No presente trabalho foram realizados estudos da atividade biológica de complexos imínicos de Cu(II) e Zn(II) derivados da isatina, principalmente frente a células tumorais HeLa. Sabe-se que estes complexos se ligam ao DNA, podendo causar clivagens simples e duplas na sua estrutura, em presença de peróxido de hidrogênio, através de um mecanismo predominantemente oxidativo. Os complexos de Cu(II) geram espécies reativas de oxigênio (EROs) e, além disto, atuam sobre a mitocôndria como agentes desacopladores. Sabe-se ainda que esses compostos interagem com proteínas específicas, como por exemplo a topoisomerase humana IB e as quinases dependentes de ciclinas (CDKs), inibindo significativamente sua atividade, ou a proteassoma, frente à qual apenas uma inibição moderada foi observada. Os ensaios in vitro desenvolvidos nesta tese, permitiram evidenciar a capacidade de os complexos de intercalar no DNA e RNA, além de clivar o primeiro biopolímero. Os resultados obtidos in celullo, evidenciaram a dependência do cobre para a citotoxicidade dos complexos sendo estes compostos capazes de estimular a necrose das células HeLa. Além disso, os resultados demonstraram que estes compostos são capazes de interferir no ciclo celular, interrompendo-o em fase G2/M e de desencadear um desequilíbrio oxidativo. Os principais alvos intracelulares dos complexos, em células HeLa, são a Mitocôndria, pois interferem em seu funcionamento diminuindo o seu potencial de membrana, e o DNA clivando-o. Ademais, pretendeu-se, através de um estudo sistemático por microscopia Raman confocal, identificar danos celulares provocados pelos complexos, especialmente uma grande alteração no núcleo celular de células HeLa após o tratamento com o complexo [Cu(isaepy)]+. Através de ensaios de viabilidade, também foi possível demonstrar que a superexpressão de glicoproteína-P para linhagem MES-AS/Dx5 não resulta na resistência dessas células frente aos compostos testados, e que os complexos não interferem no funcionamento desta glicoproteína. Também foi observado, através dos experimentos com células HaCaT, que o complexo [Zn(isaepy)]2+ é capaz de interferir no ciclo autofágico celular. / In the present work, the synthesis and characterization of oxindolimine complexes of Cu(II) and Zn(II) were carried out. R is known that these complexes bind to DNA and can cause single and double cleavages in their structure, in the presence or absence of hydrogen peroxide, through a predominantly oxidative mechanism. Cu(II) complexes generate reactive oxygen species (ROS) and, in addition, act on mitochondria as decoupling agents. These compounds are also known to interact with specific proteins, such as human topoisomerase IB and cyclin-dependent kinases (CDKs), inhibiting significantly their activity, or the proteasome, against which only moderate inhibition has been observed. The in vitro assays developed in this thesis have demonstrated the ability of these complexes in intercalating at DNA and RNA, in addition to cleaving the first biopolymer. The results in cellulo evidenced the dependence on the copper for the cytotoxicity of the complexes, that can stimulate the necrosis in HeLa cells. In addition, the results demonstrated that these compounds are capable of interfering in the cell cycle, stopping it at G2/M phase and triggering an oxidative imbalance. The main intracellular targets of the complexes, in HeLa cells, are the Mitochondria, where they interfere in its function, diminishing its membrane potential, and the DNA, causing its cleavage. Further, it was intended, through a systematic study by confocal Raman microscopy, to identify cellular damage triggered by the complexes. Particularly, a large change in the cell nucleus of HeLa cells was demonstrated after treatment with the \'[Cu(isaepy)] POT.+\' complex. Through viability assays, it was also demonstrated that overexpression of P-glycoprotein in MES-SA/Dx5 lineage does not result in the resistance of these cells to the tested compounds, and that the complexes do not interfere in the functioning of this glycoprotein. Finally, it was observed, in experiments with HaCaT cells, that \'[Zn(isaepy)] POT.2+\' complex can interfere in the autophagic cell cycle.

