CORRELATION-ANALYSIS IN STRUCTURE AND CHROMATOGRAPHIC DATA OF ORGANOPHOSPHORUS COMPOUNDS BY GAI

This approach is undertaken to examine the correlation ability of the general a(N)-index (GAI) to predict chromatographic behavior. The test is performed on various types of organophosphorus compounds. The results demonstrate that the GAI possesses a good correlation with chromatographic properties.

Analysis of primary aromatic amines using precolumn derivatization by HPLC fluorescence detection and online MS identification

2-(2-Phenyl-1H-phenanthro-[9,10-d]imidazole-1-yl)-acetic acid (PPIA) and 2-(9-acridone)-acetic acid (AAA), two novel precolumn fluorescent derivatization reagents, have been developed and compared for analysis of primary aromatic amines by high performance liquid chromatographic fluorescence detection coupled with online mass spectrometric identification. PPIA and AAA react rapidly and smoothly with the aromatic amines on the basis of a condensation reaction using 1-ethyl-3-(3dimethylaminopropyl)-carbodiimide (EDC) as dehydrating catalyst to form stable derivatives with emission wavelengths at 380 and 440 nm, respectively. Taking six primary aromatic amines (aniline, 2-methylaniline, 2-methoxyaniline, 4-methylaniline, 4-chloroaniline, and 4-bromoaniline) as testing compounds, derivatization conditions such as coupling reagent, basic catalyst, reaction temperature and time, reaction solvent, and fluorescent labeling reagent concentration have also been investigated. With the better PPIA method, chromatographic separation of derivatized aromatic amines exhibited a good baseline resolution on an RP column. At the same time, by online mass spectrometric identification with atmospheric pressure chemical ionization (APCI) source in positive ion mode, the PPIA-labeled derivatives were characterized by easy-to-interpret mass spectra due to the prominent protonated molecular ion m/z [M + H](+) and specific fragment ions (MS/MS) m/z 335 and 295. The linear range is 24.41 fmol-200.0 pmol with correlation coefficients in the range of 0.9996-0.9999, and detection limits of PPIA-labeled aromatic amines are 0.12-0.21 nmol/L (S/N = 3). Method repeatability, precision, and recovery were evaluated and the results were excellent for the efficient HPLC analysis. The most important argument, however, was the high sensitivity and ease-of-handling of the PPIA method. Preliminary experiments with wastewater samples collected from the waterspout of a paper mill and its nearby soil where pollution with aromatic amines may be expected show that the method is highly validated with little interference in the chromatogram.

Urinary naphthalene and phenanthrene as biomarkers of occupational exposure to polycyclic aromatic hydrocarbons.

OBJECTIVES: The study investigated the utility of unmetabolised naphthalene (Nap) and phenanthrene (Phe) in urine as surrogates for exposures to mixtures of polycyclic aromatic hydrocarbons (PAHs). METHODS: The report included workers exposed to diesel exhausts (low PAH exposure level, n = 39) as well as those exposed to emissions from asphalt (medium PAH exposure level, n = 26) and coke ovens (high PAH exposure level, n = 28). Levels of Nap and Phe were measured in urine from each subject using head space-solid phase microextraction and gas chromatography-mass spectrometry. Published levels of airborne Nap, Phe and other PAHs in the coke-producing and aluminium industries were also investigated. RESULTS: In post-shift urine, the highest estimated geometric mean concentrations of Nap and Phe were observed in coke-oven workers (Nap: 2490 ng/l; Phe: 975 ng/l), followed by asphalt workers (Nap: 71.5 ng/l; Phe: 54.3 ng/l), and by diesel-exposed workers (Nap: 17.7 ng/l; Phe: 3.60 ng/l). After subtracting logged background levels of Nap and Phe from the logged post-shift levels of these PAHs in urine, the resulting values (referred to as ln(adjNap) and ln(adjPhe), respectively) were significantly correlated in each group of workers (0.71 < or = Pearson r < or = 0.89), suggesting a common exposure source in each case. Surprisingly, multiple linear regression analysis of ln(adjNap) on ln(adjPhe) showed no significant effect of the source of exposure (coke ovens, asphalt and diesel exhaust) and further suggested that the ratio of urinary Nap/Phe (in natural scale) decreased with increasing exposure levels. These results were corroborated with published data for airborne Nap and Phe in the coke-producing and aluminium industries. The published air measurements also indicated that Nap and Phe levels were proportional to the levels of all combined PAHs in those industries. CONCLUSION: Levels of Nap and Phe in urine reflect airborne exposures to these compounds and are promising surrogates for occupational exposures to PAH mixtures.

