Nott Katherine (2007). Synthèse de dérivés tensioactifs de virginiamycine et étude de leurs propriétés (Thèse de doctorat). Gembloux, Académie universitaire Wallonie-Europe, Faculté Universitaire des Sciences Agronomiques, 317 p., 66 tabl., 79 fig. Résumé : Suite à la purification du facteur M1 de la virginiamycine, des dérivés ont été synthétisés et purifiés. Deux types de mono-dérivés ont été obtenus : des esters avec des acides gras (modification de M1 au niveau de lhydroxyle en C-14) et des oximes (liaison chimiosélective) dérivées dacides aminés (réaction avec le carbonyle cétonique en C-16). Des di-dérivés ont également été produits en modifiant simultanément ces deux sites réactionnels avec un acide gras dune part et un aminooxy acétyle acide aminé dautre part. Lidentité des dérivés a été confirmée par un ensemble de techniques spectrales (infrarouge, masse et résonance magnétique nucléaire). Leurs propriétés tensioactives fondamentales ont été étudiées et un criblage de leurs activités antimicrobiennes a été réalisé. Laugmentation simultanée des caractères hydrophobe et hydrophile de M1 (cas des di-dérivés) est nécessaire pour lui conférer un caractère tensioactif marqué. Les di-dérivés présentent des caractéristiques tensioactives (cinétique dadsorption et formation de micelles) similaires voire supérieures à celles dautres tensioactifs classiques de la littérature et de certains biosurfactants tels que les lipopeptides de Bacillus subtilis. La synthèse de di-dérivés a augmenté la capacité de M1 à pénétrer dans un modèle membranaire. Le rôle favorable de M1 sur certaines propriétés de surface a été mis en évidence par comparaison des propriétés des di-dérivés avec celles de molécules témoins de type amide formées entre un acide gras et un acide aminé. La gamme de di-dérivés synthétisés a permis de contribuer aux études des relations structure fonction dans le domaine des tensioactifs. Le criblage des activités antibactériennes des dérivés a montré limportance des fonctions hydroxyle et cétone pour lactivité antibiotique initiale de M1. Les di-dérivés ainsi que les molécules témoins synthétisées présentent une activité vis-à-vis de certaines bactéries et moisissures. Cela pourrait être attribué à la capacité de ces molécules à déstabiliser les membranes de ces microorganismes. Nott Katherine (2007). Synthesis of surface active derivatives of virginiamycin and study of their properties (PhD thesis in french). Gembloux, Belgium, University Academy Walloon Region-Europe, Gembloux Agricultural University, 317 p., 66 tabl., 79 fig. Summary : Following the purification of the M1 factor of virginiamycin, derivatives have been synthesised and purified. Two types of mono-derivatives have been obtained : esters with fatty acids (modification of M1 at its C-14 hydroxyl) and oximes (chemoselective ligation) with aminooxylated amino acids (reaction with the ketone carbonyl at C-16). Bis-derivatives have also been produced by simultaneously modifying the two reactive sites with a fatty acid on one side and an aminooxylated amino acid on the other. The identity of each derivative has been confirmed by a combination of spectral techniques (infrared, mass and nuclear magnetic resonance). Their fundamental tensioactive properties have been studied and screening of their activity against microorganisms has been undertaken. The simultaneous increase of M1s hydrophobic and hydrophilic character (the case of the bis-derivatives) was necessary to render M1 surface active. The bis-derivatives have surface active characteristics (adsorption kinetics and micelle formation) similar or even superior to those of classical surfactants of the literature and of some biosurfactants such as Bacillus subtiliss lipopeptides. The synthesis of the bis-derivatives has enhanced M1s capacity to penetrate a biological membrane model. M1s positive impact on some surface properties has been shown by comparison with amide type molecules obtained by reacting a fatty acid with an amino acid. The range of the synthesised bis-derivatives has allowed this work to contribute to the studies of the relationships between surfactants structures and their properties. The screening of the derivatives antibacterial activities has shown the importance of the hydroxyl and ketone groups for M1s initial antibiotic activity. The bis-derivatives and the reference molecules show an activity against some bacteria and fungi. This may be due to their capacity to destabilise the microorganisms membranes.

