The exploitation of the relationship between the chemical and physical properties of materials is the hallmark of advancing science throughout the world. The basic understanding of how and why molecules react and interact with each other in different environments allows for the discovery and implementation of new materials and devices that not only advance the state of human life but continually change the planet. The work described in this dissertation generally falls under three diverse categories: functionalization of fullerenes, investigation of host/guest interactions in solution, and the synthesis and characterization of ion containing polymers. The separation and functionalization of fullerenes is a recent and exciting area of research. The separation methods outlined are intended to increase the availability of endohedral metallofullerenes by decreasing their cost of production. Functionalized fullerene species were achieved through Bingel and Prato reactions to provide materials with novel functional groups. These materials may be further utilized in photovoltaic or other organic electronic devices. The characterization of noncovalent interactions between different molecules in solution is the focus of supramolecular chemistry. Isothermal Titration Calorimetry stands out as one of the best, among the many methods used to elucidate the characteristics of these systems. The binding of bis- imidazolium and paraquat guests with macrocyclic host molecules has been explored in this work. The measurements of the association constants for these systems will aid in the ongoing synthesis of new host/guest systems. Ion containing polymers were synthesized and characterized for their use in electroactive devices. Imidazolium containing polymers with bulky anions were synthesized on low glass transition polymer chains. These materials had enhanced ion conductivity and may eventually be used in electronic actuator materials. / Ph. D.

Advanced analytical techniques were utilized to investigate the intermolecular forces in several nanostructured materials. Techniques including, but not limited to, isothermal titration calorimetry (ITC), variable temperature Fourier transform infrared (FTIR) spectroscopy, and ultraviolet-visible (UV-Vis) thermal curves were used to study the fundamental interactions present in various nanomaterials, and to further probe the influence of these interactions on the overall behavior of the material. The areas of focus included self-assembly of surfactant micelles, polycation complexation of DNA, and temperature-dependent hydrogen bonding in polymeric systems. ITC was successfully used to determine the low critical micelle concentration (CMC) for a novel gemini surfactant with limited water solubility. CMCs were measured at decreasing methanol molar fractions (xMeOH) in water and the resulting linear relationship between CMC and methanol concentration was used to mathematically extrapolate to a predicted CMC at xMeOH = 0. Using this technique, the CMC value for the novel gemini surfactant was predicted to be 0.037 ± 0.004 mM. This extrapolation technique was also validated with surfactant standards. ITC was also used to investigate the binding thermodynamics of polyplex formation with polycations and DNA. The imidazolium-containing and trehalose-based polycations were both found to have endothermic, entropically driven binding with DNA, while the adenine-containing polycation exhibited exothermic DNA binding. In addition, ITC was also used to confirm the stoichiometric binding ratio of linear polyethylenimine and DNA polyplexes as determined by a novel NMR method. Dynamic light scattering (DLS) and zeta potential measurements were also performed to determine the size and surface charge of polyplexes. Circular dichroism (CD) and FTIR spectroscopies provided information regarding the structural changes that may occur in the DNA upon complexation with polymers. UV-Vis thermal curves indicated that polyplexes exhibit a greater thermal stability than DNA by itself. Variable temperature FTIR spectroscopy was used to quantitatively compare the hydrogen bonding behavior of multi-walled carbon nanotube (MWCNT)-polyurethane composites. Spectra were collected from 35 to 185 deg C for samples containing various weight percent loadings of MWCNTs with different hydrogen bonding surface functionalities. Peak fitting analysis was performed in the carbonyl-stretching region for each sample, and the hydrogen-bonding index (Rindex) was reported. Rindex values were used to quantitatively compare all of the composite samples in regards to temperature effects, weight percent loadings of MWCNTs, and the different functionalizations. In general, higher weight percent loadings of the MWCNTs resulted in greater Rindex values and increased hydrogen bond dissociation temperatures. In addition, at 5 and 10 wt% loadings the initial Rindex values displayed a trend that tracked well with the increasing hydrogen bonding capacity of the various surface functionalities. / Ph. D.

