Tesis sobre el tema "Molecular hybrid"

Los surfactantes son moléculas anfifílicas, con una cabeza solvofílica y una cola solvofóbica. Cuando la concentración de surfactante en solución es suficientemente alta, las moléculas se agregan entre ellas para proteger las partes solvofóbicas del contacto con el medio. Tales agregados pueden tener forma y tamaño muy diferentes, dependiendo del surfactante y de las condiciones del sistema. La auto-organización de los surfactantes (self-assembly), debida a un compromiso energético y entrópico de su estructura molecular, es la clave que permite observar cristales líquidos muy ordenados. En presencia de un precursor inorgánico y dependiendo de las interacciones que este precursor establece con el surfactante, se puede observar la formación del material híbrido. Los materiales híbridos constituyen un paso intermedio fundamental para la síntesis de los materiales mesoporosos ordenados, los cuales se obtienen eliminando la matriz orgánica (surfactante) del substrato inorgánico.
El presente estudio tiene como principal objetivo estudiar bajo cuales condiciones los sistemas formados por un surfactante, un precursor inorgánico y un solvente, se auto-organizan para dar lugar a estructuras híbridas muy ordenadas. En particular nos proponemos individuar cuales son las características más importantes que los precursores inorgánicos deberían tener para poder observar la formación de materiales mesoporosos ordenados.
Simulaciones Monte Carlo en el colectivo canónico han sido utilizadas para analizar la agregación de los surfactantes en estructuras complejas, como micelas, cilindros organizados en forma hexagonal, o laminas, a partir de configuraciones totalmente desordenadas. Con particular interés hemos analizado el rango de condiciones que llevan a la formación de las estructuras cilíndricas, y estas mismas estructuras han sido comparadas en función de algunas importantes características morfológicas, como el tamaño de poro, el grosor de las paredes, la presencia y accesibilidad de los grupos funcionales en los poros. El modelo usado representa las moléculas de surfactante y de precursor inorgánico como cadenas de segmentos en una red tridimensional que discretiza el espacio en sitios de volumen unitario. Este modelo no entra en el detalle de las características físicas y químicas de las moléculas, pero permite reproducir su agregación en estructuras complejas en un tiempo de cálculo muy razonable. La separación de fase ha sido también evaluada recorriendo a una teoría de campo medio, la quasi-chemical theory, que, aunque no pueda predecir la formación de estructuras ordenadas, ha sido muy útil para confirmar los resultados de las simulaciones, sobretodo cuando no se observa formación de fases ordenadas.
El estudio de surfactantes distintos, uno modelado por una cadena lineal y otro con una cabeza ramificada, nos ha permitido evaluar algunas diferencias estructurales de los materiales obtenidos. La ramificación de la cabeza, que merecería un estudio más profundo del que hemos descrito en este trabajo, ha evidenciado unas interesantes consecuencias en el tamaño de los poros. Este mismo surfactante con cabeza ramificada ha sido elegido para la síntesis de agregados cilíndricos utilizados como templates en la formación, agregación, y condensación de una capa de sílica modelada a través de un modelo atomístico. En particular, hemos aislado uno de los cilindros presentes en los cristales líquidos de estructura hexagonal, y a su alrededor hemos simulado la formación de una capa de sílica utilizando un modelo atomístico. De esta forma, hemos obtenido un poro típico de una estructura mesoporosa más realista, sin necesidad de asumir una forma mas o menos cilíndrica del template, por ser este generado de la auto-agregación del surfactante.
Surfactants are amphiphilic molecules with a solvophilic head and a solvophobic tail. When the surfactant concentration in a given solution is high enough, the molecules aggregate between them to shield the solvophobic part from the contact with the solvent. Such aggregates can show very different sizes and shapes, according to the surfactant and the conditions of the system. The surfactants self-assembly, being due to an energetic and entropic compromise of their molecular structure, is fundamental to observe the formation of very ordered liquid crystals. In the presence of an inorganic precursor and depending on the interactions established between such a precursor and the surfactant, it is possible to synthesize a hybrid material. Hybrid materials are the key step for the formation of periodic ordered mesoporous materials, which can be obtained by eliminating the organic soft matter (the surfactants) from the inorganic framework. Periodic ordered mesoporous materials represent an important family of porous materials as they find a large number of applications in several industrial fields, such as separations, catalysis, sensors, etc. In the last decade, the range of potential applications has increased with the possibility of functionalizing the pore walls by incorporating organic groups during the synthesis, or with post-synthesis treatments.
In this work, we are interested in studying the formation of ordered materials when hybrid organic-inorganic precursors are used. Lattice Monte Carlo simulations in the NVT ensemble have been used to study the equilibrium phase behavior and the synthesis of self-assembling ordered mesoporous materials formed by an organic template with amphiphilic properties and an inorganic precursor in a model solvent. Three classes of inorganic precursors have been modeled: terminal (R-Si-(OEt)3) and bridging ((EtO)3-Si-R-Si-(OEt)3)) organosilica precursors (OSPs), along with pure silica precursors (Si-(OEt)4). Each class has been studied by analyzing its solubility in the solvent and the solvophobicity of the inorganic group.
At high surfactant concentrations, periodic ordered structures, such as hexagonally-ordered cylinders or lamellas, can be obtained depending on the OSPs used. In particular, ordered structures were obtained in a wider range of conditions when bridging hydrophilic OSPs have been used, because a higher surfactant concentration was reached in the phase where the material was formed. Terminal and bridging OSPs produced ordered structures only when the organic group is solvophilic. In this case, a partial solubility between the precursor and the solvent or a lower temperature favored the formation of ordered phases.
With particular interest, we have analyzed the range of conditions leaving to the formation of cylindrical structures, which have been evaluated according to the pore size distribution, the pore wall thickness, the distribution and the accessibility of the functional organic groups around the pores. The phase behavior has been also evaluated by applying the quasi-chemical theory, which cannot predict the formation of ordered structures, but was very useful to confirm the results of simulations, especially when no ordered structures were observed.
The study of the phase and aggregation behavior of two different surfactants, one modeled by a linear chain of head segments and the other modeled by a branched-head, permitted us to evaluate some structural differences of the materials obtained.

The interaction of polymers and a solid surface modifies the polymer properties near the surface (the so-called interphase) in comparison to those of the bulk polymers. A clear explanation of the origin of this modification in the polymer properties is still missing. The aim of my PhD thesis has been the study of the mechanical properties of nanocomposite materials and the analysis of the behavior of polymers in the interphase region under deformation. Coarse-grained simulations have been performed for a model system of silica nanoparticles (NPs) embedded in atactic polystyrene (PS). In this case molecular details are important only in a small spatial region of the interphase. The rest of the polymer has bulk-like behavior which can be described by continuum mechanics. Therefore, it is convenient to simulate the region of interest by molecular dynamics (MD) and to treat the rest of the nanocomposite by continuum mechanics methods. To fulfill this we developed a new hybrid molecular – continuum simulation method for polymers. In our model the center of the simulation box is treated by MD. This region is surrounded by a continuum domain which is described by a finite element approach. To the best of our knowledge, the present work is the first attempt to use simultaneously MD and FE methods in simulations of polymers. It has been the main motivation of this work to develop a new hybrid scheme for polymers. Coupling a MD to a FE method requires a lot of modifications in both the MD and FE domains. The introduction of my thesis contains a short review on the existing hybrid schemes and modifications needed to couple the two domains. Difficulties to couple them such as transferring the information between two domains and equilibrating the continuum domain are explained. Different methods and techniques to overcome these difficulties as well as the advantages and disadvantages of each method are described briefly. These methods, however, are limited to liquid and crystalline solid materials. They have to be modified to be capable of simulating polymers. In the present PhD thesis we have explained the technical difficulties to couple a MD to a FE model for polymers in the MD domain and how we tackled these problems. Modifications in the FE domain have been done by researchers in the Applied Mechanics Department of the University of Erlangen. The current work has involved a strong collaboration with them to integrate a modified MD domain into a FE domain. In the second chapter of the thesis, the mechanical properties of a pure polystyrene matrix as well as a polystyrene matrix filled with bare silica nanoparticles are investigated by MD simulations at the coarse-grained level. The stress-strain curve of polystyrene has been computed for a range of temperatures below and above the glass transition. The Young’s modulus of polystyrene obtained from the stress-strain curve has been compared to experimental and atomistic simulation data. By studying the local segmental orientation and the local structure of the polymer near the nanoparticle surface under deformation, we have found that the segments close to the silica nanoparticle surface are stiffer than those in the bulk. The thickness of the interphase has been estimated. We have shown that the Young’s modulus of the studied nanocomposite increases by increasing the volume fraction of the nanoparticle. The results of interphase studies under deformation as described in this section are important input parameters for the FE simulations in the present hybrid scheme; this will explained in chapter four. In hybrid simulations the usual periodic boundary conditions of MD cannot be used as the MD domain is surrounded by a FE domain. In hybrid schemes boundary conditions should allow an information transfer through the boundary region between two domains. Therefore, I developed new non-periodic boundary conditions, so-called stochastic boundary conditions (SBC), which are able to transfer information (forces and deformations) between the two domains and to minimize the artifacts in the dynamics. In the SBC ensemble we have defined a set of auxiliary particles, so-called anchor points, in the boundary region. The anchor points are harmonically coupled to the MD particles. They play an important role to transfer the information between the MD and FE domains. Particles in the boundary region are forced to mimic the bulk behavior by employing a stochastic dynamics in the boundary region. This minimizes the artificial influence of the anchor points and the vacuum on the polymers in the center of the box. The SBCs are explained in more detail in the third chapter. We have validated these boundary conditions by comparing the results of coarse-grained polystyrene melts under nonperiodic and regular periodic boundary conditions. Excellent agreement is found for thermodynamic, structural, and dynamic properties. The new hybrid molecular – continuum method for polymers is explained in more detail in chapter four. Due to the significant difference between the time steps in the two domains, we employed a staggered coupling procedure in which the continuum domain has been described as a static region while the MD domain has been treated dynamically. The Arlequin method has been used for the static coupling of the MD to the FE domain. The information transfer between them has been realized in a coupling region which contains the above mentioned anchor points. In this region two descriptions are valid, i.e., the particle and the continuum one. The total energy is blended by a weighting factor. Atactic PS and a PS silica nanocomposite have been simulated in a coarse-grained representation to validate the new hybrid scheme. The deviations between data from the hybrid method and pure FE simulations have been computed for quantities such as reaction forces and the Cauchy stress. The sources of the observed deviations are discussed in some detail. Finally, the fifth chapter summarizes the results obtained in this PhD work, and discusses possibilities to extend the current hybrid model to new problems such as larger deformations.

