En raison de l’omniprésence des hétérocycles azotés et de leurs propriétés biologiques, une attention particulière est accordée au développement de méthodologie pour leur synthèse et leur fonctionnalisation. L’étude de la fonctionnalisation d’énamides constitue une thématique importante car ces motifs s’avèrent être des outils synthétiques polyvalents permettant d’accéder à des dérivés hétérocycliques complexes. Les réactions de couplage Pd-catalysées constituent une méthode de choix rapide et efficace pour la synthèse d'énamides, notamment à partir de phosphates d'énols issus de lactames, d’imides ou d’amides. Le premier chapitre de ce travail porte sur le couplage organopalladié C-P de phosphines boranes secondaires chirales ou achirales avec des phosphates d’énols. Ce couplage C-P original, réalisé dans des conditions douces, conduit aux énamido-phosphines boranes correspondantes et offre de nombreuses possibilités pour la constitution d’une librairie de phosphines originales. Parallèlement à ce travail, l’addition nucléophile d’anions phosphures sur divers ène-carbamates acycliques conduit à des acides alpha-aminés béta-phosphorés originaux, porteurs d’un carbone quaternaire en alpha de l’azote. Le deuxième chapitre de la thèse porte sur la préparation et la caractérisation de chromophores organiques originaux basés sur un noyau pyrazinique et qui sont susceptibles de présenter des propriétés de fluorescence. Ces composés sont conçus pour former des nouveaux systèmes sensibilisateurs de cations de lanthanides, et être utilisés comme sensibilisateurs organiques pour l'imagerie moléculaire dans le proche infrarouge. / On account of the ubiquity of nitrogen heterocycles and their biological properties, the great attention is paid to developing methodologies of their synthesis and functionalization. For this purpose, the study of functionalization of enamides constitutes an important topic due to the utility of these motifs in the construction of complex heterocyclic derivatives. Palladium-catalyzed reactions of cross- coupling are rapid and efficient methods of choice for synthesis of enamides particularly starting from enol phosphates derived from lactams, imides or amides. The first chapter of the thesis evokes the original C-P coupling reaction of chiral and achiral secondary phosphine boranes with different enol phosphates in mild reaction conditions, leading to corresponding enamido-phosphine boranes. This methodology permits the construction of libraries of novels phosphines. Also, the reaction of nucleophilic addition of phosphide anions onto various enecarbamates acyclic was elaborated, giving an access to original beta-phosphino alpha-amino acids, bearing the quaternary carbon on alpha position to nitrogen. The second chapter is devoted to the preparation and characterization of organic chromophores based on the pyrazinic core, which are likely to exhibit the fluorescence properties. These compounds were designed to form new sensitizing systems for lanthanide cations and could be used as organic sensitizers for molecular imaging in near infrared.

The present thesis provides a systematic investigation of coordination polymers of 3d, rare-earth (4f) and main group element (Bi) using both rigid aromatic, flexible aliphatic linkers. Luminescent sensing behavior towards nitro aromatics, metal ions and ferroelectric behavior have been investigated using some of the prepared compounds. The possible usefulness of lone pair on the structure has been investigated using bismuth based coordination polymers. The thermal and optical behavior of lanthanide coordination polymers (Ce, Pr and Nd) have also been studied. Chapter 1 An Overview of Coordination Polymer (CP) Compounds This chapter presents a brief introduction to coordination polymer (CP) compounds. Starting from the brief historical background on coordination compounds, this chapter shed light on some earlier developments in this family of compounds by Yaghi, Robson and others. The usefulness of carboxylate and imidazolates in construction of some important coordination polymer compounds like MOF-5, HKUST-1, ZIFs, MIL-53, UiO-66, CD-MOF-1 etc has been described in detail along with its properties. The coordination polymers exhibit many important properties and some of the properties like sorption, separation, ionic conductivity, catalysis and ferroelectricity have been discussed briefly and summerized. Chapter 1 also provides the general synthetic and characterization approaches that have been employed during the present studies. Chapter 2 Part A: Adenine Based Coordination Polymers with Cyclohexane dicarboxylic acids This chapter presents the synthesis, structure and properties of four new coordination polymers [Zn4(C8H10O4)2.5(C5H4N5)3.2H2O].7H2O.2DMA (I), [Cd3(C8H10O4)2(C5H4N5)2.H2O] (II), [Cd(C8H11O4)2(C5H5N5)2.2H2O] (III), [Cd(C8H10O4)(C7H8N5O).H2O]. 