No description available.

No description available.

This thesis contains 7 chapters detailing the background, uses and syntheses of novel [2.2]paracyclophane compounds. Where applicable, their use in asymmetric synthesis is described. Within chapter 1, a brief description of the history of [2.2]paracyclophane and the development of its chemistry is given, this includes its basic reactivity and that of its derivatives. A short introduction of its use in asymmetric synthesis is also included. Finally, a very brief review of novel applications of the [2.2]paracyclophane motif in polymer and medicinal chemistry is given. Chapter 2 outlines the synthesis of (S)-4-butylsulfinyl[2.2]paracyclophane and the subsequent extensive optimisation of directed metalation conditions. A summary of the analytical data and syntheses of 11 novel 4,5-disubstituted [2.2]paracyclophane compounds is presented.

Clay minerals are the most abundant minerals near the earth’s surface and play very important roles in biogeochemical processes. They have been found very useful in various industrial applications. The surface properties of clay minerals such as high specific surface area (SSA) and cation exchange capacity (CEC) make them able to act as catalysts, supports and sorbents of toxic and radioactive chemicals. However, their role during the biodegradation of crude oil hydrocarbons is not well understood. The main aim of this research project was to investigate the capabilities of the various forms and types of clay minerals in supporting the microbial degradation of crude oil hydrocarbons so as to gain better understanding of their potential role in the bioremediation of oil polluted sites. The role of clays in hydrocarbon removal was investigated in aqueous clay/oil microcosm experiments with a hydrocarbon degrading microorganism community. The clays used for this study were bentonite, palygorskite, saponite and kaolinite. Clays were treated to produce acid activated clays and organoclays; homoionic interlayer bentonites were also used in this study. The study identified volatilization and adsorption as processes that will take place alongside biodegradation and therefore needed to be accounted for in the assessment of the effects of the clays. The study indicated that acid activated clays, organoclays, untreated kaolinite, K-bentonite, Zn-bentonite and Cr-bentonite were inhibitory to biodegradation of the hydrocarbons, via different mechanisms, whereas Ca-bentonite and Fe-bentonite were stimulatory to biodegradation with about 80% removal of the total petroleum hydrocarbons (TPH) due to biodegradation. The ‘local bridging effect’ and polarization of the interlayer water were identified as two opposing influences arising from the interlayer cations of clay minerals that probably determine the extent of biodegradation of the hydrocarbons. Adsorption of hydrocarbons was significant during biodegradation especially with unmodified palygorskite, Zn-bentonite and K-bentonite as each of them caused more than 40% removal of TPH by adsorption in the experimental microcosm containing 5:1 ratio (w/w) of clay to oil. The process of adsorption of aromatic compounds in the crude oil was believed to take place via cation-π interactions. The correlation between extent of biodegradation and surface area is more robust than that between extent of biodegradation and CEC. The same trend applies with adsorption indicating that both biodegradation and adsorption are more surface area dependent than CEC.

No description available.

Chapter 2 describes the chemoenzymatic synthesis of (-)epibatidine from a known cis-dihydrodiol. Crucia to the synthesis is a [3.3] sigmatropic rearrangement reaction. Two [3.3] sigmatropic rearrangements are described ; an allylazide rearrangement and an allylcyanate to isocyanate rearrangement. The synthesis was completed in eleven steps, yielding (~) -epibatidine in 21% yield. Chapter 3 describes the synthesis and characterisation of allytic cyetic sulphates from known cis~ tetrahydrodiols. These cyclic sulphates are ubiquitous synthetic intermediates, commonly used as electrophiles. Also described is the synthesis of a series of trans-1 ,2-chloro chlorosulphates. These compounds are by-products in the formation of cyclic sulphates and can be avoided by careful control of the reaction conditions. Chapter 4 describes the small-scale biotransformations of a series of substituted phenol metabolites, using the toluene dioxygenase (TOO) enzyme. The cyclohexenone cis-dial products are characterised fully and their absolute configurations are established using a variety of methods, including circular dichroism and stereochemical correlation. Pseudomonas putida UV4 and E.coli were used as sources of TOO for these reactions. Also described is the large-scale biotransformation of two of these phenols. The chemical synthesis of the cyclohexenone cis-diol products from known cistetrahydrodiols is also described as an alternative route to these compounds. Finally, the biotransformation of several substituted anilines using TOO is also described.