L'ADN est en permanence exposé à un grand nombre d'événements dommageables déclenchées par des agents endogènes et exogènes. De nombreux travaux expérimentaux ont fourni des informations cruciales sur les propriétés structurelles et la réparation de certains des lésions de l'ADN. Cependant, il manque une vision mécanistique ou énergétique sur leur formation. La biochimie computationnelle a émergé comme un outil puissant pour comprendre les réactions biochimiques et les propriétés électroniques de systèmes complexes.Dans cette thèse, nous étudions la formation de lésions complexes intra-brin et inter-brin. Ces lésions tandem constituent une puissant menace à l'intégrité du génome, en raison de leur haute fréquence mutagenique. Tout d'abord, nous discutons l'attaque d'une liaison covalente entre un radical pyrimidinique. En comparant avec les bases isolees, nos simulations hybrides Car-Parrinello demontrent que la reactivité de la thymine et de la cytosine radicalaires sont inversees dans l'environnement B-helical. De plus, nos resultats montrent egalement une deformation plus importante pour la lesion G[8-5]C.Nous rationalisons également la plus grande réactivité des cytosines par rapport aux purines vers la formation multi-etapes de lésions complexes inter-brins par condensation avec un site C4' abasique. Ces résultats bases sur des simulations avec solvatation explicite et combines a la théorie de la fonctionnelle de la densité sont en accord avec les données expérimentales
DNA is continuously exposed to a vast number of damaging events triggered by endogenous and exogenous agents. Numerous experimental studies have provided key information regarding structural properties of some of the DNA lesions and their repair. However, they lack in mechanistic or energetic information pertaining to their formation. Computational Biochemistry has emerged as a powerful tool to understand biochemical reactions and electronic properties of large systems.In this thesis we study the formation of inter- and intra-strand cross-links. These tandem lesions pose a potent threat to genome integrity, because of their high mutagenic frequency. First, we discuss the formation of complex defects which arise from the attack of a pyrimidine radical onto guanine. In comparison with the reactivity of isolated nucleobases, our hybrid Car-Parrinello Molecular Dynamics simulations reveal that the reactivity of hydrogen-abstracted thymine and cytosine is reversed within a B-helix environment. Further, our data also suggest a more severe distortion of the B-helix for G[8-5]C.Second, we rationalize the higher reactivity of cytosine vs. purines toward the multistep formation of inter-strand crosslinks with a C4' oxidized a basic site, which is in qualitative agreement with experiments on isolated nucleobases, using explicit solvent simulations combined to density functional theory

Cette thèse porte sur les méta-heuristiques hiérarchiques parallèles adaptatives pour l'échantillonnage conformationnel. Étant un problème hautement combinatoire et multlmodal, l'échantillonnage conformationnel requière la construction d'approches hybrides à large échelle. Après une analyse dei modèles mathématiques, nécessitant l'examen des différentes formulations du champ de force, nous avons proposé une étude des opérateurs de variation et des méthodes de recherche locale adaptés au problème ainsi que leur hybridation dynamique et adaptative. Cette étude nous a conduit à la proposition de mécanismes d'adaptation des paramètres des algorithmes utilisés en fonction du processus d'évolution. Dans cette thèse, nous proposons également des algorithmes adaptatifs hybndes hiérarchiques distribués, fortement extensibles. L'expérimentation, basée sur l'utilisation de multiples modèles parallèles, démontre la grande efficacité de ces algorithmes. En effet, les résultats obtenus montrent que des RMSD moyens en dessous de 1.0 A peuvent être obtenus sur des instances difficiles des problèmes de prédiction de la structure des protéines et de docking moléculaire. La validation des approches hybrides proposées a été effectuée sur Grid'5000, une grille expérimentale d'échelle nationale composée d'environ 5000 coeurs de calcul. Une image système a été développée en utilisant Globus pour permettre des déploiements distribués à large échelle. L'approche hiérarchique distribuée construite a été ainsi déployée sur plusieurs grappes, avec près de 1000 coeurs de calcul
The thesis proposes an extensive analysis of adaptive hierarchical parallel metaheuristics for ab initio conformational sampling. Standing as an NP, combinatorial, highly multi-modal optimization problem, conformational sampling requires for high-performance large scale hybrid approaches to be constructed. Following an incremental definition, minimum complexity conformational sampling mathematical models are first analyzed, entailing a review of different force field formulations. A comprehensive analysis is conducted on a large set of operators and local search algorithms including adaptive and dynamic mechanisms. As determined by the analysis outcomes, complex a priori and online parameter tuning stages are designed. finally, highly scalable hierarchical hybrid distributed algorithm designs are proposed. Experimentation is carried over multiple parallelization models with afferent cooperation topologies. Expenmentations resulted in unprecedented results to be obtained. Multiple perfect conformational matches have been determined, on highly difficult protein structure prediction and molecular docking benchmarks, with RMSD average values below 1.0A. The validation of the proposed hybrid approaehes was performed on Grid'5000, a French computational grid, with almost 5000 computational cores. A Globus Toolkit hased Grid'SOOO system image has been developed, sustaining large scale distributed deployments. The constructed hierarchical hybrid distributed algorithm has been deployed on multiple clusters, with almost 1000 computing cores. Finally, a parallel AutoDock version was developed using the ParadisEO framework, integrating the developed algorithms

This thesis sets to understand key limiting steps in organic solar cells (OSCs) and hybrid organic-inorganic light-emitting diodes (HyLEDs) and to provide routes to more environmentally friendly and lower cost devices. As well as studying organic optoelectronic devices, hybrid organic-inorganic approaches are also explored from both a fundamental point of view (quantum dot/organic solar cells) to a more technological one (air-stable, low cost light emitting diodes). The origin of the opencircuit voltage in bilayer solar cells is studied using transient optoelectronic techniques to probe the charge distribution in the active layer and the lifetime of charge carriers under working conditions. Furthermore, these techniques are applied to hybrid quantum dot/organic bilayer solar cells and provide a quantitative analysis of the non-geminate recombination in the device and its influence on the open-circuit voltage. The thesis also explores the use of water-soluble donors for OSCs and led to first true water-soluble donor.
Este trabajo de tesis proporciona las bases para el análisis detallado de los pasos limitantes del funcionamiento de celdas solares orgánicas (OSCs) y de los lightemitting diodos híbridos orgánico-inorgánicos (HyLED); además de procurar las rutas para la preparación de nuevos tipos de dispositivos económicos y seguros para el medio ambiente. El origen del voltaje de circuito abierto en celdas solares de doble capa ha sido estudiado mediante técnicas de optoelectrónica transientes para investigar la distribución de cargas en el estado activo y los tiempos de vida de las cargas bajo las condiciones de trabajo. Además, estas técnicas han sido aplicadas a celdas solares híbridas quantum dots/doble capa orgánica consiguiendo un análisis cuantitativo de la recombinación no-geminial en el dispositivo y su influencia sobre el voltaje de circuito abierto. La tesis también explora el uso de donantes solubles en agua para OSCs y llevó al primer verdadero donante soluble en agua.

Il rinforzo di elastomeri mediante l’utilizzo di cariche (filler) inorganiche (nerofumo, SiO2) è ampiamente impiegato nell'industria dei pneumatici per ottenere e potenziare le proprietà meccaniche dei materiali. In particolare, recenti studi hanno dimostrato che il controllo della morfologia delle particelle di SiO2, la loro funzionalizzazione superficiale e la loro distribuzione all'interno della matrice polimerica (interazioni filler-filler e interazioni filler-gomma) svolgono un ruolo chiave per ottenere e migliorare le proprietà meccaniche. Questi risultati suggeriscono che l'utilizzo di filler con struttura e funzionalità controllabili, in grado di migliorare contemporaneamente le interazioni filler-filler e filler-gomma, possa essere un approccio promettente e innovativo per il miglioramento delle proprietà dei materiali compositi utilizzati nell’industria dei pneumatici. Tra i materiali presenti e studiati in letteratura, i PoliSilsesQuiossani (PSQs) sono una nuova classe di materiali ibridi organici-inorganici che presentano o conferiscono, se inclusi in polimeri, una serie di proprietà interessanti per una possibile applicazione industriale (ad esempio stabilità termica, proprietà meccaniche, ecc). Tuttavia, il controllo e l’effetto dell’introduzione dei PSQs nei polimeri è un fenomeno complesso e sono necessari ulteriori studi per stabilire le relazioni tra la struttura/morfologia e le proprietà impartite ai nanocompositi. L'obiettivo di questo lavoro di dottorato è quindi quello di studiare e valutare l’utilizzo di PSQs con diverse strutture molecolari (cage o ladder) come filler innovativi in nanocompositi potenzialmente sfruttabili nelle formulazioni dei pneumatici. In particolare, è stata messa a punto una nuova sintesi dove SiO2 e cage-PSQs (POSS) appartengono alla stessa struttura molecolare (SiO2@POSS). La sintesi prevede una silanizzazione della SiO2 mediante l’utilizzo di un silano e la successiva reazione con diverse quantità di OctaMethacrylPOSS in presenza di un attivatore radicalico (dicumilperossido), il quale permette l’attivazione dei gruppi reattivi del POSS e del silano. SiO2@POSS è stato poi utilizzato come filler in Stirene Butadiene per la preparazione di nanocompositi (SBR/SiO2@POSS). Dopo aver verificato l’effettiva funzionalizzazione del POSS in SiO2@POSS mediante spettroscopia IR e NMR, le interazioni tra SiO2@POSS e il polimero sono state studiate mediante SEM, AFM e NMR. I risultati hanno mostrato un’elevata adesione all’interfaccia tra i due materiali, un aumento della rigidità delle catene polimeriche e una notevole copertura delle particelle di filler con strati di polimero confermando quindi un’elevata interazione filler-polimero nel materiale finale. Queste proprietà hanno notevoli conseguenze dal punto di vista meccanico migliorando significativamente il rinforzo del polimero, diminuendo la dissipazione di energia sotto sforzo, portando ad una potenziale riduzione del filler nel materiale finale. Un approccio simile, è stata utilizzato per la preparazione di nanocompositi di Polibutadiene (PB) contententi PSQs a struttura mista (cage e ladder) funzionalizzati con gruppi tiolo (SH-NBBs) altamente reattivi. Le misure 1H NMR e di swelling hanno mostrato una forte correlazione tra la struttura e le interazioni polimero-filler (PB-NBBs) con conseguente diminuzione della mobilità delle catene polimeriche. Le misure dinamo meccaniche (DMTA) hanno confermato che piccole quantità di NBBs forniscono un notevole rinforzo e che il controllo della struttura degli NBB sembra essere fondamentale per le performance dei nanocompositi. In conclusione, i risultati evidenziano un chiaro contributo della struttura dei PSQs nel favorire regioni di gomma legata che impartiscono particolare rinforzo ai nanocompositi. Ciò rappresenta un punto di grande rilievo poiché consente di esplicitare l’azione dei PSQs come filler molecolare innovativo.
The reinforcement of elastomers (e.g. PolyButadiene PB, Styrene Butadiene Rubber SBR) by addition of inorganic fillers (carbon black, SiO2) is a practice widely employed in tire industry. In particular, the control SiO2 NPs morphology, surface functionalities, and their networking within the polymer matrix (i.e. filler-filler and filler-rubber interactions) plays a key role in achieving desired mechanical properties. These outcomes suggest that the utilization of fillers with tailorable structure and functionalities, able to simultaneously enhance the networking and the interaction with rubber, may be a promising strategy for upgrading the composites properties. Emerging fillers which seems to be suitable candidates are Polysilsesquioxanes (PSQs), a novel class of hybrid materials which exhibit or impart, if included in composites, a number of beneficial properties (e.g. thermal stability, mechanical properties, etc…). Stimulated by this background, the aim of this work is to explore the possibility to employ PSQs with different molecular structure (cage or ladder-like) as innovative fillers in rubber nanocomposites potentially exploitable in tires formulation. In detail, a novel hybrid filler, SiO2@POSS, where SiO2 and cage-like PSQs (POSS) belong to the same functional structure, has been developed by grafting on silanized SiO2 different loadings of OctaMethacrylPOSS, using a surface reaction mediated by dicumylperoxide. The hybrid filler was then employed for preparing SBR/SiO2@POSS nanocomposites, which display outstanding mechanical properties. This has been associated to the peculiar structure of SiO2@POSS, constituted by NPs aggregates partially interconnected and decorated by POSS nanounits which, thanks to the high number of reactive functionalities, promote the formation of a tight filler network which immobilizes filler and rubber, afford a relevant reinforcement and improve the hysteretical properties. A similar approach, has been applied for study the properties of PB nanocomposites including PSQs with tailorable cage or ladder-like structure. Swelling experiments and, more in depth, 1H NMR revealed a significant relation between NBBs architecture and their interactions with the polymer, resulting in restricted rubber chains mobility and significant reinforcement. In summary, the whole results suggest that PSQs can be promising fillers, which grant the transfer of the advanced properties of these nanounits to the final nanocomposites.

