Although the benefits of ICP-MS are well documented, the determination of analytes at low levels in high concentrations of matrix elements has proved difficult. As ICP-MS is a 'flow into' instrument the deposition of salts throughout the system is a common cause of significant loss of signal. The application of desolvation of aluminosilicate samples, to aid in the production of more robust plasma conditions, was investigated to increase the efficiency of the ICP in processing the sample. The performance of the ICP-MS was monitored with different cone arrangements and by running the skimmer cones at elevated temperatures. An alternative to modification of the instrument is to employ chemical modification of the sample and hence the separation of Au and Pt from an aluminosilicate matrix via the use of solid phase extraction (SPE) columns were investigated as a means of dealing with high levels of dissolved solids. OVB based SPE columns were found to give high retentions of Au and Pt when chelated with ammonium pyrrolidinediethylcarbamate (APOC). A second alternative that avoided digestion of the aluminosilicate matrices, was to carry out the analysis using laser ablation (LA). LA-ICP-MS is becoming increasingly used for trace elemental analysis but as yet no universal calibration method is available. The general problems associated with matrix matched standards are inherent as the ablation mechanism and plasma conditions can differ dramatically with very small changes in matrix composition. Hence the addition of chromophores was employed to increase the absorption of the laser energy. The use of vanillic, nicotinic and pyrazinoic acid were used to improve the ablation of pressed powder discs at the laser wavelength of 213 nm. Synthetic aluminosilicate discs and standard additions were both employed for the calibration and determination of Ti.

Les besoins actuels en produits de fertilisation et notamment pour le traitement des carences chez le végétal sont en constante augmentation. Cependant, de plus en plus soucieuse de l’environnement, les industries productrices de ces compléments alimentaires souhaitent proposées des solutions de traitements plus durables tant au niveau de leur production que de leur devenir une fois épandue dans la parcelle. Par ailleurs, il a été établi que les cellules végétales peuvent être considérées comme de vraies usines à molécules. Les hydroxyacides en C3 fabriqués par la machinerie cellulaire présentent par exemple de nombreuses propriétés de chélation et de transport. La présence de fonction hydroxyles et carboxyliques leur confèrent en effet la capacité de pouvoir enserrer des métaux et de permettre leur déplacement entre tous les compartiments des cellules, mais aussi entre les différents organes de la plante. Par ailleurs, la présence de ces mêmes molécules au sein des réactions biologiques (respiration, photosynthèse) font d’elles des métabolites assimilables et donc potentiellement dégradables. Les travaux de cette thèse ont donc eu pour objectif de mettre en place une catalyse chimio-enzymatique afin de produire les molécules les plus semblables aux hydroxyacides en C3 végétaux. Dans cette démarche de biomimétisme, nous avons mis au point un protocole de fabrication d’hydroxyacides à partir de glycérol et de carbonate de glycérol dans des conditions similaires au milieu vivant : dans l’eau, à des températures faibles et à pression atmosphérique. Nous avons ainsi réussi à synthétiser des hydroxyacides tel que l’acide glycérique, le 2-oxo1,3-dioxolan-4-carboxylique et l’hémiacétal du carbonate de glycérol. Les travaux de thèse ont également permis de mettre au point une méthode analytique complète pour la visualisation et la quantification de la majorité des hydroxyacides en C3 élaborés selon ce protocole opératoire. Cette méthode regroupe des techniques de caractérisations globales telles que l’Infra-rouge, l’HPLC, l’HPIC, et des analyses plus fines comme la LCMS de haute résolution et la RMN 1D et 2D. Nous avons par ailleurs optimisé la synthèse des hydroxyacides en C3 à partir du glycérol et du carbonate de glycérol grâce à la mise en place d’un plan d’expérience. Les molécules fabriquées présenteraient des propriétés de complexants susceptibles d’être utilisés en agronomie dans le but de remplacer les chélatants actuels issues de réactions plus polluantes de la pétrochimie et générant des substances nocives pour la santé des sols agricoles une fois appliqués. / The current need for fertilization products, and particulary for the treatment of plant deficiencies, is constantly increasing. However, more and more environmentally concerned, industries producing these food complements aim at finding more sustainable treatment solutions both in preparing these substances and in controlling their degradation once on crops. Moreover, it is established that plant cells can be considered as true molecular factories. For example, the C3 hydroxy acids produced by the cellular machinery have many chelating and transport properties. The presence of hydroxyl and carboxylic functions give them the ability to enclose the metals and to allow their displacement through all the compartments of the cells and also through the different organs of the plant. Moreover, as they are involved in biological reactions (respiration, photosynthesis), these molecules can potentially be used in cellular metabolism or degraded. The work presented herein has been designed with the aim of producing the most similar hydroxy C 3 –acids’s plant molecules by establishing a chemo-enzymatic catalysis. Inspired by biological and chemical natural processes, we have developed a protocol for manufacturing hydroxy acids from glycerol and glycerol carbonate under natural conditions ie in water, at low temperature and at atmospheric pressure. We have also produced hydroxy acids such as glyceric acid, 2-oxo1,3-dioxolan-4-carboxylic acid and glycerol carbonate hemiacetal. The thesis also allowed us to develop a complete analytical method for the observation and the quantification of the majority of C3 hydroxy acids, produced according to our operating protocol. This method combines global characterization techniques such as HPLC, HPIC and more complex analyses such as HR-LCMS and 1D and 2D NMR. We have also optimized the synthesis of C3 hydroxyacids from glycerol and glycerol carbonate through the implementation of an experimental design. Our bioinspired molecules are potential complexing agents that could be used in agronomy, in order to replace the current chelating molecules obtained from petrochemistry, known for having harmful impact on agricultural soils.

