ABSTRACT Hydrophobic organic pollutants (HOPs) are in general characterized by high toxicity, long environmental half-life and high bio-accumulation factors. Due to their hydrophobicity, HOPs tend to sorb onto particles in environment. The influence of the dissolved organic matters (DOMs) on the sorption partition coefficient is observed because of their interactions with HOPs. This binding between DOM and HOPs increases apparent solubility and mobility of the HOPs in natural aquatic system. On the purpose of obtaining data closer to the real world, many aquatic factors, such as the concentration and types of DOM, pH value and ionic strength, are studied intensively recently. There are many studies about the mechanisms in the association of DOM and HOPs. Most of them assume achievement of equilibrium in their measurement. Recently, it was reported (Engebretson and von Wandruszka, 1998) that slow, revering, and even oscillating kinetics are observed. It is great concern and interest to those related studies in literatures. Complicated kinetic may in fact be a cause of the reproducibility problems for measurements of HOPs associated with both humic acid and metals. As such, by monitoring fluorescence intensity, we investigate the equilibrium kinetic of pyrene in HA solutions. In this study, results show that there are two stages of the fluorescence intensity after pyrene spiked into HA solutions: First, the fluorescence intensity decreases steeply due to the first dispersion of pyrene and the reaction of pyrene and HA (the front is dominance). Secound, fluorescence intensity decreases gently because of wall-effect. The dispersion rate of pyrene in HA solutions is difference with HA molecular size and quantity. As the ionic strength rising, cations reacting with specific binding sites on HA, the molecules¡¦ configuration of HA is changed, and less obstruct for dispersing of pyrene. It works as well as little molecular quantity. For second stage when ionic strength rising, wall- associations is less because of the hydrophobic-binding of pyrene and LHA is more stronger. Furthermore, it is not observed the ¡§migration¡¨ of Mg2+ within the LHA molecular structure as described by Engebretson and von Wandruszka .The reasons that make different results may depend on the species of humic acid. Therefore, the observations of Engebretson and von Wandruszka could not be used directly questioning those results in literatures. In addition, the effects of various cations (Mg2+, Ca2+and Sr2+) on Kdom are studied. It is believed different cation reacts with different specific binding sites on HA. As such, both charge density and affinity of cation with specific binding sites on HA should be considered in discussing the effects of metal ionic on the binding constants between PAHs and DOM.

Bidentate ligands are a commonly used class of ligands in catalysis that generate highly-active and selective catalysts. Such bidentate ligands, however, often suffer from synthetic challenges, which can be alleviated by the use of simpler monodentate ligands that assemble through non-covalent interactions to mimic the structure of bidentate ligands at the metal center. To produce a strongly assembled catalyst complex, the Hamilton receptor motif was utilized. Hamilton receptors form six hydrogen bonds with complementary guests and have binding affinities for barbiturates of up to 104 M-1 in CDCl3. Complete bifurcation of the Hamilton scaffold produces a modular ligand structure that allows for modification of either end of the supramolecular ligand structure. Similarly, the barbiturate guest can be synthetically altered creating both chiral guests and guests with differing amounts of steric bulk. Both experimental titration data and density functional theory calculations show that steric bulk discourages binding of the guest while a pre-organized host encourages guest inclusion. Electronic effects on the bifurcated Hamilton system were studied by varying the electron donating or withdrawing ability of the benzamide moiety on the host molecule. Electron withdrawing moieties produce more acidic amide hydrogens on the host which are able to participate in stronger hydrogen bonds with the guest resulting in a stronger host-guest complex. The effects of substitutions on the barbiturate guest were examined as well, and increased steric bulk on the guest resulted in decreased affinities with the host. The bifurcated Hamilton receptor ligands were examined in the palladium-catalyzed Heck reaction of iodobenzene with butyl acrylate. Pd2(OAc)4 was used as a control and all reaction yields with the diphenylphosphine ligand-stabilized Pd were greater than or equal to those obtained with Pd2(OAc)4 alone. The reaction rates did not correlate with the determined binding constants, suggesting that phosphine substitution on the guest plays a larger role than affinity of the complex for the guest. Reaction temperatures were varied, and at lower temperatures the yields increased implying that the strength of the hydrogen bonds between the metal complex and the guest does play a secondary role in the catalysis. This dissertation includes previously published co-authored material.

