No / This study shows that prostaglandins in human FM55 melanoma cells and epidermal melanocytes are produced by COX-1. Prostaglandin production in FM55 melanoma cells was unrelated to that of melanin suggesting that the two processes can occur independently. ¿-Melanocyte stimulating hormone (¿-MSH), which had no effect on melanin production in FM55 cells, stimulated PGD2 production in these cells without affecting PGE2. While cAMP pathways may be involved in regulating PGD2 production, our results suggest that ¿-MSH acts independently of cAMP, possibly by regulating the activity of lipocalin-type PGD synthase. This ¿-MSH-mediated effect may be associated with its role as an immune modulator. / The Wellcome Trust

No / The Flinders Sensitive Line (FSL) rat is a genetic animal model of depression. Following recent findings that the brain fatty acid composition of FSL is characterised by increased arachidonic acid (AA), we used electrospray tandem mass spectrometry and 1H-NMR to examine lipid species in different brain areas. Cholesterol and sphingolipids were increased in the hypothalamus of the FSL rats. Furthermore, arachidonic acid-containing phosphatidylcholine species (AA-PC) were elevated with PC16:0/20:4, PC18:1/20:4 and PC18:0/20:4 (p<0.003) increased in the hypothalamus and striatum. In contrast, there was a decrease in some docosahexaenoic acid (DHA)-containing species, specifically PC18:1/22:6 (p<0.003) in the striatum and PE18:1/22:6 (p<0.004) in the prefrontal cortex. Since no significant differences were observed in the erythrocyte fatty acid concentrations, dietary or environmental causes for these observations are unlikely. The increase in AA-PC species which in this animal model may be associated with altered neuropathy target esterase activity, an enzyme involved in membrane PC homeostasis, may contribute to the depressive phenotype of the FSL rats.

No / Prostanoids modulate the activity of human pregnant myometrium and their functional role can be appreciated through characterisation of prostanoid receptors and tissue concentration of prostanoids. We have applied a lipidomic approach to elucidate the profile of prostanoids in human non-labouring and labouring myometrium. We have identified a total of nineteen prostanoids including prostacyclin, thromboxanes, prostaglandins and dihydro-prostaglandins. Prostacyclin was the predominant prostanoid in both non-labouring and labouring myometria, with PGD2 and PGF2¿ being the second most abundant. Although the total amount of prostanoids was increased in the labouring tissue, PGE2 and 13,14-dihydro-15-keto-PGE2 were the only prostanoids to increase significantly at early and late labour (p¿0.001). Our data suggest that PGF2¿ plays an important role in parturition, whilst the increase in PGE2 could occur to facilitate cervical dilation and relaxation of the lower myometrium during labour. Although the elevation in TXA2 was less marked than expected, in terms of translation to function even a relatively small increase in the level of this potent spasmogen may have significant effects.

No / Lipid mediators are produced from the oxidation of polyunsaturated fatty acids through enzymatic and free radical-mediated reactions. When subject to oxygenation via cyclooxygenases, lipoxygenases, and cytochrome P450 monooxygenases, polyunsaturated fatty acids give rise to an array of metabolites including eicosanoids, docosanoids, and octadecanoids. These potent bioactive lipids are involved in many biochemical and signaling pathways, with inflammation being of particular importance. Moreover, because they are produced by more than one pathway and substrate, and are present in a variety of biological milieus, their analysis is not always possible with conventional assays. Liquid chromatography coupled to electrospray mass spectrometry offers a versatile and sensitive approach for the analysis of bioactive lipids, allowing specific and accurate quantitation of multiple species present in the same sample. Here we explain the principles of this approach to mediator lipidomics and present detailed protocols for the assay of enzymatically produced oxygenated metabolites of polyunsaturated fatty acids that can be tailored to answer biological questions or facilitate assessment of nutritional and pharmacological interventions.