Adsorption on solid surfaces from solution is a fundamental property of a surfactant. It might even be the most important aspect of surfactant behavior, since it influences many applications, such as cleaning, detergency, dispersion, separation, flotation, and lubrication. Consequently, fundamental investigations of surfactant adsorption are relevant to many areas. The main aim of this thesis has been to elucidate the adsorption properties, primarily on the solid/water interface, of a particular class of polyhydroxyl based surfactants: the alkyl glucosides. By the use of ellipsometry, the equilibrium and kinetic aspects of adsorption on titanium dioxide with respect to structural effects has been studied. Furthermore, the effects of small amounts of cationic surfactant additives on the adsorption on silica have been investigated. The results have been compared with similar studies for other nonionic surfactants. We have found that the surfactant structure has a strong effect on the adsorption properties. An increase in the surfactant chain length increases the cooperativity of the system. An increase in the head group polymerization decreases the cooperativity and the plateau adsorbed amount at equilibrium. The effect of surfactant structure on the adsorption kinetics depends on the concentration relative to the cmc, while the there is a decrease in the rate of desorption with increasing hydrophobic chain length independent of the concentration. The adsorption/desorption process is concluded to be diffusion driven, as suggested by the model used. When comparing these results with studies on ethylene oxide based surfactants, we conclude that the two types of surfactants exhibit similar trends on surfaces onto which they adsorb. Adsorption from binary surfactant solutions is even more interesting than adsorption from single surfactant solutions, since it brings us one step closer to the systems used in applications. In addition, adsorption from a mixture can be very different from adsorption from any of the single surfactants in the mixture. Alkyl glucosides alone do not adsorb on silica, but addition of small amounts of a cationic surfactant to the alkyl glucoside solution allows for adsorption on silica. A comparison between the adsorption and bulk properties has shown that mixed micellization explains most, but not all, effects of the coadsorption properties. Changing the pH in the mixed systems reveals that a surfactant with a pH-dependent charge and the ability to adapt its charge to the environment, e.g. a surface, enhances the adsorbed amount over a wider range of pH values than a purely cationic surfactant. It is well known that alkyl glucosides and ethylene oxides adsorb differently on different types of hydrophilic surfaces. As a consequence, replacing ethylene oxides with alkyl glucosides might not be all straight-forward; however, we have shown that the effect of the surface can be eliminated by the use of a cosurfactant. / <p>QC 20101018</p>

The focus of this thesis has been on the effects of segregation in mixtures of amphiphilic molecules. Two different systems were investigated: fluorocarbon-hydrocarbon surfactant mixtures and lipid-surfactant mixtures. In fluorocarbon-hydrocarbon surfactant mixtures the repulsive interactions between the chains can lead to a demixing into different types of coexisting micelles, fluorocarbon rich and hydrocarbon rich. From NMR self-diffusion measurements such a demixing was found to occur in the mixture of the partially fluorinated surfactant HFDePC and C16TAC. We furthermore suggested a demixing also within the micelles to explain 19F-NMR line width data and results from neutron scattering. In lipid-surfactant mixtures, a segregation of the molecules may instead be caused by a difference in the preferred curvature of the lipid and the surfactant residing within the same aggregate. Using a surfactant selective electrode, binding isoterms of four different cationic surfactants (C12TAC, C14TAC, C16TAC and HFDePC) to preformed lipid (GMO) vesicles were determined. Perforated vesicles were observed by cryo-TEM in the mixture with C16TAC. To explain the results from the binding isoterms, the formation of pores in the bilayer was regarded as a cooperative process, similar to micelle formation. The surfactant accumulates at the edges of the pores, and increasing the surfactant concentration results in an increased number of pores with a constant surfactant/lipid ratio at the edges. The lipid-surfactant mixtures were also studied at the solid/solution interface using AFM. An adsorbed mesh structure, a counterpart to the bulk perforated lamellar phase, was observed for the first time.

