Influenza A (IVA) continues to pose a growing global threat even as current medications are becoming less effective. One of the main avenues of research into new anti-IVA drugs is its homotetrameric Matrix 2 proton channel (M2A), without which the virus would be unable to release its viral RNA into the host cell. The drug amantadine used to bind and block M2A until near-ubiquitous resistance formed as an M2A-S31N mutation, starting around 1995 and proceeding to 2005 when amantadine was disallowed for use as an anti-IVA drug. The standard organic structure currently being used for M2A inhibitor research comprises an adamantyl foot group, a heterocyclic aryl body group, and a cyclic head group. A sample set of compounds with this standard structure was compared and reviewed, focusing on positive and negative moieties and modifications. Modifications on the foot group were all more or less detrimental, body groups with two heteroatoms were advantageous, and larger head groups appeared better. Four other scaffolds known to literature were proposed for further study due to beneficial aspects of each. Where most anti-M2A research deals exclusively with organic compounds, metals and their potential in drugs have been almost entirely ignored due to the increased toxicity they bring. Free copper was found in past research to be the only first-row transition metal to show significant M2A-inhibitory activity, proposed to do so by binding the H37 cluster that acts as a pH-dependent control switch for the channel. Six overall-neutral copper complexes were synthesized as a combination of amantadine, cyclooctylamine, and null scaffolds with two of either acetate or acetamide arms as chelators. The complexes were found to block both M2A-WT and M2A-S31N. Along with CuCl¬¬2, though, they had little to no effect on M2A-H37A, providing confirming evidence that the copper binds at the H37 tetrad. Only one complex, Cu(cyclooctylamineiminodiacetate), outperformed CuCl2 in channel block studies and efficacy against two IVA strains, but all of the complexes were found to have lower cytotoxicity. Because M2-H37 is highly conserved, these complexes show promise for further testing against all strains of influenza A. Five net-divalent copper complexes were then synthesized with multiple aza or amine groups as chelators. The complexes failed to show any significant activity against M2A, however, which was thought to be due to size or polarity rejection or electromagnetic repulsion. One of the ligands, though, an adamantyl derivative of a tetraaza macrocycle, was a novel compound, and its copper complex, along with two others, were unknown to the CCDC database. The three complexes were characterized by X-ray diffraction and discussed.

The research presented in this thesis focuses on developing new functional polymeric materials that can conduct ions, H+, or OH- or Li+. The motivation behind this work was to understand the similarities and/or differences in the structure property relationships between polymer membranes and the conductivity of H+ and OH- ions, and between polymer membranes and the anhydrous conductivity of H+ and Li+ ions. This understanding is critical to developing durable polymer membranes with high H+, OH- and Li+ ion conductivity for proton exchange membrane fuel cells (PEMFCs), alkaline anion exchange membrane fuel cells (AAEMFCs) and lithium ion batteries respectively. Chapter 1 describes the basic functioning of PEMFCs, AAEMFCs and lithium ion batteries, the challenges associated with each research topic, and the fundamental mechanisms of ion transport. The proton conducting properties of poly(4-vinyl-1H-1,2,3-triazole) were investigated on a macroscopic scale by impedance spectroscopy and microscopic scale by solid state MAS NMR. It was found that proton conductivity is independent of molecular weight of the polymer, but influenced by orders of magnitude by the presence of residual dimethylformamide. To improve the mechanical properties of otherwise liquid-like 1H-1,2,3-triazole functionalized polysiloxane homopolymers, hybrid inorganic-organic proton exchange membranes (PEMs) containing 1H-viii 1,2,3-triazole grafted alkoxy silanes were synthesized, using sol-gel chemistry. This method enabled self-supporting membranes having proton conductivity comparable to uncrosslinked homopolymers. One of the biggest challenges with AEMs for use in AAEMFCs is finding a cationic polyelectrolyte that is chemically stable at elevated temperatures in high pH environment. Novel triazolium ionic salts were developed, having greater chemical stability under alkaline conditions compared to existing imidazolium ionic salts. However, the chemical stability of triazolium cations was not sufficient for AAEMFC applications. Excellent chemical stability of (C5H5)2Co+ in 2 M NaOH at 80°C over 30 days was demonstrated and polymerizable vinyl functionalized cobaltocenium monomers were synthesized. This work paves the way for future development of AEMs containing cobaltocenium moieties to facilitate hydroxide ion transport. Polymers containing covalently attached cyclic carbonates were synthesized and doped with lithium triflate and their lithium ion conductivities were investigated. The findings highlight the importance of high charge carrier density and flexibility of the polymer matrix to achieve high lithium ion conductivity. These results are similar to the key factors influencing anhydrous proton transport.

