Dissertations / Theses on the topic 'Small ion'

L’objectiu de la present tesi doctoral consisteix en desenvolupar molècules policícliques de baix pes molecular que tinguin com a diana tres canals iònics específics: la viroporina A/M2 del virus de la grip, el receptor purinèrgic dependent de lligand P2X7 i el receptor glutamatèrgic dependent de lligand N-metil-D-Aspartat, per tal de modular-los d’una manera tal que n’evitin o millorin el desenvolupament dels processos patogènics associats a aquestes proteïnes i/o que permetin ser emprades com a eines de recerca. En el capítol 1 es presenta una introducció general del paper dels canals iònics, així com una descripció més específica de cadascun dels 3 canals objecte d’estudi en aquesta Tesi. Els objectius d’aquest treball es detallen en el capítol 2, després del qual, en el capítol 3 es presenten un seguit d’anàlegs per contracció d’anell del fàrmac comercial Amantadina, resultant-ne els primers inhibidors duals del canal M2 del virus de la Influenza A descrits en la bibliografia, actius sobre la soca salvatge (wt) i sobre el mutant resistent a fàrmacs V27A (Rey-Carrizo, M. et al. J. Med. Chem. 2013, 56, 9265). Seguidament en la part A del capítol 4 es gràcies a estudis in silico, s’observa com un dels inhibidors triples presenta un mode d’unió diferent sobre els canals wt i V27A, que podria estar directament relacionat amb el mecanisme de resistència a fàrmacs del mutant V27A (Rey-Carrizo, M., et al. J. Med. Chem. 2014, 57(13), 5738). En el capítol 5 es completa el treball presentant per primera vegada la proba experimental d’una possible explicació del mecanisme de resistència a fàrmacs del mutant V27A. (Barniol-Xicota, M., et al. manuscrit acceptat al J. Med. Chem.). Com a continuació en el capítol 6 s’explora una diana diferent de la viroporina M2: l’hemaglutinina (HA) (Leiva, R., et al. manuscrit pendent d’enviar a J. Med. Chem.). El capítol 7 representa el primer treball que marca l’inici de la línia de recerca d’antagonistes del receptor P2X7 en el grup. (Barniol-Xicota, M., et al. manuscrit en revisió al Bioorg. Med. Chem. Lett.). Finalment, en el capítol 8, es presenten els primers exemples descrits a la bibliografia de multi-target directed ligands (MTDL) amb els receptors NMDA i P2X7 com a dianes. (Karou, O., et al. manuscrit pendent d’enviar a ACS Med. Chem. Lett.). Deixant de banda la recerca de compostos bioactius en la part B del capítol 4 es descriu un estudi teòric i experimental d’un alquè altament piramidalitzat, derivat de l’estructura d’un compost bioactiu detallat en la part A del mateix capítol. (Rey-Carrizo, M. et al. Angew. Chem. Int. Ed. 2014, 53, 8195).

In living systems, ion channels are membrane transport proteins that provide pathways for the passive diffusion of ions through lipid membranes. The flow of ions across membranes is the basis of many important physiological processes, including but not limited to the regulation of membrane potential, transepithelial transport and cell volume. While many efforts have been made to understand the biological roles of natural ion channels, the biological activities of artificial ion channels remain largely unknown. Recently, it was reported that a small molecule 1, which forms synthetic chloride (Cl–) channels in membranes via self-assembly, is capable of modulating vascular functions. In this thesis, novel small molecules that are structurally similar to 1 are shown to form artificial ion channels in membranes. Together with 1, the effects of these small molecules on the contractile activities of smooth muscles and epithelial ion transport are explored. The therapeutic implications of the findings are also discussed. A collection of small molecules was screened using liposome-based fluorescence assays. In these assays, the ability of the synthetic compounds to modulate membrane potential was monitored. The screening yielded compound 3 that formed synthetic potassium (K+) channels in liposomal membranes, although the liposome-based fluorescence experiments suggested that 3 also transported Cl–. Two derivatives of 3, namely, compounds 2 and 4 were also examined. Single-channel recording experiments suggested that 2 forms synthetic Cl– channels in liposomal membranes. The effects of compounds 2 and 3 on the functions of the vascular smooth muscle are explored. Using confocal imaging, it was shown that both 2 and 3 counteracted the effects of high-K+ depolarizing solution on membrane potential and intracellular Ca2+ concentration ([Ca2+]i) in cultured vascular smooth muscle cells. 2 and 3 also relaxed mice aortic rings pre-contracted with high-K+ solution. These observations can be explained in terms of the Cl– transporting functions of 2 and 3. To determine the potential for developing the compounds into bronchodilators, the effects of compounds 1 and 3 on the contractile activities of the airway smooth muscle (ASM) were explored using organ bath technique. The contractile activities of the trachea isolated from Sprague-Dawley (SD) rats were first characterized. Among the contractile agents used, only potassium chloride (KCl), cholinergic agonists, serotonin and endothelin-1 were contractile to the SD rat trachea. 1 and 3 relaxed the ASM pre-contracted with KCl, whereas the contractions induced by other agonists were not affected. The ability of compounds 2, 3 and 4 to modulate ion transport across cultured epithelia was tested by the short-circuit current measurement technique. It was shown that the compounds were capable of inducing Cl– secretion when applied to the apical side of airway and colonic epithelia. Importantly, the synthetic compounds induced apical Cl– secretion in immortalized cystic fibrosis (CF) bronchial epithelia. This suggests that the synthetic compounds may be used to correct the anion transport defect in CF epithelia. In summary, the small-molecule based synthetic ion channels demonstrated two important general functions of natural ion channels, namely, the regulation of membrane potential and epithelial ion transport.
published_or_final_version
Chemistry
Doctoral
Doctor of Philosophy

We create a dual-species ultracold neutral plasma (UNP) by photo-ionizing Yb and Ca atoms in a dual-species magneto-optical trap. Unlike single-species UNP expansion, these plasmas are well outside of the collisionless (Vlasov) approximation. We observe the mutual interaction of the Yb and Ca ions by measuring the velocity distribution for each ion species separately. We model the expansion using a fluid code including ion-ion friction and compare with experimental results to obtain a value of the Coulomb logarithm of Λ= 0.04.

Using ion-trapping techniques, selected laboratory experiments on ion-molecule reactions of astrophysical interest have been performed. For the first time a carbon beam source has been integrated into an ion trapping machine for studying collisions between ions and neutral carbon atoms and molecules. Results are presented for the interaction of D3+ ions stored in a ring-electrode trap (RET), with a beam of hot neutral carbon molecules, Cn (n = 1, 2, 3). The measured reaction rate coefficients are up to a factor two smaller than values presently used in astrophysical models. In order to complete our knowledge about the ion chemistry involving three carbon atoms, detailed investigations of reactions of C3+, C3H+ and C3H3+ with H2 and HD have been performed between 15 K and room temperature. These studies have been performed in a second apparatus, a variable-temperature 22-pole trap machine (VT-22PT). Results include reactive collisions, deuteration and radiative association. It is discussed in connection with the increase in lifetime of the C3+ + H2 collision complexes with falling temperature, what could be responsible for producing more C3H+ at 15 K. Tunneling is excluded. In C3+ + HD collisions an isotope effect has been detected, the C3D+ product ions being slightly more abundant than C3H+. Comparison of the reaction of C3H+ primary ions with HD and H2 gas revealed that the deuterated molecules are significantly more reactive. The process of radiative association of C3H+ and for the first time of C3+ with hydrogen molecules has been observed. An analysis of the data shows that radiative association becomes slower, if the neutral reactant is deuterated. Finally, the theoretical prediction from ab initio calculations that C3H3+ does not exchange an H for a D in collisions with HD, has been proven in an ion trap experiment. Careful analysis of all competing processes allows the conclusion that the rate coefficient is smaller than 4x10-16 cm3s-1 at 15 K
Unter Verwendung von zwei Speicherapparaturen wurden ausgewählte, astrophysikalische wichtige Ionen-Molekülreaktionen untersucht. Durch die Kombination einer Kohlenstoffquelle mit einem Ionenspeicher, in dem so Reaktionen zwischen Ionen und Kohlenstoffmolekülen oder -atomen untersucht werden können, wurde Neuland betreten. Es werden Ergebnisse vorgestellt für die Reaktion von D3+ Ionen, die in einem Ringelektrodenspeicher gefangen sind, mit einem Strahl von heißen Cn (n = 1, 2, 3). Die gemessenen Ratenkoeffizienten sind nur halb so groß wie die Werte, die in astrophysikalischen Modellen verwendet werden. Um die Kenntnis über alle möglichen Reaktionen, bei denen drei C-Atome beteiligt sind, abzurunden, wurden zwischen 15 K und Zimmertemperatur die Reaktionen zwischen C3+, C3H+ und C3H3+ Ionen mit H2 und HD in vielen Details untersucht. Diese Experimente wurden in einer zweiten Apparatur durchgeführt, in der ein temperaturvariabler 22-Polspeicher das zentrale Element ist (VT-22PT). Berichtet werden Ergebnisse zu reaktiven Stößen, zur Deuterierung von Kohlenwasserstoffen und zur Strahlungsassoziation. In der Diskussion bleibt offen, was - in Verbindung mit der von 300 K zu 15 K zunehmenden Lebensdauer - der Grund dafür sein kann, daß die Bildung des exothermen Produkts C3H+ anwächst. Der Tunneleffekt scheidet aus. Bei der Reaktion C3+ + HD wurde ein Isotopeneffekt beobachtet, das C3D+ Produkt wird etwas häufiger gebildet als C3H+. Ein Vergleich der Reaktion zwischen C3H+ Ionen mit HD bzw. H2 zeigt, daß das deuterierte Molekül wesentlich reaktiver ist. Es wurden Ratenkoeffizienten für die Strahlungsassoziation von H2 Molekülen mit C3H+ und erstmals mit C3+ Ionen gemessen. Die Auswertung der Daten zeigt, dass der Prozeß langsamer abläuft, wenn der neutrale Stoßpartner deuteriert ist. Schließlich wurde experimentell die theoretische Vorhersage überprüft, dass C3H3+ keinen H-D Austausch mit HD eingeht. Eine sorgfältige Analyse aller konkurrierenden Prozesse ergab, dass bei 15 K der Raten koeffizient kleiner als 4x10-16 cm3s-1 ist

