In this dissertation, I use Fourier transform ion cyclotron resonance mass spectrometry (FTICR-MS) to study the structure and energetics of gas phase ions. Infrared multiphoton dissociation spectroscopy (IRMPD) is a technique for measuring the IR spectrum of gas phase ions in a Penning trap. I use this technique to investigate the conformation of cucurbituril complexes, terminal diamines, and protonated amino acids. Cross sectional areas by Fourier transform ion cyclotron resonance mass spectrometry (CRAFTI) is a technique developed by the Dearden lab to measure the cross section of gas phase ions. In this work, I further develop a fundamental understanding of this technique. I investigate the role that dissociation plays in this and other FTICR-MS techniques. I also show that the principles of the CRAFTI technique can be used to measure the pressure inside the cell of an FTICR-MS. This technique, linewidth pressure measurement (LIPS), allows for a quantitative measurement and comparison of CRAFTI cross sections. To demonstrate the improvements to the technique, I measure the CRAFTI cross sections for the 20 standard amino acids and compare these to literature values measured by ion mobility measurements.

This dissertation investigates Fourier transform ion cyclotron resonance mass spectrometry (FTICR-MS) based techniques to study the impact of molecular structure on conformation and binding energetics. A novel method to determine collison cross sectional areas using FTICR (CRAFTI), initially developed by the Dearden lab, was applied to study the conformations of molecular systems with unique structural attributes in an attempt to explore the molecular range of CRAFTI. The systems chosen for CRAFTI studies include crown-ether alkylammonium complexes and biogenic amino acids. The results were found to be consistent with expected behavior, and strongly correlated with experimental measurements made using ion mobility spectrometry (IMS) and predictions from computations. The analytical sensitivity of CRAFTI was highlighted by its ability to distinguish the normal and branched structural isomers of butylamine. Besides conformation characterization, quantitative evaluation of binding was undertaken on metal ion-cryptand complexes on the FTICR instrument using sustained off-resonance irradiation-collision-induced dissociation (SORI CID) method. Complex formation and dissociation was found to be a strong function of both guest and host sizes which impacted steric selectivity, and polarizability. The results demonstrate the ability of FTICR to simultaneously determine structure, conformation and binding thereby providing comprehensive molecular characterization.

Humic substances (HS) are described as a complex mixture of organic molecules formed by incomplete decomposition of plant, animal and microbial matter. They are found in soil, water and air and have many environmental roles, e.g. water retention and metal ion binding in soil. Despite their importance, the molecular composition of HS is poorly understood. This is mostly because of an inability to separate individual molecules from these complex mixtures and then characterise them by standard analytical methods such as NMR and MS. In order improve the understanding of these important mixtures I have studied them using a high-resolution analytical method, Fourier transform ion-cyclotron resonance mass spectrometry (FTICR MS). Initial efforts focussed on testing the, fast, automated data analysis of the large data sets produced. Two pieces of software were compared and the reliability of the formulae assigned by these was critically evaluated. This confident formula assignment was then applied to study the consequences of different ionisation and instrumental parameters on the mass spectra obtained. The use of laser desorption/ionisation (LDI) without the need to employ a matrix required in matrix assisted laser desorption/ionisation (MALDI) was explored. A comparison of LDI and electrospray ionisation (ESI) FTICR MS of natural organic matter samples showed that these methods ionise complementary sets of compounds. The LDI ionised compounds were characterised as aromatics or condensed aromatics and compounds belonging to lower oxygen classes (maximum number at O8), while ESI ionised higher oxygen classes (maximum number at O16) with a vast majority of compounds classified as aliphatic based on their modified aromaticity index. MALDI and LDI spectra produced very similar data with over 90% matching formulas implying that fragmentation is not caused by LDI, as taught previously. My work showed that to maximize the coverage by FTICR MS of the molecular space occupied by these complex mixtures, multiple ionization methods must be used. As a particularly convenient and readily deployable ionization technique, LDI should be included in standard analytical protocols for FTICR MS analysis of NOM. I have explored different parameters and experimental settings to obtain a fuller coverage of the molecular space of NOM, this showed that different experimental conditions enhance peak intensities in different m/z regions of the FTICR MS spectra and that information can be obtained outside of the narrow 200-700 m/z window. To gain chemical and structural information about humic substances beyond what is currently known, experiments aimed to label HS using different isotopes and at specific sites were developed and tested. Two methylation reactions were of particular interest. A methylation that selectively targeted carboxylic acid groups and incorporated deuterium in the form of CD3 groups. An international standard, Suwannee River fulvic acid, was methylated and analysed by high-resolution mass spectrometry in order to gain information on the number and distribution carboxylic acid groups. This proved challenging due to the reactivity of the unknown molecules being difficult to determine in advance. Additionally, the peak separation being reduced to as low as 1.5 mDa pushed the instrument resolution and assignment confidence to their limits. The second methylation method explored used 13CH3I, a nonselective agent reacting with any labile proton, particularly attaching 13CH3 groups to carboxylic, phenolic and alcoholic OH groups. I prepared a methylated sample of fulvic acid from a Red Moss raised bog (Balerno, near Edinburgh) ready for analyses by high field NMR. This investigation yielded structures of a number of phenolic compounds for the first time by NMR.