Anhydrous proton conducting polymers are highly sought after for applications in high temperature polymer electrolyte membrane fuel cells (PEMFCs). N-heterocycles (eg. imidazole, triazole, and benzimidazole), owing to their amphoteric nature, have been widely studied to develop efficient anhydrous proton transporting polymers. The proton conductivity of N-heterocyclic polymers is influenced by several factors and the design and development of polymers with a delicate balance among various synergistic and competing factors to provide appreciable proton conductivities has been a challenging task. In this thesis, the proton transport (PT) characteristics of polymers functionalized with two diverse classes of functional groups - N-heterocycles and phenols have been investigated and efforts have been made to develop the molecular design criteria for the design and development of efficient proton transporting functional groups and polymers. The proton conduction pathway in 1H-1,2,3-triazole polymers is probed by employing structurally analogous N-heterocyclic (triazole, imidazole, and pyrazole) and benz-N-heterocyclic (benzotriazole, benzimidazole, and benzopyrazole) polymers. Imidazole-like pathway was found to dominate the proton conductivity of triazole and pyrazole-like pathway makes only a negligible contribution, if any. Polymers containing benz-N-heterocycles exhibited higher proton conductivity than those with the corresponding N-heterocycles. Pyrazole-like functional groups, i.e. the molecules with two nitrogen atoms adjacent to each other, were found not to be good candidates for PT applications. A new class of proton transporting functional groups, phenols, has been introduced for anhydrous PT. One of the highlighting features of phenols over N-heterocycles is that the hydrogen bond donor/acceptor reorientation can happen on a single -OH site, allowing for facile reorientational dynamics in Grotthuss PT and enhanced proton conductivities in phenolic polymers. Unlike the case of N-heterocycles, comparable conductivities were achieved between poly (3,4,5-trihydroxy) styrene and the corresponding small molecule, pyrogallol. This observation suggests that reorientation should be considered as a crucial design parameter for PT functional groups. The PT characteristics of phenol-based biaryl polymers are studied and compared with the analogous phenol-based linear styrenic polymers. The two-dimensional disposition of -OH moieties in biaryl polymers, although resulted in lower apparent activation energies (Ea), did not improve the net proton conductivity due to the accompanying increase in glass transition temperature (Tg). Thus, the ease of synthesis and lower Tg values of phenol-based styrene polymers make the styrenic polymer architecture preferable over the biaryl architecture. Finally, the synthesis of a series of poly(3,4-dihydroxy styrene)-b-polystyrene block copolymers has been demonstrated via anionic polymerization. These block copolymers will provide an opportunity to systematically investigate the effect of nanoscale morphology on proton transport.

Sodium/proton exchangers are ubiquitous secondary active transporters that can be found in all kingdoms of life. These proteins facilitate the transport of protons in exchange for sodium ions to help regulate internal pH, sodium levels, and cell volume. Na+/H+ exchangers belong to the SLC9 family and are involved in many physiological processes including cell proliferation, cell migration and vesicle trafficking. Dysfunction of these proteins has been linked to physiological disorders, such as hypertension, heart failure, epilepsy and diabetes. The goal of my thesis is to establish the molecular basis of ion exchange in Na+/H+ exchangers. By establishing how they bind and catalyse the movement of ions across the membrane, we hope we can better understand their role in human physiology. In my thesis, I will first present an overview of Na+/H+ exchangers and their molecular mechanism of ion translocation as was currently understood by structural and functional studies when I started my PhD studies. I will outline our important contributions to this field, which were to (i) obtain the first atomic structures of the same Na+/H+ exchanger (NapA) in two major alternating conformations, (ii) show how a transmembrane embedded lysine residue is essential for carrying out electrogenic transport, and (iii) isolate and recorde the first kinetic data of a mammalian Na+/H+ exchanger (NHA2) in an isolated liposome reconstitution system.