No presente trabalho foram realizados estudos da atividade biológica de complexos imínicos de Cu(II) e Zn(II) derivados da isatina, principalmente frente a células tumorais HeLa. Sabe-se que estes complexos se ligam ao DNA, podendo causar clivagens simples e duplas na sua estrutura, em presença de peróxido de hidrogênio, através de um mecanismo predominantemente oxidativo. Os complexos de Cu(II) geram espécies reativas de oxigênio (EROs) e, além disto, atuam sobre a mitocôndria como agentes desacopladores. Sabe-se ainda que esses compostos interagem com proteínas específicas, como por exemplo a topoisomerase humana IB e as quinases dependentes de ciclinas (CDKs), inibindo significativamente sua atividade, ou a proteassoma, frente à qual apenas uma inibição moderada foi observada. Os ensaios in vitro desenvolvidos nesta tese, permitiram evidenciar a capacidade de os complexos de intercalar no DNA e RNA, além de clivar o primeiro biopolímero. Os resultados obtidos in celullo, evidenciaram a dependência do cobre para a citotoxicidade dos complexos sendo estes compostos capazes de estimular a necrose das células HeLa. Além disso, os resultados demonstraram que estes compostos são capazes de interferir no ciclo celular, interrompendo-o em fase G2/M e de desencadear um desequilíbrio oxidativo. Os principais alvos intracelulares dos complexos, em células HeLa, são a Mitocôndria, pois interferem em seu funcionamento diminuindo o seu potencial de membrana, e o DNA clivando-o. Ademais, pretendeu-se, através de um estudo sistemático por microscopia Raman confocal, identificar danos celulares provocados pelos complexos, especialmente uma grande alteração no núcleo celular de células HeLa após o tratamento com o complexo [Cu(isaepy)]+. Através de ensaios de viabilidade, também foi possível demonstrar que a superexpressão de glicoproteína-P para linhagem MES-AS/Dx5 não resulta na resistência dessas células frente aos compostos testados, e que os complexos não interferem no funcionamento desta glicoproteína. Também foi observado, através dos experimentos com células HaCaT, que o complexo [Zn(isaepy)]2+ é capaz de interferir no ciclo autofágico celular. / In the present work, the synthesis and characterization of oxindolimine complexes of Cu(II) and Zn(II) were carried out. R is known that these complexes bind to DNA and can cause single and double cleavages in their structure, in the presence or absence of hydrogen peroxide, through a predominantly oxidative mechanism. Cu(II) complexes generate reactive oxygen species (ROS) and, in addition, act on mitochondria as decoupling agents. These compounds are also known to interact with specific proteins, such as human topoisomerase IB and cyclin-dependent kinases (CDKs), inhibiting significantly their activity, or the proteasome, against which only moderate inhibition has been observed. The in vitro assays developed in this thesis have demonstrated the ability of these complexes in intercalating at DNA and RNA, in addition to cleaving the first biopolymer. The results in cellulo evidenced the dependence on the copper for the cytotoxicity of the complexes, that can stimulate the necrosis in HeLa cells. In addition, the results demonstrated that these compounds are capable of interfering in the cell cycle, stopping it at G2/M phase and triggering an oxidative imbalance. The main intracellular targets of the complexes, in HeLa cells, are the Mitochondria, where they interfere in its function, diminishing its membrane potential, and the DNA, causing its cleavage. Further, it was intended, through a systematic study by confocal Raman microscopy, to identify cellular damage triggered by the complexes. Particularly, a large change in the cell nucleus of HeLa cells was demonstrated after treatment with the \'[Cu(isaepy)] POT.+\' complex. Through viability assays, it was also demonstrated that overexpression of P-glycoprotein in MES-SA/Dx5 lineage does not result in the resistance of these cells to the tested compounds, and that the complexes do not interfere in the functioning of this glycoprotein. Finally, it was observed, in experiments with HaCaT cells, that \'[Zn(isaepy)] POT.2+\' complex can interfere in the autophagic cell cycle.

The alkali metal graphite intercalates and the conducting polymers polyacetylene and polypyrrole are reviewed and compared. Polyacetylene was synthesized by Luttinger's method and doped by exposure to caesium vapour. The doped and undoped polyacetylene were characterized by neutron powder diffraction. Hydrogen absorption and subsequent pyrolysis of caesium doped polyacetylene were studied. Mass spectrum analysis of the gases evolved at 300°C showed methane and other alkanes, indicating H₂ addition to the polymer chain followed by methane elimination. The graphite intercalates C₈Cs and C₂₄Cs reacted irreversibly with acetylene, neutron powder diffraction indicating graphite and two new substances. Mass spectrum analysis of gases evolved on heating showed ethylene, butene and butadiene, suggesting a polymerization. Polypyrrole was synthesized electrochemically and characterized by cyclic voltammetry. Gram quantities of polypyrrole doped with BF^-₄ and C10^-₄ were prepared electrochemically under high vacuum conditions to achieve high purity and avoid oxygen doping. Perchlorate doped polypyrrole prepared in an oxygen-free environment proved dangerously unstable, especially when dry. The neutron scattering law for a harmonic oscillator and the energy level splitting pattern of a 1-D rotor in a cos3θ hindering potential are reviewed and applied to solid acetonitrile. Intense lines in the neutron spectrum at 140 and 190 cm^-1 are assigned to methyl group torsions with barriers to rotation of 400 and 734 cm^-1. Hydrogen is reversibly physisorbed by intercalates C₂₄K, C₂₄Rb and C₂₄Cs at 100K to form compounds C₂₄M(H₂)₂. Neutron spectra of H₂, HD and D₂ physisorbed by C₂₄Rb and C₂₄Cs at energy transfers between 0.3-3 meV and 10-200 meV (1 meV = 8.065 cm^-1) were measured and assigned to rotational tunnelling and librations of hydrogen molecules in two sites of different dimensions. The cos2θ barriers to rotation were 57 and 78 meV respectively in C₂₄Rb(H₂)_x and 51 and 78 meV in C₂₄Cs(H₂)_x. A structural model is proposed for the metal layers with the hydrogen molecules in the layers and perpendicularly oriented.