El desarrollo de nuevas membranas de sílice ha ido ganando cada vez más importancia en los últimos años. Se propone una nueva metodología para la modificación del material de membrana de sílice. Un nuevo material de membrana de sílice hidrófobico y dopado con cobalto ha ido desarrollado. El nuevo material se preparó por la hidrólisis catalizada por ácido y el proceso de condensación de ortosilicato de tetraetilo (TEOS) y metiltrietoxisilano (MTES). Los resultados mostraron que la estabilidad térmica del nuevo material se ve reforzada por proceso de dopaje con cobalto. Se logró un material de membrana de sílice microporosa hidrófoba con alta estabilidad térmica de hasta 560 °C en atmósfera oxidante y una distribución de tamaño de poro estrecha. El nuevo material se usó para la preparación de nuevas membranas. Las membranas híbridas dopadas con cobalto mostraron mejores resultados en comparación con las híbridas no dopadas respeto la selectividad de los gases.
Development of new silica membranes properties, e.g., molecular sieving properties, has been increasingly gaining importance in the last few years. A new methodology for modification of silica membrane material is proposed. A novel silica membrane material, referred to as hydrophobic metal-doped silica, was developed by cobalt-doping within the organic templated silica matrix (hybrid silica). The novel material was prepared by the acid-catalyzed hydrolysis and condensation process of tetraethylorthosilicate (TEOS) and methyltriethoxysilane (MTES). The results showed that the thermal stability of the organic templated silica matrix was enhanced by cobalt-doping process. A hydrophobic microporous silica membrane material with high thermal stability up to 560 °C in oxidizing atmosphere and a narrow pore size distribution was achieved. The novel material was used for preparation of novel supported silica membranes. The cobalt-doped hybrid membranes showed better results compared with the non-doped hybrid one concerning the ideal selectivity of gases.

Population structure, gene flow and dispersal are some of the most commonly estimated population parameters in population genetics, evolutionary biology and conservation genetics. The primary aim of thesis is to test the precision and accuracy of genetic estimates of population structure, gene flow and dispersal. The controlled replicated Drosophila melanogaster experiments of known effective population size (Ne = 14.3) and dispersal rate (m = 0.0025 - 0.04) all adhered to Wright??s demographic island model. Three statistical approaches were empirically tested: 1) the conversion of population structure to gene flow using FST, RST, SHUA and PhiST ; 2) the private alleles method to estimate gene flow; 3) a Bayesian assignment method to estimate dispersal (BAYESASS 1.2). Even in the best-case scenario, almost all current methods except SHUA significantly underestimate population structure, and consequently overestimate gene flow and dispersal when applied to real populations. It was crucial to ensure that the manipulated rate of gene flow was correctly defined. This led to three supporting investigations of hybrid performance, inversion polymorphisms and effective population size. The hybrid performance investigation demonstrated that the manipulated rate of gene flow had not been unexpectedly inflated by hybrid vigour or reduced by breakdown. These experiments also demonstrated that close inbreeding is not a necessary precondition for hybrid vigour or breakdown, which is important for conservation strategies involving induced dispersal. The investigation of inversion polymorphisms ensured that the manipulated rate of gene flow was not affected by selection on inverted regions. The effective population size investigation used a temporal estimation method to confirm that the Ne was accurately predicted by an N:Ne ratio of 0.286. Additionally this experiment showed that the single-sample estimation methods implemented by ONeSAMP or LDNE resulted in downwardly biased estimates of Ne in structured populations. In conclusion these results call into question the confidence that biologists may have in some of the most widely used molecular tools in conservation biology.

Artificial photosynthesis is broadly defined as the process of solar energy conversion into chemical fuels and represents a promising route towards alleviating the global energy crisis. In this context, the development of photocathodes for the use in photoelectrochemical cells is an attractive approach for the storage of solar energy in the form of a chemical energy carrier (e.g. H$_{2}$ and CO$_{2}$-reduction products from H$_{2}$O and CO$_{2}$). However, molecular catalyst-based photocathodes remain scarcely reported and typically suffer from low efficiencies and/or stabilities due to inadequate strategies for interfacing the molecular component with the light-harvesting material, with benchmark systems continuing to rely on precious metal components. In this thesis, the straightforward preparation of a p-silicon|mesoporous titania|molecular catalyst photocathode assembly that is active towards proton reduction in aqueous media is first established. The mesoporous TiO$_{2}$ scaffold acts as an electron shuttle between the silicon and the catalyst, while also stabilising the silicon from passivation and enabling a high loading of molecular catalysts. When a Ni bis(diphosphine)-based catalyst is anchored on the surface of the electrode, a catalytic onset potential of +0.4 V vs. RHE and a high turnover number of 1 $\times$ 10$^{3}$ was obtained from photoelectrolysis under UV-filtered simulated solar irradiation at 1 Sun after 24 hours. Notwithstanding its aptitude for molecular catalyst immobilisation, the Si|TiO$_{2}$ photoelectrode showed great versatility towards different types of catalysts and pH conditions, highlighting the flexible platform it represents for many potential reductive catalysis transformations. The Si|TiO$_{2}$ scaffold was extended towards solar CO$_{2}$ reduction via the immobilisation of a novel phosphonated cobalt bis(terpyridine) catalyst to achieve the first precious metal-free, CO$_{2}$-reducing molecular hybrid photocathode. Reducing CO$_{2}$ in both organic-water and purely aqueous conditions, the activity of this photocathode was shown to be affected by its environment and reached record turnover numbers for CO production by a molecular photocathode under optimal conditions, maintaining stable activity for more than 24 hours. Critically, in-depth electrochemical and in situ resonance Raman and infrared spectroelectrochemical investigations provided key insights into the nature of the surface-bound Co complex under reducing conditions. While demonstrating the power and precision offered by such in situ spectroelectrochemical techniques, these studies ultimately alluded to a catalytic mechanism that contrasts with that reported for the in-solution (homogeneous) catalyst. Overall, this affords a distinct mechanistic pathway that unlocks an earlier catalytic onset and enables photoelectrochemical activity. Finally, in the context of improving product selectivity in molecular-based CO$_{2}$ reduction, polymers based on the cobalt bis(terpyridine) motif were synthesised and immobilised on inverse opal-type electrodes designed specifically to accommodate large molecules. Rational design of the polymers' co-monomers was aimed towards the provision of an artificial environment for the active complex that would influence product selectivity, which was ultimately demonstrated by the improvement of a H$_{2}$:CO product ratio of 1:2 (molecule) to 1:6 (polymer). Further studies of this all-in-one system included modulating its degree of cross-linkage as well as a CO$_{2}$ reducing demonstration photocathode on a Si|inverse-opal TiO$_{2}$ scaffold.

Molecular dynamics simulations are a very usefultool to study the behavior and interaction of atoms and molecules in chemicaland bio-molecular systems. With the fast rising complexity of such simulationshybrid systems with both, multi-core processors (CPUs) and multiple graphics processingunits (GPUs), become more and more popular. To obtain an optimal performance thisthesis presents and evaluates two different hybrid algorithms, employing allavailable compute capacity from CPUs and GPUs. The presented algorithms can beapplied for short-range force calculations in arbitrary molecular dynamicssimulations
Molekylärdynamiska simulationer är ett mycket lämpligt verktyg för att studera beteendet och växelspelet av atomer och molekyler inom kemiska och biomolekylära system. Hybrida datorsystem som innehåller såväl processorer med multipla kärnor (CPU:er) som flera grafikprocessorer (GPU:er) blir populära i växande utsträckning. Vi undersöker två olika hybrida algoritmer som använder den hela beräkningsförmågan av CPU:er och GPU:er för att få ut den optimala beräkningsprestandan. De presenterade algoritmerna kan användas i godtyckliga molekylärdynamiska simulationer med potentialer av kort räckvidd.