In my dissertation, I use a Fourier Transform Ion Cyclotron Resonance Mass Spectrometer (FTICR-MS) to investigate supramolecules. Cross-sectional areas by Fourier transform ICR (CRAFTI), a novel technique for measurements of collision cross sections by FTICR, is demonstrated for the first time. The CRAFTI method measures the total "dephasing cross section" for removal of the ions from the coherent packet in the FTICR cell, including contributions not only from momentum transfer but also from reactive collisions including those leading to collisional dissociation. Experimental CRAFTI collision cross sections correlate linearly with theoretically computed results and with results obtained using ion mobility measurements. Different collision gases, including Xe, N2, Ar, and SF6, are all appropriate for the CRAFTI technique when the experiments are done at proper kinetic energies. The CRAFTI technique was applied to characterize the molecular shape of complexes of alkyl mono- and n-alkyldiamine with cucurbit[n]uril in the gas phase. The CRAFTI results are consistent with corresponding computational geometries. The CRAFTI technique was combined with SORI-CID (sustained off-resonance irradiation collision induced dissociation) for characterization of complexes of α,ω-alkyldiammonium with cucurbit[n]urils (n=5, 7 and 8) and cucurbituril derivatives. The results demonstrate that for bigger cucurbiturils, the complexes have the alkyldiamine tails threaded through the cavity of the host; for smaller cucurbiturils, the complexes have the tails of the alklydiamines external to the portal of the host.Capping molecules for larger CBn to form larger containers were also investigated. Using SORI-CID methods, CB7, a bigger cucurbituril cage, was found to form a more stable complex with Gu+ (guanidinium). Several neutral guests (benzene, fluorobenzene and toluene) were trapped in CB7 cavity to form inclusion complexes.