4H2O (IV), (CHDA = cyclohexane dicarboxylic acid, ad = adenine, DMA = dimethylacetamide, 9-HEA = 9-hydroxyethyl adenine). The compound I and II forms three-dimensional structure having distinct arrangements of 1,4-CHDA and adenine units with Zn and Cd metals respectively. The molecular complex unit is observed in compound III with 1,2-CHDA and adenine. Compound IV forms two-dimensional structure with 9-HEA and 1,2-CHDA. The observation of base-pairing interactions in the above compounds is noteworthy. In compounds I, II and IV amino groups are appears to be free and utilized for the detection of nitro aromatic explosives through fluorescence quenching. The results revealed that the emission behavior of the present compounds is greatly influenced by the hydroxyl nitroaromatic analyses like indophenol, dinitrophenyl and trinitrophenols with very low detection limits. The compound I also exhibits considerable sensitivity towards metal ion detection, especially Fe2+/Fe3+, Cr3+, Ag+ and Hg2+ ions in solution. The presence of free nitrogen sites in compound II has been explored for the base catalyzed Knoevenagel condensation reaction, the quantitative yields are observed with various aldehyde substrates. Part B: Adenine Based Coordination Polymer with Oxydiacetic acid: [Cd2(C4H4O5)2(C5H5N5)].H2O.DMA The synthesis, structure and properties of a Cd based coordination polymer with oxydiacetic acid and adenine, [Cd2(C4H4O5)2(C5H5N5)].H2O. DMA is described. The compound has a two-dimensional structure formed by the connectivity involving Cd and oxydiacetic acid. The adenine ligand binds with the Cd metal center through the pyrimidine nitrogen and hangs in the inter layer spaces. The layers are stacked in a ABAB.... fashion and the inter layer spaces occupied by the dimethyl amine and water molecules. The water molecules are very labile and its removal can be accomplished by heating the sample at 100°C, which is also confirmed by the single crystal XRD, PXRD and IR studies. The availability of free amino groups of adenine molecule has been utilized for the detection of nitroaromatics, especially nitrophenols with good sensitivity. The amino group was also found to be useful in catalyzing Knoevenagel condensation reactions. Chapter 3: Rare-Earth Metal Carboxylates: Ln2(µ3-OH)(C4H4O5)2(C4H2O4)].2H2O [Ln=Ce, Pr and Nd] This chapter describes synthesis, structure and properties of series of rare-earth based compounds, [Ln2(µ3-OH)(C4H4O5)2(C4H2O4)].2H2O (Ln = Ce, Pr and Nd). The malic acid and fumaric acid form part of the structure. The lanthanide centers are connected by the malate units to form a two dimensional layers, which are pillared by fumarate units forming the three-dimensional structure. Overall, structure can be described as I2O1 type inorganic in two-dimension (Ln-O-Ln layers) and organic in one dimension. The extra framework water molecules form a dimer and occupy the channels. The robustness of the framework was reflected in terms of facile removal and reinsertion of the water molecules, which is also confirmed by single crystal XRD, variable temperature IR and cyclic TGA study. The presence of water dimers and weakly interacting water chain suggested the possibility of proton migration in these compounds. Proton conductivity studies reveal the conductivity values of ~2.85 x 10-6 Ω-1cm-1 at 98% relative humidity. The optical studies revealed an up-conversion behavior involving more than one photon for the neodymium compound. Chapter 4: Bismuth Carboxylates with Brucite and Fluorite Related Structures The synthesis, structure and properties of three new bismuth based coordination polymers have been described in this chapter. The compounds [C4N2H10][Bi(C7H4NO4)(C7H3NO4)].H2O (I), [Bi(C5H3N2O4) (C5H2N2O4)] (II) and [Bi(µ2-OH)(C7H3NO4)] (III) were isolated employing hydrothermal condition with three different heterocyclicdicarboxylic acids, 3,6-pyridinedicarboxylic acid, 4,5-imidazoledicarboxylic acid and 3,4-pyridinedicarboxylic