Orientador: Gilberto De Nucci / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas / Made available in DSpace on 2018-08-07T21:47:07Z (GMT). No. of bitstreams: 1 Ilha_JaimedeOliveira_D.pdf: 2018294 bytes, checksum: fc9af33a98eb54d6384725e7874b1b46 (MD5) Previous issue date: 2006 / Resumo: O desenvolvimento de técnicas de ionização à pressão atmosférica foi de fundamental importância para que a cromatografia líquida de alta eficiência associada à espectrometria de massas se transformasse em uma solução de rotina, possibilitando o desenvolvimento de métodos quantitativos robustos, com elevado desempenho e alta sensibilidade e especificidade. Neste contexto, o recente desenvolvimento da técnica de fotoionização à pressão atmosférica é de particular interesse, já que é capaz ionizar uma série de substâncias farmacologicamente ativas dificilmente contempladas pelas técnicas anteriores, como, por exemplo, esteróides e outros compostos não polares. Todavia, sobretudo em nosso meio, ainda são poucos os trabalhos que apresentam métodos desenvolvidos para a quantificação de drogas em estudos farmacocinéticos com o emprego dessa técnica. Inserido nesse contexto, este trabalho tem como objetivo o desenvolvimento e avaliação de métodos para a quantificação de drogas em estudos farmacocinéticos utilizando a técnica de fotoionização, tendo como objeto de estudo o anastrozol e as di-hidropiridinas. As avaliações incluíram, entre outras, comparações entre métodos de ionização e estudo da influência do tipo de dopante utilizado. A partir das referidas avaliações e da experiência adquirida com o desenvolvimento de diferentes métodos analíticos, considera-se que esta interface tem o potencial de proporcionar um desempenho igualmente satisfatório quando empregada na avaliação de moléculas passíveis de análise pela aplicação dos métodos de ionização tradicionais, como é o caso da eletronebulização. Para moléculas de pequena afinidade a prótons, a introdução do anisol como substância dopante permitiu que fosse atingida uma eficiência de 10 a 100 vezes maior no processo de ionização dessas substâncias. A utilização de acetona ou anisol, adicionada diretamente à fase móvel, demonstrou ser também uma abordagem interessante, já que diminui o número de equipamentos envolvidos no processo e simplifica a operação diária, além de garantir que a razão entre o fluxo do dopante e do eluente seja constante, o que é importante para reduzir a variabilidade da eficiência de ionização. Verificou-se também que tal abordagem não traz prejuízos à coluna cromatográfica. Os métodos desenvolvidos com o emprego desta interface demonstraram ser adequadamente sensíveis, específicos, precisos e exatos, atendendo assim aos quesitos de validação de métodos bioanalíticos para quantificação de fármacos em matrizes biológicas. Por fim, ao possibilitar a análise de novos compostos, assim como aumentar a sensibilidade dos métodos bioanalíticos em função da maior eficiência de ionização, esta técnica traz uma contribuição importante para a quantificação de fármacos e, em particular, para a realização de estudos de biodisponibilidade relativa / Abstract: The development of atmospheric pressure ionization techniques has been of utmost importance to turn high performance liquid chromatography coupled to mass spectrometry into a routine solution, enabling the development of robust, high performance, high sensitivity and specific quantitative methods. In this sense, the recent development of the atmospheric pressure photoionization technique is specially interesting, as it is making possible the ionization of a group active pharmacological entities hardly addressed by the traditional techniques, as is the case of steroid and other non polar compounds. However, especially in our region, there are only few organizations developing methods for drug quantification in pharmacokinetic studies by means of this technique. Within this setting, the present work aims at the development and evaluation of drug quantification methods for pharmacokinetic studies using photoionization, having anastrozole and dihydropyridine drugs as case studies. Tests performed have included, among others, the comparison of ionization methods and the evaluation of the influence of the dopant selected. Taking into account the evaluations and the acquired experience with the development of distinct analytical methods, it is believed this interface is capable to equally perform satisfactorily when applied to the evaluation of molecules handled by traditional ionization methods, as is the case of electrospray. For low proton affinity molecules, the use of anisole as dopant allowed to enhance the ionization efficiency by 10 to 100 fold. Acetone or anisol directly added to the mobile phase has also shown to be an interesting approach, as few apparatus are required, thus simplifying daily operations. This also assures a constant dopant flow rate as compared to the eluant flow rate, which is relevant to reduce variability on the ionization efficiency. It was also verified this approach does not damage the chromatographic column. Methods developed with this interface have shown to be sensitive, specific, precise and accurate, therefore meeting the requirements for bioanalytical method validation used for quantative determination of drugs in biological matrices. At last, by supporting the analysis of new compounds, as well as by increasing the sensitivity of bioanalytical methods due to a better ionization efficiency, this technique brings an important contribution to drug quantification and, in particular, to the performance of relative bioavailability studies / Doutorado / Doutor em Farmacologia