Broadening the spectrum available to solar cells towards infrared wavelengths is one way to increase efficiency of organic solar devices. This thesis explores the possibilities of these organic heterojunction devices and two different material classes in thin films and organic solar devices: tin phthalocyanines (SnPcs) and aza-bodipys. To estimate the efficiency reachable under sunlight, model calculations are done for single and tandem cells. These calculations include a distinction between the optical gap and the electrical gap and the splitting of the quasi-Fermi levels. With a number of assumptions, e.g. a fill factor (FF) and an external quantum efficiency (EQE) within the absorption range of 65%, the resulting efficiencies are 15% in a single cell and of 21% in a tandem cell. Halogenation is known to lower the energy levels of molecules without chang-ing the optical band gap. Three different fluorinated and chlorinated SnPcs are investigated and compared to the neat SnPc. While chlorination of SnPc worsens the transport properties of the active layer leading to a lowered FF, the fluorina-tion of SnPc results in the intended increase in VOC and, consequently, efficiency for planar heterojunctions. In bulk heterojunction, however, fluorination does not change the efficiency probably due to the unstably bound fluorine. One method to modify the ionization potential (IP) and the absorption of the second material class, the aza-bodipys, is the annulation of the benzene ring. The energy levels determined by CV and UPS measurement and DFT-calculation show very good agreement and can be linked to a decrease in VOC: The Ph4-bodipy (not benzannulated) device has an efficiency of 1.2% with an EQE reaching up to 800nm and a VOC of almost 1V. The Ph2-benz-bodipy device shows a Voc of 0.65V and an efficiency of 1.1%, the EQE reaching up to 860nm. The variation of the molecule’s end groups to vary their IP is successfully employed for three different benz-bodipys: The variation results in a decrease of the optical gap from 1.5eV for the phenyl group, to 1.4eV for the MeO group, and 1.3eV for the thiophene group with the effective gap and the VOC following this trend. Efficiencies of 1.1% and 0.6% in combination with C60 can be reached in mip-type devices. Ph2-benz-bodipy is then optimized into a single cell with an efficiency of 2.9%. In a tandem cell with DCV6T-Bu4:C60, a Voc of 1.7V, a FF of 57% and an efficiency of 5% is reached. / Die Erweiterung des verfügbaren Spektrums in den Infrarotbereich ist eine Möglichkeit, die Effizienz organischer Solarzellen zu erhöhen. Diese Arbeit erkundet das Potential dieser Heteroübergänge und zwei Materialklassen in dünnen Schichten und Bauelementen: Zinnphthalozyanine (SnPc) und aza-Bodipys. Um die potentielle Effizienz abzuschäötzen, werden Modellberechnungen für Einzel- und Tandemzellen durchgeführt, unter Berücksichtigung des Unterschieds von optischer und elektrischer Bandlücke und der Quasiferminiveauaufspaltung. Mithilfe einiger Annahmen (z.B. Füllfaktor (FF) und externe Quanteneffizienz (EQE) gleich 65%) lässt sich die Einzelzelleffizienz auf 15%, die Tandemzelleffizienz auf 21% abschätzen. Halogenierung kann die Energieniveaus organischer Moleküle herabsetzen, ohne die optische Bandlücke zu verändern. Drei verschiedene chlorierte und fluorierte SnPcs werden mit dem reinen SnPc verglichen. Während die Chlorierung die Transporteigenschaften der aktiven Schicht und den FF verschlechtern, erhöht die Fluorierung wie erwartet Leerlaufspannung (VOC) und Effizienz im flachen Übergang, nicht jedoch in der Mischschicht, vermutlich aufgrund des nicht stabil gebundenen Fluors. Ein Weg, Ionisationspotential (IP) und Absorption der aza-Bodipy zu verändern, ist die Anelierung des Benzenrings. Die durch CV und UPS ermittelten und mittels DFT errechneten Energieniveaus stimmen gut überein und führen zu einer Verringerung der VOC: Die Zelle mit nichtaniliertem Ph4-bodipy zeigt eine Effizienz von 1.2%; das EQE reicht bis 800nm, die VOC beträgt fast 1V. Die Ph2-benz-bodipy-Zelle zeigt eine VOC von 0.65V und eine Effizienz von 1.1%, das EQE reicht bis 860nm. Der Austausch der Endgruppen zur Vergrößerung des IP, erfolgreich angewandt auf drei Benz-Bodipy-Verbindungen, führt zu einer Verringerung der optischen Bandlücke: von 1.5eV (Phenyl) über 1.4eV (MeO) zu 1.3eV (Thiophen); effektive Bandlücke und Voc folgen diesem Trend. Effizienzen von 1.1% und 0.6% in Kombination mit C60 werden in mip-Zellen erreicht. Ph2-benz-bodipy zeigt in einer optimierten nip-Zelle sogar eine Effizienz von 2.9%. Eine Tandemzelle mit DCV6T-Bu4:C60 zeigt eine Voc von 1.7V, einen FF von 57% und eine Effizienz von 5%.