Détermination des interactions microscopiques entre les actinides et les substances humiques présentes dans l’environnementUne quantité pondérable de plutonium a été introduite dans l’environnement lors d’essais nucléaires ou d’accidents civils. Les zones contaminées, nécessitant une surveillance particulière, sont devenues des lieux d’études très intéressants pour comprendre le comportement du plutonium dans l’environnement. Jusqu’à peu de temps encore, il était admis que le plutonium introduit dans les sols était relativement immobile en raison de sa propension à se sorber fortement sur les roches et de sa faible solubilité dans l’eau. Cependant, des études menées sur des zones contaminées montrent que les substances humiques, omniprésentes dans l’environnement, peuvent influencer la spéciation d’un métal et donc sa migration. C’est pourquoi, il est indispensable de connaître l’influence des substances humiques sur la spéciation du plutonium pour comprendre le transport de celui-ci dans un milieu naturel. Toutefois, en raison de la nature complexe et hétérogène de la matière organique naturelle, il est difficile de décrire de façon microscopique les interactions entre substances humiques et le plutonium. En effet, les substances humiques forment un mélange hétérogène de supra-molécules polydispersées produites par des réactions chimiques ou biochimiques durant la transformation naturelle de matière organique animale, végétale ou microbienne.Le but de ces travaux est d’évaluer à l’échelle de moléculaire les phénomènes de complexation des actinides par la matière organique naturelle. Ces recherches s’organisent autour de deux axes : la caractérisation de dizaines de milliers de molécules dans chaque échantillon de substances humiques naturelles et la détermination des molécules responsables de la vectorisation des actinides dans l’environnement.La mise au point d'une méthodologie a permis de mettre en évidence, pour la première fois, quelques molécules responsables de la complexation des actinides dans des échantillons de matière organique naturelle. Les résultats obtenus montrent l’influence de l’origine du prélèvement de la matière organique sur le type de molécules complexantes. Cette étude montre, également, que la vectorisation des actinides par la matière organique résulte d’une interaction avec un ensemble de molécules présentant des affinités plus ou moins forte pour le métal. Ces résultats semblent être en accord avec les modélisations macroscopiques NICA-DONNAN (approches continue) utilisés actuellement. / Large amount of plutonium has been introduced into the environment as a result of nuclear weapons testing, and nuclear power-plant accidents. Contaminated areas, which need a particular survey, have become a very interesting place to study and understand the plutonium behaviour in the environment. Until few years ago, it was admitted that plutonium introduced into subsurface environment is relatively immobile, owing to its low solubility in ground water and strong sorption onto rocks. However, studies of contaminated areas show that humic substances, which are ubiquitous in environment, can alter the speciation of metal ion, e.g. plutonium, and thus their migration. These humic substances are major components of the natural organic matter in soil and water as well as in geological organic deposits such as lake sediments, peats and brown coals. They are complex heterogeneous mixtures of polydispersed supra-molecules formed by biochemical and chemical reactions during the decay and transformation of plant and microbial remains. The knowledge of the impact of humic substances on the plutonium migration is required to assess their transport in natural systems. However, due to the complex and heterogeneous nature of humic substances, there are a lot of difficulties in the description of microscopic interactions. The aim of this PhD thesis is to evaluate as precisely as possible interactions between actinides and humic substances. This work is divided in two parts: on the one hand humic substances will be separated to identify each component, on the other hand the speciation of actinides with characterized humic substances will be studied. In the first part of this study, new methods are developed to study the speciation of actinides with humic substances using two kinds of mass spectrometers: an ICP-MS and a high resolution mass spectrometer using various ionization devices (ESI, APCI, DART, APPI) in order to determine all active molecules for the complexation.In the second part, a new way of humic substances separation had been developed using an electrophoresis capillary apparatus. This efficient separation technique allows to simplify the characterisation of the complex heterogeneous mixtures without changing speciation of the chemical system.This study will lead to point out some molecules responsible for complexation of actinides by the humic substances.

This dissertation investigates non-covalent macromolecular chemistry using Fourier transform ion cyclotron resonance mass spectrometry (FTICR-MS) based techniques. The included studies reveal the impact of molecular structure on conformation and binding energetics. Supramolecules that might be too heavy to be dissociated in single collision-induced dissociation (CID) were dissociated using sustained off-resonance collision induced dissociation (SORI-CID) techniques. Relative binding energies and thresholds were evaluated for various macromolecular host-guest systems. Besides the non-covalent binding energies, conformation characterization was undertaken by a novel method to determine collision cross sectional areas using FTICR (CRAFTI, and multi-CRAFTI), initially developed by the Dearden lab. The systems chosen for further understanding of macromolecular interactions include calixarene-alkali metal complexes, cucurbit[5]uril-alkali halide complexes and cryptand-alkali metal complexes. The results were found to be consistent with expected behavior, and strongly correlated with predictions from computations. Size- and shape selectivity, as well as host-guest polarizability, are the main factors that govern the non-covalent macromolecular interactions that control complex conformation and dissociation. The results demonstrate the ability of FTICR to simultaneously determine binding energy, structure and conformation, which are the most important aspects for determination of comprehensive molecular characterization.

