L’imagerie moléculaire est devenue incontournable pour le diagnostic et le traitement de cancers. Cette discipline regroupe un ensemble de techniques telles que la tomodensitométrie (CT), l’Imagerie par Résonance Magnétique (IRM), l’imagerie optique ou encore l’imagerie nucléaire (tomographie par émission de positons TEP, tomographie d’émission monophotonique TEMP). Chacune de ces techniques possède ses propres avantages et inconvénients et ne peut apporter à elle seule des informations anatomiques et fonctionnelles suffisantes. Les travaux actuels sont portés sur la conception de systèmes dits multimodaux afin de combiner les avantages de différentes techniques, voire de bénéficier d’un effet synergique. De par leur sensibilité comparable et leur complémentarité, coupler l’imagerie nucléaire à l’imagerie optique devient alors avantageux. La conception des systèmes monomoléculaires (MOMIA) contenant deux fonctions détectables par imagerie nucléaire (complexe de radiométaux) et imagerie optique (sonde fluorescente) nécessite en amont la mise au point d’outils de synthèses performants. La première partie de ce travail de thèse est consacrée à la synthèse d’agents chélatants bifonctionnels à base de polyamines macrocycliques, destinés à une utilisation en imagerie médicale. Ces agents doivent présenter d’excellentes propriétés de coordination vis-à-vis du métal visé, et posséder une fonction de greffage pour assurer le couplage avec une biomolécule vectrice. L’accès à de tels systèmes a nécessité le développement d’outils de synthèse efficaces de précurseurs macrocycliques dérivés du cyclène et du 13aneN4. L’introduction sélective de diverses fonctions de greffage visant principalement les résidus de type lysine a permis la préparation de plusieurs familles de composés, dont certains ont pu être « bioconjugués» à des peptides ou anticorps au sein du laboratoire ou dans le cadre de diverses collaborations. Plus particulièrement, la facilité d’utilisation du système « DOTAGA anhydride » a permis l’introduction aisée d’unités DOTA sur des nanoparticules ou des anticorps monoclonaux. Egalement, l’introduction d’une fonction alcyne a permis l’accès à de nouvelles briques moléculaires préparées par « click chemistry ». Dans une seconde partie sont présentés les travaux relatifs à la synthèse d’agents bimodaux originaux. Pour accéder à de tels systèmes, l’introduction d’un fluorophore de la famille des bodipys a été envisagée. L’absence de travaux antérieurs relatifs au couplage d’une polyamine cyclique et une entité bodipy a nécessité la préparation préalable d’un système modèle « DOTA bodipy », permettant de s’assurer par des études photophysiques que la présence des complexes métalliques macrocycliques ne va pas, ou peu, interférer avec les propriétés de fluorescence du bodipy. L’utilisation d’un espaceur « acide aminé » a alors permis d’accéder à de nouveaux bodipys porteurs de deux groupes fonctionnels en position méso. La fonctionnalisation a posteriori de ces briques de construction a permis l’introduction en dernier lieu d’unités macrocycliques N- et/ou C- fonctionnalisés. La préparation de système émettant dans le proche I.R. a été également envisagée. / Molecular imaging became a major tool for the diagnosis and the treatment of cancers. This research field includes different techniques, such as Tomography (CT), Magnetic Resonance Imaging (MRI), Optical Imaging or nuclear Imaging (PET Positron Emission Tomography, SPECT Single Photon Emission Computed Tomography). Each imaging modality has its own strengths and weaknesses, and thus, combining different and complementary systems can overcome inherent limitations associated with any one individual techniques and improve the accuracy of disease diagnosis and enhancing patient management. In particular dual-modality Optical/Nuclear imaging may find important preclinical and clinical applications. One possible approach seeks to fuse the two imaging systems into one molecule (MonOmolecular Multimodality Imaging Agent [MOMIA]) in order to ensure the same biodistribution of the two probes. Our strategy consists in combining a DOTA-like compound allowing complexation of radiometal for nuclear imaging (SPECT or PET) with a bodipy moiety, valuable probe those fluorescent properties can be finely adjusted. The first part of this work is dedicated to the synthesis of bifunctional chelating agents based on macrocyclic polyamines for medical imaging application. These compounds must show excellent coordination properties towards the aimed radiometal and possess a grafting function to allow the coupling with a biomolecule. Powerful and general routes for the synthesis of a wide range of N- and C-functionalized macrocycles derived from cyclen and 13aneN4 are described, which enable to access to a wide range of new BFCs by introduction of different functional groups reactive towards primary amines, such as carboxylic acid, isothiocyanate or anhydride function. Some compounds were conjugated to different biomolecules, such as peptides or antibodies. Morever, the introduction of an alkyne function yields a novel family of bifunctional agents allowing chemoselective attachment to functionalized biomolecules or to modified amino acids using « click chemistry ». In a second part, we focused on the introduction of a bodipy moeity to obtain new bimodal agents for dual Optical/Nuclear imaging. Interestingly, the attachment of the polyaminocarboxylate (DOTA derivative) to the bodipy makes it soluble in water and complexation of different metal cations of interest in the macrocyclic cavity does not significantly alter the luminescence properties of the whole system. In addition, the functionalization of the meso position by using an appropriate linker between the bodipy and DOTA-like units, i.e. a 4-nitrophenylalanine derivative, could provide a new bimodal tag for labeling antibodies or peptides. Optimisation of the second generation bodipy-DOTA, i.e. derivatization reaction to reach the near-IR range or introduction of C-functionalised macrocycles was also investigated.