The research presented in this thesis includes a detailed investigation into factors influencing ionic conductivity in the crystalline polymer electrolyte PEO₆:LiPF₆. It has previously been shown that preparing PEO₆:LiPF₆ with PEO modified with larger –OC₂H₅ end groups increases ionic conductivity by one order of magnitude [¹],primarily due to disruption of the crystal structure caused by the inclusion of the larger end groups. In this study it is shown that by reducing PEO molecular weight in crystalline PEO₆:LiPF₆ ionic conductivity is also increased. This was attributed to an increasing concentration of polymer chain end regions upon lowering molecular weight resulting in the creation of more defects, as well as possible increases in crystallite size resulting in longer continuous pathways for ion transport. Similar results were observed using both polydispersed and monodispersed PEO to prepare complexes. In addition, it is demonstrated here that ionic conductivity in crystalline polymerelectrolytes is not confined to PEO₆:LiXF₆ (X=P, As, Sb)[²][³] type materials. The structures and ionic conductivity data are reported for a series of new crystalline polymer complexes: the alkali metal electrolytes. They are composed of low molecular weight PEO and different alkali metal hexafluoro salts (Na⁺, K⁺ and Rb⁺), and include the best conductor poly(ethylene oxide)₈:NaAsF₆ discovered to date [⁴], with a conductivity 1.5 orders of magnitude higher than poly(ethylene oxide)₆:LiAsF₆. A new class of solid ion conductor is reported: the crystalline small-molecule electrolytes. Such materials consist of lithium salts dissolved in low molecular weight glyme molecules [CH₃O(CH₂CH₂O)[subscript(n)]CH₃, n=1-12], forming crystalline complexes [⁵][⁶]. These materials are soft solids unlike ceramic electrolytes and unlike polymer electrolytes they are highly crystalline, are of low molecular weight and have no polydispersity. By varying the number of repeat units in the glyme molecule, many complexes may be prepared with a wide variety of structures. Here, ionic conductivity and cation transference number (t₊) data for several such complexes is presented [⁷][⁸][⁹].These complexes have appreciable ionic conductivities for crystalline complexes and their t₊ values vary markedly depending on the glyme molecule utilized. The differences in t₊ values can be directly attributed to differences in their crystal structures. [¹] Staunton, E., Andreev, Y.G. & Bruce, P.G. Factors influencing the conductivity of crystalline polymer electrolytes. Faraday Discussions 134, 143-156 (2007). [²] Gadjourova, Z., Andreev, Y.G., Tunstall, D.P. & Bruce, P.G. Ionic conductivity in crystalline polymer electrolytes. Nature 412, 6846 (2001). [³] Stoeva, Z., Martin-Litas, I., Staunton, I., Andreev, Y.G. & Bruce, B.G. Ionic Conductivity in the Crystalline Polymer Electrolytes PEO₆:LiXF₆, X = P, As, Sb. J. Am. Chem. Soc. 125, 4619-4626(2003). [⁴] Zhang, C., Gamble, S., Ainsworth, D., Slawin, A.M.Z., Andreev, Y.G. & Bruce, P.G. Alkali metal crystalline polymer electrolytes. Nature Materials 8, 580-584 (2009). [⁵] Henderson, W.A., Brooks, N.R., Brennessel, W.W. & Young Jr, V.G. Triglyme-Li⁺ Cation Solvate Structures: Models for Amorphous Concentrated Liquid and Polymer Electrolytes (I). Chem. Mater. 15, 4679-4684 (2003). [⁶] Henderson, W.A., Brooks, N.R. & Young Jr, V.G. Tetraglyme-Li⁺ Cation Solvate Structures: Models for Amorphous Concentrated Liquid and Polymer Electrolytes (II). Chem. Mater. 15, 4685-4690 (2003). [⁷] Zhang, C., Andreev, Y.G. & Bruce, P.G. Crystalline small-molecule electrolytes. Angewandte Chemie, International Edition 46, 2848-2850 (2007). [⁸] Zhang, C., Ainsworth, D., Andreev, Y.G. & Bruce, P.G. Ionic Conductivity in the Solid Glyme Complexes [CH₃O(CH₂CH₂O)[subscript(n)]CH₃]:LiAsF₆ (n = 3,4). J. Am. Chem. Soc. 129, 8700- 8701 (2007). [⁹] Zhang, C., Lilley, S.J., Ainsworth, D., Staunton, E., Andreev, Y.G., Slawin, A.M.Z. & Bruce, P.G. Structure and Conductivity of Small-Molecule Electrolytes [CH₃O(CH₂CH₂O)[subscript(n)]CH₃]:LiAsF₆ (n = 8-12). Chem. Mater. 20, 4039-4044 (2008).

Firstly, a detailed study of the higher Rydberg states of C₆H₆ and C₆D₆ was performed using mass-resolved polarisation-dependent (2+1) REMPI spectroscopy. Three long series of gerade Rydberg states (two nd and possibly one ng) converging on the first ionisation energy, previously observed up to n=8, were extended up to n=30. By scanning the two-photon energy up to the ionisation limit, coherent two-photon ZEKE-PFI spectra of the ionic states of benzene-h₆ and -d₆ were obtained for the first time. The vibrational structure in the ZEKE spectrum is essentially the same as in the (2+1) REMPI spectra of Rydberg states but different from the (1+1') ZEKE spectrum reported previously. Substitution effects and the influence of lowering the symmetry on the Rydberg states were also investigated by comparing studies of C₆H₅F, C₆H₅Cl, p-C₆H₄F₂ and o-C₆H₄F₂ molecules. Second, the Rydberg and ionic states of CF₃I have been studied using both REMPI and zero kinetic energy pulse-field ionisation (ZEKE-PFI) photoelectron spectroscopy. The ground state of the ion was characterized using coherent two-photon (one-colour) ZEKE-PFI spectroscopy. The 6p Rydberg states were studied using two-photon REMPI spectroscopy with linear and circular polarised light. The strongest members with Ω=2 were identified and used as resonant intermediates in two-colour (2+1') ZEKE-PFI experiments, which allowed the unambiguous assignment of the majority of the vibrational structure of the intermediate states. Third, multiphoton pathways to the lowest cluster of ion-pair states of ICl and I₂, at energies close to the dissociation limit, are presented. These very high vibrational levels are detected in the anion (Cl^- and I^-) or cation (I⁺) channel by pulsed field ionisation. Using a variable time delay before field ionisation, ion pair states up to 50 cm^-1 below the dissociation limit are observed to survive for at least 2 μs, indicating a stabilisation process analogous to that operating in high Rydberg electronic states. The analogy between these stabilised ion-pair states and ZEKE (zero electron kinetic energy) states suggests calling them ZIKE (zero ion kinetic energy) states. The atomic ion yield signal is highly structured both above and below the free ion threshold, indicating the role of doorway states which are coupled to the dense ion-pair vibrational manifold near dissociation. This coupling appears to be very efficient and competes successfully with radiative decay and further up-pumping that would result in ionisation. One difference with ZEKE spectroscopy is that these initially prepared states have to undergo both an electronic transition as well as a large angular momentum change, in order to be stabilised. Fourth, molecular photofragment spectroscopy has been used to obtain new insight into the ultraviolet photodissociation of ozone. The formation of O₂(b¹Σ⁺_g) following absorption in the Huggins band (335-352 nm) of O₃ has been observed for the first time. The nascent O₂(b¹Σ⁺_g) photofragment was detected using two-colour resonance enhanced multiphoton ionisation (REMPI), and the 3sσ_g¹Π_g Rydberg state as the resonant intermediate state. Finally, a new VUV generation technique (laser induced plasma), which may be used for spectroscopic studies, has been characterised. Some preliminary results using this new VUV generation source for single photon ionisation and ion-pair production studies of polyatomic molecules (CH₃Br and CH₃I) have been obtained. In addition, high resolution ion-pair formation from CH₃Br using coherent VUV laser radiation generated by four wave mixing has been recorded in both CH₃⁺ and Br^- channels.

