In the early 2000s, hydrogen sulfide (H₂S) was added to the family of molecules known as gasotransmitters, a class of endogenously produced and freely diffusing biological signaling molecules. Since this discovery, biologists and chemists have sought to understand the physiological roles of H₂S and to elucidate the potential benefits of exogenous H₂S delivery. As a result, many synthetic small molecule donor compounds have been created to deliver H₂S in response to various biologically relevant stimuli. Furthermore, macromolecular and supramolecular H₂S donor systems have been created to protect donors in the biological milieu, extend release kinetics, or control H₂S release conditions. Thus, H₂S-donating nanostructures with precisely tuned release rates provide invaluable tools for further investigating the biological roles and therapeutic potential of H₂S. This work describes two polymer micelle systems for the controlled delivery of H₂S. The first system is based on H2S-releasing polymer amphiphiles with varying degrees of a plasticizing comonomer incorporated into the core-forming block. The glass transition temperature of the core-forming block varied predictably with incorporation of the plasticizing comonomer. Accordingly, the half-life of H₂S release decreased from 4.2 h to 0.18 h with increasing core-forming block mobility. The second system is based on H₂S releasing polymer amphiphiles with varying degrees of crosslinking in the core-forming block. The crosslinked system was designed to achieve control over H₂S release rate with minimal dilution of donor in the core-forming block. The half-life of H₂S release increased from 117 min to 210 min with increasing crosslink density in the core-forming block, further demonstrating that H₂S release rates can be precisely controlled by tuning micelle core mobility. Beyond control over H₂S release rate, further study of the biological roles of H₂S requires donor systems with precisely triggered release. To this end, this dissertation also discusses efforts to investigate fundamental micelle–unimer relationships. This section includes an evaluation of the impact of core-forming block mobility on micelle–unimer coexistence utilizing a model polymer amphiphile system. Unimer populations correlated with glass transition temperatures of the core-forming block, suggesting the need to consider micelle core mobility when discussing polymer chain phase behavior of amphiphilic block copolymers. Finally, this work discloses new methods for the radical polymerization of poly(olefin sulfones) with control over molecular weight. POSs are a unique class of polymers with great potential for stimuli-responsive depolymerization to generate sulfur dioxide (SO₂), a signaling gas related to H₂S. / Doctor of Philosophy / Hydrogen sulfide (H2S) is commonly known for its pungent odor and toxicity. Despite this negative stigma, H2S has been revealed as a vital signaling molecule in both plants and animals. This discovery has prompted the coordination of biologists and chemists in an effort to better understand the roles of H2S in the body. Driven by this motive, great interest has centered around the development of finely tuned molecules designed to generate H2S in the body, termed H2S donors. A variety of synthetic H2S donors have been reported with various conditions enabling release. Building on this work, the development of polymeric H2S donors with tunable release rates will enable investigation into the complex behavior of H2S in the body. The first half of this dissertation focuses on the design and synthesis of two polymeric H2S donor systems for the controlled release of H2S. These systems take advantage of sequestering the H2S donating species inside a polymeric nanostructure in water called a micelle. Because H2S release requires a triggering molecule to enter the polymeric nanostructure, release rate can be tuned by modifying the mobility of the structure. The first system discussed demonstrates this concept by increasing the flexibility of the micelle core. As expected, H2S release rates increased with increasing flexibility. The second system discussed advances this idea by limiting mobility within the micelle core, rather than increasing flexibility. Accordingly, H2S release rates decreased with decreasing mobility within the micelle core. The latter half of this dissertation broadly explores the development of polymeric signaling gas delivery vehicles with triggered release conditions. We first investigate the impact of polymer chain flexibility on the formation of micelles in water. Polymer chain flexibility significantly impacted the balance between micelles and unassembled polymer chains in solution, suggesting the need to consider this characteristic when designing donor systems for precise release conditions. Lastly, we discuss the development of controlled polymerization techniques for poly(olefin sulfones). We envision that poly(olefin sulfones) will be a useful class of polymers in the design of donor systems relying on triggered depolymerization for release of the signaling gas sulfur dioxide.

