A method has been developed to analyse PAHs in solid environmental matrices using an in-situ PFE-GC-MS method. The method involves the use of 2 g of alumina as the in-situ clean-up sorbent, in order to remove interferences and impurities in the soils that could contaminate the instrument. By using this method, samples from two sites have been analysed for PAHs content, specifically (i) soils from a contaminated former Tar Works site, and (ii) urban road dust from Newcastle upon Tyne, UK. It was found that particle size was a significant parameter in both cases, showing a higher concentration (from 9 to 1404 mg/kg in the Tar Works, and 0.5 to 95 mg/kg in the road dust site) in the smaller grain size (< 250 μm); this is important when considering the ingestion exposure pathway as smaller particles are more likely to be ingested by children via hand-to-mouth behaviour. In addition, the source of the PAHs was investigated in the anthropogenically contaminated areas; it was found that pyrogenic sources (higher molecular weight PAHs, 4-5-6 rings) of PAHs were significantly more abundant compared to petrogenic sources (lower molecular weight PAHs: 2-3 rings). Generally the lower molecular weight such as naphthalene, acenaphthene, acenaphthylene and fluorene were found in lower concentration than fluoranthene, pyrene and other higher molecular weight PAH. In the case of the Tar Works lower molecular weights PAH were showing individual PAH concentration below 50 mg/kg whereas higher molecular weights were showing individual concentrations up to 270 mg/kg. The same trend was observed in the road dust samples, and was clearly identified by using ratios of PAH concentration to demonstrate dominance of pyrogenic sources. In this latter case, the pyrogenic sources were clearly identified as vehicle exhaust. However, other sources were identified such as the road pavement and the tire debris as potential sources of PAHs in urban areas. In the former case the PAH distribution was attributed to the locations of the chemicals productions areas in the former industrial site. The mean daily oral intake was used as an estimate of the environmental health risk from the sites; values of PAH intake were determined based on the PAH individual concentration and compared against known values. Risk was often present for pyrogenic PAHs in road dust and soil samples. Further investigation of the environmental health risk was realized using a physiologically-based extraction test on soil samples from the former Tar works; the results, using a fed-version of the test, showed elevated bioaccessibilities of PAHs, mainly due to the presence of food and the lipophilicity of PAHs, however other PAH properties could influence their individual mobilizations such as the molecular weight, the ring number and the liquid-to-soil ratio. It was noticed that the risk can be evaluated differently and can show different conclusions depending on the risk assessment chosen. Overall, the determination of PAHs in environmental soil and urban dust samples has highlighted the necessity to assess the potential impact on human health of their presence. The use of the fed-version of the physiologically-based extraction test is one tool that could be used to assess the environmental health risk to humans. This tool was shown to be robust using an inter-laboratory study, as values for total PAH content and bioaccessible fractions were within the same acceptable range.

In assessing human health risk of potentially toxic elements (PTEs), it is not the concentration of PTEs in the environmental matrices that is of greatest concern but the fraction that is absorbed into the body via the exposure pathways. The determination of this fraction (i.e. the bioaccessible fraction) through the application of bioaccessibility protocols is the focus of this work. The study investigated human health risk of PTEs (As, Cd, Cr, Cu, Pb, Mn, Ni and Zn) from oral ingestion of soil / dust, inhalation of urban street dust and air-borne dust (PM10). To assess health risk via oral ingestion of soil and dust, total PTEs were determined in twenty nine soil samples collected from children’s playing fields and ninety urban street dusts collected from six cities. Analysis of total PTE content in these samples via ICP-MS revealed high Pb concentrations (> 450 mg/kg) in 3 playground soils and 32 urban street dusts. Detailed quantitative risk assessment (DQRA) carried out in the playgrounds showed that no significant possibility of significant harm exist in the playgrounds. The concentration of Pb from a particular dust sample based on 50 mg/day ingestion rate that a child might possibly ingest to reach the estimated tolerable daily intake was calculated and it exceeded the tolerable daily intake for oral ingestion in 4 cities. The bioaccessible PTEs were determined both in the soil and dust samples using the Unified BARGE method and the result showed that in all the samples, the PTEs solubilised more in the gastric phase than in the intestinal phase. A new method has been developed; simulated epithelial lung fluid (SELF) and was used to assess the respiratory bioaccessibility of Pb from inhalable urban dust (<10 µm). Low bioaccessibility (<10 %) was recorded in all the samples analysed.