Catalyst, additive and substrate effects in intramolecular aromatic additions of alpha-diazoketones

This thesis is focused on transition metal catalysed reaction of α-diazoketones leading to aromatic addition to form azulenones, with particular emphasis on enantiocontrol through use of chiral copper catalysts. The first chapter provides an overview of the influence of variation of the substituent at the diazo carbon on the outcome of subsequent reaction pathways, focusing in particular on C-H insertion, cyclopropanation, aromatic addition and ylide formation drawing together for the first time input from a range of primary reports. Chapter two describes the synthesis of a range of novel α-diazoketones. Rhodium and copper catalysed cyclisation of these to form a range of azulenones is described. Variation of the transition metal catalyst was undertaken using both copper and rhodium based systems and ligand variation, including the design and synthesis of a novel bisoxazoline ligand. The influence of additives, especially NaBARF, on the enantiocontrol was explored in detail and displayed an interesting impact which was sensitive to substituent effects. Further exploration demonstrated that it is the sodium cation which is critical in the additive effects. For the first time, enantiocontrol in the aromatic addition of terminal diazoketones was demonstrated indicating enantiofacial control in the aromatic addition is feasible in the absence of a bridgehead substituent. Determination of the enantiopurity in these compounds was particularly challenging due to the lability of the products. A substantial portion of the work was focused on determining the stereochemical outcome of the aromatic addition processes, both the absolute stereochemistry and extent of enantiopurity. Formation of PTAD adducts was beneficial in this regard. The third chapter contains the full experimental details and spectral characterisation of all novel compounds synthesised in this project, while details of chiral stationary phase HPLC and 1H NMR analysis are included in the appendix.

Rapid separation of biologically important low molecular weight compounds by microchip electrophoresis and ultra-fast performance liquid chromatography

The research work in this thesis reports rapid separation of biologically important low molecular weight compounds by microchip electrophoresis and ultrahigh liquid chromatography. Chapter 1 introduces the theory and principles behind capillary electrophoresis separation. An overview of the history, different modes and detection techniques coupled to CE is provided. The advantages of microchip electrophoresis are highlighted. Some aspects of metal complex analysis by capillary electrophoresis are described. Finally, the theory and different modes of the liquid chromatography technology are presented. Chapter 2 outlines the development of a method for the capillary electrophoresis of (R, S) Naproxen. Variable parameters of the separation were optimized (i.e. buffer concentration and pH, concentration of chiral selector additives, applied voltage and injection condition).The method was validated in terms of linearity, precision, and LOD. The optimized method was then transferred to a microchip electrophoresis system. Two different types of injection i.e. gated and pinched, were investigated. This microchip method represents the fastest reported chiral separation of Naproxen to date. Chapter 3 reports ultra-fast separation of aromatic amino acid by capillary electrophoresis using the short-end technique. Variable parameters of the separation were optimized and validated. The optimized method was then transferred to a microchip electrophoresis system where the separation time was further reduced. Chapter 4 outlines the use of microchip electrophoresis as an efficient tool for analysis of aluminium complexes. A 2.5 cm channel with linear imaging UV detection was used to separate and detect aluminium-dopamine complex and free dopamine. For the first time, a baseline, separation of aluminium dopamine was achieved on a 15 seconds timescale. Chapter 5 investigates a rapid, ultra-sensitive and highly efficient method for quantification of histamine in human psoriatic plaques using microdialysis and ultrahigh performance liquid chromatography with fluorescence detection. The method utilized a sub-two-micron packed C18 stationary phase. A fluorescent reagent, 4-(1-pyrene) butyric acid N-hydroxysuccinimide ester was conjugated to the primary and secondary amino moieties of histamine. The dipyrene-labeled histamine in human urine was also investigated by ultrahigh pressure liquid chromatography using a C18 column with 1.8 μm particle diameter. These methods represent one of the fastest reported separations to date of histamine using fluorescence detection.

Synthesis and reactivity of pyridine substituted α-diazocarbonyl compounds and exploration of rhodium carboxylates as asymmetric catalysts