Electrochemical capacitors, now often termed supercapacitors, are high power electrochemical energy storage devices that complement or replace high power batteries in applications ranging from wind turbines to hybrid engines to uninterruptable power supplies to electronic devices. My dissertation explores the applications of relatively uncommon techniques for both supercapacitor material syntheses and gaining better mechanistic understanding of factors impacting electrochemical performance of supercapacitors. From fundamental ion electroadsorption studies made possible by using small angle neutron scattering (SANS), to the systematic investigations of coating thickness and microstructure in metal oxide / carbon nanocomposite electrodes realized through the novel use of the atomic layer deposition (ALD) technique, new avenues of material characterization and fabrication have been studied. In this dissertation I first present the motivation to expand the knowledge of supercapacitor science and technology, and follow with an in-depth literature review of the state of the art. The literature review covers different types of supercapacitors, the materials used in the construction of commercial and exploratory devices, an exploration of the numerous factors which affect supercapacitor performance, and an overview of relevant materials synthesis and characterization techniques The technical objectives for the work performed in this dissertation are then presented, followed by the contributions that I made in this field in my two primary research thrusts: advances to the understanding of ion electroadsorption theory in both aqueous and organic electrolytes through the development of a SANS-based methodology, and advances to metal-oxide carbon nanocomposites as electrodes through the use of ALD. The understanding of ion electro-adsorption on the surface of microporous (pores < 2 nm) solids is largely hindered by the lack of experimental techniques capable of identifying the sites of ion adsorption and the concentration of ions at the nanoscale. In the first research thrust of my dissertation, I harness the high penetrating power and sensitivity of neutron scattering to isotope substitution to directly observe changes in the ion concentration as a function of the applied potential and the pore size. I have conducted initial studies in selected aqueous and organic electrolytes and outlined the guidelines for conducting such experiments for the broad range of electrode-ions-solvent combinations. I unambiguously demonstrate that depending on the solvent properties and the solvent-pore wall interactions, either enhanced or reduced ion electro-adsorption may take place in sub-nanometer pores. More importantly, for the first time I demonstrate the route to identify the critical pore size below which either enhanced or reduced electrosorption of ions takes place. My studies experimentally demonstrate that poor electrolyte wetting in the smallest pores may indeed limit device performance. The proposed methodology opens new avenues for systematic in-situ studies of complex structure-property relationships governing adsorption of ions under applied potential, critical for rational optimization of device performance. In addition to enhancing our understanding of ion sorption, there is a critical need to develop novel supercapacitor electrode materials with improved high-energy and high-power characteristics. The formation of carbon-transition metal oxide nanocomposites may offer unique benefits for such applications. Broadly available transition metal oxides, such as vanadium oxide, offer high ion storage capabilities due to the broad range of their oxidation states, but suffer from high resistivities. Carbon nanomaterials, such as carbon nanotubes (CNT), in contrast are not capable to store high ion content, but offer high and readily accessible surface area and high electrical conductivity. In the second research thrust of my thesis, by exploiting the ability of atomic layer deposition (ALD) to produce uniform coatings of metal oxides on CNT electrodes, I demonstrated an effective way to produce high power supercapacitor electrodes with ultra-high energy capability. The electrodes I developed showed stable performance with excellent capacitance retention at high current densities and sweep rates. Electrochemical performance of the oxide layers were found to strongly depend on the coating thickness. Decreasing the vanadium oxide coating thickness to ~10 nm resulted in some of the highest values of capacitance reported to date (~1550 F·g⁻¹VOx at 1 A·g⁻¹ current density). Similar methodology was utilized for the deposition of thin vanadium oxide coatings on other substrates, such as aluminum (Al) nanowires. In this case the VOₓ coated Al nanowire electrodes with 30-50% of the pore volume available for electrolyte access show volumetric capacitance of 1390-1950 F cc⁻¹, which exceeds the volumetric capacitance of porous carbons and many carbon-metal oxide composites by more than an order of magnitude. These results indicated the importance of electrode uniformity and precise control over conformity and thickness for the optimization of supercapacitor electrodes.

Low-earth orbit (LEO) contains plasma which can impact satellite charging and radio frequency (RF) communications. Quantifying both the composition and movement of ions in LEO can improve efficiency of the forecasting models that predict the impact plasma will have on satellite communications and accuracy of global positioning satellite measurements. Two instruments known as the Retarding Potential Analyzer (RPA) and the Ion Drift Meter (IDM) have been used in tandem to measure ionospheric properties including ion temperature, velocity, and density. These instruments are costly and occupy large areas on a spacecraft. In recent years, space mission budgets have diminished. This change has driven innovation towards creating new instruments which are compatible with smaller and cheaper satellites yet still yield measurements of comparable quality. This thesis presents the design of a new instrument that encompasses the functionality of both the RPA and IDM, known as the Plasma Velocity Vector Instrument for Small Satellites (PVVISS). PVVISS has compact form factor and low power requirements, making it a viable option for smaller, low cost nano-satellite sized missions. Missions utilizing the PVVISS sensor will allow increased exploration of the ionospheric impact on satellite communications.

Small angle X-ray scattering (SAXS) has been widely used in polymer science to study the nano-scale morphology of various polymers. The data obtained from SAXS give information about sizes and shapes of macromolecules, characteristic distances of partially ordered materials, pore sizes, and so on. The understanding of these structural parameters is crucial in polymer science in that it will help to explain the origin of various properties of polymers, and guide design of future polymers with desired properties. We have been able to further develop the contrast variation method in SAXS to study the morphology of Nafion 117CS containing different alkali metal ions in solid state. Contrast variation allows one to manipulate scattering data to obtain desired morphological information. At room temperature, only the crystalline peak was found for Na⁺-form Nafion, while for Cs⁺-form Nafion only the ionic peak was observed. The utilization of one dimensional correlation function on different counterion forms of Nafion further demonstrates the necessity of contrast variation method in obtaining more detailed morphological information of Nafion. This separation of the ionic peak and the crystalline peak in Nafion provides a means to independently study the crystalline and ionic components without each other's effect, which could be further applied to other ionomer systems. We also designed time resolved SAXS experiments to study the morphological development during solution processing Nafion. As solvent was removed from Nafion dispersion through evaporation, solid-state morphological development occurred through a variety of processes including phase-inversion, aggregation of interacting species (e.g., ionic functionalities), and crystallization of backbone segments. To probe the real-time morphological development during membrane processing that accurately simulates industrial protocols, a unique sample cell has been constructed that allows for through-film synchrotron SAXS data acquisition during solvent evaporation and film formation. For the first time, this novel experiment allows for a complete analysis of structural evolution from solution/dispersion to solid-state film formation, and we were able to show that the crystallites within Nafion develop later than the formation of ionic domains, and they do not reside in the cylindrical particles, but are dispersed in solution/dispersion. Besides bulk morphology of Nafion, we have also performed Grazing Incident SAXS to study the surface morphology of Nafion. We were able to manipulate the surface morphology of Nafion via neutralizing H⁺-form Nafion with different large organic counterions, as well as annealing Nafion thin films under different temperatures. This not only allows to obtain more detailed information of the nano-structures in Nafion thin films, but also provides a means to achieve desired morphology for better fuel cell applications. We have also been able to study the polymer chain conformation in solution via measuring persistence length by utilizing solution SAXS. Different methods have been applied to study the SAXS profiles, and the measured persistence lengths for stilbene and styrenic alternating copolymers range from 2 to 6 nm, which characterizes these copolymers into a class of semi-rigid polymers. This study allows to elucidate the steric crowding effect on the chain stiffness of these polymers, which provides fundamental understanding of polymer chain behaviors in solution. Self-assembling in block copolymers has also been studied using SAXS. We established a morphological model for a multiblock copolymer used as a fuel cell material from General Motors®, and this morphological model could be used to explain the origins of the mechanical and transport properties of this material. Furthermore, several other block copolymers have been studied using SAXS, which showed interesting phase separated morphologies. These morphological data have been successfully applied to explain the origins of various properties of these block copolymers, which provide fundamental knowledge of structure-property relationship in block copolymers.
Ph. D.

This project investigated directed energy techniques for modifying organic films. These techniques show great promise for creating materials with unique, tailored properties. In this work, ion and electron beams were used to fabricate spatially-defined polymer features in nanometre-scale film of small molecules. An alternative pathway to the direct on-surface fabrication of polymer surface coatings was also investigated and showed that a room temperature, atmospheric pressure plasma can facilitate coupling of small molecules at a catalytic surface. In all cases, it was possible to control the optical properties, chemistry, solubility and hardness of the polymer films by varying the processing parameters.