acid respectively. The structures of all the compounds have linkages between Bi2O2 and the corresponding dicarboxylate forming a simple molecular unit in I, a bilayer arrangement in II and a three-dimensional extended structure in III. The topological arrangement of the nodal building units in the structures resembles brucite related layers in II and fluorite related arrangement in compound III. By utilizing the secondary interactions, the structure of III can be correlated to a Kagome related net. The observation of such classical inorganic related structures in the bismuth carboxylates is noteworthy. Heterogeneous catalytic studies indicate Lewis acidic nature in the bismuth center in all three compounds. Chapter 5: Solvent dependent Delamination, Restacking and Ferroelectric studies in a Two-Dimensional Compound [NH4][Ag3(C9H5NO4S)2(C13H14N2)2].8H2O This chapter describes synthesis, structure, water dependent delamination/restacking and ferroelectric behavior in a layered coordination polymer compound, [NH4][Ag3(C9H5NO4S)2(C13H14N2)2].8H2O. The compound has a two-dimensional structure with the water molecules occupying the inter-lamellar spaces. The lattice water molecules can be fully removed and reinserted, which accompany the crystalline-amorphous-crystalline transformation. This transformation resembles the collapse/delamination and re-stacking of the layers. This transformation has also been investigated by in-situ IR and PXRD studies. The presence of a natural dipole (anionic framework and cationic ammonium ions) along with the non-centrosymmetric space group gives rise to a room-temperature ferroelectric behavior to the compound with saturation polarization (Ps) of 1.95 μC/cm2 and remnant polarization of 0.63 μC/cm2. The temperature dependent dielectric measurements indicate that the ferroelectric-paraelectric transformation occurs at 320 K. The ferroelectric-paraelectric transformation also follows the crystalline-amorphous-crystalline transitions.

Dreiwertige Actinide (An(III)) und Lanthanide (Ln(III)) stellen im Falle ihrer Inkorporation eine ernste Gefahr für die Gesundheit des Menschen dar. An(III) sind künstlich erzeugte, stark radioaktive Elemente, die insbesondere bei der nuklearen Energiegewinnung in Kernkraftwerken entstehen. Durch Störfälle oder nicht fachgerechte Lagerung radioaktiven Abfalls können sie in die Umwelt und die Nahrungskette des Menschen gelangen. Ln(III) sind hingegen nicht radioaktive Elemente, die natürlicherweise vorkommen und für vielfältige Anwendungen in Technik und Medizin abgebaut werden. Folglich kann der Mensch sowohl mit An(III) als auch Ln(III) in Kontakt kommen bzw. sie inkorporieren. Es ist daher von enormer Wichtigkeit, das Verhalten dieser Elemente im menschlichen Körper aufzuklären. Während makroskopische Vorgänge wie Verteilung, Anreicherung und Ausscheidung bereits sehr gut untersucht sind, ist das Wissen hinsichtlich der chemischen Bindungsform (Speziation) von An(III) und Ln(III) in Körperflüssigkeiten noch sehr lückenhaft. In der vorliegenden Arbeit wurde daher erstmals die chemische Bindungsform von Cm(III) und Eu(III) in natürlichem menschlichem Urin (in vitro) spektroskopisch aufgeklärt und die gebildeten Komplexe identifiziert. Hierzu wurden auch grundlegende Untersuchungen zur Komplexierung von Cm(III) und Eu(III) in synthetischem Modellurin sowie mit den urinrelevanten organischen Modellliganden Harnstoff, Alanin, Phenylalanin, Threonin und Citrat durchgeführt und die noch unbekannten Komplexbildungskonstanten bestimmt. Abschließend wurden alle experimentellen Ergebnisse mit Literaturdaten und Vorherberechnungen mittels thermodynamischer Modellierung verglichen. Auf Grund der hervorragenden Lumineszenzeigenschaften von Cm(III) und Eu(III) konnte insbesondere auch die Eignung der zeitaufgelösten laserinduzierten Fluoreszenzspektroskopie (TRLFS) als Methode zur Untersuchung dieser Metallionen in unbehandelten, komplexen biologischen Flüssigkeiten demonstriert werden. Die Ergebnisse dieser Arbeit liefern damit neue Erkenntnisse zu den biochemischen Reaktionen von An(III) und Ln(III) in Körperflüssigkeiten auf molekularer Ebene und tragen zu einem besseren Verständnis der bekannten, makroskopischen Effekte dieser Elemente bei. Darüber hinaus sind sie die Grundlage weiterführender in-vivo-Untersuchungen.:1 Motivation und Zielstellung 2 Speziationsbestimmung exogener Schwermetalle in Biofluiden 2.1 