Non-polar semifluorinated amphiphiles,synthesis-nanostructuration in 2D and 3D

Ce travail de thèse s'inscrit dans le domaine des molécules amphiphiles semi-fluorées et s'étend de la synthèse de nouvelles architectures à l'investigation de leurs propriétés d'auto-assemblage à 2D et à 3D. Il s'articule principalement autour de l'élaboration et de l'étude de films fins obtenus par auto-assemblage d'amphiphiles semi-fluorés, avec pour objectif de créer des surfaces décorées par des nanodomaines de tailles et formes contrôlées. La première partie de ce travail analyse la compression de nano-objets auto-assemblés constitués de diblocs FnHm(F(CF2)n(CH2)mH), conduisant à la formation de films composites à plusieurs niveaux de structuration à l'échelle nanométrique (développement d'une bicouche (F8H20) ou d'inflorescences (Fl0H16) au dessus du tapis de micelles). La deuxième partie est consacrée à la synthèse et à l'étude du comportement d'une nouvelle famille de tétrablocs semi-fluorés (CnF2n+1CH2)(Cm-2H2m3)CH-CH(CnF2n+1CH2)(Cm-2H2m-3), di(FnHm) . Ils présentent une transition réversible du 1er ordre avant la fusion entre une phase modulée ruban et une phase lamellaire de type hexatique B. L'imagerie de la surface (à l'échelle du nanomètre par AFM), sur films transférés (ou obtenus par spin-coating) révèle qu'ils s'auto-assemblent en micelles de surface dont la compression engendre la formation d'une seconde couche superposée, elle-même composée de micelles de surface. Dans une dernière partie, une nouvelle famille d'amphiphiles triaffines FnHmEOx (Fn = CnF2n+1;Hm = CmH2m+1;EOx = CH3(OC2H4)xO) récemment synthétisée au sein de l'équipe, a fait l'objet d'une étude de leur aptitude à la nanostructuration à l'interface eau/air (2D) et dans l'eau (3D).This work deals with semifluorinated amphiphiles, from the synthesis of new architectures to the investigation of their self-assembly in 2D and 3D. It is principally based on the elaboration and study of thin films obtained by self-assembly of semifluorinated alkanes in order to create surfaces decorated with nanodomains weIl defined in size and shape. The first part of this work analyses the compression of self assembled nanometric objects constituted by FnHm diblocks (F(CF2)n(CH2)mH), leading to hitherto unknown organized nanometric composite arrangements (bilayer (FBH20) or crystalline like-inflorescences (Fl0H16) in coexistence with the initial monolayer of micelles). The second part is dedicated to the synthesis and the study of the behavior of a new familly of semifluorinated tetrablocks, di(FnHm) (CnF2n+1CH2)(Cm-2H2m-3)CH-CH(CnF2n+1CH2)(Cm-2H2m-3).They present a reversible first order transition before melting, between a modulated smectic phase and a lamellar hexatic B arrangement. As assessed by AFM, transferred or spin-coated films consist of two sublayers of dis crete surface micelles. In the last part, the nanostructuration at the air /water interface and in water of a new triaffine architecture FnHmEOx (Fn = CnF2n+1;Hm = CmH2m+1;EOx= CH3(OC2H4)xO) was investigated

Non-polar semifluorinated amphiphiles,synthesis-nanostructuration in 2D and 3D

Ce travail de thèse s'inscrit dans le domaine des molécules amphiphiles semi-fluorées et s'étend de la synthèse de nouvelles architectures à l'investigation de leurs propriétés d'auto-assemblage à 2D et à 3D. Il s'articule principalement autour de l'élaboThis work deals with semifluorinated amphiphiles, from the synthesis of new architectures to the investigation of their self-assembly in 2D and 3D. It is principally based on the elaboration and study of thin films obtained by self-assembly of semifluori

Amphiphiles semi-fluorés non-polaires (Synthèse-nanostructuration d espaces à 2D et 3D)