京都大学 / 0048 / 新制・課程博士 / 博士(人間・環境学) / 甲第22708号 / 人博第958号 / 新制||人||227(附属図書館) / 2020||人博||958(吉田南総合図書館) / 京都大学大学院人間・環境学研究科相関環境学専攻 / (主査)教授 内本 喜晴, 教授 高木 紀明, 教授 中村 敏浩 / 学位規則第4条第1項該当 / Doctor of Human and Environmental Studies / Kyoto University / DFAM

No description available.

<p>During the past fifty years, mass spectrometry, often hyphenated with chromatography, has developed into the most widely used technique for the quantitative and qualitative analysis of increasingly complex mixtures of (bio)organic molecules.</p> <p>One important aspect of this development concerns the relationship between the structure (atom connectivity) of a molecule and the mass spectrum obtained by electron ionization (EI). In this context, from 1960 - 1990, a wealth of studies has appeared that uses a variety of novel experimental techniques, often in conjunction with isotope labelling, to probe the structure, stability, reactivity and dissociation characteristics of the radical cations generated by EI of various classes of molecules. One highlight was the discovery of surprisingly stable distonic ions and the role they play in the dissociation chemistry of ionized molecules.</p> <p>However, mechanistic proposals based upon experimental observations can often only be considered as tentative. Synergy between experiment and theory would be ideal to remedy this situation, but it was not until recent spectacular advances in computer technology and software that this approach could be implemented. It has led to the growing realization that many rearrangement reactions of radical cations in the rarefied gas-phase involve catalysis. Proton-transport catalysis (PTC) is a prime example : here, a neutral species induces an ion to isomerize via hydrogen-bridged radical cations (HBRCs) as intermediates. An exemplary case described in this thesis concerns the ion-molecule reaction of the cyanamide ion with a single H₂O molecule : experiment and theory indicate that the H₂O molecule catalyzes the swift transformation of NH₂-CN^·⁺ into the more stable carbodiimide ion HN=C=NH^·⁺.</p> <p>The thesis exploits the synergy of tandem mass spectrometry and computational chemistry to study the role of catalysis in the association and dissociation reactions of several systems of radical cations. During these studies, a new type of a catalyzed reaction was discovered: "ion-catalysis", where an organic cation promotes the otherwise prohibitive rearrangement of a neutral. Ion-catalysis is proposed to explain the unexpected loss of NH₂O^· from low-energy N-hydroxyacetamide ions CH₃C(=O)NHOH^·⁺ : the molecular ion rearranges into the HBRC [O=C-C(H₂)--H--N(H)OH]^·⁺ whose acetyl (cation) component catalyzes the transformation NHOH^· --> NH₂O^·. Another highlight involves a hybrid reaction, in which both the ion and the neutral component of an incipient HBRC catalyze one another to rearrange into more stable isomers.</p> <p>Catalysis may also play an important role in astrochemistry and a question addressed in this context is whether pyrimidine, a key component of DNA, may be generated by ion-molecule reactions. It appears that the acrylonitrile ion (AN) does not react with HCN to produce ionized pyrimidine, instead it isomerizes by PTC. However, the reaction of the ion with its neutral counterpart does not involve catalysis, but rather cyclization into the pyrimidine ion ! A related topic concerns the structures of covalently bound dimers of the ubiquitous interstellar molecules HCN and HNC. Neutralization-Reionization Mass Spectrometry in conjunction with model chemistry calculations leaves little doubt that the elusive dimers HN=C=C=NH and HC=N-C=NH are kinetically stable in the rarefied gas-phase, whereas HC=N-N=CH is not.</p> <p>The structure of ions may also be probed by interactions with selected neutral molecules rather than dissociative collision experiments (MS/MS). An exciting case involves the differentiation of isomeric heterocyclic ions by ion-molecule reactions with dioxygen. Here, too, model chemistry calculations play an essential role in understanding the mechanism and the scope of the reaction.</p> / Doctor of Philosophy (PhD)