Block copolymers have been extensively applied in diverse fields including packaging, electrolytes, delivery devices, and biosensors. Multiple investigations have been carried out on polymeric materials for cargo delivery purpose to understand how they behave over time. Block copolymer micelles (BCMs) have demonstrated superiority to deliver cargo, especially in drug delivery due to their encapsulation of hydrophobic agents. This dissertation will mainly study BCMs for potential applications in cargo delivery. Methods to study BCMs, including NMR spectroscopy, relaxometry and diffusometry, can provide valuable molecular information, such as chemical structure, translational motion, inter- or intramolecular interaction, dynamics, and exchange kinetics. Therefore, this dissertation describes applications of versatile NMR methods to reveal the fundamental behaviors of block copolymer self-assemblies, such as their dynamic stability, cargo partitioning, polymer chain exchange, and chain distribution in solution. We have investigated two BCM systems. Poly(ethylene oxide)-b-(ε-caprolactone) (PEO-PCL) is a model system to study BCM dynamic stability. PEO-PCL can self-assemble into spherical micelles at 1% w/v in D2O-THF-d8 mixed solvents. We used NMR diffusometry to quantify diffusion coefficients and populations of micelles and unimers (i.e. free polymer chains in solution) over a range of temperature (21 – 50 °C) and solvent composition (10 – 100 vol % THF-d8). By mapping the micelle-unimer coexistence phase diagrams, we are able to enhance our ability to understand and design micelle structure and dynamics. Moreover, we can also probe the chain exchange kinetics between micelles using a new technique we developed – time-resolved NMR spin-lattice relaxation (T1) or TR-NMR. This technique is an analog to time-resolved small-angle neutron scattering (TR-SANS), which can monitor specific signal intensity changes caused after mixing of isotope-labeled micelle solutions. A second system, Pluronic® F127 (PEO99PPO69PEO99) is a test system to study BCM structure and dynamic changes upon drug uptake. Pluronic® F127 is a commercial copolymer that can solubilize different hydrophobic drugs in micelles. We successfully encapsulated three model drugs into Pluronic® F127 BCMs and investigated the effects of polymer concentration and drug composition on drug partitioning fractions. Also, we proposed to design and synthesize a series of block copolymers with varied glass transition temperatures in core-forming blocks. Using NMR diffusometry, we have measured the existing unimer concentrations in micellar solutions and correlated these results with chain mobility and internal chemical composition. Lastly, we have extended our expertise in NMR and polymers into the study of ion-containing polymer systems (polyelectrolytes). A critical problem in polymer science is the inability to reliably measure the molecular weight of polyelectrolytes. We are developing methods to solve this problem by using NMR diffusometry, rheology, scattering, and scaling theories to accomplish general molecular weight measurements for polyelectrolytes. In short, this dissertation describes studies to provide more perspectives on structural and dynamic properties at various time and length scales for polymeric materials. NMR measurements, in combination with many other advanced techniques, have given us a better picture of soft matter behaviors and provided guidance for synthesis and processing efforts, especially in block copolymer micelles for delivery purposes. / Doctor of Philosophy / Block copolymers have been extensively applied in diverse fields in packaging, electrolytes and nano-scale drug delivery carriers. In the area of cancer treatment, only a limited number of drug nanocarriers have been approved for clinical applications. Therefore, it is very important to understand the principles behind drug delivery for targeted purposes. There have been many studies on polymeric delivery carriers but their behaviors have not been completely understood. Therefore, we have tremendous interest in unraveling the mysteries in those polymeric systems. Among a multitude of techniques to study block copolymer materials, the NMR method serves as a potent tool for its non-destructive, chemical-specific and isotope-selective merits. NMR can provide basic information about block copolymer self-assembly and other polymeric properties, such as chemical structure, molecular interactions and diffusion coefficients of species of interests. Chapters 3, 4, 5, 6, and 7 have investigated different classes of polymeric materials, mainly block copolymer micelles, for their structure and stability, exchange kinetics of polymer chains or cargo, and translational properties. Greater understanding about the fundamental properties of these polymeric systems, is essential for enabling new applications and new research areas.