Actinide und Lanthanide 2.2 Biochemisches Verhalten exogener Schwermetalle im Menschen 2.3 Speziationsbestimmung von Metallen 3 Komplexbildung von Curium(III) und Europium(III) mit organischen Modellliganden 3.1 Lumineszenzspektroskopische Eigenschaften von Curium(III) und Europium(III) in Wasser 3.2 Harnstoff – Hauptbestandteil des menschlichen Urins 3.3 Citronensäure – ubiquitäres Biomolekül0 3.4 Aminosäuren – Grundbausteine des Lebens 4 Speziation von Curium(III) und Europium(III) in menschlichen Urinproben 4.1 Charakterisierung und Analyse der natürlichen menschlichen Urinproben 4.2 Bestimmung der Speziation von Curium(III) und Europium(III) in Modellurin 4.3 Bestimmung der Speziation von Curium(III) und Europium(III) in menschlichem Urin 5 Diskussion 5.1 Vergleich der Komplexbildungseigenschaften von Curium(III) und Europium(III) 5.2 Thermodynamische Modellierung der Speziation von Curium(III) und Europium(III) in menschlichem Urin 5.3 Ausblick 6 Experimentelles / In case of incorporation, trivalent actinides (An(III)) and lanthanides (Ln(III)) pose a serious health risk to humans. An(III) are artificial, highly radioactive elements which are mainly produced during the nuclear fuel cycle in nuclear power plants. Via hazardous accidents or nonprofessional storage of radioactive waste, they can be released in the environment and enter the human food chain. In contrast, Ln(III) are nonradioactive, naturally occurring elements with multiple applications in technique and medicine. Consequently it is possible that humans get in contact and incorporate both, An(III) and Ln(III). Therefore, it is of particular importance to elucidate the behaviour of these elements in the human body. While macroscopic processes such as distribution, accumulation and excretion are studied quite well, knowledge about the chemical binding form (speciation) of An(III) and Ln(III) in various body fluids is still sparse. In the present work, for the first time, the speciation of Cm(III) and Eu(III) in natural human urine (in vitro) has been investigated spectroscopically and the formed complex identified. For this purpose, also basic investigations on the complex formation of Cm(III) and Eu(III) in synthetic model urine as well as with the urinary relevant, organic model ligands urea, alanine, phenylalanine, threonine and citrate have been performed and the previously unknown complex stability constants determined. Finally, all experimental results were compared to literature data and predictions calculated by thermodynamic modelling. Since both, Cm(III) and Eu(III), exhibit unique luminescence properties, particularly the suitability of time-resolved laser-induced fluorescence spectroscopy (TRLFS) could be demonstrated as a method to investigate these metal ions in untreated, complex biofluids. The results of this work provide new scientific findings on the biochemical reactions of An(III) and Ln(III) in human body fluids on a molecular scale and contribute to a better understanding of the known macroscopic effects of these elements. Furthermore, they are the basis of subsequent in vivo investigations.:1 Motivation und Zielstellung 2 Speziationsbestimmung exogener Schwermetalle in Biofluiden 2.1 Actinide und Lanthanide 2.2 Biochemisches Verhalten exogener Schwermetalle im Menschen 2.3 Speziationsbestimmung von Metallen 3 Komplexbildung von Curium(III) und Europium(III) mit organischen Modellliganden 3.1 Lumineszenzspektroskopische Eigenschaften von Curium(III) und Europium(III) in Wasser 3.2 Harnstoff – Hauptbestandteil des menschlichen Urins 3.3 Citronensäure – ubiquitäres Biomolekül0 3.4 Aminosäuren – Grundbausteine des Lebens 4 Speziation von Curium(III) und Europium(III) in menschlichen Urinproben 4.1 Charakterisierung und Analyse der natürlichen menschlichen Urinproben 4.2 Bestimmung der Speziation von Curium(III) und Europium(III) in Modellurin 4.3 Bestimmung der Speziation von Curium(III) und Europium(III) in menschlichem Urin 5 Diskussion 5.1 Vergleich der Komplexbildungseigenschaften von Curium(III) und Europium(III) 5.2 Thermodynamische Modellierung der Speziation von Curium(III) und Europium(III) in menschlichem Urin 5.3 Ausblick 6 Experimentelles

