Les travaux réalisés au cours de cette thèse ont consisté en l’élaboration d’édifices multi-chromophoriques pour des applications en cellules solaires organiques. La conception de ces nouveaux matériaux a été guidée par trois paramètres : (i) l’augmentation de la planéité pour une meilleure organisation intermoléculaire ; (ii) la modulation de la fenêtre spectrale d’absorption pour capter un maximum de photons ; (iii) l’enrichissement électronique des matériaux pour faciliter la séparation des charges. Notre choix s’est porté sur les hydrocarbures aromatiques polycycliques, de part leurs propriétés structurantes bien connues. La synthèse du 2-bromodibenzo[g,p]chrysène a été réalisée par des réactions de type Scholl intramoléculaires, puis sa dérivatisation a permis de synthétiser des matériaux correspondants. La mono-fonctionnalisation d’un synthon benzo[1,2-b:3,4-b’:5,6-b’’]trithiophène a également été effectuée. Des BODIPYs dithiényles α-fusionnés ont ensuite été synthétisés selon une procédure originale de couplages oxydants intramoléculaires, permettant d’obtenir des composés plans, fonctionnalisés et fonctionnalisables, tout en contournant la chimie contraignante du pyrrole. L’obtention de dyades et triades à base de DPPs, de BODIPY et de triphénylamines ont permis d’obtenir des composés panchromatiques et d’étudier les phénomènes d’extinction de la fluorescence par spectroscopies statiques et ultrarapides. Un dernier projet a porté sur des édifices de type D-A-D à base de BODIPYs et amines aromatiques tertiaires. / The projects developed in this thesis consisted in the elaboration of multi-chromophoric scaffolds towards applications in bulk heterojunction organic solar cells. The design of the materials was guided by three main parameters: (i) the increase of the planarity to observe a better intermolecular organization; (ii) the broadening of the spectral absorption window in order to maximize the number of absorbed photons; (iii) the increase of the electronic density in order to facilitate the charge separation. First, the structural properties of mono-functionalized polycyclic aromatic hydrocarbons (PAH) were investigated with the synthesis of 2-bromodibenzo[g,p]chrysene by Scholl type reactions, followed by its functionalization and the development of related materials. Then we also focused on another PAH: benzo[1,2-b:3,4-b’:5,6-b’’]trithiophene and its subsequent functionalization. α-Fused dithienyl BODIPYs were then built according to an original procedure based on intramolecular oxidative coupling reactions. Substituted and functionalizable planar compounds were obtained bypassing the instability of the pyrrole ring chemistry. Subsequently, the elaboration of dyads and triads based on DPPs, BODIPY and triphenylamines led to the examination of the fluorescence quenching process by static and ultrafast spectroscopies. A last project consisted in the study and applications of D-A-D edifices based on BODIPYs and ternary aromatic amines.

Le travail présenté dans ce mémoire avait pour but de synthétiser de nouvelles molécules dont l’architecture donne accès à des complexes hétérobimétalliques aux propriétés intéressantes pour l’imagerie médicale multimodale. Dans ce manuscrit plusieurs points principaux ont donc été abordés. La première partie de se travail porte sur la synthèse et la caractérisation des ligands. Nous décrivons dans ce manuscrit la synthèse de cinq nouveaux ligands hétérobismacrocycliques basés sur l’association d’une porphyrine et d’un ou de plusieurs dérivés du cyclène. Ces ligands présentent la particularité d’être solubles en milieux aqueux. Au cours des synthèses, nous avons ciblé les améliorations à apporter à notre travail et élaboré une nouvelle voie de synthèse qui permet d’accéder, en seulement six étapes, à un ligand composé d’une porphyrine, d’un dérivé du cyclène et d’une fonction amine libre qui permettra de greffer le ligand sur un vecteur biologique. La seconde partie de ce manuscrit porte sur l’incorporation de centres métalliques dans les ligands synthétisés ainsi que l’étude de leur efficacité en tant qu’agent de contraste de l’IRM. Nous décrivons la synthèse de cinq complexes de gadolinium (III) et de trois complexes hétérobimétalliques associant du gadolinium (III) et du cuivre (II). En effet, le gadolinium est actuellement utilisé dans les agents de contraste de l’IRM et un des isotopes du cuivre, le cuivre-64, est utilisé en imagerie PET. Nous décrivons un protocole de mesure de la relaxivité des complexes à haut et à bas champs magnétiques. Cinq complexes présentent des valeurs de relaxivité quatre fois supérieures à celles des agents de contraste commerciaux de l’IRM. Le dernier chapitre de ce travail porte sur la synthèse, la caractérisation et les études photophysiques de quatre antennes moléculaires associant des porphyrines et des BODIPY. Nous avons développé deux voies de synthèses originales. La première est basée sur la création de liaisons bore-oxygène en substituant les atomes de fluor portés par l’atome de bore des BODIPY. L’autre voie de synthèse utilise la réaction de cycloaddition dipolaire d’Huisgen. Nous décrivons des études photophysiques qui mettent en évidence des transferts d’énergie du BODIPY vers la porphyrine Nous avons mis en évidence le premier exemple de transfert d’énergie d’une porphyrine vers un BODIPY grâce à un système “blue” BODIPY étendu couplé à des porphyrines par une réaction de chimie “click”. / The goal of my PhD thesis was to synthesize new molecules, which give access to heterobimetallic complexes with interesting properties for multimodal imaging. In this manuscript, several main points have been studied. The first part of this work concerns the synthesis and characterization of ligands. We describe here the synthesis of five new ligands based on the association of one porphyrin and one or several cyclen derivatives. Those ligands are water-soluble. During the synthesis, we have targeted improvements to our work and developed a new synthetic pathway, which allowed us to obtain one ligand incorporating a porphyrin, a cyclen derivative and a free amine function. This function could be activated to further graft the ligand onto a biological vector. The second part of this manuscript describes the chelation of metallic centers into the ligands and the study of their efficiency as MRI contrast agents. We describe the synthesis of five gadolinium (III) complexes and three heterobimetallic complexes associating gadolinium (III) with copper (II). Indeed, gadolinium is currently used in contrast agents for MRI and the radioactive isotope of copper, copper-64 is used in PET imaging. We describe also a procedure to measure the relaxivity of the gadolinium complexes at low and high magnetic fields. Five complexes exhibit relaxivity values five times larger than commercially available MRI contrast agents. The last part of this work is related to the synthesis, characterization and photophysical studies of four molecular antennas incorporating porphyrins and BODIPY. We describe two original synthetic pathways. The first one is based on the formation of boron-oxygen bonds by substitution of the fluorine atoms bound to BODIPY boron atom. The second synthetic pathway involves the Huisgen’s dipolar cycloaddition. We describe photophysical data and give evidences of the energy transfer from BODIPY to porphyrin. We present also the first example of energy transfer from porphyrin to BODIPY in the system obtained by “click” chemistry involving an extended “blue” BODIPY.