Yes / Amphiphilic diblock copolymers, poly(2-(diethylamino)ethyl methacrylate-co-2-(dimethylamino)ethyl methacrylate)-b-poly(2-(dimethylamino)ethyl methacrylate), P(DEAEMA-co-DMAEMA)-b-PDMAEMA with various amounts of DEAEMA have been synthesized by RAFT polymerization. Their micellization in water has been investigated by scattering measurements over a wide pH range. It appeared that the polymers self-assembled into pH sensitive star like micelles. For a given composition, when the pH is varied the extent of aggregation can be tuned reversibly by orders of magnitude. By varying the copolymer composition in the hydrophobic block, the onset and extent of aggregation were shifted with respect to pH. This class of diblock copolymer offers the possibility to select the range of stimuli-responsiveness that is useful for a given application, which can rarely be achieved with conventional diblock copolymers consisting of homopolymeric blocks. / European Science Foundation (ESF), Engineering and Physical Sciences Research Council (EPSRC), BP (Firm), Birmingham Science City, Advantage West Midlands (AWM), European Regional Development Fund (ERDF)

Yes / AB and ABA di- and triblock copolymers where A is the hydrophilic poly(oligoethylene glycol methacrylate) (POEGMA) block and B is a thermo-responsive sulfobetaine block [2-(methacryloyloxy) ethyl] dimethyl-(3-sulfopropyl) ammonium hydroxide (PDMAPS) were synthesised by aqueous RAFT polymerisation with narrow dispersity (ĐM ≤ 1.22), as judged by aqueous SEC analysis. The di- and triblock copolymers self-assembled in salt-free water to form micelles with a PDMAPS core and the self-assembly of these polymers was explored by SLS and TEM analysis. The micelles were shown, by DLS analysis, to undergo a micelle-to-unimer transition at a critical temperature, which was dependent upon the length of the POEGMA block. Increasing the length of the third, POEGMA, block decreased the temperature at which the micelle-to-unimer transition occurred as a result of the increased hydrophilicity of the polymer. The dissociation of the micelles was further studied by SLS and synchrotron SAXS. SAXS analysis revealed that the micelle dissociation began at temperatures below that indicated by DLS analysis and that both micelles and unimers coexist. This highlights the importance of using multiple complementary techniques in the analysis of self-assembled structures. In addition the micelle-to-unimer morphology transition was employed to encapsulate and release a hydrophobic dye, Nile Red, as shown by fluorescence spectroscopy. / Engineering and Physical Sciences Research Council (EPSRC), University of Warwick

Yes / Sequential ring-opening and reversible addition–fragmentation chain transfer (RAFT) polymerization was used to form a triblock copolymer of tetrahydropyran acrylate (THPA), 5-methyl-5-allyloxycarbonyl-1,3-dioxan-2-one (MAC) and L-lactide. Concurrent deprotection of the THPA block and crystallization-driven self-assembly (CDSA) was undertaken and allowed for the formation of cylindrical micelles bearing allyl handles in a short outer core segment. These handles were further functionalized by different thiols using photo-initiated thiol–ene radical reactions to demonstrate that the incorporation of an amorphous PMAC block within the core does not disrupt CDSA and can be used to load the cylindrical nanoparticles with cargo. / Royal Society (Great Britain), Engineering and Physical Sciences Research Council (EPSRC), European Research Council (ERC)

Quaternary ammonium lipids containing long hydrocarbon-chains can cause deleterious effects when administered to many types of microorganisms. Some compounds have potent activity against spermatozoa and the HIV virus. Consequently, quaternary ammonium lipids are key components in spermicidal and antiseptic formulations. Surface-active quaternary ammonium lipids, containing a hydrophobic and hydrophilic moiety, will aggregate into micelles when dissolved in water above a narrow concentration range, termed the critical micelle concentration (CMC). This project investigates how the CMC relates to spermicidal and microbicidal properties. The CMC’s of the AD-nX and AT-nX compounds [see documents for figures] were determined by conductivity measurements. Relationships among the CMC and factors such as alkyl-chain length, head-group size, counteranion, and biological activity are discussed. [See document for figures of ADn and ATn] / Master of Science