Cette thèse est le résultat d’une cotutelle entre l'Université de Pau et des Pays de l'Adour (UPPA) à Pau, en France et l'Université Christian Albrecht (CAU) à Kiel, en Allemagne. Dans le cadre de cette collaboration internationale, des méthodes bio-analytiques sont développées pour analyser quantitativement et qualitativement des peptides et protéines marquées par le couplage de la chromatographie avec la spectrométrie de masse. Les peptides et les digestats des protéines sont marquées selon un protocole optimisé par des lanthanides en utilisant des composés à base de DOTA. La séparation des peptides est réalisée par IP-RP-nanoHPLC. Des données complémentaires sont acquises par MALDI-MS pour l'identification et par ICP-MS pour la quantification. Dans ce contexte, une étape de pré-nettoyage en ligne est développée et mise en œuvre dans le protocole de séparation par nanoHPLC. Cette étape permet l'élimination efficace des réactifs appliqués en excès et ainsi la diminution du bruit de fond lié à la présence de métaux lors des analyses par ICP-MS. Les données obtenues sont alors plus facile à interpréter, la sensibilité des signaux des peptides n’étant par ailleurs pas modifié. L'extraction en phase solide (SPE) appliquée comme alternative entraîne des pertes importantes de peptides et peut être considérée comme inadaptée pour l'analyse quantitative. Des additifs pour éluants de nanoHPLC, tels que l'EDTA et le HFBA sont testés et jugés non bénéfiques pour l'analyse des échantillons peptidiques normaux. HFBA peut être reconsidéré pour une application spéciale sur des peptides très hydrophiles. Des peptides marqués sont développés. Leur utilisation en quantité connue pourrait permettre la quantification rapide et simple d'un échantillon de digestat à faible complexité. De plus, cet ensemble de peptides permet la superposition fiable des chromatogrammes, et ainsi de comparer des données complémentaires obtenues par l’analyse d’échantillon par ICP-MS et MALDI-MS. Expériences d'application avec le couplage laser femtoseconde avec ICP-MS sont effectuées sur des plaques métalliques de MALDI MS et montrent des résultats très prometteurs. Pour cela, les échantillons préalablement identifiés par MALDI-MS sont analysés par fsLA-ICP-MS. Les premières tentatives de quantification sur la plaque en acier modifiée sont satisfaisantes et donnent des résultats répondant aux attentes. L’optimisation des paramètres de MALDI-MS facilite l’identification des peptides. / This PhD thesis was a Cotutelle between the Université de Pau et des Pays de l’Adour (UPPA) in Pau, France and the Christian-Albrechts University (CAU) in Kiel, Germany. In the course of this international collaboration, bio-analytical methods for the quantitative and qualitative analysis of labelled peptides and proteins were developed, which were based on the hyphenation of chromatography with mass spectrometry. Peptides and protein digests were lanthanide labelled using DOTA-based compounds according to an optimised protocol. Separation on the peptide level was performed using IP-RP-nanoHPLC. Complementary data sets were acquired using MALDI-MS for identification and ICP-MS for quantification. In this context, an online precleaning step was developed and implemented in the nanoHPLC separation routine, which allowed for effective removal of excess reagents. This lead to lowered metal backgrounds during ICP-MS measurements and thus better data interpretability, while guarding peptide recovery at a maximum level. An alternative offline purification using solid phase extraction (SPE) resulted in important peptide losses and can be considered unsuitable for quantitative analysis. Additives to the nanoHPLC eluents, such as HFBA and EDTA were tested and not deemed beneficial for the analysis of normal peptide samples. HFBA can be reconsidered for special application on very hydrophilic peptide species. A set of labelled peptides was developed, which due to application of known quantities could be employed for quick and simple quantification of a low complexity digest sample. In addition this peptide set allowed for the reliable superposition of chromatograms, enabling sample comparability especially for complementary ICP-MS and MALDI-MS data. Experiments for application of fsLA-ICP-MS on MALDI-MS target plates were conducted and showed very promising results. For this purpose, samples that were already identified using MALDI-MS were supposed to be remeasured using fsLA-ICP-MS. First quantification attempts on the modified steel target plate were successful and in the range of expectance. Adjusted parameters for MALDI-MS allowed for proper peptide identifications.