This thesis concerns the exploitation of the site isolation concept in cascade sequences that facilitate rapid construction of complex polycyclic molecules. Site isolation is the anchoring of mutually destructive reagents onto solid supports to prevent their mutual deactivation.

Σε αυτή τη Διπλωματική εργασία μελετάται η ταλαντωτική συμπεριφορά μιας κυκλικής πλάκας γραφενίου προκειμένου να διαπιστωθεί αν μπορεί να λειτουργήσει σαν νανομηχανική συσκευή ανίχνευσης μάζας. Για το λόγο αυτό δημιουργήθηκε και χρησιμοποιήθηκε ένα μοντέλο πεπερασμένων στοιχείων. Σε αυτό το μοντέλο οι αλληλεπιδράσεις μεταξύ των ατόμων και οι σχετικές κινήσεις αυτών προσομοιώθηκαν με κατάλληλα ελατήρια των οποίων η δυσκαμψία έχει υπολογιστεί χρησιμοποιώντας την ενέργεια δεσμού από τη θεωρία των μορίων. Ακόμη, τα άτομα του άνθρακα προσομοιώνονται με μάζες στη θέση των ατόμων άνθρακα. Το αναπτυχθέν μοντέλο αναπαριστά το δίσκο του γραφενίου σαν ορθότροπο υλικό. Προκείμενου να αποκτηθεί μια καλή εικόνα της συμπεριφοράς του κυκλικού γραφενίου γίνεται αρχικά διερεύνηση της ελεύθερης ταλάντωσης για διάφορες διαμέτρους αυτού. Επιπλέον, εξετάζεται η ταλαντωτική συμπεριφορά του γραφενίου με την προσκόλληση μάζας διαφόρων μεγεθών και σε διάφορες θέσεις πάνω στο γραφένιο κατά μήκος της ακτίνας του. Η επεξεργασία των μοντέλων έχει ως αποτέλεσμα τις φυσικές συχνότητες ταλάντωσης του γραφενίου και τις αντίστοιχες ιδιομορφές των φύλλων γραφενίου με ή χωρίς την προσκολλημένη μάζα παρέχοντας τα ταλαντωτικά τους χαρακτηριστικά. Επομένως, έχοντας δημιουργήσει μοντέλα για διάφορες διαμέτρους και μάζες μπορεί να εξεταστεί και να αποκτηθεί μια πλήρης εικόνα για την ενδεχόμενη ταλαντωτική συμπεριφορά του κυκλικού μονοστρωματικού δίσκου γραφενίου σαν αισθητήριο μάζας. / In this Diploma thesis is studied the vibrational behavior of a circular graphene sheet so as to investigate if this can operate as a nanomechanical system of mass sensing. For this purpose a finite elements’ model was created and being used. In this model the interatomic interactions and their relative positions are simulated by equivalent spring elements whose stiffness derived by corresponding potential energies provided by molecular theory and expressing the resistance in relative movements between carbon atoms under deformation. Moreover, the inertial effects of the system are simulated by using appropriate lumped masses in atomic positions. The model created represents the graphene plate as an orthotropic material. In order to obtain a full view of the behavior of circular graphene, firstly is been done investigation of its free vibration for different diameters of the plate. After that, is studied the Vibrational behavior with a mass lying on it. The solution gives the natural frequencies and corresponding mode shapes of vibration of individual graphene sheets and graphene-attached mass systems providing their vibrational characteristics. Subsequently, assuming the geometric characteristics of graphene as well as the weight and position of the attached mass as the global design parameters, a parametric study on mass sensing characteristics is presented in order to examine the potential behavior of a circular graphene monolayer as mass sensor.