Solids handling can contribute to a significant portion of the operational costs of a wastewater treatment plant, contributing up to 50% of the total expenses in certain instances. Sludge dewatering and drying therefore become necessary not only from the operational perspective, but also from the economical viewpoint. The J-Vap process combines the above-mentioned processes, by pressure filtration of sludge followed by application of vacuum and heat. However, when cationic polymer conditioned sludge is dewatered in the J-Vap, the polymer is suspected to interact with the filter media at high temperatures, resulting in the formation of a skin layer that hinders efficient dewatering. The first part of the study has looked at various digestion processes and how they affect the skin formation phenomenon. The results showed that temperature played a significant role in determining the amount of polymer that adhered to the filter media. The second part of the study focused on different kinds of digestion processes and their effects on extracellular polymeric substances, bound water content and dewatering. Bound water tests were used to determine the maximum achievable solids concentration on dewatering. Bound water content of solids obtained from field centrifuges run at different torques and g values were evaluated and fitted on a standard graph obtained from lab pressed sludge with different solids concentration. The bound water was seen to decrease with increasing solids content till 20%, after which a nearly constant 1.0 g of bound water was present for every gram of dry solids seen. The results indicate that nearly 50% solids concentration could be achieved on mechanical dewatering. In reality, only 30 to 35% solids concentration was attained both in the lab and on the field. It was determined that dilatometry attributed the increase in cake solids to the decrease in bound water. However, the use of bound water as a predictive tool for determining cake solids was not practical since the bound water calculations use the solids content in the calculations. / Master of Science

Les protéines du lait bovin sont la source la plus importante en peptides bioactifs qui permettraient de maintenir le capital-Santé du consommateur. Nous nous sommes intéressés aux peptides inhibiteurs de l'enzyme de conversion de l'angiotensine I (ECA) et aux caséinophosphopeptides (CPP) chélateurs de minéraux pour étudier in vitro leur mécanisme d'interaction avec leurs cibles moléculaires. En effet, les peptides d'origine alimentaire, inhibiteurs de l'ECA (IEC) contribueraient à une prévention de l'hypertension. Pour comprendre la relation entre la séquence de ces peptides et leur pouvoir IEC, les paramètres d'inhibition de l'ECA somatique de poumon de lapin, qui possède 2 domaines N et C ayant chacun un site actif, par des peptides (FALPQYLK, FALPQY, ALPMHIR, IPP et VPP) issus de protéines du lait et des peptides dérivés ont été étudiés. De plus, l'interaction entre certains de ces peptides avec l'ECA somatique humaine a été caractérisée par la technologie Biacore®. La cartographie des sites de liaison de FALPQY en compétition avec le captopril (inhibiteur compétitif des 2 sites actifs de l'ECA) et le peptide BPP-11b (inhibiteur sélectif du domaine C de l'ECA) montre que ce peptide se fixe au niveau des 2 sites actifs de l'ECA. Par ailleurs, les CPP sont un bon moyen de corriger les carences minérales car ils sont capables de former des complexes solubles avec les cations, améliorant ainsi leur biodisponibilité. L'interaction entre le CPP [bêta]-CN (f1-25)4P et Ca2+, Mg2+, Zn2+ et Cu2+ a été étudiée par microcalorimétrie de titration isotherme : 1 mole de CPP fixe 2 moles de Ca2+, de Mg2+ ou de Zn2+ à pH 8, avec des constantes d'affinité faibles, mais ne fixe pas Cu2+ / Bovine milk proteins are the most important source of bioactive peptides. These peptides may contribute to maintain optimal health state. In the current study, we attempted to elucidate in vitro the molecular interaction mode between both angiotensin I-Converting enzyme (ACE) inhibitory peptides and mineral-Chelating caseinophosphopeptides (CPP). Indeed, ACE inhibitory peptides from food may