Zentrales Thema dieser Dissertation ist die Untersuchung anorganisch/organischer Hybridsysteme (HIOS) mit besonderem Fokus auf den speziellen Prozessen an der Grenzfläche beider Materialklassen. Organische Moleküle, in Verbindung mit anorganischen Halbleitern haben ein großes Potenzial für Anwendungen in zukünftigen optoelektronischen Hybridbauteilen, indem sie Vorteile zweier unterschiedlicher Welten kombinieren. Entscheidend für die Herstellung von hybriden Strukturen ist das Verständnis der Wechselwirkungen an der Grenzfläche zwischen organischem und anorganischem Material. In dieser Arbeit werden diese Wechselwirkungen analysiert, um eine Wachstumskontrolle an der Grenzfläche zwischen konjugierten organischen Molekül und anorganischem Halbleiter zu ermöglichen. Hierfür werden unterschiedliche Ansätze verfolgt: Im ersten Teil der Arbeit wird die Wechselwirkung des Modellsystems Sexiphenyl (6P) an der Grenzfläche zu ZnO untersucht, sowie das Wachstum des Moleküls mittels verschiedener Methoden kontrolliert. Das daraus gewonnene Wissen kann im zweiten Teil dazu verwendet werden einen hybriden ZnO/6P/ZnO-Stapel zu realisieren, bei dem die organische Schicht ohne Beeinträchtigung der Kristallstruktur, mit definierten Grenzflächen bis hin zur atomaren/molekularen Ebene, überwachsen werden kann. Der letzte Teil der Arbeit befasst sich mit der optischen Echtzeit-Beobachtung während des organischen Wachstums verschiedener Moleküle. Dadurch ist es möglich Veränderungen von Struktureigenschaften und Wechselwirkungen zwischen Molekülen und dem Substrat zerstörungsfrei zu bestimmen, während diese aufgewachsen werden. Hierdurch können schlussendlich mögliche Mechanismen aufgezeigt werden, um elektronische und optische Wechselwirkung an der Grenzfläche zwischen organischem Molekül und anorganischen Halbleitern zu analysieren, sowie Wachstumsprozesse weiter zu verstehen und kontrollieren.
The central subject of this thesis are hybrid inorganic/organic systems (HIOS) with a focus on the specific processes at the interface between the two material classes. Organic molecules used together with inorganic semiconductors, have a great potential for future optoelectronic applications in hybrid components, by combining the advantages of two dissimilar worlds. Decisive for the production of hybrid structures is the understanding of the interactions at the interface between organic and inorganic material. In this thesis, the interactions are analyzed to enable growth control at the interface between conjugated organic molecules and inorganic semiconductors. In the first part of the thesis, the interaction of the model system sexiphenyl (6P) at the interface with ZnO, as well as approaches to control the growth of the molecule are being investigated. The knowledge gained here is used in the second part to realize a hybrid ZnO/6P/ ZnO stack, in which the organic layer can be overgrown without affecting the crystal structure, exhibiting defined interfaces down to the atomic/molecular level. The last part of the thesis deals with real time optical observation during organic growth of different molecules. By this changes in structural properties and interactions between molecules and the substrate can be non-destructively determined as they are growing. Ultimately, a comprehensive insight into the optical and electronic interactions at the interface between organic molecules and inorganic semiconductors can be gained and possible control mechanisms are shown.

This Ph.D. thesis describes the versatility of amine triphenolate complexes to be used either as self-assembling molecular scaffolds with applications in material sciences and molecular recognition, like titanium (IV) µ-oxo TPA complexes, or as active catalysts in homogeneous and heterogeneous catalysis, mainly vanadium (V) TPA complexes. In Chapter 1, the principles of self-assembly are listed, i.e. control on the electronic properties and size discrimination for the realization of supramolecular structures, error-checking, and efficiency, in the way of building up ordered and highly-structured entities under mild conditions. Different examples are proposed, but the analysis is mainly focused on the possibility of applying self-assembly in metal coordination chemistry in order to design highly ordered and functional systems, that may find applications in catalysis or material sciences. In this view, the coordination chemistry and the behaviour in solution of Ti(IV) TPA complexes are presented and in particular the possibility to switch between mononuclear and dinuclear µ-oxo species, depending on the steric nature of peripheral substituents, as well as the feasibility to build up highly functional Ti(IV) molecular scaffolds. A brief introduction on V(V) TPA complexes is reported as well, especially on their Lewis acid nature and structural characteristics that make them be considered as functional models of natural vanadium-dependent haloperoxidases and be used as active catalysts in oxygen transfer reactions. As the realization of new efficient and functional supramolecular systems supposes the design of the right building blocks, in Chapter 2, the modification of amine triphenolate skeleton is proposed. The functionalization strategy that has been adopted is based on a click-type oxime bond formation upon reaction of an aldehyde group, which can be effectively and selectively inserted on TPA ligands through the so-called Duff reaction, and a wide variety of alkoxyamines. In this way, the ligand skeleton has been efficiently decorated with polar and positively charged moieties, such as TEG arms and imidazolinium residues, and with pyrene groups. The functionalization has interested diverse positions of the ligand and even a double functionalization of two different positions on the same tri-phenolamine can be achieved. Chapter 3 deals with titanium (IV) amine triphenolate complexes and with the thermodynamic stability in solution of a Ti(IV) complex obtained by complexation with tris-(2-hydroxy-3-phenylbenzyl)amine. In more details, the reaction gives rise to a mononuclear complex, which upon reaction with water stereoselectively self-assembles into a highly stable, inert, dinuclear, heterochiral S6-symmetric µ-oxo TPA complex. Highly decorated Ti(IV) µ-oxo TPA complexes can be efficiently obtained by effecting the complexation reaction on functionalized ligands reported in Chapter 2, or by directly functionalizing Ti(IV) µ-oxo TPA complexes, which bear six aldehyde groups in para and/or meta positions, with the appropriate alkoxyamine. The functionalization strategy enables to construct stable and spatially ordered materials. In particular, two different Ti(IV) µ-oxo TPA complexes, bearing pyrene groups in para and meta positions, respectively, have been used as molecular receptors for fullerene. Fluorescence spectroscopies and DOSY-NMR analyses clearly indicate that pyrene groups on titanium complexes interact with fullerene through π-π interactions. Additionally, interactions between pyrene groups in para position on Ti(IV) µ-oxo TPA complex and SWCNTs (single walled carbon nanotubes) has been studied as well. Even in this case, fluorescence studies have been carried out and AFM images clearly show that CNTs are covered from Ti(IV) µ-oxo TPA complexes, highlighting the possibility to use such these systems for the design of ordered and functional supramolecular structures. Finally, in Chapter 4, the catalytic activity of V(V) TPA complexes is studied, both in sulfoxidation and aerobic oxidative C-C cleavage reactions. Firstly, the activity of an electron-poor V(V) TPA complex, bearing six chloro groups in ortho and para positions, is investigated in sulfoxidation reactions in presence of hydrogen peroxide as terminal oxidant. The reactions are performed with high yields and selectivities (catalyst loading down to 0.001% and TONs up to 89000). Both reaction rates and selectivities confirm the higher activity of the new catalyst with respect to the ones reported in literature. Moreover, modification of V(V) complexes through oxime bond formation has also led to the realization of organogelator-derived complexes, which have been found to form organogels in dioxane. Lastly, functionalization of V(V) complexes with positively charged moieties makes it possible to obtain water-soluble micelles, upon solubilisation with SDS (sodium dodecyl sulphate). The micellar like system has been tested in aerobic oxidative C-C cleavage of vicinal diols, with high selectivity and quite short reaction times. The compartmentalization of the catalytic system allowed its recycling and reuse for three times by extraction of products with organic solvents.
Questa tesi di dottorato descrive la sintesi e la funzionalizzazione di complessi amminotrifenolati di titanio (IV) e vanadio (V) per applicazioni in reazioni di riconoscimento molecolare e in catalisi. Nel Capitolo 1, sono illustrati i principi che regolano il self-assembly, quali controllo, correzione degli errori ed efficienza. E’ mostrato come questi possano essere applicati per la realizzazione di entità ordinate e strutturate in chimica di coordinazione, per la costruzione di sistemi metallo-supramolecolari, con applicazione in catalisi o scienze dei materiali. In quest’ottica, sono studiati la chimica di coordinazione e il comportamento in soluzione di complessi TPA di titanio (IV) e in particolare la capacità di fornire specie mono- o dinucleari a seconda dell’ingombro sterico dei sostituenti periferici e la possibilità di costruire scaffolds molecolari di titanio (IV) altamente funzionalizzati. Inoltre, è riportata una breve introduzione sui complessi TPA di vanadio (V), in particolar modo sulla loro proprietà di acidi di Lewis e sulle loro caratteristiche strutturali, che fanno sì che vengano considerati dei modelli funzionali delle aloperossidasi naturali vanadio-dipendenti e quindi vengano utilizzati come catalizzatori in reazioni di trasferimento di ossigeno. Nel Capitolo 2, viene proposta una strategia sintetica per modificare lo scheletro trifenolamminico. La funzionalizzazione prevede la formazione di un legame ossimico, mediante una reazione click-simile tra un’aldeide, che può essere selettivamente introdotta sul legante mediante reazione di Duff, e una varietà di alcossiammine. In questo modo, lo scheletro del legante può essere efficientemente decorato con residui polari e carichi positivamente, come residui TEG o imidazolinio, e con gruppi pirene. La funzionalizzazione può coinvolgere diverse posizioni del legante, così come una doppia derivatizzazione di posizioni differenti sulla stessa trifenolammina. Nel Capitolo 3, è presentata la possibilità di ottenere dei complessi dinucleari µ-oxo amminotrifenolati di titanio (IV) per reazione di complessazione della tri-(2-idrossi-3-fenilbenzil)ammina con Ti(Oi-Pr)4. Più in dettaglio, il complesso mononucleare, che si forma dalla reazione, in presenze di tracce d’acqua è in grado di auto-assemblarsi in maniera stereoselettiva, dando origine a un complesso dinucleare, altamente stabile, inerte, eterochirale, con simmetria S6. La funzionalizzazione del complesso può essere ottenuta efficacemente mediante una duplice via: effettuando la reazione di complessazione sui leganti funzionalizzati riportati in Capitolo 2, oppure funzionalizzando direttamente complessi TPA µ-oxo di titanio (IV), che portano sei gruppi aldeidici in para e/o meta, con un’appropriata alcossiammina. La strategia di funzionalizzazione permette di costruire dei materiali stabili e spazialmente ordinati. In particolare, due complessi µ-oxo di titanio che portano gruppi pirene rispettivamente in para e meta sono stati utilizzati come recettori molecolari per il fullerene. Spettroscopie di fluorescenza ed esperimenti DOSY-NMR indicano chiaramente che i gruppi pirene sui complessi di titanio interagiscono con il fullerene mediante interazioni π-π. Come ulteriore applicazione, sono state studiate le interazioni tra gruppi pirene dei complessi TPA µ-oxo di titanio e nanotubi di carbonio (SWCNTs). Anche in questo caso, sono stati condotti studi di fluorescenza e analisi AFM mostrano chiaramente che i nanotubi sono rivestiti dai complessi di titanio, evidenziando la possibilità di usare questi sistemi per generare strutture supramolecolari ordinate e funzionali. Infine, nel Capitolo 4, è studiata l’attività catalitica di complessi TPA d vanadio (V), sia in reazioni di solfossidazione che in reazioni di cleavage aerobico ossidativo di legami C-C. Prima di tutto, viene analizzata l’attività catalitica di un complesso di vanadio (V) elettron-povero, portante sei atomi di cloro in posizioni orto e para, in reazioni di solfossidazione in presenza di perossido d’idrogeno come ossidante terminale. Le reazioni sono condotte con alte rese e selettività, anche in presenza dello 0.001% di catalizzatore, con TON fino a 89000. Le velocità di reazione e le selettività confermano una attività maggiore del catalizzatore rispetto ai catalizzatori riportati in letteratura. In più, la modificazione di complessi TPA di vanadio (V) mediante formazione di un’ossima ha portato anche alla realizzazione di complessi funzionalizzati con catene organogelator e alla formazione di organogel in diossano. In conclusione, la funzionalizzazione di complessi TPA di vanadio (V) con residui carichi positivamente permette di ottenere micelle solubili in acqua, in seguito a solubilizzazione con SDS (sodio dodecil solfato). Il sistema micellare è stato poi testato in reazioni di cleavage aerobico ossidativo di legami C-C di dioli vicinali, con elevate selettività e tempi di reazione relativamente bassi. Il sistema catalitico può essere inoltre riciclato e riutilizzato fino a tre volte in seguito a estrazione dei prodotti con solventi organici

