This thesis examines the synthesis of conformationally constrained β-amino acids and β- peptides, and the electron transfer properties of the latter when immobilised on gold. Additionally, cross metathesis on gold was investigated as a method for surface functionalisation. Chapter One introduces the concepts of electron transfer in nature, how it is facilitated by the secondary structure in α-peptides, and why β-peptides might be useful for studying electron transfer. This is followed by a discussion of the properties of β-peptides, including the enhanced stability and variety of helical secondary structures and the greater potential for functionalisation of the peptide backbone when compared to α-peptides. Finally, the conformational constraints of ring-systems on cyclic amino acids is discussed, with reference to the stabilising effect of these compounds on peptide secondary structures. Chapter Two describes the electrochemical analysis of β-hexapeptides immobilised on gold. The chapter is prefaced by a discussion of the important electron transfer mechanisms for peptides, the fabrication of peptide-gold self-assembled monolayer (SAM) interfaces, and the electron transfer in helical α-peptides. β-Peptides containing an electroactive ferrocene moeity were immobilised on gold and studied using cyclic voltammetry and chronoamperometry. The latter method was used to examine the dependence of the electron transfer rate on overpotential, thereby determining the likely mode of electron transfer through the β-peptides SSβ₆Fc, Fcβ₆SS and SC₁₅β₆Fc. These peptides exhibited very weak dependence on overpotential, characteristic of electron transfer behaviour of an electron hopping mechanism (which is also thought to occur in helical α-peptides). Both the dipole moment of the peptides and the structure of the sulfurlinker group were found to be important in determining the rate of electron transfer. Conversely, the equivalent α-peptide SSα₆Fc exhibited electron transfer behaviour characteristic of the less efficient tunnelling mechanism, which is thought to operate in strand-like peptides. Chapter Three examines the application of cross metathesis, using a Grubbs' second generation catalyst, as a means to functionalise olefin-terminated self-assembled monolayers on gold. Abstract iv Firstly, an introduction into the limited published research on cross metathesis on both planar surfaces and nanoparticles is given. Olefin-terminated thiol 3.18, suitable for immobilisation on gold, and solution phase olefin-terminated ferrocene 3.10 were synthesised as reactants for cross metathesis studies. An analytical methodology was developed involving the cross metathesis of surface-immobilised 3.18 with ferrocene 3.10 in dichloromethane, whereby the concentration of electroactive cross metathesis product 3.22 was monitored electrochemically as a function of time. The concentration of surface-immobilised product 3.22 was determined by integration of the oxidation peak area and found to be highly dependent on both the concentration of immobilised olefin reactant 3.18 and reaction time. Furthermore, the surface concentration of ferrocenyl model disulfide 3.21 and thiol 2.18 decayed markedly upon addition of Grubb's catalyst, as revealed by the decrease in the oxidation peak area, which suggested that catalystmediated desorption was occurring. Chapter Four details the solution-phase synthesis of ferrocene- and thiol-functionalised β- hexapeptides used in both the electron transfer studies described in chapter two, and in the determination of secondary structure using circular dichroism and NMR techniques. The synthesis of simple model compounds 4.14, 4.16 and 4.18 established the incompatibility of the deprotection of methyl and benzyl ester protecting groups with protected-thiol and disulfide linkers, leading to the use of N-hydroxysuccinmide-activated sulfur-linkers 4.20 and 4.22 in further synthesis. A number of β-hexapeptides were synthesised by amide coupling of β- tripeptides functionalised at the N- and C-termini. Structural studies of the methanol soluble β- hexapeptide 4.60 suggested that the covalent attachment of ferrocene moeity to the C-terminus of a β-peptide did not disrupt the formation of a 14-helix in solution. β-peptides containing functionality at both the C- and N-termini (such as SSβ₆Fc, SSβ₆Et and acetyl-protected SC₁₅β₆Fc) were not suitable for solution phase structural studies; however, molecular modelling suggested that helical conformations are the most stable these β-peptides in solution phase. Chapter Five outlines the synthesis of novel cyclic β-amino acids by two different general synthetic routes. The first uses an efficient conjugate addition/fluorination reaction of α,β- unsaturated esters with lithiated chiral secondary amines to prepare the novel cyclopentyl- and cyclohexyl-based fluorinated β-amino acids 2.43a and 2.43b. The high diastereoselectivity of this reaction, which introduces two stereocentres into the achiral unsaturated esters, is directed by the configuration of the attacking amine. The second methodology utilizes the versatile ringclosing metathesis reaction in the synthesis of novel cyclic β-amino acids. A stereoselective Abstract v trans-alkylation of olefinic β-amino acids gave the required β-dienes 5.62 and 5.77. Optimised cyclisation yields were achieved with a Grubb's 2nd generation catalyst for diene 5.62 and Grubb's 1st generation catalyst for diene 5.77, to give the trans-cycloheptyl- and cyclooctylbased β-amino acids 5.63 and 5.78, respectively. The attempted synthesis of cyclononyl-based β-amino acid 5.87 using both catalysts yielded only cyclic dimer products 5.88 and 5.89. The trans configuration of the 5.62 diene was confirmed by x-ray crystallography. Chapter Six is an experimental chapter and outlines the electrochemical setup and analysis, and the synthesis, purification and characterisation of compounds described in this thesis.