La cryoconcentration a un grand potentiel pour produire des aliments liquides de haute qualité organoleptique et nutritionnelle. En plus, du point de vue énergétique, elle s’avère très compétitive face aux technologies de concentration comme l’évaporation sous vide, l’ultrafiltration, la nanofiltration et l’osmose inverse. Malgré ces avantages substantiels et le développement considérable qu’a connu cette technologie, la cryoconcentration est toujours considérée comme une opération commercialement fiable seulement dans des applications limitées à des produits tels que les jus de fruits, les extraits de café, du thé et des herbes aromatiques. Ainsi, le but principal de ce projet de doctorat est de comprendre l’impact de la cryoconcentration sur les paramètres physico-chimiques et compositionnels du lait écrémé et de l’utiliser comme une étape de concentration dans un procédé de fabrication de lait concentré, de lait concentré stérilisé et de poudre de lait écrémé. Le premier objectif portait sur l’étude de l’effet de la cryoconcentration à effet cascade sur les micelles de caséines, les propriétés rhéologiques et la couleur du lait écrémé concentré pendant cinq semaines de conservation. En utilisant un lait écrémé (fraichement fourni par Natrel) comme témoin avec une teneur en matière sèche totale de X = 9,24 %, trois cycles de cryoconcentration étaient réalisés. Ce traitement a permis d’atteindre des concentrations de 1,6X, 2,3X et 2,7X au cycle 1, 2 et 3, respectivement. Concernant les micelles de caséines, les résultats obtenus n’ont montré aucune différence significative entre l’effet des trois cycles de cryoconcentration sur la distance inter-micellaire et la forme sphérique des caséines. Cependant, avec l’augmentation du cycle de cryoconcentration, la taille des micelles de caséines avait tendance à se déplacer vers de plus petites tailles avec une modification de la distribution de leur diamètre moyen. Les résultats obtenus ont également montré qu’à tous les cycles de cryoconcentration, les micelles de caséines étaient caractérisées par des distributions monomodales où environ 60 % du volume total occupé par les micelles de caséines ont une taille de 100-200 nm. Comparé au lait-témoin, les résultats ont également montré que la cryoconcentration améliore la couleur en augmentant la valeur L* (indice de blancheur) du lait cryoconcentré au-dessus de 67; ce qui est similaire à celui d’un lait entier (non écrémé), et ce, dès le premier cycle de cryoconcentration. Aucune différence significative n’a été observée entre la valeur L* du lait aux trois cycles de cryoconcentration. Enfin, pendant le stockage du lait écrémé cryoconcentré, ses propriétés d’écoulement ont changé, car, une transition d’un comportement newtonien à non-newtonien a été observée à partir de la quatrième semaine à une concentration de 2,7X de matière sèche totale. En plus, une légère augmentation de la taille des micelles de caséines a été observée pendant cette période. Le deuxième objectif de ce projet de doctorat consistait à réaliser une étude comparative sur l’effet de la stérilisation sur la qualité d’un lait écrémé concentré par cryoconcentration, par évaporation sous vide et par osmose inverse pendant l’entreposage. Les résultats ont montré que la stérilisation a augmenté près de 9 fois le coefficient de consistance du lait évaporé contre 2 fois pour le lait cryoconcentré et le lait concentré par osmose inverse. Pendant l’entreposage, la charge nette des protéines du lait produit par évaporation a diminué, alors que celle des protéines du lait cryoconcentré et celui concentré par osmose inverse sont restées plus stables. Le troisième objectif avait pour but de réaliser une étude comparative entre la cryoconcentration, l’évaporation sous vide et l’osmose inverse, comme étape de pré-concentration du lait écrémé, en vue d’en produire du lait écrémé en poudre et d’évaluer les propriétés physico-chimiques et techno-fonctionnelles des poudres. Tout d’abord, l’observation de la morphologie, de la forme et l’analyse de la taille ont révélé que la surface des particules était lisse avec un petit nombre de sous-structures visibles sur la surface de l’échantillon issu de l’évaporation sous vide et de l’osmose inverse. La poudre du lait cryoconcentré et celle du lait concentré par osmose inverse avaient moins de particules fragmentées et plus de particules de grandes tailles que la poudre de lait évaporé. À la granulométrie (taille de particule) de 250 µm, la poudre de lait cryoconcentré avait trois fois le volume (%) de la poudre de lait concentré par osmose inverse et la poudre de lait évaporé sous vide. Après reconstitution, les micelles de caséines dans du lait reconstitué à partir de la poudre obtenue en utilisant du lait écrémé cryoconcentré présentaient la plus grande taille suivie de celle du lait reconstitué à partir de poudre obtenue avec du lait concentré par osmose inverse avec des pics de distribution se situant à 190 nm et à 164 nm, respectivement, pour la poudre obtenue par cryoconcentration et celle obtenue par osmose inverse. Malgré la différence de techniques de pré-concentration, toutes les poudres présentaient un indice de solubilité élevé (> 85%). Cependant, les poudres de faible granulométrie (75 µm) ont présenté une faible solubilité, ce qui est normal pour cette granulométrie. Pour la dispersion, c’est seulement à la granulométrie optimale (105 µm) que toutes les poudres ont montré les plus grands indices de dispersion. Cependant, elles n’ont pas présenté une bonne dispersion (< 90%) selon les normes de la fédération