The importance of fluorine in a wide array of different areas within chemistry and biochemistry has been demonstrated time and time again. Fluorine-containing products range from essential substituents in pharmaceuticals and relatively long-lived tracers for PET imagining, to fluoropolymers with outstanding properties, to essential components in most of the strongest acids available to chemists today. Fluorine’s extreme electronegativity makes it a truly unique element, but its acute toxicity in its elemental F2 form makes it difficult to handle, prompting researchers to explore different options for incorporating this important element into a variety of different molecular scaffolds. Due to the remarkable thermodynamic and kinetic stabilities of C-F bonds, methods for forming and breaking these cleanly, and under relatively mild conditions, are in high demand. Fortunately, transition metals have greatly aided in this process. However, fluoroorganometallic chemistry is much less developed than transition metal chemistry involving hydrocarbons, and certainly less understood. One of the primary reasons for this relative dearth of fluoroorganometallic complexes is the difficulty associated with their synthesis. In this work, important steps towards perfluoroalkyl chain-growth within the coordination sphere of a transition metal will be presented, stemming in part from the synthesis and characterization of novel cobalt fluoride and bis(perfluoroalkyl) complexes. As important electrophiles, fluoroalkenes have primarily been used as monomers for the formation of important fluoropolymers. However, their direct reactivity with organics remains rare and is usually difficult to control, with limited substrate scopes. Herein, the formation of stable N-heterocyclic fluoroalkene adducts as versatile synthons for the incorporation of fluoroalkene fragments into various chemical environments will be introduced. By forming these adducts, the inconvenience of manipulating fluorinated gases in further reactions can be avoided, and the N-heterocyclic fragment is shown to aid in directing substitutions involving polyfluoroalkenyl imidazolium salts and organic nucleophiles to form a variety of C-E (E = C, N, O, S) and C-M bonds (M = Mn, Mo). The ease with which C-F bonds are manipulated in these systems is quite remarkable, as the substitution reactions occur cleanly and efficiently at room temperature, to form a variety of new bonds without the need for a transition metal. By expanding on the fundamental reactivity between N-heterocyclic carbenes and fluoroalkenes, attempts were made to correlate the observed reactivity with certain electronic and steric parameters unique to the utilized carbenes. Although a correlation has not yet been established, the effects of atypical steric constraints in a cyclic (alkyl)(amino)carbene were demonstrated, wherein the initial point of attack by the carbene on the fluoroalkene was modified. It is hoped that this work will eventually lead to new roles for organocatalysts in fluoroalkene transformations.

No description available.

Perfluoroalkyl carboxylates (PFCAs) and perfluoroalkane sulfonates (PFSAs)are anthropogenic fluorinated surfactants that have been detected in almost every environmental compartment studied, yet their production and applications are far outweighed by those of other higher molecular weight fluorinated surfactants used in commerce. These fluorinated surfactants are widely incorporated in commercial products, yet their post-application fate has not been extensively studied. This thesis examines various biological and environmental processes involved in the fate of these surfactants upon consumer disposal. Specific focus was directed towards the environmental chemistry of polyfluoroalkyl phosphate esters (PAPs), perfluoroalkyl phosphonates (PFPAs), and perfluoroalkyl phosphinates (PFPiAs), and their potential roles as sources of perfluoroalkyl acids (PFAAs) in the environment. PAPs are established biological precursors of PFCAs, while PFPAs and PFPiAs are newly discovered PFAAs in the environment. Incubation with wastewater treatment plant (WWTP) microbes demonstrated the ability of PAPs to yield both fluorotelomer alcohols (FTOHs), which are established precursors of PFCAs, and the corresponding PFCAs themselves. WWTP biosolids-applied soil-plant microcosms revealed that PAPs can significantly accumulate in plants along with their degradation metabolites. This has implications for potential wildlife and human exposure through the consumption of plants grown and/or livestock raised on farmlands that have been amended with contaminated biosolids. A number of compound-and environmental-specific factors were observed to significantly influence the partitioning of PFPAs and PFPiAs between aqueous media and soil, as well as, aquatic biota during sorption and bioaccumulation experiments respectively. In both processes, PFPAs were primarily observed in the aqueous phase, while PFPiAs predominated in soil and biological tissues, consistent with the few environmental observations of these chemicals made to date. Detection of the PAP diesters (diPAPs), PFPiAs, and fluorotelomer sulfonates (FTSAs),all of which are used commercially, in human sera is evidence of human exposure to commercial fluorinated products, but the pathways by which this exposure occurs remain widely debated. Overall, this work presents novel findings on the environmental fate of commercial fluorinated surfactants and each of the process studied shows a clear link between the use of commercial products and the fluorochemical burden currently observed in the environment.