Thesis (Ph. D.)--State University of New York at Binghamton, Materials Science, 2005. / Numerals in chemical formula in title are "subscript" in t.p. of printed version. Includes bibliographical references.

Depuis près de 55 ans, TIGF exploite, dans le sud-ouest de la France deux stockages de gaz naturel en aquifère. Le gaz stocké est essentiellement composé de méthane (CH4 à plus de 90 %), mais il contient également d’autres hydrocarbures légers (< C4H10), du diazote (N2), du dioxyde de carbone (CO2), de produits soufrés (H2S, mercaptans) et des composés métalliques présents sous formes de traces ou ultra-traces. L’objectif de la thèse est l’étude du transfert de ces composés vers l’aquifère avec comme cas d’étude : le mercure. Un dispositif expérimental a donc été conçu et développé pour (i) mesurer la solubilité dans l’eau du mercure gazeux présent dans le gaz stocké, ainsi que (ii) pour étudier les phénomènes d’adsorption sur la roche dans les conditions de pression (60 bar) et de température (45°C) du réservoir naturel. Les résultats expérimentaux obtenus en laboratoire ont été utilisés dans un modèle numérique afin de simuler le comportement du réservoir et évaluer notamment les quantités de mercure susceptibles de rester en son sein lors de l’exploitation du stockage. / For nearly 55 years, TIGF operates two gas storages in an aquifer in the southwest of France. The stored gas is mainly composed of methane (CH4 over 90%) but it also contains other light hydrocarbons (<C4H10), nitrogen (N2), carbon dioxide (CO2), sulfur compounds (H2S, mercaptans) and some metallic compounds at traces or ultra traces level. The objective of this thesis was to study the transfer of these compounds to the aquifer with special regard to mercury. An experimental device has been designed and developed to measure (i) the mercury solubility in water and (ii) to study the phenomena of adsorption on the rock in the natural reservoir’s conditions (60 bar and 45°C). The laboratory results were used in a numerical code to simulate the behavior of the reservoir and assess the mercury amount that may remain in it during the storage operation.

Friction Stir Welding (FSW) is a rapidly growing solid state welding process and has been a proven method for welding high strength aluminium alloys which were formerly not recommended for joining by conventional fusion welding methods. Based on the information acquired from previous studies, to obtain a defect free Friction Stir (FS) weld with suitable strength, three basic requirements need to be fulfilled (i) Filling of the cavity created behind the tool pin during its traverse and ensuring satisfactory contact of filled material with newly generated surface (on advancing side trailing edge of the pin) (ii) Disrupting and distributing the oxide layer at the initial weld interface (iii) Adequate level of mixing of both side material (Adjacent and Retreating side) in similar welding. In the case of dissimilar welding mixing is desired in controlled amount (to prevent or curtail formation of intermetallics) depending on material combination. Failure to achieve the first precondition results in void. Second and third precondition are interconnected for similar FSW as adequate mixing in weld helps in disruption and distribution of oxide layer at initial weld interface. Failure to achieve this, results in Joint Line Remnant (JLR). Metal to metal contact cannot be established due to the presence of JLR (aligned oxide particles) and subsequently initial interface is left unwelded which deteriorate the static and dynamic strength of friction stir welds. The problem aggravates while friction stir welding materials with tenacious contaminant layer. Therefore, appropriate stirring (which entails large deformation and mixing) of initial weld interface is essential for successful FS welds. Hence, process aspects assisting mixing of adjacent (Advancing and Retreating side) materials need to identified and studied, which are missing in former studies. Experiments are conducted with classical FS tool (possessing frustum shaped/tapered circular pin) to analyse the effect of welding parameters (tool rotation speed, traverse speed, plunge depth, tool tilt and tool position w.r.t initial interface) and tool runout by changing these parameters over a range. Tool rotation speed, traverse speed, plunge depth and tool position with initial interface are changed continuously and tool tilt and tool runout are changed in discrete steps. Tool geometry is considered to be a prime parameter controlling the magnitude of mixing, as interaction of rotating tool with initial abutting base metal interface makes the process mechanism complex, unlike other solid state welding process, namely forge welding, diffusion welding, friction welding, explosive welding, ultrasonic welding and roll bonding. Furthermore, due to asymmetric nature of material flow in FSW process, the material located in different locations with respect to the tool is subjected to different levels of deformation. For this purpose experiments have been carried out to analyse the effect of different tool geometrical aspects on level of mixing and material flow. On the other hand, visualizing flow and mixing in metals is debatable as insertion of marker material in the weld line can alter the nature of material flow in the weld due to different material flow characteristics of the base and marker materials and introduction of additional interfaces. Further, using dissimilar materials for flow studies cannot be considered for comparison with similar friction stir welds as their flow properties are different. Therefore, an alternate experimental strategy is devised in these studies using physical modelling approach which is effective and helps in identifying and quantifying mixing observed under different tooling and process conditions. In the present investigation, plasticine of primary colours is adopted and the hue attribute of colour is used to study and quantify intermixing. Yellow and Blue plasticine are placed on advancing and retreating sides respectively. The degree of mixing is indicated by the intensity of generated green. Digital images of the cross section in weld nugget region are taken. To obtain hue component of these digital images the RGB color-maps are converted to HSV color-maps. Overall, these studies help in formulating the guidelines which are useful during tool design, and administering the process to obtain a defect free well mixed welds. Based on the experimental results following conclusions are derived. 