Photosensitizing effects of xenobiotics are of increasing concern in public health since modern lifestyle often associates sunlight exposure with the presence of chemical substances in the skin. An important number of chemicals like perfumes, sunscreen components, or therapeutic agents have been reported as photosensitizers. In this context, a considerable effort has been made to design a model system for photosafety assessment. Indeed, screening for phototoxicity is necessary at the early phase of drug discovery process, even before introducing drugs and chemicals into clinical therapy, to prevent undesired photoreactions in humans. In the case of new pharmaceuticals, their phototoxic potential has to be tested when they absorb in the regions corresponding to the solar spectrum, that is, for wavelengths >290 nm. So, there is an obvious need for a screening strategy based on in vitro experiments. The goal of the present thesis was the photochemical study of different photoactive drugs to investigate the key molecular aspects responsible for their photosensitivity side effects. In a first stage, rosuvastatin was considered in chapter 3 as representative compound of the statin family. This lipid-lowering drug, also known as “superstatin”, contains a 2-vinylbiphenyl-like moiety and has been previously described to decompose under solar irradiation, yielding stable dihydrophenanthrene analogues. During photophysical characterization of rosuvastatin, only a long-lived transient at ca. 550 nm was observed and assigned to the primary photocyclization intermediate. Thus, the absence of detectable triplet-triplet absorption and the low yield of fluorescence ruled out the role of the parent drug as an efficient sensitizer. In this context, the attention was placed on the rosuvastatin main photoproduct (ppRSV). Indeed, the photobehavior of this dihydrophenanthrene-like compound presented the essential components needed for an efficient biomolecule photosensitizer i.e. (i) a high intersystem crossing quantum yield (ΦISC =0.8), (ii) a triplet excited state energy of ca. 67 kcal mol−1 , and (iii) a quantum yield of singlet oxygen formation (Φ∆) of 0.3. Furthermore, laser flash photolysis studies revealed a triplet-triplet energy transfer from the triplet excited state of ppRSV to thymidine, leading to the formation of cyclobutane thymidine dimers, an important type of DNA lesion. Finally, tryptophan was used as a probe to investigate the Type I and/or Type II character of ppRSV-mediated oxidation. In this way, both an electron transfer process giving rise to the tryptophanyl radical and a singlet oxygen mediated oxidation were observed. On the basis of the obtained results, rosuvastatin, through its major photoproduct ppRSV, should be considered as a potential sensitizer. Then, itraconazole (ITZ), a broad-spectrum antifungal agent, was chosen as main character of chapter 4. Its photochemical properties were investigated in connection with its reported skin photosensitivity disorders. Steady state photolysis, fluorescence and phosphorescence experiments were performed to understand ITZ photoreactivity in biological media. The drug is unstable under UVB irradiation, suffering a primary dehalogenation of the 2,4-dichlorophenyl moiety that occurs mainly at the ortho-position. In poorly H-donating solvents, as acetonitrile, the major photoproduct arises from intramolecular attack of the initially generated aryl radical to the triazole ring. In addition, reduced compounds resulting from homolytic cleavage of the C-Cl bond in ortho or para positions and subsequent Habstraction from the medium are obtained to a lesser extent. In good H-donating solvents, such as ethanol, the main photoproducts are formed by reductive dehalogenation. Furthermore, irradiation of a model dyad containing a tryptophan unit and the reactive 2,4-dichlorophenyl moiety of itraconazole leads to formation of a new covalent link between these two substructures revealing that homolysis of the C-Cl bond of ITZ can result in alkylation of reactive amino acid residues of proteins, leading to formation of covalent photoadducts. Therefore, it has been established that the key process in the photosensitization by itraconazole is cleavage of the carbon-halogen bond, which leads to aryl radicals and chlorine atoms. These highly reactive species might be responsible for extensive free radical-mediated biological damage, including lipid peroxidation or photobinding to proteins. In chapter 5, photobehavior of imatinib (IMT) was addressed. This is a promising tyrosine kinase inhibitor used in the treatment of some types of human cancer, which constitutes a successful example of rational drug design based on the optimization of the chemical structure to reach an improved pharmacological activity. Cutaneous reactions, such as increased photosensitivity or pseudoporphyria, are among the most common nonhematological IMT side effects; however, the molecular bases of these clinical observations have not been unveiled yet. Thus, to gain insight into the IMT photosensitizing properties, its photobehavior was studied together with that of its potentially photoactive anilino-pyrimidine and pyridyl-pyrimidine fragments. In this context, steady-state and time resolved fluorescence, as well as laser flash photolysis experiments were run, and the DNA photosensitization potential was investigated by means of single strand breaks detection using agarose gel electrophoresis. The obtained results revealed that the drug itself and its anilino-pyrimidine fragment are not DNA-photosensitizers. By contrast, the pyridyl-pyrimidine substructure displayed a marked photogenotoxic potential, which was associated with the generation of a long-lived triplet excited state. Interestingly, this reactive species was efficiently quenched by benzanilide, another molecular