Ce travail de thèse s'inscrit dans le domaine des molécules amphiphiles semi-fluorées et s'étend de la synthèse de nouvelles architectures à l'investigation de leurs propriétés d'auto-assemblage à 2D et à 3D. Il s'articule principalement autour de l'élaboration et de l'étude de films fins obtenus par auto-assemblage d'amphiphiles semi-fluorés, avec pour objectif de créer des surfaces décorées par des nanodomaines de tailles et formes contrôlées. La première partie de ce travail analyse la compression de nano-objets auto-assemblés constitués de diblocs FnHm(F(CF2)n(CH2)mH), conduisant à la formation de films composites à plusieurs niveaux de structuration à l'échelle nanométrique (développement d'une bicouche (F8H20) ou d'inflorescences (Fl0H16) au dessus du tapis de micelles). La deuxième partie est consacrée à la synthèse et à l'étude du comportement d'une nouvelle famille de tétrablocs semi-fluorés (CnF2n+1CH2)(Cm-2H2m3)CH-CH(CnF2n+1CH2)(Cm-2H2m-3), di(FnHm) . Ils présentent une transition réversible du 1er ordre avant la fusion entre une phase modulée ruban et une phase lamellaire de type hexatique B. L'imagerie de la surface (à l'échelle du nanomètre par AFM), sur films transférés (ou obtenus par spin-coating) révèle qu'ils s'auto-assemblent en micelles de surface dont la compression engendre la formation d'une seconde couche superposée, elle-même composée de micelles de surface. Dans une dernière partie, une nouvelle famille d'amphiphiles triaffines FnHmEOx (Fn = CnF2n+1;Hm = CmH2m+1;EOx = CH3(OC2H4)xO) récemment synthétisée au sein de l'équipe, a fait l'objet d'une étude de leur aptitude à la nanostructuration à l'interface eau/air (2D) et dans l'eau (3D).This work deals with semifluorinated amphiphiles, from the synthesis of new architectures to the investigation of their self-assembly in 2D and 3D. It is principally based on the elaboration and study of thin films obtained by self-assembly of semifluorinated alkanes in order to create surfaces decorated with nanodomains weIl defined in size and shape. The first part of this work analyses the compression of self assembled nanometric objects constituted by FnHm diblocks (F(CF2)n(CH2)mH), leading to hitherto unknown organized nanometric composite arrangements (bilayer (FBH20) or crystalline like-inflorescences (Fl0H16) in coexistence with the initial monolayer of micelles). The second part is dedicated to the synthesis and the study of the behavior of a new familly of semifluorinated tetrablocks, di(FnHm) (CnF2n+1CH2)(Cm-2H2m-3)CH-CH(CnF2n+1CH2)(Cm-2H2m-3).They present a reversible first order transition before melting, between a modulated smectic phase and a lamellar hexatic B arrangement. As assessed by AFM, transferred or spin-coated films consist of two sublayers of dis crete surface micelles. In the last part, the nanostructuration at the air /water interface and in water of a new triaffine architecture FnHmEOx (Fn = CnF2n+1;Hm = CmH2m+1;EOx= CH3(OC2H4)xO) was investigated.STRASBOURG-Sc. et Techniques (674822102) / SudocSudocFranceF

Thermal Behavior and High- and Low-Temperature Phase Structures of Gemini Fluorocarbon/Hydrocarbon Diblocks