provide a natural and safe alternative to prevent hypertension. In order to better understand the relationship between the sequence of ACE inhibitory peptides and their inhibitory potency, the inhibition parameters of rabbit lung somatic ACE (that possesses 2 domains, N and C, which are both catalytically active) by bovine milk peptides (FALPQYLK, FALPQY, ALPMHIR, IPP, and VPP) and other peptides with related sequence were investigated. Moreover, the interaction between some peptides and their derivatives with human somatic ACE was analyzed by Biacore® technology. The mapping of FALPQY-ACE interaction sites in competition with captopril (a competitive inhibitor for both sites) and also with BPP-11b (a selective inhibitor of the C-Domain active site) showed that FALPQY binds at or near the two active sites located on the 2 domains of ACE. In addition, CPP efficiently bind cations of nutritional interest by forming soluble complexes which prevent the precipitation of minerals at alkaline pH and increasing thus their bioavailability. The interaction between [beta]-CN (f1-25)4P, and Ca2+, Mg2+, Zn2+, and Cu2+ cations, was characterized by isothermal titration calorimetry: 1 mole of [beta]-CN (f1-25)4P binds 2 moles of Ca2+, Mg2+, and Zn2+ at a pH 8, with a low affinity, but does not bind Cu2+ cation

Le RXP470.1 est l’un des premiers inhibiteurs puissants de la MMP-12, une métalloprotéase à zinc impliquée dans de nombreuses pathologies comme l’athéroclérose et la bronchopneumopathie obstructive chronique (BPCO). Pour comprendre les bases moléculaires contrôlant l’interaction de cet inhibiteur avec sa cible, des approches pluridisciplinaires associant des relations structure-activité, avec des études de cristallographie de complexes enzymes inhibiteurs et d’études de microcalorimétrie, décrivant les contributions enthalpiques et entropiques impliquées dans la formation des complexes, ont été réalisées dans ce travail de thèse. Les affinités de trois analogues du RXP470.1 ont été tout d’abord déterminées. Puis quatre structures cristallographiques de complexes enzyme/inhibiteur décrivant le mode d’interaction duRXP470.1 et de ces trois analogues ont été obtenues avec des résolutions de 1.15 Å, 1.50 Å, 1.50Å et 1.30 Å, respectivement. Parallèlement les études de microcalorimétrie ont été menées pour étudier les facteurs énergétiques contrôlant l’interaction du RXP470.1 avec la MMP-12. Les résultats indiquent que la présence d’une chaîne latérale très longue et hydrophobe en position P1’de l’inhibiteur s’insérant dans la cavité S1’ de la MMP-12 est essentielle à la très bonne affinité de cet inhibiteur pour la MMP-12. Cette interaction met essentiellement en jeu un effet entropique très important de - 4 kcal/mol. L’interaction du RXP470.1 est aussi essentiellement dirigée par une forte augmentation d’entropie (-TDS= -10 kal/mol) et une composante enthalpique beaucoup plus faible (DH= -2.5 kcal/mol), et ce malgré l’observation dans le cristal de nombreuses interactions entre l’inhibiteur et le site actif de la MMP-12. L’étude de microcalorimétrie met aussi en lumière la prise d’un proton au cours de la formation du complexe enzyme inhibiteur impliquant deux résidus chargés négativement en solution, le résidu catalytique Glu219 et le groupe phosphoryle chélatant du zinc dans l’inhibiteur. Cette étude révèle aussi que si le groupe phosphoryle est considéré comme un chélatant faible de l’atome de zinc, il impose néanmoins des contraintes directionnelles très importantes qui ont un impact sur le positionnement des autres parties de l’inhibiteur dans le site actif de l’enzyme. Ce dernier effet pourrait expliquer pourquoi un certain nombre d’interactions entre l’inhibiteur et l’enzyme ne sont pas optimisées et pourquoi la variation d’enthalpie pour former le complexe reste relativement faible. Cette étude ouvre maintenant la voie à d’autres études en plaçant au centre des futurs travaux le rôle du groupe chélatant dans la conception des inhibiteurs de MMP, ainsi de nouveaux inhibiteurs puissants et sélectifs d’autres MMP devraient voir le jour grâce à ce travail et aux résultats obtenus. / RXP470.1 is one of the first highly potent and selective inhibitor