Cette thèse a pour but l'étude de l’interaction des impulsions laser brèves et ultra-intenses avec des cibles de petite taille. Nous nous intéressons surtout des phénomènes liés à l’accélération des ions aux granges énergies. L'outil principal de cette étude est notre code Particle-in-Cell (PIC) bidimensionnel, qui est capable d'effectuer le calcul du mouvement des particules et de l'évolution des champs en régime relativiste et sans collisions. Ce mémoire présente la théorie de l’accélération d’ions par laser, les simulations numériques des différents régimes d'accélération, ainsi que les algorithmes mis en œuvre dans notre code. Les nouveaux résultats obtenus dans le cadre de cette thèse concernent trois cas principaux: 1) l’interaction des impulsions laser intenses avec des cibles de la masse limitée; 2) l’accélération des protons par laser dans des gouttelettes fines d’eau vaporisé; 3) le transport latéral des électrons chauds dans une feuille mince et son effet sur l’accélération d’ions. Nos études théoriques et les simulations numériques sont appliquées pour l'interprétation des résultats des deux expériences récentes réalisées par les équipes de recherche en Allemagne et en France. Ces expériences montrent une accélération efficace d’ions dans les conditions prévues dans nos travaux théoriques. Le spectre énergétique et le nombre des protons accélérés dans les feuilles minces de la surface limitée et dans les gouttelettes d’eau se comportent conformément aux nos prévisions. Le modèle théorique développé dans cette thèse considère l'accélération des ions en deux étapes. Le champ du laser n'interagit pas directement avec les ions du plasma du à sa masse très élevée. Par contre, les électrons chauds, générés pendant l’interaction de l'impulsion laser avec une cible, produisent les champs électrostatiques importants qui accélèrent les ions aux hautes énergies. Ces champs peuvent être amplifiés si la masse de la cible est suffisamment petite. Nous considérons que la cible a une masse limitée, si toutes ses dimensions sont comparables avec la taille du faisceau laser dans la zone d'interaction. Ces cibles permettent de réduire la dispersion des électrons chauds, et donc d'améliorer la transformation de l'énergie cinétique d'électrons dans l’´energie des ions. Nos simulations numériques indiquent que la taille de cible transverse optimale est égale au diamètre du faisceau laser. Les expériences récentes avec des feuilles minces de la surface limitée ont confirmé que la transformation de l’énergie laser `a l’énergie des ions est plus efficace, l’énergie des ions est plus élevée, et la divergence du faisceau d’ions diminue avec la diminution de la surface de feuille. La physique de l’interaction d'un faisceau laser avec les gouttelettes d’eau est plus complexe, car il faut prendre en compte plusieurs facteurs tels que l'ionisation inhomogène des atomes de la gouttelette et la recombinaison, sa position dans le focus de laser, les collisions des électrons etc. Nous avons modélisé l’interaction de l’impulsion laser avec une gouttelette de diamètre de 100 nm. Dans un petit agrégat des atomes irradié par laser, les électrons sont expulsés par la force pondéromotrice et, pas conséquent, les ions sont accélérés par la force de Coulomb. Nous avons réussi d'expliquer la formation d'un pic dans la fonction de distribution des protons en énergie par l'effet de la répulsion mutuelle entre deux espèces des ions. Finalement, nous avons étudié le transport latéral des électrons dans le cas de l'incidence rasante du faisceau laser sur la cible mince plaine. Avec une série des simulations nous avons démontré qui le transport des électrons accélérés est réalisé par deux mécanismes complémentaires: par le guidage des électrons chauds sur la surface d’avant de la feuille par les champs quasi statiques électrique et magnétique et par la recirculation des électrons entre les faces l'arrière et l'avant de la cible
The presented thesis is based on a theoretical study of the interaction of femtosecond laser pulses with small-size targets and related phenomena, mainly acceleration of ions. We have employed our relativistic collisionless two-dimensional particle-in-cell code to describe the interaction and subsequent ion acceleration. The theory of ion acceleration and related physics (for example, electron heating mechanisms) have been reviewed as well as computational algorithms used in our simulation code. In the thesis, our obtained results are organized into three main parts: 1) interaction of an intense laser pulse with mass-limited targets; 2) laser proton acceleration in a water spray target; 3) lateral hot electron transport and ion acceleration in thin foils. Our theoretical and numerical studies are accompanied with recent experimental results obtained by cooperating research groups on enhanced ion acceleration in thin foils of reduced surface and on proton acceleration in a cloud of water microdroplets. Since the field of nowadays operating lasers is not sufficient to accelerate directly ions to high energies due to their at least 1000 times larger mass-to-charge ratio compared with electrons, the ion acceleration is mediated by hot electrons creating strong electrostatic fields (a population of electrons heated by the laser wave) in targets of sizes higher or comparable with the laser wavelength or by Coulomb force between ions after electron expulsion in small clusters. Due to reduced target dimensions, the mass-limited targets, defined as the targets having all dimensions comparable with the laser spot size, limit the spread of hot electrons and, thus, the electron kinetic energy is transferred to ions more efficiently. We found via 2D PIC simulations that the optimum transverse target size is about the laser beam diameter. The enhancement of proton energy, laser-to-proton conversion efficiency, and narrower ion angular spread have been observed in recent experiments with thin foil sections and have confirmed our previous theoretical studies. The physics of the laser pulse interaction with water spray is rather complex and includes many phenomena (microdroplet ablation by laser prepulse, inhomogeneous droplet ionization, laser focal spot position in the spray, recombination and collisional effects in the surrounding target material, etc.). We have carried out numerical simulations of the laser pulse interaction with a water microdroplet of diameter of 100 nm, which gives an insight into the physics of ion acceleration in the spray. One can observe a pronounced peak in the proton energy spectra at the cutoff energy, which was explained by mutual interaction between protons and oxygen ions. Finally, we have studied two mechanisms of lateral electron transport in a thin foil - the first is due to hot electron guiding along the foil front surface by generated quasi-static electric and magnetic fields, and the second is caused by the hot electron recirculation (reversing of the normal component of electron velocity when the electron propagating through the foil starts to escape into vacuum, while the transverse velocity is largely unaltered). We found that only a small number of electrons can be guided along the foil surface for large incidence angles (60° and more) of the laser beam on the foil surface, whereas the majority of electrons is laterally transported towards foil edges due to the recirculation through the thin foil. However, electrons guided along the surface can be accelerated to several times higher energy than the recirculating electrons, which enhances the energy of accelerated ions from foil edges

Abstract Electron-ion coincidence spectroscopy has been used to study the fragmentation behaviour of small molecules in two distinct cases: to resolve the state specific fragmentation patterns of HgBr₂ and HgCl₂ subsequent to UV ionization, and to distinguish the dissociation behaviour of various chlorinated methanes (CH₃Cl, CH₂Cl₂, CHCl₃ and CCl₄) subsequent to X-ray irradiation. The mercury-compound work has revealed details on the electronic structure and dissociation dynamics of the valence states which were previously unknown. The study on the chlorinated methanes has found new details on the exact pathways of the appearance of a specific fragment and also investigates the speed of the dissociation in the four different chlorinated methane molecules. The results from the electron-ion coincidence spectroscopic experiments are presented and analysed together with theoretical and computational support.

Glycosaminoglycans (GAGs) are sulfated polysaccharides that mediate a variety of extracellular interactions. Heparan sulfate (HS) is one of the most prominent GAGs on human cell surfaces. Both endogenous proteins, such as growth factors, and exogenous proteins, such as pathogen surface proteins, recognize and bind GAGs to gain access to human cells. Oligosaccharides and other structural analogs of HS and GAGs have been evaluated for a variety of therapeutic targets including angiogenesis and infectious diseases. Development of compounds to block HS-protein interactions has primarily focused on optimizing the degree and orientation of anionic substituents on a scaffold, to mimic HS structure, but their utility is diminished by their large size and non-specific interactions with many proteins. To overcome these limitations, it has been demonstrated that replacing N-sulfo groups on heparin with non-anionic N-arylacyl groups increased affinity and selectivity for binding different heparin-binding proteins. However, the heparin-derived compounds in that work were heterogeneous polysaccharides. Strategies to obtain small, structurally-defined and lower charge ligands are needed to ultimately obtain specific bind-and-block antagonists of HS-binding proteins. This study addresses these challenges by synthesizing N-arylacyl O-sulfonated aminoglycosides as small molecule, structurally-defined ligands to identify novel structures that selectively bind to HS-binding proteins. This study details development of new HPLC and LC-MS methods to separate, characterize, and purify amphiphilic oligosaccharides. The development of these methods enabled the synthesis of a panel of N-arylacyl O-sulfonated aminoglycosides. The compounds in this panel were screened for affinity and selectivity in binding with HS-binding proteins. This work demonstrates for the first time the selective binding of small amphiphilic oligosaccharides with HS-binding proteins. Significantly, individual compounds demonstrate heparin-like affinity for binding with select HS-binding proteins. Structural differences between the N-arylacyl O-sulfonated aminoglycosides, including changing the aminoglycoside core or the structure of the N-arylacyl moiety, are shown to impart specificity for these compounds to selectively bind different HS-binding proteins.

The presented thesis investigates the transfer of drug molecules across interfaces that mimic biological membrane barriers. The permeability of drug molecules across biological membrane mimics has been investigated in a novel artificial membrane permeation assay configuration using an in situ time-dependent approach and reproducible rotation of the membrane. A method to determine the membrane permeability from the knowledge of measured permeability and the applied stirring rate is presented. The initial transient of the permeation response, previously not observed in situ, is investigated and its importance in data evaluation is discussed. The permeability coefficients of 31 drugs are optimised for the conditions found in vivo and a correlation with the fraction absorbed in humans is presented. The evidence for ionic and/or ion-pair flux across the artificial membrane obtained from measurement of permeability at different pH is supported by the investigation of the permeation assay with external membrane polarisation. The permeability coefficient of the solute's anionic form is determined. Liquid/liquid electrochemistry has been used to study the transfer of ionized species across the interface between water and 1,2-dichloroethane. An alternative method to study the transfer of partially ionised drug molecules employing a rotating liquid/liquid interface is presented. In addition, a bipolar electrochemical cell with a rotating-disc electrode is developed and its properties investigated in order to verify the hydrodynamics of the rotating artificial membrane configuration. Finally, in support of the electrochemical techniques used is this thesis, a detailed preparation and evaluation of the silver/silver sulphate reference electrode is presented.

