Marie Hubert-Roux

Role of Cationization and Multimers Formation for Diastereomers Differentiation by Ion Mobility-Mass Spectrometry

AbstractStereochemistry plays an important role in biochemistry, particularly in therapeutic applications. Indeed, enantiomers have different biological activities, which can have important consequences. Many analytical techniques have been developed in order to allow the identification and the separation of stereoisomers. Here, we focused our work on the study of small diastereomers using the coupling of traveling wave ion mobility and mass spectrometry (TWIMS-MS) as a new alternative for stereochemistry study. In order to optimize the separation, the formation of adducts between diastereomers (M) and different alkali cations (X) was carried out. Thus, monomers [M + X]+ and multimers [2M + X]+ and [3M + X]+ ions have been studied from both experimental and theoretical viewpoints. Moreover, it has been shown that the study of the multimer [2Y + M + Li]+ ion, in which Y is an auxiliary diastereomeric ligand, allows the diastereomers separation. The combination of cationization, multimers ions formation, and IM-MS is a novel and powerful approach for the diastereomers identification. Thus, by this technique, diastereomers can be identified although they present very close conformations in gaseous phase. This work presents the first TWIMS-MS separation of diastereomers, which present very close collision cross section thanks to the formation of multimers and the use of an auxiliary diastereomeric ligand. Figureᅟ

Enantiomeric differentiation of aromatic amino acids using traveling wave ion mobility-mass spectrometry

The present work describes the first differentiation of enantiomers using the coupling of traveling wave ion mobility and mass spectrometry (TWIM-MS). This study was carried out on amino acids, the building blocks of proteins, which together with nucleotides, polysaccharides or lipids, are the main constituents of all living organisms. Herein, the enantiomers of aromatic amino acids (AA) such as phenylalanine, tryptophan and tyrosine are differentiated by TWIM-MS through their cationisation with copper(II) and multimer formation with D-proline (Pro) as a chiral reference compound. This methodology can be considered as an alternative approach to conventional methods for the separation of enantiomers. Moreover, quantification of the enantiomers can be performed easily and quickly using TWIM-MS analysis of the ionic complex [(DPro)2+D/LAA+CuII–H]+.

Rapid analysis of polyester and polyethylene blends by ion mobility-mass spectrometry

In this work ion mobility-mass spectrometry (IM-MS) coupled to an atmospheric solid analysis probe (ASAP) was used for the characterization of polymer blends involving biodegradable polymers (poly(lactic acid) (PLA), poly(butylene succinate) (PBS)) and poly(ethylene) (PE). Interestingly both PLA and PBS yielded by ASAP an ionization ion series corresponding to cyclic oligomers that were nearly identical to those obtained by conventional Py-GC-CI/MS. However from the drift-time vs. m/z plot of a PLA–PE blend, the ion series of both polymers can be readily identified, as the PLA ions are significantly more compact than the PE ions. From this 2D plot specific mass spectra can be extracted which are almost identical to those of each polymer alone. This work highlights the potential of ASAP–IM-MS to achieve a very fast analysis of complex polymer blends. It was demonstrated that coupling gas phase ion separations (IM) with direct and weakly discriminant ionization techniques (ASAP) significantly enhances the dynamic range of accessible concentrations and polymer polarities, opening a new avenue to carry out more complex “materiomics” studies.

Rapid analysis of lubricants by atmospheric solid analysis probe-ion mobility mass spectrometry.

Formulated lubricants are complex mixtures composed of base oil(s) and additives with various functions (detergents, corrosion inhibiter, antioxidant, viscosity modifiers, etc.). Because of the aliphatic nature of base oil and the chemical diversity of additives, the characterization of lubricant is currently a long and complex process. The comprehensive analysis of lubricant samples involves several techniques such as nuclear magnetic resonance, mass spectrometry, chromatography and infrared spectroscopy. The coupling of atmospheric solid analysis probe (ASAP) with ion mobility-mass spectrometry (IM-MS) has been shown to be an efficient tool for the characterization of complex mixture containing vaporizable polar to non-polar compounds. This approach affords the coupling of a direct ionization technique that does not require sample preparation, with a bi-dimensional separation method with high peak capacity. In this work, we show that ASAP-IM-MS is a suitable method for rapid and direct characterization of lubricant samples. Indeed, base oil and additives yielded, by ASAP, ions series which could be separated by IM-MS. Molecular additives such as Zn-dithiocarbamate, phosphite, thiophosphate and Alkyl diphenylamine were ionized as molecular ions [M](+•) or protonated molecules [M + H](+), depending of their polarity. In some cases, fragment ions were observed, confirming the additive identification. In addition, high molecular weight polymeric additives such as poly(alkyl methacrylate) (PAM) were pyrolized in the ASAP source leading to characteristic fragment ions. ASAP-IM-MS is shown to be a powerful tool for studying complex mixtures, allowing the first comprehensive analysis of lubricants in just a few minutes.

