Mediating gel formation from structurally controlled poly(electrolytes) through multiple "head-to-body" electrostatic interactions

Tuning the chain-end functionality of a short-chain cationic homopolymer, owing to the nature of the initiator used in the ATRP polymerisation step, can be used to mediate the formation of a gel of this poly(electrolyte) in water. While a neutral end group gives a solution of low viscosity, a highly homogeneous gel is obtained with a phosphonate anionic moiety, as characterized by rheometry and diffusion NMR. This novel type of supramolecular control over poly(electrolytic) gel formation could find potential use in a variety of applications in the field of electroactive materials

Study of Supramolecular Interactions between Lanthanide Complexes and Amino Acids : Application in Protein Crystallography

Ces travaux de thèse présentent les différentes approches explorées dans le but de développer une méthode d’étude du mode d’interaction en solution entre un complexe de lanthanide de type tris-dipicolinate [Ln(DPA)3]3- et des protéines. La principale méthode développée avec succès est basée sur la mesure de diffusion par RMN de ces systèmes, qui mettent en jeu des lanthanides paramagnétiques. Après une étape d’optimisation sur un système simple diamagnétique, l’influence du paramagnétisme a été évaluée. Il apparait qu’un temps de relaxation T1 raccourci n’empêche pas systématiquement la mesure d’un coefficient de diffusion, et qu’il est donc possible de combiner les atouts de la RMN paramagnétique et ceux des mesures de diffusion pour caractériser finement l’interaction supramoléculaire impliquant un système paramagnétique. La méthode de mesure de diffusion montre ainsi son intérêt comme première étape d’une étude complète par RMN et Modélisation Moléculaire de systèmes biologiques. Cette méthode permet de caractériser une interaction supramoléculaire entre un complexe de lanthanide paramagnétique et différents partenaires en solution (petite molécule, peptide intrinsèquement désordonné ou protéine). Elle est applicable même dans le cas d’une interaction faible ou d’un système très dynamique. En outre, le potentiel analytique du paramagnétisme du complexe peut être exploité, et les expériences de RMN paramagnétique apportent ainsi des informations supplémentaires sur le détail de l’interaction. Le complexe [Ln(DPA)3]3-, qui est utilisé pour la détermination de structures cristallines, permet ainsi de comparer les structures d’un système protéine/complexe à l’état solide (cristal) et en solution. La méthodologie RMN décrite dans cette thèse a été ensuite utilisée pour caractériser divers systèmes supramoléculaires au laboratoire. Une étude combinant mesure de diffusion, RMN paramagnétique et Modélisation Moléculaire illustre l’intérêt de cette méthode pour un système impliquant encore une fois un complexe de lanthanide paramagnétique.This PhD work presents the different approaches I have explored in order to develop a method to study in solution the interaction mode between a tris-dipicolinate lanthanide complex [Ln(DPA)3]3- and proteins. The main method successfully developed is based on NMR diffusion measurements of these systems with the use of paramagnetic lanthanides. After an optimization step on a simple diamagnetic system, the influence of the paramagnetism was evaluated. It appeared that a shortened relaxation time T1 did not systematically prevent the measurement of a diffusion coefficient, and that it was thus possible to combine the advantages of paramagnetic NMR and diffusion measurements to finely characterize a supramolecular interaction involving a paramagnetic system. The diffusion measurement method seems interesting as the first step of a complete NMR and Molecular Modeling study of biological systems. This method allows to characterize a supramolecular interaction between a paramagnetic lanthanide complex and its different partners in solution (small molecule, intrinsically disordered peptide or protein). It is applicable even in the case of a weak interaction or a very dynamic system. Furthermore, the analytical potential of the paramagnetism of the complex can be exploited, and paramagnetic NMR experiments provide additional information on the details of the interaction. The [Ln(DPA)3]3- complex, which is used for crystal structure determination, thus allows comparison of the structures of a protein/complex system in the solid state (crystal) and in solution. The NMR method developed in this work was then successfully used to characterize various supramolecular systems in the laboratory. A study combining diffusion measurements, paramagnetic NMR and Molecular Modeling illustrates the interest of this method with a system involving once again a paramagnetic lanthanide complex

Etude des interactions supramoléculaires entre complexes de lanthanides et acides aminés : application en cristallographie des protéines

