Synthesis of novel surface active agents via copper mediated living radical polymerisation : synthetic and mechanistic study

The synthesis of polyethylene glycol)-based surface active agents was undertaken via copper mediated living radical polymrisation. In a first approach, polyethylene glycol) was used as macroinitiator for the synthesis of polyethylene glycol) methyl ether-b-poly(methyl methacrylate) (MeOPEG-b- PMMA) block copolymers. The living character of the polymerisation was demonstrated, but MeOPEG was found to be a slow initiator. In a second approach, MeOPEG was used as a methacrylate macromonomer (MeOPEG-MA). Graft polymers were obtained by polymerisation in toluene and water, and various block copolymers, aiming to increase the hydrophobicity character of the final molecules, were also synthesised. The kinetics of the polymerisation was then studied, and various oxygen containing molecules were found to influence the polymerisation by polarity effect on the solution and potential competitive coordination with the ligands on the copper catalyst. Finally, the physical properties of the block and graft copolymers synthesised were tested. Thermal analyses, surface properties of the PMMA block copolymers and aggregates formation in aqueous solution were investigated

Surface-initiated SET living radical polymerisation for the synthesis of silica–polymer core–shell nanoparticles

We report the use of surface-initiated single-electron transfer living radical polymerisation (SI SET-LRP) to prepare inorganic–organic core–shell nanoparticles with functional grafted chains of high molecular weight. The potential of SI SET-LRP is demonstrated by the preparation of a series of silica–polymer core–shell materials from a silica nanoparticle template bearing a bromo ester initiating group in the presence of a free initiator, with detailed kinetic investigations using methyl acrylate and tert-butyl acrylate. Under optimised polymerisation conditions, concentrated polymer brushes with grafting densities as high as 0.8 chains per nm2 and relatively high molecular weight polymer grafts (degree of polymerisation, DPn, up to 1000) were achieved whilst employing a heterogeneous copper(0) wire catalyst at low polymerisation temperatures. Under optimal conditions, the polymer shell grows similarly to the free polymer with increasing monomer conversion to produce well-defined monodisperse particles with a narrow size distribution. The particle uniformity results in the formation of particle assemblies that display long-range 2D and 3D order, as characterised by electron microscopy

Étude par sous-structuration des vibrations transmises au système main-bras des cyclistes

Depuis quelques années dans le domaine du cyclisme de route, le confort des vélos est devenu un élément au moins aussi recherché que la performance. Le confort est une préoccupation majeure pour 90 % des cyclistes. Les cyclistes sur route passionnés enfourchent leurs vélos pendant plusieurs centaines d’heures chaque année. Ils souhaitent donc utiliser un vélo qui aura la capacité de réduire les vibrations générées par la route. Un sondage réalisé auprès de 320 cyclistes a montré que les vibrations transmises au niveau de la main sont considérées comme la plus grande source d’inconfort. Ce travail a permis de développer une approche permettant d’estimer le niveau de vibrations transmis au niveau de la main du cycliste par sous-structuration. Les méthodes de sous-structuration permettent de prédire le comportement dynamique d’un assemblage de structures par caractérisation de chacune des structures prise séparément. Bien que ces méthodes existent depuis des dizaines d’années, aucune étude n’avait investigué l’assemblage de deux structures par sous-structuration lorsqu’une d’entre elles est l’Humain. L’approche proposée consiste à mesurer la réponse biodynamique du système main-bras en posture cycliste et à prédire la puissance vibratoire au niveau de la main du cycliste à l’aide d’une méthode de sous-structuration. Cette thèse présente les éléments importants issus de ces travaux. Deux méthodes de couplage ont été identifiées et testées pour prédire l’influence du système main-bras sur le comportement dynamique de structures mécaniques simples. La variabilité de réponse du système main-bras de plusieurs sujets a été analysée. Des caractéristiques communes à plusieurs sujets ont été identifiées dans la réponse biodynamique de leurs systèmes main-bras. Finalement, l’importance relative du cycliste par rapport au vélo sur le comportement dynamique de l’assemblage vélo – cycliste au niveau de la main a conduit au développement d’une méthode de caractérisation de la réponse vibratoire des vélos seuls