L'obésité est une maladie multifactorielle qui constitue un facteur de risque de nombreuses pathologies, notamment les maladies cardiovasculaires, le diabète et les maladies neurodégénératives. Des études épidémiologiques récentes suggèrent un effet obésogène des contaminants environnementaux, mais peu d'informations sont disponibles sur leur effet potentiel sur le métabolisme des lipoprotéines hépatiques. L'objectif de cette étude était de déterminer l'effet de polluants environnementaux de la famille des hydrocarbures aromatiques polycycliques (HAP) sur trois récepteurs des lipoprotéines, le récepteur des LDL (LDL-R), le lipolysis-stimulated lipoprotein receptor (LSR) et le scavenger receptor B1 (SR-B1) ainsi que sur les ATP binding cassette transporter A1 (ABCA1) et G1 (ABCG1) en utilisant des modèles cellulaires et/ou animaux. Les études par immunoblots et immunofluorescence in vitro ont révélé que l'exposition de cellules Hepa1-6 au B[a]P diminue de manière significative les taux de protéine LSR, LDL-R et ABCA1, alors qu’aucune modification significative du taux et de l’activité du LSR n’a été observée lors d’une exposition au pyrène ou au phénanthrène. L’analyse en temps réel par PCR et les études avec la lactacystine ont révélé que cet effet était dû principalement à une augmentation de la dégradation par le protéasome plutôt qu’à une diminution de la transcription ou à une augmentation de la dégradation lysosomale. En outre, les ligand-blots ont révélé que les lipoprotéines exposées au B[a]P avaient une affinité réduite pour le LSR ou le LDL-R. Des souris C57Bl/6RJ ont été traitées par le B[a]P (0,5 mg / kg, i.p) toutes les 48 h pendant 15 jours. Le gain de poids observé est accompagné d’une augmentation des taux de triglycérides et de cholestérol plasmatiques, du taux de cholestérol hépatique, et d’une diminution du taux de LDL-R et ABCA1 chez animaux traités au B[a]P par rapport aux témoins. Les corrélations observées entre les taux de LSR et de LDL-R hépatiques chez les souris contrôle ne sont plus observées chez les souris traitées au B[a]P, ce qui suggère un dérèglement du métabolisme des lipoprotéines hépatiques. Ces résultats suggèrent que la prise de poids induite par le B[a]P est peut-être liée à son action inhibitrice sur le LSR et le LDL-R, ainsi que sur l’ABCA1 et le métabolisme des lipoprotéines hépatiques, ce qui conduit à un statut lipidique modifié chez les souris traitées au B[a]P, donnant ainsi un nouvel éclairage sur les mécanismes sous-jacents de la contribution des polluants tels que le B[a]P à la perturbation de l'homéostasie lipidique, susceptible de contribuer à la dyslipidémie associée à l'obésité / Obesity is a multifactorial disorder that represents a significant risk factor for many pathologies including cardiovascular diseases, diabetes and neurodegenerative diseases. Recent epidemiological studies suggest potential obesogenic effects of environmental contaminants, but little information is available on their potential effect on hepatic lipoprotein metabolism. The objective of this study was to determine the effect of the common environmental pollutants, belonging to polycyclic aromatic hydrocarbon (HAP) on three lipoprotein receptors, the LDL-receptor (LDL-R), the scavenger receptor B1 (SRB1) and the lipolysis-stimulated lipoprotein receptor (LSR) as well as the ATP binding cassette transporters A1 (ABCA1) and G1 (ABCG1) using cell and/or animal models. Immunoblot and immunofluorescence in vitro studies revealed that exposure of Hepa1-6 to benzo[a]pyrene (B[a]P) significantly decreased LSR, LDL-R and ABCA1 protein levels, whereas no significant changes in protein levels and LSR activity where observed upon cell treatment with pyrene or phenanthrene. Real-time PCR analysis, lactacystin and chloroquine studies revealed that this effect was due primarily to increased proteasome-mediated degradation rather than to decreased transcription or to increased lysosomal degradation. Furthermore, ligand blots revealed that lipoproteins exposed to B[a]P displayed markedly decreased binding to LSR or LDL-R. C57Bl/6RJ mice were treated with B[a]P (0.5 mg/kg, i.p) every 48 h for 15 days. The increased weight gain observed was accompanied by increased plasma triglycerides and cholesterol levels, increased liver cholesterol content, and decreased LDL-R, ABCA1, ABCG1 and SR-B1 protein levels in B[a]P-treated animals as compared to controls. Correlations observed between hepatic LSR and LDL-R levels in control mice were no longer observed in B[a]P treated mice, suggesting a potential dysregulation of hepatic lipoprotein metabolism.Taken together, these results suggest that B[a]P-induced weight gain may be due its inhibitory action on LSR and LDL-R, as well as ABCA1 and lipoprotein metabolism in the liver, which leads to the modified lipid status in B[a]P-treated mice, thus providing new insight into mechanisms underlying the involvement of pollutants such as B[a]P in the disruption of lipid homeostasis, potentially contributing to dyslipidemia associated with obesity