The thermal behavior and phase structure of two series of gemini fluorocarbon/hydrocarbon diblock amphiphiles with the general formula (C_<i>n</i>F_2<i>n</i>+1CH₂)­(C_{<i>m</i> – 2}H_{2<i>m</i> – 3})­CH–CH­(C_<i>n</i>F_2<i>n</i>+1CH₂)­(C_{<i>m</i> – 2}H_{2<i>m</i> – 3}), with <i>n</i> = 8, 10 and <i>m</i> = 6, 12, 14, 16, 18, 20 (abbreviated as di­(<i>FnHm</i>)), have been investigated by differential scanning calorimetry, polarized optical and freeze–fracture transmission electron microscopies, dilatometry, and small-angle X-ray scattering (SAXS). The various terms of the series exhibit the same thermal behavior, essentially composed of two exothermal transitions, a low-temperature event that corresponds to the melting of the hydrocarbon chains at <i>T</i>_H and a high-temperature transition associated with the melting of the fluorocarbon chains at <i>T</i>_F. Below <i>T</i>_H, a disordered plastic rotator phase, M_LT, and above <i>T</i>_H, a lamellar phase, M_HT, were determined by SAXS experiments. Above <i>T</i>_F, the compounds eventually clear into the isotropic liquid. In the M_HT phase, both the <i>Fn</i> and <i>Hm</i> blocks are segregated from each other, forming sublayers with sharp interfaces, as revealed by the five lamellar orders and remarkable sharpness of the SAXS peaks. In the M_LT phase, the partial crystallization of the aliphatic blocks when the temperature is lowered leads to the disruption of the aliphatic sublayers into rows of ribbons arranged according to pseudohexagonal and/or rectangular arrangements with different lattice sizes (<i>p</i>2<i>gg</i> symmetry). The <i>Fn</i> segments form the fluorinated continuum. In support of SAXS, molecular packing models of the tetrablocks are proposed on the basis of the temperature/volume variations of di­(<i>F</i>10<i>H</i>20) and di­(<i>F</i>10<i>H</i>16) in both high- and low-temperature phases, as determined by dilatometry. It is notable that the arrangements found for di­(<i>FnHm</i>) are completely different from those previously reported for <i>FnHm</i> diblocks, revealing the influence of the linker unit on the solid-state behavior of the tetrablocks

Stacking of Self-Assembled Surface Micelles in Ultrathin Films

Nonpolar fluorophilic/lipophilic tetrablock amphiphiles are investigated on the surface of water and on solid substrates using compression isotherms, Brewster angle microscopy, and atomic force microscopy. At low pressures, the tetrablocks form monolayers of closely packed surface hemimicelles. Further compression causes a 2D/3D transition. At the end of the plateau, half of the deposited material is expelled forming a second monolayer on top of the initially formed monolayer. Both layers of the films consist of surface micelles, thus providing the first example of spontaneous or compression-driven stacking of self-assembled nano-objects

Collective Activation of MRI Agents via Encapsulation and Disease-Triggered Release

An activation mechanism based on encapsulated ultrasmall gadolinium oxide nanoparticles (Gd oxide NPs) in bioresponsive polymer capsules capable of triggered release in response to chemical markers of disease (i.e., acidic pH, H₂O₂) is presented. Inside the hydrophobic polymeric matrices, the Gd oxide NPs are shielded from the aqueous environment, silencing their ability to enhance water proton relaxation. Upon disassembly of the polymeric particles, activation of multiple contrast agents generates a strong positive contrast enhancement of >1 order of magnitude

Short Soluble Coumarin Crosslinkers for Light-Controlled Release of Cells and Proteins from Hydrogels

Materials that degrade or dissociate in response to low power light promise to enable on-demand, precisely localized delivery of drugs or bioactive molecules in living systems. Such applications remain elusive because few materials respond to wavelengths that appreciably penetrate tissues. The photocage bromohydroxycoumarin (Bhc) is efficiently cleaved upon low-power ultraviolet (UV) and near-infrared (NIR) irradiation through one- or two-photon excitation, respectively. We have designed and synthesized a short Bhc-bearing crosslinker to create light-degradable hydrogels and nanogels. Our crosslinker breaks by intramolecular cyclization in a manner inspired by the naturally occurring ornithine lactamization, in response to UV and NIR light, enabling rapid degradation of polyacrylamide gels and release of small hydrophilic payloads such as an ∼10 nm model protein and murine mesenchymal stem cells, with no background leakage

