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<p> The use of gamma radiation to initiate the iodination of methane in liquid phase was studied using a semi-batch technique whereby the methane was bubbling through a column of iodine solution in a reactor. Yields of CH3I and CH2I2 lower than 10% and G < 500 were obtained as contrasted with the 60% yield and G=7xl0^7 reported in the gas-phase reaction. In view of the propensity of the iodine as a radical scavenger and the endothermic nature of the reaction, various attempts to improve the low yields were carried out. Results are eiven that indicate the chances of achieving a laree G value for liquid-phase reaction are very low even if the operating conditions are optimized. </p> / Thesis / Master of Engineering (MEngr)

Chapter 1 provides a general introduction on the role of bioisosterism of fluorine aiming to improve the pharmacokinetics properties of lead compounds. GABAA receptors specifically, synaptic GABAA receptors, extrasynaptic GABAA receptors and GABAA rho receptors are then presented. Compounds that exhibit agonist and partial agonist effects at these receptors are also discussed. The applications of some compounds as GABAA receptor PET radiotracers are also described. Chapter 2 details the synthesis of two fluorinated analogues of muscimol, fluoromuscimol and trifluoromethylmuscimol. Fluoromuscimol was obtained from the lithiation of a Boc-protected isoxazole followed by in-situ fluorination using NFSI, whereas trilfuoromethylmuscimol was obtained from the coupling of a heteroaryl iodide with trifluoromethylcopper species, which was generated in-situ from MFSDA in the presence of CuI. Fluoromuscimol and trifluoromethylmuscimol were assessed on human synaptic, (α₁β₂γ₂), extrasynaptic, (α₄β₂δ) and ρ₁ subunits of the GABAA receptor. The biological results show that fluoromuscimol exhibits greater maximum response in comparison to GABA at the extrasynaptic GABAA receptors (α₄β₂δ), but lower overall potency, whereas trifluoromethylmuscimol was inactive at all the tested GABAA receptors. Chapter 3 discusses the synthesis and late stage fluorination of diaryliodonium salts as precursors to fluoromuscimol. Application of iodonium salts as precursors for nucleophilic fluorination in PET studies are also highlighted. The last part of this chapter focuses on the synthesis of iodomuscimol as a potential alternative SPECT radiotracer to fluoromuscimols in probing GABA binding sites on GABAA receptors.

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A method for purification and radiolabelling phosphoglucose isomerase was devised in order to develop a sensitive quantitative radioimmunoassay for the detection of the enzyme irrespective of its catalytic activity. For four genetic variants of PGI no difference in the molecular specific activity was observed. In one variant (PGI-Denton), liver and heart tissue extracts, and in mature erythrocytes (as compared to normal erythrocytes), a decreased molecular specific activity was observed which initially may imply that these samples contain cross-reactive material which is not catalytically active.

Pharmaceuticals are group of organic substances with significant worldwide consumption in human and veterinary medicine. These compounds may be metabolized in the organism, but in some cases they remain unchanged and both are usually excreted via renal excretion in the native form or as metabolites. Large quantities of pharmaceuticals and their metabolites contaminate municipal wastewater. The wastewater treatment plants are unable to remove these substances completely, so they contaminate surface water, groundwater and soil as well. Due to the biological activity of pharmaceuticals, long - term effect may cause bacterial resistance, endocrine influence, DNA and renal damages in non-target organisms. The phytoextraction and the translocation of radiolabeled diclofenac with 125 I were experimentally studied by using of in vitro cultivated plants Helianthus annuus and Zea mays. Efficiency od phytoextraction was monitored as decrease of radioactivity of tested substance [125 I]diclofenac in Murashige-Skoog cultivation medium. Both species are able to extract tested substance during 8 to 10 days of cultivation, with efficiency approximately 85 % using Zea mays and 79 % using Helianthus annuus. Better extraction ability of diclofenac was observed at Helianthus annuus - 80 mg/ kg of dry weight compared...

This thesis reports progress in three major aspects of σ-bonded organometallic porphyrins that are described in the published papers found in chapters 4, 5 and 6. meso-Iodoporphyrins, which were prepared in a rapid, selective and high yielding methodology from the respective 1-palladioporphyrins or bromoporphyrins, are important starting materials for further functionalisations of porphyrins. Their utility was confirmed in a palladium-catalysed coupling reaction and this novel synthetic strategy could potentially be applied for iodine/bromine exchange on other organic substrates.. A 1-palladioporphyrin was also utilised to optimise the reaction conditions leading to the formation of porphyrinylphosphine oxides. This synthetic strategy simplified the challenging optimisation of the palladium-catalysed reaction and has great potential to be applied in other catalytic processes. Subsequently a suite of porphyrinylphosphine oxides was prepared under the optimised catalytic conditions. These macrocycles, which represent a new class of porphyrins, were isolated cleanly in very high yields. Detailed spectroscopic investigations as well as X-ray single crystal analysis demonstrated their structures unambiguously and established their potential as ligands for supramolecular chemistry. The coordinating properties of phosphine oxides in general and porphyrinylphosphine oxides in particular, towards Mg(II) centred porphyrins were examined in further experiments. Triphenylphosphine oxide showed a strong affinity towards Mg(II) porphyrins and the calculated displacement constant of 5.3 × 105 M-1 was two orders of magnitude larger than any other Mg(II) porphyrin-ligand binding constant reported thus far. Di- and triporphyrin arrays consisting of Mg(II) porphyrin coordinated to free base and Ni(II) porphyrinyl mono- and bis-phosphine oxides were also prepared in high yields. Spectroscopic studies indicated that these porphyrin oligomers exhibit strong inter-porphyrin electronic interaction. A Mg(II) porphyrinylphosphine oxide dimer was also isolated in a satisfactory yield. The large self-association constant of 5.5 × 108 M-1 confirmed the strong affinity of porphyrinylphosphine oxides towards Mg(II) porphyrins and established these complexes as the first strongly bound synthetic Mg(II) porphyrin analogues of the "special pair" of the photosynthetic reaction centre.

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Made available in DSpace on 2014-10-09T12:49:16Z (GMT). No. of bitstreams: 0 / Made available in DSpace on 2014-10-09T14:01:35Z (GMT). No. of bitstreams: 1 10188.pdf: 5903999 bytes, checksum: 589e8e4f7615479d8cb852a13aa871cf (MD5) / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / Tese (Doutoramento) / IPEN/T / Instituto de Pesquisas Energeticas e Nucleares - IPEN/CNEN-SP / FAPESP:99/11406-9