Broadening the spectrum available to solar cells towards infrared wavelengths is one way to increase efficiency of organic solar devices. This thesis explores the possibilities of these organic heterojunction devices and two different material classes in thin films and organic solar devices: tin phthalocyanines (SnPcs) and aza-bodipys. To estimate the efficiency reachable under sunlight, model calculations are done for single and tandem cells. These calculations include a distinction between the optical gap and the electrical gap and the splitting of the quasi-Fermi levels. With a number of assumptions, e.g. a fill factor (FF) and an external quantum efficiency (EQE) within the absorption range of 65%, the resulting efficiencies are 15% in a single cell and of 21% in a tandem cell. Halogenation is known to lower the energy levels of molecules without chang-ing the optical band gap. Three different fluorinated and chlorinated SnPcs are investigated and compared to the neat SnPc. While chlorination of SnPc worsens the transport properties of the active layer leading to a lowered FF, the fluorina-tion of SnPc results in the intended increase in VOC and, consequently, efficiency for planar heterojunctions. In bulk heterojunction, however, fluorination does not change the efficiency probably due to the unstably bound fluorine. One method to modify the ionization potential (IP) and the absorption of the second material class, the aza-bodipys, is the annulation of the benzene ring. The energy levels determined by CV and UPS measurement and DFT-calculation show very good agreement and can be linked to a decrease in VOC: The Ph4-bodipy (not benzannulated) device has an efficiency of 1.2% with an EQE reaching up to 800nm and a VOC of almost 1V. The Ph2-benz-bodipy device shows a Voc of 0.65V and an efficiency of 1.1%, the EQE reaching up to 860nm. The variation of the molecule’s end groups to vary their IP is successfully employed for three different benz-bodipys: The variation results in a decrease of the optical gap from 1.5eV for the phenyl group, to 1.4eV for the MeO group, and 1.3eV for the thiophene group with the effective gap and the VOC following this trend. Efficiencies of 1.1% and 0.6% in combination with C60 can be reached in mip-type devices. Ph2-benz-bodipy is then optimized into a single cell with an efficiency of 2.9%. In a tandem cell with DCV6T-Bu4:C60, a Voc of 1.7V, a FF of 57% and an efficiency of 5% is reached.:1 Introduction 13 2 Physics of Organic Solids 15 2.1 Organic Molecular Crystals . . . . . . . . . . . . . . . . . . . . . 15 2.1.1 Delocalization in Conjugated Systems . . . . . . . . . . . . 16 2.2 Energies and Excitations . . . . . . . . . . . . . . . . . . . . . . . 17 2.2.1 Organic Molecules . . . . . . . . . . . . . . . . . . . . . . 17 2.2.2 Organic Solids . . . . . . . . . . . . . . . . . . . . . . . . . 21 2.2.3 Excitons . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22 2.3 Charge Carriers . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24 2.3.1 Doping of Organic Semiconductors . . . . . . . . . . . . . 26 3 Physics of Photovoltaics 29 3.1 Photovoltaics in General 29 3.1.1 pn-Junction 31 3.1.2 Quasi-Fermi Levels . . . . . . . . . . . . . . . . . . . . . . 37 3.1.3 pin-Concept - Semipermeable Membranes . . . . . . . . . 40 3.1.4 Efficiency Limits . . . . . . . . . . . . . . . . . . . . . . . 41 3.2 Organic Solar Cells . . . . . . . . . . . . . . . . . . . . . . . . . . 43 3.2.1 Organic Heterojunctions . . . . . . . . . . . . . . . . . . . 45 3.2.2 Recombination Processes . . . . . . . . . . . . . . . . . . . 50 3.2.3 Transport Layers – pin-Concept in OSC . . . . . . . . . . 52 4 Materials and Experimental Setups 57 4.1 Materials . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 57 4.1.1 Buckminsterfullerene C60 . . . . . . . . . . . . . . . . . . . 