1. Following process aspects: tool geometry, interface offset, tool rotation and tool runout demonstrate a significant impact on material mixing and breaking and dispersion of initial interface in weld nugget. Tool tilt, plunge depth, tool traverse exhibit negligible effect on degree of mixing. 2. Increase in tool rotation speed (with other parameters fixed) improves mixing substantially but can be increased to a certain limit after which voids emerge due to loss of weld nugget material in the form of flash. 3. Reducing the weld pitch (i.e. increasing tool rotation speed for a given tool traverse speed) reduces the size of the weld nugget and vice versa. Tool traverse speed largely affects advancing side material and rotation speed affects retreating side material. Therefore, for higher weld pitch advancing side material (yellow plasticine) dominates the weld nugget, whereas for lower weld pitch retreating side material (blue plasticine) dominates the weld nugget. 4. The extended macro-structural feature commonly observed in FS welds occurs under influence of plunge depth. Consequently, this macro-structural feature serves as the demarcation point between shoulder affected and pin induced material flow in FS weld. 5. The degree of mixing and subsequent elimination of JLR, improves, when original interface is offset on the advancing side w.r.t tool axis for all the tools investigated in the present study. Triangular and square pin generate larger pin induced mixing which intensifies further with interface on advancing side, indicating tools with such profiles to possess larger safe zone with better mixing characteristics 6. At zero interface offset with all the process parameters fixed, tapered triangular and square pin profile tools produce welds with maximum mixing. For pins with faces, material is transported in lumps around the pin. The size of lump increases with lesser number of faces on pin. Material in the vicinity of the pin experiences spinning/whirling movement. The volume of material experiencing spinning in a single tool revolution depends on (a) weld-pitch (lesser volume of material for smaller weld pitch and vice versa) and (b) number of faces on the pin (lesser volume of material for greater number of faces and vice versa). Therefore, circular pin which can be considered to be made of infinite faces, spinning of material occurs at micro level for relatively smaller weld pitch. 7. For classical FS tool (tapered circular/frustum shape), there exists an optimum ratio (shoulder diameter/pin diameter) situated between 2.7 to 3.6 to produce void free well mixed welds. Tools with ratio of 2.7 and below possess a tendency to produce welds with void but with better mixing in weld region. Tools with ratio of 3.6 and above possess a tendency to produce void free welds but with poor mixing in weld region. Voids appear and grow under following circumstances (a) with increase in pin diameter (for a fixed shoulder diameter), (b) with decrease in shoulder diameter (for a fixed pin diameter), (c) with decrease in pin taper (for a fixed shoulder diameter and top diameter of pin). Pin length has no effect on void formation. However, it is obvious, length of root defect increases with decrease in pin length. The tooling guidelines established in this study through plasticine work can be extended to metallic friction stir welds of various thickness plates by proportionately increasing or decreasing the tool dimensions as long as they fall in the recommended range. 8. Smaller pin diameter tools exhibit higher optimum weld pitch (but with lower degree of mixing) when compared to larger pins (but with higher degree of mixing). Optimum weld pitch represents weld pitch resulting in void free welds. Consequently, tools with higher optimum weld pitch help in welding at a better rate. 9. Tool runout is replicated through tools with eccentric pins. It is interesting to note that, all the tools with pin eccentricities do not assist in mixing but tools with only certain eccentricities (0.3 and 0.6mm assisted in mixing in the present investigation). It implies that tool runout of certain values facilitate mixing in weld. On the other hand density of void increases with eccentricity of pin/tool runout. 10. In dissimilar FSW investigated with plasticine A, B, C and D possessing different flow stresses (flow stresses ascending in the order of A, B, C and D) and strain rate sensitivity of 0.24, 0.22, 0.19 and 0.18 respectively, following inferences are drawn (i) For combination A and B, weldability improves when plasticine B is on Advancing Side (AS) and A is on Retreating Side (RS). The level of mixing also improves when interface is on AS (w.r.t tool axis) for this handedness. On the contrary, severe discontinuities emerge when plasticine B is on RS and A is on AS, especially when interface is closer to the tool pin axis. (ii) For combination A and C, weldability improves when C is on AS and A is on RS. The level of mixing also enhances when interface is on AS (w.r.t tool axis) for this handedness. (iii) For combination A and D, joining is poor for both the handedness. However, nature of defect is different in both the combinations. Cracks are observed when A is located on AS and voids emerge when D is located on AS. On the other hand, placing A on AS results in weld thinning. (iv) For combination B and C, there is no appreciable change in terms of weldability and level of mixing. Both the handedness in this combination yielded fairly similar results. (v) For combination B and D, though discontinuities do not emerge with change in handedness, mixing in weld improves when B is on AS unlike to its location on RS. (vi) For combination C and D, there is no appreciable change in terms of defect formation and level of mixing with change in handedness. Both the handedness in this combination yield fairly similar results.