Modern studies on charge transfer reaction and conductivity measurements of DNA have shown that the electrical behavior of DNA ranges from that of an insulator to that of a wide bandgap semiconductor. Based on this property of DNA, a metal-semiconductor-metal photodetector is fabricated using a self-assembled layer of deoxyguanosine derivative (DNA base) deposited between gold electrodes. The electrodes are lithographically designed on a GaN substrate separated by a distance L (50nm < L < 100nm). This work examines the electrical and optical properties of such wide-bandgap semiconductor based biomaterial systems for their potential application as photodetectors in the UV region wherein most of the biological agents emit. The objective of this study was to develop a biomolecular electronic device and design an experimental setup for electrical and optical characterization of a novel hybrid molecular optoelectronic material system. AFM results proved the usage of Ga-Polar substrate in conjugation with DG molecules to be used as a potential electronic based sensor. A two-terminal nanoscale biomolectronic diode has been fabricated showing efficient rectification ratio. A nanoscale integrated ultraviolet photodetector (of dimensions less than 100 nm) has been fabricated with a cut-off wavelength at ~ 320 nm.

The present study aims at generating the basic knowledge of hybrid technology and examines the magnitude of heterosis for yield through evaluation of eight parents along with 28 F1 hybrids and 25 F1 and 10 parents. The hybrids along with their parents were evaluated in the field-experiment carried out in Bologna, precision phenotyping platform at different levels of water stress and in near-field condition via a basket method to assess yield and root traits. The F1 hybrids were evaluated based on mid and best parent values as well as general and specific combining ability effects. The results showed >20% of mid parent heterosis, indicating the scope for exploitation of heterosis in durum wheat. Valnova x Miki was the best hybrid combination in both experiments followed by Karim x Valnova and Karim x Morocco. Based on the WSTI, three F1 hybrids (Valnova x Miki, Iride x Miki and Svevo x Miki) and one parent (Svevo) were identified as drought tolerant. These results suggest that hybrids do better under water stress but specific hybrid combinations need to be developed to realize higher performance under drought prone environments. To understand the genetic control of flowering time, 384 durum lines were assessed in 13 environments to determine five pheno-environments. Genotyping was conducted with 35K Axiom array to generate 7,740 polymorphic SNPs. In total, 47 significant QTLs were identified for flowering time consistently across the environments. The candidate gene search indicated seven novel genes, namely PRR7, GRF, SVP, RRP6L1, Hd6, TCP1, and COP1/RGA in addition to a number of already known regulatory photoperiodic genes, PPD-A and PPD-B and vernalization genes VRN1, VRN2 and VRN3. In summary, the results obtained from these experiments indicated sufficient heterosis in durum wheat and helped in physiological and molecular characterization of the best heterotic combinations and flowering time.

CD45, also known as Leukocyte-common antigen (LCA), is a type-1 receptor-like protein tyrosine phosphatase (PTPase), which contains two PTPase domains, the membrane proximal domain (DI) and the membrane distal domain (D2). It is uniquely expressed on the surface of all leukocytes and their hematopoietic precursors and plays an important role in immunoreceptor signaling. In this study, I identified a novel CD45-interacting protein, Fyb, through screening human leukocyte cDNA library with a modified yeast two-hybrid system. Fyb is an adaptor protein mainly involved in the regulation of T cell receptor-induced integrin clustering and adhesion. It contains several regions with potential to mediate protein-protein interactions and has been shown to bind to the Src family kinase Fyn, the adapter protein SLP-76, Ena/VASP proteins, the adapter protein SKAP55, and SKAP55-HOM in T cell receptor signaling. I also demonstrated that the interaction of Fyb with CD45 was through involves the C-terminal region of Fyb, where several tyrosine residues, such as Tyr 594 and Tyr624, are critical for its interaction with other proteins in signaling. The interaction of Fyb with CD45 is phosphotyrosine-dependent since Src kinase is required for the interaction. Mutation analysis revealed that the tyrosine residue 624 of Fyb is the pivotal tyrosine residue involved in its association with CD45, whereas tyrosin 594 was not found to be required for binding. By mutation of CD45, it was demonstrated that the phosphatase catalytic D1 domain of CD45 was involved in the interaction with Fyb. More significantly, I found that only the substrate-trapping mutant (Asp to Val), but not the wild type CD45 interacted with Fyb, suggesting that Fyb is a potential CD45 substrate. Furthermore, I demonstrated the association of the C-terminal fragment of Fyb with CD45 in mammalian cells. However, I was not able to determine the interaction of the wild type Fyb with CD45 in 293 cells.

PTP-PEST is a soluble intracellular phosphatase that is ubiquitously expressed in mammalian tissues. The biological importance of this enzyme is highlighted by the fact that it is essential for murine embryogenesis and that it has been implicated in actin dynamics as well as other processes such as immunoreceptor signalling and cell death. Having five proline-rich regions in its C-terminal tail, PTP-PEST has a large potential for protein:protein interactions, several of which are known. To better understand the physiological importance of PTP-PEST, we explored the possibility that other substrates or binding partners existed. To this end, we carried out a modified yeast two-hybrid assay using full-length PTP-PEST with the D199A substrate trapping mutation as bait and screened a library of cDNA clones from 17-day-old mouse embryos. Screening identified the cytosolic adaptor protein, SKAP-HOM, as a novel substrate of PTP-PEST and GST pull-down assays confirmed this interaction in HeLa299 cells. We showed that PTP-PEST's PTP-domain and proline-1 region are essential for this interaction, as are SKAP-HOM's Y260 residue and SH3 domain. Further mutagenesis studies revealed that PTP-PEST residues S39 and S434 play a role in inhibiting and promoting the interaction with SKAP-HOM, respectively. Preliminary evidence was also obtained suggesting that p59fyn kinase plays a role in promoting the PTP-PEST D199A:SKAP-HOM interaction through a mechanism other than SKAP-HOM phosphorylation. Understanding the biological significance of this interaction could lead to novel discoveries in the fields of cell metastasis and inflammation.
PTP-PEST est une phosphatase soluble intracellulaire qui est exprimée de façon ubiquitaire dans les tissus de mammifères. L'importance biologique de cette enzyme relève du fait qu'elle est essentielle durant l'embryogénèse chez la souris, et qu'elle est de plus impliquée dans l'organisation dynamique du cytosquelette d'actine, ainsi que dans d'autres processus tels la signalisation par les immunorécepteurs et la mort cellulaire. Avec ses cinq régions riches en motifs proline dans la région C-terminale, PTP-PEST possède un large potentiel d'interactions protéine : protéine, parmi lesquelles plusieurs sont déjà identifiées. Afin de mieux comprendre l'importance physiologique de PTP-PEST, nous avons exploré la possibilité de l'existence d'autres substrats ou ligands. À cette fin, nous avons développé un test modifié de levures à deux-hybrides, utilisant une construction pleine longueur de PTP-PEST insérée d'une mutation de piégeage de ligands D199A comme appât. Suite à l'analyse d'une banque d'ADNc provenant d'embryons de souris de 17 jours, nous avons identifié une protéine adaptatrice cytosolique, SKAP-HOM, en tant que nouveau substrat de PTP-PEST. L'essai de capture de la protéine GST a de plus confirmé cette interaction dans les cellules HeLa299. Nos résultats démontrent que le domaine PTP de PTP-PEST, ainsi que la région proline-1, sont essentiels à cette interaction, tout comme le résidu Y260 et le domaine SH3 de SKAP-HOM. Une analyse de mutagénèse plus approfondie a identifié les résidus S39 et S434 de PTP-PEST comme jouant respectivement un rôle dans l'inhibition et dans la promotion de l'interaction avec SKAP-HOM. Nous avons aussi obtenus des résultats préliminaires suggérant que la protéine kinase p59fyn joue aussi un rôle dans la promotion de l'interaction PTP-PEST D199A:SKAP-HOM, par un mécanisme autre que la phosphorylation de SKAP-HOM. La compréhension de l'importance biologique de cette interaction pour

This dissertation explores the use of photoelectron imaging spectrometry to probe the molecular electronic structure of various chemical systems, with an emphasis on photoelectron angular distributions. Experimental ion generation, mass selection, laser photodetachment, and photoelectron ion imaging were all done in a photoelectron imaging spectrometer described in detail. Results from simplistic systems, OH- and CH-, are used to illustrate the general and fundamental capabilities of imaging spectroscopy and angular distributions. This illustration is then expanded when both qualitative and quantitative analyses of photoelectron angular distributions are used to aid in the understanding of the electronic structure of several heterocyclic aromatic systems. First a qualitative analysis aids in the exploration of the electronic structure of thiophenide, C₄H₃S⁻, and furanide, C₄H₃O⁻. Ground and excited C₄H₃S and C₄H₃O radical states are observed, and bond dissociation energies are defined. Next, a new model used to qualitatively analyze photoelectron angular distributions resulting from mixed s - p hybrid states is presented and applied to detachment from pyridinide, C₅H₄N⁻; as a benchmark system. Before further exploring this model, the synthesis of several deuterated heterocyclic compounds is presented in order to determine the experimentally produced systems in our experimental setup. The electronic structure of the resultant molecules oxazolide, C₃H₂NO⁻, and thiazolide, C₃H₂NS⁻; are then investigated. Using this new qualitative model, the mixed s - p states model, to evaluate the angular distributions of the systems, the hybridization of the anion molecular orbitals is probed. Comparison of the photoelectron angular distributions that are modeled for each heterocyclic aromatic system yields several trends relating aromatic stabilization, molecular hybridization, and bond dissociation energies. A new qualitative model is then presented to evaluate photoelectron angular distributions resulting from mixed p - d states and applied to detachment from NO⁻. Finally, new ideas and directions are proposed.