57 4.1.2 Transport Materials . . . . . . . . . . . . . . . . . . . . . . 59 4.2 Sample Preparation . . . . . . . . . . . . . . . . . . . . . . . . . . 61 4.3 Experimental Methods . . . . . . . . . . . . . . . . . . . . . . . . 65 4.3.1 Characterization of Thin Layers . . . . . . . . . . . . . . . 65 4.3.2 Characterization of Solar Cells . . . . . . . . . . . . . . . . 69 4 Contents 5 Efficiency of an Organic Solar Cell 75 5.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 75 5.2 Theoretical Model . . . . . . . . . . . . . . . . . . . . . . . . . . . 76 5.2.1 The Power Conversion Efficiency . . . . . . . . . . . . . . 76 5.2.2 Optical Gap and Short-Circuit Current Density . . . . . . 76 5.2.3 Open-Circuit Voltage and Splitting of Quasi-Fermi Levels . 77 5.3 Calculation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 79 5.3.1 Single Heterojunction Solar Cells . . . . . . . . . . . . . . 79 5.3.2 Tandem Heterojunction Solar Cells . . . . . . . . . . . . . 80 5.3.3 Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . 81 6 Tin Phthalocyanines in Organic Solar Cells 83 6.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 83 6.2 Material Analysis . . . . . . . . . . . . . . . . . . . . . . . . . . . 84 6.3 Solar Cells . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 88 6.3.1 Planar Heterojunctions . . . . . . . . . . . . . . . . . . . . 89 6.3.2 Bulk Heterojunctions . . . . . . . . . . . . . . . . . . . . . 91 6.3.3 Photoelectron Spectroscopy . . . . . . . . . . . . . . . . . 95 6.3.4 Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . 96 7 Benzannulation of Aza-Bodipy Dyes 97 7.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 97 7.2 Properties of Bodipys . . . . . . . . . . . . . . . . . . . . . . . . . 99 7.2.1 Chemical Preparation . . . . . . . . . . . . . . . . . . . . 99 7.2.2 Solution and Thin Film Properties . . . . . . . . . . . . . 99 7.3 Solar Cells . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 104 7.3.1 Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . 108 8 Effect of End Group Variation on Aza-Bodipy Dyes 111 8.1 Thin Film Properties . . . . . . . . . . . . . . . . . . . . . . . . . 111 8.1.1 Optical Properties . . . . . . . . . . . . . . . . . . . . . . 112 8.1.2 Energetic Properties . . . . . . . . . . . . . . . . . . . . . 113 8.1.3 Morphology . . . . . . . . . . . . . . . . . . . . . . . . . . 114 8.2 Solar Cells . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 115 8.2.1 Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . 121 9 Optimization of Infrared Absorbing Organic Solar Cells 123 9.1 Optimization of the Single Cell . . . . . . . . . . . . . . . . . . . 123 9.1.1 Optimized Single Device . . . . . . . . . . . . . . . . . . . 128 9.1.2 Device Lifetime . . . . . . . . . . . . . . . . . . . . . . . . 129 9.2 Tandem Solar Cells . . . . . . . . . . . . . . . . . . . . . . . . . . 131 9.2.1 Summary and Outlook . . . . . . . . . . . . . . . . . . . . 136 10 Summary and Outlook 139 Bibliography 145 List of Abbreviations 165 Acknowledgments 167 / Die Erweiterung des verfügbaren Spektrums in den Infrarotbereich ist eine Möglichkeit, die Effizienz organischer Solarzellen zu erhöhen. Diese Arbeit erkundet das Potential dieser Heteroübergänge und zwei Materialklassen in dünnen Schichten und Bauelementen: Zinnphthalozyanine (SnPc) und aza-Bodipys. Um die potentielle Effizienz abzuschäötzen, werden Modellberechnungen für Einzel- und Tandemzellen durchgeführt, unter Berücksichtigung des Unterschieds von optischer und elektrischer Bandlücke und der Quasiferminiveauaufspaltung. Mithilfe einiger Annahmen (z.B. Füllfaktor (FF) und externe Quanteneffizienz (EQE) gleich 65%) lässt sich die Einzelzelleffizienz auf 15%, die Tandemzelleffizienz auf 21% abschätzen. Halogenierung kann die Energieniveaus