O desenvolvimento desta tese foi direcionado ao estudo da química iônica, em fase gasosa, de alguns compostos organo-metálicos, como: Ge(OEt)4, Ti(i-Pro)4, BU3SnOMe, GeE4, GeMe4, SiMe4 e Me6Si2NH. Foram abordados vários aspectos da química iônica destes compostos desde o estudo dos seus processos de fragmentação, a reatividade de cátions e ânions derivados destes compostos, a fotodisssociação de espécies hipervalentes formadas a partir de reações de adição, e por último foram obtidos dados sobre a afinidade protônica de ânions derivados de germânio. Além disto, foram promovidas outras investigações experimentais destinadas á obtenção de informações sobre a estrutura de espécies hipervalentes e a análise de substâncias químicas desconhecidas contendo átomos de Ge. Os resultados obtidos em algumas investigações são conclusivos, e por isto em alguns casos não foi criada uma seção voltada exclusivamente para as conclusões. Mesmo assim, algumas observações podem ser destacadas. De modo geral, os alcóxidos metálicos reagem com íon fluoreto através de reações de adição-eliminação formando complexos pentacoordenados, que no caso dos derivados de germânio e titânio, absorvem radiação infravermelha de um laser de CO2, e por absorção multifotônica promovem sucessivos processos de eliminação de espécies neutras simples. O mesmo comportamento não é observado nas alquilas metálicas. Os cátions derivados destes compostos são poderosos ácidos de Lewis, e sofrem reações de adição-eliminação com diversos substratos neutros, do tipo base de Lewis. O mais surpreendente foi à observação de reações de abstração de ligantes como CH3- por alguns destes cátions, e a subseqüente formação, em alguns casos, de espécies formadas através de reações de troca de ligantes. A afinidade protônica de alguns ânions formados através da fotodissociação de espécies hipervalentes, derivadas de germânio, foi obtida por meio de reações de abstração de prótons com substratos de afinidade protônica conhecida. Foi possível caracterizar a acidez dos ácidos conjugados destes ánions como sendo próxima a das mercaptanas. / The present thesis describes the study of the gas-phase ion chemistry of a number of organometallic compounds such as Ge(OEt)4, Ti(i-Pro)4, BU3SnOMe, GeE4, GeMe4, SiMe4 and Me6Si2NH. Several aspects of the ion chemistry of these compounds were investigated including fragmentation processes in their mass spectra, reactivity of cations and anions obtained from these compounds by electron ionization, photodissociation of hypervalent species formed by nucleophilic addition, and the proton affinity of a number of germanium-containing anions. Additional experimental investigations were carried out to characterize the structure of hypervalent studies and to explore analytical applications of unknown germanium-containing substrates. The results in several cases are sufficiently conclusive such that a general section of conclusions was considered unnecessary. For example, the metal alkoxides studied in this work react with fluoride ion in the gas-phase by an addition-elimination mechanism that initially results in the formation of a pentacoordinated species. The germanium and titanium pentacoordinated species absorb readily infrared radiation from a CO2 laser and undergo successive elimination of sim pie neturals by sequential mutiphoton absorption. This behavior is not observed for the metal alkyls. Cations derived from these compounds are powerful Lewis acids and are capable of promoting addition-elimination reactions with several neutral substrates that can act as Lewis bases. The most surprising reactions have been the abstraction of methide (formally a CH3- ion) by some of these cations followed, in the case of some Si- and Ge-containing ions, by a ligand exchange reaction. The proton affinity of Ge-containing anions obtained from the photodissociation of hypervalent precursors was established using the bracketing technique by studying the proton abstraction reaction with a number of substrates of well-known proton affinities. The absolute values derived for the proton affinities of these species, and the corresponding gas-phase acidities of the conjugate acids are close to the values of similar mercaptans.