Les membranes fluorées sont utilisées en particulier dans les dénommées piles à combustible à membrane électrolyte polymère. Grâce à sa grande mobilité en protons, le célèbre ionomer Nafion® (Dupont) est un matériau de référence pour les applications liées aux piles à combustible. En présence d’eau ou d’autres solvants hydrophiles la membrane se sépare en une matrice polymérique hydrophobe et une sous-phase aqueuse contenant des clusters d’eau et ions, dont les tailles et la connectivité augmente quand la quantité d’eau augmente [1]. Quelle est la morphologie du Nafion et la structure du solvant, dans de tels systèmes?Il a été récemment montré [2] sur des simulations de large systèmes que plusieurs modèles morphologiques reproduisent les données expérimentales de diffusion, évoquant l’incapacité des mesures de diffusion seules à élucider la véritable structure du Nafion.Néanmoins, un modèle ’aléatoire’ décrit dans [2], c’est à dire l’unique modèle étudié sans présumer d’une structure initiale particulière, n’a pas pu reproduire les données expérimentales.Générer en simulations moléculaires des configurations du système qui soient vraiment décorrélées de la configuration initiale reste un vrai défi statistique. Les échelles de temps réalisables ne permettent simplement pas d’obtenir des mouvements significatifs du polymère (comme des transitions de conformations, repliements de chaînes, etc.). Nous proposons ainsi dans cette étude un nouveau modèle de Nafion à morphologie aléatoire. Un algorithme récemment développé est utilisée pour générer des chaînes de Nafion avec des chemins et des points de départ aléatoires. Une différence majeure avec le modèle aléatoire dans [2] est que nous ne construisons pas nos systèmes à une densité proche de la densité finale. Pour ne pas démarrer avec des chaînes trop enchevêtrées, les systèmes sont initialement préparés à une densité en dessous de la référence expérimentale. La densité après équilibration est de nouveau proche de l’expérience. Bien qu’il soit facilement envisageable d’améliorer les nouveaux algorithmes, nous démontrons ici qu’avec la présente version plusieurs séries de configurations compatibles avec les données expérimentales de diffusion disponibles peuvent être générées et équilibrées. Douze large systèmes de Nafion à morphologie aléatoire sont construits avec des positions initiales des atomes ainsi que des quantités d’eau et des longueurs de chaînes (Nafion/Hyflon) différentes. Ils sont équilibrés puis simulés sur plusieurs dizaines de nanosecondes. Après équilibration, les structures sont, comme indiqué ci-dessus,compatibles avec les données expérimentales de diffusion. En plus nous étudions un modèle ressemblant à celui de Schmidt-Rohr and Chen [3], c’est à-dire le plus récent modèle morphologique. Avec ce modèle, les données expérimentales sont également reproduites de manière satisfaisante, d’où la prolongation du débat sur la structure du Nafion. La cohésion entre les valeurs calculées et celles mesurées expérimentalement incite à des analyses plus en détails de ces configurations obtenues. Nous caractérisons et analysons les structures locales, intermédiaires et à grande échelle avec divers paramètres structuraux et distributions des tailles de domaines. Nous calculons donc, par exemple, des fonctions de distribution radiale (rdf), des facteurs de structure (S(q)) totaux et partiels tout comme des nombres et des tailles de clusters hydrophiles (selon la définition