fragment of IMT. Clearly, integration of the photoactive pyridyl-pyrimidine moiety in a more complex structure strongly modifies its photobehavior, which in this case is fortunate as it leads to an improved toxicological profile. Thus, on the bases of the experimental results, direct in vivo photosensitization by IMT seems unlikely. Instead, the reported photosensitivity disorders could be related to indirect processes, such as the previously suggested impairment of melanogenesis or the accumulation of endogenous porphyrins. Finally, a possible source of errors in the TEMPO/EPR method for singlet oxygen detection was analyzed. For many biological and biomedical studies, it is essential to detect the production of 1O2 and to quantify its production yield. Among the available methods, detection of the characteristic 1270 nm phosphorescence of singlet oxygen by time-resolved near infrared (TRNIR) emission constitutes the most direct and unambiguous approach. An alternative indirect method is electron paramagnetic resonance (EPR) in combination with trapping. This is based on the detection of the TEMPO free radical formed after oxidation of TEMP (2,2,6,6- tetramethylpiperidine) by singlet oxygen. Although the TEMPO/EPR method has been largely employed, it can produce misleading data. This was demonstrated by the present study, where the quantum yields of singlet oxygen formation obtained by TRNIR emission and by the TEMPO/EPR method were compared for a set of well-known photosensitizers. The results revealed that the TEMPO/EPR method leads to significant overestimation of singlet oxygen yield when the singlet or triplet excited state of the photosensitizers were efficiently quenched by TEMP, acting as electron donor. In such case, generation of the TEMP+• radical cation, followed by deprotonation and reaction with molecular oxygen gives rise to a EPR detectable TEMPO signal that is not associated with singlet oxygen production. This knowledge is essential for an appropriate and error-free application of the TEMPO/EPR method in chemical, biological and medical studies. / Nardi, G. (2014). MECHANISTIC STUDIES ON THE PHOTOTOXICITY OF ROSUVASTATIN, ITRACONAZOLE AND IMATINIB [Tesis doctoral no publicada]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/48535 / TESIS

The interest in the detail knowledge about elementary electronic processes during photogeneration of charge carriers, which allow achieving higher efficiency of organic solar cells, grows with advent of the commercial organic solar cells production. The thesis is focused on study of photogeneration of charge carriers in organic semiconductors, especially in -conjugated polymer materials. First part of the thesis summarized state of the art in studies of photogeneration of charge carriers in polymer solar cells. Subsequent experimental and results part are focused on study of polymeric solar cells prepared from electron donor polymers MDMO-PPV, Tg-PPV, PCDTBT and PCBTDPP and electron acceptor derivates of fullerenes PC60BM and PC70BM. Results of the thesis are divided in tree main parts: 1) study of charge transfer between electron donor and electron acceptor materials by optical methods, 2) study of charge transfer between electron donor and electron acceptor materials by optoelectrical methods and 3) development of organic solar cells on flexible substrates. The last part is focused largely on deposition methods of active materials thin layer.

Key issues in improving small molecule organic solar cells (SMOSC) are the need for new absorber materials and optimized active layer morphology. This thesis deals with the improvement of SMOSC on the donor material side. Promising donor materials (D) are provided by dicyanovinyl endcapped oligothiophenes DCV2-nT (n = 3, . . . , 6) synthesized in the group of Prof. Bäuerle at the University of Ulm. Here, DCV2-nT (n = 3, 5) with different alkyl side chains are characterized. Side chain variations mainly influence the aggregation of molecules in pristine films as well as in blend films with the commonly used acceptor (A) fullerene C60. With changes in the layer morphology, important physical properties in thin film like absorption spectra, energy levels, as well as excited state properties are changed. The focus of this work are excited state properties accessed by photoinduced absorption spectroscopy (PIA). PIA probes the long living excited states in pristine and blend films, i. e. triplet excitons, anions, and cations. For a series of four dicyanovinyl-terthiophenes DCV2-3T (without side chains, with two methyl, two butyl, and four butyl side chains) a systematic study of the effect of alkyl side chains on the aggregation in neat and blend film is discussed. In consequence the efficiency of the energy transfer mechanism between DCV2-3T and C60 is affected. It turns out that in solution spectra and cyclic voltammetry (CV) measurements, the variation of alkyl side chains has almost no influence. However, in thin film there is strong impact on the molecular arrangement confirmed by strongly varying absorption spectra, ionization potentials, and surface roughnesses. Furthermore, PIA measurements reveal that the energy transfer efficiency between D and A in general decreases with increasing side chain length, but is most efficient for a compound with methyl side chains. For blends of dicyanovinyl-quinquethiophenes (DCV2-5T) with C60, the layer morphology is influenced by two different methods. On one hand substrate heating is applied while deposition of the active layer, on the other hand DCV2-5Ts with different alkyl side chains (four methyl and four butyl side chains) are used. Deposition on a heated substrate (80°C) results in an improved solar cell performance, assigned to the formation of a sufficient phase separation of D and A phase in the active layer. This leads to reduced