Cette thèse s’intéresse à la photo-ionisation de systèmes atomiques et moléculaires en phase gazeuse à l’aide d’harmoniques d’ordre élevé, un rayonnement cohérent dans le domaine de l’extrême ultraviolet (10-100 eV) sous la forme de trains d’impulsions attosecondes (1 as = 10-18 s). Dans un premier temps, les dynamiques électroniques au cours de l’auto-ionisation de gaz rares sont étudiées par interférométrie électronique. L’auto-ionisation résulte de l’interférence entre un chemin d’ionisation direct et un chemin résonant pour lequel l’atome reste transitoirement piégé dans un état excité.L’amplitude de la transition associée à ces processus est accessible via des expériences de photo-ionisation dans le domaine spectral (sur synchrotron par exemple), mais ce n’est pas le cas de la phase qui est pourtant essentielle à la compréhension de la dynamique électronique.Nous avons développé plusieurs méthodes interférométriques afin de mesurer la phase spectrale associée aux transitions électroniques vers des résonances de Fano dans les gaz rares.A partir des informations dans le domaine spectral, nous avons reconstruit pour la première fois la dynamique d'auto-ionisation ultra-rapide dans le domaine temporel et observé les interférences électroniques donnant lieu au profil de raie asymétrique. Dans un second temps, la photo-ionisation de molécules de NO est étudiée dans le référentiel moléculaire et utilisée comme un polarimètre afin de caractériser complètement l’état de polarisation du rayonnement harmonique, et en particulier de distinguer la partie du rayonnement polarisée circulairement d’une éventuelle partie dépolarisée. Nous présentons les résultats des mesures de polarimétrie moléculaire dans le cas de la génération d’harmoniques par un champ à deux couleurs polarisées circulairement en sens opposé. Ces études, complétées par des simulations numériques, permettent de proposer des conditions optimales de génération de rayonnement harmonique polarisé circulairement et contribuent à ouvrir la voie vers des études de dichroïsme circulaire ultrarapide dans la matière. / In this work, photoionzation of atomic and molecular species in the gas phase is investigated with high-harmonic radiation. In a first part, electronic dynamics in the autoionization process of rare gases in studied with electron interferometry. This method gives access to the spectral phase of the transition to the autoionizing state, and allows there construction of the entire autoionization dynamics. The ultrafast electronic dynamics, as well as the build-up of the celebrated asymmetric Fano profile, are observed experimentally for the first time. In a second part, photoionization of NO molecules in the molecular frame is used as a polarimeter to completeley characterize the polarization state of high-harmonics. In particular, this method can address the challenging disentanglement of the circular and unpolarized components of the light. The experimental results, completed by numerical simulations, allow defining optimal generation conditions of fully circularly-polarized harmonics for advanced studies of ultrafast dichroisms in matte

Abstract In this thesis, different spectroscopic methods are used for studying metals. Electron spectroscopy is applied for the study of binding energy shifts between atomic vapor and solid metals. Photoionization and Auger decay of high temperature aluminum vapors are investigated. Ionization of atomic chromium metal vapor by light absorption is studied with synchrotron radiation and time-of-flight ion mass spectroscopy. Optical spectroscopy is used for studying light emission from electric arc furnace plasma in experimental apparatuses developed during this work. Experimental techniques and sample preparation methods are presented. / Original papers The original publications are not included in the electronic version of the dissertation. Huttula, M., Jänkälä, K., Mäkinen, A., Aksela, H., & Aksela, S. (2008). Core shell electron spectroscopy on high temperature vapors: 2s photoionization and Auger decay of atomic aluminium. New Journal of Physics, 10(1), 13009. https://doi.org/10.1088/1367-2630/10/1/013009 Huttula, M., Partanen, L., Mäkinen, A., Kantia, T., Aksela, H., & Aksela, S. (2009). KLL Auger decay in free aluminum atoms. Physical Review A, 79(2). https://doi.org/10.1103/physreva.79.023412 Aksela, S., Kantia, T., Patanen, M., Mäkinen, A., Urpelainen, S., & Aksela, H. (2012). Accurate free atom–solid binding energy shifts for Au and Ag. Journal of Electron Spectroscopy and Related Phenomena, 185(8–9), 273–277. https://doi.org/10.1016/j.elspec.2012.05.007 Mäkinen, A., Patanen, M., Aksela, S., & Aksela, H. (2012). Atom-solid 3p level binding energy shift of transition metals Cr, Mn, Fe, Co, and Ni. Journal of Electron Spectroscopy and Related Phenomena, 185(12), 573–577. https://doi.org/10.1016/j.elspec.2012.12.006 Mäkinen, A., Niskanen, J., & Aksela, H. (2012). Relative photoionization cross section of Cr atoms in the valence region. Physical Review A, 85(5). https://doi.org/10.1103/physreva.85.053411 Mäkinen, A., Niskanen, J., Tikkala, H., & Aksela, H. (2013). Optical emission from a small scale model electric arc furnace in 250–600 nm region. Review of Scientific Instruments, 84(4), 43111. https://doi.org/10.1063/1.4802833