internationale du lait (FIL). Indépendamment de la taille et du prétraitement, toutes les poudres ont également une faible mouillabilité. Ainsi, ce projet a apporté une contribution aux connaissances sur l’utilisation de la cryoconcentration comme alternative prometteuse dans la fabrication du lait concentré, concentré stérilisé et du lait en poudre. / Cryoconcentration has great potential to produce foods of high nutritional and organoleptic quality. Moreover, it can be very competitive in comparison with vacuum evaporation and reverse osmosis. Despite these substantial benefits and the considerable technological developments, the use of cryoconcentration at industrial scale is still limited. However, some products are produced by cryoconcentration at high scale such as concentrated fruit juices, coffee and tea extracts, as well as different flavorings. Thus, the aim of this project was to study effect of cryoconcentration on skim milk properties and to use this technique as a concentration step for the production of concentrated skim milk and skim milk powder. The first objective was aimed to study the effects of cryoconcentration carried out in a cascade effect on skim milk properties such as casein micelles, color and rheological properties of concentrated skim milk during five weeks of storage. Fresh skim milk with X = 9.24% total dry matter was used as feed material (control). By using three cryoconcentration cycles, it was possible to reach concentrations of: 1.6X, 2.3X and 2.7X at the end the 1st, 2nd and 3rd cryoconcentration cycles, respectively. Moreover, the obtained results showed that cryoconcentration cycle had no significant effect on the inter-micellar distance and the spherical shape of the caseins, but an increase of the cryoconcentration cycle modified the distribution of the mean particle size of the casein micelles towards the smaller units. Furthermore, at all cryoconcentration cycles, monomodal distributions of the micelles particle size were observed where about 60% of the total volume was occupied by the casein micelles which have a size of 100-200 nm. Moreover, the obtained results clearly showed that cryoconcentration significantly improved the color of the cryoconcentrated skim milk by increasing the L* value up to 67 which is similar to that of whole milk. Finally, during storage, a transition from Newtonian to non-Newtonian behavior of the cryoconcentrated skim milk corresponding to the one obtained at the end of the 3rd cycle (2.7X) was observed from the fourth week of storage with a slight increase of size of the caseins micelles. The aim of the second objective was to compare the effect of sterilization on the quality of concentrated skim milk obtained by cryoconcentration, vacuum evaporation and reverse osmosis during storage. The results showed that sterilization increased viscosity of the evaporated milk nearly 9 times versus 2 times the viscosity of the cryoconcentrated milk and the concentrated milk by reverse osmosis. During storage, the protein net charge of milk produced by vacuum evaporation decreased, while that of cryoconcentrated milk and reverse osmosis remained more stable. The aim of the third objective was to study the pre-concentration of milk by cryoconcentration for the manufacture of skim milk powder in comparison with vacuum evaporation and reverse osmosis. The physico-chemical characterization and techno-functional properties of the powder was also carried out. Observation of powder morphology, shape and particle size analyses revealed that the surface of the particles was smooth with a small number of substructures visible on the surface of the sample from vacuum evaporation and reverse osmosis. The powder of the cryoconcentrated milk and those of the concentrated milk by reverse osmosis had fewer fragmented particles and larger particles than the evaporated milk powder. At the particle size of 250 µm, the cryoconcentrated milk powder had three times the volume of the milk powder concentrated by reverse osmosis and vacuum evaporation. After reconstitution, the casein micelles of the powder obtained from cryoconcentrated milk showed the largest size followed by that obtained from concentrated skim milk by reverse osmosis with distribution peaks at 190 nm and 164 nm, respectively, for the powder obtained from cryoconcentrated milk and reverse osmosis concentrated milk. Despite the differences in the pre-concentration techniques, all the powders had a high solubility index (> 85%), but the powders with small granulometry (75 µm) showed a low solubility. For dispersion, only the optimum particle size (105 µm) showed the greatest dispersion index, but they did not show good dispersion (< 90%) according to the international dairy federation (IDF) standard. Irrespective of size and pre-treatment, all powders have low wettability. Thus, this project contributed to knowledge advancement on the use of cryoconcentration as a promising technique in the manufacture of concentrated sterilized skim milk and skim milk powder.