abstract: Global photovoltaic (PV) module installation in 2018 is estimated to exceed 100 GW, and crystalline Si (c-Si) solar cell-based modules have a share more than 90% of the global PV market. To reduce the social cost of PV electricity, further developments in reliability of solar panels are expected. These will lead to realize longer module lifetime and reduced levelized cost of energy. As many as 86 failure modes are observed in PV modules [1] and series resistance increase is one of the major durability issues of all. Series resistance constitutes emitter sheet resistance, metal-semiconductor contact resistance, and resistance across the metal-solder ribbon. Solder bond degradation at the cell interconnect is one of the primary causes for increase in series resistance, which is also considered to be an invisible defect [1]. Combination of intermetallic compounds (IMC) formation during soldering and their growth due to solid state diffusion over its lifetime result in formation of weak interfaces between the solar cell and the interconnect. Thermal cycling under regular operating conditions induce thermo-mechanical fatigue over these weak interfaces resulting in contact reduction or loss. Contact reduction or loss leads to increase in series resistance which further manifests into power and fill factor loss. The degree of intermixing of metallic interfaces and contact loss depends on climatic conditions as temperature and humidity (moisture ingression into the PV module laminate) play a vital role in reaction kinetics of these layers. Modules from Arizona and Florida served as a good sample set to analyze the effects of hot and humid climatic conditions respectively. The results obtained in the current thesis quantifies the thickness of IMC formation from SEM-EDS profiles, where similar modules obtained from different climatic conditions were compared. The results indicate the thickness of the IMC and detachment degree to be growing with age and operating temperatures of the module. This can be seen in CuxSny IMC which is thicker in the case of Arizona module. The results obtained from FL ii aged modules also show that humidity accelerates the formation of IMC as they showed thicker AgxSny layer and weak interconnect-contact interfaces as compared to Arizona modules. It is also shown that climatic conditions have different effects on rate at which CuxSny and AgxSny intermetallic compounds are formed. / Dissertation/Thesis / Masters Thesis Materials Science and Engineering 2018

O desenvolvimento desta tese foi direcionado ao estudo da química iônica, em fase gasosa, de alguns compostos organo-metálicos, como: Ge(OEt)4, Ti(i-Pro)4, BU3SnOMe, GeE4, GeMe4, SiMe4 e Me6Si2NH. Foram abordados vários aspectos da química iônica destes compostos desde o estudo dos seus processos de fragmentação, a reatividade de cátions e ânions derivados destes compostos, a fotodisssociação de espécies hipervalentes formadas a partir de reações de adição, e por último foram obtidos dados sobre a afinidade protônica de ânions derivados de germânio. Além disto, foram promovidas outras investigações experimentais destinadas á obtenção de informações sobre a estrutura de espécies hipervalentes e a análise de substâncias químicas desconhecidas contendo átomos de Ge. Os resultados obtidos em algumas investigações são conclusivos, e por isto em alguns casos não foi criada uma seção voltada exclusivamente para as conclusões. Mesmo assim, algumas observações podem ser destacadas. De modo geral, os alcóxidos metálicos reagem com íon fluoreto através de reações de adição-eliminação formando complexos pentacoordenados, que no caso dos derivados de germânio e titânio, absorvem radiação infravermelha de um laser de CO2, e por absorção multifotônica promovem sucessivos processos de eliminação de espécies neutras simples. O mesmo comportamento não é observado nas alquilas metálicas. Os cátions derivados destes compostos são poderosos ácidos de Lewis, e sofrem reações de adição-eliminação com diversos substratos neutros, do tipo base de Lewis. O mais surpreendente foi à observação de reações de abstração de ligantes como CH3- por alguns destes cátions, e a subseqüente formação, em alguns casos, de espécies formadas através de reações de troca de ligantes. A afinidade protônica de alguns ânions formados através da fotodissociação de espécies hipervalentes, derivadas de germânio, foi obtida por meio de reações de abstração de prótons com substratos de afinidade protônica conhecida. Foi possível caracterizar a acidez dos ácidos conjugados destes ánions como sendo próxima a das mercaptanas. / The present thesis describes the study of the gas-phase ion chemistry of a number of organometallic compounds such as Ge(OEt)4, Ti(i-Pro)4, BU3SnOMe, GeE4, GeMe4, SiMe4 and Me6Si2NH. Several aspects of the ion chemistry of these compounds were investigated including fragmentation processes in their mass spectra, reactivity of cations and anions obtained from these compounds by electron ionization, photodissociation of hypervalent species formed by nucleophilic addition, and the proton affinity of a number of germanium-containing anions. Additional experimental investigations were carried out to characterize the structure of hypervalent studies and to explore analytical applications of unknown germanium-containing substrates. The results in several cases are sufficiently conclusive such that a general section of conclusions was considered unnecessary. For example, the metal alkoxides studied in this work react with fluoride ion in the gas-phase by an addition-elimination mechanism that initially results in the formation of a pentacoordinated species. The germanium and titanium pentacoordinated species absorb readily infrared radiation from a CO2 laser and undergo successive elimination of sim pie neturals by sequential mutiphoton absorption. This behavior is not observed for the metal alkyls. Cations derived from these compounds are powerful Lewis acids and are capable of promoting addition-elimination reactions with several neutral substrates that can act as Lewis bases. The most surprising reactions have been the abstraction of methide (formally a CH3- ion) by some of these cations followed, in the case of some Si- and Ge-containing ions, by a ligand exchange reaction. The proton affinity of Ge-containing anions obtained from the photodissociation of hypervalent precursors was established using the bracketing technique by studying the proton abstraction reaction with a number of substrates of well-known proton affinities. The absolute values derived for the proton affinities of these species, and the corresponding gas-phase acidities of the conjugate acids are close to the values of similar mercaptans.

