaded proteins, which could retain biological activity. This contrasts with standard thermal radical conditions that lead to complete protein inactivation.

Anomerization of Acrylated Glucose During Traveling Wave Ion Mobility Spectrometry

AbstractAnomerization 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 α- and β-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 α-anomer, and was only observed for the THF sample. In ESI-TWIMS-MS, a signal was measured at the drift time expected for the α-anomer for both the THF and DMAC samples, in apparent contradiction to the MS/MS results, which indicated that the α-anomer was not present in the DMAC sample. However, MS/MS experiments performed after TWIMS separation revealed that ammonium adducts of the α-anomer produced from each sample, although exhibiting the same collision cross section, were clearly different. Indeed, while the α-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 β/α inter-conversion upon injection in the TWIMS cell, as supported by theoretical calculation and dynamic molecular modeling. Graphical Abstractᅟ