organischer Moleküle herabsetzen, ohne die optische Bandlücke zu verändern. Drei verschiedene chlorierte und fluorierte SnPcs werden mit dem reinen SnPc verglichen. Während die Chlorierung die Transporteigenschaften der aktiven Schicht und den FF verschlechtern, erhöht die Fluorierung wie erwartet Leerlaufspannung (VOC) und Effizienz im flachen Übergang, nicht jedoch in der Mischschicht, vermutlich aufgrund des nicht stabil gebundenen Fluors. Ein Weg, Ionisationspotential (IP) und Absorption der aza-Bodipy zu verändern, ist die Anelierung des Benzenrings. Die durch CV und UPS ermittelten und mittels DFT errechneten Energieniveaus stimmen gut überein und führen zu einer Verringerung der VOC: Die Zelle mit nichtaniliertem Ph4-bodipy zeigt eine Effizienz von 1.2%; das EQE reicht bis 800nm, die VOC beträgt fast 1V. Die Ph2-benz-bodipy-Zelle zeigt eine VOC von 0.65V und eine Effizienz von 1.1%, das EQE reicht bis 860nm. Der Austausch der Endgruppen zur Vergrößerung des IP, erfolgreich angewandt auf drei Benz-Bodipy-Verbindungen, führt zu einer Verringerung der optischen Bandlücke: von 1.5eV (Phenyl) über 1.4eV (MeO) zu 1.3eV (Thiophen); effektive Bandlücke und Voc folgen diesem Trend. Effizienzen von 1.1% und 0.6% in Kombination mit C60 werden in mip-Zellen erreicht. Ph2-benz-bodipy zeigt in einer optimierten nip-Zelle sogar eine Effizienz von 2.9%. Eine Tandemzelle mit DCV6T-Bu4:C60 zeigt eine Voc von 1.7V, einen FF von 57% und eine Effizienz von 5%.:1 Introduction 13 2 Physics of Organic Solids 15 2.1 Organic Molecular Crystals . . . . . . . . . . . . . . . . . . . . . 15 2.1.1 Delocalization in Conjugated Systems . . . . . . . . . . . . 16 2.2 Energies and Excitations . . . . . . . . . . . . . . . . . . . . . . . 17 2.2.1 Organic Molecules . . . . . . . . . . . . . . . . . . . . . . 17 2.2.2 Organic Solids . . . . . . . . . . . . . . . . . . . . . . . . . 21 2.2.3 Excitons . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22 2.3 Charge Carriers . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24 2.3.1 Doping of Organic Semiconductors . . . . . . . . . . . . . 26 3 Physics of Photovoltaics 29 3.1 Photovoltaics in General 29 3.1.1 pn-Junction 31 3.1.2 Quasi-Fermi Levels . . . . . . . . . . . . . . . . . . . . . . 37 3.1.3 pin-Concept - Semipermeable Membranes . . . . . . . . . 40 3.1.4 Efficiency Limits . . . . . . . . . . . . . . . . . . . . . . . 41 3.2 Organic Solar Cells . . . . . . . . . . . . . . . . . . . . . . . . . . 43 3.2.1 Organic Heterojunctions . . . . . . . . . . . . . . . . . . . 45 3.2.2 Recombination Processes . . . . . . . . . . . . . . . . . . . 50 3.2.3 Transport Layers – pin-Concept in OSC . . . . . . . . . . 52 4 Materials and Experimental Setups 57 4.1 Materials . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 57 4.1.1 Buckminsterfullerene C60 . . . . . . . . . . . . . . . . . . . 57 4.1.2 Transport Materials . . . . . . . . . . . . . . . . . . . . . . 59 4.2 Sample Preparation . . . . . . . . . . . . . . . . . . . . . . . . . . 61 4.3 Experimental Methods . . . . . . . . . . . . . . . . . . . . . . . . 65 4.3.1 Characterization of Thin Layers . . . . . . . . . . . . . . . 65 4.3.2 Characterization of Solar Cells . . . . . . . . . . . . . . . . 69 4 Contents 5 Efficiency of an Organic Solar Cell 75 5.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 75 5.2 Theoretical Model . . . . . . . . . . . . . . . . . . . . . . . . . . . 76 5.2.1 The Power Conversion Efficiency . . . . . . . . . . . . . . 76 5.2.2 Optical Gap and Short-Circuit Current Density . . . . . . 76 5.2.3 Open-Circuit Voltage and Splitting of Quasi-Fermi Levels . 77 5.3 Calculation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 79 5.3.1 Single Heterojunction Solar Cells . . . . . . . . . . . . . . 79 5.3.2 Tandem Heterojunction Solar Cells . . . . . . . . . . . . . 