Le peptide f1-8 (Pf1-8) obtenu par hydrolyse trypsique de la β-lactoglobuline a démontré plusieurs caractéristiques d'intérêt. En effet, outre sa capacité d'auto-assemblage et son caractère hydrophobe, il fait partie d'un groupe de peptides (tels que les peptides f9-14, f15-40, f142-148 de la β-lactoglobuline) ayant la capacité de se lier à certaines protéines du lait et de modifier le profil de dénaturation thermique de la β-lactoglobuline, probablement par des interactions hydrophobes avec le noyau hydrophobe de la protéine. Les caséines (CN) représentent à elles seules près de 80% de la totalité des protéines de lait bovin. Leur acidification à pH 4,6 engendre des changements structurels majeurs dans la micelle qui précipite au voisinage du point isoélectrique. L'objectif de ce projet était d'étudier les changements des propriétés physicochimiques des CN micellaires en présence du peptide Pf1-8. Ce peptide a été produit par hydrolyse trypsique d'un isolat de protéines de lactosérum, isolé par ultrafiltration, concentré par osmose inverse et purifié par lavages successifs et par centrifugation (pureté de 91%). Différentes solutions modèles (pH 6,6) avec des ratio CN: Pf1-8 de 1: 1, 5: 1 et 10: 1 (concentrations respectives de 2,5: 2,5, 2,5: 0,5 et 2,5: 0,25 mg / mL) ont été testées. Pour chaque solution dont les pHs variaient de 6,6 à 2,6, la solubilité de la CN, la taille et la potentielle interaction des protéines avec le Pf1-8 ont été déterminées par SEC-HPLC et SDS-PAGE. Aucune précipitation de la CN n'a été observée dans toute la plage de pH testée pour la solution à un ratio de 1: 1. Cependant, pour des échantillons à un ratio de 10: 1 et 5: 1 de CN: f1-8, une précipitation a été observée à pH 4,6. Les analyses par SDS-PAGE et SEC-HPLC ont démontré la formation d'agrégats impliquant le Pf1-8 et une ou plusieurs espèces caséiques pour tous les pHs testés, et une augmentation de la solubilité ainsi qu’une diminution de la taille des CN micellaires. Par conséquent, ces résultats démontrent que le peptide Pf1-8 est capable de modifier les propriétés physicochimiques de la CN, représentant ainsi un stabilisant potentiel des protéines dans les formulations laitières. / The peptide f1-8 (Pf1-8) obtained by tryptic hydrolysis of β-lactoglobulin has demonstrated several characteristics of interest. Indeed, in addition to its capacity for self-assembly and its hydrophobicity, it is part of a group of peptides (such as peptides f9-14, f15-40, f142-148 of β-lactoglobulin) having the ability to bind to some milk proteins (like β-lactoglobulin and α-lactalbumin) and change the thermal denaturation profile, probably by hydrophobic interactions with the hydrophobic core of β-lactoglobulin. Caseins (CNs) alone account for nearly 80% of the total bovine milk protein. Their acidification at pH 4.6 causes major structural changes in the micelle and are precipitated in the vicinity of isoelectric point. The goal of this project was to study the changes in the physicochemical properties of micellar CN in the presence of peptide Pf1-8. This peptide was produced by tryptic hydrolysis of a whey protein isolate, isolated by ultrafiltration, concentrated by reverse osmosis and water washed by centrifugation to purify (91% purity). Different model solutions (pH 6.6) with CN:Pf1-8 ratios of 1:1, 5:1 and 10:1 (respective concentrations of 2.5:2.5, 2.5:0.5, and 2.5:0.25 mg/mL) were tested. For each solution, the solubility of the CN, size by SEC-HPLC, and protein-interaction by SDS-PAGE were determined at various pHs ranging from 6.6 to 2.6. No CN precipitation was observed in the whole range of pH tested for the solution at 1:1 ratio. However, for samples at ratio 10:1 and 5:1 of CN:f1-8, the precipitation was observed at pH 4.6. Analyses by SDS-PAGE and SEC-HPLC demonstrated the formation of aggregates involving Pf1-8 and one or more CNs for all tested pHs, and increase in the solubility, and decrease in the size. Consequently, our results demonstrate that Pf1-8 peptide can modify the physicochemical properties of CN thus representing as a potential protein stabilizer in dairy formulations.

