The investigations to be presented in this thesis arose from studies on the respiration of mitochondria isolated from pig skeletal muscle. These animals developed the syndrome of Malignant Hypermedia after exposure to halothane - a halogenated hydrocarbon used as an inhalation anesthetic agent.

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Halogenated Polycyclic Aromatic Hydrocarbons (X-PAHs) are ubiquitous contaminants that are thought to be generated by processes such as chemical industries and incomplete combustion, including waste incineration and electronic waste (e-waste) burning. X-PAHs are a concern for environmental and human health because they are toxic, mutagenic, and are expected to be more lipophilic than the parent compounds. To study these compounds in the environment, an analytical method was developed, utilizing large-volume injection via a programmable temperature vaporizing (PTV) inlet, using environmental samples from an e-waste area and in Guangzhou, China. The concentrations of 26 X-PAHs were measured in atmospheric particulate matter (PM), house dust (HD), and sediment. In general, the X-PAH concentrations in PM were low, with concentrations ranging from <0.078 to 41.81 pg/m³. There was no significant difference in X-PAH concentrations in PM between the e-waste area and Guangzhou. These concentrations are of the same order of magnitude as previous studies of X-PAHs in PM. These data suggest that e-waste activities are not a significant source of X-PAHs in atmospheric PM. The concentrations of X-PAHs in HD samples ranged from <0.0372 to 3575 pg/g dry weight. In general, there was no significant difference between E-waste and Guangzhou HD concentrations. The profiles of X-PAHs in PM and HD were different, suggesting that there are additional sources for X-PAHs inside homes other than outdoor air. The concentrations of X-PAHs in sediment samples from an e-waste site ranged from <104 to 2890 pg/g dry weight. The X-PAH profile in sediment more closely resembled the X-PAH profile of PM. / Graduation date: 2011

The identification and isolation of bacteria capable of dehalogenating highly chlorinated aromatic compounds is currently a time consuming process, therefore the ability to predict the potential of a site to naturally remediate contamination is limited. This work has assessed a selection of modern molecular biological techniques to detect the presence of specific dehalogenase enzymes or the genes encoding them, as an indicator of a contaminated site's potential to perform remediation naturally. DNA and protein based detection strategies were tested in a variety of formats. DNA detection of dehalogenase genes was assessed by varieties of hybridisation probing and PCR detection. Protein based detection utilised specific antibody based detection of dehalogenases from bacterial proteomes. A combined technique exploiting the specificity of antibody detection and the sensitivity of PCR amplification was assessed by ribosomal display. DNA based detection techniques demonstrated a high sensitivity but lacked the required level of specificity for use in routine testing, with the exception of single specific primer PCR which was demonstrated to detect specific changes in a bacterial population following contamination. Protein based detection lacked the sensitivity necessary for a field based detection system but the potential for specifically fingerprinting bacterial species was observed. The ribosomal display technique, although combining sensitivity and specificity, could not be fully evaluated during the course of this work.

Halogenated alkenes are a group of commercially important chemicals. For example tetrafluoroethylene is the monomer used for the production of poly- tetrafluoroethylene, hexachloro-1:3-butadiene is a by-product from the manufacture of chlorinated solvents and perchloroethylene is widely used as a dry cleaning agent. Due to possible exposure to haloalkenes and the nephrotoxicity observed in animal studies, concern has been expressed for the potential of these compounds to cause toxicity to man. Animal studies have shown that these compounds undergo inter-organ metabolism and are bioactivated by enzymes of glutathione processing. The metabolites are delivered to the kidney where they cause proximal tubular cell necrosis. This site-specific toxicity is due to accumulation of the metabolites via specific transport mechanisms and bioactivation via the enzyme C-S lyase present in high amounts in the proximal tubules. The aim of this research was to investigate the mechanisms of toxicity of haloalkene S'-conjugates in vitro using cultures of rat and human proximal tubular cells. This study demonstrates that human proximal tubular cells are sensitive to haloalkene. -conjugate toxicity, particularly DC VC. Human exposuredata has shown that workers exposed to trichloroethylene (Bimer et al, 1993) and perchloroethylene (Mutti et al, 1992) excrete nephrotoxic metabolites and markers of renal damage respectively. In the light of these findings and the toxicity of DCVC in HPT cells, exposure to halogenated alkenes should be controlled and those exposed monitored.