80 5.3.3 Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . 81 6 Tin Phthalocyanines in Organic Solar Cells 83 6.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 83 6.2 Material Analysis . . . . . . . . . . . . . . . . . . . . . . . . . . . 84 6.3 Solar Cells . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 88 6.3.1 Planar Heterojunctions . . . . . . . . . . . . . . . . . . . . 89 6.3.2 Bulk Heterojunctions . . . . . . . . . . . . . . . . . . . . . 91 6.3.3 Photoelectron Spectroscopy . . . . . . . . . . . . . . . . . 95 6.3.4 Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . 96 7 Benzannulation of Aza-Bodipy Dyes 97 7.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 97 7.2 Properties of Bodipys . . . . . . . . . . . . . . . . . . . . . . . . . 99 7.2.1 Chemical Preparation . . . . . . . . . . . . . . . . . . . . 99 7.2.2 Solution and Thin Film Properties . . . . . . . . . . . . . 99 7.3 Solar Cells . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 104 7.3.1 Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . 108 8 Effect of End Group Variation on Aza-Bodipy Dyes 111 8.1 Thin Film Properties . . . . . . . . . . . . . . . . . . . . . . . . . 111 8.1.1 Optical Properties . . . . . . . . . . . . . . . . . . . . . . 112 8.1.2 Energetic Properties . . . . . . . . . . . . . . . . . . . . . 113 8.1.3 Morphology . . . . . . . . . . . . . . . . . . . . . . . . . . 114 8.2 Solar Cells . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 115 8.2.1 Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . 121 9 Optimization of Infrared Absorbing Organic Solar Cells 123 9.1 Optimization of the Single Cell . . . . . . . . . . . . . . . . . . . 123 9.1.1 Optimized Single Device . . . . . . . . . . . . . . . . . . . 128 9.1.2 Device Lifetime . . . . . . . . . . . . . . . . . . . . . . . . 129 9.2 Tandem Solar Cells . . . . . . . . . . . . . . . . . . . . . . . . . . 131 9.2.1 Summary and Outlook . . . . . . . . . . . . . . . . . . . . 136 10 Summary and Outlook 139 Bibliography 145 List of Abbreviations 165 Acknowledgments 167

La maladie de Fabry est une maladie héréditaire de surcharge, dont la transmission est liée au chromosome X qui résulte d'un déficit de l'[alpha]-galactosidase A. Le déficit enzymatique mène à une augmentation de glycosphingolipides, notamment le globotriaosylcéramide (Gb[indice inférieur 3]), dans les tissus et fluides biologiques. Le Gb[indice inférieur 3] est donc un biomarqueur ou indicateur de la présence de cette maladie chez les patients Fabry. Nous voulions évaluer la faisabilité de procéder à un projet pilote de recherche en vue d'un dépistage néonatal urinaire de la maladie de Fabry.La variation de l'excrétion du Gb[indice inférieur 3]/créatinine urinaire chez des enfants normaux dans la période néonatale jusqu'à l'âge de 6 mois est inconnue. Cette constatation nous a conduits au questionnement suivant : existe-t-il une variation dans la quantité du Gb[indice inférieur 3]/créatinine urinaire excrétée chez des enfants normaux de 0 à 6 mois de vie? Afin de répondre à cette question, nous avons procédé à une étude permettant de doser le Gb[indice inférieur 3]/créatinine chez des enfants normaux par spectrométrie de masse en tandem et ce, en comptant sur la collaboration des parents à effectuer un total de treize prélèvements d'urine pendant une période de 6 mois. Nous avons d'ailleurs évalué ladite collaboration des parents à nous faire parvenir les échantillons d'urine de leur bébé durant cette période. Nous avons utilisé une méthode par spectrométrie de masse en tandem avec des échantillons d'urine séchée sur papier filtre pour analyser simultanément le Gb[indice inférieur 3] total urinaire et la créatinine à différents temps soit 2, 3, 4, 6, 10, 14, 21, 28 jours, de même qu'à 2, 3, 4, 5 et 6 mois chez 37 filles