d’un cluster). La dynamique de diverses espèces dans le système est également examinée,par exemple au travers des déplacements carrés moyens (msd) et des coefficients de diffusion. Ces simulations sont probablement à la limite de ce qui est réalisable aujourd’hui avec des simulations ’full-atom’ du type MD. Nous espérons que ce travail fera avancer le débat sur la structure et la dynamique de ces matériaux importants. / Perfluorinated membranes are used in particular in polymer electrolyte fuel cells(PEFC). The well-known ionomer Nafion® (Dupont) is, due to its high proton mobility,a reference material for fuel cell applications. In water or other hydrophilic solvents themembrane segregates into a hydrophobic backbone matrix and a hydrophilic sub-phasecontaining clusters of both water and ions, where the cluster sizes and connectivity increasewith increasing water content [1].What is the Nafion morphology and the structure of the solvent in such systems? It hasbeen shown recently [2] on large simulated systems that several morphological modelsfit the experimental scattering data, suggesting the inability of scattering experimentsalone to elucidate the true structure of Nafion. However, a ’random’ model describedin [2], i.e. the only explored model that did not assume a particular initial structure,could not reproduce the experimental data.It remains a real computational challenge to generate in molecular simulations systemconfigurations which are really decorrelated from the initial one. The time scales thatcan be achieved simply do not allow to obtain significant motions of the polymer (e.g.conformational changes, folding, etc.). We thus propose in this work a new randommodel of Nafion. A newly developped algorithm is used to generate Nafion chains withrandom growth paths and random starting points. A significant difference with therandom model in [2] is that we do not build our systems at a density close to the finalone. In order not to start with too much entangled chains, the systems are initiallybuilt at a density below the experimental one. The density after equilibration is againclose to the experimental one.Even though further improvements of the new algorithms can easily be envisaged,we demonstrate here that with the present version several sets of configurations thatare compatible with the available scattering data can be generated and equilibrated.Twelve large random Nafion systems are built with different initial positions of theatoms as well as different water contents and side chain lengths (Nafion/Hyflon). Theyare equilibrated and then simulated for several ten nanoseconds. After equilibration,the structures are, as mentioned, compatible with the experimental scattering data. Inaddition we study a model similar to the one by Schmidt-Rohr and Chen [3], i.e. thenewest morphological model of Nafion. The experimental scattering data are also satisfactorilyreproduced with this model, hence, the prolonged debate over the structureof Nafion.This agreement gives confidence that a more detailed analysis of the so-obtained configurationsis scientifically warranted. We characterize and analyze the local, intermediateand large-scale structures by various structural parameters and domain size distributions.We therefore compute, for example, radial distribution functions (rdf), total andpartial structure factors (S(q)) as well as numbers and sizes of hydrophilic clusters (dependingon the definition of a cluster). The dynamics of various species in the systemis also investigated, e.g. via the computation of the mean square displacements (msd)and the self-diffusion coefficients. These simulations are probably at the limit of whatcan today be achieved with all-atom molecular simulations of the MD type. We hopethat this work will advance the ongoing debate