This thesis explored new methods for understanding the fate and transport of halogenated organic contaminants in the environment. A theoretical method of hazard assessment of chemical mixtures containing large numbers of components was developed and its application illustrated using polychlorinated alkanes, toxaphene, and halogenated dibenzo-para-dioxins and furans. Partitioning properties predicted by high-throughput quantitative structure property relationships were used to locate mixture constituents on plots displaying equilibrium phase distribution in various environmental compartments and the potential for bioaccumulation and long range transport. Potentially hazardous components were identified graphically for more detailed assessments. The applicability of XAD-resin based passive air samplers (XAD-PAS) for studying neutral polyfluoroalkyl substances (nPFAS) in the atmosphere was tested empirically. XAD-PASs have sufficiently high uptake capacity to yield temporally averaged nPFAS concentrations over period as long as a year. When applied as part of the Global Atmospheric Passive Sampling network, nPFAS were found to be truly global contaminants.

This thesis explored new methods for understanding the fate and transport of halogenated organic contaminants in the environment. A theoretical method of hazard assessment of chemical mixtures containing large numbers of components was developed and its application illustrated using polychlorinated alkanes, toxaphene, and halogenated dibenzo-para-dioxins and furans. Partitioning properties predicted by high-throughput quantitative structure property relationships were used to locate mixture constituents on plots displaying equilibrium phase distribution in various environmental compartments and the potential for bioaccumulation and long range transport. Potentially hazardous components were identified graphically for more detailed assessments. The applicability of XAD-resin based passive air samplers (XAD-PAS) for studying neutral polyfluoroalkyl substances (nPFAS) in the atmosphere was tested empirically. XAD-PASs have sufficiently high uptake capacity to yield temporally averaged nPFAS concentrations over period as long as a year. When applied as part of the Global Atmospheric Passive Sampling network, nPFAS were found to be truly global contaminants.

The purpose of this investigation is threefold: (1) to examine in detail the cycloaddition of halogenated ketenes and carbonyl compounds, (2) to study the decarboxylation of the resulting halogenated 2-oxetanones,and (3) to investigate the effect of halogens in the halogenated 2-oxetanones on the nucleophilic addition reaction.

Diss. (sammanfattning) Stockholm : Karol. inst., 2005. / Härtill 4 uppsatser.

>Magister Scientiae - MSc / Antimicrobials are chemical compounds that destroy or inhibit the growth of microorganisms. The majority of these antimicrobials are actually natural products or natural product derived with key examples being the pioneer antibiotics penicillin and cephalosporin. Antimicrobials are an extremely important class of therapeutic agents; however, the development of drug resistance and slow pace of new antibiotic discovery is one of the major health issues facing the world today. There is therefore a crucial need to discover and develop new antibacterial agents. In this study, the potential of marine algae as a source of new antibiotics was explored. Crude organic extracts and chromatographic fractions obtained from small-scale extraction of 17 different marine algae were used to prepare a pre-fractionated library that would be tested against several disease causing microorganisms. The activity of the pre-fractionated library and purified compounds was determined against a panel of drug resistant microorganisms namely Acinetobacter baumannii ATCCBAA®-1605™, Enterococcus faecalis ATCC® 51299™, Escherichia coli ATCC® 25922™, Staphylococcus aureus subsp. aureus ATCC® 33591™ and Candida albicans ATCC® 24433™. Finally, cytotoxicity tests of 50 selected library extracts and isolated compounds were done against two cell lines namely MCF-7 (breast cancer) and HEK-293 (kidney embryonic).