The ß-carbolines norharman and harman structurally resemble the synthetic compound 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) that is known for its ability to damage neuromelanin-containing dopaminergic neurons of the substantia nigra and thereby induce parkinsonism. MPTP is, however, not normally present in the environment whereas the ß-carbolines are present in cooked food and tobacco smoke. In this thesis it was demonstrated that norharman and harman had affinity to melanin and were retained in neuromelanin-containing neurons of frogs up to 30 days post-injection (the longest survival time examined). It was also demonstrated that norharman induced neurodegeneration, activation of glia cells and motor impairment in mice. Furthermore, this compound induced ER stress and cell death in PC12 cells. An in vitro model of dopamine melanin-loaded PC12 cells was developed in order to study the effect of melanin on norharman-induced toxicity. In this model, melanin seemed to attenuate toxicity induced by low concentrations of norharman. After exposure to the highest concentration of norharman, melanin clusters were disaggregated and there was an increased expression of stress proteins and caspases-3, known to be involved in apoptosis. The polycyclic aromatic hydrocarbon, 7,12-dimethylbenz[a]anthracene was demonstrated to have a CYP1A1-dependent localization in endothelial cells in the choroid plexus, in the veins in the leptomeninges and in the cerebral veins of mice pre-treated with CYP1-inducers. These results demonstrate that the distribution of environmental compounds could be influenced by the presence of neuromelanin and expression of CYP enzymes in the brain and that norharman may induce neurotoxic effects in vivo and in vitro.

Les hydrocarbures aromatiques polycycliques (HAP) sont des polluants organiques persistants qui sont présents en mélange complexe dans l’environnement et notamment dans les milieux aquatiques. Ils s’adsorbent sur les particules en suspension, s’accumulent dans les sédiments et dans les premiers maillons de la chaîne trophique. L’objectif de cette étude était de mesurer les effets à long terme d’une contamination par des HAP chez un modèle de vertébrés : le poisson zèbre. Dans un premier temps, des embryons ont été exposés pendant les 4 premiers jours de leur développement sur du sédiment naturel enrobé de 3 HAP individuel (phénanthrène, pyrène et benzo[a]pyrène) puis transférés et élevés en eau propre. Dans un deuxième temps, des poissons ont été exposés par voie alimentaire tout au long du cycle de vie et dès le premier repas à 3 fractions de HAP à doses environnementales enrobées sur les aliments : une fraction pyrolytique (PY) extraite d’un sédiment échantillonné dans la Seine et deux fractions pétrogéniques (un fuel lourd (HO) provenant de l’Erika et un pétrole brut type Arabian light (LO)). Les effets à long terme sur la croissance, la survie, la reproduction et le comportement ont été évalués à différents âges. Ces effets ont pu être observés à plusieurs échelles, i.e. de la molécule, aux tissus et organes puis à l’échelle de l’individu. Globalement, chez les poissons contaminés, la croissance est ralentie, la survie larvaire diminuée chez les HO, la fonction reproduction est altérée fortement à la fois au niveau hormonal, tissulaire et phénotypique ainsi que les réponses comportementales léthargiques ou hyper-réactives selon les cas. L’exposition par voie sédimentaire a révélé des effets visibles lorsque les individus atteignaient 6 mois soulignant l’existence d’effets tardifs, notamment sur les réponses comportementales, d’une exposition très précoce y compris chez la descendance. Quant à l’exposition par voie alimentaire, elle a montré une gradation des effets. Toutes fonctions confondues, les résultats obtenus permettent d'établir une hiérarchie dans la toxicité des fractions étudiées : PY < LO ≈ HO. L'approche multi-échelle utilisée dans ce travail a permis, en partant d'informations acquises au niveau moléculaire, tissulaire et individuel, d'aboutir à une compréhension intégrée des conséquences qu'une exposition à des HAP peut avoir sur l'aptitude à la survie des poissons dans leur milieu naturel ainsi qu'à leur capacité à participer au renouvellement des générations futures. / Polycyclic aromatic hydrocarbons (PAHs) are persistent organic pollutants (POPs) which are found in complex mixtures in the environment including aquatic ecosystems. They adsorb on particles, accumulate in sediment and in the first link of the food web. The aim of this study was to measure long term effects of PAHs contamination on a vertebrate model : the zebrafish. In a first study, embryos