This thesis extends the recently reported ground state sideband cooling of the axial motion of a single ion to a broader frequency range of the axial motion, the radial motion and ion crystals. Once cold, coherent control of these different configurations is demonstrated. The experimental work in this thesis uses 40Ca+ ions that can be coherently addressed on a narrow linewidth optical transition at 729 nm. The technique of axialization that resonantly couples the two radial modes of motion is used to enhance laser Doppler cooling leading to mean phonon occupation numbers in the low hundreds for both modes. The sideband cooling technique is then used to simultaneously cool both the motional modes to within one phonon of the ground state for the first time evers. Sideband cooling is then also employed to cool the axial modes of many ion Coulomb crystals in two different configurations. For two ions in a 1D chain, motional occupation numbers of nbar_COM=0.30(4) and nbar_B=0.07(3) are achieved. For two ions in a planar 2D configuration the result for the two modes are nbar_T=nbar_COM < 0.1. This technique is scaled up to demonstrate ground state occupation of up to 10 ions in the planar configuration. The axial mode of motion of a single motion is used to characterise the coherent addressing capabilities in our system through optical and motional Ramsey spectroscopy. We observe optical coherence times of 1.78(4) ms and motional coherence times of 590(12) ms. Dynamical decoupling techniques are shown to extend these coherence times. Furthermore, basic decoherence models are validated in high-lying non-thermal motional states that are prepared by a sideband heating technique. Progress towards entangling gates is demonstrated using a bichromatic laser beam to prepare non-classical states of motion.

The cation–π interaction has been long-established to play an important role in molecular recognition, supramolecular chemistry, and molecular biology. In contrast, its potential application in small-molecule catalysis, especially as a selectivity-determining factor in asymmetric synthesis has been overlooked until very recently. This dissertation begins with an extensive literature review on the state-of-the-art research on the application of cation–π interactions in non-enzymatic catalysis of organic and organometallic transformations. The research in this field has been largely inspired and guided by the related biosynthetic systems incorporating the same type of interactions.

Chemistry and Chemical Biology

This thesis describes initially the development of novel MeV ion micro-beam techniques. It then discusses their application to the measurement of the diffusion of small molecules in polymeric and biological matrices which hitherto were not possible. The matrices studied were skin tissue, human hair, polymeric cable insulation and hydrophilic polymers. The important novel aspects of the techniques are: Use of 3He scanning ion microbeam. Use of dual uncollimated charged particle detectors to measure induced nuclear reaction products. Use of a very thin window detector capable of detecting X-rays from elements heavier than beryllium. Fast freezing of samples with liquid nitrogen to freeze diffusion profiles and eliminate sample deformation. Use of a liquid nitrogen cooled target stage to both retain water and effectively eliminate beam heating effects when exposing samples to vacuum and the ion microbeam respectively.

The study of protein/peptide folding, misfolding, structure, and interactions are vital to understanding complex biological problems. The work presented in this thesis describes the development and application of mass spectrometry -based techniques to investigate protein structure, aggregation and interference with aggregation, providing insights into the self-assembly and inhibition of several disease-related peptides. Mass spectrometry has evolved significantly over the past decade, its applications varying from small molecules to macromolecules. Travelling wave ion mobility spectrometry (TWIMS), when combined with mass spectrometry (MS), has the unique and unrivalled capability of separating molecular ions based on their collision cross-sectional area in addition to their mass-to-charge ratio, thus facilitating structural studies of co-populated protein conformations and structural isomers of protein complexes that cannot be separated by molecular weight alone. One biological system that has benefitted enormously from such advances is the study of in vitro amyloid formation. The ability of amyloidogenic protein/peptides to assemble into insoluble fibrils is the basis of a vast array of human disorders. Human islet amyloid polypeptide (hIAPP) is one such peptide able to readily assemble into amyloid fibrils in vitro at neutral pH, despite being intrinsically disordered. Identifying oligomeric states occupied between monomer and final fibrils creates an enormous challenge, given that few techniques are able to separate and characterise such lowly-populated and transient species. In addition to characterisation of fibril precursors, recent research has focussed on the identification of small molecule inhibitors of the amyloid cascade and understanding their mechanism of action is of great interest to this field. In the work presented here, the power of TWIMS-MS has been harnessed to achieve the separation and characterisation of oligomeric precursors of the type-2 diabetes-related peptide hIAPP along with IAPP mutants and peptides corresponding to its core sequence. In addition, the effects of small molecule inhibitors on oligomer population and fibril formation have been studied and described in detail. Further, an experimentally simple, in vitro MS-based screen has been developed and implemented that provides rapid and accurate analysis of protein aggregation and its inhibition. All of the results highlight the powers of MS to provide important insights into the mechanism of amyloid formation and demonstrate the potential of this approach for screening for novel inhibitors of disease-related amyloid assembly.

In this work, the Collision Induced Dissociation under Energy Control method was extended to study the fragmentation of gas-phase biomolecules adenine (H5C5N5) and porphyrin FeTPPCl (C44H28N4FeCl). The population distribution for each dissociation channel has been experimentally determined as a function of the excitation energy of the parent molecular ions at a well-determined initial charge state. In collisions between Cl+ and adenine (Ade) at 3keV, the fragmentation pattern of Ade2+ is dominated by the loss of H2CN+ and the successive emission of HCN. The energy distribution of the parent dications confirms the successive emission dynamics. A specific decay channel is observed, i.e., the emission of a charged H2CN+ followed by the emission of HC2N2. In Kr8+-FeTPPCl collisions at 80keV, parent ions FeTPPCl1+,2+,3+ are observed, along with the corresponding decay patterns. It is found that in the first step the dominant low-energy-cost decay channel is the emission of Cl0 independent of the initial charge state of FeTPPClr+ (r=1-3). For the resulted dication FeTPP2+, the dominant fragmentation channel is the neutral evaporation; for the trication however, the dominant fragmentation channel is the asymmetrical fission. In the case of H+ and F+ impact at 3keV, due to the different reaction windows opened in the two collision systems, different fragmentation patterns are observed. Furthermore, nH2 loss processes are observed. Additionally, the production yield of the negative ion emerged in F2+-Ade collision at 30keV is measured to be about 1% using a new experimental approach.

A large scale automated test set was designed and built to address the varied accelerated life test requirements of the GaAs industry. GaAs low-noise/small-signal MESFETs with 1 x 300 micron gate peripheries and 3 different gate structures were subjected to a 1000 hour high temperature storage test: 1) to compare the reliability performance and manufacturability of a) recessed-gate MESFETs with TiPdAu gates b) realigned self-aligned gate (RSAG) MESFETs with TiWN_x Schottky and TiPdAu overlay c) planarized self-aligned gate (PSAG) MESFETs with TiWN_x Schottky and TiPdAu overlay. 2) to study the changes in I_dss, R_g, R_o, g_m, and V_p over time and their effects upon MAG (Maximum Available Gain). 3) to study failure criteria and their applicability toward accurate life predictions. The recessed-gate devices suffered from Au/GaAs channel interdiffusion resulting in substantial dc parameter degradation above 225°C with an activation energy of 1.7 eV. Although the most widely used device structure in the GaAs industry, its process is not conducive to parameter uniformity. The realigned self-aligned gate (RSAG) devices are an initial attempt at the fabrication of a self-aligned gate analog MESFET. They were found to exhibit excellent electrical characteristics, but their reliability performance was unpredictable due to the critical nature of the .5 micron TiPdAu gate overlay realignment to a 1 micron TiWN_x Schottky. Planarized self-aligned gate (PSAG) devices were found to be readily manufacturable and to exhibit excellent reliability. The use of a decrease in MAG was found to be a more meaningful failure criterion than a 20% change in I_dss, which is employed extensively in the literature.
Master of Science

Electrochemical methods have been used to study electron transfer reactions at the interface between an aqueous phase of less than 1 femto liters in volume and a bulk organic phase. The small aqueous phase is formed at the end of a slightly recessed platinum electrode. When a negative potential is applied between the Pt electrode and the aqueous phase, Ru(NH3)63+ in the aqueous phase could be reduced to Ru(NH3)62+. Because the volume of the aqueous phase is very small, the electrochemically formed Ru(NH3)62+ could instantly reach the interface between the aqueous phase and the organic phase which contains 7,7,8,8-Teteracyanoquinodimethane (TCNQ), and be oxidized to form Ru(NH3)63+ by giving electrons to TCNQ at the interface. Our results showed a positive shift in the E1/2 comparing the reaction undertaken in the recessed cavity and the bulk solution.