The aim of this thesis was to identify some functionality related characteristics of pharmaceutically relevant solid materials and to study the effect of their variation on processing behaviour and product performance. For this purpose, particles with different characteristics were prepared under a variety of conditions by crystal agglomeration, wet granulation and spray drying. The effect of particle size distribution on the evolution of the tablet microstructure during and after compression was investigated. The compression behaviour of particles with different nominal strength and degrees of agglomeration was studied and the influence of the surfactant concentration of amorphous particles on the compression behaviour was examined. The response of the powders to compression was described with the help of various techniques characterising the microstructure and tensile strength of the tablets produced. Furthermore, a method suitable for observing drug release from single matrix granules was developed and used to study the effect of granule porosity and compaction pressure on the drug release process. The particle size distribution did not influence the evolution of the tablet porosity or the tensile strength during compression, but it could have an effect on the evolution of the tablet microstructure during short-term storage, depending on the instability mechanism. The compression behaviour of particles prepared by crystal agglomeration and wet granulation was dependent on their degree of agglomeration and their failure strength. For particles with similar solid state properties and compression behaviour, the surface energy appears to have an effect on the bonding strength of adsorption bonds acting at interparticulate junctions. Using the method developed to observe the drug release from single matrix granules, reproducible data was obtained enabling the drug release process to be characterised. Depending on the type of matrix and the compaction pressure, the drug release rate could be enhanced or retarded.

The interactions between anionic, crosslinked gels and cationic surfactants have been investigated. When exposed to oppositely charged surfactant, the gel collapses into a dense complex of polyion and micelles. During deswelling, the gel phase separates into a micelle-rich, collapsed surface phase, and a swollen, micelle-free core, both still part of the same network. As more surfactant is absorbed, the surface phase grows at the expense of the core, until the entire gel has collapsed. Polyacrylate (PA) gels with dodecyl- (C12TAB), and cetyltrimethylammonium bromide (C16TAB), as well as hyaluronate gels with cetylpyridinium chloride, have been studied. Kinetic experiments have been performed on macro- as well as microgels, using micromanipulator assisted light microscopy for the latter. A surfactant diffusion controlled deswelling model has been employed to describe the deswelling. The deswelling kinetics of PA microgels have been shown to be controlled by surfactant diffusion through the stagnant layer surrounding the gel, as the surface phase is relatively thin for the major part of the deswelling. For macroscopic PA gels the surface phase is thicker, and the kinetics with C12TAB were therefore also influenced by diffusion through the surface phase, while for C16TAB they were dominated by it. Relevant parameters have also been determined using equilibrium experiments. An irregular, balloon-forming deswelling pattern, mainly found for macrogels, as well as unexpectedly long lag times and slow deswelling for microgels, are reported and discussed. The microstructure of fully collapsed PA/C12TAB complexes has been studied using small-angle X-ray scattering. A cubic Pm3n structure was found at low salt concentration, which melted into a disordered micellar phase as the salt concentration was increased. Further increasing the salt concentration dissolved the micelles, resulting in no ordering.

