Marion Rollet

Separation of Parent Homopolymers from Polystyrene-b-poly(ethylene oxide)-b-polystyrene Triblock Copolymers by Means of Liquid Chromatography: 1. Comparison of Different Methods

Separation of parent homopolymers, polystyrene and poly(ethylene oxide), from the triblock copolymer polystyrene-b-poly(ethylene oxide)-b-polystyrene was investigated by means of liquid chromatography techniques. Overall suitability was evaluated and compared for size exclusion chromatography, (SEC), liquid chromatography under critical conditions of enthalpic interactions (LC CC), and liquid chromatography under limiting conditions of desorption (LC LCD). Among these techniques, LC LCD was the only one able to fully separate block copolymers from both their parent homopolymers in one single run. The efficiency of the separation was proven by (1)H NMR analysis of previously collected fractions.

Indolinic nitroxides: evaluation of their potential as universal control agents for nitroxide mediated polymerization

Indolinic nitroxides derived from 2,2-diphenyl-3-phenylimino-2,3-dihydroindol-1-yloxyl (DPAIO) nitroxide were designed to improve the bulk polymerization of methacrylate derivatives. The corresponding alkoxyamines were prepared by reacting alkyl halide and nitroxide in the presence of tin hydride and PbO2. The replacement of one phenyl ring at the C-2 position on the nitroxide by either a neopentyl or an isopropyl group led to compounds with faster decomposition kinetics and better selectivity for the C–ON bond homolysis. The alkoxyamines derived from these two nitroxides were used to control the polymerization of methyl methacrylate and were also tested for the polymerization of styrene as a model for mono-substituted monomers. The shift of the molar mass distribution during the NMP of styrene showed for the first time that pure homopolymerization of styrene and methacrylate derivatives could be controlled by the same nitroxide, thus opening the way to a universal nitroxide for NMP.

Lysine-tagged peptide coupling onto polylactide nanoparticles coated with activated ester-based amphiphilic copolymer: a route to highly peptide-functionalized biodegradable carriers.

Efficient biomolecule conjugation to the surface of biodegradable colloidal carriers is crucial for their targeting efficiency in drug/vaccine delivery applications. We here propose a potent strategy to drastically improve peptide immobilization on biodegradable polylactide (PLA) nanoparticles (NPs). Our approach particularly relies on the use of an amphiphilic block copolymer PLA-b-poly(N-acryloxysuccinimide-co-N-vinylpyrrolidone) (PLA-b-P(NAS-co-NVP)) as NP surface modifier, whose the N-succinimidyl (NS) ester functions of the NAS units along the polymer chain ensure N-terminal amine peptide coupling. The well-known immunostimulatory peptide sequence derived from the human interleukin 1β (IL-1β), VQGEESNDK, was coupled on the NPs of 169 nm mean diameter in phosphate buffer (pH 8, 10 mM). A maximum amount of 2 mg immobilized per gram of NPs (i.e. 0.042 peptidenm(-2)) was obtained. Introduction of a three lysine tag at the peptide N-terminus (KKKVQGEESNDK) resulted in a dramatic improvement of the immobilized peptide amounts (27.5 mg/g NP, i.e. 0.417 peptidenm(-2)). As a comparison, the density of tagged peptide achievable on surfactant free PLA NPs of similar size (140 nm), through classical EDC or EDC/NHS activation of the surface PLA carboxylic end-groups, was found to be 6 mg/g NP (i.e. 0.075 peptidenm(-2)), showing the decisive impact of the P(NAS-co-NVP)-based hairy corona for high peptide coupling. These results demonstrate that combined use of lysine tag and PLA-b-P(NAS-co-NVP) surfactant represents a valuable platform to tune and optimize surface bio-functionalization of PLA-based biodegradable carriers.

Polymerization Initiated by Organic Electron Donors

Polymerization reactions with organic electron donors (OED) as initiators are presented herein. The metal-free polymerization of various activated alkene and cyclic ester monomers was performed in short reaction times, under mild conditions, with small amounts of organic reducing agents, and without the need for co-initiators or activation by photochemical, electrochemical, or other methods. Hence, OED initiators enabled the development of an efficient, rapid, room-temperature process that meets the technical standards expected for industrial processes, such as energy savings, cost-effectiveness and safety. Mechanistic investigations support an electron-transfer initiation pathway that leads to the reduction of the monomer.

End-group cleavage in MALDI of ATRP-made polystyrene: a silver-catalyzed reaction during sample preparation.