on the structure and dynamics of theseimportant materials. / Perfluorierte Membranen werden insbesondere in Polymerelectrolyt-Brennstoffzellen(PEFC) eingesetzt. Das wohlbekannte Ionomer Nafion® (Dupont) ist wegen seinerhohen Protonenbeweglichkeit ein Referenzmaterial für solche Anwendungen in Brennstoffzellen.Die Membran separiert in Wasser oder anderen hydrophilen Lösungsmittelin eine hydrophobe Polymermatrix und eine hydrophile Subphase, die Cluster mitWasser und Ionen enthält. Dabei vergroeßern sich die Ausdehnung der Cluster und ihreKonnektivität mit zunehmendem Wassergehalt [1].Welche ist die Morphologie des Nafions und die Struktur des Lösungsmittels in diesenSystemen? Es ist jüngst anhand großer simulierter Systeme gezeigt worden [2], dassmehrere morphologische Modelle die experimentellen Streudaten wiedergeben können,was nahelegt, dass solche Streudaten alleine nicht geeignet sind, die wahre Strukturdes Nafion aufzudecken. Ein in [2] beschriebenes ’Zufallsmodell’, d.h. das einzigeder untersuchten Modelle, das keine besondere Anfangsstruktur annahm, konnte dieexperimentellen Daten allerdings nicht wiedergeben.In molekularen Computersimulationen Konfigurationen zu erzeugen, die wirklich nichtmehr mit der angenommenen Anfangskonfiguration korreliert sind, bleibt eine echteHerausforderung. Die erreichbaren Zeitskalen sind zu kurz, um eine signifikante Bewegungdes Polymers (z.B Konformationsänderungen, Faltungen, usw.) zuzulassen. Indieser Arbeit wird daher ein neues Zufallsmodell für Nafion vorgestellt. Ein neuentwickelterAlgorithmus erzeugt Nafionketten mit zufälligem Wachstumspfad ausgehendvon zufälligen Anfangspunkten. Ein signifikanter Unterschied zu dem Zufallsmodellvon [2] ist, dass hier nicht versucht wird, die Systeme bei einer Dichte vergleichbarder experimentellen Dichte aufzubauen. Anstattdessen werden die Systeme, um alzustarkes Verknäuelung zu vermeiden, anfangs bei einer deutlich kleineren Dichte erzeugt.Nach äquilibrierung ist die Systemdichte wieder in etwa gleich der experimentellen.Wiewohl weitere Verbesserungen des neu Algorithmuses leicht ins Auge gefaßt werdenkönnen, so kann hier doch gezeigt werden, dass mit der gegenwärtigen VersionKonfigurationen erzeugt und äquilibriert werden können, die mit den verfügbarenStreudaten kompatibel sind. Zwölf große Nafion Zufallssysteme, mit verschiedenenAnfangspositionen der Atome, verschiedenem Wassergehalt und Längen der Seitenketten(Nafion/Hyflon) werden aufgebaut. Diese werden äquilibriert und mehrerezehn Nanosekunden lang simuliert. Nach der äquilibrierung sind die Strukturen, wieerwähnt, kompatibel mit den experimentellen Streudaten. Weiterhin wird ein Modellähnlich dem von Schmidt-Rohr und Chen [3], d.h. dem neuesten morphologischen Modellfür Nafion, studiert. Auch hier werden die experimentellen Streudaten zufriedenstellendwiedergegeben, daher die weiterhin bestehende Debatte über die Struktur desNafion.Die gefundenen übereinstimmungen lassen darauf vertrauen, dass eine detaillierte Analyseder simulierten Konfigurationen wissenschaftlich sinnvoll ist. So wird die Strukturder Systeme auf verschiedenen Längenskalen charakterisiert, zum Beispiel durch radialePaarverteilungsfunktionen (rdf), totale und partielle Strukturfaktoren (S(q)) sowieAnzahl- und Größenverteilungen hydrophiler Cluster (abhängig von der Definition einesClusters). Die Dynamik einzelner Spezies im System wird ebenfalls untersucht, zumBeispiel durch die Berechnung der mittleren quadratischen Verschiebungen (msd) undder Selbstdiffusionskoeffizienten. Diese Simulationen sind wahrscheinlich an der Grenzedessen, was heute mit ’all-atom’ molekularen MD-Simulationen möglich ist. Ich vertrauedarauf, dass diese Arbeit dennoch einen Fortschritt in der aktuellen Debatte überdie Struktur und Dynamik dieser wichtigen Materiale darstellt.