Different modes of assisted ventilation were investigated in cats before and after lung lavage and after instillation of surfactant. The activity of single units of slowly adapting pulmonary stretch receptors (PSRs) in the vagal nerve and the integrated phrenic nerve activity were recorded. The instantaneous impulse frequency (fimp) of PSRs was calculated and related to transpulmonary pressure (Ptp), tidal volume (Vt) and the calculated energy storage of the lung (ΣP*ΔV). Respiratory rate (RR), inspiratory and expiratory time, and Vt were measured, and their coefficients of variation were calculated. During assist control (A/C) ventilation with different pressure waveforms, PNA was shorter and lower in amplitude with squarewave pressure waveform than with linear and sinusoidal pressure waveforms in cats with normal lungs, concomitantly with earlier peak fimp during inspiration and prolonged fimp during expiration. The type of pressure waveform can thus influence the spontaneous breathing effort during A/C ventilation. Proportional assist ventilation (PAV) is a new mode of assisted ventilation which servo-controls the applied airway pressure continuously in proportion to the breathing effort. After lung lavage and surfactant instillation, PAV improves ventilation markedly, with lower PNA and oesophageal pressure deflection and higher RR and variability of breathing, compared to CPAP. In addition, an earlier and higher maximal fimp was observed during PAV. Under conditions of low work and maintained control of breathing, PAV seems to be an attractive mode of ventilatory support. Low-threshold (LT) and high-threshold (HT) PSRs respond to the surfactant content of the lung partly independent of Ptp and Vt in spontaneously breathing cats, implying a possible effect of surfactant on PSRs. The PSR fimp normalized to ΣP*ΔV confirmed these findings and showed that LT and HT PSRs are intrinsically the same. After instillation of surfactant, compliance and PSR activity increased, but the breathing still remained shallow and rapid, suggesting a control of breathing less dominated by PSR activity.

A method is described for preset-count irradiations between 1 and 100 ions singling-out individual ions from an ion beam with more than a billion ions arriving per second. The ion tracks are etched in a conductometric system with real-time evaluation of the acquired data. The etch process can be interrupted when reaching a preset channel diameter. Cylindrical channels are obtained by adding surfactants to the etch solution forming a self-assembled barrier between etching medium and polymer. Asymmetric etching of single ion tracks leads to pH sensitive conical pores with diode-like properties. Using etched channels as template, homogeneous and multilayer magnetic single-wires are electrodeposited. The magnetoresistivity of the wires is studied. Single-track applications comprise critical apertures (cylindric, conic, necked), asymmetric pores (pH sensitive, biospecific), Giant Magneto Resistance sensors, and spintronic devices. On the basis of studies with individual ion tracks we tackled tilted multiporous systems such as ion beam lithography with a masked ion beam leading to micro-structures with inclined walls and anisotropic superhydrophobic ion track textures, analogous to biological shingle structures on butterfly wings. We demonstrated qualitatively, that the asymmetry of the texture translates into motion under ultrasonic agitation. This could lead to the development of rotary drives.

In this thesis technical nonionic surfactants are studied using multivariate techniques. The surfactants studied were alkyl ethoxylates (AEOs) and alkyl polyglucosides (APGs). The aquatic toxicity of the surfactants towards two organisms, a shrimp and a rotifer, was examined. The specified effect was lethality, LC50, as indicated by immobilisation. In a comparative study, the LC50 values obtained were used to develop two different types of model. In the log P model the toxicity was correlated to log P alone, while in the multivariate model several physicochemical variables, including log P, were correlated to the toxicity. The multivariate model gave smaller prediction errors than the log P model. Further, the change in reactivity when a surfactant mixture was added to dissolving pulp under alkaline conditions was studied, using the amount of residual cellulose as a measure of the reactivity. Ten AEO/APG mixtures were tested, and the mixture with greatest potential was studied in more detail. An optimum in the amount of added surfactant was found that seems to coincide, according to surface tension measurements, with the CMC.