Ce travail de thèse, essentiellement de nature expérimentale, s’inscrit dans le domaine de la physique moléculaire en phase gazeuse avec des applications en astrophysique. Il porte sur l’étude de la photoexcitation et de la relaxation de molécules de la famille des cyanopolyynes qui sont détectées dans plusieurs objets du milieu interstellaire (nuages moléculaires, comètes) et dans les atmosphères planétaires comme celle de Titan. Ces composés participent à la chimie du carbone dans ces milieux en interagissant avec le rayonnement interstellaire ou avec le flux solaire dans le domaine spectral de l’ultraviolet du vide (VUV). La structure électronique excitée de plusieurs cyanopolyynes neutres a été étudiée avec la spectroscopie d’absorption par transformée de Fourier. Ces expériences ont permis d’identifier les états de Rydberg et de mesurer la section efficace absolue de photoabsorption. Parmi les processus de relaxation ouverts suite à la photoexcitation VUV, les voies d’ionisation et d’ionisation dissociative ont été explorées de façon détaillée à l’aide du rayonnement synchrotron SOLEIL ou du rayonnement laser du Centre Laser de l'Université Paris-Sud. Des informations variées (potentiels d’ionisation vers les premiers états électroniques, fréquences vibrationnelles, couplages vibroniques, etc) ont été obtenues sur les cations de cyanopolyynes via l’utilisation de la spectroscopie de photoélectrons de seuil et de la spectroscopie de photoélectrons d’énergie cinétique nulle. Enfin, la détection par spectrométrie de masse des fragments cationiques issus de l’ionisation dissociative a permis de mesurer leur énergie d’apparition et de déterminer leur voie de formation à l’aide de calculs DFT menés par un collaborateur. / This PhD thesis presents essentially an experimental work dealing with gas-phase molecular physics with astrophysical applications. The goal of the PhD is the study of the photoexcitation and relaxation of cyanopolyyne molecules that have been detected in different interstellar objects (molecular clouds, comets), and in planetary atmospheres (e.g. Titan). These molecules contribute to the carbon chemistry of these media by interacting with the interstellar radiation or with the solar flux in the vacuum ultraviolet range (VUV). The excited electronic structure of neutral cyanopolyynes was studied by absorption spectroscopy with a VUV Fourier-transform spectrometer. These experiments allowed us to identify the Rydberg states, and to measure the absolute photoabsorption cross section.Among the different open relaxation processes following a VUV photoexcitation, ionisation and dissociative ionisation have been investigated in detail using SOLEIL synchrotron radiation or laser sources of Centre Laser de l’Université Paris-Sud. Data on the ionisation potentials toward the first electronic states, vibrational frequencies, vibronic couplings, etc. were obtained on cyanopolyyne cations with the use of threshold photoelectron spectroscopy and zero-kinetic-energy photelectron spectroscopy. Finally, cationic species created by dissociative ionisation of cyanopolyynes were detected by mass spectrometry. The threshold energies were measured and the formation channel of these fragments was determined with the help of DFT calculations performed by a collaborator.