were exposed on natural sediment spiked with 3 individual PAH (phenanthrene, pyrene and benzo[a]pyrene) during the first four days of their development. In a second study, to evaluate the consequences of long-term chronic exposure to PAHs, zebrafish were exposed, from their first meal (5 days post fertilisation) until they became reproducing adults, to diets spiked with three PAHs fractions at environmentally relevant concentrations (0.3X, 1X and 3X; with the 1X concentration being in the range of 4.6-6.7 μg.g-1 for total quantified PAHs). The fractions used were representative of PAHs of pyrolytic (PY) origin or of two different oils of differing compositions (a heavy fuel (HO) and a light crude oil (LO)). Long term effects on growth, survival, reproduction and behavior were evaluated at different ages. Effects were observed at molecule, tissue, organ and individual scales. In general, for contaminated fish, growth was reduced, larval survival decreased in HO, and reproduction was strongly impaired at hormonal, tissue and phenotypic levels, and behavioral responses were lethargic or hyperactive depending on fractions and stages. Sediment exposure still revealed visible effects when fish were 6 month old. These results hereby showed significant late effects, especially in behavioral responses after an early exposure, including in larvae issued from contaminated fish. In spiked diets contaminated fish, we observed a gradation of effects. Combining all functions, we established of hierarchy in toxicity in the studied fractions: PY < LO ≈ HO. Finally, our results gathered at a multiscale from molecule, to tissue and individuals, indicate that PAH mixtures of different compositions, representative of situations encountered in the wild, can promote lethal and sublethal effects which are likely to be detrimental for fish survival and recruitment into future generations.

This dissertation reports the synthesis and characterization of semi-fluorinated polymers derived from the polymerization of bisphenols with fluoroalkenes. A series of diverse bisphenols were chosen from popular commercial bisphenols and new polycyclic aromatic hydrocarbon (PAH) derived bisphenols requiring synthesis. Step-growth condensation polymerization of bisphenols with three different fluoroalkene types was performed while probing polymerization conditions and the structure/properties relationship of the resulting fluoropolymers. The fluoroalkene monomers were chosen from bis(trifluorovinyloxy)biphenyl (TFVE), perfluorocyclohexene (PFCH), and perfluoro acyclic monomers, namely, perfluoro(4-methyl-2-pentene) and 1-perfluoroheptene to undergo this chemistry. This work is divided into four parts based on the polymerization methodology. The first section focuses on the development of a new class of fluorinated arylene vinylene ether (FAVE) and their chain extended polymers prepared via base-catalyzed step-growth polymerization of PAH bisphenols with the TFVE monomer. These reactions afforded polymers containing controlled terminal and enchained fluoroalkenylenes for latent reactivity such as post polymerization functionalization, chain extension, and/or crosslinking. In general, these PAH cores resulted in polymers with improved thermal properties The second portion describes the investigation of step-growth addition/elimination polymerizations of PAH bisphenols and PFCH to prepare a new class of fluoropolymers containing alternating rigid PAH linkages and enchained PFCH vinylene ether moieties in the backbone. The third section covers the preparation and characterization of semi-fluorinated poly(aryl ether sulfone)s by nucleophilic addition/elimination reactions of PFCH with sulfone bisphenols. From commercially bisphenols combined with PAH bisphenols, we introduced the industrially valuable and property enhancing diaryl sulfone unit in a series of semi-fluorinated copolymers. This modular approach greatly expands access to partially fluorinated aryl ether sulfone polymers intended for high performance applications in optoelectronics, separation/purification membranes, and composites. Finally, in the fourth section, a new class of semifluorinated polymers was synthesized via nucleophilic addition/elimination reactions of acyclic perfluoroalkenes with bisphenols. In particular, environmental concerns for biopersistent and highly regulated perfluorooctanoic acid (PFOA) is the driver for using perfluoroheptene, which is derived cleanly by the decarboxylation of these pollutants in one step. This provided a new class of semi-fluorinated materials with promising properties including thermal stable, processability, and transparent film formation.