The primary objective of this thesis was the preparation of a series of pyridine-containing α-diazocarbonyl compounds and subsequent investigation of the reactivity of these compounds on exposure to transition metal catalysts. In particular, the reactivity of the pyridyl α-diazocarbonyls was compared to that of the analogous phenyl α-diazocarbonyl compounds to ascertain the impact of replacement of the phenyl ring with pyridine. The first chapter initially provides a brief introduction into α-diazocarbonyl chemistry, comprising a compendium of well-established and recently developed methods in the preparation of these compounds, as well as an outline of the reactivity of these versatile substrates. The substantive element of this introductory chapter comprises a detailed review focused on transition metal-catalysed transformations of heterocyclic α-diazocarbonyl compounds, highlighting the extraordinary diversity of reaction products which can be accessed. This review is undertaken to set the work of this thesis in context. The results of this research are discussed in the second and third chapters together with the associated experimental details, including spectroscopic and analytical data obtained in the synthesis of all compounds during this research. The second chapter describes the preparation of a range of novel pyridine-containing α-diazocarbonyl compounds via a number of synthetic strategies including both acylation and diazo transfer methodologies. In contrast to the phenyl analogues, the generation of the pyridine α-diazocarbonyl substrates was complicated by a number of factors including the inherent basicity of the pyridine ring, tautomerism and existence of rotamers. Rhodium- and copper-mediated transformations of the pyridine-containing α-diazocarbonyl compounds is discussed in detail displaying very different reactivity patterns to those seen with the phenyl analogues; oxidation to 2,3- diketones, 1,2-hydride shift to form enones and oxonium and sulfonium ylide formation/rearrangement are prominent in the pyridyl series, with no evidence of aromatic addition to the pyridine ring. The third chapter focuses on exploration of novel chiral rhodium(II) catalysts, developed in the Maguire team, in both intermolecular cyclopropanations and intramolecular C–H insertion reactions. In this chapter, the studies are focused on standard α-diazocarbonyl compounds without heteroaryl substituents. The most notable outcome was the achievement of high enantiopurities for intramolecular C–H insertions, which were competitive with, and even surpassed, established catalyst systems in some cases. This work has provided insight into solvent and temperature effects on yields as well as enantio- and diastereoselectivity, thereby providing guidance for future development and design of chiral rhodium carboxylate catalysts. While this is a preliminary study, the significance of the results lie in the fact that these are the first reactions to give substantial asymmetric induction with these novel rhodium carboxylates. While the majority of the α-diazocarbonyl compounds explored in this work were α-diazoketones, a number of α-diazoesters are also described. Details of chiral stationary phase HPLC analysis, single crystal analysis and 2D NMR experiments are included in the Appendix (Appendix III-V).

Polycyclic aromatic hydrocarbons (PAHS) (I): Toxicity, population exposure and involved foods

Food is one of the main exogenous sources of genotoxic compounds. In heated food products, polycyclic aromatic hydrocarbons (PAHs) represent a priority group of genotoxic, mutagenic and/or carcinogenic chemical pollutants with adverse long-term health effects. People can be exposed to these compounds through different environments and via various routes: inhalation, ingestion of foods and water and even percutaneously. The presence of these compounds in food may be due to environmental contamination, to industrial handling and processing of foods and to oil processing and refining. The highest levels of these compounds are found in smoked foods, in seafood which is found in polluted waters, in grilled meats and, to a lesser extent, in vegetable fats and oils. Lower levels of PAHs are found in vegetables and in cereals and its products.

Polycyclic aromatic hydrocarbons (PAHS) (I): Measures of prevention and control

Measures of prevention and control against polycyclic aromatic hydrocarbons (PAHs) focus on an official food control, a code of best practice to reduce PAHs levels by controlling industry and in the development of a chemopreventive strategy. Regulation (EU) 835/2011 establishes maximum levels of PAHs for each food group. In addition, Regulations (EU) 333/2007 and 836/2011 set up the methods of sampling and analysis for its official control. Scientific studies prove that the chemopreventive strategy is effective against these genotoxic compounds effects. Most chemopreventive compounds studied with proven protective effects against PAHs are found in fruit and vegetables.

Alkali-metal salts of aromatic carboxylic acids: Liquid crystals without flexible chains

The alkali-metal salts of meta-substituted benzoic acids exhibit a smectic A mesophase at high temperatures. These compounds are examples of liquid crystals without terminal alkyl chains. The influence of the metal ion and of the type of substituents on the transition temperatures is discussed. Compounds with the substituent in the ortho- and para-positions are non-mesomorphic. The crystal structures of the compounds Rb(C7H4ClO2)(C7H4ClO2H), Na(C7H4IO2)(H2O), K(C7H4ClO2)(C7H4ClO2H) and Rb(C7H4BrO2)(C7H4BrO2H) have been determined by X-ray crystallography. These compounds possess a layerlike structure in the solid state. ((C) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)

Polycyclic aromatic hydrocarbon (PAH) dispersion and deposition to vegetation and soil following a large scale chemical fire

Polycyclic aromatic hydrocarbons (PAHs) were determined in soil and vegetation following a large scale chemical fire involving 10,000 ton of polypropylene. In comparison with sites outside the plume from the fire, PAH concentrations were elevated in grass shoots (by up to 70-fold) and in soil (by up to 370-fold). The pattern of PAH dispersion under the plume was dependent on the physical-chemical properties of individual PAHs. The lighter, least hydrophobic PAHs were dispersed into the environment at greater distances than heavier, more hydrophobic PAHs. At the most distant sampling point (4.5 km) under the plume, the low molecular weight PAHs were still considerably elevated in vegetation samples compared to control sites. Dispersion appeared to be regulated by the compounds partitioning between the vapour and particulate phase, with dry particulate deposition occurring closer to the fire source than gaseous deposition. For all PAHs, the fire resulted in greater contamination of soils compared to grasses, with the relative ratio of plant/soil contamination decreasing as hydrophobicity increased.