Plasmonics nanostructures are becoming remarkably important as tools towards manipulating photons at the nanoscale. They are poised to revolutionize a wide range of applications ranging from integrated optical circuits, photovoltaics, and biosensing. They enable miniaturization of optical components beyond the "diffraction limit'' as they convert optical radiation into highly confined electromagnetic near-fields in the vicinity of subwavelength metallic structures due to excitation of surface plasmons (SPs). These strong electromagnetic fields generated at the plasmonic "hot spots'' raise exciting prospects in terms of driving nonlinear effects in active media. The area of active plasmonics aims at the modulation of SPs supported at the interface of a metal and a nonlinear material by an external control signal. The nonlinear material changes its refractive index under an applied control signal, thereby resulting in an overall altered plasmonic response. Such hybrid nanostructures also allow for the creation of new kinds of hybrid states. This not only provides tools for designing active plasmonic devices, but is also a means of re-examining existing conventional rules of light-matter interactions. Therefore, the need for studying such hybrid plasmonic nanostructures both theoretically and experimentally cannot be understated. The present work seeks to advance and study the control of SPs excited in hybrid systems combining active materials and nanometallics, by an external optical signal or an applied voltage. Different types of plasmonic geometries have been explored via modeling tools such as frequency domain methods, and further investigated experimentally using both near-field and far field techniques such as scanning near field optical microscopy and leakage radiation microscopy respectively. First, passive SP elements were studied, such as the dielectric plasmonic mirrors that demonstrate the ability of gratings made of dielectric ridges placed on top of flat metal layers to open gaps in the dispersion relation of surface plasmon polaritons (SPPs). The results show very good reflecting properties of these mirrors for a propagating SPP whose wavelength is inside the gap. Another passive configuration employed was a plasmonic resonator consisting of dielectric-loaded surface plasmon polariton waveguide ring resonator (WRR). Also, a more robust variant has been proposed by replacing the ring in the WRR with a disk (WDR). The performance in terms of wavelength selectivity and efficiency of the WDRs was evaluated and was shown to be in good agreement with numerical results. Control of SPP signal was demonstrated in the WRR configuration both electro-optically and all-optically. In the case of electro-optical control, the dielectric host matrix was doped with an electro-optical material and combined with an appropriate set of planar electrodes. A 16% relative change of transmission upon application of a controlled electric field was measured. For all-optical control, nonlinearity based on trans-cis isomerization in a polymer material is utilized. More than a 3-fold change between high and low transmission states of the device at milliwatt control powers ( ~100 W/cm^2 intensity) was observed. Beyond the active control of propagating surface plasmons, further advancement can be achieved by means of nanoscale plasmonic structures supporting localized surface plasmons (LSP). Interactions of molecular excitations in a pi-conjugated polymer with plasmonic polarizations are investigated in hybrid plasmonic cavities. Insights into the fundamentals of enhanced light-matter interactions in hybrid subwavelength structures with extreme light concentration are drawn, using ultrafast pump-probe spectroscopy. This thesis also gives an overview of the challenges and opportunities that hybrid plasmonic functionalities provide in the field of plasmon nano optics.
Las nanoestructuras plasmónicas han adquirido una importante relevancia como herramientas capaces de manipular los fotones en la nanoescala, y pueden llegar a revolucionar un amplio abanico de aplicaciones tales como los circuitos ópticos integrados, la fotovoltaica o los dispositivos biosensores. Dichas estructuras hacen posible la miniaturización de los componentes ópticos más allá del “límite de difracción” de la luz, ya que convierten la radiación óptica en campos electromagnéticos fuertemente confinados en la proximidad de estructuras metálicas de tamaño inferior a la longitud de onda mediante la excitación de plasmones de superficie (SPs). Estos campos electromagnéticos tan intensos generados en los llamados “puntos calientes” plasmónicos brindan perspectivas muy interesantes para la generación de efectos no lineales en medios activos. El área de investigación denominado plasmónica activa busca la modulación de los SPs sostenidos por la intercara entre un metal y un material no lineal mediante una señal de control externa. El índice de refracción del material no lineal cambia bajo la aplicación de la señal de control, lo cual da lugar a la modificación de la respuesta plasmónica. Estas nanoestructuras híbridas también hacen posible la aparición de nuevos tipos de estados híbridos, lo cual proporciona tanto herramientas para diseñar dispositivos plasmónicos activos como mecanismos que permiten re-examinar las reglas convencionales de la interacción luz materia. Por lo tanto, es necesario el estudio de dichas nanoestructuras plasmónicas híbridas de manera teórica y experimental. En este trabajo de tesis se analiza el control de los SPs excitados en sistemas híbridos que combinan materiales activos y nanoestructuras metálicas mediante una señal óptica externa o un voltaje aplicado. Se han investigado distintos tipos de geometrías plasmónicas utilizando herramientas de simulación basadas en métodos en el dominio de la frecuencia, y posteriormente se han caracterizado experimentalmente dichas geometrías mediante técnicas de campo cercano y de campo lejano tales como la microscopía óptica de campo cercano y la microscopía basada en pérdidas radiativas, respectivamente. En primer lugar se estudiaron elementos plasmónicos pasivos, en particular espejos plasmónicos dieléctricos que demuestran la capacidad que tienen las redes periódicas de caballones de material dieléctrico colocados sobre una superficie metálica plana para abrir intervalos prohibidos en la relación de dispersión de los plasmones de superficie propagantes o plasmones-polaritones de superficie (SPPs). Los resultados muestran que dichos espejos poseen muy buenas propiedades reflectantes para SPPs cuya energía está en el intervalo prohibido. Otra configuración pasiva analizada fueron los resonadores plasmónicos basados en anillos de guía de onda plasmónica fabricada a partir de estructuras dieléctricas sobre metal (WRR, del inglés waveguide ring resonator ). Asimismo, se propone una versión más robusta de resonador plasmónico, basada en la sustitución del anillo del WRR por un disco (WDR, del inglés waveguide disk resonator). Se ha evaluado el funcionamiento de los WDRs en términos de selectividad en longitud de onda y de eficiencia, y los resultados obtenidos presentan un buen acuerdo con las predicciones numéricas. Pasando a las configuraciones activas, se demuestra el control de la señal plasmónica en configuración WRR por medios tanto electro-ópticos como completamente ópticos. En el caso del control electro-óptico, el material dieléctrico que compone el WRR estaba dopado con un componente electro-óptico y a la estructura pasiva se le añadió un conjunto de electrodos planos. Bajo la aplicación de un campo eléctrico externo, se midió un cambio relativo en la transmisión a través de la guía plasmónica del 16%. En cuanto al control puramente óptico, se utilizó la no linealidad de un material polimérico con origen en una isomerización trans-cis. En este caso se detectó un factor 3 entre los estados de alta y baja transmisión del dispositivo con potencias de control del orden de milivatios (intensidad del haz óptico de control de unos 100W/cm2 aproximadamente). Además del control activo de los plasmones de superficie propagantes, la utilización de nanoestructuras plasmónicas que poseen resonancias plasmónicas localizadas puede dar lugar a nuevos fenómenos. En esta tesis también se han estudiado las interacciones entre las excitaciones moleculares en un polímero pi-congujado con las polarizaciones plasmónicas en nanocavidades plasmónicas híbridas. Utilizando espectroscopia de tipo bombeo-sonda con pulsos ultrarrápidos, se han analizado diversos aspectos del aumento en la interacción luz-materia para estructuras híbridas de dimensiones inferiores a la longitud de onda sometidas a concentraciones de luz muy altas. Por último, esta tesis también proporciona una visión general de los desafíos y posibilidades que las funcionalidades plasmónicas híbridas ofrecen en el campo de la nano-óptica basada en plasmones de superfície.

From molecules to living organisms and from atoms to planets a variety of physical phe- nomena operate at different temporal and spatial scales. Understanding the nature of those phenomena is crucial for advancing new technologies in many disciplines. In micro and nanofluidics as the operational dimensions are downsized to smaller scales the surface-to- volume ratio increases and the surface phenomena become dominant. Numerical modelling is the key for obtaining a better insight into the processes involved. The Achilles heel of fine grain microscopic numerical simulations is their computational cost. Simulating a multiscale phenomenon with an accurate microscopic description is extremely demand- ing computationally. On the contrary, simulations of multiscale phenomena based only on macroscopic descriptions cannot fully capture the physics of the multiscale systems. In order to confront this dilemma multiscale frameworks, called hybrid codes, have been de- veloped to couple the microscopic and macroscopic description of a system and to facilitate the exchange of information. The aim of this research project is to establish and implement a robust hybrid molecular- continuum method for micro- and nano-scale fluid flows. Towards that direction a hybrid multiscale method named as Point Wise Coupling (PWC) has been developed. PWC aims to circumvent the limitations of the existing hybrid continuum/atomistic approaches and deliver a modular and applicable methodology. In the PWC, the whole domain is covered with the macroscopic solver and the microscale model enters as a local refinement. Ad- ditionally, numerical techniques based on neural networks are employed to minimise the cost of the molecular solver and reduce the outcomes’ variability induced by the fluctuating nature of the atomistic data. Molecular studies have been performed (i) to obtain a better insight of the interfacial phenomena in the solid/liquid interfaces, and (ii) to study the parametrisation of the molec- ular models and mapping of atomistic information to hybrid frameworks. Specifically, the impact of parameters, such as surface roughness and stiffness, to slip process is studied. PWC framework has been employed to study a number of fundamental test cases in- cluding Poiseuille flow of polymeric fluids, isothermal slip Couette flow and slip Couette flow with heat transfer. Attention is drawn to the boundary condition transfer from the continuum solver to the atomistic description. In the performed hybrid studies the effects of the numerical optimisation techniques (linear interpolation, neural networks) to simu- lations’ accuracy, stability and efficiency are studied. The outcomes of the simulations suggest that the neural networks scheme enhance the simulation’s efficiency by minimising the number of atomistic simulations and at the same time act as a smoothing operator for reducing the oscillations’ strength of the atomistic outputs.