recombination losses and closed percolation paths. The morphological change can be correlated to an increased lifetime of cations. In blends deposited on a heated substrate, the donor cation lifetime increases by almost one order of magnitude from around 10 μs to ≈ 80 μs. This increase of carrier lifetime is both detected optically by PIA as well as electrically by impedance spectroscopy. The increase in lifetime is consequently assigned to a better spatial separation of positive and negative charges induced by the phase separation. Comparing DCV2-5T with methyl and butyl side chains results in a similar effect: The dicyanovinyl-quinquethiophene with methyl side chains leads to an improved solar cell device performance compared to devices comprising the compound with butyl side chains as donor. The improved device performance is again accompanied by an increase in cation lifetime detected by PIA.:Contents Publications 1. Introduction 2. Organic semiconductors 2.1. Introduction 2.2. Optical excitations in organic semiconductors 2.2.1. Energy levels: single molecules to molecular solids 2.2.2. Absorption and emission spectra 2.3. Transport in organic semiconductors 2.3.1. Exciton motion 2.3.2. Charge transport 2.3.3. Amorphous organic semiconductors 3. Organic photovoltaics 3.1. Introduction 3.2. Solarenergyconversion 3.2.1. Quasi Fermi levels 3.2.2. p-n junction 3.3. Organic solar cells 3.3.1. Charge generation mechanisms 4. Experimental methods 4.1. Sample preparation 4.2. Photoinduced absorption spectroscopy 4.2.1. PIA setup 4.2.2. Recombination dynamics 4.3. Solar cell characterization 4.3.1. External quantum efficiency 4.3.2. J-V characteristics 4.4. Absorption and emission spectroscopy 4.5. Determination of energy levels 4.5.1. Ultraviolet photo electron emission spectroscopy 4.5.2. Cyclic voltammetry 4.6. Atomic force microscopy 4.7. Density functional theory calculations 4.8. Impedance spectroscopy 5. Dicyanovinyl-oligothiophenes 5.1. Introduction 5.2. The DCV2-nT:C60 interface 5.3. Processability 6. Side chain variations on DCV2-3T 6.1. Introduction 6.2. Density functional theory calculations 6.2.1. Excited state transitions 6.3. Absorption and Emission in solution and thin film 6.3.1. Blend layer absorption spectra 6.3.2. Photoluminescence spectra of neat and blend films 6.4. Energy levels of the DCV2-3T series 6.5. Atomic force microscopy 6.6. Photoinduced absorption spectroscopy 6.6.1. PIA signatures of charged states 6.6.2. Recombination dynamics 6.6.3. Efficiency of the ping pong effect 6.7. Conclusion 7. Influencing the morphology of DCV2-5T:C60 blend layers 7.1. Introduction 7.2. Properties of the DCV2-5T:C60 interface 7.2.1. Analysis of the DCV2-5T triplet transition 7.2.2. Analysis of the DCV2-5T cation transitions 7.2.3. Suggested energy level scheme for neat and blend layer 7.3. Temperature evolution of excited state properties 7.4. Effect of substrate heating on excited state lifetime and generation rate 7.4.1. Solar cell devices 7.4.2. Photoinduced absorption 7.4.3. Impedance spectroscopy 7.5. Conclusion 8. Side chain variations on DCV2-5T 8.1. Introduction 8.2. Atomic force microscopy 8.3. Energy levels 8.4. Mip solar cells 8.4.1. Flat heterojunctions 8.4.2. Bulk heterojunctions 8.4.3. Discussion of Voc 8.5. Photoinduced absorption 8.5.1. Comparison at room temperature 8.6. Conclusion 9. Conclusion and Outlook 9.1. Conclusion 9.2. Outlook A. Appendix Bibliography / Die Entwicklung neuer Absorber-Materialien sowie die Morphologie der photo- aktiven Schicht sind zentrale Themen hinsichtlich der Optimierung organischer Solarzellen aus kleinen Molekülen. In der vorliegenden Arbeit werden diese beiden Aspekte von Seiten des Donor-Materials (D) her behandelt. Die Material- klasse der Dicyanovinyl-Oligothiophene DCV2-nT(n=3,...,6) (synthetisiert in der Arbeitsgruppe von Prof. Bäuerle an der Universität Ulm) dient dabei als Ausgangspunkt. Insbesondere werden DCV2-nT-Moleküle (n = 3, 5) mit verschiedenen Alkyl-Seitenketten charakterisiert. Die Variation der Seitenketten beeinflusst in erster Linie die Anordnung der Moleküle in Einzel- sowie in Mischschichten mit dem typischerweise verwendeten Akzeptor-Material Fulleren C60 (A). Als Folge der Schichtmorphologie ändern sich physikalische Eigenschaften wie u. a. Absorptions- spektren, Energieniveaus sowie die Eigenschaften angeregter Zustände. Angeregte Zustände, wie Triplett-Exzitonen, Anionen und Kationen werden in dieser Arbeit mittels photoinduzierter Absorptionsspektroskopie (PIA) charakterisiert. Anhand einer Serie von vier Dicyanovinyl-Tertiophenen DCV2-3T (ohne Seiten- ketten, mit zwei Methyl-, zwei Butyl-, und vier Butyl-Seitenketten) werden systematisch Einflüsse der Seitenketten auf die Aggregation der Moleküle in Einzel- und Mischschichten untersucht. Besonderes Augenmerk liegt dabei auf dem Effekt der Seitenketten auf den Energie-Transfer-Mechanismus zwischen D und A. In Lösungsmittelspektren und Cyclovoltammetrie-Messungen ist fast keine Änderung durch die Seitenketten erkennbar. Im Dünnfilm hingegen besteht ein starker Einfluss auf die molekulare Anordnung, erkennbar in einer starken Variation der Absorptionsspektren, Ionisationspotentiale und Oberflächen-Topographie. PIA- Messungen zeigen weiterhin, dass im Allgemeinen die Effizienz des Energie-Transfer- Mechanismus mit zunehmender Länge der Alkyl-Ketten abnimmt. Der effizienteste Transfer besteht jedoch für die Verbindung mit Methyl-Seitenketten. In Mischschichten aus Dicyanovinyl-Quinquethiophenen (DCV2-5T) und C60 werden hier zwei Methoden zur Beeinflussung der Schichtmorphologie verfolgt. Zum einen wird die aktive Schicht auf einem geheizten Substrat abgeschieden, zum anderen werden DCV2-5T-Moleküle mit Methyl- und Butyl-Seitenketten als Donor verwendet. Das Abscheiden der aktiven Schicht auf einem geheizten Substrat (80 °C) führt zu einer verbesserten