of MMP-12, a zinc protease involved in several human diseases such as atherosclerosis and chronic obstructive pulmonary disease (COPD). To understand the molecular determinants controlling the interaction of RXP470.1 with MMP-12 active site, a multidisciplinary approach combining structure-activity data, crystallography and microcalorimetry have been performed on RXP470.1 and its three analogues. The affinities of the three RXP470.1 analogues have been determined. Then, fourcrystal structures of MMP-12 in interaction with these inhibitors have beendetermined at high resolution, 1.15 Å, 1.50 Å, 1.50 Å et 1.30 Å, respectively. These data have indicated that the presence of a long hydrophobic side chain in the P1’ position of the RXP470.1, which enters deeply inside the S1’ cavity of MMP-12, is playing a key role in the inhibitor affinity. The contribution of this side chain is mostly entropic (-TDS - 4 kcal/mol). The interaction of RXP470.1 with MMP-12 is also mostly driven by a sizeable entropy increase (-TDS= -10 kal/mol) and a more modest enthalpy contribution (DH= -2.5 kcal/mol), despite the observation in the crystal structure of several contacts between inhibitor and MMP-12 active site. Furthermore, this study reveals that the binding of RXP470.1 to MMP-12 is linked to a proton uptake involving two negatively charged residues, the catalytic Glu219 and the phosphoryl group of the inhibitor. Furthermore, despite that the phosphoryl group is considered as a weak zincbinding group, this study highlights that the interactions of this group with the active site zinc atom involved strong directionality between these two groups. This effect has strong impact on the positioning of the other parts of the inhibitor in the MMP-12 active site. This last effect could be responsible for the modest enthalpy increase associated with the binding of RXP470.1 to MMP-12, by preventing the optimization of several interactions between the inhibitor and the enzyme. The results indicate that the role of the zinc-binding group should be better consider in the future. Finally this study opens a new vision in this field and should allow the design of new selective inhibitors of other MMPs.

Ce travail de thèse démontre l’importance d’intégrer des outils théoriques à des observations expérimentales dans le but d’étudier le rôle des interactions non-covalentes et plus précisément de la dispersion dans la chimie des métaux de transition. Plusieurs thèmes ont ainsi été abordés comme les interactions d’empilement entre chélates de métaux de transition à l’état solide; l’influence de la chiralité sur l’oligomérisation en solution de complexes plans carrés de Rh(I) isonitrile; la stabilité et inactivité inhabituelles de complexes de type cis-platine en solution concentrée. Les résultats obtenus par titration calorimétrique isotherme ont permis d’évaluer la capacité de méthodes théoriques à reproduire avec précision les résultats expérimentaux. Les calculs ont démontré qu’un traitement théorique approprié des effets de la dispersion et de la solvatation, donne des valeurs cohérentes avec les résultats expérimentaux. Cependant, des améliorations supplémentaires sont nécessaires. / This thesis has shown the importance of integration of theoretical calculations and experimental investigations in studying the role of non-covalent interactions and particularly dispersion interactions in transition metal chemistry. Several subjects were addressed, such as stacking interactions of chelates in transition metal complexes in solid state, influence of chirality on the oligomerization of Rh(I) isonitrile complexes in solution and the stability of the cis-platin type complexes in concentrated solutions. Isothermal titration calorimetry proved to be very useful in the studies by providing accurate experimental data on the thermochemistry of addressed processes. This data was used to gauge the ability of the theoretical methods to accurately reproduce the experimental results. Calculations have shown that the proper treatment of dispersion effects and solvation by theoretical models gives values in relatively good agreement with experiments, but further improvements are needed.