[ES] La presente tesis doctoral titulada "Nanodispositivos mesoporosos híbridos funcionalizados con enzimas para detección, liberación controlada y comunicación molecular" se centra en el diseño, preparación, caracterización y evaluación de distintos nanodispositivos híbridos orgánico-inorgánicos utilizando como soporte nanopartículas tipo Janus de oro y sílice mesoporosa, que se equipan con enzimas, especies fluorescentes y puertas moleculares. Como conclusión general, los estudios realizados muestran que la incorporación de enzimas sobre nanopartículas permite introducir funciones de reconocimiento con alta especificidad y diseñar nanodispositivos avanzados para distintas finalidades. La combinación de nanopartículas híbridas con grupos orgánicos como puertas moleculares, efectores enzimáticos y especies cromo- fluorogénicas o fármacos puede resultar muy versátil; y se espera que los resultados obtenidos puedan inspirar el desarrollo de nuevos materiales inteligentes con aplicación en distintas áreas como la nanomedicina y la detección de moléculas de interés.
[CAT] La present tesi doctoral titulada "Nanodispositius mesoporosos híbrids funcionalitzats amb enzims per a detecció, alliberació controlada i comunicació molecular" es centra en el disseny, preparació, caracterització i avaluació de distints nanodispositius híbrids orgànic-inorgànics utilitzant com a suport nanopartícules tipus Janus d'or i sílice mesoporosa, que s'equipen amb enzims, espècies fluorescents i portes moleculars. Com a conclusió general, els estudis realitzats mostren que la incorporació d'enzims sobre nanopartícules permeten introduir funcions de reconeixement amb alta especificitat i dissenyar nanodispositius avançats per a distintes finalitats. La combinació de nanopartícules híbrides amb grups orgànics com portes moleculars, efectors enzimàtics i espècies cromo-fluorogèniques o fàrmacs pot resultar molt versàtil; i s'espera que els resultats obsessos inspiren el desenvolupament de nous materials intel·ligents amb aplicació en distintes àrees com la nanomedicina i la detecció de molècules d'interés.
[EN] This PhD thesis entitled "Enzyme-functionalized hybrid mesoporous nanodevices for sensing, controlled release and molecular communication" is focused on the design, synthesis, characterization and evaluation of several hybrid organic-inorganic nanodevices using Janus gold-mesoporous silica nanoparticles as scaffolds, equipped with enzymes, fluorescent species and molecular gates. In conclusion, these studies show that the incorporation of enzymes on nanoparticles allows to introduce recognition capabilities with high specificity and to design advanced nanodevices for different purposes. The combination of hybrid nanoparticles with organic groups such as molecular gates, enzymatic effectors and chromo-fluorogenic species or drugs can be very versatile; and we hope that the obtained results inspire the development of new smart materials with application in different areas such as nanomedice and sensing.
Llopis Lorente, A. (2019). Enzyme-functionalized hybrid mesoporous nanodevices for sensing, controlled release and molecular communication [Tesis doctoral no publicada]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/117612
TESIS

Comprendre les propriétés des interfaces molécules/métaux est d’une importance capitale pour la spintronique organique. La première partie porte sur l’étude des propriétés magnétiques de molécules de phtalocyanine de manganèse. Nous avons montré que les premières couches moléculaires forment des colonnes avec un arrangement antiferromagnétique sur la surface de Co(100). Ces dernières mènent à de l’anisotropie d’échange. La seconde partie porte sur l’étude d’une molécule à transition de spin, la Fe(phen)2(NCS)2, sublimée sur différentes surfaces. Nous avons identifié les états de spin d’une molécule unique sur du Cu(100). De plus, nous avons commuté l’état de spin d’une molécule unique pourvu qu’elle soit suffisamment découplée du substrat
Understanding the properties of molecules at the interface with metals is a fundamental issue for organic spintronics. The first part is devoted to the study of magnetic properties of planar manganese-phthalocyanine molecules and Co films. We evidenced that the first molecular layers form vertical columns with antiferromagnetic ordering on the Co(100) surface. In turn, these molecular columns lead to exchange bias. The second part is focused on the study of a spin-crossover complex, Fe(phen)2(NCS)2 sublimed on different metallic surfaces. We identified the two spin states of a single molecules on Cu(100). By applying voltages pulses, we switched the spin state of a single molecule provided that it is sufficiently decoupled from the substrate

Le développement d’un médicament prend en moyenne plus de 10 ans pour un coût de 1 Mrd de dollars. Pour accélérer le processus et diminuer le coût, on utilise des méthodes in-silico lors de l’étape de découverte qui consiste à cribler ~10⁵ molécules de type médicament pour proposer quelques candidats à l’étape préclinique. Le critère majeur est l’affinité entre la molécule potentielle et la cible biologique. L’interaction se passant dans notre corps: cette affinité doit être prédite dans l’eau et le médicament doit être soluble dans l’eau pour avoir accès à la cible. Globalement, les effets de solvatation ont un rôle important dans la conception de médicaments. Numériquement, pour un champ de force donné, la solvatation peut être étudiée par des méthodes de simulation exactes mais coûteuses, par des modèles de continuum rapides mais qui ignorent la nature moléculaire du solvant, enfin par des théories des liquides approximatives mais capables de garder l’information moléculaire du solvant tout en diminuant le temps de calcul. L’objectif de cette thèse étant la prédiction des énergies libres d’hydratation (ELH) de molécules de type médicament par des méthodes qui soient les plus précises et plus rapides possibles, elle se concentre sur deux approches originales: Le Monte-Carlo hybride à 4ème dimension, une nouvelle méthode pour calculer les ELH selon le principe de Jarzynski à partir simulations courtes hors-équilibre pendant lesquelles on introduit ou retire le soluté doucement depuis le solvant avec un paramètre de couplage dépendant du temps. Nous montrons que cette approche est capable de prédire les ELH de molécules de type pharmaceutique 4-6 fois plus rapidement que l’approche classique de perturbation de l’énergie libre. La théorie de la fonctionnelle de densité moléculaire, une approche de théorie des liquides qui permet l’étude des propriétés de solvatation de n’importe quelle soluté rigide. Dans son état actuel, dans l’approximation hyper-netted-chain couplée à une correction de pression, nous montrons qu’elle est capable de prédire les ELH des mêmes molécules avec une précision de respectivement 0.5 ou 1.0 kcal/mol par rapport aux simulations ou aux données expérimentales, avec une accélération de calcul de l’ordre de 10³-10⁴ par rapport aux simulations. H4D-MC est considéré ici comme une source de références pour développer plus avant la MDFT, elle-même une méthode suffisamment rapide pour être envisagée dans un processus de criblage haut-débit
The development of a drug takes on average over 10 yr. for a cost of 1B dollars. To speed up the process, and reduce its cost, in-silico methods are used at the drug discovery stage. It consists of screening ~10⁵ drug-like molecules to propose few candidates to the pre-clinical stages. The main criterion is the affinity between the potential drug molecule and biological target. As the interaction happens the body, these affinities need to be predicted in water and the molecule needs to be water-soluble to access the receptor. Overall, solvation properties play an important role in drug design. Numerically, for a given force-field, solvation can be studied either with exact but time-consuming simulation methods, fast continuum models that lose the molecular nature of the solvent, or approximate liquid state theories that keep the solvent molecular information while speeding-up the computation. In this thesis, we focus on the prediction of the hydration free energies (HFE) of drug-like molecules with methods that are as fast and precise as possible, and we concentrate on two original approaches: Hybrid-4th-dimension Monte Carlo, a novel method that computes the HFEs according to the Jarzynski principle from short non-equilibrium simulations in which the solute is inserted or removed from the solvent with a time-depending coupling parameter. This approach is shown to predict the HFEs of drug-like molecules 4-6 times faster than the classical free energy perturbation approach. Molecular density functional theory, a liquid-state-theory approach that allows the study of the equilibrium solvation properties of any rigid solute. In its current level, the hyper netted-chain approximation coupled with a pressure correction, it is shown to predict the HFEs of drug-like molecules within 0.5 and 1.0 kcal/mol of simulations and experimental data, respectively, for an average computational speed-up 10³-10⁴ with respect to simulations. H4D-MC is considered here as a source of reference data for MDFT developments. MDFT is itself fast enough to be foreseen in a high-throughput screening pipeline

Les commutables moléculaires sont des molécules qui peuvent moduler leurs propriétés (physiques, chimiques) sous l'influence d'un stimulus externe). Les remarquables propriétés des objets ont suscité un vif intérêt dans l'électronique moléculaire, et plus généralement, dans le domaine des matériaux multifonctionnels. Ce projet de thèse s'est inscrit dans le cadre d'une première collaboration entre les équipes ERMMES et Polymères de l'Institut Parisien de Chimie Moléculaire (IPCM). L' objectif a consisté à développer des voies de synthèses générales de (nano)matériaux hybrides à partir de commutables moléculaires magnétiques. Ce travail s'est essentiellement appuyé sur l'utilisation de complexes à transition de spin ainsi que sur une famille de composés cyanurés Fe/Co photomagnétiques. Ces systèmes ont été fonctionnalisés à leur périphérie, sur les ligands "scorpionates" de type tris(pyrazolyl)borate utilisés pour leur préparation. L'influence du groupement fonctionnel sur les propriétés des différents commutables a ensuite été étudiée, afin de déterminer les meilleurs candidats pour la conception des matériaux hybrides. Finalement, la déposition ou l'intégration des commutables magnétiques fonctionnalisés sur surfaces ou dans des polymères organiques respectivement, a été approchée par différentes méthodes en solution. Ce manuscrit reprend ainsi l'ensemble de ces études
Molecular switchesare molecules that can asdjust their(chemical, physical) properties in response to an external stimulus. The fascinating properties of molecular switches have drawn most attention in molecular electronics and more generally in advances materials research. This PhD project was developped at the frontiers of ERMMES and Polymeres research themes, in the framework of a first collaboration. Our major interest was to establish reliable synthetic routes for the design of hybrid (nano)materials based on magnetic molecular switches. The work was particularly focused on spin crossover complexes and a family of photomagnetic cyanide-bridged Fe/Co cages. These switches were first functionalized at their periphery, on the tris(pyrazolyl)borate capping ligand used for their synthesis. The functionalization influence on the switches properties were carried out to target the best candidates for hybrid materials design. Then, we dedicated efforts on the intergration of magnetic molecular switches into two main classes of materials, (i) surfaces and (ii) organic polymers, through wet-chemistry approaches. This manuscript combines this set of studies