This PhD work presents the different approaches I have explored in order to develop a method to study in solution the interaction mode between a tris-dipicolinate lanthanide complex [Ln(DPA)3]3- and proteins. The main method successfully developed is based on NMR diffusion measurements of these systems with the use of paramagnetic lanthanides. After an optimization step on a simple diamagnetic system, the influence of the paramagnetism was evaluated. It appeared that a shortened relaxation time T1 did not systematically prevent the measurement of a diffusion coefficient, and that it was thus possible to combine the advantages of paramagnetic NMR and diffusion measurements to finely characterize a supramolecular interaction involving a paramagnetic system. The diffusion measurement method seems interesting as the first step of a complete NMR and Molecular Modeling study of biological systems. This method allows to characterize a supramolecular interaction between a paramagnetic lanthanide complex and its different partners in solution (small molecule, intrinsically disordered peptide or protein). It is applicable even in the case of a weak interaction or a very dynamic system. Furthermore, the analytical potential of the paramagnetism of the complex can be exploited, and paramagnetic NMR experiments provide additional information on the details of the interaction. The [Ln(DPA)3]3- complex, which is used for crystal structure determination, thus allows comparison of the structures of a protein/complex system in the solid state (crystal) and in solution. The NMR method developed in this work was then successfully used to characterize various supramolecular systems in the laboratory. A study combining diffusion measurements, paramagnetic NMR and Molecular Modeling illustrates the interest of this method with a system involving once again a paramagnetic lanthanide complex.Ces travaux de thèse présentent les différentes approches explorées dans le but de développer une méthode d’étude du mode d’interaction en solution entre un complexe de lanthanide de type tris-dipicolinate [Ln(DPA)3]3- et des protéines. La principale méthode développée avec succès est basée sur la mesure de diffusion par RMN de ces systèmes, qui mettent en jeu des lanthanides paramagnétiques. Après une étape d’optimisation sur un système simple diamagnétique, l’influence du paramagnétisme a été évaluée. Il apparait qu’un temps de relaxation T1 raccourci n’empêche pas systématiquement la mesure d’un coefficient de diffusion, et qu’il est donc possible de combiner les atouts de la RMN paramagnétique et ceux des mesures de diffusion pour caractériser finement l’interaction supramoléculaire impliquant un système paramagnétique. La méthode de mesure de diffusion montre ainsi son intérêt comme première étape d’une étude complète par RMN et Modélisation Moléculaire de systèmes biologiques. Cette méthode permet de caractériser une interaction supramoléculaire entre un complexe de lanthanide paramagnétique et différents partenaires en solution (petite molécule, peptide intrinsèquement désordonné ou protéine). Elle est applicable même dans le cas d’une interaction faible ou d’un système très dynamique. En outre, le potentiel analytique du paramagnétisme du complexe peut être exploité, et les expériences de RMN paramagnétique apportent ainsi des informations supplémentaires sur le détail de l’interaction. Le complexe [Ln(DPA)3]3-, qui est utilisé pour la détermination de structures cristallines, permet ainsi de comparer les structures d’un système protéine/complexe à l’état solide (cristal) et en solution. La méthodologie RMN décrite dans cette thèse a été ensuite utilisée pour caractériser divers systèmes supramoléculaires au laboratoire. Une étude combinant mesure de diffusion, RMN paramagnétique et Modélisation Moléculaire illustre l’intérêt de cette méthode pour un système impliquant encore une fois un complexe de lanthanide paramagnétique

Etude des interactions supramoléculaires entre complexes de lanthanides et acides aminés : application en cristallographie des protéines