(EN) Ambient mass spectrometry defines the versatile group of methods providing analysis of solid sample surfaces and liquids in an open atmospheric pressure environment, where the sample is simultaneously accessible to another treatment. Ambient mass spectrometry is a sharply developing research area in the analytical chemistry. It provides fast, direct analysis of objects without any sample pretreatment with the use of the mass spectrometer. Desorption electrospray ionization (DESI) and desorption atmospheric pressure photoionization (DAPPI) equipped with software control of the sample holder were investigated in this doctoral thesis. These methods use a spray of solvents for desorption and ionization molecules from solid substrate and they are suitable tools for mass spectrometry imaging (MSI) of low molecular organic compounds, where the chemical identity of molecules present on a surface is examined as a function of spatial distribution. This project deals with applications and instrumental development. As for the applications, the position of the defense glands on insect bodies, separation of the lipids in complex mixtures on thin-layer chromatography (TLC) plates, or steroid metabolites in woman urine during pregnancy were thus investigated. As for the instrumental development, the most...

Advances in experimental physics, specifically light sources emitting at an attosecond time scale, has enabled the time resolution of atomic processes like photoionization. Recent developments have allowed these sources to produce light with non-linear polarization. There exists various theoretical methods that can simulate experimental set-ups that make use of these attosecond sources. The aim of this thesis project was to extend two of these methods to be able to simulate circularly polarized light in order to both better model experimental results and come up with new potentially interesting experiments. This has resulted in an extended version of the Random Phase Approximation with Exchange method capable of simulating an ionization process by light of arbitrary polarization, as well as well as an extended version of the NewStock package that is capable of time-resolved simulation of matter interactions with arbitrary light pulses.

L'interaction des puissantes impulsions laser avec les gaz atomiques et moléculaires entraîne l’émission de flashs exceptionnellement brefs de lumière XUV grâce au processus de génération harmonique d'ordre élevé (GHOE) de la fréquence laser fondamentale. Ce rayonnement ultra-bref, dans la gamme attoseconde (10⁻¹⁸ s), permet des investigations détaillées de la dynamique électronique ultra-rapide dans la matière. Le travail de cette thèse consiste à étudier les délais de photoionisation au voisinage de différents types de résonances, en utilisant la technique Rainbow RABBIT. Il s'agit d'une technique interférométrique à deux couleurs (XUV + IR) qui permet d'accéder au temps nécessaire à l'électron pour s'échapper du potentiel atomique avec une haute résolution. Nous nous intéressons particulièrement à deux cas: i) les résonances auto-ionisantes spectralement étroites (dizaines de meV) et ii) les minima de type Cooper ayant une largeur spectrale de quelques eV. L'effet de ces structures de continuum sur la dynamique d'ionisation correspondante est étudié. / The interaction of intense laser pulses with atomic and molecular gases results in exceptionally short bursts of XUV light, through the process of high-order harmonic generation of the fundamental laser frequency. This ultrashort radiation, in the attosecond (10⁻¹⁸ s) range, allows detailed investigations of ultrafast electron dynamics in matter. The work of this thesis consists in studying the photoionization delays close to different types of resonances, using the Rainbow RABBIT technique. This is a two-color interferometric technique (XUV + IR) that allows access to the time required for the electron to escape the atomic potential with high resolution. We are particularly interested in two cases: i) autoionizing resonances which are spectrally narrow (tens of meV) and ii) Cooper-type minima which have a spectral width of some eV. The effect of these continuum structures on the corresponding ionization dynamics is studied.

The circumgalactic medium (CGM) is thought to contain the massive reservoir of gas exchanged over the course of galactic evolution, including the fuel for future star formation and the remnants of a galaxy’s merger history. Models and observations suggest that the CGM has a very low density, and faint optical or UV emission from this gas is exceedingly difficult to detect. This thesis is a combination of simulations, instrumentation and observations aimed at ultimately understanding the distribution and kinematics of ionized gas in the CGM. We present a suite of small-box hydrodynamic simulations created to study the interaction between smooth gas inflow and supernovae-driven outflow at the disk-halo interface where the galactic disk transitions into the CGM. They track the fate and kinematic evolution of gas accreting onto the galactic disk and find evidence of partial mixing with the enriched outflow. We use equilibrium photoionization models to create mock surface brightness maps of Ha and OVI emission. These observables motivate the need for new instrumentation and in suit, we present the newly commissioned Circumgalactic Ha Spectrograph (CHaS): a custom integral field unit (IFU) spectrograph tailored to detect low-surface brightness optical emission in the low-redshift universe. CHaS is deployed in the focal plane of the MDM Observatory Hiltner 2.4-meter telescope, conducting wide-field (10' x 10') spectral imaging with a competitive survey speed proportional to the high instrument grasp. A microlens array segments the field of view into > 60,000 spectra with a spatial resolution of 2.6'' and a resolving power of R ~ 10,000. Accordingly, CHaS is capable of resolving structure on scales less than 1 kpc (at 10 Mpc) and distinguishing emission lines separated by less than 40 km/s. As designed, a 50-100h exposure with CHaS would be the deepest H-alpha image and velocity field ever obtained, reaching a surface brightness of a few mR on scales of a few arcmin. Shorter, hour-long integrations with CHaS reveal a detailed map of the denser interstellar medium and bright emission at the disk-halo interface. We present results for three early commissioning targets: NGC 4631, NGC 7331 and NGC 1068, including high-resolution velocity maps and detections of new extended emission line regions far into the halo. We report a previously unnoted ribbon of ionized gas around NGC 1068, extending tens of kpc from the galactic disk beyond the known outer filamentary structure. Ongoing observations will provide a deeper probe of ionized gas far into the CGM of many nearby galaxy targets, detecting faint extended emission and mapping the velocity of ionized gas beyond the disk.