Neste trabalho estudou-se a complexação do poli(acrilato de sódio), PAS, com aminpentacianoferrato de sódio,APCF. As reações de complexação ocorreram imediatamente com a formação de uma coloração amarela com total solubilização do polímero na solução 0,032 M molar do complexo. As soluções mostraram-se estáveis por 48 h e após esse período observou-se alterações na natureza do complexo polimérico com a formação de precipitado. O UV foi usado como ferramenta de caracterização do complexo. O máximo de absorção obtido após dissolução imediata foi de 405 nm com desvio para o azul (398 nm) e um pequeno efeito hipercrômico. As amostras mantidas à temperatura ambiente por mais de 48 h deram origem a precipitados, que como a solução, absorveram com máximo de 364, 389 e 398 nm. O Complexo PAS-APCF foi também caracterizado através de FTIR por ATR e apresentou pequenas variações no espectro do material de partida (PAS). Um incremento na intensidade da deformação axial assimétrica do grupo carboxilato (1651 cm-1) e a presença do estiramento em 2055 cm-1 do grupo cianeto, diferentemente do APCF (2048 cm-1), confirmaram a formação do complexo PAS-APCF. As freqüências de absorção observadas para o complexo foram compatíveis com a presença de estruturas mono e bidentadas de complexação. As análises de TGA e DSC também foram utilizadas para a caracterização das estruturas. O estudo modelo envolvendo a complexação de sais sódicos de diácidos orgânicos de diferentes tamanhos de cadeia (oxalato, malonato, succinato, glutarato e adipato), diferentemente do PAS, promoveu um desvio para o vermelho na frequência máxima de absorção junto de um pequeno efeito hipercrômico (421 nm). Esta variação pode também ser observada quando do emprego de acetato de sódio, indicando, provavelmente, apenas a formação de estruturas monodentadas / In this work we studied the complexation of poly (sodium acrylate), PAS, with sodium amminepentacyanoferrate, APCF. The complexation reactions occurred immediately with the formation of a yellow color with complete solubility of the polymer solution in 0.032 M molar complex. The solutions were stable for 48 h and after this period saw changes in the nature of the polymeric complex with the formation of precipitate. The spectrophotometry was used as a tool for characterization of the complex. The maximum absorption was obtained immediately after dissolution of 405 nm with a shift to the blue (398 nm) and a small hyperchromic effect. The samples kept at room temperature for more than 48 h resulted in precipitates that as the solution, absorbed with a maximum of 364, 389 and 398 nm. Complex PAS-APCF was also characterized by using FTIR and ATR spectra showed small variations in the starting material (PAS). An increase in the intensity of the asymmetric axial deformation of the carboxylate group (1651 cm-1) and the stretch at 2055 cm-1 group cyanide, unlike APCF (2048 cm-1), confirmed the formation of the PAS-APCF. The absorption frequencies observed for the complex were consistent with the presence of mono and bidentate complexation. The TGA and DSC were also used to characterize the structures. The study model involving the complexation of sodium salts of organic diacids of different chain sizes (oxalate, malonate, succinate, glutarate and adipate), unlike PAS, held a red shift in the frequency of maximum absorption with a small effect hyperchromic (421 nm). This variation may also be observed when employing sodium acetate, indicating probably the formation of only monodentate structures