Efficient click-addition sequence for polymer–polymer couplings

Controlled radical polymerization methods and click chemistry form a versatile toolbox for creating complex polymer architectures. However, the incompatibility between the functional groups required for click reactions and the reaction conditions of radical polymerization techniques often limits application. Here, we demonstrate how combining two complementary click reactions in a sequence circumvents compatibility issues. We employ isocyanate-amine addition on a polymer obtained by RAFT without purification, thus allowing us to work at exact equimolarity. The addition of commercially available amine-functional azido or strained alkyne compounds, yields orthogonally modified polymers, which can be coupled together in a subsequent strain promoted cycloaddition (SPAAC). The efficiency of this reaction sequence is demonstrated with different acrylate, methacrylate, and acrylamide polymers giving block copolymers in high yield. The resulting diblock copolymers remain active towards RAFT polymerization, thus allowing access to multiblock structures by simple chain extension. The orthogonality of the isocyanate-amine reaction, SPAAC and RAFT polymerization (both in terms of monomer and chain end groups) is a key advantage and offers access to functional and challenging polymer architectures without the need for stringent reaction conditions or laborious intermediate purifications

Synthesis of mannosylated and PEGylated nanoparticles via RAFT emulsion polymerisation, and investigation of particle-lectin aggregation using turbidimetric and DLS techniques

Recent developments in controlled radical polymerisation presents an attractive way of producing biocompatible polymeric nanoparticles for a wide range of applications. With this motivation, well defined P (ManAm) and P(PEGA) coated nanoparticles in a range of different sizes have been synthesised via RAFT emulsion polymerisation. The particles were used to precisely investigate the effect of particle size on lectin binding with Concanavalin A, and validate the use of online DLS measurements for lectin-glycoparticle aggregation studies. Larger particles were found to have an enhanced aggregation by both UV–Vis turbidimetric and DLS aggregation studies. The DLS technique was shown to be robust up to an aggregate diameter of c.500 nm for aggregation tests, and was not affected by any dilution or light scattering effects that typically hinder the common use of turbidimetry in particle aggregation studies

Selective patterning of gold surfaces by core/shell, semisoft hybrid nanoparticles

The generation of patterned surfaces with well-defined nano- and microdomains is demonstrated by attaching core/shell, semisoft nanoparticles with narrow size distribution to microdomains of a gold-coated silicon wafer. Near monodisperse nanoparticles are prepared using reversible addition-fragmentation chain transfer (RAFT) polymerization, initiated from a silica surface, to prepare a polystyrene shell around a silica core. The particles are then used as-prepared, or after aminolysis of the terminal thiocarbonyl group of the polystyrene shell, to give thiol-terminated nanoparticles. When gold-coated silicon wafers are immersed into very dilute suspensions of these particles (as low as 0.004 wt%), both types of particles are shown to adhere to the gold domains. The thiolated particles adhere selectively to the gold microdomains, allowing for microdomain patterning, while particles that contain the trithiocarbonate functionality lead to a much more even coverage of the gold surface with fewer particle aggregations

Random integrals and correctors in homogenization

International audienceThis paper concerns the homogenization of a one-dimensional elliptic equation with oscillatory random coefficients. It is well-known that the random solution to the elliptic equation converges to the solution of an effective medium elliptic equation in the limit of a vanishing correlation length in the random medium. It is also well-known that the corrector to homogenization, i.e., the difference between the random solution and the homogenized solution, converges in distribution to a Gaussian process when the correlations in the random medium are sufficiently short-range. Moreover, the limiting process may be written as a stochastic integral with respect to standard Brownian motion. We generalize the result to a large class of processes with long-range correlations. In this setting, the corrector also converges to a Gaussian random process, which has an interpretation as a stochastic integral with respect to fractional Brownian motion. Moreover, we show that the longer the range of the correlations, the larger is the amplitude of the corrector. Derivations are based on a careful analysis of random oscillatory integrals of processes with long-range correlations. We also make use of the explicit expressions for the solutions to the one-dimensional elliptic equation