A novel method of preparing substituted pyridines has been developed. This method uses readily available [3-ketoesters and amidrazone as starting materials. The pyridines obtained do not require purification and different substitution patterns, not available by known methods, can be obtained. The formation of 1,2,3-tricarbonyl compounds was achieved by oxidation of the alcohol precursors, following two different methods. a-Chloro-ct-acetoxy-f3-dicarbonyls were prepared in excellent yields and were shown to react as tricarbonyl equivalents in the formation of 1,2,4-triazines. Regioselective condensation reactions were observed between different amidrazones with tricarbonyl and tricarbonyl equivalents to produce a series of novel 1,2,4-triazines in good yields with no contamination by any regioisomer. When 1,2,4-triazines were obtained from a-chloro-a-acetoxy-P-dicarbonyls, 2.5 equivalents of amidrazone were required. However, decomposition of a-chloro-a-acetoxy-P-dicarbonyls prior to reaction with 1 equivalent of amidrazone yielded the 1,2,4-triazines in good yields. These 1,2,4-triazines underwent aza Diels-Alder cycloaddition reactions with 2,5- norbornadiene to give a series of novel 2,3,6-trisubstituted pyridines. The pyridines bearing electron withdrawing groups as substituents could also be obtained in a 'one- pot' reaction from their corresponding tricarbonyls or tricarbonyl derivatives. The 1,2,4- triazines bearing electron donating groups could be converted to their corresponding pyridines either by changing the reaction conditions or, when possible, by conversion of the electron donating group into a more electron withdrawing substituent by oxidation (e.g. sulphoxide substituent). Pyridines bearing a sulphoxide substituent undergo nucleophilic substitutions, giving great scope to introduce different functionality in the C-6 of the pyridines.

Studies in Benzimidazo[2,1-a]isoquinoline Chemistry by Michael John Donaghy B. Sc. (Hons.) Ellipticine, a member of the pyrido[4,3-b]carbazole alkaloid family first isolated in 1959 from the leaves of the plant Ochrosia Elliptica has been shown to possess anti-cancer activity against various tumours. Ellipticine is thought to undergo biological oxidation to give the more active 9-hydroxyellipticine that is subsequently converted to a highly reactive quinone-imine intermediate. The quinone-imine is then thought to interact with bionucleophiles in the body promoting cell death. The aim of the project was to synthesise a series of benzimidazo[2,1-a]isoquinolines. The benzimidazo[2,1-c]isoquinolines were similar in general structure to ellipticines and should therefore undergo similar biological reactions. The target benzimidazo[2,1-a]isoquinolines have been screened to evaluate their ability to inhibit the enzyme topoisomerase II that is involved in DNA replication and ultimately cell reproduction. The target compounds have also been evaluated by the American National Cancer Institute.