et 39 garçons normaux. Le traitement quantitatif des données de la créatinine et du Gb[indice inférieur 3] urinaire a été fait par le logiciel QuanLynx (Waters). Nous avons divisé la variable du temps en quatre périodes pour les fins d'analyses statistiques : (1) < 6 jours; (2) 6-29 jours; (3) 30-90 jours; (4) > 90 jours. Nous avons procédé à des analyses statistiques comparatives du rapport Gb[indice inférieur 3]/créatinine de 728 échantillons pour les deux cohortes en fonction du temps. Une analyse de variance a été faite pour évaluer l'effet de l'âge et du sexe sur le rapport du logarithme du Gb[indice inférieur 3]/créatinine urinaire et l'effet de l'âge et du sexe sur la quantité d'excrétion de la créatinine urinaire seulement. Nous avons observé un effet significatif de l'âge sur la créatinine (p < 0.0001). En ce qui concerne les résultats du rapport du Gb[indice inférieur 3]/créatinine, il y a une augmentation non significative de la médiane dans les périodes 1 et 2 pour les garçons (Période 1: Médiane 53.9; Min-Max 0 - 369.3 [micro]g/mmol créatinine; Période 2: Médiane 92.5; Min-Max 0 - 611.1 [micro]g/mmol créatinine ; p = 1.0000). Chez les filles, l'excrétion du Gb[indice inférieur 3]/créatinine est plus élevé à la naissance et présente une tendance à l'accroissement entre les périodes 1 et 2 (Période 1: Médiane 59.5; Min-Max 0 - 669.9 [micro]g/mmol créatinine; Période 2: Médiane 96.1; Min-Max 0 - 456.1 [micro]g/mmol créatinine ; p = 1.0000). Par ailleurs, l'excrétion du Gb[indice inférieur 3]/créatinine chez les garçons diminue de façon significative entre les périodes 2 et 4 (Période 2: Médiane 92.5; Min-Max 0 - 611.1 [micro]g/mmol créatinine; Période 4: Médiane 14.6; Min-Max 0 - 158.5 [micro]g/mmol créatinine ; p < 0.0001); au niveau des filles, il y a une diminution non significative de la médiane de la période 2 à la période 3 (Période 2 : Médiane 96.1; Min-Max 0 - 456.1 [micro]g/mmol créatinine ; Période 3 : Médiane 35.6; Min-Max 0 - 254.4 [micro]g/mmol créatinine p = 0.2290) et une légère augmentation à la période 4 (Période 4 : Médiane 42.7; Min-Max 0 - 617.2 [micro]g/mmol créatinine). Ainsi, nous pouvons constater qu'il existe une grande variabilité de l'excrétion du Gb[indice inférieur 3]

BACKGROUND:The widespread utilization of organic compounds in modern society and their dispersion through wastewater have resulted in extensive contamination of source and drinking waters. The vast majority of these compounds are not regulated in wastewater outfalls or in drinking water while trace amounts of certain compounds can impact aquatic wildlife. Hence it is prudent to monitor these contaminants in water sources until sufficient toxicological data relevant to humans becomes available. A method was developed for the analysis of 36 trace organic contaminants (TOrCs) including pharmaceuticals, pesticides, steroid hormones (androgens, progestins, and glucocorticoids), personal care products and polyfluorinated compounds (PFCs) using a single solid phase extraction (SPE) technique with ultra-high performance liquid chromatography coupled to tandem mass spectrometry (UHPLC-MS/MS). The method was applied to a variety of water matrices to demonstrate method performance and reliability.RESULTS:UHPLC-MS/MS in both positive and negative electrospray ionization (ESI) modes was employed to achieve optimum sensitivity while reducing sample analysis time (<20min) compared with previously published methods. The detection limits for most compounds was lower than 1.0 picogram on the column while reporting limits in water ranged from 0.1 to 15ng/L based on the extraction of a 1L sample and concentration to 1mL. Recoveries in ultrapure water for most compounds were between 90-110%, while recoveries in surface water and wastewater were in the range of 39-121% and 38-141% respectively. The analytical method was successfully applied to analyze samples across several different water matrices including wastewater, groundwater, surface water and drinking water at different stages of the treatment. Among several compounds detected in wastewater, sucralose and TCPP showed the highest concentrations.CONCLUSION:The proposed method is sensitive, rapid and robust / hence it can be used to analyze a large variety of trace organic compounds in different water matrixes.