Perfluoroalkyl carboxylates (PFCAs) and perfluoroalkane sulfonates (PFSAs)are anthropogenic fluorinated surfactants that have been detected in almost every environmental compartment studied, yet their production and applications are far outweighed by those of other higher molecular weight fluorinated surfactants used in commerce. These fluorinated surfactants are widely incorporated in commercial products, yet their post-application fate has not been extensively studied. This thesis examines various biological and environmental processes involved in the fate of these surfactants upon consumer disposal. Specific focus was directed towards the environmental chemistry of polyfluoroalkyl phosphate esters (PAPs), perfluoroalkyl phosphonates (PFPAs), and perfluoroalkyl phosphinates (PFPiAs), and their potential roles as sources of perfluoroalkyl acids (PFAAs) in the environment. PAPs are established biological precursors of PFCAs, while PFPAs and PFPiAs are newly discovered PFAAs in the environment. Incubation with wastewater treatment plant (WWTP) microbes demonstrated the ability of PAPs to yield both fluorotelomer alcohols (FTOHs), which are established precursors of PFCAs, and the corresponding PFCAs themselves. WWTP biosolids-applied soil-plant microcosms revealed that PAPs can significantly accumulate in plants along with their degradation metabolites. This has implications for potential wildlife and human exposure through the consumption of plants grown and/or livestock raised on farmlands that have been amended with contaminated biosolids. A number of compound-and environmental-specific factors were observed to significantly influence the partitioning of PFPAs and PFPiAs between aqueous media and soil, as well as, aquatic biota during sorption and bioaccumulation experiments respectively. In both processes, PFPAs were primarily observed in the aqueous phase, while PFPiAs predominated in soil and biological tissues, consistent with the few environmental observations of these chemicals made to date. Detection of the PAP diesters (diPAPs), PFPiAs, and fluorotelomer sulfonates (FTSAs),all of which are used commercially, in human sera is evidence of human exposure to commercial fluorinated products, but the pathways by which this exposure occurs remain widely debated. Overall, this work presents novel findings on the environmental fate of commercial fluorinated surfactants and each of the process studied shows a clear link between the use of commercial products and the fluorochemical burden currently observed in the environment.

Perfluoroalkyl acids (PFAAs) are a family of synthetic substances used in a wide variety of consumer and industrial applications, including non-stick and stain-resistant products. PFAAs, specifically perfluorinated sulfonates and carboxylates, are chemically stable and virtually non-biodegradable in the environment. In recent years, PFAAs have been detected in tissues and blood of humans and wildlife. Furthermore, PFAAs have a tendency to bioaccumulate and biomagnify in biota. Perfluorooctane sulfonate and perfluorooctanoate are known to be toxic when animals are exposed to environmentally-relevant levels, but scientists and regulators are challenged with determining and predicting their modes of action. There is some evidence to suggest that PFAAs can impact the thyroid hormone (TH) pathway and neurodevelopment. The studies presented in this thesis investigated the developmental effects and potential modes of action of newer PFAAs that are being introduced into the global market place. Egg injection experiments were performed in domestic chicken (Gallus gallus domesticus) embryos to assess the in ovo toxicity of perfluorohexane sulfonate (PFHxS) and perfluorohexanoate (PFHxA) during development. Real-time RT-PCR was used to measure the transcription of candidate genes in the liver and cerebral hemisphere of day 21-22 embryos. Candidate genes were selected based on their responsiveness to PFAA exposure in an in vitro screening assay conducted previously. In ovo exposure to PFHxS decreased embryo pipping success and overall growth at 38,000 ng/g; several orders of magnitude higher than concentrations reported in wild bird eggs. The expression of TH-responsive genes, including type II and III 5'-deiodinase, neurogranin, and octamer motif binding factor 1, were induced. In addition, PFHxS diminished free thyroxine (T4) levels in plasma. PFHxA had no affect on pipping success, gene expression or T4 levels in chicken embryos at the doses assessed. The transcriptional profiles in the cerebral hemisphere of chicken embryos exposed to 890 and 38,000 ng/g PFHxS were compared to a solvent control using microarray technology. The expression of 78 different genes were significantly altered (fold change > 1.5, p < 0.001) by PFHxS. Functional analysis showed that PFHxS affected genes involved in tissue development and morphology and cellular assembly and organization. Pathway and interactome analysis suggested that gene expression may be affected through integrin receptors and signaling pathways via TH–dependent and –independent modes of action. It is expected that the findings presented in this thesis will be of general relevance and importance to regulatory agencies and of interest to research scientists and risk assessors.