Cleavage of the labile halide termination upon matrix-assisted laser desorption/ionization (MALDI) has always been reported as a major concern in mass analysis of polystyrene prepared by atom transfer radical polymerization (ATRP). By studying this issue using nuclear magnetic resonance (NMR) and electrospray ionization-mass spectrometry, we evidence here that the ionization step is not involved in this deleterious process. Instead, removal of the halogen was shown to readily occur upon interaction of the silver salt (AgTFA) used as the cationizing agent in mass spectrometry, either in solution or in the solid-state when performing solvent-free sample preparation. In solution, this silver-induced reaction mostly consists of a nucleophilic substitution, leading to polystyrene molecules holding different terminations, depending on relative nucleophilicity of species present in the liquid-phase solution composition. In chloroform supplemented with AgTFA, trifluoroacetate-terminated PS were evidenced in ESI-MS spectra but experienced end-group cleavage in MALDI. In contrast, the major methoxy-terminated PS macromolecules formed when the silver-catalyzed nucleophilic substitution was performed in methanol were generated as intact gas-phase ions using both ionization techniques. This controlled and fast modification could hence be advantageously used as a rapid sample pretreatment for safe MALDI mass analysis of ATRP-made polystyrene.

A post-polymerization functionalization strategy for the synthesis of sulfonyl (trifluoromethanesulfonyl)imide functionalized (co)polymers

In this Communication, we report the synthesis of a series of potassium sulfonyl (trifluoromethanesulfonyl)imide (STFSI) derivatives, bearing at one extremity the STFSI group and at the other extremity either bromo, azido or amine groups. The resultant STFSI derivatives were subsequently used in the post-polymerization functionalization of (co)polymers to yield functionalized (co)polymers by exploiting the highly efficient coupling reactions, namely alkylation, amidation and alkyne–azide cycloaddition.

Separation of parent homopolymers from polystyrene and poly(ethylene oxide) based block copolymers by liquid chromatography under limiting conditions of desorption-3. Study of barrier efficiency according to block copolymers' chemical composition.

Liquid Chromatography under Limiting Conditions of Desorption (LC LCD) is a powerful separation tool for multicomponent polymer systems. This technique is based on a barrier effect of an appropriate solvent, which is injected in front of the sample, and which decelerates the elution of selected macromolecules. In this study, the barrier effects have been evaluated for triblock copolymers polystyrene-b-poly(ethylene oxide)-b-polystyrene (PS-b-PEO-b-PS) according to the content of polystyrene (wt% PS) and PEO-block molar mass. PS-b-PEO-b-PS samples were prepared by Atom Transfer Radical Polymerization (ATRP). The presence of respective parent homopolymers was investigated by applying optimized LC LCD conditions. It was found that the barrier composition largely affects the efficiency of separation and it ought to be adjusted for particular composition range of block copolymers.

Adduction of ammonium to polylactides to modify their dissociation behavior in collision-induced dissociation

RATIONALE The goal of this work was to modify the dissociation pathways of polylactide (PLA) holding benzyl and hydroxyl terminations, in order to circumvent coincidence of product ions generated during collisional activation of sodiated chains, which prevented their reliable characterization. METHODS Benzyl-, hydroxyl-terminated PLAs were ionized as ammonium adducts in positive ion mode electrospray and subjected to collision-induced dissociation (CID). Tandem mass spectrometry (MS/MS) experiments were conducted in a quadrupole time-of-flight (QTOF) instrument for safe assignment of product ions based on their elemental composition derived from accurate mass measurements. RESULTS Adduction of ammonium to PLAs was found to induce chain fragmentation via charge-assisted processes, in great contrast to the charge-remote mechanisms experienced by sodiated molecules. The main reaction produced ions containing the ω termination only, hence allowing straightforward end-group determination. Other minor pathways were studied in detail to establish dissociation rules for ammoniated PLAs. Some reactions were found to be end-group specific, highlighting the higher reactivity of ammonium than alkali ion adducts. CONCLUSIONS Changing the usually employed sodium-cationizing agent to ammonium was shown to induce dramatic changes in the CID behavior of PLAs. This was a simple and efficient approach to address issues encountered for end-group analysis of the particular PLA studied here.

Catalyst- and Initiator-Free Radical Addition under Mild Conditions: A Macromolecular Conjugation Tool

A catalyst/initiator-free radical addition reaction performed under mild conditions (water, 30 °C) with high yields is reported for the first time. This reaction implies simple pH-mediated alkoxyamine dissociation followed by addition onto olefinic substrates. The versatility and relevance of this selective reaction for macromolecular conjugation and engineering are shown through the syntheses of block copolymers, as well as hydrogels containing in situ-loaded proteins, which could retain biological activity. This contrasts with standard thermal radical conditions that lead to complete protein inactivation.