Quasi-continuous measurement of benzene, toluene, ethylbenzene and isomers of xylene in northern England has been performed using an automated thermal desorption - gas chromatography - flame ionisation detector (TD-GC-FID) system. The TD-GC-FID system was mounted in a mobile laboratory, together with a TEOM (Tapered Element Oscillating Microbalance) system for particulate monitoring, and a weather station. Both systems have been applied to urban and suburban sites in order to examine the behaviour of BTEX aromatics at these localities, under a range of boundary layer environments. Measurement of BTEX aromatics and particulate matter has also been performed within a bus depot, a site which was effectively isolated from the free boundary layer overnight, to contrast the behaviour of BTEX in sunlit and non-sunlit atmospheres. Time series analysis of the concentration ratios of individual BTEX aromatics has been performed and diurnal seasonality has been demonstrated at a number of sites. Significant differential removal of individual BTEX aromatics has been found to occur overnight. Relative removal rates have been measured for this period, and values indicate that accepted tropospheric transformation mechanisms of the BTEX aromatics are not responsible. The available experimental and theoretical evidence collected in this research serves to support the supposition that a physical process, which is related to atmospheric temperature, volatility of individual BTEX aromatics, and pressures of individual BTEX aromatics, governs nocturnal differentiation of the concentration of BTEX aromatics. A postulated effect, which may contribute to nocturnal differential, is preferential absorption of particular BTEX aromatics to a liquid organic carbon phase, which has been shown to be associated with diesel carbonaceous combustion aerosol. The latter supposition has been partially corroborated by the findings of a separate study exploring the composition of carbonaceous combustion aerosol by GCMS, XRF, DTA, DSC, and FTIR.

A Q-switched Nd:YAG laser is used to remove ballpoint pen ink from 'Roma', a 100% cotton rag art paper. The laser was operated at 1064 run, pulse duration 87 ns, and using a nominal fluence of 41 ± 12 Jcm-2. By shortening the pulse length (63 and 26 ns), using a Glan-Thompson prism the ink removal threshold was reduced to 24 ± 7 and 20 ± 6 Jcm-2 respectively. The physical damage to the paper is observed under SEM and found to be less disruptive to the surface fibres than contemporary mechanical methods of ink removal; scalpel and eraser. The tensile strength of laser treated paper is measured and found to remain unaffected below ink removal threshold fluences, although there is an increased tendency to tear at laser treatment sites. Repeat testing with artificially aged laser treated samples shows a marked decrease in tensile strength in comparison with an aged reference. Laser treated paper (nominal fluence of 41 ± 12 Jcm2, pulse length 87 ns) is tested for evidence of thermal degradation, via oxidation and depolymerisation. The tests include the Russell effect test for the presence of peroxides (oxidation), the methylene blue test for the presence of carboxyl groups (oxidation), FTIR spectroscopy to determine the presence of carboxyl, carbonyl, and conjugated groups (oxidation), and GC/MS to test for the presence of sugars (depolymerisation). The tests suggest that there is thermal degradation predominantly via depolymerisation. This is supported by repetition of the tests on laser treated samples prepared in an argon atmosphere. The laser treated paper is subjected to accelerated ageing in a humid oven to simulate natural is considered to be a reaction between the sizing agent (gelatin) and sugars formed during depolymerisation The tests are repeated on 'Roma' paper laser treated with shorter laser pulses (nominal fluence 24 ± 7 and 20 ± 6 Jcm-2, pulse durations of 63 and 26 ns), and this is found to have significantly less physical and chemical effect on the paper. Accelerated ageing of short pulse laser treated samples did not result in colour changes with respect to reference samples, indicating a more limited chemical interaction with the paper.