Rapid analysis of lubricants by atmospheric solid analysis probe-ion mobility mass spectrometry

Formulated lubricants are complex mixtures composed of base oil(s) and additives with various functions (detergents, corrosion inhibiter, antioxidant, viscosity modifiers, etc.). Because of the aliphatic nature of base oil and the chemical diversity of additives, the characterization of lubricant is currently a long and complex process. The comprehensive analysis of lubricant samples involves several techniques such as nuclear magnetic resonance, mass spectrometry, chromatography and infrared spectroscopy. The coupling of atmospheric solid analysis probe (ASAP) with ion mobility-mass spectrometry (IM-MS) has been shown to be an efficient tool for the characterization of complex mixture containing vaporizable polar to non-polar compounds. This approach affords the coupling of a direct ionization technique that does not require sample preparation, with a bi-dimensional separation method with high peak capacity. In this work, we show that ASAP-IM-MS is a suitable method for rapid and direct characterization of lubricant samples. Indeed, base oil and additives yielded, by ASAP, ions series which could be separated by IM-MS. Molecular additives such as Zn-dithiocarbamate, phosphite, thiophosphate and Alkyl diphenylamine were ionized as molecular ions [M](+•) or protonated molecules [M + H](+), depending of their polarity. In some cases, fragment ions were observed, confirming the additive identification. In addition, high molecular weight polymeric additives such as poly(alkyl methacrylate) (PAM) were pyrolized in the ASAP source leading to characteristic fragment ions. ASAP-IM-MS is shown to be a powerful tool for studying complex mixtures, allowing the first comprehensive analysis of lubricants in just a few minutes.

Direct TLC/MALDI-MS coupling for modified polyamidoamine dendrimers analyses.

Polyamidoamine (PAMAM) are synthetic dendrimers which present attractive properties for the biological and biomedical fields, as they proved to be efficient drug and gene carriers. In order to increase their transfection efficiency, chemical modifications of the amino end-groups had been reported. In this work, the synthesis of the ammonia-cored G1(N) PAMAM and the consecutive chemical modification with glycine or phenylalanine amino-acids were monitored using the coupling of thin layer chromatography (TLC) with matrix-assisted laser desorption ionization-mass spectrometry (MALDI-MS). Thus, the monitoring of the PAMAM synthesis included the identification of the by-products such as defective structures of PAMAM dendrimers as well as the study of phenylalanine-grafted PAMAM oligomer distribution.

Atmospheric Solid Analysis Probe-Ion Mobility Mass Spectrometry: An Original Approach to Characterize Grafting on Cyclic Olefin Copolymer Surfaces.

A cyclic olefin copolymer (COC) was grafted with aryl layers from aryldiazonium salts, and then we combined infrared spectrometry, atomic force microscopy (AFM), and ion mobility mass spectrometry with atmospheric solid analysis probe ionization (ASAP-IM-MS) to characterize the aryl layers. ASAP is a recent atmospheric ionization method dedicated to the direct analysis of solid samples. We demonstrated that ASAP-IM-MS is complementary to other techniques for characterizing bromine and sulfur derivatives of COC on surfaces. ASAP-IM-MS was useful for optimizing experimental grafting conditions and to elucidate hypotheses around aryl layer formation during the grafting process. Thus, ASAP-IM-MS is a good candidate tool to characterize covalent grafting on COC surfaces.

Evaluation of atmospheric solid analysis probe ionization coupled to ion mobility mass spectrometry for characterization of poly(ether ether ketone) polymers

Recently, the interest of the coupling between atmospheric solid analysis probe (ASAP) and ion mobility-mass spectrometry has been revealed in the field of polymers. This method associates a direct ionization technique with a bi-dimensional separation method. Poly(ether ether ketones) (PEEK) belong to the family of the poly(aryl ether ketones) (PAEK) which are high performance aromatic polymers usually used in aerospace, electronics and nuclear industries. PEEK are important commercial thermoplastics with excellent chemical resistance and good mechanical properties. Because of their low solubility, few structural characterization studies of PEEK have been reported. In mass spectrometry, only MALDI-TOF analyses for polymer synthesis monitoring have been described with the use of strong acids such as sulfuric acid. This work demonstrates that ASAP is particularly efficient for analysis of PEEK in a solvent free approach with the production of intact small oligomers (n≤2). Five types of PEEK oligomers with different end-groups were evidenced. With MALDI-TOF, the same end-groups with almost the same relative abundance were obtained which support the hypothesis that the oligomers detected in ASAP are intact small oligomers and not fragments or pyrolysis products. This is particularly interesting as generally the ASAP analysis of polymers yields pyrolysis products with the loss of end-group information. The end-groups assignments have been confirmed by tandem mass spectrometry (MS/MS) experiments on the M(+) molecular ions, which allowed highlighting some specific neutral or radical losses as well as two diagnostic product ions. Thus, ASAP-IM/MS/MS proves to be a fast and efficient alternative way to characterize low solubility polymers such as PEEK.