In order to improve the synthetic route for diazonium perfluoroalkyl benzenesulfonylimide (PFSI) zwitterionic monomers, N-deacetylation of the coupling product was proposed to replace the reduction of aromatic amine intermediates. A series of hydrolysis methods, such as acid and base catalyzed refluxing, were explored for the N-deacetylation to obtain the PFSI aromatic amine. Factors such as temperature, concentration of acid/base and the time needed for the reaction to take place were investigated in an attempt to optimize the reaction condition. The basic hydrolysis was preferred since it was expected to carry out the N-deacetylation and debromination in one batch reaction. N-deacetylation in base at high concentrations was successful, however, side reaction of the perfluorovinyl ether occurred. It was discovered that the best N-deacetylation method is to reflux/sonicate the coupling product with acid in methanol for six hours. The intermediates and purified products were characterized with 1HNMR, 19FNMR, GC-MS and IR.

There is a growing interest in assessing the neurotoxic potential and endocrine disrupting properties of perfluoroalkyl compounds (PFCs). Several studies have reported in vitro and in vivo effects related to neuronal development, neural cell differentiation, pre- and post- natal development and behaviour. PFC exposure altered hormone levels (e.g. thyroid hormone, estrogen, and testosterone) and the expression of hormone-responsive genes in mammalian and aquatic species. Hormone-mediated events are critical in central nervous system development and function, especially those controlled by thyroid hormones (THs). The studies presented in this thesis are the first to assess the effects of PFCs on primary cultures of neuronal cells in two avian species; the domestic chicken (Gallus domesticus) and herring gull (Larus argentatus). The following TH-responsive genes were examined using real-time RT-PCR: type II iodothyronine 5’-deiodinase (D2), D3, transthyretin (TTR), neurogranin (RC3), octamer motif binding factor (Oct-1), and myelin basic protein (MBP). Several PFCs were shown to alter mRNA expression levels of genes associated with the TH pathway in avian neuronal cells. It was determined that short-chained PFCs (<8 carbons) altered the expression of TH-responsive genes to a greater extent than long-chained PFCs (≥8 carbons). Although several significant changes in mRNA expression were observed in TH-responsive genes following PFC exposure in chicken embryonic neuronal (CEN) cells (Chapter 2), there were fewer changes in herring gull embryonic neuronal (HGEN) cells (Chapter 3). The mRNA levels of D2, D3, TTR, and RC3 were altered following treatment with several short-chained PFCs in CEN cells. Oct-1 and RC3 expression were induced following treatment with several short-chained PFCs in HGEN cells. These studies are the first to report that PFC exposure alters mRNA expression in primary cultures of avian neuronal cells and provide insight into the possible mechanisms of action of PFCs in the avian brain.

Perfluoroalkyl acids (PFAAs) are a family of synthetic substances used in a wide variety of consumer and industrial applications, including non-stick and stain-resistant products. PFAAs, specifically perfluorinated sulfonates and carboxylates, are chemically stable and virtually non-biodegradable in the environment. In recent years, PFAAs have been detected in tissues and blood of humans and wildlife. Furthermore, PFAAs have a tendency to bioaccumulate and biomagnify in biota. Perfluorooctane sulfonate and perfluorooctanoate are known to be toxic when animals are exposed to environmentally-relevant levels, but scientists and regulators are challenged with determining and predicting their modes of action. There is some evidence to suggest that PFAAs can impact the thyroid hormone (TH) pathway and neurodevelopment. The studies presented in this thesis investigated the developmental effects and potential modes of action of newer PFAAs that are being introduced into the global market place. Egg injection experiments were performed in domestic chicken (Gallus gallus domesticus) embryos to assess the in ovo toxicity of perfluorohexane sulfonate (PFHxS) and perfluorohexanoate (PFHxA) during development. Real-time RT-PCR was used to measure the transcription of candidate genes in the liver and cerebral hemisphere of day 21-22 embryos. Candidate genes were selected based on their responsiveness to PFAA exposure in an in vitro screening assay conducted previously. In ovo exposure to PFHxS decreased embryo pipping success and overall growth at 38,000 ng/g; several orders of magnitude higher than concentrations reported in wild bird eggs. The expression of TH-responsive genes, including type II and III 5'-deiodinase, neurogranin, and octamer motif binding factor 1, were induced. In addition, PFHxS diminished free thyroxine (T4) levels in plasma. PFHxA had no affect on pipping success, gene expression or T4 levels in chicken embryos at the doses assessed. The transcriptional profiles in the cerebral hemisphere of chicken embryos exposed to 890 and 38,000 ng/g PFHxS were compared to a solvent control using microarray technology. The expression of 78 different genes were significantly altered (fold change > 1.5, p < 0.001) by PFHxS. Functional analysis showed that PFHxS affected genes involved in tissue development and morphology and cellular assembly and organization. Pathway and interactome analysis suggested that gene expression may be affected through integrin receptors and signaling pathways via TH–dependent and –independent modes of action. It is expected that the findings presented in this thesis will be of general relevance and importance to regulatory agencies and of interest to research scientists and risk assessors.