This thesis examines the synthesis of conformationally constrained β-amino acids and β- peptides, and the electron transfer properties of the latter when immobilised on gold. Additionally, cross metathesis on gold was investigated as a method for surface functionalisation. Chapter One introduces the concepts of electron transfer in nature, how it is facilitated by the secondary structure in α-peptides, and why β-peptides might be useful for studying electron transfer. This is followed by a discussion of the properties of β-peptides, including the enhanced stability and variety of helical secondary structures and the greater potential for functionalisation of the peptide backbone when compared to α-peptides. Finally, the conformational constraints of ring-systems on cyclic amino acids is discussed, with reference to the stabilising effect of these compounds on peptide secondary structures. Chapter Two describes the electrochemical analysis of β-hexapeptides immobilised on gold. The chapter is prefaced by a discussion of the important electron transfer mechanisms for peptides, the fabrication of peptide-gold self-assembled monolayer (SAM) interfaces, and the electron transfer in helical α-peptides. β-Peptides containing an electroactive ferrocene moeity were immobilised on gold and studied using cyclic voltammetry and chronoamperometry. The latter method was used to examine the dependence of the electron transfer rate on overpotential, thereby determining the likely mode of electron transfer through the β-peptides SSβ₆Fc, Fcβ₆SS and SC₁₅β₆Fc. These peptides exhibited very weak dependence on overpotential, characteristic of electron transfer behaviour of an electron hopping mechanism (which is also thought to occur in helical α-peptides). Both the dipole moment of the peptides and the structure of the sulfurlinker group were found to be important in determining the rate of electron transfer. Conversely, the equivalent α-peptide SSα₆Fc exhibited electron transfer behaviour characteristic of the less efficient tunnelling mechanism, which is thought to operate in strand-like peptides. Chapter Three examines the application of cross metathesis, using a Grubbs' second generation catalyst, as a means to functionalise olefin-terminated self-assembled monolayers on gold. Abstract iv Firstly, an introduction into the limited published research on cross metathesis on both planar surfaces and nanoparticles is given. Olefin-terminated thiol 3.18, suitable for immobilisation on gold, and solution phase olefin-terminated ferrocene 3.10 were synthesised as reactants for cross metathesis studies. An analytical methodology was developed involving the cross metathesis of surface-immobilised 3.18 with ferrocene 3.10 in dichloromethane, whereby the concentration of electroactive cross metathesis product 3.22 was monitored electrochemically as a function of time. The concentration of surface-immobilised product 3.22 was determined by integration of the oxidation peak area and found to be highly dependent on both the concentration of immobilised olefin reactant 3.18 and reaction time. Furthermore, the surface concentration of ferrocenyl model disulfide 3.21 and thiol 2.18 decayed markedly upon addition of Grubb's catalyst, as revealed by the decrease in the oxidation peak area, which suggested that catalystmediated desorption was occurring. Chapter Four details the solution-phase synthesis of ferrocene- and thiol-functionalised β- hexapeptides used in both the electron transfer studies described in chapter two, and in the determination of secondary structure using circular dichroism and NMR techniques. The synthesis of simple model compounds 4.14, 4.16 and 4.18 established the incompatibility of the deprotection of methyl and benzyl ester protecting groups with protected-thiol and disulfide linkers, leading to the use of N-hydroxysuccinmide-activated sulfur-linkers 4.20 and 4.22 in further synthesis. A number of β-hexapeptides were synthesised by amide coupling of β- tripeptides functionalised at the N- and C-termini. Structural studies of the methanol soluble β- hexapeptide 4.60 suggested that the covalent attachment of ferrocene moeity to the C-terminus of a β-peptide did not disrupt the formation of a 14-helix in solution. β-peptides containing functionality at both the C- and N-termini (such as SSβ₆Fc, SSβ₆Et and acetyl-protected SC₁₅β₆Fc) were not suitable for solution phase structural studies; however, molecular modelling suggested that helical conformations are the most stable these β-peptides in solution phase. Chapter Five outlines the synthesis of novel cyclic β-amino acids by two different general synthetic routes. The first uses an efficient conjugate addition/fluorination reaction of α,β- unsaturated esters with lithiated chiral secondary amines to prepare the novel cyclopentyl- and cyclohexyl-based fluorinated β-amino acids 2.43a and 