ABSTRACT Key words: PCDD/FS , aromatic precursor compounds , transition metal catalysts , chlorine donor , surface of fly ash particles In the last 20 years , increasing concern has focused on the environmental chemicals that mimic hormone functions , some of them toxic , which producing cancer , suppression of the immune system , and death from undefined causes . These chemicals are not made intentionally , but are formed as contaminants in combustion sources , including PCDD/FS of dioxin-like compounds that emitted from municipal solid waste incinerators (MWSI) and hazardous waste incinerators (HWI) . This study investigated the role that fly-ash plays in the formation of PCDD/FS using a commercial scale fluidized bed waste incinerators (FBWI) , which rated capacity at 3750000 kcal/hr (LHV) . In this design , a lay of sand is placed on the bottom of the combustion chamber. During combustion, the hot gases are channeled through the sand and crushed solid waste at relatively high velocity . This generated about eight times more mass of fly-ash will be produced from combustion zone than the others, and also makes much greater of PCDD/FS through the air pollutants control devices(APCD) to emission stack . The general reaction in this formation pathway is an interaction between an aromatic precursor compound and chlorine promoted by a transition metal catalyst on a reactive fly-ash surface. Since these reactions involve heterogenous chemistry , the rate of emissions is less depended on reactant concentration than conditions that promote formation such as temperature , retention time , transition metal catalysts (e , g,. Cu , Fe , Pb , Zn , Sn) and availability on catalytic surfaces of fly ash particle . These forming conditions will be proceeding a series of well study and experiment on fly-ashes from 4 zones (F1 , F2 ,F3 , F4) of FBWI . PCDD/FS synthesis from combustion of FBWI can potentially be explained by three principal mechanisms that results can be divided into several major parts as follows¡G 1. The fly-ash from zone F3 generated about 47 times more mass of PCDD/FS than zone F1 . 2. The F3 fly-ash proved to be the most active catalytic (Cu , Zn) medium , despite similarities with respect to specific surface area and average pore diameters . In addition , there are up to 75.9 percent by weight of Zn and 97.6 percent of Cu has been found in F3 of overall ashes. 3. In both fly- ash and transition metal catalysts in formation mechanisms are the dominant controlling factor for rates of PCDD/FS.

Per- and polyfluoroalkyl substances (PFASs) are man-made fluorinated compounds that havebeen detected in humans, the environment, and wildlife. The strong C-F bonds contribute tothe high thermal stability of some PFASs and make them extremely resistant to degradationunder normal environmental conditions. The commonly studied classes of PFASs areperfluoroalkyl carboxylic acids and perfluoroalkyl sulfonic acids. Though the phase-out ofperfluorooctane sulfonic acid and perfluorooctanoic acid for some time, they were the mostfrequent compounds measured and detected in biota.In this study, the total oxidisable precursor (TOP) assay, which is a method used to indirectlymeasure and estimate PFAS precursors, was evaluated. Different parameters were studied tounderstand their effects on oxidation of precursor compounds following TOP assay method(e.g., oxidation rate, pH of the oxidation solution and different washing steps during solidphaseextraction)The results from this experiment showed that the target precursors were oxidised and part ofthe proportion of the compounds formed ranged from 37 to 100% (molar ratio). Whenperforming TOP assay, it was shown that some precursors oxidised before 0.5 h while otherprecursors were oxidised after 4 hours. However, it was still unknown what products wereformed when some precursors were oxidised e.g., 7:3 fluorotelomer carboxylic acid (7:3-FTCA) and 10:2 fluorotelomer unsaturated carboxylic acid (10:2- FTUCA) because of animbalance of precursors to degradation products (molar to molar ratio).When the washing steps for solid-phase extraction were evaluated for potential losses ofprecursors, it could be seen that the ammonium acetate and the 20% methanol in Milli-Q waterled to the loss of some precursors. These results showed precautions were needed wheninterpreting the results using TOP assay.

Les travaux de thèse concernent la synthèse et la vectorisation d'analogues de la combrétastatine A-4, une molécule naturelle connue pour ses propriétés anti-vasculaires et cytotoxiques. Ces recherches se situent à l’interface de la chimie et de la biologie.D'une part, des études en méthodologie de synthèse, mettant en œuvre des réactions de couplages entre des composés diazo-précurseurs et des halogénoarènes ou des amines ont été réalisées dans le but de fournir des outils de synthèse nécessaires à la constitution de chimiothèques. Ces études ont conduit à la synthèse des 2-pyridilalkylamines à partir de pyridotriazole et d’amines, à la synthèse du motif 1,1-diaryléthyl via une réaction green ainsi qu'à l’accès au noyau benzofurane à travers une réaction « one-pot ».D’autre part, des analogues duaux de l'isocombrétastatine A-4, inhibiteurs de la tubuline et des histones désacétylases ont été développés. L'évaluation biologique de ces analogues a permis d’identifier deux molécules « lead » dont les activités antiprolifératives sur des lignées cellulaires cancéreuses sont de l'ordre du nanomolaire. D'excellents résultats d'inhibition de la polymérisation de la tubuline et de l’histone déacétylase 8 ont également été observés.Finalement, des essais de vectorisation de quelques analogues de l’isoCA-4 sous forme de liposomes ou d’ADC ont été réalisés. / The thesis reports the synthesis and vectorization of combretastatin A-4 analogues, a natural molecule known for its anti-vascular and cytotoxic properties. Our research work is at the chemistry-biology interface.On the first hand, synthetic methodology studies were performed, indeed coupling reactions between diazo-precursors and haloarenes or amines have been carried out providing new and interesting synthethic tools. These studies led to the synthesis of 2-pyridylalkylamines from pyridotriazole and amines, as well as to the synthesis of the 1,1-diarylethylene compounfs via a green reaction and finally to access to the benzofuran ring through a one-pot fashion reaction ".On the other hand, dual targeting analogs of isocombretastatin A-4 with tubulin and histone deacetylases inhibition properties have been developed. The biological evaluation of these analogs allowed us to identify two lead molecules whose antiproliferative activities on cancer cell lines are in the order of nanomolar. These molecules showed an excellent tubulin polymerization and histone deacetylase 8 inhibitions.Finally, vectorization assays of some isoCA-4 analogs using liposomes or ADCs were performed.