What structural information can ion trap mass spectrometry bring for the characterization of permethylated cyclodextrins

Cyclodextrins (CDs) are cyclic oligosaccharides composed of six, seven and eight a-1,4-linked D-glucopyranose units for the a-, band g-CD, respectively. These macrocyclic molecules have a truncated cone-shaped structure whose hydrophobic cavity enables the formation of inclusion complexes thus allowing various pharmaceutical applications. Indeed, CDs and derivatives are commonly used as drug excipients to improve drug solubility, bioavailability and stability. Permethylated CDs usually comprise a large number of positional and regional isomers. Therefore, it is essential to characterize their structures by determining their substitution patterns and their degree of substitution (DS: i.e. the number of methyl groups per glucopyranose unit). Direct injection mass spectrometry is known to be an easy and fast method to achieve CD characterization. In fact, quadrupole mass spectrometry with electrospray ionization (ESI) or atmospheric pressure chemical ionization (APCI) has been used to determine the DS for DiMe-b-CD, Me-b-CD, and sulfobutylether-CD. Ion trap mass spectrometry (ITMS), has, however, been rarely described in the literature for this purpose. Ion trap mass spectrometry is based on the trapping of ions in a symmetrical three-dimensional electric radiofrequency field under appropriate conditions. The quantity of ions in the trap and the depth of the potential well need to be optimized as they greatly influence the quality and reliability of the data. The quantity of ions in the trap is controlled by the ion current control (ICC). When the trap is overloaded, space charge effects impair the quality of mass spectra as the signal intensity is reduced. For quantitative experiments, the linearity deviates at high concentration thus reducing the dynamic range. Furthermore, ions with identical m/z value interfere with each other to a much greater extent than ions of different m/z values because they move on similar ion trajectories. The other parameter which needs to be adjusted is the target mass, a parameter given by the instrument supplier whose values will optimize different voltages for ion transmission and the depth of the pseudo-potential well. The ions with masses close to the value of the target mass will be the best trapped. Here we describe our experiments using ESI-ITMS to characterize permethylated b-CDs. The parameters that we needed to optimize on the ion trap mass spectrometer are described and the structural information provided by MS experiments is more particularly discussed. The Me-b-CD Cavasol W7 M Pharma was obtained from Wacker Chemie AG (Burghausen, Germany). Its DS is in the range 1.7–1.9. The other permethylated b-cyclodextrin (PMCD) was synthesized in the Laboratoire de Pharmacie Galénique (Rouen, France). HPLC grade acetonitrile (MeCN), methanol (MeOH), and ammonium acetate were supplied by VWR (Fontenaysous-Bois, France). Deionized water (18 MV) was obtained from a Waters Milli-Q apparatus (Waters, SaintQuentin-Yvelines, France). For ESI-MS analysis, CD samples were prepared in water and then diluted in MeOH/ H2O (50:50, v/v) or MeCN/ H2O (50:50, v/v) to a concentration of 1 ngmL . In some cases, 5mL of terscience.wiley.com) DOI: 10.1002/rcm.3535 NaCl (1 mg mL ) were added to 500mL of the CD solutions. ESI mass spectra were recorded on an Esquire–LC ion trap mass spectrometer equipped with an ESI source and the Esquire control 6.16 data system (Bruker Daltonics, Wissembourg, France). The ESI parameters were: capillary voltage 4 kV, end plate volatage 3.5 kV and skimmer voltage 62 V. Nitrogen was used as the drying (flow rate of 5 L min , 3008C) and nebulizing (7psi pressure) gas. The samples were flow injected at 3mL min 1 by means of a syringe pump (ColePalmer, Vernon Hills, IL, USA). Positive ions were detected using the standard scan at normal mass resolution: the scan speed was 13000 m/z units s 1 and the mass resolution was 0.6m/z units at half peak height (FWHM) over a range m/z 50–2200. Helium was the buffer gas and the pressure in the ion trap was 1.2 10 5 mbar. The values of spectra averages and rolling average were 10 and 5, respectively. For all the target mass values tested, the corresponding values of cone voltage (voltage differential between the capillary exit and the skimmer) and trap drive (depth and shape of the pseudo potential well) are listed in Table 1. For MS experiments, each precursor ion was selected with an isolation width of 2m/z units and was excited by a voltage of between 1.2 and 1.3 V. The low mass cut-off value (LCMO) was set at 28% of the precursor ion m/z value. When experiments are performed in water, CDs are mainly detected as MNaþ species but adducts with Kþ and NH4 are also observed. To enhance the formation of these adducts, NaCl or NH4CH3CO2 is usually added. Ammonium salts are often preferred in ESI-MS because they are more volatile. The spectra obtained here,

Tandem mass spectrometry of low solubility polyamides.

The structural characterization of polyamides (PA) was achieved by tandem mass spectrometry (MS/MS) with a laser induced dissociation (LID) strategy. Because of interferences for precursor ions selection, two chemical modifications of the polymer end groups were proposed as derivatization strategies. The first approach, based on the addition of a trifluoroacetic acid (TFA) molecule, yields principally to complementary bn and yn product ions. This fragmentation types, analogous to those obtained with peptides or other PA, give only poor characterization of polymer end-groups [1]. A second approach, based on the addition of a basic diethylamine (DEA), permits to fix the charge and favorably direct the fragmentation. In this case, bn ions were not observed. The full characterization of ω end group structure was obtained, in addition to the expected yn and consecutive fragment ions.