Solarzellenleistung, was auf die Bildung einer hin- reichenden Phasenseparation von D- und A-Phasen in der aktiven Schicht zurückzuführen ist. Die Phasenseparation bewirkt eine Reduktion von Rekombinationsverlusten und die Bildung geschlossener Perkolationspfade. Die morphologische Änderung korreliert mit einem Anstieg der Ladungsträger-Lebensdauer um fast eine Größenordnung von etwa 10 μs auf ≈ 80 μs. Der Anstieg kann sowohl optisch durch PIA, als auch elektrisch mittels Impedanz-Spektroskopie detektiert werden. Eine höhere Lebensdauer der Ladungsträger kann letztlich auf eine größere räumlichen Separation der positiven und negativen Ladungsträger zurückgeführt werden, induziert durch die Phasenseparation. Ein Vergleich von DCV2-5T-Molekülen mit Methyl- und Butyl-Seitenketten führt zu ähnlichen Resultaten: Solarzellen mit DCV2-5T substituiert mit Methyl- Seitenketten sind effizienter als die der butyl-substituierten Moleküle. Dies korreliert wiederum mit einer signifikant erhöhten Lebensdauer der Ladungsträger in Mischschichten der methyl-substituierten Verbindung.:Contents Publications 1. Introduction 2. Organic semiconductors 2.1. Introduction 2.2. Optical excitations in organic semiconductors 2.2.1. Energy levels: single molecules to molecular solids 2.2.2. Absorption and emission spectra 2.3. Transport in organic semiconductors 2.3.1. Exciton motion 2.3.2. Charge transport 2.3.3. Amorphous organic semiconductors 3. Organic photovoltaics 3.1. Introduction 3.2. Solarenergyconversion 3.2.1. Quasi Fermi levels 3.2.2. p-n junction 3.3. Organic solar cells 3.3.1. Charge generation mechanisms 4. Experimental methods 4.1. Sample preparation 4.2. Photoinduced absorption spectroscopy 4.2.1. PIA setup 4.2.2. Recombination dynamics 4.3. Solar cell characterization 4.3.1. External quantum efficiency 4.3.2. J-V characteristics 4.4. Absorption and emission spectroscopy 4.5. Determination of energy levels 4.5.1. Ultraviolet photo electron emission spectroscopy 4.5.2. Cyclic voltammetry 4.6. Atomic force microscopy 4.7. Density functional theory calculations 4.8. Impedance spectroscopy 5. Dicyanovinyl-oligothiophenes 5.1. Introduction 5.2. The DCV2-nT:C60 interface 5.3. Processability 6. Side chain variations on DCV2-3T 6.1. Introduction 6.2. Density functional theory calculations 6.2.1. Excited state transitions 6.3. Absorption and Emission in solution and thin film 6.3.1. Blend layer absorption spectra 6.3.2. Photoluminescence spectra of neat and blend films 6.4. Energy levels of the DCV2-3T series 6.5. Atomic force microscopy 6.6. Photoinduced absorption spectroscopy 6.6.1. PIA signatures of charged states 6.6.2. Recombination dynamics 6.6.3. Efficiency of the ping pong effect 6.7. Conclusion 7. Influencing the morphology of DCV2-5T:C60 blend layers 7.1. Introduction 7.2. Properties of the DCV2-5T:C60 interface 7.2.1. Analysis of the DCV2-5T triplet transition 7.2.2. Analysis of the DCV2-5T cation transitions 7.2.3. Suggested energy level scheme for neat and blend layer 7.3. Temperature evolution of excited state properties 7.4. Effect of substrate heating on excited state lifetime and generation rate 7.4.1. Solar cell devices 7.4.2. Photoinduced absorption 7.4.3. Impedance spectroscopy 7.5. Conclusion 8. Side chain variations on DCV2-5T 8.1. Introduction 8.2. Atomic force microscopy 8.3. Energy levels 8.4. Mip solar cells 8.4.1. Flat heterojunctions 8.4.2. Bulk heterojunctions 8.4.3. Discussion of Voc 8.5. Photoinduced absorption 8.5.1. Comparison at room temperature 8.6. Conclusion 9. Conclusion and Outlook 9.1. Conclusion 9.2. Outlook A. Appendix Bibliography

G protein-coupled receptors (GPCRs) form the biggest family of membrane receptors and are involved in numerous physiological processes. Collectively, these receptors are also prominently targeted by the pharmaceutical industry due to their implications in multiple diseases and disorders. GPCR signaling is tightly regulated. Several kinases, activated downstream of the receptor, initiate negative feedback loops; and arrestins play a crucial role in these regulatory processes by desensitizing the ligand–activated receptor and promoting its endocytosis. By doing so, arrestins control the duration and the amplitude of signal transduction at the cell surface. In the last few years, several non-canonical roles have also been attributed to arrestins, such as the post-endocytic activation of several signalling pathways, or the regulation of crosstalks between GPCRs and various other signalling events. My thesis project was aimed at providing a better understanding of the non-canonical functions of arrestins. The first objective of my research work was to investigate a possible reciprocal effect of the activation of the extracellular signal-regulated kinases 1 and 2 (ERK1/2) on GPCR signaling. We demonstrated that stimulation of ERK1/2, either by a cell surface receptor or a constitutively active mutant, leads to a reduction in steady-state expression levels of many GPCRs at the cell surface. This receptor redistribution mechanism is dependent on beta-arrestins phosphorylation. In vitro kinase assays combined with complementation experiments in mouse embryonic fibroblasts (MEFs) lacking beta-arrestins, revealed that beta-arrestin-2 phosphorylation on Ser14 and Thr276 is essential for the ERK1/2-promoted GPCR sequestration. This ERK1/2- and arrestins mediated regulatory process was found to result in a global dampening of cell responsiveness. The second objective of my research work was to identify and develop a small organic compound that inhibits the interaction between arrestins and the adaptor protein AP-2, without interfering with the recruitment of arrestin to the receptor. This inhibitor, named Barbadin, was found to specifically block endocytic processes that are dependent on the interaction between arrestins and the appendage