Contribution to the study of surface-active and membrane propreties of esters derived from glycine betaine

The objective of this doctoral research is to contribute to the study of surface active and membrane properties of esters derived from glycine betaine. In this context, esters of glycine betaine (alkylbétaïnate chlorides: CnBC, n = 10-16) were obtained using a new synthetic methodology. Glycine betaine (activated by thionyl chloride) and the primary fatty alcohols were used as basic raw materials for the chemical synthesis of CnBC. Some parameters to optimize the synthesis were studied, such as the nature of the organic solvent, the temperature, the molar ratio of reactants and the concentration of the latter in the reaction medium. Next, the surface active and membrane properties of CnBC were characterized using several instrumental techniques such as Langmuir film balance, isothermal titration calorimetry, fluorescence spectrometry and zeta potential and particle size measurements. Hexadécylbétaïnate chloride (C16BC) was synthesized with better performance under the following conditions: absence of a catalyst/base, a solvent of medium polarity (2-methyl-2-butanol), a temperature of 45°C, a molar ratio of betainyl chloride/1-hexadecanol of 3/1 and a concentration of reactants of 0.132 mol/L. Decylbetainate chloride (C10BC) dodecylbetainate chloride (C12BC) and tetradecylbetainate chloride (C14BC) were obtained using the optimal conditions for the synthesis of C16BC. Concerning the interfacial organization of CnBC, C10BC and C12BC did not form insoluble monolayers at the air-water at 20°C compared to their counterparts, C14BC and C16BC. The study of the monolayer of C16BC in various conditions of the aqueous subphase showed that the pH and monovalent anions (OHˉ, Brˉ, NO3ˉ, ClO4ˉ) did not influence the behavior of the monolayer compared to that in water with Clˉ as counterion while the temperature beyond 25°C, the divalent anions (HPO42-, SO42-) and the ionic strength of sodium sulfate (Na2SO4) affected it in term of interfacial area occupation of the molecules. Interactions between CnBC and model membranes have shown that in water, CnBC, regardless of the length of the alkyl chain, have highly penetreted into the negatively charged lipid monolayers (dipalmitoylphosphatidylserine and dipalmitoylphosphatidic acid), whereas their penetration was average and low into monolayers formed by lipids with small polar head (dipalmitoylphosphatidylethanolamine and cholesterol, CHOL) and lipid with large polar head (palmitoyloleoylphosphatidylcholine, POPC), respectively. In salted buffer, the adsorption of C16BC at the air-water interface and onto the surfaces of the lipid monolayers was instantaneous, and in all cases, the penetrating power was above the presumed pressure of biological membranes. C16BC formed miscible and stable mixtures with POPC and sphingomyelin while an almost ideal behavior was observed for its mixtures with CHOL. An affinity of C16BC for the membrane bilayer containing CHOL was also observed. The adsorption of CnBC onto the surfaces of bilayers was alkyl chain-dependent. C10BC, C14BC and C16BC did not significantly perturbed membranes even at high surfactant concnetrations compared to C12BC that has highly perturbed membranes without solubilizing them. In all cases, particles of positive charge and larger than those of membrane bilayers prepared were formed in the presence of high amounts of CnBC.L’objectif de cette recherche doctorale est de contribuer à l’étude de propriétés tensioactives et membranaires d’esters dérivés de la glycine bétaïne. Dans ce contexte, des esters de la glycine bétaïne (des chlorures d’alkylbétaïnate : CnBC, n = 10-16) ont été obtenus en utilisant une nouvelle méthodologie de synthèse. La glycine bétaïne (activée par le chlorure de thionyle) et les alcools gras primaires ont été utilisés comme matières premières de base pour la synthèse par voie chimique des CnBC. Quelques paramètres d’optimisation de la synthèse ont été étudiés, tels que la nature du solvant organique, la température, le rapport molaire de réactants et la concentration de ces derniers dans le milieu réactionnel. Ensuite, les propriétés tensioactives et membranaires des CnBC ont été caractérisées en utilisant quelques techniques instrumentales telles que la Balance à film de Langmuir, la Calorimétrie de Titration Isotherme, la Spectrométrie de fluorescence et les mesures du potentiel zêta et de la taille des particules. Le chlorure d’hexadécylbétaïnate (C16BC) a été synthétisé avec un meilleur rendement dans les conditions suivantes : absence de catalyseur/base, un solvant de polarité moyenne (le méthyl-2-butanol-2), une température de 45°C, un rapport molaire dichlorure de bétaïnyle/1-hexadecanol de 3/1 et une concentration en réactants de 0,132 mol/L. Le chlorure de décylbétaïnate (C10BC), le chlorure de dodécylbétaïnate (C12BC) et le chlorure de tétradécylbétaînate (C14BC) ont été obtenus en utilisant les conditions optimales de synthèse de C16BC. Concernant l’organisation interfaciale des CnBC, le C10BC et le C12BC n’ont pas formé de monocouches insolubles à l’interface air-eau à 20°C comparativement à leurs homologues, le C14BC et le C16BC. L’étude de la monocouche de C16BC dans les conditions variées de la sous-phase aqueuse a montré que le pH et les anions monovalents (OHˉ, Brˉ, NO3ˉ, ClO4ˉ) n’ont pas influencé le comportement de la monocouche comparativement à celle dans l’eau avec le Clˉ comme contre-ion tandis que la température au-delà de 25°C, les anions divalents (HPO42-, SO42-) ainsi que la force ionique du sulfate de sodium (Na2SO4) l’ont influencé en ce qui concerne l’aire d’occupation des molécules à l’interface. Les interactions entre les CnBC et les membranes modèles ont montré que dans l’eau, les CnBC, indépendamment de la longueur de la chaîne alkyle, ont fortement pénétré dans les monocouches formées de lipides chargés négativement (dipalmitoylphosphatidylsérine et acide dipalmitoylphosphatidique) tandis que leur pénétration a été moyenne et faible dans les monocouches formées de lipides avec tête polaire petite (dipalmitoylphosphatidyléthanolamine et cholestérol, CHOL) et de lipide avec tête polaire volumineuse (palmitoyloleoylphosphatidylcholine, POPC), respectivement. Dans le tampon salin, l’adsorption de C16BC à l’interface air-eau et sur les surfaces des monocouches lipidiques a été instantanée, et dans tous les cas, son pouvoir pénétrant a été au dessus de la pression présumée des membranes biologiques. Le C16BC a formé des mélanges miscibles et stables avec le POPC et la sphingomyéline tandis qu’un comportement presque idéal a été observé pour ses mélanges avec le CHOL. Une affinité du C16BC pour la membrane bicouche contenant le CHOL a été également observée. L’adsorption des CnBC sur les surfaces des bicouches a été fonction de la longueur de la chaîne alkyle. Le C10BC, le C14BC et le C16BC n’ont pas significativement perturbé les membranes même à des concentrations élevées en TA comparativement au C12BC qui les a fortement perturbées sans pour autant les solubiliser. Dans tous les cas, des particules de charge positive et de taille supérieure à celle des membranes bicouches préparées ont été formées en présence de quantités élevées des CnBC.Université de liège/Gembloux Agro-Bio Tec