Le but du travail est d'étudier la structure supramoléculaire de mélanges de tensioactif hydrophile, n-octyl-beta-glucoside (C8G1), et d'un extractant d'ions métalliques hydrophobe, le tributyl-n-phosphate (TBP), en présence d'eau, d'huile et de sels. Les systèmes classiques d'extraction ionique (composés d'une phase aqueuse, d'huile et d'extractant dont le but est d'extraire un soluté de la phase polaire sont passés en revue. L'aspect colloïdal et les transitions de phases que l'on retrouve dans ces systèmes sont souvent décrits singulièrement. Nous avons transposé l'approche « diagramme de phases » issue de la physico-chimie des systèmes moléculaires organisés à ces systèmes d'extractant afin d'orienter globalement l'analyse de ces systèmes complexes. La discussion est basée sur des considérations géométriques. Un modèle thermodynamique a été développé en considérant les contraintes d'empilement des ces extractants dans le film moléculaire formant les micelles inverses d'extractant dans l'huile. Ce modèle a permis de prédire la solubilité de l'eau au sein de ces micelles inverses ainsi que leurs tailles obtenues expérimentalement. Dans une deuxième partie, le comportement physico-chimique des phases aqueuses et organiques composées respectivement d'eau/C8G1 et de TBP/huile/eau ont été étudiées, en s'intéressant particulièrement aux effets de sels, par des techniques de diffusion de rayons X aux petits angles, diffusion dynamique de la lumière et de spectroscopie UV-visible. Dans la dernière partie la description complète de la microémulsion en faisant varier la balance hydrophile-hydrophobe du mélange C8G1 et TBP a été obtenue en combinant des mesures de diffusion de neutrons aux petits angles et d'analyse chimique (Karl-Fischer, Carbone Organique Total, ICP-OES…). Le comportement co-surfactant du TBP a été déterminé par comparaison aux co-surfactants classiques que sont les n-alcools (4
The presented work describes the supramolecular structure of mixtures of a hydrophilic surfactant n-octyl-beta-glucoside (C8G1), and the hydrophobic metal ion extractant tributylphosphate (TBP) in n-dodecane/water as well as in the presence of salts.In the first part, basic solvent extraction system, composed of water, oil and extractant, will be introduced. The focus, however, lies on the extraction of multivalent metal ions from the aqueous phase. During this extraction process and in the following thermodynamic equilibrium, aggregation and phase transition in supramolecular assemblies occur, which are already described in literature. Notably, these reports rest on individual studies and specific conclusions, while a general concept is still missing. We therefore suggest the use of generalized phase diagrams to present the physico-chemical behaviour of (amphiphilic) extractant systems. These phase diagrams facilitated the development of a thermodynamic model based on molecular geometry and packing of the extractant molecules in the oil phase. As a result, we are now in the position to predict size and water content of extractant aggregates and, thus, verify the experimental results by calculation.Consequently, the second part presents a systematic study of the aqueous and organic phase of water/C8G1 and water/oil/TBP mixtures. The focus lies on understanding the interaction between metal ions and both amphiphilic molecules by means of small angle x-ray scattering (SAXS), dynamic light scattering (DLS) and UV-Vis spectroscopy. We confirmed the assumption that extraction of metal ions is driven by TBP, while C8G1 remains passive. In the third and last part, microemulsions of C8G1, TBP, water (and salt) and n-dodecane are characterized by small angle neutron scattering (SANS), and chemical analytics (Karl Fischer, total organic carbon, ICP-OES,...). The co-surfactant behaviour of TBP was highlighted by comparison to the classical n-alcohol (4

Naturally Enhanced Ion Acoustic Lines (NEIALs) are enhancements (often over an order of magnitude in power) observed in ion line spectra in incoherent scatter radar data. To date, there has been no conclusive evidence supporting a single production process which explains all observations of NEIALs. A specially designed interferometric radar system has been used to determine the field line height distribution and field line footpoint of observed NEIALs. This system is the EISCAT Svalbard Radar Aperture Synthesis Imaging experiment, known as EASI. Optical observations were taken with the co-located Auroral Structures and Kinetics facility to compare NEIAL positions to locations of optical phenomena. Results show that the production theories of ‘beam-driven Langmuir waves’ and ‘solitary kinetic Alfv´en waves’ (SKAW) outlined in this thesis, consistently describe observed phenomena during two separate intervals. During the first interval on the 24 January 2012, the ‘non-resonant’ regime of ‘beam-driven Langmuir waves’ dominated, with the ‘resonant’ regime occurring infrequently, throughout approximately half of the interval. The remaining enhancements were only possible through SKAW or other wave interactions. Observations from the second interval on the 27 March 2012 agree best with the ‘resonant’ regime of the Langmuir wave theory. However, a number of time steps may have been enhanced by other production mechanisms, most likely SKAW. Radar-derived parameter analysis of these and four other NEIAL intervals in past data was also undertaken. The results showed the existence of ‘weak’ NEIALs at times surrounding ‘strong’ NEIAL enhancements. Other than the two aforementioned theories, the majority of others were eliminated independently for all six time intervals using this method.

Neurons in poikilotherms must operate over the animal's natural temperature range if they are to survive. The effects of temperature on various cellular processes can vary dramatically, which suggests that it may be difficult to design a circuit that behaves consistently over a temperature range. Previous work in the crab Cancer borealis (Tang et al., 2010, 2012) showed that the pyloric rhythm of the stomatogastric ganglion (STG) maintains its bursting duty cycle and phase relationships over a temperature range of 7 to 23 °C. Rinberg et al., 2013 also observed this phase invariance over a temperature range in the three cell pyloric pacemaker kernel.

To explore the effects of temperature on this system, we implemented a computational model of the STG pacemaker kernel (Soto-Treviño et al., 2005), that simulates two electrically coupled cells and includes temperature dependences, represented as Q10's. Separate Q10's were assigned for maximal conductance, rate of activation and inactivation. We also assigned a Q10 for the buffering rate of intracellular Ca2+. All Q10's were selected randomly from 1 to 4, except the maximal conductance Q10's that were set to 1.6. Maximal conductance values at the reference temperature of 11 °C were initially set to the values selected by Soto-Treviño et al., 2005. Each model was run over a range of 7 to 23 °C.

While some Q10 values, such as those for mKCa, mKd and Ca2+ buffering are critical for appropriate temperature scaling, the system is only moderately sensitive to others such as hNa, CaT and CaS and largely insensitive to Q10 values for slower conductances such as A, Nap, IMI and leak.

Overall, we find that robust neuronal behavior can be achieved over a temperature range within a subset of Q10-space. Within our model, certain Q10's are tightly constrained while others can be chosen over a relatively wide range. This provides insight into the relative contribution of different ionic conductances to high-level neuronal dynamics.

Computational methods, including homology modelling, in-silico dockings, and molecular dynamics simulations have been used to study the functional dynamics and interactions of K⁺ channels. Molecular models were built of the inwardly rectifying K⁺ channel Kir2.2, the bacterial homolog K⁺ channel KirBac3.1, and the twin pore (K2P) K⁺ channels TREK-1 and TRESK. To investigate the electrostatic energy profile of K⁺ permeating through these homology models, continuum electrostatic calculations were performed. The primary mechanism of KirBac3.1 gating is believed to involve an opening at the helix bundle crossing (HBC). However, simulations of Kir channels have not yet revealed opening at the HBC. Here, in simulations of the new KirBac3.1-S129R X-ray crystal structure, in which the HBC was trapped open by the S129R mutation in the inner pore-lining helix (TM2), the HBC was found to exhibit considerable mobility. In a simulation of the new KirBac3.1-S129R-S205L double mutant structure, if the S129R and the S205L mutations were converted back to the wild-type serine, the HBC would close faster than in the simulations of the KirBac3.1-S129R single mutant structure. The double mutant structure KirBac3.1-S129R-S205L therefore likely represents a higher-energy state than the single mutant KirBac3.1-S129R structure, and these simulations indicate a staged pathway of gating in KirBac channels. Molecular modelling and MD simulations of the Kir2.2 channel structure demonstrated that the HBC would tend to open if the C-linker between the transmembrane and cytoplasmic domain was modelled helical. The electrostatic energy barrier for K⁺ permeation at the helix bundle crossing was found to be sensitive to subtle structural changes in the C-linker. Charge neutralization or charge reversal of the PIP2-binding residue R186 on the C-linker decreased the electrostatic barrier for K⁺ permeation through the HBC, suggesting an electrostatic contribution to the PIP2-dependent gating mechanism. Multi-scale simulations determined the PIP2 binding site in Kir2.2, in good agreement with crystallographic predictions. A TREK-1 homology model was built, based on the TRAAK structure. Two PIP2 binding sites were found in this TREK-1 model, at the C-terminal end, in line with existing functional data, and between transmembrane helices TM2 and TM3. The TM2-TM3 site is in reasonably good agreement with electron density attributed to an acyl tail in a recently deposited TREK-2 structure.