There is a growing interest in assessing the neurotoxic potential and endocrine disrupting properties of perfluoroalkyl compounds (PFCs). Several studies have reported in vitro and in vivo effects related to neuronal development, neural cell differentiation, pre- and post- natal development and behaviour. PFC exposure altered hormone levels (e.g. thyroid hormone, estrogen, and testosterone) and the expression of hormone-responsive genes in mammalian and aquatic species. Hormone-mediated events are critical in central nervous system development and function, especially those controlled by thyroid hormones (THs). The studies presented in this thesis are the first to assess the effects of PFCs on primary cultures of neuronal cells in two avian species; the domestic chicken (Gallus domesticus) and herring gull (Larus argentatus). The following TH-responsive genes were examined using real-time RT-PCR: type II iodothyronine 5’-deiodinase (D2), D3, transthyretin (TTR), neurogranin (RC3), octamer motif binding factor (Oct-1), and myelin basic protein (MBP). Several PFCs were shown to alter mRNA expression levels of genes associated with the TH pathway in avian neuronal cells. It was determined that short-chained PFCs (<8 carbons) altered the expression of TH-responsive genes to a greater extent than long-chained PFCs (≥8 carbons). Although several significant changes in mRNA expression were observed in TH-responsive genes following PFC exposure in chicken embryonic neuronal (CEN) cells (Chapter 2), there were fewer changes in herring gull embryonic neuronal (HGEN) cells (Chapter 3). The mRNA levels of D2, D3, TTR, and RC3 were altered following treatment with several short-chained PFCs in CEN cells. Oct-1 and RC3 expression were induced following treatment with several short-chained PFCs in HGEN cells. These studies are the first to report that PFC exposure alters mRNA expression in primary cultures of avian neuronal cells and provide insight into the possible mechanisms of action of PFCs in the avian brain.

There is a growing interest in assessing the neurotoxic potential and endocrine disrupting properties of perfluoroalkyl compounds (PFCs). Several studies have reported in vitro and in vivo effects related to neuronal development, neural cell differentiation, pre- and post- natal development and behaviour. PFC exposure altered hormone levels (e.g. thyroid hormone, estrogen, and testosterone) and the expression of hormone-responsive genes in mammalian and aquatic species. Hormone-mediated events are critical in central nervous system development and function, especially those controlled by thyroid hormones (THs). The studies presented in this thesis are the first to assess the effects of PFCs on primary cultures of neuronal cells in two avian species; the domestic chicken (Gallus domesticus) and herring gull (Larus argentatus). The following TH-responsive genes were examined using real-time RT-PCR: type II iodothyronine 5’-deiodinase (D2), D3, transthyretin (TTR), neurogranin (RC3), octamer motif binding factor (Oct-1), and myelin basic protein (MBP). Several PFCs were shown to alter mRNA expression levels of genes associated with the TH pathway in avian neuronal cells. It was determined that short-chained PFCs (<8 carbons) altered the expression of TH-responsive genes to a greater extent than long-chained PFCs (≥8 carbons). Although several significant changes in mRNA expression were observed in TH-responsive genes following PFC exposure in chicken embryonic neuronal (CEN) cells (Chapter 2), there were fewer changes in herring gull embryonic neuronal (HGEN) cells (Chapter 3). The mRNA levels of D2, D3, TTR, and RC3 were altered following treatment with several short-chained PFCs in CEN cells. Oct-1 and RC3 expression were induced following treatment with several short-chained PFCs in HGEN cells. These studies are the first to report that PFC exposure alters mRNA expression in primary cultures of avian neuronal cells and provide insight into the possible mechanisms of action of PFCs in the avian brain.