Aufkonvertierungs-Nanokristalle (UCNPs), wie NaYF4 Kristalle, welche mit Yb3+ and Er3+ Ionen dotiert sind, emittieren höher energetisches Licht im ultravioletten/sichtbaren und nahinfraroten Bereich, nachdem sie mit weniger energiereichem nahinfraroten Licht angeregt wurden. Damit besitzen sie einzigartige optische Eigenschaften, wie verschiedenfarbige Emissionsbanden, verringerte Hintergrundfluoreszenz, größere Eindringtiefen in organisches Probenmaterial und eine hohe Lichtstabilität. Diese Eigenschaften sind besonders in der optischen Bioanalyse, in medizinischen und technischen Anwendungen von Vorteil. In dieser Arbeit werden die photophysikalischen und spektralen Eigenschaften von UCNPs im Ensemble und an Einzelpartikeln untersucht. Ein dafür entwickeltes konfokales Mikroskop ermöglicht Einzelpartikelmessungen bis in den Sättigungsbereich der UCNPs bei hohen Laser Anregungsleistungsdichten (P). Die erste Studie dieser Arbeit umfasst Ensemble- und Einzelpartikelmessungen an Kern und Kern-Schale 𝛽-NaYF4 Kristallen, welche mit 20% Yb3+ und 1% bis 3% Er3+ Ionen dotiert sind, wobei die optischen Eigenschaften P-abhängig über sechs Größenordnungen untersucht wurden. Die zweite Studie diskutiert die Einflüsse bei starker Änderung der Yb3+/Er3+ Ionen Dotierung anhand von drei verschiedenen Probensystemen. Diese unterscheiden sich sowohl in der Partikelgröße als auch in der Synthesevorschrift. Bei der dritten Studie wurde die direkte Anregung von Yb3+ mit der von Nd3+ Ionen an Nd/Yb/Er dotierten NaYF4 Partikeln bezüglich des aufkonvertierten Lumineszenz Verhaltens in Wasser verglichen. In weiteren Messungen wurde sowohl der Lumineszenz Resonanz Energie Transfer (LRET) ausgehend von einem UCNP zu dem Farbstoff Sulforhodamine B, als auch plasmonische Wechselwirkungen von Au-Schale UCNPs bei Einzelpartikelmessungen untersucht. / Upconversion nanoparticles (UCNPs), such as, NaYF4 crystals co-doped with Yb3+ and Er3+ ions, emit higher energetic light in the UV/vis and NIR range under lower energetic NIR excitation. This generates unique optical properties, for example, multi-colour band emissions, reduced background fluorescence, deeper tissue penetration depths and high photostability rendering UCNPs attractive options for bioimaging, medicinal and engineering applications. In this thesis the influence of multi-factor parameters on the photo-physical and spectroscopic properties of UCNPs are investigated under ensemble and single particle (SP) condition. For this purpose, a confocal laser scanning microscope was constructed to enable the characterisation of individual UCNPs up to their saturation conditions at high laser power densities (P). At first, ensemble and SP studies of core- and core-shell 𝛽-NaYF4 crystals co-doped with 20% Yb3+ and 1% to 3% Er3+ are performed over a P-range of six orders of magnitude. The second part of this thesis discusses influences in a wide variation in Yb3+/Er3+ ion doping concentration. Thereby, three different sample sets of varying size have been studied, using different synthesis approaches. A comparison of the Nd- and Yb-excitation of Nd/Yb/Er triple-doped NaYF4 UCNPs regarding their upconversion luminescence performance in water is provided in the third section of the thesis. In further studies, the process of luminescence resonance energy transfer (LRET) from an UCNP to the sulforhodamine B dye and the plasmonic interaction of an Au-shelled UCNP have been examined at the SP level.

No description available.