Doutoramento em Engenharia Química
Among various methods for the separation of hydrogen containing mixtures, membrane technology has received special attention due to its simplicity of operation, moderate energy consumption, cost effectiveness, it is environmentally friendly and can be easily coupled with other separation methods. In particular, inorganic membranes exhibit relevant advantages such as high thermal, chemical and mechanical stabilities, minor plasticization and better control of pore size distribution. They can be divided into five main families: metallic and ceramic proton conducting membranes (dense phases), and silica, zeolite and carbon molecular sieve membranes (porous materials). With more than 200 framework types, zeolites possess uniform molecular pore dimensions and unique properties for catalytic, ion exchange, adsorption and membrane applications. This thesis is essentially devoted to zeolite (titanosilicate) membranes for hydrogen and light gases separation. Titanosilicates offer important benefits over the remaining zeolites: they are usually synthesized without organic templates, can be prepared under moderate pH conditions, exhibit novel possibilities of isomorphous framework substitution, and generally offer strong alkalinity. The main objectives of this dissertation were: (i) synthesis and characterization of titanosilicate membranes. The materials structure and morphology were examined by X-ray diffraction (XRD) and scanning electron microscopy with energy dispersive X-ray spectroscopy (SEM/EDS); the dynamic characterization of membranes was accomplished by permeation assays with pure gases; (ii) deep analysis of experimental results, with the objective to disclose the mass transport mechanisms that prevail in the membrane; (iii) accurate modeling of permeation data using theoretically sound approaches like the generalized Maxwell-Stefan (MS) formalism; (iv) development of new MS thermodynamic factors to represent the surface diffusion of pure and multicomponent gases through microporous membranes. Here, several important (though less studied) isotherms were tested, the influence of the solid loading upon surface diffusivity was deeply evaluated, and the predictive ability of the whole model was validated. The hydrothermal synthesis and characterization of AM-2 and AM-3 powder and supported membranes have been performed. Altogether, ca. thirty and more than one hundred syntheses of AM-2 and AM-3 powder, respectively, have been accomplished, and eight AM-2 and twenty AM-3 membranes have been prepared on tubular -alumina and stainless-steel supports by seeding and secondary growth. All powders were characterized by XRD and/or SEM, and three AM-2 and seven AM-3 membranes were dynamically tested. The permeation of pure gases at programmed temperature and fixed transmembrane pressure drop ( P) was carried out in order to evaluate the membranes quality and identify the governing transport mechanisms (e.g. viscous flow, Knudsen regime, surface diffusion, activated gaseous diffusion). Additionally, more than one hundred permeance measurements were conducted at various temperatures and pressures using different gases (H2, He, N2, O2 and CO2). The best AM-3 membrane was studied in detail at P=0.5, 1.0 and 1.5 bar, at fixed and programmed temperatures between 304 and 394 K, using H2, He, N2, O2 and CO2. The results provided selectivities towards hydrogen up to 3.5, and disclosed in all cases an activated behavior typical of surface diffusion, a small contribution of viscous flow due to macro-defects, and a minor contribution of Knudsen mechanism due to meso-defects. The gas permeation was accurately modeled using Maxwell-Stefan theory, achieving an average deviation of only 3.42 % for all molecules. The rigorous MS thermodynamic factors of various relevant isotherms – Toth, Dubinin-Astakhov (DA) and Dubinin-Radushkevich (DR) – were derived in this work for the first time, with the objective to model the permeation of pure and mixed gases through zeolite membranes. The DA and DR isotherms received special attention, taking into account they are often adopted to represent the adsorption equilibrium of most industrial adsorbents that possess a welldeveloped porous structure, especially of carbonaceous origin. The MS factors for DA and DR isotherms were validated using equilibrium and flux data for methane/silicalite-1, ethane/silicalite-1 and (methane,ethane)/ silicalite-1 systems according to the following procedure: (i) the unary isotherms were fitted to the corresponding data, while their binary expressions were predicted from the previous ones; (ii) the influence of surface loading upon methane and ethane diffusivities was carefully assessed; (iii) the MS diffusion parameters of each gas were obtained from unary permeation data; (iv) the MS counter-sorption diffusivities were then predicted using the Vignes correlation; (v) the separation of methane/ethane mixtures using the silicalite-1 membrane was totally predicted using the new MS thermodynamic factors combined with the binary isotherms. The results demonstrated the validity of this approach, particularly if DA isotherm is selected. Besides the main focus of this PhD on membranes, ion exchange experiments and modeling were also included. The removal of ionic contaminants (Cd2+ and Hg2+) from aqueous solutions was studied using synthesized stannosilicate AV- 6 and titanosilicate ETS-4. In the case of the Cd2+/K+/AV-6 system, the kinetic removal was modeled with Maxwell-Stefan (MS) and Nernst-Plank (NP) equations, while equilibrium was modeled with mass action law and activity coefficients in both solution (Debye-Hu ckel and Pitzer models) and exchanger (Wilson model) phases. The experimental data proved the ion exchange ability of AV-6 to sorb cadmium(II), and excellent results were achieved for the equilibrium isotherm (deviations around 6.6 %) and kinetic modeling (MS, 3.74 %; NP, 3.71 %). It was shown that the solid phase is clearly non-ideal. The investigation of the ternary system (Cd2+,Hg2+)/Na+/ETS-4 confirmed the large capacity of ETS-4 (5.44 meq g-1) and its selectivity towards both toxic metals, particularly Cd2+. However, the trends of the ion exchange kinetics were very distinct, because the internal diffusivity of cadmium(II) is higher than that of mercury(II). These results are in accordance with the effective ionic radius of both species, namely, 102 pm for Hg2+ and only 95 for Cd2+.
Entre diversos métodos de separação de misturas gasosas contendo hidrogénio, os processos membranares têm recebido uma atenção especial devido à sua simplicidade de operação, consumo moderado de energia, boa relação custo-eficiência, vantagens para o meio ambiente, e podem ser facilmente combinados com outros métodos de separação. Em particular, as membranas inorgânicas exibem vantagens relevantes, podendo citar-se as estabilidades térmica, química e mecânica elevadas, plasticização reduzida e um melhor controlo da distribuição do tamanho dos poros. Estas podem ser divididas em cinco famílias principais: metálicas e cerâmicas densas (membranas densas); e de sílica, zeolíticas e de peneiro molecular de carbono (membranas porosas). Com mais de 200 estruturas, os zeólitos possuem poros uniformes de dimensão molecular e propriedades únicas para aplicações catalíticas, de permuta iónica, de adsorção e membranares. Esta dissertação dedica-se fundamentalmente a membranas zeolíticas (titanossilicatos) para a separação de hidrogénio e gases leves. Os titanossilicatos oferecem vantagens importantes em relação aos restantes zeólitos: são geralmente sintetizados sem agentes orgânicos estruturantes e sob condições moderadas de pH, exibem novas possibilidades de substituição isomórfica da matriz, e oferecem geralmente uma forte alcalinidade. Os objetivos principais desta dissertação foram: (i) síntese e caracterização de membranas de titanossilicatos. A estrutura dos materiais e a sua morfologia foram examinadas por difração de raios-X (DRX) e microscopia eletrónica de varrimento acoplada a espectroscopia de energia dispersiva de raios-X (SEM/EDS). A caracterização dinâmica das membranas foi efetuada com ensaios de permeação utilizando gases puros; (ii) análise aprofundada dos resultados experimentais, com o objetivo de compreender os mecanismos de transporte de massa que prevalecem na membrana; (iii) modelação rigorosa dos dados de permeação, seguindo abordagens como o formalismo de Maxwell-Stefan (MS); (iv) derivação de novos fatores termodinâmicos de MS para representar a difusão superficial de gases puros e misturas através de membranas microporosas. Foram investigadas isotérmicas importantes, (mesmo que pouco utilizadas na literatura), a dependência da difusividade superficial com a concentração no sólido, e a capacidade preditiva de todo o modelo. A síntese hidrotérmica e a caracterização dos titanossilicatos AM-2 e AM-3 foram efetuadas com o material na forma de pó e suportado em membranas. Realizaram-se cerca de trinta sínteses de cristais de AM-2 e mais de uma centena de AM-3, para além de oito membranas de AM-2 e vinte membranas de AM-3 suportadas em tubos de -alumina e de aço inoxidável, recorrendo ao método do crescimento secundário. Todos os cristais obtidos foram caracterizados por DRX e/ou S SEM, e testaram-se dinamicamente três SEM membranas de AM-2 e sete membranas de AM-3. A permeação de gases puros a temperatura programada e a pressão transmembranar fixa ( P) foi realizada com o objetivo de avaliar a qualidade das membranas e identificar os mecanismos de transporte envolvidos (fluxo viscoso, regime de Knudsen, difusão superficial, difusão gasosa ativada). Foram concluídas mais de uma centena de medições de permeação a várias temperaturas e pressões usando gases diferentes (H2, He, N2, O2 e CO2). A melhor membrana de AM-3 foi estudada em detalhe para P = 0,5, 1,0 e 1,5 bar, a temperatura fixa e a temperatura programada entre 304 e 394 K, usando H2, He, N2, O2 e CO2. Os resultados obtidos evidenciaram seletividades para o hidrogénio até 3,5, comportamento ativado típico de difusão superficial em todos os casos, uma pequena contribuição de fluxo viscoso devido a macrodefeitos e uma contribuição residual do mecanismo de Knudsen atribuível a meso-defeitos. A permeação gasosa foi modelada rigorosamente usando o formalismo de Maxwell-Stefan, apresentando um desvio médio de apenas 3,42% para todas as moléculas simultaneamente. Os fatores termodinâmicos de MS para as isotérmicas de Toth, Dubinin- Astakhov (DA) e Dubinin-Radushkevich (DR) foram derivados neste trabalho, com o objetivo de modelar a permeação de gases puros e misturas através de membranas zeolíticas. As isotérmicas de DA e DR receberam uma atenção especial, tendo em conta que são frequentemente adotadas para representar o equilíbrio de adsorção da maioria dos adsorventes industriais que têm uma estrutura porosa bem definida, especialmente com origem carbonácea. Os fatores de Maxwell-Stefan para DA e DR foram validados com dados experimentais de equilíbrio e de fluxo dos sistemas metano/silicalite-1, etano/silicalite-1 e (metano,etano)/silicalite-1 de acordo com o seguinte procedimento: (i) os parâmetros das isotérmicas dos gases puros foram ajustados aos dados correspondentes, e as isotérmicas binárias foram previstas a partir das anteriores; (ii) a influência da concentração do sólido sobre as difusividades superficiais do metano e do etano foi analisada cuidadosamente; (iii) os parâmetros de difusão de MS de cada gás foram obtidos a partir dos dados de permeação mono-componente; (iv) os coeficientes de difusão multicomponente de MS foram estimados com a correlação de Vignes; (v) a separação de misturas metano/etano usando uma membrana de silicalite-1 foi totalmente prevista com recurso aos novos fatores termodinâmicos de MS combinados com as isotérmicas binárias. Os resultados comprovaram a validade desta abordagem, especialmente no caso da isotérmica de DA. Apesar de a área principal deste doutoramento estar relacionada com membranas, foram incluídas experiências de permuta iónica e sua modelação. A remoção de contaminantes tóxicos (Cd2+ e Hg2+) de soluções aquosas foi estudada usando o estanhossilicato AV-6 e o titanossilicato ETS-4. No caso do sistema Cd2+/K+/AV-6, a cinética de remoção foi modelada com as equações de Maxwell-Stefan (MS) e de Nernst-Plank (NP), enquanto o equilíbrio foi modelado com a lei da ação das massas expressa em atividades, usando-se coeficientes de atividade na solução (modelos de Debye-Hückel e Pitzer) e no permutador (modelo de Wilson). Os dados experimentais evidenciaram a capacidade de permuta do AV-6 para sorver cádmio(II) e obtiveram-se resultados excelentes para a isotérmica de equilíbrio (desvios de 6,6 %) e para a modelação cinética (MS = 3,74 %; NP = 3,71%). Ficou ainda demonstrado que a fase sólida é claramente não-ideal. A investigação do sistema ternário (Cd2+,Hg2+)/Na+/ETS-4 confirmou a elevada capacidade do ETS-4 (5,44 meq g-1) e a sua seletividade para os dois metais tóxicos, particularmente para o Cd2+. Contudo, o comportamento das cinéticas de permuta iónica foi muito distinto, uma vez que a difusividade interna do cádmio(II) é superior à do mercúrio(II). Estes resultados estão de acordo com o raio iónico efetivo de ambas as espécies, ou seja, 102 pm para o Hg2+ e apenas 95 pm para o Cd2+.