La presente tesis doctoral, que lleva por título “Diseño de nuevos nanomateriales híbridos con puertas moleculares como nanodispositivos para aplicaciones terapéuticas” está centrada en el desarrollo de nuevos materiales funcionales híbridos orgánico-inorgánicos para aplicaciones de liberación controlada. Los dos capítulos de la presente tesis en los que se describen los resultados obtenidos (el segundo y el tercer capítulos) están directamente relacionados con el uso de las nanopartículas mesoporosas de sílice como matriz inorgánica en el desarrollo de nuevos materiales híbridos orgánico-inorgánicos para aplicaciones en liberación controlada. Aun así, los resultados se han dividido en dos capítulos, dependiendo del estímulo aplicado para la liberación de la molécula encapsulada. En uno de los capítulos, los diferentes materiales desarrollados se basan en nanodispositivos controlados enzimáticamente, mientras que en el otro capítulo es un cambio de pH o de fuerza electroestática (en los dos casos debido a la presencia de un microorganismo patógeno) el que causa la consecuente liberación de la carga. En el caso de los nanodispositivos controlados enzimáticamente, los cuales se describen en el Capítulo 2, se desarrollaron tres sólidos diferentes. El primer ejemplo se basó en el diseño, síntesis y caracterización de nanopartículas mesoporosas de sílice recubiertas con sales de azopiridinio, que se hidrolizan en presencia de esterasas y reductasas, las cuales se encuentran en la microflora del colon. Estas sales, que contienen un enlace azoico, se seleccionaron para una posible liberación selectiva en el colon. Los estudios de viabilidad celular e internalización se llevaron a cabo con células HeLa, así como los estudios de liberación del agente quimioterapéutico camptotecina. Un segundo ejemplo se centró en el diseño, síntesis, caracterización y aplicaciones de un nuevo nanodispositivo que responde a la presencia de proteasas para liberación controlada, empleando nanopartículas de sílice cubiertas con el polímero -poli-L-lisina. En este caso, se pretendía evaluar dos mecanismos diferentes de anclaje del polímero y los dos dieron resultados positivos, aunque presentaron diferentes perfiles de liberación en cada caso. También se realizaron estudios de viabilidad e internalización celular con este nuevo nanodispositivo, así como la liberación de camptotecina en células HeLa. Finalmente, el último nanodispositivo que responde a la acción de un enzima; incluye el diseño y aplicación de un “scaffold” 3D inteligente con puertas moleculares, el cual consiste en la combinación de nanopartículas mesoporosas de sílice con puertas y biomateriales porosos clásicos. En este caso, las nanopartículas mesoporosas de sílice se cubrieron con poliaminas y ATP. Estas nanopartículas se incorporaron durante la síntesis de un “scaffold” de gelatina, el cual se preparó mediante técnicas de prototipado rápido (RP). En presencia de fosfatasa ácida se induce la liberación del colorante encapsulado en los poros de las nanopartículas. La fosfatasa ácida se seleccionó como estímulo activador de este material diseñado, ya que es un enzima cuya concentración se emplea para evaluar la actividad de los osteoclastos en procesos de remodelación ósea y como marcador en metástasis de huesos. Estas propiedades abren posibilidades de uso de esta combinación en el diseño de materiales funcionales para la preparación de numerosos “scaffolds” avanzados con puertas moleculares, que puedan ayudar en aplicaciones de medicina regenerativa y terapias de cáncer de huesos. Con respecto al otro tipo de nanodispositivos, que se muestra en el Capítulo 3, se ha evaluado el posible uso de las nanopartículas mesoporosas de sílice con puertas moleculares como posibles vehículos para la liberación controlada de fármacos cuando un microorganismo patógeno está presente. En este caso, el diseño y desarrollo de nuevos materiales híbridos orgánico-inorgánicos se ha basado en el uso de nanopartículas mesoporosas de sílice como matriz inorgánica, cubiertas con entidades moleculares orgánicas que podrían responder a un cambio en el pH del ambiente o a un cambio en la fuerza electroestática, debido a la presencia de un microorganismo patógeno, tales como hongos o bacterias. Uno de estos nanodispositivos desarrollados demuestra las aplicaciones y propiedades antifúngicas de un soporte cargado con tebuconazol y cubierto con moléculas que actúan de puerta molecular dirigida mediante un cambio de pH. El otro material presenta aplicaciones antibacterianas contra bacterias gram-positivas y gram-negativas, ya que se utiliza un nanodispositivo cargado con vancomicina y funcionalizado con -poli-L-lisina. En los dos casos, se ha demostrado que el uso de la nanoformulación puede mejorar la efectividad del fármaco encapsulado, mejorando y ampliando el espectro de acción del mismo, lo cual abre un gran abanico de posibilidades en aplicaciones de estos nanodispositivos en el tratamiento de infecciones. En resumen, se puede concluir que en la presente tesis se han desarrollado nuevos sólidos híbridos orgánico-inorgánicos, así como se han descrito las aplicaciones de estos nanodisposotivos como sistemas de liberación controlada. Los resultados obtenidos podrían ser útiles en futuros diseños de materiales híbridos avanzados en biotecnología, biomedicina y, concretamente, en aplicaciones terapéuticas (como terapias contra el cáncer, tratamiento de infecciones, medicina regenerativa, etc.)
Mas Font, N. (2014). Design of new hybrid nanomaterials with molecular gates as nanodevices for therapeutic applications [Tesis doctoral no publicada]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/48491
TESIS

There are seven living species of gars in two genera (Lepisosteiformes: Actinopterygii). In my first chapter, I estimate phylogenetic relationships among six of them using DNA data generated from four complete mitochondrial loci (cytb, CR, 12S, and 16S) and a single, partial nuclear locus--recombination activating protein 1 (RAG1) intron. A single outgroup taxon, the bowfin (Amia calva), was included in my analyses. Regardless of optimality criterion (genetic distance, parsimony, maximum likelihood, and Bayesian inference), a single, well-supported phylogeny estimate emerged. Both sister genera (Atractosteus and Lepisosteus) were monophyletic. Within Atractosteus, A. spatula paired with A. tropicus in the absence of data from A. tristoechus. Within Lepisosteus I recovered two sister pairings of species: L. platyrhincus and L. oculatus; and L. ossues and L. platostomus. I estimated the phylogenetic position of the seventh gar species, A. tristoechus, using DNA data generated from several partial mitochondrial loci and 105 morphological characters. In this analysis, within a monophyletic Atractosteus I recovered a well-supported sister pairing between A. spatula and A. tristoechus, with A. tropicus sister to the pair. My molecular phylogenies largely agree with recent morphologically-based phylogenies aside from the positions of L. ossues and L. platostomus. Using dates associated with the best fossil data available (244 Ma minimal age of the node joining bowfins to gars, and 100 Ma for Lepisosteidae), I estimated divergence dates under a relaxed molecular clock model in a Bayesian framework. Estimated ages for lineages ranged from approximately 50 Ma for Lepisosteus, 23 Ma for the split between L. oculatus and L. platyrhincus, 28 Ma on the L. osseus and L. platostoms divergence, and 30 Ma for the node uniting A. spatula and A. tropicus--dates ranging from the Early Eocene to the Early Miocene. In my second chapter, I conducted basic phylogeographic investigations into the geographical structuring of gene genealogies built with mitochondrial D-loop sequences from 115 individual gars, belonging to five species (A. spatula, L. osseus, L. platostomus, L. platyrhincus and L. oculatus) and collected from a broad array of localities. Across species, across localities, I found some phylogeographic structuring in L. osseus and L. oculatus. I found one unique set of haplotypes confined to L. osseus in the Pee Dee River drainage of North Carolina. The level of molecular divergence between these and other L. osseus haplotypes was similar to that among gar species. I found evidence that there might be mixing of haplotypes across a contact zone between L. platyrhincus and L. oculatus in the Florida Panhandle. I found significant molecular divergence among populations of L. osseus and L. oculatus distributed among drainages to the Gulf of Mexico. However little genetic divergence was detected among populations of L. osseus, L. platostomus and L. oculatus within the Mississippi River basin. In my third chapter I present pilot work into characterizing the origins of a population of morphologically unusual gars in eastern Wisconsin. The longnose gar, Lepisosteus osseus, and the shortnose gar Lepisosteus platostomus are native to Wisconsin. In the Fox and Wolf River systems in eastern Wisconsin there is a third form that superficially resembles the spotted gar, L. oculatus (not previously reported to occur in Wisconsin) in that is exhibits heavy head and body pigmentation and a relatively short, broad snout. After initial molecular phylogenetic analyses showed that these gars did not belong to L. oculatus, results of more detailed molecular investigations, coupled with simple morphological findings, are consistent with the hypothesis that these unusual gars may be hybrids of L. platostomus and L. osseus. Further molecular and morphological investigations must be conducted to definitively infer hybrid status for these unusual gars.

Thesis (Ph. D.)--Chemical and Biomolecular Engineering, Georgia Institute of Technology, 2008.
Koros, William J., Committee Chair ; Breedveld, Victor, Committee Member ; Jones, Christopher W., Committee Member ; Kumar, Satish, Committee Member ; Nair, Sankar, Committee Member.

This study used the yeast two-hybrid system to identify novel proteins interacting with the orphan receptor RVR. Two gene products were pulled out of two independent screens. We named them L5B and RVRin62. The RVRint62 was characterized in this research. RVRint62 is a partial cDNA clone of approximately 2.2 kb, which is expressed in most tissues. It interacts with both members of the RVR/Rev-erb$ alpha$ subfamily of the nuclear receptor superfamily. The domains of RVR responsible for the interaction with RVRint62 were characterized as the C-terminal of the LBD and the signature motif. The interaction domain of RVRint62 is situated in the first 300 amino acids of its N-terminus. The motif LXXLL, found in many co-regulatory proteins that interact with nuclear receptors, is also found in RVRint62. However, the LXXLL motif is not required for interaction with RVR. The potential modulating role of RVRint62 on RVR activity remains to be determined.

This dissertation is concerned with the chemistry of the hexarhenium selenide cluster and its use as a synthetic building block. Two themes underlay the research presented here: (1) to create of novel supramolecular arrays and (2) to provide possible solutions to problems associated with the synthesis of inorganic-organic hybrid materials. Star-shaped scaffolding was used to develop a molecular Tinkertoy kit containing pieces which incorporate a variety of angles. Further functionalization of a molecular Tinkertoy based upon TPyP by incorporation of metal ions was discussed and examined along with the new electrochemical and photophysical properties observed. A new metallodendrimer motif containing clusters a the core, within the branches, and on the periphery was developed and discussed. Also addressed is the hitherto unseen electrochemical communication between [Re6(μ3-Se)8]2+ clusters bridged by an organic moiety. Possible solutions to problems involved with the synthesis of inorganic-organic hybrid materials were provided, as well as a demonstration-of-feasibility synthesis demonstrating the successful copolymerization of [Re6(μ3-Se)8]2+ vinylpyridine derivative with styrene.

In this work the semiclassical hybrid dynamics is extended in order to be capable of treating open quantum systems considering finite baths. The corresponding phenomena, i.e. decoherence and dissipation, are investigated for various scenarios.