Une étude conjointe du CEA et d'AREVA la Hague a montré qu'une des voies d'amélioration majeure des usines de traitement/recyclage du combustible nucléaire usagé, actuelles et futures, concerné le domaine de l'analyse. En effet, le suivi et le pilotage des procédés déployés dans ces usines nécessitent de nombreuses analyses générant de grandes quantités d'effluents radioactifs. Réduire les volumes mis en jeu lors de ces analyses permettrait donc de réduire la nocivité des échantillons et des effluents et donc d'accroitre la sureté pour le personnel et de réduire l'impact sur l'environnement et le coût de fonctionnement des usines. Parmi toutes les analyses effectuées, la mesure d'acidité libre est la plus fréquente, car c'est un paramètre indispensable pour pouvoir piloter correctement le procédé. C'est pourquoi, ces travaux de thèse ont abouti à l'amélioration de la méthode de mesure via une réduction d'échelle de l'analyse et une automatisation du protocole de mesure. Deux voies ont été étudiées : - le titrage par injection séquentielle (SIA), qui est un dispositif de 25 L de volume et qui par rapport à la méthode d'analyse de référence, réduit 1000 fois le volume d'échantillon nécessaire à l'analyse, 8 fois le temps d'analyse et 40 fois le volume d'effluents générés. - le titrage ballist-mix emploie un dispositif microfluidique qui, après intégration et réduction des composants, peut atteindre un volume de 25 mL et offre des performances analytiques comparables à celles obtenues en SIA. La méthode par SIA a été validée sur des solutions chargées en uranium alors que la technologie utilisée pour développer les titrages ballist-mix est en cours de validation. Cependant le principe opératoire du titrage ballist-mix est plus avantageux puisqu'il simplifie le travail de développement analytique du fait de la possibilité de simuler en avance les phénomènes physicochimiques ayant lieu lors du titrage / A joint study between the CEA and Areva La Hague has shown that chemical analysis is a crucial parameter for achieving a better performance in present and future spent nuclear fuel reprocessing plants. In fact, each plant’s process monitoring and control require a significant amount of laboratory analysis leading in overall to a considerable amount of nuclear waste. Hence, reducing the sample’s required volume for analysis would reduce its toxicity and subsequent waste, therefore increasing personnel safety, decreasing the environmental impact and the plant’s operation cost. Among the process control analytical workload, the free acidity measurement has been identified as a key analysis due to its measurement frequency. For this reason, the main objective of this research has been focused in the improvement of a reference method for free acidity measurement. The following work has been divided in two main studies seeking for the reduction of the sample volume and the automation of the analytical method protocol: - Sequential Injection Analysis (SIA) titration, whose application requires the employment of a device occupying a 25 L space, and which reduces 1000 fold the sample volume per analysis, 8 times the analysis time and 40 fold the amount of waste generated when compared to the reference analytical method. - Ballist-mix titration, whose analytical performance is equivalent to the SIA titration, but whose implementation is done inside a microfluidic device occupying a volume as low as 25 mL after integration of all of the elements needed for analysis. At the present time, the SIA titration has been validated using nitric acid samples containing uranyl cations, whereas the ballist-mix titration is being validated with the same sample conditions. However, this last analytical technique features a simplified operating principle which allows the user to shorten the analytical development process by opening the possibility to simulate the process before any experimentation

Ce travail de thèse a été consacré au développement de nouvelles méthodologies de caractérisation des affinités intermoléculaires par le biais de la calorimétrie de titration isotherme (ITC), après validation de systèmes modèles par l'intermédiaire des spectroscopies UV-visible, RMN et de l'électrophorèse capillaire. Nous avons en particulier montré que la mise en place et le couplage d'expériences non conventionnelles avec les protocoles classiques permettait d'améliorer la caractérisation calorimétrique, avec notamment une diminution parfois spectaculaire des incertitudes liées aux paramètres thermodynamiques. Ce potentiel de l'analyse globale d'expériences différenciées a été évalué sur un plan théorique, permettant ainsi la définition et l'optimisation des expériences à mettre en oeuvre en fonction du type de complexe étudié. L'exploitation expérimentale de ces stratégies a également