The research presented in this thesis started with the idea to study alcohols as modifiers and dopants in differential ion mobility spectrometry (d-IMS) to produce complicated chemical signatures to explore a concept of chemical labels for product security application. D-IMS is a gas phase atmospheric pressure separation and detection technique which distinguishes compounds based on differences in their ions mobility as their travel under a low and high electric field. The hypothesis was that alcohols will form typical d-IMS products such as protonated monomers and proton bound cluster ions. However, the very first experiments revealed unexpected phenomena which included changes in the mobility of ions over a narrow range of concentrations that could not be explained by existing theory. Another observation was the apparent regeneration of reactant ions. It became evident that the observed phenomena had not been described in the open literature and that addressing the research-questions that were being raised would be essential for the determination of alcohols by d-IMS and its use in medical applications for toxicity screening and monitoring of alcohols. The above discovery shifted the research objective towards a fundamental and comprehensive study on the behaviour of alcohols in d-IMS. This thesis describes designed experiments and constructed systems allowing the efficient study of effect of concentration, electric field and temperature on the d-IMS responses of alcohols. The results of those studies demonstate: extensive fragmentation of alcohols, including previously undescribed fragmentation patterns with regeneration of the hydrated proton; new phenomena of adduct ion formation within the d-IMS drift tube, observed in the case of methanol within a narrow range of concentration; and self-modification of the alpha function of alcohols. This knowledge was exploited by developing an non-invasive analytical method for recovery, separation and detection of toxins from human saliva (including alcohols, diols and GHB) using TD-GC-d-IMS (thermal desorption - gas chromatography d-IMS) within a full range of toxicological concentration levels.

The aim of this semester project is the introduction to the problematic of ion fields, where and under what circumstances they originate and extinct and the techniques of measurement. The project will deal with the atmosphere and the electrical field of the Earth. I will consider the composition of the atmosphere and the principles of origin and extinction of ions. I am going to mention the division of ions and their influence on the living organisms. Another topic to be dealt with is the methods for measuring the air ions and the small currents. Gradually we are going to learn the known methods of the measuring of air ions. We are going to get a closer look at the method of measuring with the cylindrical aspiration capacitor. We are also going to deal with the problem of measuring very low currents, where they originate and how it is possible to compensate them. The outcome of the project should be the concept and later the creation of the sonde for the measuring of the ion fields itself.

Neste trabalho foram realizadas, no Laboratório Pelletron do Instituto de Física da Universidade de São Paulo, medidas de coincidência entre partículas com momentos relativos pequenos para os sistemas 160+10B e 160+ 12C nas energias de 62,5 e 64,0 MeV, respectivamente. Para isso, foi utilizado um hodoscópio composto de 14 telescópios do tipo E-E, capazes de medir a energia tanto de partículas pesadas (Z>2) como leves (Z2). A partir dessas medidas foram obtidos espectros de diferença dos módulos das velocidades (vdif) e funções correlação em momento relativo (prel) para vários pa res de partículas. A análise do espectro de vdif permite determinar a proporção relativa entre as duas seqüências de emissão possíveis para um dado par de partículas. A região da anticorrelação na função correlação permite obter informações sobre a escala temporal referente ao intervalo de tempo entre a emissão da primeira e da segunda partícula. Para o ajuste tanto do espectro de vdif como da função correlação foi utilizado um programa que simula a emissão sequencial de duas partículas a partir de um núcleo composto, no qual a fração das sequências de emissão e a escala temporal são parâmetros ajustáveis. Correlações envolvendo somente partículas leves forneceram resultados para as escalas temporais da ordem de 10-20 s a 10-19 s, compatíveis com evaporação sequencial de um núcleo composto. Correlações envolvendo partículas leves e pesadas forneceram escalas temporais da ordem de 10-20s compatíveis com a fissão de núcleos residuais após a emissão de uma partícula leve.
Particle-particle correlation measurements at small relative momenta for the 160+10B and 160+ 12C systems at Elab = 62.5 and 64 MeV, respectively, were performed at the University of São Paulo - Pelletron Laboratory. The experimental setup consisted of a hodoscope composed by fourteen triple telescopes which provide the energy for both light (Z 2 ) and heavy (Z>2) particles. Velocity difference (vdifl) spectra a nd correlation functions at small relative momenta were obtained for many particle pairs. The velocity difference spectrum provides information about the emission order for the particles. The anticorrelation region in the correlation function provides information about the time between the first and second emission. A simulation code that calculates sequencial emission from a compound nucleus and for which the emission order and time scale are parameters was used to fit both the vdiff spectrum and the correlation function. The time scales obtained for light particle correlations are between 10-20 and 10-19 s and they are in agreement with predictions for the evaporation of compound nuclei. Correlations between light and heavy particles give time scales of about 10 -20 which are compatible with fission of the residual nuclei after a light particle emission.

Nous avons étudié les propriétés volumiques de copolymères diblocs neutres-chargés dissymétriques. Ces molécules sont composées d'une courte partie neutre de poly(éthylène propylène) (PEP) ou de poly(tert-butyl styrène) (PtBs), et d'une longue partie chargée (polyélectrolyte) poly(styrène sulfonate) sodium (PSSNa) de taux de sulfonation supérieur à 80. Des expériences de diffusion de neutrons aux petits angles et de diffusion quasi-élastique de la lumière ont montré que ces copolymères s'auto-assemblent en solution aqueuse en micelles sphériques : coeur composé de l'auto-association des parties neutres en mauvais solvant, duquel émergent les parties chargées en une grande couronne qui peut être vue comme une brosse polyélectrolyte en géométrie sphérique. La forme et la taille des coeurs hydrophobes ont été trouvées invariantes en fonction de la concentration en polymère et de la concentration en électrolyte ajouté (sel monovalent, NaCl). Cette invariance a permis de déterminer les facteurs de structure des solutions (images des interactions) : les interactions électrostatiques ordonnent les solutions même dans le régime dilué (régime sans contact entre micelles). Dans le régime dilué sans sel ajouté, les parties polyélectrolytes (composant la couronne micellaire) ont été trouvées avec une conformation étendue (quasi-bâtons). Avec du sel ajouté, cette conformation devient de plus en plus flexible dès que la concentration en sel est supérieure à la concentration interne en sel d'une micelle. Dans le régime concentré sans sel ajouté, l'apparition d'un pic polyélectrolyte aux petites échelles, typique de la formation d'un semi dilué de polyélectrolytes, a été mise en évidence. De manière surprenante, cet ordre polyélectrolyte coexiste avec l'ordre entre micelles. L'influence du nombre de chaîne par micelle (nombre d'agrégation) a été discutée. Avec du sel ajouté, le pic polyélectrolyte disparaît, tandis que les solutions restent ordonnées. La distribution des contre-ions a été étudiée par des expériences de diffusion de rayons x aux petits angles. Les contre-ions Na+ ont été remplacés par d'autres contre-ions (typiquement Cs+ et TMA+) par dialyse des solutions. Dans le cas des micelles de faible nombre d'agrégation, la distribution des contre-ions a été trouvée en accord avec la distribution donnée par l'équation de Poisson-Bolztmann autour d'un bâton. Dans le cas des micelles de grand nombre d'agrégation, une forte corrélation entre contre-ions, due au recouvrement des différents nuages, a été mise en évidence. Enfin, la concentration micellaire critique (concentration à partir de laquelle des micelles existent) et l'équilibre des solutions ont été étudiés par électrophorèse capillaire. Les résultats ne sont pas encore bien compris : il existe, quelle que soit la concentration en polymère, 20% de chaînes libres (non associées en micelles).