Classés parmi les Polluants Organiques Persistants, les Hydrocarbures Aromatiques Polycycliques (HAP) sont des composés ubiquitaires dans l'environnement, auxquels l'Homme est exposé principalement via l'ingestion d'aliments contaminés. Les HAP sont connus depuis les années 1990 comme pouvant être neurotoxiques tant chez l'Homme que chez l'animal. Le transfert des HAP entre la mère et le foetus via le placenta ainsi que la présence de ces composés dans le lait maternel ont été montrés à plusieurs reprises, posant ainsi la question du risque lié à une exposition survenant lors de phases précoces du développement de l'individu. Parce que ce risque n'a été que partiellement étudié, le travail de thèse présenté dans ce manuscrit a eu pour objectif d'évaluer la toxicité à court et à long terme pour le système nerveux en développement, d'un mélange de 16 HAP ingéré par la rate gestante et/ou allaitante. Les HAP ont été administrés via un aliment contaminé à deux doses, 2 et 200 µg/kg/jour La dose la plus faible correspond aux niveaux de contamination environnementale via l'alimentation de la mère pendant les périodes de gestation et/ou d'allaitement. Les résultats montrent que l'exposition périnatale au mélange de HAP n'a pas induit d'effets à court terme sur le développement neuromoteur et sensoriel des jeunes rats. En revanche, une augmentation à long terme des niveaux d'activité et d'anxiété a été relevée chez les animaux exposés. Par ailleurs, des modifications du métabolisme énergétique cérébral, évalué par l'activité enzymatique de la cytochrome oxydase sur des coupes de cerveaux prélevés à différents âges ont été observées, notamment au niveau du système limbique. La mesure des concentrations de HAP dans le compartiment cérébral des ratons a montré la présence de l'ensemble des molécules mères, y compris chez les animaux témoins, ce qui laisse supposer l'existence d'un bruit de fond environnemental non négligeable dans ce type d'étude. Finalement, plusieurs facteurs modulent la toxicité induite, parmi lesquelles la période d'exposition, et l'administration d'un mélange et non d'une molécule seule. En conclusion, ce travail a permis de mettre en évidence, chez le rat, une neurotoxicité retardée suite à une exposition précoce à un mélange de 16 HAP tant sur le plan comportemental que métabolique, ce qui pose la question du risque pour l'Homme, et en particulier pour l'individu en développement, d'une exposition à ce type de composés / Compounds in the environment to which human is exposed mainly through ingestion of contaminated food. PAHs are known since the 1990s as being neurotoxic both in humans and in animals. PAH transfer between mother and fetus through the placenta, and the presence of these compounds in breast milk have been shown, thus raising the question of risk exposure occurring during early stages of development of the individual. Because this risk was only partially studied, the thesis presented in this manuscript was designed to assess the short-term and long-term toxicity for the developing nervous system, of a mixture of 16 PAHs ingested by the pregnant and / or breastfeeding rat. PAHs were administered via a contaminated food at two doses, 2 and 200 µg/kg /day dose. The lowest one corresponds to the levels of environmental contamination via the mother's diet during gestation and/or lactation. The results show that perinatal exposure to the mixture of PAHs did not induce short-term effects on neuromotor and sensory development on pups. In contrast, a long-term increase in activity and anxiety levels was observed in the exposed animals. In addition, changes in cerebral energy metabolism, as assessed by the enzymatic activity of cytochrome oxidase on brain sections taken at different ages were observed, particularly in the limbic system. Measures of the concentrations of PAHs in the pup brain compartment showed the presence of all the parent compounds, including control animals, suggesting the existence of an environmental noise significant. Finally, several factors modulate PAH toxicity, including the exposure period, and the administration of a mixture instead of a single molecule. In conclusion, this work has highlighted, in rats, delayed neurotoxicity due to early exposure to a mixture of 16 PAHs, which raises the question of risk to humans, and in particular for the individual developing exposure to such compounds