Poly(bromoethyl acrylate) : a reactive precursor for the synthesis of functional RAFT materials

Postpolymerization modification has become a powerful tool to create a diversity of functional materials. However, simple nucleophilic substitution reactions on halogenated monomers remains relatively unexplored. Here we report the synthesis of poly(bromoethyl acrylate) (pBEA) by reversible addition–fragmentation chain transfer (RAFT) polymerization to generate a highly reactive polymer precursor for postpolymerization nucleophilic substitution. RAFT polymerization of BEA generated well-defined homopolymers and block copolymers over a range of molecular weights. The alkylbromine-containing homopolymer and block copolymer precursors were readily substituted by a range of nucleophiles in good to excellent conversion under mild and efficient reaction conditions without the need of additional catalysts. The broad range of nucleophilic species that are compatible with this postmodification strategy enables facile synthesis of complex functionalities, from permanently charged polyanions to hydrophobic polythioethers to glycopolymers

A New Methodology for Assessing Macromolecular Click Reactions and Its Application to Amine--Tertiary Isocyanate Coupling for Polymer Ligation.

Click reactions have provided access to an array of remarkably complex polymer architectures. However, the term "click" is often applied inaccurately to polymer ligation reactions that fail to respect the criteria that typify a true "click" reaction. With the purpose of providing a universal way to benchmark polymer-polymer coupling efficiency at equimolarity and thus evaluate the fulfilment of click criteria, we report a simple one-pot methodology involving the homodicoupling of α-end-functionalized polymers using a small-molecule bifunctional linker. A combination of SEC analysis and chromatogram deconvolution enables straightforward quantification of the coupling efficiency. We subsequently employ this methodology to evaluate an overlooked candidate for the click reaction family: the addition of primary amines to α-tertiary isocyanates (α-(t)NCO). Using our bifunctional linker coupling strategy, we show that the amine-(t)NCO reaction fulfills the criteria for a polymer-polymer click reaction, achieving rapid, chemoselective, and quantitative coupling at room temperature without generating any byproducts. We demonstrate that amine-(t)NCO coupling is faster and more efficient than the more common amine-tertiary active ester coupling under equivalent conditions. Additionally, we show that the α-(t)NCO end group is unprecedentedly stable in aqueous media. Thus, we propose that the amine-(t)NCO ligation is a powerful new click reaction for efficient macromolecular coupling.Dr Maarten Danial for providing the cyclic peptide.This is the final version of the article. It first appeared from the American Chemical Society via http://dx.doi.org/10.1021/jacs.5b1183

Development of a gemcitabine-polymer conjugate with prolonged cytotoxicity against a pancreatic cancer cell line

Gemcitabine (GEM) is a nucleoside analogue of deoxycytidine with limited therapeutic efficacy due to enzymatic hydrolysis by cytidine deaminase (CDA) resulting in compromised half-life in the bloodstream and poor pharmacokinetics. To overcome these limitations, we have developed a methacrylate-based GEM-monomer conjugate, which was polymerized by reversible addition–fragmentation chain transfer (RAFT) polymerization with high monomer conversion (∼90%) and low dispersity (<1.4). The resulting GEM-polymer conjugates were found to form well-defined sub-90 nm nanoparticles (NPs) in aqueous suspension. Subsequently, the GEM release was studied at different pH (∼7 and ∼5) with and without the presence of an enzyme, Cathepsin B. The GEM release profiles followed a pseudo zero-order rate and the GEM-polymer conjugate NPs were prone to acidic and enzymatic degradation, following a two-step hydrolysis mechanism. Furthermore, the NPs exhibited significant cytotoxicity in vitro against a model pancreatic cell line. Although, the half-maximal inhibitory concentration (IC50) of the GEM-monomer and -polymer conjugate NPs was higher than free GEM, the conjugates showed superiorly prolonged activity compared to the parent drug