2.43b. The high diastereoselectivity of this reaction, which introduces two stereocentres into the achiral unsaturated esters, is directed by the configuration of the attacking amine. The second methodology utilizes the versatile ringclosing metathesis reaction in the synthesis of novel cyclic β-amino acids. A stereoselective Abstract v trans-alkylation of olefinic β-amino acids gave the required β-dienes 5.62 and 5.77. Optimised cyclisation yields were achieved with a Grubb's 2nd generation catalyst for diene 5.62 and Grubb's 1st generation catalyst for diene 5.77, to give the trans-cycloheptyl- and cyclooctylbased β-amino acids 5.63 and 5.78, respectively. The attempted synthesis of cyclononyl-based β-amino acid 5.87 using both catalysts yielded only cyclic dimer products 5.88 and 5.89. The trans configuration of the 5.62 diene was confirmed by x-ray crystallography. Chapter Six is an experimental chapter and outlines the electrochemical setup and analysis, and the synthesis, purification and characterisation of compounds described in this thesis.

Malgré l'intérêt croissant que représente dans le domaine de l'emballage alimentaire la conception raisonnée de structures composites aux propriétés de transfert contrôlées, la compréhension des transferts de gaz et de vapeurs avec l'ajout de particules dans des polymères reste complexe. En vue d'apporter un nouvel éclairage à ce verrou scientifique, les travaux de thèse se sont focalisés sur les trois parties suivantes : - contribuer à une meilleure compréhension des transferts de matière dans les composites. Pour ce faire, une analyse exhaustive des données expérimentales de transfert de gaz et de vapeurs disponibles dans la littérature a été menée pour les nano- et micro-composites et une comparaison de ces données a été réalisée avec des modèles de tortuosité, basés sur des paramètres géométriques ; - comprendre et modéliser la perméabilité dans des composites avec deux phases perméables. Pour cela, les transferts de vapeur d'eau dans un composite (fibre de paille/bio-polyester) chargé avec des particules perméables ont été mesurés et décrits en détail, et une comparaison de ces données avec des modèles analytiques issus d'autres champs disciplinaires, prenant en compte la perméabilité dans la particule et dans la matrice, a été menée. Cette étude a mis en avant le manque de modèles adaptés pour la prédiction de la perméabilité dans les composites contenant des particules perméables ; - développer une nouvelle approche multi-échelle pour la prédiction de la perméabilité dans des composites prenant en compte les propriétés de transfert dans les particules et dans la matrice polymérique avec une représentation 2D de la structure du composite. Afin d'atteindre un niveau satisfaisant de validation du modèle, la détermination des paramètres expérimentaux tels que la diffusion dans les particules doit être améliorée. Cette nouvelle approche de modélisation ouvre la voie à la création d'outils d'ingénierie inverse pour le design de structures composites, ajustés aux besoins des aliments en termes de propriétés barrières. / Despite the global growing interest in the food packaging field for the design of tailored composite structures with controlled mass transfer properties, the understanding of the modulation of the mass transfer properties with the incorporation of particles in polymer still remains very complex. In order to throw light on this scientific problem, the thesis work was focused on the following parts: - providing a better understanding of mass transfer in composites. In this purpose an analysis of all experimental gas and vapour permeability data available in the literature has been carried out in nano- and micro- composites and a comparison of these data with predictions from tortuosity models based on few geometrical inputs has been achieved; - performing a detailed study of water vapour mass transfer in composites (wheat straw fibres/bio-polyester). These data were compared with the prediction of bi-phasic analytical models coming from other disciplinary fields. This part of the work has highlighted the lack of comprehensive and complete models for the prediction of permeability in composite with permeable particles; - developing of an innovative multi-scale approach for the prediction of mass transfer in bi-phasic composites considering both the particle and the polymer matrix properties with realistic 2D geometry of the composite structures has been proposed. For the sake of reaching a satisfactory validation level of the model, some experimental improvements are still needed to increase the accuracy of input parameters such as diffusivity of the particles.This new modelling approach open the way for the creation of a reverse-engineering toolbox for the design of tailor made composites structures, tightly adjusted to barrier properties requirements of the packed food.