A series of boron-containing conjugated microporous polymers with hierarchical porous structures have been readily prepared via typical transition metal-catalyzed coupling reactions. The distribution of micro- and mesopores in the networks as well as the specific surface areas are tunable via tailoring the structures of the building blocks. The distinct capability of the resulting Lewis acid-based neutral porous polymers to selectively capture fluoride ions provides a high-efficiency conversion into stable anionic porous polymers. For the first time, fluoride anion binding to boron atoms in a solid sample was essentially characterized by solid-state 11B MAS NMR spectroscopy, clearly revealing such an efficient conversion from a neutral network to a negatively charged one only through Lewis acid–base adduct formation. Upon a simple ion-exchange process, various heavy metal cations were facile to be loaded into the networks of the anionic porous polymers. Furthermore, the cobalt(II)-loaded porous polymers were shown to promote the stoichiometric homocoupling reactions of the different aryl Grignard regents, and exert distinct size selectivities for the homocoupling products, highly dependent on their porous structures. Such a successful loading strategy might be used for design and synthesis of new types of zeolite-like porous polymers with desirable catalytic properties for a certain organic transformation, as well as other functional materials.

Transition-metal chemistry in ionic liquids (IL) has achieved intrinsic fascination in the last few years. The use of an IL as environmental friendly solvent, offers many advantages over traditional materials synthesis methods. The change from molecular to ionic reaction media leads to new types of materials being accessible. Room-temperature IL have been found to be excellent media for stabilising transition-metal clusters in solution and to crystallise homo- and heteronuclear transition-metal complexes and clusters. Furthermore, the use of IL as solvent provides the option to replace high-temperature routes, such as crystallisation from the melt or gas-phase deposition, by convenient room- or low-temperature syntheses. Inorganic IL composed of alkali metal cations and polynuclear transition-metal cluster anions are also known. Each of these areas will be discussed briefly in this contribution. / Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.

Ionic liquids (ILs) have made a great impact on materials science and are being explored for potential applications in several disciplines. In this article, we briefly highlight the current state-of-the-art techniques employing ILs as new crystallisation media, working as neutral solvent, template or charge compensating species. The use of an IL as environmental friendly solvent offers many advantages over traditional crystallisation methods. The change from molecular to ionic reaction media leads to new types of materials being accessible. Room temperature ILs have been found to be excellent solvent systems for the crystallisation of a wide range of substances and morphologies ranging from nanoscopic crystals to micro- and even to macroscopic crystals. Moreover, high temperature routes, such as crystallisation from melts or gas phase deposition, have been replaced by convenient room or low temperature syntheses, employing ILs as reaction media. / Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.

The goal of this work was the study of evolutionary algorithms and utilization of them for digital circuit design. Especially, a genetic programming and its different manipulation with building blocks is mentioned in contrast to a genetic algorithm. On the basis of this approach, I created and tested a hybrid method of electronic circuit design. This method uses spread schemes according to the genetic algorithm for the pattern problems witch are solved by the genetic programming. The method is more successful and have faster convergence to a solution in difficult electronic circuits design than a common algorithm of the genetic programming.

<p dir="ltr">This paper aims to gain a deep understanding of up-to-date research and development on modular self-reconfigurable robots (MSRs) through a thorough survey of market demands and published works on <i>design methodologies</i>, <i>system integration</i>, <i>advanced controls</i>, and <i>new applications</i>. Some limitations of existing mobile MSR are discussed from the reconfigurability perspective of mechanical structures, and a novel MSR system is proposed to address the identified limitations of existing MSRs. The comprehensive set of <i>Functional Requirements</i> (FRs) of MSRs is discussed, from which the mechanical designs of MSR were created, and the system was prototyped and built for testing. Three main innovations of the designed modules for MSR are to (1) share torque power, (2) customize the size for a given task, and (3) have a low number of actuated motors while still maintain a motion with high <i>Degrees of Freedom</i> (DoF) to overcome the constraints by the power capacities of individual motors; this helps to increase reconfigurability, reduce cost, and reduce the size of conventional MSRs.</p>

No description available.