This thesis explores the structures and structural changes of supramolecular host-guest systems, proteins, and other small molecules in the gas phase, utilizing a combination of computational modeling and experimental data. The primary instruments employed were a Fourier transform ion cyclotron resonance mass spectrometer (FTICR-MS) and an ion mobility mass spectrometer (IM-MS). In the IM-MS experiments, the focus was on investigating the binding behavior of cyclodextrin macrocycles—specifically α, β, and γ-cyclodextrin—with per-fluoroalkane substances (PFAS), which are pervasive environmental contaminants. This investigation involved measuring ion-neutral collision cross sections and using computational modeling to determine whether PFAS compounds bind inside or outside the cyclodextrin cavity. The results indicate that only β-cyclodextrin binds PFAS compounds internally, attributed to its seven-fold symmetry and the localized hydrogen bonding network across the macrocycle's secondary face. Conversely, α and γ-cyclodextrin appear to favor collapsing inward, enhancing internal hydrogen bonding while keeping the PFAS bound externally. The FTICR-MS instrument was used for time-resolved CRAFTI (TR-CRAFTI) collision cross section measurements on various systems, including tetraalkylammoniums (TAA), cytochrome C, and β-cyclodextrin host-guest complexes. This involved activating gas-phase ions using sustained off-resonance irradiation (SORI) activation, followed by a variable delay for collisional cooling. Subsequently, a CRAFTI measurement was conducted to obtain a timeresolved view of the collision cross section. Initial findings suggest the feasibility of measuring and modeling structural changes post-activation over varying time scales, ranging from approximately 100 milliseconds to 10 seconds, depending on the size and complexity of the system being studied.

L'objectif premier de ce travail de thèse était de développer des analyses métabolomiques non ciblées de vins en bouteilles afin de déchiffrer les informations chimiques relatives à l’évolution de leurs compositions avec le temps. Cette recherche initiale était fondée sur l'hypothèse que, lors de l'analyse, les vins en bouteilles gardent une mémoire chimique des paramètres environnementaux à l’œuvre au moment de leur élaboration (gestion du vignoble, pratiques œnologiques, climat, terroir). Une seconde hypothèse reposait sur la nécessité d’étudier le passé pour anticiper l’évolution de la qualité du vin du point de vue de sa composition chimique. À cet effet et pour la première fois dans la science du vin, la Spectrométrie de Masse à Résonance Cyclotronique des Ions et à Transformée de Fourier (FTICR-MS), la Chromatographie Liquide couplée à la Spectrométrie de Masse (UPLC-Q-TOF-MS), la spectroscopie de Fluorescence d’Excitation et d’Émission (EEMF) et les statistiques multivariées ont été combinées. Le développement méthodologique a révélé l'avantage de coupler les mesures de masses exactes par FTICR-MS à la discrimination des isomères par UPLC-Q-TOF-MS afin d'étendre la gamme des métabolites détectables. Ces outils ont été appliqués à l'identification de marqueurs de vieillissement sur des séries verticales de vins rouges et blancs de Bourgogne, y compris sur des vins très anciens (millésimes inconnus) considérés comme des points extrêmes d'évolution, introduisant ainsi la notion de verticalomics. La caractérisation d'une série de vins blancs de Bourgogne (Chardonnay) a révélé que les espaces chimiques spécifiquement liés à des pratiques œnologiques (SO2 ajouté lors du pressurage, niveau de débourbage ou perméabilité du bouchon) pourraient être déchiffrés, bien que les signatures de millésimes étaient les plus significatives. Des expériences similaires sur les vins de Champagne (Chardonnay, et mélanges de Chardonnay, Pinot noir et Pinot Meunier) après la prise de mousse et le vieillissement sur lattes ont mis en évidence l'effet d'hormesis associé à l'oxygénation du vin. Enfin, les analyses non ciblées d'extraits de raisin et des vins correspondants provenant de différentes appellations et élaborés par le même vigneron ont révélé qu’il était possible de lire des signatures liées au terroir, en particulier après quelques années de vieillissement en bouteille. Plus largement, nos résultats fournissent une description globale sans précédent de la composition chimique du vin et de sa modification par le vieillissement. / The main objective of this work was to develop non-targeted metabolomics analyses of bottled wines in order to decipher chemical informations from the time-related evolution of their composition. This original research was based on the hypothesis that, when analyzed, bottled wines would still hold chemical memories of envionmental parameters (vineyard management, oenological practices, climate, terroir…) at the moment of their elaboration, even after several years of ageing. A second hypothesis was that in order to anticipate the future evolution of the wine quality in terms of chemical composition, it is necessary to know what it was in the past. To that purpose, and for the first time in wine science, Fourier Transform Ion Cyclotron Resonance – Mass Spectrometry (FTICR-MS), Liquid Chromatography coupled with mass spectrometry (UPLC-Q-ToF-MS), Excitation Emission Matrix Fluorescence (EEMF) and multivariate statistics were used in combination. Methodological develoments revealed the advantage of coupling exact mass measurements by FTICR-MS to isomeric discrimination by UPLC-Q-ToF-MS in order to extend the range of detectable metabolites. Such tools were applied to the identification of ageing markers in vertical series of red and white wines from Burgundy, including very old wines (unknown vintages) considered as evolution end points, thus introducing the concept of verticalomics. The characterization of series of white wines from Burgundy (Chardonnay) revealed that chemical spaces specifically related to eonological practices (SO2 addition at pressing, settling level, and permeability of the stopper) could indeed be deciphered although the vintage signatures were confirmed to be the most significant. Similar experiments on Champagne wines (Chardonnay, and blends of Chardonnay, Pinot noir and Pinot Meunier) after the "prise de mousse" and the ageing "sur lattes" further highlighted the hormesis effect associated with the oxygenation of wine. Finally, non-targeted analyses of series of grape extracts and corresponding wines from different appelations – though elaborated by the same winemaker – revealed that terroir-related signatures could be indeed read in wines, in particular after a few years of bottle ageing. Altogether our results provide an unprecedented comprehensive description of the chemical composition of wine and its modification through ageing.