This PhD work presents the different approaches I have explored in order to develop a method to study in solution the interaction mode between a tris-dipicolinate lanthanide complex [Ln(DPA)3]3- and proteins. The main method successfully developed is based on NMR diffusion measurements of these systems with the use of paramagnetic lanthanides. After an optimization step on a simple diamagnetic system, the influence of the paramagnetism was evaluated. It appeared that a shortened relaxation time T1 did not systematically prevent the measurement of a diffusion coefficient, and that it was thus possible to combine the advantages of paramagnetic NMR and diffusion measurements to finely characterize a supramolecular interaction involving a paramagnetic system. The diffusion measurement method seems interesting as the first step of a complete NMR and Molecular Modeling study of biological systems. This method allows to characterize a supramolecular interaction between a paramagnetic lanthanide complex and its different partners in solution (small molecule, intrinsically disordered peptide or protein). It is applicable even in the case of a weak interaction or a very dynamic system. Furthermore, the analytical potential of the paramagnetism of the complex can be exploited, and paramagnetic NMR experiments provide additional information on the details of the interaction. The [Ln(DPA)3]3- complex, which is used for crystal structure determination, thus allows comparison of the structures of a protein/complex system in the solid state (crystal) and in solution. The NMR method developed in this work was then successfully used to characterize various supramolecular systems in the laboratory. A study combining diffusion measurements, paramagnetic NMR and Molecular Modeling illustrates the interest of this method with a system involving once again a paramagnetic lanthanide complex.Ces travaux de thèse présentent les différentes approches explorées dans le but de développer une méthode d’étude du mode d’interaction en solution entre un complexe de lanthanide de type tris-dipicolinate [Ln(DPA)3]3- et des protéines. La principale méthode développée avec succès est basée sur la mesure de diffusion par RMN de ces systèmes, qui mettent en jeu des lanthanides paramagnétiques. Après une étape d’optimisation sur un système simple diamagnétique, l’influence du paramagnétisme a été évaluée. Il apparait qu’un temps de relaxation T1 raccourci n’empêche pas systématiquement la mesure d’un coefficient de diffusion, et qu’il est donc possible de combiner les atouts de la RMN paramagnétique et ceux des mesures de diffusion pour caractériser finement l’interaction supramoléculaire impliquant un système paramagnétique. La méthode de mesure de diffusion montre ainsi son intérêt comme première étape d’une étude complète par RMN et Modélisation Moléculaire de systèmes biologiques. Cette méthode permet de caractériser une interaction supramoléculaire entre un complexe de lanthanide paramagnétique et différents partenaires en solution (petite molécule, peptide intrinsèquement désordonné ou protéine). Elle est applicable même dans le cas d’une interaction faible ou d’un système très dynamique. En outre, le potentiel analytique du paramagnétisme du complexe peut être exploité, et les expériences de RMN paramagnétique apportent ainsi des informations supplémentaires sur le détail de l’interaction. Le complexe [Ln(DPA)3]3-, qui est utilisé pour la détermination de structures cristallines, permet ainsi de comparer les structures d’un système protéine/complexe à l’état solide (cristal) et en solution. La méthodologie RMN décrite dans cette thèse a été ensuite utilisée pour caractériser divers systèmes supramoléculaires au laboratoire. Une étude combinant mesure de diffusion, RMN paramagnétique et Modélisation Moléculaire illustre l’intérêt de cette méthode pour un système impliquant encore une fois un complexe de lanthanide paramagnétique

The absence of surface D-alanylation, localized on lipoteichoic acid, impacts the Clostridioides difficile way of life and antibiotic resistance

D-alanylation of surface polysaccharides reduces the affinity and efficacy of cationic antimicrobial compounds (CAMPs) on the bacterial surface. In C. difficile (CD), the localization of D-alanylation is unknown and its implication in antibiotic resistance is not elucidated. The aim of our study is to determine the site of D-alanylation in CD and investigate its role in antibiotic susceptibility.A Δdlt mutant was first constructed. The two major CD polysaccharides, type II polysaccharide (PSII) and lipoteichoic acid (LTA) from the Δdlt mutant and its parental strain were purified. NMR analysis of the polysaccharides revealed the presence of D-alanine on the LTA of the parental strain, but not on the LTA of the Δdlt mutant. In addition, no D-alanine function was identified on purified PSII. Our results therefore highlight the exclusive D-alanylation of LTA in CD. The Δdlt mutant has multiple phenotypes, including greater surface hydrophobicity, increased motility, decreased adherence and increased biofilm formation than the parental strain. In addition, antibiotic susceptibility tests have noteworthy shown increased sensitivity of the Δdlt mutant to bacitracin, teicoplanin and daptomycin. The Dlt1 inhibitor, targeting DltA and already described in Staphylococcus aureus and Enterrococci, was also tested in CD. Our results support the interest in D-alanylation as a potential therapeutic target in the treatment of CD infections

Mild and efficient bromination of poly(hydroxyethyl acrylate) and its use towards ionic-liquid containing polymers

International audienceAn original and mild bromination protocol allows a poly(hydroxyethyl acrylate) polymer synthesized by ATRP to be converted readily and quantitatively into its corresponding poly(bromoethyl acrylate) analogue. We show that the latter can be used as a common precursor towards ionic-liquid containing polymer

Redox-responsive 1D-assembly built from cucurbit[8]uril and a water-soluble metalloporphyrin-based tecton