permis l'étude de complexations problématiques sur le plan analytique, dans le cadre de complexes impliquant des molécules telles que les cyclodextrines ou l'albumine, et s'inscrivant dans des applications liés aux domaines de l'environnement et de la santé. Ainsi, nos stratégies ont levé les difficultés liées aux complexes athermiques, aux complexes de faibles affinités, aux équilibres multiples et aux faibles solubilités de l'un ou l'autre des partenaires de la complexation. Enfin, l'évaluation d'un nouveau modèle de traitement thermo-cinétique du thermogramme ITC a été réalisée, accroissant encore le potentiel de cette technique vis-à-vis de la caractérisation des interactions moléculaires. / This work was dedicated to the development of new isothermal titration calorimetry (ITC) methodologies for the characterization of intramolecula affinities, after validation of model system via capillary electrophoresis, UV-visible and NMR spectroscopy. We have demonstrated that the coupling of unconventional experiments with the conventional protocols generally improves the calorimetric characterization, with a dramatic decrease of the uncertainties on thermodynamic parameters. The potential of global analysis applied to differentiated experiments was evaluated on a theoretical level, allowing the definition of optimal experiments, depending on the type of studied complex. These strategies also enabled, on a experimental point of view, the study of complexations which cannot be analyzed by conventional approaches, in the case of complexes involving cyclodextrins or albumin. Indeed, our strategies overcomes the difficulties associated with athermic complexes, with complexes of low affinity, with multiple equilibria and with the low solubility of interacting partners. Finally, the evaluation of a new thermo-kinetic treatment of ITC thermograms has been achieved, further increasing the potential of this technique in the characterization of molecular interactions.

Gegenstand der vorliegenden Arbeit ist die Synthese und Strukturaufklärung von neuartigen, chromophoren Barbituraten, welche als selektive Chemosensoren verwendet werden können. Als Schlüsselverbindungen dienten 5-(4-Nitrophenyl)-barbiturate, deren Enolisierungsfähigkeit systematisch untersucht wurden. Des Weiteren konnten SCHIFFschen Basen, Pyridinium-Barbiturat-Betain-Farbstoffe sowie ein fluoreszenzaktive Naphthalimid synthetisiert werden, in welchen der Barbitursäure-Substituent ebenfalls elektronenschiebende Eigenschaften aufweist. Die individuelle Interaktion der Barbiturate mit der Solvensumgebung wurde mittels Lineare-Solvatations-Energie (LSE)- Beziehungen unter Verwendung der empirischen Lösungsmittelparameter nach KAMLET-TAFT und CATALÁN untersucht. Besonderes Augenmerk lag auf dem Studium der molekularen Erkennung von ausgewählten Chromophoren mit Nukleinbasen und strukturell verwandten Verbindungen. Hierzu gelang es die supramolekularen Bindungsphänomene über Wasserstoffbrücken und die Beeinflussung des chromophoren Systems sowohl im Festkörper als auch in Lösung zu verfolgen.

The main purpose of the report is to present possible reasons and solutions for variation in quality of sugar used in confectionery manufacturing, with focus on chocolate manufacturing, at Cloetta Sverige AB in Ljungsbro. The project has its purpose to optimize the quality of both the sugar and manufacturing processes in a long-term perspective, since the variation in quality of the sugar affects, more or less, all manufacturing processes and causes yield losses.   Cloetta Ljungsbro uses a pneumatic conveying system to transfer the sugar within the factory and when unloading the sugar from delivery trucks. A various of different analyses were performed in order to study the sugar quality; water content analyses in forms of Karl Fischer titration and particle size distribution analyses with help from sieving. During the sugar sampling time period, an observation of the air pressure used by the road tanker while unloading sugar at Cloetta and the lead time as sugar was delivered was executed. Moreover, data of the dew point in the pneumatic conveying system and, both temperature and humidity in the sugar silos, were collected.   As a result, most of the sugar particles breakage occurred somewhere between the delivery road tanker and while in the storage silos. Most likely it is due to the use of high pressure when unloading the sugar that the particle size distribution of the sugar varies, but also causes the temperature to reach a higher temperature than recommended. Furthermore, the water content of the sugar was higher in the beginning of the autumn. Further investigations of the effect of unloading the sugar and storage of sugar should be done, but also analyse the air velocity used within the pneumatic conveying system.