domain of the b-subunit of AP-2. We demonstrated its value as an analytical tool in studying the role of the arrestins in GPCR signaling, such as cAMP production and ERK1/2 activation. These results support the concept that beta-arrestin/AP-2-dependent signaling is important to both G protein-dependent and -independent pathways. The third objective of my research work was to develop a BRET-based biosensor able to detect signal-dependent PTEN conformational changes. This biosensor was validated by monitoring PTEN activation induced by targeted mutations affecting key intramolecular interactions or by modulating signalling pathways that impact PTEN function. We also demonstrated the value of this biosensor in studying PTEN/protein interactions using two known interactors that activate PTEN, beta-arrestin-2 and RhoA. Finally, we uncovered PTEN activation by several GPCRs, previously unknown as PTEN regulators. Given the central role of the tumor suppressor PTEN in oncogenesis, this biosensor could also provide a precious tool for anti-cancer drug research. To conclude, my research work highlighted non-canonical mechanisms for arrestins to activate GPCR-dependent signaling pathways, such as cAMP, ERK1/2 and PTEN, as well as negatively regulate GPCR signaling upon phosphorylation by ERK1/2. This work was made possible by the development of new tools: a beta-arrestin inhibitor named Barbadin and a PTEN BRET-based biosensor that have both shown their usefulness in studying beta-arrestin noncanonical signaling. / Les récepteurs couplés aux protéines G (RCPG) représentent la plus grande famille de récepteurs membranaires et sont impliqués dans un grand nombre de processus physiologiques. Cette famille de récepteurs constitue aussi une cible majeure dans la recherche pharmaceutique au vu de son importance dans de nombreuses pathologies. La signalisation des RCPG est étroitement régulée. Plusieurs kinases activées en aval du récepteur initient des boucles de régulation négative. Les arrestines jouent un rôle clé dans ces processus de régulation en favorisant la désensibilisation du récepteur activé par le ligand, suivie de son endocytose. Ainsi, les arrestines contrôlent la durée et l’amplitude de la transmission du signal à la surface de la cellule. Ces dernières années, plusieurs rôles non-canoniques ont été attribués aux arrestines comme l’activation de voies de signalisation post-endocytiques, ou la modulation de la régulation croisée entre les RCPG et d’autres acteurs de la signalisation cellulaire. Le premier objectif de mon travail de recherche est d’examiner l’effet réciproque de l’activation des kinases ERK1/2 (extracellular signal-regulated kinases 1/2) sur la signalisation des RCPG. Nous avons démontré que la stimulation de ERK1/2, soit par un récepteur de surface soit par l’utilisation d’un mutant constitutivement actif, conduit à la baisse de l’expression de surface basale de nombreux RCPG. Des essais kinases in vitro, combinés à des expériences de complémentation dans des fibroblastes embryonnaires de souris (MEF), où les gènes beta-arrestine-1/2 ont été supprimés, démontrent l’importance de la phosphorylation par ERK1/2 des résidus Ser14 et Thr276 dans ce mécanisme de séquestration des RCPG. Cette régulation, contrôlée par ERK1/2 et arrestine, conduit à une baisse globale de la capacité de réponse de la cellule aux stimuli extracellulaires. Le deuxième objectif de mon travail de recherche est d’identifier et de développer une petite molécule organique qui inhibe l’interaction entre l’arrestine et la protéine adaptatrice du complexe d’endocytose AP-2, sans toutefois empêcher la formation du complexe arrestine/récepteur. Cet inhibiteur, nommé Barbadin, bloque sélectivement les processus d’internalisation dépendants de l’interaction entre arrestine- et la sous-unité beta2 de la protéine adaptatrice AP-2. Barbadin représente le premier inhibiteur des fonctions d’arrestine, et nous avons démontré son utilité comme outil analytique pour déterminer la contribution des arrestines dans l’activation de plusieurs voies de signalisation en aval des RCPG, telles que la production d’AMP cyclique (AMPc) ou l’activation des kinases ERK1/2. Nos résultats démontrent l’importance du complexe arrestine/AP-2 dans la signalisation dépendante et indépendante des protéines G. Le troisième objectif de mon travail de recherche est de développer un biosenseur BRET capable de mesurer les changements de conformation du suppresseur de tumeur PTEN. Nous avons validé ce biosenseur en mesurant l’activation de PTEN suite à des mutations ciblées déstabilisant les interactions intramoléculaires au sein de cette protéine ou en modulant différentes voies de signalisation qui affectent sa fonction. Nous avons démontré l’intérêt de ce nouvel outil dans l’étude des interactions entre PTEN et des partenaires protéiques, en utilisant deux interacteurs connus pour activer PTEN : b-arrestine-2 et RhoA. Finalement, en utilisant ce biosenseur, nous avons démontré pour la première fois la capacité de plusieurs RCPG à induire l’activation de PTEN. Étant donné le rôle central de PTEN dans le développement tumoral, ce biosenseur constitue aussi un outil précieux pour la recherche de nouveaux médicaments anticancer. Ainsi, au travers de ces trois lignes directrices, nous avons pu mettre en lumière de nouveaux rôles non-canoniques des arrestines, soit dans l’activation de voies de signalisation, (comme la production d’AMPc, l’activation de ERK1/2 ou de PTEN), soit comme régulateur négatif de la signalisation des RCPG après phosphorylation par ERK1/2. Ce travail a été rendu possible par le développement de nouveaux outils pour l’étude des RCPG : un inhibiteur de beta-arrestine, Barbadin, et un biosenseur BRET de PTEN ; tous deux ayant démontré leur utilité dans l’étude des voies de signalisation non-canoniques des arrestines.