Synthèses et propriétés physicochimiques de dérivés de la glycine betaine

audience: researcher, professional, student, popularizationDesign of new surfactants is of considerable interest in order to obtain materials with specific physico-chemical properties for targeted applications. Among them, quaternary ammonium surfactants are widely employed in pharmaceutical and cosmetic industries. Unfortunately, as a consequence of their widespread use and strong resistance to biodegradation, those chemical surfactants may persist in wastewater treatment systems at relatively high concentrations and can cause a disturbance of the ecological equilibrium. In this context, glycine betaine based surfactants are of increasing interest today thanks to their higher biodegradability and low environmental impact. For example, alkylbetaines and alkylamidobetaines are produced on the industrial scale and are used as amphoteric surfactants less irritating compared to sodium dodecylsulfate (SDS) in cosmetics. In this study, new surface-active agents based on glycine betaine and issued from the green chemistry are synthesized. Very simple synthetic methodologies led to different betaine derivatives (esters, thioesters, amides). Their physico-chemical properties are investigated in order to give insights about the key parameters to take into account for the formulation of betaine derived compound preparations for cosmetic or pharmaceutical purposes.Projet Technos

Alkylbetainate chlorides: Synthesis and behavior of monolayers at the air-water interface

In this study, cationic alkylbetainate chloride surfactants (CnBC, n = 10–16) are synthesized using more environment-friendly reagents (glycine betaine, thionyl chloride and primary alcohols) than in previous works (chloroacetyl chloride, trimethylamine and primary alcohols). The interfacial behavior of the CnBC monolayers is studied onto aqueous subphases at 20 °C using the Langmuir through technique. Different experimental conditions including pH, temperature, sodium salts and Na2SO4 ionic strength are investigated. The results obtained have shown that the CnBC with a hydrocarbon chain length ≥ 14 are able to form insoluble monolayers. The C16BC monolayer stability checked by the compression–expansion cycles has shown a superimposition of isotherms in the whole liquid-condensed region and an irreversible rearrangement of the molecules at high compression. The C16BC monolayer is not influenced by the pH and the presence of monovalent anions but it is influenced by the temperature, the divalent anions and the ionic strength. It has exhibited a great stability whatever the experimental conditions

Penetration behaviour of alkylbetainate chlorides into lipid monolayers

peer reviewe

Larvicidal Activity of Inorganic Salts Against Anopheles Stephensi and Culex Quinquefasciatus

Mosquitoes transmit serious human diseases, causing millions of deaths worldwide every year and the development of resistance to chemical insecticides resulting in rebounding vectorial capacity. In this study, the larvicidal bioassays for activities of aqueous solutions of weak acid [(NH4)2SO4 and NaH2PO4] and weak base (Na2CO3 and NaHCO3) inorganic salts against late instar larvae of disease vectors Anopheles stephensi and Culex quinquefasciatus were carried out under laboratory settings. The four inorganic salts showed varied levels of larvicidal activities after 24 h-exposure on Anopheles stephensi and Culex quinquefasciatus larvae in a dose-dependent fashion. However, the larvicidal activities were relatively higher in Na2CO3 (LC50 = 3162 and 447 ppm) and NaHCO3 (LC50 = 5623 and 398 ppm) solutions as compared to those in (NH4)2SO4 (LC50 = 7943 and 1995 ppm) and NaH2PO4 (LC50 = 7943 and 7120 ppm). The present study showed that the inorganic salts Na2CO3, NaHCO3, (NH4)2SO4 and NaH2PO4 could serve as potential larviciding agents considering their low toxicity. Therefore, this study provides a first report on the larvicidal activity of the inorganic salts on mosquito larvae of disease vectors

Adherence of staphylococcus aureus to catheter tubing inhibition by quaternary ammonium compounds

Introduction: S. aureus is a Gram positive bacterium which is responsible for a wide range of infections. This pathogen has also the ability to adhere to biotic or abiotic surface such as central venous catheter (CVC) and to produce a biofilm. The aim of this study was to evaluate the effect of hexadecyltrimethyl ammonium bromide (HTAB) and Hexadecylbetainate chloride (HBC) on Staphylococcus aureus adherence to the catheter tubing and on bacteria growth. Methods: broth microdilution method was used to determine the Minimal Inhibitory Concentration (MIC). The detection of slime production was done by Congo Red Agar method, and the adherence of bacteria to the catheter tubing was evaluated by the enumeration of bacteria on plate counts. Results: the results of this study showed that the MICs of HTAB were ranged from 0.125 to 0.5 µg/mL, and those of HBC fluctuated between 2 to 8 µg/mL. HTAB and HBC inhibited bacteria adhesion on the surface of the catheter tubing. Conclusion: this study showed that HTAB and HBC can prevent the adherence of S. aureus strains to the surface of catheter tubing, suggesting that they could be used to prevent the risk of catheter related bloodstream infections. The Pan African Medical Journal 2016;2