<p>This dissertation discusses theoretical methods for describing photoionization in different systems in the context of time-dependent and time-independent non-relativistic and time-independent relativistic systems. We introduce a multichannel quantum defect theory (MQDT) model for describing photoionization in the context of pump-probe experiments. The basics of MQDT are introduced and specialized to the argon atom. Two energy regimes are studied in detail and compared to the experiment: (i) a perturbative calculation describing the dynamics of an autoionizing wave packet, (ii) a time-resolved calculation describing the two-photon ionization of a deeply bound wave packet. In both cases, the model accurately describes the relative ionization with respect to the two spin-orbit split thresholds of the ion and the oscillations shown in the delay between the pump and probe. We finalize with a brief presentation, which is primarily pedagogical, of how to use MQDT inside a finite box.</p> <p>Next, we use MQDT to describe the ytterbium atom in different energy regimes and varying degrees of approximation. The motivation behind this lies in the context of quantum information science, but our study is only concerned with calculating atomic properties. We start with a minimal MQDT model to describe the data observed in the experiment, followed by the presentation of an ab initio two-electron model. Both models compare very well to the experiment, and the ab initio method compares favorably with older spectroscopic results. In addition, we show unpublished results that incorporate the hyper-fine effects into the approximate model.</p> <p>Finally, we present an implementation of the two-electron variational R-matrix method for the Dirac equation, including the complete derivation of the solution of the Dirac equation in a central potential. We provide explicit analytic forms for the solutions of the Coulomb potential and use them to derive the generalized quantum defect parameters. A discussion of the variational R-matrix method for the Dirac equation in single and multichannel contexts is presented, with sample calculations for the beryllium and radium atoms. A chapter that summarizes and points to future work for each one of the projects concludes the work.</p>

A new experimental approach is reported that focuses on photoionization mass spectrometry of primary photofragments. Photodissociation of molecules and radicals is carried out by using a tunable, pulsed dye laser. Nascent photofragments are subsequently photoionized by time-correlated vacuum-ultraviolet (VUV) radiation, so that only single-photon ionization occurs. Several experimental approaches are used in order to optimize pulsed radiation sources in the VUV that are suitable for pump-probe experiments. Laser systems that rely on frequency tripling in suitable non-linear media are used as an intense VUV radiation source of narrow bandwidth and limited tuning range. Monochromatized laser-produced plasma radiation is also used, which provides tunable VUV radiation throughout the entire VUV energy regime (8-25 eV). Ionized photofragments are finally detected by time-of-flight mass spectrometry. This experimental approach is used in order to investigate the following issues: * Absolute photoionization cross sections of atomic and molecular photofragments are derived from photoionization mass spectrometry. This is shown for the photolysis of chlorine dioxide (OClO), chlorine monoxide (ClO) and ozone (O3). The latter species generates O(1D), so that photoionization and autoionization of this excited species was studied for the first time. * Quantum states and quantum state distributions are derived from photoion yields of primary photofragments in order to characterize photodissociation processes. This is shown for the predissociation of OClO, which yields vibrationally excited ClO in its electronic ground state. * Branching ratios and quantum yields of competing photochemical pathways are determined from photoionization mass spectrometry. The accuracy of this approach is superior to other techniques. These investigations allowed us to investigate photolysis processes of molecules and radicals that are of significant importance with respect to recent issues of atmospherical photoprocesses, such as polar ozone depletion.