Assessment of Polycyclic Aromatic Hydrocarbons in an Urban Soil Dataset

We compare a suite of Polycyclic Aromatic Hydrocarbons (Parent PAHs) in soils and air across an urban area (Belfast UK). Isomeric PAH ratios suggest that soil PAHs are mainly from a combustion source. Fugacity modelling across a range of soil temperatures predicts that four ring and larger PAHs from pyrene to indeno[1,2,3–cd]pyrene all partition strongly (>98%) to the soil compartment. This modelling also implies that these PAHs do not experience losses through partitioning to other phases (air, water) due to soil temperature effects. Such modelling may help in understanding the overall contaminantdistribution in soils. The air and soil data together with modelling suggests that care must be taken when considering isomeric ratios of compounds with mass lighter than 178 (i.e. phenanthrene and anthracene) in the soil phase. Comparison of duplicate and replicate samples suggest that field sampling of duplicates dominates uncertainty and validated methodologies for selection of field duplicates and lab splitting are required. As the urban soil four ring PAHs are at equilibrium in the soil phase, and have characteristic ratios that are dominated by a combustion source that is a single controlling factor over spatial distribution, methods that calculate background concentrations can be compared.

Detection Limits of Organic Compounds Achievable with Intense, Short-Pulse Lasers

Many organic molecules have strong absorption bands which can be accessed by ultraviolet short pulse lasers to produce efficient ionization. This resonant multiphoton ionization scheme has already been exploited as an ionization source in time-of-flight mass spectrometers used for environmental trace analysis. In the present work we quantify the ultimate potential of this technique by measuring absolute ion yields produced from the interaction of 267 nm femtosecond laser pulses with the organic molecules indole and toluene, and gases Xe, N2 and O2. Using multiphoton ionization cross sections extracted from these results, we show that the laser pulse parameters required for real-time detection of aromatic molecules at concentrations of one part per trillion in air and a limit of detection of a few attomoles are achievable with presently available commercial laser systems. The potential applications for the analysis of human breath, blood and tissue samples are discussed.

Degradation of the polycyclic aromatic hydrocarbon (PAH) fluorene is retarded in a Scots pine ectomycorrhizosphere

Polycyclic aromatic hydrocarbons (PAHs) are an important class of persistent organic pollutants (POPs) in the environment and accumulate in forest soils. These soils are often dominated by ectomycorrhizal (EcM) roots, but little is known about how EcM fungi degrade PAHs, or the overall effect of field colonized EcM roots on the fate of PAHs. The ability of eight EcM fungi to degrade PAHs in liquid culture spiked with ¹⁴C labelled PAHs was investigated. Microcosms were used to determine the impact of naturally colonized mycorrhizal pine seedlings on PAH mineralization and volatilization. Only two EcM fungi (Thelephora terrestris and Laccaria laccata) degraded at least one PAH and none were able to mineralize the PAHs in pure culture. Where degradation occurred, the compounds were only mono-oxygenated. EcM pine seedlings did not alter naphthalene mineralization or volatilization but retarded fluorene mineralization by 35% compared with unplanted, ectomycorrhizosphere soil inoculated, microcosms. The EcM fungi possessed limited PAH degrading abilities, which may explain why EcM dominated microcosms retarded fluorene mineralization. This observation is considered in relation to the 'Gadgil-effect', where retarded litter decomposition has been observed in the presence of EcM roots. © New Phytologist (2004).

Neutron Scattering of Aromatic and Aliphatic Liquids

Organic solvents, such as cyclohexane, cyclohexene, methylcyclohexane, benzene and toluene, are widely used as both reagents and solvents in industrial processes. Despite the ubiquity of these liquids, the local structures that govern the chemical properties have not been studied extensively. Herein, we report neutron diffraction measurements on liquid cyclohexane, cyclohexene, methylcyclohexane, benzene and toluene at 298 K to obtain a detailed description of the local structure in these compounds. The radial distribution functions of the centres of the molecules, as well as the partial distribution functions for the double bond for cyclohexene and methyl group for methylcyclohexane and toluene have been calculated. Additionally, probability density functions and angular radial distribution functions were extracted to provide a full description of the local structure within the chosen liquids. Structural motifs are discussed and compared for all liquids, referring specifically to the functional group and aromaticity present in the different liquids.

Reduction vs acetalisation of some carbonyl-compounds by means of methylselenol and lewis-acids

Aliphatic ketones and aromatic carbonyl compounds on reaction with methylselenol :and a Lewis acid, are shown to undergo acetalisation and/or reduction to methyl selenide, the unexpected reduction reaction being predominant in most cases.