Orientador: Lauro Tatsuo Kubota / Tese (doutorado) - Universidade Estadual de Campinas, Instituto de Quimica / Made available in DSpace on 2018-08-15T10:20:51Z (GMT). No. of bitstreams: 1 Dias_JailsonCardoso_D.pdf: 1120921 bytes, checksum: 080b276b57f19a203109def137925235 (MD5) Previous issue date: 2010 / Resumo: O contexto geral deste trabalho se insere na área de desenvolvimento de métodos analíticos para a separação cromatográfica e detecção de íons em biocombustíveis. Diversos procedimentos de otimização (uni e multivariada) foram executados inicialmente visando estabelecer as melhores condições para uma separação eficiente e seletiva dos diferentes analitos. Posteriormente, os principais parâmetros analíticos foram investigados a fim de avaliar o desempenho e a aplicabilidade de cada método pré-estabelecido. Ao todo, três metodologias foram otimizadas, validadas e aplicadas para a análise de bioetanol, sendo a primeira para a determinação dos íons acetato e nitrato e as demais para a determinação dos íons ferro(II), ferro(III) e cobre (sistemas de eluição a base dos ácidos dipicolínico e quelidâmico). As técnicas de cromatografia líquida por troca iônica com detecção condutimétrica (CLTI-DC) e cromatografia líquida por quelação de íons com detecção fotométrica (CLQI-DF) foram utilizadas para os compostos aniônicos e os íons metálicos, respectivamente. De maneira geral, os resultados obtidos evidenciaram o desempenho analítico satisfatório para os três métodos desenvolvidos. Com exceção do ferro(II), todos os demais analitos apresentaram baixos níveis de detectabilidade, da ordem de mg L. Finalmente, diversas amostras de álcool etílico hidratado combustivel (AEHC) foram analisadas diretamente, sem a necessidade de pré-tratamento, para demonstrar a aplicabilidade de cada método / Abstract: The overall context of this work is in the area of development of analytical methods for the chromatographic separation and detection of ions in biofuels. Several optimization procedures (uni- and multivariate) were performed initially in order to establish the best conditions for an efficient and selective separation of different analytes. Subsequently, the main analytical parameters were investigated to assess the performance and applicability of each method. In all, three methods were optimized, validated and applied to the analysis of fuel ethanol, the first being for the determination of nitrate and acetate and the others for the determination of iron(II), iron(III) and copper (eluents based on dipicolinic and chelidamic acids). The techniques of high performance ion-exchange chromatography with conductivity detection (HPIEC-CD) and high performance chelation ion chromatography with photometric detection (HPCIC-PD) were used for the anionic compounds and metal ions, respectively. Overall, the results showed good analytical performance for the three methods developed. With the exception of the iron(II), all other analytes were detected at mg L levels. Finally, several samples of hydrated fuel ethanol were analyzed with no pretreatment to demonstrate the applicability of each method / Doutorado / Quimica Analitica / Doutor em Ciências

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Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Botany and Ecology Candidate: Kamila Zemanová Supervisor: PharmDr. Jana Karlíčková, Ph.D. Title of Thesis: Interaction of phenylpropionic acids with copper Copper is an essential trace element which is essential for our body. It has a significant effect on the correct functioning of important organs and it plays an important role in the transfer of electrons at the major enzymatic pathways as a prostetic group. On the other hand, excess or deficiency of copper in the human body can cause many diseases. Phenylpropionic acids are group of substances which can have antioxidant, anti-inflammatory and anticancer effects. They are involved in the scavenging of free radicals and reactive oxygen species. In this diploma thesis, I tested copper chelating activity of six phenylpropionic acids at different pHs by spectrofotometric methods using a hematoxylin and a bathocuproinedisulfonic acid disodium salt as an indicator. 3-(3,4-dihydroxyphenyl)propionic acid showed the highest chelating potential but only using a hematoxylin. KEYWORDS: Copper, Phenylpropionic acids, Antioxidants, Chelating activity, Hematoxylin, Bathocuproin

Exposure to arsenic (As) in water, the ubiquitous toxin that poses adverse health risks to tens of millions, is the result of both anthropogenic and geochemical mobilization. Despite recent publicity and an increased public awareness, the dangers associated with arsenic exposure rank among the top priorities of public health agencies globally. Existing sequestration applications mainly include reductions and adsorption with zero-valent metals and their oxides. The performance of adsorption media is known to preferentially favor aqueous As(V) over As(III) due to the charge of the dissolved oxyanion. Magnetic nanoparticles (MNP) have been the focus of multidisciplinary research efforts for the removal of aqueous toxic metals and metalloids since they can be magnetically separated from the treated water. This improves isolation and allows for regeneration of the MNP, reducing cost and resource consumption. This research is focused on As(III & V) sequestration through the use of synthetic ligands N,N’bis(2-mercaptoethyl)isophthalamide (abbreviated BDTH2) and 2,2’- (isophthaloybis(azanaediyl))bis-3-mercaptopropanoic acid (abbreviated ABDTH2). Additionally, As(III) sequestration with ABDTH2 functionalized on silica core-shell MNP (ABDTH2 MNP), magnetite MNP (ABDTH2@MNP), and commercial silica beads (ABDTH2 Si60) is demonstrated. Both BDTH2 and ABDTH2are effective precipitation agents for the removal of As(III) through the formation of S-As covalent bonds. ABDTH2MNP reduced a 200 ppb As(III) batch solution to below 10 ppb at pH 5,7, and 9. Additionally, complete removal was achieved in the presence of anions at concentrations of 200, 500, and 1000 ppb. This system was evaluated for the removal of total arsenic from industrial solutions accumulated during the production of renewable biogas in landfills. Direct precipitation with BDTH2 and ABDTH2 was inhibited by the complex matrix. However, batch removal with ABDTH2@MNP was effective in removing 82% of the inorganic arsenic. Sequestration of arsenic and speciation from these industrial solutions remains a challenge.

Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Candidate: Barbora Gorová Supervisor: Assoc Prof. Přemysl Mladěnka, Pharm.D., Ph.D. Title of thesis: Iron-chelating properties of fruit extracts of various elderberries Inorganic iron is the major food source of iron in humans. It plays role in many biochemical reactions. Thus, iron metabolism disorders can lead to different diseases associated with lack of iron or iron overload. One of the possible treatment modalities of the latter represents the administration of iron chelators. Elderberry, Sambucus nigra L. (Adoxaceae), has been used in traditional medicine. The fruits of elderberry are a rich source of cyanidin-based anthocyanins as the main component. There are important differences, both in chemical and physical properties between several cultivars of elderberry. Anthocyanins might interact with metals in the gastrointestinal tract by formation of chelates. However, data on metal interactions with anthocyanins are sparse. The main aim of this study was to perform the analysis of interaction of iron with elderberry fruit extracts as a rich and cheap source of anthocyanins with cyanidin as the aglycon. In this in vitro study ten elderberry fruit exctracts were tested for iron chelating activities...

La famille des Arenaviridae contient des virus transmis par les rongeurs responsables notamment de graves fièvres hémorragiques dont la fièvre de Lassa qui infecte chaque année 300 000 personnes. L’absence de solutions thérapeutiques efficaces (vaccins et/ou antiviraux) en fait une priorité d’étude. Il est donc urgent d’identifier de nouvelles cibles thérapeutiques et des antiviraux spécifiques associés. Le génome des Arénavirus code pour deux nucléases possédant des fonctions cruciales pour la survie du virus. La protéine L possède un domaine endonucléase indispensable à la réplication virale réalisant le mécanisme de vol de coiffe. La protéine NP comporte un domaine exonucléase impliqué dans l’échappement au système immunitaire de l’hôte infecté. Ces deux enzymes possèdent un mécanisme d’action commun métal-dépendant de clivage de leur ARN substrat. Ce projet :1) se propose d’apporter la preuve de concept que ces deux enzymes sont de nouvelles cibles thérapeutiques pour combattre les Arénavirus.2) se base sur le criblage préalable d’une chimiothèque de 1ère génération sur l’endonucléase d’un Arénavirus et la découverte d’une famille de dicéto-­‐acides (DCAs) inhibitrice de son activité. Au cours de ce travail de thèse, une chimiothèque de 2nde génération de 22 composés a été synthétisée. Des voies de synthèses nouvelles et originales ont été développées. Les composés ont été évalués par des méthodes biophysiques pour leur capacité à se lier aux enzymes cibles, ont été évalués comme potentiels inhibiteurs dans des tests d’activité in vitro, et in cellula dans un test en mini-­‐génome. Certains composés se sont montrés de bons ligands, actifs in vitro et in cellula. / The Arenaviridae family comprises viruses transmitted by rodents responsible for several diseases such as hemorragic fevers among which Lassa fever infects 300,000 people each year. The current lack of effective vaccines and/or antivirals makes the development of therapeutic solutions of high priority. The genome of Arenaviruses encodes for two nucleases bearing crucial functions for virus survival. The L protein bears an endonuclease domain essential for viral replication through the cap-­‐snatching mechanism. The NP protein has an exonuclease domain involved in anti-­‐immune activity. Both enzymes share a common mode of action as they cleave their RNA substrate via a metal-­‐dependant (Mg2+) strategy. This work intends to :1) consider these two enzymes as novel Arenavirus therapeutic targets.2) take over a preliminary screening of a 1st generation of ligands on an Arenavirus endonuclease. Diketo-­‐acids (DKAs) have been discovered as potential inhibitors of its activity. To this end, a library of 2nd generation of 22 compounds was synthetized thanks to the development of an optimized synthesis pathway. Compounds were further evaluated by biophysical methods for their ability to bind therapeutic targets, as potential inhibitors in an in vitro assay and in cellula in a mini-­‐genome assay. Some of them are active in vitro and in cellula

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