L’objectif de cette thèse est d’étudier les interactions entre polyélectrolytes (PE) de charges opposées par analyse frontale continue en électrophorèse capillaire (FACCE) et par titration calorimétrique isotherme (ITC), en fonction de la force ionique du milieu et des paramètres physico-chimiques relatifs aux deux partenaires (taux de charge chimique, masse molaire, ramification). Un copolymère statistique d’acrylamide et de 2-acrylamido-2-méthyl-propane sulfonate (PAMAMPS) de taux de charge variant entre 15% et 100% a été synthétisé et caractérisé pour cette étude. En tant que polycation modèle, la poly(L-lysine) a été retenue, sous sa forme linéaire (PLL) ou ramifiée / hyperbranchée (DGL). Des mesures par turbidimétrie ont permis d’étudier la stabilité des complexes de polyélectrolytes (PEC) en fonction de la force ionique du milieu. La détermination de la stœchiométrie des PEC par 1H-RMN a permis d’établir une règle générale pour prédire les stœchiométries de charge des PEC. Les paramètres thermodynamiques d’interactions (constantes et stœchiométries d’interaction, contribution entropique et enthalpique) ont été déterminés, par le tracé systématique des isothermes d’adsorption, en considérant le modèle d’interactions des sites indépendants de même énergie. Une dépendance linéaire entre le logarithme des constantes d’interactions et le logarithme de la force ionique a été observée. Cette dépendance en force ionique confirme le caractère entropique des interactions entre PE de charges opposées. Elle permet aussi de quantifier le nombre de contre-ions relargués lors de la formation du PEC. Cette quantité de contre-ions libérés a pu être comparée à la quantité totale de contre-ions condensés. Cette modélisation permet, en outre, de prédire les constantes d’interaction pour des taux de charge intermédiaires et à différentes forces ioniques. / The aim of this thesis is to study the interactions between oppositely charged polyelectrolytes (PE) by frontal analysis continuous capillary electrophoresis (FACCE) and isothermal titration calorimetry (ITC) as a function of the ionic strength of the medium and the physico-chemical properties related to the two partners (chemical charge density, molar mass, ramification). Statistical copolymers of acrylamide and 2-acrylamido-2-methyl-propane sulfonate (PAMAMPS) with chemical charge densities varying between 15% and 100% were synthesized and characterized for this study. Poly(L-lysine) under their linear (PLL) or ramified/hyperbranched (DGL) forms were used as model polycations. Turbidity measurements allowed the study of the stability of the polyelectrolyte complexes (PEC) as a function of the ionic strength of the medium. PEC charge stoichiometries were measured by 1H-NMR, and a general predictive rule that estimates the PEC charge stoichiometry was enounced. The thermodynamic binding parameters (binding constant, stoichiometry, enthalpic and entropic contributions) were determined, by systematically plotting the isotherms of adsorption, and using the model of independent and identical interacting sites. A linear dependence between the logarithm of the binding constants and the logarithm of the ionic strength was observed. This linear dependence confirmed the entropic character of the interactions between oppositely charged PE and allowed quantifying the number of released counter-ions that were compared to the total number of condensed counter-ions. Furthermore, this modelling allowed predicting the binding constants for intermediate chemical charge densities and at different ionic strengths.

La thérapie photodynamique (PDT) est un traitement alternatif du cancer plus ciblé et moins invasif que les modalités traditionnelles. La Temoporfine (mTHPC, nom sous forme médicamenteuse : Foscan®), est l'un des PS les plus puissants cliniquement approuvés. Cependant, sa faible solubilité en milieu aqueux a provoqué plusieurs complications lors de son administration. La présente étude vise à mettre au point des nanoparticules constituées d’une molécule anticancéreuse couplée à la cyclodextrine intégré dans un liposome (drug-in-cyclodextrin-in-liposome, DCL) en couplant deux systèmes d'administration indépendants : les complexes d'inclusion cyclodextrine-mTHPC et les vésicules liposomales pour améliorer le transport et la pénétration de la mTHPC dans le tissu cible. La formation de complexes d'inclusion entre les cyclodextrines et la mTHPC a été étudiée en détail. Sur la base de ces données, des mTHPC-DCL à simple et double charge ont été préparées, optimisées et caractérisées. Il a été démontré que les mTHPC-DCL sont stables et que presque tous les mTHPC-DCL sont liés à β-CDs dans la lumière aqueuse interne des liposomes. L'influence des DCLs sur l'accumulation, la distribution et l'efficacité photodynamique de la mTHPC a été étudiée dans des modèles cellulaire en monocouche et sphéroïde multicellulaires 3D d’adénocarcinome de pharynx humain (HT29). En utilisant des sphéroïdes, nous avons démontré que le DCL à base de triméthyl-β-CD fournissait une accumulation homogène de la mTHPC dans tout le volume des sphéroïdes tumoraux, suggérant ainsi une distribution optimale de la mTHPC. / Photodynamic therapy (PDT) is an alternative cancer treatment which offers a more targeted and less invasive treatment regimen compared to traditional modalities. Temoporfin (mTHPC, medicinal product name: Foscan®), is one of the most potent clinically approved PS. However, its poor solubility in aqueous medium caused several complications of its administration. The present study is aimed at the development of drug-in-cyclodextrin-in-liposome (DCL) nanoparticles by coupling two independent delivery systems: cyclodextrin/mTHPC inclusion complexes and liposomal vesicles to improve the transport and penetration of mTHPC to the target tissue. The formation of inclusion complexes between cyclodextrins and mTHPC was studied in detail. Based on these data, single and double loaded mTHPC-DCLs have been prepared, optimized and characterized. It was demonstrated that mTHPC-DCLs are stable and almost all mTHPC is bound to β-CDs in the inner aqueous liposome lumen. The influence of DCLs on mTHPC accumulation, distribution and photodynamic efficiency was studied in human adenocarcinoma HT29 cellular monolayer and spheroid models. Using 3D multicellular HT29 tumor spheroids we demonstrated that trimethyl-β-CD-based DCL provides homogenous accumulation of mTHPC across tumor spheroid volume thus supposing optimal mTHPC distribution.