Manipulating light by controlling surface plasmons on metals is being discussed as a means for bridging the size gap between micrometer-sized photonic circuits and nanometer-sized integrated electronics. Plasmonic waveguides based on metal nanoparticles are of particular interest for circumventing the diffraction limit, thereby enabling high-speed communication over short-range distances in miniaturized micro-components. However, scalable, inexpensive fine-tuning of particle assemblies remains a challenge and near-field probing is required to reveal plasmonic interactions. In this thesis, self-assembled waveguides should be produced on DNA scaffolds. DNA origami is an extremely versatile and robust self-assembly method which allows scalable production of nanostructures with a fine control of assemblies at the nanoscale. To form the plasmonic waveguides, six-helix bundle DNA origami nanotubes are used as templates for attachment of highly monodisperse and monocrystalline gold nanoparticles with an inter-particle distance of 1-2 nm. In the first part of this thesis, the effects of parameters which are involved in assembly reactions are systematically investigated. The assembly yield and binding occupancy of the gold nanoparticles are determined by an automated, high-throughput image analysis of electron micrographs of the formed complexes. As a result, unprecedented binding site occupancy and assembly yield are achieved with the optimized synthesis protocol. In addition, waveguides with different sizes of gold nanoparticles and different inter-particle distances, quantum dots attachments to the waveguides and multimerization of the waveguides are successfully realized. In the second part of this thesis, direct observation of energy transport through a self-assembled waveguide towards a fluorescent nanodiamond is demonstrated. High-resolution, near-field mapping of the waveguides are studied by electron energy loss spectroscopy and cathodoluminescence imaging spectroscopy. The experimental and simulation results reveal that energy propagation through the waveguides is enabled by coupled surface plasmon modes. These surface plasmon modes are probed at high spatial and spectral resolutions. The scalable self-assembly approach presented here will enable the construction of complex, sub diffraction plasmonic devices for applications in high-speed optical data transmission, quantum information technology, and sensing. / Die Manipulation des Lichts durch die Kontrolle von Oberflächenplasmonen auf metallischen Oberflächen und Nanopartikeln gilt als vielversprechende Methode zur Überbrückung der Größen-Lücke zwischen Mikrometer-großen photonischen und nanometer-großen elektronischen Schaltkreisen. Plasmonische Wellenleiter basierend auf metallischen Nanopartikeln sind vom besonderen Interesse, da sie die Umgehung des Beugungslimits und somit eine Hochgeschwindigkeitskommunikation über kurze Distanzen in immer kleiner werdenden Schaltkreisen ermöglichen könnten. Allerdings ist die skalierbare und kostengünstige Anordnung von Partikeln eine große Herausforderung und es werden Nahfelduntersuchungen benötigt um plasmonische Interaktionen detektieren zu können. Das Ziel dieser Arbeit ist die Selbstassemblierung von multi-partikel Wellenleitern auf DNA Gerüsten. Die Verwendung von DNA-Origami bietet eine äußerst vielseitige Plattform zur skalierbaren Herstellung von Nanostrukturen mittels Selbstassemblierung und ermöglicht eine präzise Kontrolle der Anordnungen im Nanobereich. Für den Aufbau der plasmonischen Wellenleiter werden DNA-Origami Nanoröhren, bestehend aus sechs Helices als Templat für die Anbindung von monodispersen und monokristallinen Goldnanopartikeln mit einem interpartikulären Abstand von 1-2 nm verwendet. Im ersten Abschnitt dieser Arbeit werden die beeinflussenden Faktoren dieser Assemblierungsreaktion systematisch untersucht. Die Ausbeute der assemblierten Strukturen und die Besetzung der Bindungsstellen werden durch eine automatisierte und effiziente Bildanalyse von Elektronenmikroskopieaufnahmen ausgewertet. Durch die Entwicklung eines optimierten Syntheseprotokolls werden bisher unerreichte Assemblierungsausbeuten ermöglicht. Zusätzlich erfolgen die experimentelle Realisierung von Strukturen mit verschieden großen Goldnanopartikeln und unterschiedlichen interpartikulären Abständen, sowie die Anbindung von Quantenpunkten an die Wellenleiter und eine Verknüpfung der assemblierten Strukturen. Der zweite Abschnitt dieser Dissertation befasst sich mit der Untersuchung des Energietransports in selbstassemblierten Wellenleitern über einen fluoreszierenden Nanodiamanten. Dazu erfolgen hochaufgelöste Nahfeldmessungen der Wellenleiter mittels Elektronenenergieverlustspektroskopie und Kathodolumineszenz-mikroskopie. Die experimentellen Ergebnisse und zusätzlich durchgeführte Simulationen bestätigen eine durch gekoppelte Oberflächenplasmonenmoden induzierte Weitergabe der Energie innerhalb des Wellenleiters. Diese Oberflächenplasmonenmoden werden bei hoher räumlicher und spektraler Auflösung untersucht. Das hier umgesetzte Konzept der Selbstassemblierung wird den Aufbau komplexer plasmonischer Geräte für Anwendungen im Bereich der optischen Hochgeschwindigkeitsdatenübertragung, der Quanteninformations-technolgie und der Sensorik ermöglichen.