L'objectif de cette thèse était de développer des matériaux biodégradables (nano-)composites à libération contrôlée de pesticides, afin d'améliorer leur efficacité et limiter leurs impacts sur l'environnement (pertes par lessivage, dégradation etc.). La stratégie a consisté à réaliser par extrusion des matériaux à base de gluten de blé et de nanoparticules d'argile pour moduler la libération d'un herbicide modèle (l'éthofumesate) introduit dans la matrice. Combinée au gluten, l'utilisation d'argiles vise à moduler les propriétés de transfert de matière en jouant 1/sur des phénomènes de sorption (affinité entre pesticide et argiles), et 2/sur des phénomènes de diffusion (structure des composites gluten/argiles). Cette étude a soulevé différentes questions scientifiques : • Identifier les mécanismes impliqués dans les phénomènes de sorption et de désorption de l'éthofumesate sur différentes argiles • Comprendre comment la présence des nanoparticules d'argiles dans une matrice de gluten de blé pouvait induire des changements de propriétés du matériau telles que la sensibilité à l'eau et la vitesse de biodégradation, en lien avec les modifications structurales. • Identifier le déterminisme des modifications des propriétés de transfert de l'éthofumesate dans les « matériaux complets » (gluten-nanoparticules d'argiles-éthofumesate) dans des systèmes modèles et en conditions réelles (sol agricole).C'est grâce à une démarche intégrée, associant des outils d'étude appartenant à des domaines de compétences complémentaires comme la science des matériaux, les matériaux nanocomposites, l'agronomie, la formulation de pesticides et la modélisation des propriétés de transfert, qu'il a été possible de répondre aux différents objectifs scientifiques. Cette étude contribue ainsi à une meilleure compréhension des mécanismes de transfert de composés d'intérêt au sein de matériaux à base d'agropolymères en présence de nanoparticules d'argile. Elle a notamment permis de pondérer l'importance de la structure nanocomposite, par rapport aux phénomènes de sorption, lorsqu'on s'intéresse à la modulation des propriétés de transfert au sein d'un matériau. / The objectives of this study were to develop (nano)composite biodegradable materials for the controlled delivery of pesticides with the aim being to improve their efficiency and limit their negative impacts on the environment (due to leaching, degradation etc.). Our strategy has consisted in using an extrusion process to design materials based on wheat gluten and clay nanoparticules in order to fine tune the release of a model herbicide (ethofumesate) introduced into the matrix. Combined with gluten, the use of nanoclays aims to modulate transfer properties by acting on 1/ sorption phenomenon (driven by pesticide/clay affinity), and 2/diffusion phenomenon (depending on wheat gluten/clay structure). This study has led to different scientific questions : • Identify mechanisms involved in sorption/desorption behaviour of ethofumesate on different clays • Understand how the presence of nanoclays in a wheat gluten matrix was able to induce changes in material properties such as water sensitivity and biodegradation rate, in relation to structural changes • Identify the determinism of these changes in transfer properties in the case of the finished materials containing wheat gluten/nanoclay/ethofumesate, both in model medium and in real conditions (soil)Responding to these different scientific objectives has been possible using an integrated approach, combining tools of complementary skill fields such as material science, nanocomposite materials, agronomy, pesticide formulation and transfer modeling properties This study contributes to a better understanding of transfer properties of interesting compounds in the case of agropolymer based materials containing or filled with nanoclays. This work has notably enabled to balance the importance given at the nancomposite structure contribution in relation to sorption phenomenon in a context where the objective is to modulate material transfer properties.