International audienceA linear porphyrin-based tecton bearing two 4,4[Formula: see text]bipyridinium units (viologens) and two monomethyl-ether triethylene glycol-substituted phenyl substituents at the meso positions was synthesized and characterized. The latter was involved in the redox-triggered formation of linear supramolecular assemblies with cucurbit[8]uril (CB[8]) cavitands in aqueous media. The CB[8]-promoted intermolecular [Formula: see text]-dimerization of the viologen cation radicals introduced at the meso positions of the porphyrin platform has been brought to light through the diagnostic signatures of the 1:2 host-guest ternary caviplexes formed between viologen and CB[8] and by spectroscopic data collected after electrochemical reduction of the viologen-based tectons

Ionic Liquids Can Enable the Recycling of Fluorinated Greenhouse Gases

International audienceRecycling fluorinated gases that have high global warming potential is crucial for a sustainable and responsible use of mobile air conditioners. In this context, five ionic liquids with different hydrogenated or fluorinated alkyl chains in the ions were designed to improve the absorption of the refrigerant 1,1,1,2-tetrafluoroethane, commonly known as R134a. R134a is one of the most used refrigerant gases, and its global warming potential is several orders of magnitude higher than that of carbon dioxide. Gas solubility was measured between 303 and 343 K up to 3.5 bar and follows the order [C2C1Im][NTf2] < [C8C1Im][NTf2] < [C8C1Im][BETI] < [C8H4F13C1Im][NTf2] < [C8H4F13C1Im][BETI]. The R134a solubility increases in ionic liquids having fluorinated moieties in the ions, a behavior that could be linked to a more favorable entropy of solvation. R134a absorption is always selective toward atmospheric gases like nitrogen, ionic liquids with fluorinated moieties being more selective to separate R134a from ethane (C2H6) while their hydrogenated counterparts are more suited to separate R134a from perfluoroethane (C2F6). Overall, this study provides a comprehensive perspective on how the fluorination of ionic liquids can be explored to selectively recycle fluorinated greenhouse gases

Towards Electron-triggered Coordination-induced Spin State Switching in Viologen-based Metal Complexes

National audienceThe control of magnetic properties by external stimuli has attracted much interest over the past few decades and tremendous work has been achieved thereafter. 1 Our contribution to this field is based on the Coordination-induced Spin State Switching approach (CiSSS) 2 which, as its name implies, aims at changing the spin state of a metal center by modifying its coordination sphere. Therefore, based on our expertise in supramolecular chemistry and with the help of theoretical calculations, a well-suited model system was designed and eventually synthesized. In this presentation, the targeted tweezer-like molecule features a redox-responsive viologen-based hinge tethering a high affinity ligand to a magnetically active metal center. In agreement with the concept depicted below, the electrical stimulation of the hinge is expected to trigger a large amplitude molecular motion driven by the reversible, intramolecular π-dimerization of the electrochemically-generated viologen cation radicals. 3,4 This fully reversible back and forth self-locking process will enable to control the coordination/dissociation of the ligand to/from the metal center and, consequently, its spin state. The spin-state switching process will be discussed on the grounds of spectroscopic, electrochemical and spectro-electrochemical data supported by quantum calculations. Figure 1: Electron-triggered self-locking behaviour for reversible CiSSS

Towards Electron-triggered Coordination-induced Spin State Switching in Viologen-based Metal Complexes

International audienceThe control of magnetic properties by external stimuli has attracted much interest over the past few decades and tremendous work has been achieved thereafter.1 Our contribution to this field is based on the Coordination-induced Spin State Switching approach (CiSSS)2 which, as its name implies, aims at changing the spin state of a metal center by modifying its coordination sphere. Therefore, based on our expertise in supramolecular chemistry and with the help of theoretical calculations, a wellsuited model system was designed and eventually synthesized. In this presentation, the targeted tweezer-like molecule features a redox-responsive viologen-based hinge tethering a high affinity ligand to a magnetically active metal center. In agreement with the concept depicted below, the electrical stimulation of the hinge is expected to trigger a large amplitude molecular motion driven by the reversible, intramolecular π-dimerization of the electrochemically-generated viologen cation radicals.3,4 This fully reversible back and forth self-locking process will enable to control the coordination/dissociation of the ligand to/from the metal center and, consequently, its spin state. The spin-state switching process will be discussed on the grounds of spectroscopic, electrochemical and spectro-electrochemical data supported by quantum calculations.References:[1] O. Sato et al, Angew. Chem. Int. Ed. 2007, 46, 2152-2187.[2] B. Doistau et al, Magnetochemistry, 2018, 4, 5-20.[3] C. Kahlfuss et al, J. Am. Chem. Soc. 2016, 138, 15234-15242.[4] C. Kahlfuss et al, Chem. Eur. J. 2018, 24, 13009-13019