A new method for the analysis of alcohol ethoxylates (AEs) using liquid chromatography with electrospray ionisation mass spectrometry (LC/ESI-MS) is described. The procedure in. corporates a novel derivatisation step with phthalic anhydride for the analysis of E00_,o ethoxylates in a single analysis. The derivatives obtained have proved to be very stable and the negative ion spectra show reduced background ions and competing adduct formation as compared to positive ion spectra. An automated solid phase extraction (SPE) step is used to allow both pre- concentration and clean-up of the environmental samples. The addition of 40 % v/v methanol prior to loading samples provides more efficient recovery of AEs across the C12 to C18 range than previously reported in the literature, reducing hydrophobic losses. Recoveries from final effluent spiked at 100 pg/L total AE, for the 126 species analysed, were found to be in the range 55 — 117%, with approximately 100 of the individual analytes having recoveries of 90 —105 %. A method detection limit of 0.02 iig/L for individual ethoxylate components is reported with the instrument operated in scan mode over the range m/z 300 to 1300. The method was applied to sewage effluent and influent samples, with AEs determined at approximately 7 and 5000 µg/L, respectively, indicating efficient removal of AEs in the sewage treatment plant. The AEs in the final effluent consisted primarily of fatty alcohols (FAs). Similar optimisation in the extraction of sediment and sludge samples was carried out with ultrasonic, Soxhlet and accelerated solvent extraction (ASE) methodology being compared. The most efficient technique was ASE, which was then used to analyse an activated sludge sample, where again. significantly high levels of FAs, compared to other AEs, were found in the sample. This data and the final effluent data are consistent with other current monitoring data for AEs and show the importance of a method capable of extracting and ionising the free alcohol efficiently. The AE fingerprint during biodegradation studies was also accurately determined giving elucidation of mechanisms of primary degradation. Linear and branched AEs were investigated with metabolite identification also carried out for the linear AE. Biodegradation of native AEs present in sewage influent was also studied in direct discharge scenarios to aid in. risk assessment in situations where sewage treatment is absent.

A group of simple amide receptors were synthesised to investigate the effect varying the number/type of hydrogen bond donors or in preorganisation has on host/guest binding abilities. Proton NMR titrations revealed preorganised nitrogen atoms could reduce the size of the binding cleft increasing the selectivity for the smaller anions and binding affinities were increased by the addition of additional hydrogen bond donors, increasing the size of the binding cleft and the presence of sulphonamide groups. A number of receptors were also investigated as colorimetric sensors and visual colour changes were observed with the addition of guest, however further investigations revealed these could be due to deprotonation of the receptor. A fluorescent cation was also synthesised which proton NMR titrations proved had increasing binding affinities. Fluorescence titrations showed the addition of guest increased the fluorescence intensity suggesting it could possibility be used for calculating the concentration of chloride in serum samples. Cyclotrimeric receptors containing three urea/thiourea moieties were successfully synthesised by a one-pot cyclotrimerisation. However they proved to be very insoluble preventing purification and investigations of their binding ability. The presence of TBA nitrate proved to have a templating effect in the synthesis of the thiourea cyclotrimer but not the urea cyclotrimer. A step-wise cyclotrimerisation was not possible due to the lack of solubility of the products from step-one for the urea receptor and step-two for the thiourea. However Proton NMR titrations of these receptors revealed the urea/thiourea hydrogen bond donors formed stronger interactions with anionic guests than the previous amide receptors. Finally a number of substrates containing alkene moieties and bis-urea/thiourea receptors were synthesised in the hope of templating cycloaddition photochemical reactions forcing the formation of head-to-head photodimers. Unfortunately cycloaddition photochemical reactions were unsuccessful due to the lack of solubility of both the receptors and substrates preventing any investigations being carried out.