Cette thèse, menée dans le cadre d'une Convention Industrielle de Formation par la Recherche (CIFRE) avec l'entreprise MENARD, est consacrée à l'étude de la durabilité d'un procédé particulier de renforcement de sol appelé Colonnes à Module Contrôlé (CMC). Cette application consiste en la mise en place d'un réseau d'inclusions verticales semi-rigides dans un sol afin d'améliorer les caractéristiques globales du terrain avant construction. Ces travaux font suite aux travaux de thèse de François Duplan (2011-2014) sur le développement de nouveaux composites cimentaires destinés à cette application. Dans ce but, il avait optimisé des compositions de mortiers incorporant des granulats spéciaux tels que des billes d'argile expansée ou des granulats en caoutchouc issus du broyage de pneus usagés. Les effets de l'introduction de ces granulats dans les composites ont été analysés aussi bien à l'état frais qu'à l'état durci et complètent les précédentes analyses de F. Duplan, notamment en termes d'indicateur de durabilité (perméabilité aux gaz, diffusion aux ions chlorures) et de comportement mécanique à long terme (retrait et fluage). A l'issue d'une analyse environnementale de l'application, trois mécanismes potentiels de dégradation ont été sélectionnés pour des investigations sur la durabilité des CMC : l'attaque acide, l'attaque sulfatique externe et la dégradation par cristallisation de sels. La réalisation d'essais accélérés en laboratoire a permis de mettre en évidence la pertinence du ciment CEM III/C, utilisé actuellement par MENARD, dans la majorité des cas. La faible teneur en C3A de ce liant permet en effet de limiter la production d'éléments expansifs dans le cas d'une attaque sulfatique externe et sa proportion limitée en hydrates du clinker (en particulier en portlandite) ainsi que le faible rapport C/S des C-S-H assurent une meilleure tenue aux attaques acides. La dégradation par remontée capillaire et cristallisation de sels dépendant avant tout des caractéristiques du réseau poreux et des conditions d'évaporation et beaucoup moins du type de ciment, l'utilisation du ciment CEM III/C présente moins d'intérêt. L'incorporation de granulats en caoutchouc ou de billes d'argile expansée dans les composites ne modifie qu'à la marge leur tenue aux mécanismes de dégradations testés. La majorité des phénomènes de dégradation de l'application étant liée à la pénétration d'agents agressifs au cœur des composites cimentaires, la prédiction des propriétés diffusives du matériau est essentielle dans l'estimation des risques encourus par l'application. Un nouveau modèle prédictif est proposé et comporte deux échelles d'homogénéisation : la première au niveau de la pâte de ciment et la deuxième au niveau du mortier. Les résultats obtenus par ce modèle sont fidèles aux résultats expérimentaux avec des erreurs relatives inférieures à 15%. L'estimation du coefficient de diffusion est globalement plus précise pour les composites incorporant des billes d'argile expansée que pour ceux incorporant des granulats en caoutchouc, une conséquence de la forme sphérique de ces billes mieux en accord avec les hypothèses du modèle mis en œuvre. / This CIFRE PhD-thesis carried out within the framework of Convention Industrielle de Formation par la REcherche (CIFRE) with the company MENARD, focuses on the durability of a specific soil-reinforcement system called Controlled Modulus Columns (CMC) which consists in a network of semi-rigid vertical inclusions cast into the ground in order to enhance its global characteristics before building. This study comes after the PhD work conducted by François Duplan (2011-2014) on the design of new cementitious composites intended for the CMC application and incorporating innovative aggregates like expanded clay grains or rubber aggregates obtained by grinding end-of-life tyres. The effects of addition of such aggregates into the composites have been studied both at fresh and hardened states and complete Duplan previous findings in particular with regards durability indicators (gas permeability, chloride diffusion) and mechanical long-term behaviour (creep and shrinkage). Three potential degradation mechanisms have been selected for the CMC system after an environmental analysis: acid attack, external sulphate attack and salt crystallisation. Laboratory accelerated tests highlighted that CEM III/C cement, actually used by MENARD, is suitable in most of the cases. The low C3A content of this binder reduces the production of expansive products in the case of external sulphate attack and its limited clinker hydrates proportions (in particular in portlandite), along with the low C/S ratio of the C-S-H enhance the resistance to acid attack. Salt crystallisation through capillary rise primarily depends on the porous network characteristics and less on the cement ones, meaning that CEM III/C cement is less relevant in that specific case. Based on the tested degradation mechanisms, incorporating rubber aggregates or expended clay ones into the cementitious composites does not significantly affect their durability. Most of the application degradation phenomenon being linked to the ingress of aggressive agents into the composites; the prediction of their diffusive properties is crucial to assess the risks involved for the application. A new predictive model is proposed with a dual homogenisation process: the first one at the cement paste level and the second one on the mortar level. Predicted results are in agreement with ones from experimental tests with a relative error less than 15%. Diffusion coefficient estimates are globally better for composites that contain expended clay aggregates than those incorporating rubber aggregates due to spherical shape of the first in accordance with the model hypotheses.