Single UV or Near IR Triggering Event Leads to Polymer Degradation into Small Molecules

We report two polymers with UV- and NIR-removable end-caps that respond to a single light activated event by complete cleavage of the polymer backbone via a self-immolative mechanism. Two photocleavable protecting groups were used to cap the polymers; <i>o</i>-nitrobenzyl alcohol (ONB) and bromo-coumarin (Bhc). GPC and ¹H NMR confirmed complete degradation of the ONB-containing polymer in response to UV. The polymers were formulated into nanoparticles; fluorescence measurements of encapsulated Nile red confirmed release upon photolysis of the end-caps. Contrary to previous work using a similar backbone structure that degrades upon hydrolysis, here, the disassembly process and burst release of the payload are only activated on demand, illustrating the powerful capacity of light to trigger release from polymeric nanoparticles. Our design allows the signal to be amplified in a domino effect to fully degrade the polymer into small molecules. Thus, polymers and nanoparticles can reach maximal degradation without having to use intense or long periods of irradiation

Near-Infrared-Induced Heating of Confined Water in Polymeric Particles for Efficient Payload Release

Near-infrared (NIR) light-triggered release from polymeric capsules could make a major impact on biological research by enabling remote and spatio­temporal control over the release of encapsulated cargo. The few existing mechanisms for NIR-triggered release have not been widely applied because they require custom synthesis of designer polymers, high-powered lasers to drive inefficient two-photon processes, and/or coencapsulation of bulky inorganic particles. In search of a simpler mechanism, we found that exposure to laser light resonant with the vibrational absorption of water (980 nm) in the NIR region can induce release of payloads encapsulated in particles made from inherently non-photo-responsive polymers. We hypothesize that confined water pockets present in hydrated polymer particles absorb electromagnetic energy and transfer it to the polymer matrix, inducing a thermal phase change. In this study, we show that this simple and highly universal strategy enables instantaneous and controlled release of payloads in aqueous environments as well as in living cells using both pulsed and continuous wavelength lasers without significant heating of the surrounding aqueous solution

Biocompatible Polymeric Nanoparticles Degrade and Release Cargo in Response to Biologically Relevant Levels of Hydrogen Peroxide

Oxidative stress is caused predominantly by accumulation of hydrogen peroxide and distinguishes inflamed tissue from healthy tissue. Hydrogen peroxide could potentially be useful as a stimulus for targeted drug delivery to diseased tissue. However, current polymeric systems are not sensitive to biologically relevant concentrations of H₂O₂ (50–100 μM). Here we report a new biocompatible polymeric capsule capable of undergoing backbone degradation and thus release upon exposure to such concentrations of hydrogen peroxide. Two polymeric structures were developed differing with respect to the linkage between the boronic ester group and the polymeric backbone: either direct (<b>1</b>) or via an ether linkage (<b>2</b>). Both polymers are stable in aqueous solution at normal pH, and exposure to peroxide induces the removal of the boronic ester protecting groups at physiological pH and temperature, revealing phenols along the backbone, which undergo quinone methide rearrangement to lead to polymer degradation. Considerably faster backbone degradation was observed for polymer <b>2</b> over polymer <b>1</b> by NMR and GPC. Nanoparticles were formulated from these novel materials to analyze their oxidation triggered release properties. While nanoparticles formulated from polymer <b>1</b> only released 50% of the reporter dye after exposure to 1 mM H₂O₂ for 26 h, nanoparticles formulated from polymer <b>2</b> did so within 10 h and were able to release their cargo selectively in biologically relevant concentrations of H₂O₂. Nanoparticles formulated from polymer <b>2</b> showed a 2-fold enhancement of release upon incubation with activated neutrophils, while controls showed a nonspecific response to ROS producing cells. These polymers represent a novel, biologically relevant, and biocompatible approach to biodegradable H₂O₂-triggered release systems that can degrade into small molecules, release their cargo, and should be easily cleared by the body