This thesis investigates novel hole extraction interfaces and series interconnects for applications in organic photovoltaics, specifically in single junction solid-state dye-sensitized solar cells (DSSCs) and tandem DSSC/polymer bulk heterojunction solar cells. Improvements in hole extraction and device performance by using materials compatible with scalable deposition methods are presented, including tungsten- and molybdenum-disulphide (WS₂ and MoS₂), and p-type doped spiro-OMeTAD (2,2',7,7'-tetrakis-(N,N-di-p-methoxyphenylamine)9,9'-spirobifluorene) nanoparticle dispersions. WS₂ and MoS₂ hole extraction layers increase averaged short circuit currents by 20% and 16% respectively, and power conversion efficiencies by 19% and 14% respectively when compared with control devices. Similarly, doped spiro-OMeTAD nano-particle layers improved short circuit current densities by 32% and efficiencies by 9%. Tandem device interconnects using these novel hole extraction formats have been fabricated, but although devices did exhibit rectification, overall performance was poor. Possible reasons for their limited success have been analysed. Dye-sensitized solar mini-modules are also reported. In order to assure the scalability of DSSC technology, these larger area devices were constructed using doctor blade coating to deposit the hole transporter material. As well as achieving a respectable maximum power conversion efficiency of 2.6%, it has also been shown that the extent to which hole transporter infiltrates the mesoporous photoanode of these devices may be tuned by altering substrate temperature during deposition. It was found that an optimal coating temperature of 70 degrees C produced the best efficiency, with a corresponding pore-filling fraction of 41%.

Formamide is a solvent of great interest to prebiotic chemists because it is liquid over a wide range, it is less volatile than either water or HCN, and it possesses a versatile reactivity. When formamide is heated in the presence of minerals or inorganic catalysts, a variety of products including purine nucleobases are generated. Irradiation of formamide reaction solutions with ultraviolet light increases the yield and diversity of products, and eliminates the need for a mineral catalyst. We have also performed formamide reactions in the presence of pyrite, a mineral which is likely to have been available on the primordial Earth, under a variety of atmospheric conditions. Our results indicate the greatest yield and diversity of products result from the combination of a pyrite mineral catalyst, heat, UV irradiation, and a carbon dioxide atmosphere. Purine nucleobases are simple to synthesize in model reactions and they stack well in aqueous solution; it has been hypothesized that the first nucleic acids were composed of only purine bases, and that water-soluble, cationic, aromatic molecules with large stacking surfaces (“”molecular midwives””) may have aided the assembly of the earliest nucleic acid analogs. We have characterized the interactions of various intercalators with a standard DNA duplex as well as with an antiparallel homopurine DNA duplex and have determined that molecules which possess four or more rings and a curved shape interact selectively with all-purine DNA; such molecules can serve as models for putative prebiotic midwives.