The aim of this thesis work is to study the physico-chemical properties of poly(ethylene oxide), PEO, based brush polymers both in solution and at solid/aqueous interfaces. The importance of studying the surface properties of brush polymers can be related to a broad spectrum of interfacial-related applications such as colloidal stability, lubrication, detergency, protein repellency to name a few. In many applications it is desirable to form brush-like structures through simple physisorption. In this context the surface properties of PEO based brush polymers differing in molecular architecture were studied, using ellipsometry and surface force apparatus (SFA), to gain some understanding regarding the effect of molecular architecture on the formation of brush structures. The molecular architecture was varied by varying the charge/PEO ratio along the backbone. This study demonstrates that the formation of a brush structure at solid/aqueous interface is due to interplay between the attraction of the backbone to the surface and the repulsions between the PEO side chains. An optimal balance between the two antagonistic factors is required if one aims to build a well-defined brush structure at the interface. In this study the brush-like structures are formed when 25-50% of the backbone segments carry poly(ethylene oxide) side chains. Scattering techniques such as light and neutron reveal that these brush polymers are stiff-rods up to a charge to PEO ratio of 75:25. These stiff PEO brush polymer easily replace the more flexible linear PEO at the silica/water interface, the reason being that the entropy loss on adsorption is smaller for the brush polymer due to its stiff nature.  Polymer-surfactant systems play a ubiquitous role in many technical formulations. It is well known that linear PEO, which adopts random coil conformation in aqueous solution, interact strongly with the anionic surfactant, Sodium Dodecyl Sulphate (SDS). It is of interest to study the interaction between SDS and brush PEO owing to the fact that the PEO side chains have limited flexibility as compared to the linear PEO.  The interaction between brush PEO and the anionic surfactant SDS in solution are studied using different techniques such as NMR, tensiometry, SANS and light scattering. The main finding of this study is that the interaction is weaker compared to the linear PEO-SDS interactions which poses an interesting question regarding the role of chain flexibility in polymer-surfactant interactions. / QC 20100813

The overall objective of this PhD thesis research is to understand and control phase separation in mixed perfluorinated fatty acid-phospholipid surfactant systems that have applications as pulmonary surfactant (PS) mixtures, with an ultimate view of controlling film composition, morphology and mechanical properties. In this context the interaction between perfluorooctadecanoic acid (C18F), 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), the major component of native PS extract, and 1,2-dipalmitoyl-sn-glycero-3-phosphoglycerol (DPPG) has been explored in Langmuir monolayers and Langmuir–Blodgett (LB) films using a combination of atomic force microscopy (AFM), fluorescence microscopy (FM) and Brewster angle microscopy (BAM) measurements. Thermodynamic and morphological studies of binary and ternary mixed films made of C18F, DPPC and DPPG indicated that both the phospholipids and C18F were miscible over a wide range of compositions. The mixed phospholipid-C18F films contained multimolecular aggregates that were highly enriched in the phospholipids. Furthermore, it was found that the magnitude of the DPPC-C18F interaction could be modulated by altering the concentration of sodium ions in the underlying subphase. Using a highly simplified lung mimic fluid (pH 7.4, 150mM NaCl), DPPC and C18F became fully immiscible. Moreover, the performance characteristics of the mixed films demonstrated the usefulness of C18F as an additive for PS formulations. The effectiveness of a PS protein mimicking peptide was evaluated against DPPC to allow comparison with previous measurements of DPPC-C18F mixed system. The mixing thermodynamics of the peptide and DPPC in Langmuir monolayer implied a repulsive interaction between the film components. The hysteresis response of the mixed monolayer films indicated that the lipid-protein mixture improved the re-spreading of DPPC films. Moreover, molecular-level organization of the mixed films explored by both FM and BAM confirmed the formation of liquid-expanded DPPC domains in the presence of minute amount of the peptide. In order to obtain a thorough understanding of the effect of the deposition process and surfactant tail polarities on the interfacial behavior of perfluorocarbon-hydrocarbon mixed monolayer films, both BAM and AFM measurements of arachidic acid (C20) with perfluorotetradecanoic acid (C14F) and palmitic acid (C16) with C18F mixed monolayer were performed. These measurements revealed that film morphology was minimally perturbed upon its deposition onto solid substrates. Coarse grained molecular dynamics (MD) simulations of films comprised of DPPC molecules with tails of various polarities suggested that the phase separation between the monolayer components could be controlled by varying surfactant tail polarities.