Le cancer du cerveau est associé à une morbidité importante et à un fardeau économique considérable pour les systèmes de santé, les patients et leur famille. Malheureusement, on en sait toujours très peu sur l’étiologie de cette maladie. Les métaux, les métalloïdes et les fumées de soudures constituent une grande famille de cancérogènes professionnels potentiels à laquelle des millions de travailleurs sont exposés. La littérature scientifique fournit certains éléments de preuve que l’exposition professionnelle à quelques composés métalliques pourrait augmenter le risque de cancer du cerveau, mais la plupart des études publiées étaient limitées dans leur taille d’échantillons et en leurs capacités de mesurer efficacement l’exposition professionnelle à vie. Cette thèse a pour objectif de fournir de nouveaux éléments de preuve concernant l’association entre l’exposition professionnelle à certains composés métalliques et les deux principaux sous-types histologiques du cancer du cerveau, le gliome et le méningiome. Deux projets existants constituent la base de cette thèse: INTEROCC, une grande étude internationale cas-témoins sur l’association entre l’exposition professionnelle et le cancer du cerveau, incluant 2 054 cas de gliome, 1 924 cas de méningiome et 5 601 témoins, ainsi que CANJEM, une nouvelle matrice emplois-exposition basée sur plus de 30 000 emplois. CANJEM est un tableau croisé de trois axes: un axe de codes professionnels, un axe de périodes de temps et un axe d’agents chimiques. CANJEM fournit diverses mesures d’exposition à des agents professionnels sélectionnés en fonction d’un titre occupationnel et d’une période de temps. CANJEM étant un outil complexe conçu pour offrir une flexibilité considérable à l’utilisateur, les deux premiers volets de cette thèse ont été consacrés à l’examen de certaines des considérations méthodologiques associées à l’utilisation de CANJEM dans le cadre d’une étude épidémiologique. Premièrement, nous avons examiné comment la modification de la résolution des axes de codes professionnels et de périodes de temps influençait la proportion d’emplois pouvant être liés à CANJEM dans l’étude INTEROCC. Nous avons ensuite comparé l’accord de paires de versions de CANJEM pour la probabilité d’exposition et la concentration pondérée par la fréquence d’exposition de 19 composés métalliques en utilisant le coefficient d’accord de Gwet (AC2). Nous avons observé que, selon la résolution utilisée, CANJEM pouvait lier entre 70,7% et 98,1% de l’ensemble des emplois disponibles dans l’étude INTEROCC. De plus, la modification de l’axe de code professionnel avait un impact plus important que la modification de l’axe de période de temps sur les mesures d’expositions. Deuxièmement, l’évaluation par des experts est généralement considérée comme l’étalon-or dans l’évaluation rétrospective de l’exposition professionnelle. Différents seuils peuvent être appliqués à la probabilité d’exposition fournie par CANJEM afin de distinguer «exposé» de «non exposé». Nous avons comparé les rapports de cotes (RC) obtenus à l’aide de plusieurs versions de variables d’exposition binaire et cumulative pour neuf cancérogènes potentiels du poumon avec des RC obtenus à l’aide de l’évaluation par des experts. Des modèles de régression logistique inconditionnels ont été utilisés pour examiner l’association entre chaque variable d’exposition et le cancer du poumon chez 1 200 cas de cancer du poumon et 1 505 témoin issus d’une étude cas-témoin basée à Montréal. La sensibilité de l’évaluation dérivée de CANJEM par rapport à l’évaluation par experts variait de 0,12 à 0,78, tandis que la spécificité variait de 0,84 à 0,99. Dans l’ensemble, CANJEM a été capable reproduire les associations obtenues avec l’évaluation par experts, l’utilisation de seuils de probabilité de 25% ou 50% fournissant généralement les meilleurs résultats. Finalement, nous avons examiné le lien entre l’exposition professionnelle à 21 composés métalliques et le gliome ainsi que le méningiome dans l’étude INTEROCC à l’aide de régressions logistiques conditionnelles. La stratégie analytique était basée sur les observations faites dans les deux premiers volets. Nous n’avons observé aucune preuve de la présence d’association entre les agents sélectionnés et le gliome, mais la présence d’associations positives entre ces agents et le méningiome a été suggérée. Des associations statistiquement significatives ont également été observées entre le méningiome et une exposition inférieure à 15 ans aux fumées de plomb (RC (intervalle de confiance de 95%)) (1,67 (1,02-2,74)), aux composés du zinc (2,14 (1,02-3,89)), aux fumées de soudure (1,80 (1,17-2,77)), aux fumées d’oxydes métalliques (1,51 (1,03-2,21)) et entre une faible exposition cumulée au chrome VI (1,99 (1,03-3,84)) et aux fumées de brasage (1,83 (1,17-2,87)). L’évaluation rétrospective de l’exposition constitue l’un des principaux défis de l’épidémiologie professionnelle. Dans cette thèse, nous avons constaté que CANJEM, bien qu’imparfaite, était une approche appropriée pour l’évaluation de l’exposition professionnelle dans