Les sols sont le plus grand réservoir de carbone des écosystèmes terrestres, et la minéralisation des matières organiques par l’activité microbienne représente la majeure partie des flux de CO2 émis à la surface des continents.Dans ce travail, nous avons étudié les matières organiques extraites à l’eau (WEOM), qui correspondent à la fraction la plus réactive des matières organiques du sol (MOS). Nos objectifs étaient (i) d’identifier les liens de la dynamique du WEOM avec les communautés bactériennes, et avec les paramètres physico-chimiques du sol ; (ii) de réaliser une caractérisation chimique précise du WEOM.Il existe un lien fort entre la solubilité des MOS et les structures des communautés bactériennes, et une baisse de leur diversité impacte la dynamique des MOS et du WEOM, et provoque une baisse de la minéralisation des matières organiques. Une étude à l’échelle régionale a également permis d’identifier que les taux de MOS et d’argile contrôlent les quantités de WEOM et leur aromaticité. La caractérisation au niveau moléculaire a montré la présence d’un grand nombre de molécules ubiquistes dans le WEOM. À partir de ces analyses, nous avons également pu décrire les effets du couvert végétal et des propriétés physico-chimiques des sols sur la composition chimique du WEOM. / Soils are the greatest reservoir of C on the continents, and organic matter mineralisation bymicrobial activity represents the major part of the CO2 emitted by terrestrial ecosystems.In this work, we studied water-extractable organic matter (WEOM), which corresponds to themore reactive fraction of soil organic matter (SOM). Our objectives were (i) to identify therelationships of WEOM dynamics with bacterial communities, and with soil physico-chemicalparameters; (ii) to provide a precise chemical characterisation of WEOM.There is a strong link between SOM solubility and the structure of bacterial communities, andan erosion of their diversity has an impact on SOM and WEOM dynamics, and leads to adecrease in organic matter mineralisation. A study at the regional scale then allowed us to identifythat the SOM and clay contents control the quantities of WEOM and its aromaticity. TheWEOM characterisation at the molecular level revealed the presence of a large number ofubiquitous molecules in the WEOM. Based on these analyses, we were also able to describe theeffects of vegetation and soil physico-chemical properties on the chemical composition ofWEOM.

Beryllium-7 (Be-7) only decays by electron capture into lithium-7 (Li-7) with a half life of 53 days. We study the effect of ionization on this decay rate. We do so by trapping a Be-7 ion plasma in a cylindrical Malmberg-Penning trap and measuring Be-7 and Li-7 concentrations as functions of time by using Fourier transform ion cyclotron resonance mass spectrometry (FTICR-MS). We have simulated these signals in a 2-dimensional electrostatic particle-in-cell (PIC) code. The two spectrum peaks merge at high ion densities whereas at low ion densities they can be resolved. The merged peak shifts linearly according to the relative abundances of these species. We have also simulated singly-ionized beryllium-7 hydride (BeH+) and Li-7 ion plasmas at high densities. These two separate peaks shift according to their relative abundances. We describe an analytical model that explains how these peaks shift.