Tableau d’honneur de la Faculté des études supérieures et postdoctorales, 2010-2011 / La synthèse de nanoparticules d'YF₃ a été réalisée par la méthode des microémulsions inverses. Les deux variantes utilisées consistent à ajouter F₃ à une microémulsion contenant Y₃+, soit via une microémulsion, soit en phase aqueuse. La première méthode produit des particules amorphes de forme indéfinie. La seconde produit un mélange de particules octaédriques monocristallines et sphériques amorphes. Dans les deux cas, la taille est monodisperse et celle-ci peut être contrôlée. Plusieurs paramètres du système micellaire ont été caractérisés par DLS et RMN (taille des micelles inverses, nombre d'agrégation, quantité de surfactant libre, composition micellaire et aire moléculaire interfaciale). De nouvelles approches pour l'analyse des données ont été développées, basées sur la réalisation que des micelles d'une taille donnée doivent être en équilibre avec le surfactant libre à une concentration fixe unique. Un nouveau modèle a également été développé pour les micelles inverses non ioniques. Celui-ci est plus approprié pour les surfactants non ioniques, car il tient compte du volume occupé par la chaîne hydrophile du surfactant et d'une aire moléculaire interfaciale variable. Il ressort que la quantité de surfactant libre est très importante (45-100%) et augmente avec une diminution de la taille des micelles. Ceci s'explique par une perte d'entropie des chaînes hydrophiles du surfactant qui doivent adopter des conformations défavorables, à cause du manque d'espace. Finalement, le mécanisme de formation des nanoparticules a été étudié. Au début de la synthèse, les réactifs sont rapidement dispersés dans le système et consommés pour former des noyaux solides. Les noyaux plus stables croissent ensuite par un mécanisme de maturation d'Ostwald, alimentés par la dissolution des noyaux instables. La différence déterminante entre les deux méthodes de synthèse se produit au moment de la nucléation. Dans le cas de la méthode classique, celle-ci se produit entre des réactifs équimolaires lors d'un échange intermicellaire. Cette méthode génère un plus grand nombre de noyaux stables, expliquant la plus faible taille des particules. Pour la méthode à une microémulsion, la nucléation se produit avec un excès de fluorure, lors de la rencontre de micelles inverses contenant l'yttrium avec une microgouttelette de la solution de fluorure.

Les nanoparticules de fluorure d'yttrium dopées aux lanthanides possèdent des propriétés luminescentes intéressantes pour des applications en imagerie biomédicale. Nous pouvons synthétiser ces nanoparticules en micelles inverses. Pour leurs applications, les nanoparticules doivent être dispersées dans l'eau, il devient donc essentiel de fonctionnaliser leur surface. L'addition de tétraéthylorthosilicate à la microémulsion en conditions basiques forme une coquille de silice. Cependant, cette réaction génère une deuxième population de nanoparticules de silice. Plusieurs stratégies ont été tentées afin d'éliminer la formation des billes de silice. La diminution du précurseur élimine la seconde nucléation, en revanche, la coquille de silice devient trop mince pour être observable par microscopie à transmission électronique. II faut se tourner vers la spectroscopie de fluorescence, la spectroscopie de photoélectrons des rayons-X et la microscopie à transmission électronique de haute résolution pour valider la formation de la coquille de silice. La poursuite des travaux inclut la formation d'une couche fonctionnalisée sur la coquille de silice afin de faciliter la dispersion en milieu aqueux. Des études en parallèle ont également été faites sur des nanoparticules de type coeur-coquille dopées aux lanthanides. L'étude visait à valider qu'il soit possible de faire croître une coquille d'un matériau similaire à la surface du coeur, sans toutefois effectuer un mélange des deux matériaux.