Das Verstehen der elektronischen Prozesse in Nano-Hybridsystemen, bestehend aus Molekülen und Halbleiterstrukturen, eröffnet neue Möglichkeiten für optoelektronische Bauteile. Dafür benötigt es nanoskopische und gleichzeitig atomare Modelle und somit angepasste Rechenmethoden. Insbesondere "Standard"-Ansätze für die Dynamik offener Quantensysteme werden mit zunehmender Systemgröße jedoch sehr ineffizient. In dieser Arbeit wird eine neue Methode basierend auf einer stochastischen Schrödinger-Gleichung etablieren. Diese umgeht die numerischen Limits der Quanten-Mastergleichung und ermöglicht Simulationen von imposanter Größe. Ihr enormes Potenzial wird hier in Studien zu Anregungsenergietransfer und Ladungsseparation an zwei realistischen Nano-Hybridsystemen demonstriert: para-sexiphenyl Moleküle auf einer flachen ZnO Oberfläche (6P/ZnO), und ein tubuläres C8S3 Farbstoffaggregat gekoppelt an einen CdSe Nanokristall (TFA/NK). Im 6P/ZnO System findet nach optischer Anregung Energietransfer vom 6P Anteil zum ZnO statt. Direkt an der Grenzfläche können Frenkel-Exzitonen zusätzlich Ladungsseparation initiieren, wobei Elektronen ins ZnO transferiert werden und Löcher im 6P Anteil verbleiben. Beide Mechanismen werden mittels laserpulsinduzierter ultraschneller Wellenfunktionsdynamik simuliert. Danach wird die langsamere dissipative Lochkinetik im 6P Anteil studiert. Hierfür wird die eigene Simulationstechnik der stochastischen Schrödinger-Gleichung verwendet. Die Studie an der TFA/NK Grenzfläche basiert auf einer gigantischen equilibrierten Aggregatstruktur aus 4140 Molekülen. Ein generalisiertes Frenkel-Exzitonenmodell wird benutzt. Der Ansatz der stochastischen Schrödinger-Gleichung ermöglicht bemerkenswerte Einblicke in die Aggregat-interne Exzitonenrelaxation. Danach werden inkohärente Raten des Exzitonentransfers zum NK berechnet. Unterschiedliche räumliche Konfigurationen werden untersucht und es wird diskutiert, warum das Förster-Modell hier keine Gültigkeit besitzt. / Understanding the electronic processes in hybrid nano-systems based on molecular and semiconductor elements opens new possibilities for optoelectronic devices. Therefore, it requires for models which are both nanoscopic and atomistic, and so for adapted computational methods. In particular, "standard" methods for open quantum system dynamics however become very inefficient with increasing system size. In this regard, it is a key challenge of this thesis, to establish a new stochastic Schrödinger equation technique. It bypasses the computational limits of the quantum master equation and enables dissipative simulations of imposing dimensionality. Its enormous potential is demonstrated in studies on excitation energy transfer and charge separation processes in two realistic nanoscale hybrid systems: para-sexiphenyl molecules deposited on a flat ZnO surface (6P/ZnO), and a tubular dye aggregate of C8S3 cyanines coupled to a CdSe nanocrystal (TDA/NC). After optical excitation, the 6P/ZnO system exhibits exciton transfer from the 6P part to the ZnO. Close to the interface, Frenkel excitons may further initiate charge separation where electrons enter the ZnO and holes remain in the 6P part. Both mechanisms are simulated in terms of laser-pulse induced ultrafast wave packet dynamics. Afterwards, slower dissipative hole motion in the 6P part is studied. For this purpose, the own stochastic Schrödinger equation simulation technique is applied. The study on the TDA/NC interface is based on a gigantic equilibrated nuclear structure of the aggregate including 4140 dyes. A generalized Frenkel exciton model is employed. Thanks to the stochastic Schrödinger equation approach, energy relaxation in the exciton band of the TDA is simulated in outstanding quality and extend. Then, incoherent rates for exciton transfer to the NC are computed. Different spatial configurations are studied and it is discussed why the Förster model possesses no validity here.

No description available.

At low doses, relevant to nuclear incidents and accidental releases of radioactivity, the detriment of radiation extends beyond direct effects. This thesis investigates genomic instability, a subclass of non-targeted effects where damage and lethality is transmitted vertically and expressed in the progeny of cells many generations after initial radiation exposure. Through a series of experiments using clonogenic assay of human and fish cell culture, studies described in this thesis describe lethal mutations, hyper radiosensitivity and increased radioresistance – processes involving repair mechanisms that dictate survival in cells exposed to low doses. Further study investigates the difference in the relative biological effect of alpha particle radiation compared to what is expected at high doses. Results demonstrate increased radioresistance in a human cell line while also revealing increased lethality in a fish cell line confirming the need for consideration of dose-dependence as well as variance in behaviors of different cell lines and species. It is hoped the conclusions of this thesis will inspire the creation of protocols with greater attention to the indirect consequences of exposure to radiation at doses relevant to nuclear incidents and accidents. / Thesis / Master of Science (MSc)