Cette thèse porte sur l'étude de la diffraction avec le détecteur ATLAS au LHC. Après une brève introduction a la physique diffractive incluant la diffraction dure et molle, nous présenterons la production d'évènements "Jet-Gap-Jet" qui est particulirement intéressante pour tester les équations d'évolution de la Chromodynamique Quantique de Balitski Fadin Kuraev Lipatov. En utilisant des coupures permettant de sélectionner ce signal et une définition du "gap" basée sur la reconstruction des traces dans le détecteur interne d'ATLAS, nous observons un signal clair d'évènements "Jet-Gap-Jet" dans les données. A partir d'une taille de "demi-gap" de 0.8, les données ne peuvent pas être décrites de manière correcte en utilisant l'échantillon Monte Carlo des données de jets sans gap. Nous prouvons également que la production d'évènements "Jet-gap-Jet" avec les deux protons détectes dans AFP permet de réaliser un test propre de la théorie BFKL avec une luminosité de 300 pb-1. Dans la derniere partie de la these, nous presentons la production exclusive de jets et de pi+pi-. Apres la selection des donnes, le rapport signal sur bruit est de l'ordre de 5/9 (1/13) pour µ = 23 (46). Pour une luminosite integree respective de 40(300) fb-1 (pour un "pile-up" de 23(46)), cette mesure permettra d'etablir des contraintes sur les modeles theoriques dix fois plus precises qu'actuellement. La mesure de la production exclusive de pions en utilisant le detecteur ALFA permet de contraindre egalement les modeles exclusifs. Nous avons montre que les donnees accumulees par ALFA suffiront deja pour mesurer la section efficace de production et pour etudier differentes distributions comme la masse invariante du systeme pion-pion. / The thesis is devoted to the study of diffractive physics with the ATLAS detector at the LHC. After a short introduction to diffractive physics including soft and hard diffraction, we discuss Jet-Gap-Jet production at the LHC which is particularly interesting for testing the Balitski Fadin Kuraev Lipatov QCD evolution equation. Using the signal selection requirements and a gap definition based on tracks reconstructed in the ATLAS Inner Detector, we observe a clear signal of Jet-Gap-Jet events in the data. Starting from the half-gap size of 0.8 the data cannot be properly described using only the Jet Monte Carlo sample without gaps. Furthermore, we demonstrated that DPE JGJ production, with both protons tagged in the AFP stations, should provide a significant test of the BFKL theory, once the 300 pb−1 of integrated luminosity is collected. In the last part of the thesis, we discussed the processes of Central Exclusive Jet and Exclusive π+π− production. After the data selection, the signal to background ratio is found to be of about 5/9 (1/13) for < μ >= 23 (46). For a collected integrated luminosity of 40(300) fb−1 (for pile-up of 23(46)) this measurement will deliver ten times better constraints on the theoretical models than the most recent ones. The additional measurement of exclusive pion production, relying on the use of the ALFA stations, allows to constrain further the exclusive models. We demonstrated that a data sample collected by the ALFA detectors should be sufficient to measure the cross sectionand to study various distributions, especially the invariant mass of the pion-pion system.

Les couches catalytiques avec une structure ordonnée à base de nanoparticules de Pt supportées sur des nanofilaments de carbone verticalement alignés ont montré des performances intéressantes grâce à l’amélioration des propriétés du transport de matière et à une meilleure utilisation du Pt. Des études électrochimiques combinées à une modélisation mathématique ont mis en évidence l’influence du transport de protons sur les processus d’oxydo-réduction, la cinétique et le mécanisme de réduction de l’O2 (ORR), et sur H2O2 qui s’échappe des couches pendant l’ORR. Nous avons montré que (i) les protons sont impliqués dans l’étape limitante de la réaction, (ii) pour un pH ≥ 3, un plateau de courant limité par la diffusion des protons est observé et, (iii) pour un pH ≥ 3, le mécanisme de l’ORR implique non seulement les ions hydroniums mais aussi les molécules d’eau. L’intégration de ces couches catalytiques dans des PEMFCs haute température a ensuite été étudiée. Les performances obtenues sont légèrement plus basses que celles des couches conventionnelles. Un travail d’optimisation reste donc à accomplir pour améliorer les performances. / Ordered catalytic layers based on vertically aligned carbon nanofilaments with Pt nanoparticles demonstrate high efficiency for oxygen transport and Pt utilization in the catalytic layer. Electrochemical studies combined with mathematical modeling confirm the influence of the proton transport on surface red-ox processes, the kinetics and the mechanism of the O2 reduction (ORR), and on the H2O2 escape. We show that (i) protons are involved in the rate-determining step of the O2 reduction, (ii) for pH ≥ 3, a plateau corresponding to the diffusion-limited current of protons is observed and, (iii) for pH ≥ 3, the mechanism of the ORR involves not only the hydronium ions but also water molecules. The integration of these catalytic layers in high temperature PEMFCs was then studied. The performance is slightly lower than that for conventional layers. An optimization work is required to improve the performance.