My original contribution to knowledge is presented in this work, in the new application of a previously synthesised manganese (III) complex as an effective and selective oxidation catalyst. Development of a series of conditions in which epoxidation reactions can successfully be undertaken was established with both hydrogen peroxide and n-tetrabutyl ammonium oxone. Epoxidations undertaken with hydrogen peroxide were commensurate with a competitive catalase like reaction. Establishment of the factors that drive the catalase type of oxidative reaction with the Mn(DMHP)2.Cl complex, including Michaelis Menten kinetic parameters and the effects of temperature and pH, allowed for a protocol to be set up that can favour epoxidation over catalase-like dismutation of hydrogen peroxide. To coincide with epoxidation work on hydrogen peroxide, a DFT study on the proposed reaction intermediates is presented with a focus on the likely active catalytic species. The role of imidazole was probed and showed that coordination of imidazole is slightly unfavoured and will be in equilibrium in solution, which coincided with experimental observations that imidazole was required in a slight excess for successful epoxidation. This work further demonstrated that in acidic conditions an oxomanganese(V) species is highly favoured and corresponds excellently to what is observed experimentally where very good conversion to epoxide of cyclooctene is achieved at pH 4.7. Work utilising n-tetrabutyl ammonium oxone as oxidant exhibited good to excellent conversions, and a trend was observed of high selectivity to strained cyclic alkenes. This was further probed by a joint study using a series of strained substrates that were synthesised and computational chemistry to determine the strains over the alkene bond. Collaborative work with the national mass spectrometry service allowed for identification of the intermediates of the reaction my mass spectrometry coupled with a UV/Vis spectroscopy study. Identification of an oxomanganese(V) species is presented in mass spectrometry as the active intermediate in epoxidations using n-tetrabutyl ammonium oxone . A study as to the effects of additive bases using cyclic voltammetry demonstrated a significant electronic effect on the oxidation potential of the catalyst as the source of the inductive effect, identification by mass spectrometry and UV/Vis showed direct evidence of axial ligation of the additive bases. Using an industrial manganese (II) catalyst in the bleaching of red stains (β-carotene and crocin), a protocol for bleaching was established, using UV/Vis as a method of analysis. Synthesis of a series of chelants which are used to stabilise the catalyst in the formulation was undertaken. Testing of the chelants in the bleaching system demonstrated their utility in the wash system across a pH range. The utility of surfactant when using chelants with the catalyst was established to give excellent bleaching and stability of the catalyst.

Pyridines occupy a central part in modern day organic chemistry. Recent studies in various fields of chemistry, biology and physics have featured numerous examples and applications of these compounds. The purpose of this study was to produce a library of polysubstituted pyridines, 2,2'-bipyridines and 2,2':6',2"-terpyridines via pathways that allowed unusual or even unique substitution patterns. To achieve a generic pyridine synthesis that delivers a diversity of products tailored to different industrial needs, a strategy by which the target molecule is constructed in a [2+2+2]-manner was chosen, i.e. the six atoms of the pyridine ring and their pendant functionalities are traced back to three building blocks, each delivering two atoms to the pyridine ring. A range of a-acetoxy-a-chloro-P-keto esters were prepared in three steps from commercially available P-keto esters through a-chlorination with sulfuryl chloride, a-acetoxylation with acetic acid and triethylamine and a second a-chlorination in good overall yields (69 — 89 %) without the need for chromatographic purification. These a-acetoxy-a-chloro-j3-keto esters served as equivalents for a,[3-diketo esters (building block 1) in the synthesis of various 1,2,4- triazines through condensation with picolinohydrazonamides or thiosemicarbazides (building block 2). A subsequent aza Diels-Alder reaction of these 1,2,4-triazines with electron-rich dienophiles (building block 3) such as 2,5-norbornadiene, 1-pyrrolidino- 1 -cyclopentene and 2,3-dihydrofuran furnished an array of novel polysubstitued (bi)pyridines. The two-step sequence of condensation and aza Diels-Alder reaction could be advanced into a 'one-pot' synthesis on several occasions. Furthermore, we devised a feasible synthetic alternative towards a,(3-diketo esters. Alpha-picolinoyl-3-keto esters were prepared from the same starting materials as the a-acetoxy-a¬chloro-P-keto esters in a shortened two-step sequence of a-chlorination of P-keto esters with sulfuryl chloride and replacement of the chloro group by a picolinoyl group using picolinic acid and KHCO3. The overall yields of a-picolinoyl-f3-keto esters (55 — 91 %) were comparable to those of the a-acetoxy-a-chloro-P-keto esters. Copper(II) acetate-facilitated methanolysis of a-picolinoyl-P-keto esters and immediate oxidation of the in situ generated a-hydroxy-P-keto esters by excess copper(II) acetate afforded a,(3-diketo esters which reacted with hydrazonamides in the same manner as the a-chloro-a-acetoxy-P-keto esters. However, in terms of product purity and yield the `chloroacetate route' remains the superior strategy.