les études épidémiologiques. Bien qu’il soit difficile de déterminer le rôle exact joué par chacun des agents examinés, nos résultats supportent la présence d’une association positive entre les composés métalliques et plus particulièrement les fumées métalliques et le méningiome. / Brain cancer is associated with substantial lifelong morbidity and considerable economic burden for public health systems, patients, and their families. Very little is known regarding the etiology of this disease. Metals, metalloids, and welding fumes are a large family of potential occupational carcinogens to which millions of workers are exposed. The literature provides some evidence that occupational exposure to a few metallic compounds could increase the risk of brain cancer, but most published studies were limited in sample size and ability to effectively measure lifetime occupational exposure. In this thesis, we aimed to provide new evidence concerning the association between occupational exposure to selected metallic compounds and glioma and meningioma, the two major histological subtypes of brain cancer. Two existing projects provided the basis for the thesis: INTEROCC, a large international pooled case-control study on the association between occupational exposures and brain cancer, including 2,054 glioma cases, 1,924 meningioma cases, and 5,601 controls; CANJEM a new job exposure matrix based on the expert assessment of > 30,000 jobs. CANJEM is a cross-tabulation of three axes: an occupation code axis, a time period axis, and a chemical agent axis that provides various metrics of exposure to selected occupational agents based on a job title and a time period. However, CANJEM is also a complex tool designed to offer considerable flexibility to the user. The first two components of this thesis focused on the examination of some of the methodological considerations associated with the use of CANJEM in the context of an epidemiological study. First we examined how changing the resolution of the occupational code and time period axes, affected the proportion of jobs in the INTEROCC study that could be linked to CANJEM. We then compared the agreement among pairs of versions of CANJEM for the probability and frequency weighted concentration of exposure to 19 metallic compounds using Gwet’s agreement coefficient (AC2). We observed that, depending on the resolution used, CANJEM could be linked to 70.7% to 98.1% of all jobs available in the INTEROCC study. Furthermore, we observed that varying the occupation code axis had a greater impact than varying the time period axis. Neither the metrics of exposure nor the linkage rate were strongly affected by other aspects of CANJEM examined. Second, expert assessment is usually considered the gold standard in retrospective occupational exposure assessment. Different cutpoints can be applied to the probability of exposure provided by CANJEM to distinguish “exposed” from “unexposed”. We compared odds ratios (ORs) obtained using multiple versions of a binary ever and a cumulative exposure variable for nine potential and known lung carcinogens with ORs obtained using expert assessment. Unconditional logistic regression models adjusted for potential confounders were used to examine the association between each exposure variable and lung cancer in 1,200 lung cancer cases and 1,505 controls from a Montreal based case-control study. Sensitivity of the CANJEM-derived assessment vs. the expert assessment ranged from 0.12 to 0.78 while Specificity ranged from 0.84 to 0.99. Overall, CANJEM was fairly successful in reproducing the associations obtained with the expert assessment method, with the use of probability thresholds of 25% or 50% generally providing the best results for both exposure variables. Finally, we examined the association between occupational exposure to 21 metallic compound and glioma and meningioma in the INTEROCC study using conditional logistic regression adjusted for potential confounders. The analytical strategy was based on the observations made in the two previous components. We observed no evidence of association between the selected agents and glioma, but there was evidence of positive associations between some of the agents and meningioma. Statistically significant associations with OR (95% confidence interval) were also observed between < 15 years of exposure to lead fumes (1.67 (1.02-2.74)), zinc compounds (2.14 (1.02-3.89)), soldering fumes (1.80 (1.17-2.77)), and metal oxide fumes (1.51 (1.03-2.21)) and low cumulative exposure to chromium VI (1.99 (1.03-3.84)) and soldering fumes (1.83 (1.17-2.87)) and meningioma. One of the main challenges in occupational cancer epidemiology is retrospective exposure assessment. In this thesis we found that, while imperfect, CANJEM was a cost-efficient approach to occupational exposure in epidemiological studies. Although it is difficult to determine the exact role played by individual agents examined, our results provide some support for the presence of a positive association between metallic compounds, and more particularly metallic fumes, and meningioma.