Power electronics applications in high power are normally large, expensive, spatially distributed systems. These systems are typically complex and have multiple functions. Due to these properties, the control algorithm and its implementation are challenging, and a different approach is needed to avoid customized solutions to every application while still having reliable sensor measurements and converter communication and control. This thesis proposes a synchronous digital control architecture that allows for the communication and control of devices via a fiber optic communication ring using digital technology. The proposed control architecture is a multidisciplinary approach consisting of concepts from several areas of electrical engineering. A review of the state of the art is presented in Chapter 2 in the areas of power electronics, fieldbus control networks, and digital design. A universal controller is proposed as a solution to the hardware independent control of these converters. Chapter 3 discusses how the controller was specified, designed, implemented, and tested. The power level specific hardware is implemented in modules referred to as hardware managers. A design for a hardware manager was previously implemented and tested. Based on these results and experiences, an improved hardware manager is specified in Chapter 4. A fault tolerant communication protocol is specified in Chapter 5. This protocol is an improvement on a previous version of the protocol, adding benefits of improved synchronization, multimaster support, fault tolerant structure with support for hot-swapping, live insertion and removals, a variable ring structure, and a new network based clock concept for greater flexibility and control. Chapter 6 provides a system demonstration, verifying the components work in configurations involving combinations of controllers and hardware managers to form applications. Chapter 7 is the conclusion. VHDL code is included for the controller, the hardware manager, and the protocol. Schematics and manufacturing specifications are included for the controller. / Master of Science

Discipline récente, la chimie supramoléculaire est l'un des domaines les plus fertiles de la recherche chimique. Motivé par le défi que représente la reconnaissance moléculaire sur mesure d'édifices complexes, un grand intérêt est apparu pour la conception et la synthèse des récepteurs macrocycliques polyfonctionnalisés. Nous avons récemment décrit une nouvelle classe de récepteurs moléculaires accessibles et polyvalents: les Dyn[n]arenes. Cette nouvelle classe est obtenue à partir de briques moléculaires 1,4-dithiophénols fonctionnalisés en position ortho assemblées par des liaisons disulfures. Cette stratégie de macrocyclisation contrôlée thermodynamiquement permet de produire de grandes quantités de produit final avec un moindre coût synthétique. Des récepteurs sur-mesure pour la reconnaissance d'anions, de cations et de zwitterions ont été obtenus par cette approche polyvalente. En particulier, le Dyn[4]arene octacarboxylate a montré la capacité de reconnaître sélectivement des dérivés de la lysine par via un ajustement induit asymétrique du récepteur lors de l'association. L'utilisation de ce récepteur pour reconnaître des peptides et protéines portant en position N-terminale une lysine a été étudiée. Enfin, la post-fonctionnalisation de ces Dyn[4]arenes a été explorée afin d'améliorer leur solubilité et leur propriétés de reconnaissance vis-à-vis de cibles biologiquement actives, ainsi que pour étudier la possibilité de leur greffage sur phase solide et leur utilisation en chromatographie d'affinité / As a recent discipline, supramolecular chemistry is one of the most active and fast-growing fields of chemical research. Driven by the challenge that tailored molecular recognition of complex molecules represents, a large interest has grown for the design and synthesis of multi-functionalized macrocyclic receptors. We recently described a new class of accessible and versatile molecular receptors: Dyn[n]arenes. This new class is obtained from 1,4-dithiophenols units functionalized in ortho position and assembled by disulfide linkages. This strategy of thermodynamically controlled macrocyclization allows producing large amounts of final product with a low synthetic cost. On demand receptors for anions, cations and zwitterions were obtained by this versatile approach. Particularly, the octacarboxylate-bearing dyn[4]arene showed the ability to selectively recognize Lysine derivatives via an asymmetric induced adjustment of the receptor upon the complexation. The use of this receptor to recognize N-terminal Lysine tagged peptides and proteins have been investigated. Finally, post-functionalization of Dyn[4]arenes have been explored to improve their solubility and recognition properties toward biologically active target and to investigate their solid phase grafting to be implemented in affinity chromatography

Polyketide products are useful compounds to research and industry but can be difficult to access due to their richness in stereogenic centers. Type I polyketide synthases offer unique engineering opportunities to access natural stereocontrol and resultant complex compounds. The development of a controlled in vitro platform based around type I polyketide synthases is described. It has been used to produce a small library of polyketide fragments on an unprecedented and synthetically-relevant scale and explore polyketide synthase enzymology. / text