Jutta Rieger

Guidelines for the Synthesis of Block Copolymer Particles of Various Morphologies by RAFT Dispersion Polymerization

This article presents the recent developments of radical dispersion polymerizaton controlled by reversible addition fragmentation chain transfer (RAFT) for the production of block copolymer particles of various morphologies, such as core-shell spheres, worms, or vesicles. It is not meant to be an exhaustive review but it rather provides guidelines for non-specialists. The article is subdivided into eight sections. After a general introduction, the mechanism of polymerization-induced self-assembly (PISA) through RAFT-mediated dispersion polymerization is presented and the different parameters that control the morphology produced are discussed. The next two sections are devoted to the choice of the monomer/solvent pair and the macroRAFT agent. Afterwards, post-polymerization morphological order-to-order transitions (i.e. morphological transitions triggered by extrinsic stimuli) or order-to-disorder transitions (i.e. disassembly of chains) are discussed. Assemblies based on more complex polymer architectures, such as triblock copolymers, are presented next, and finally the possibility to stabilize these structures by crosslinking is reported. The manuscript ends with a short conclusion and an outlook.

Synthesis of nanogels/microgels by conventional and controlled radical crosslinking copolymerization

This review compares conventional and controlled radical polymerization techniques and processes in preparing nano-/microgels. Special focus is made on the synthetic parameters that allow controlling their size, morphology, composition, and structural homogeneity.

Effect of the solvent composition on the morphology of nano-objects synthesized via RAFT polymerization of benzyl methacrylate in dispersed systems

A hydrophilic macromolecular RAFT (reversible addition–fragmentation chain transfer) agent (macroRAFT agent) composed of 50 mol% methacrylic acid and 50 mol% poly(ethylene oxide) monomethyl ether methacrylate end-capped by a reactive trithiocarbonate group (P(MAA-co-PEOMA)) was used in the polymerization of benzyl methacrylate (BzMA) in different media, ethanol–water and 1,4-dioxane–water mixtures. Depending on the solvent composition, the polymerization showed features of either a dispersion polymerization (monomer soluble in the initial medium) or an emulsion polymerization (monomer insoluble in the initial medium). In all cases, the RAFT mechanism led to the in situ formation of well-defined amphiphilic P(MAA-co-PEOMA)-b-PBzMA block copolymers that self-assembled during the growth step into self-stabilized nano-objects, according to a polymerization-induced micellization process. For a given composition of the block copolymer, the final morphology depended strongly on the solvent composition. The presence of the organic co-solvent was favorable to the formation of fibers while an increased amount of water favored the formation of spherical particles. Compared to the ethanol–water system, in which the non-spherical objects existed only above 77–80 vol% of ethanol, in 1,4-dioxane–water mixtures the morphological transition was observed at a lower proportion of organic co-solvent (close to 20 vol%). For a given molar mass of the macroRAFT agent and an increased molar mass of the PBzMA block in a given solvent composition (ethanol–water, 95/5, v/v), the morphology changed from spheres to fibers and then to large spheres or vesicles. The molar mass window in which fibers were obtained was wider than that observed in pure water at pH 5 using the same macroRAFT agent [X. Zhang et al., Macromolecules, 2011, 44, 4149].

Amphiphilic block copolymers from a direct and one-pot RAFT synthesis in water.

The syntheses of amphiphilic block copolymers are successfully performed in water by chain extension of hydrophilic macromolecules with styrene at 80 °C. The employed strategy is a one-pot procedure in which poly(acrylic acid), poly(methacrylic acid) or poly(methacrylic acid-co-poly(ethylene oxide) methyl ether methacrylate) macroRAFTs are first formed in water using 4-cyano-4-thiothiopropylsulfanyl pentanoic acid (CTPPA) as a chain transfer agent. The resulting macroRAFTs are then directly used without further purification for the RAFT polymerization of styrene in water in the same reactor. This simple and straightforward strategy leads to a very good control of the resulting amphiphilic block copolymers.

Amphiphilic liquid-crystal block copolymer nanofibers via RAFT-mediated dispersion polymerization

Well-defined, cholesteryl-based, amphiphilic block copolymer nanofibers have been obtained in a simple, one-pot, ethanol/water dispersion polymerization process using poly((meth)acrylic acid-co-(poly(ethylene glycol) (meth)acrylate) copolymers end-functionalized by a reactive trithiocarbonate end-group as macromolecular reversible addition–fragmentation chain transfer agents (macroRAFT agents). The resulting highly concentrated dispersions were analyzed by TEM (transmission electron microscopy), cryo-TEM, SAXS (small angle X-ray scattering) and SANS (small angle neutron scattering), which allowed the shape and size of the nanoobjects formed in situ to be fully characterized and which revealed moreover the presence of a smectic order in the hydrophobic cores. Due to this particular substructure, the nanofiber organization was observed over a broad composition range of the amphiphilic block copolymers.

Polyester nanoparticles presenting mannose residues: toward the development of new vaccine delivery systems combining biodegradability and targeting properties.

We report the synthesis of fully biodegradable polymeric nanoparticles presenting mannose residues at their surface and their interaction with lectins. A simple and versatile method was used to reach the surface functionalization of poly(D,L-lactic acid) (PLA) nanoparticles by mannose moieties: It consists in using an amphiphilic mannosylated poly(ethylene oxide)-b-poly(E-caprolactone) (PEO-b-PCL) diblock copolymer as a bioresorbable surface modifier in a simple nanoprecipitation-evaporation procedure. The size and zeta potential of the nanoparticles were found to depend on the molar copolymer/PLA ratio, demonstrating the influence of the copolymer on the formation of the nanoparticles. The bioavailability of the mannose residues as specific recognition sites on the nanoparticle surface could be demonstrated by a modified enzyme-linked lectin assay (ELLA) using biotin-labeled lectins which interact specifically with alpha-D-mannopyrannoside derivatives. Besides specific interaction by lectin-mannose complex formation, nonspecific adsorption of the proteins on the nanoparticle surface was observed. These results were fully supported by isothermal titration calorimetry experiments which suggested that the balance between specific and nonspecific interactions can be controlled by the amount of glycosylated polymer used for the preparation of the nanoparticles. Such nanoparticles are expected to be specifically recognized by mannose receptors, which are highly expressed in cells of the immune system. The targeting properties of these carrier systems combined with their potential adjuvant effects due to their size in the range of 200-300 nm make them attractive candidates as vaccine delivery systems.

Ab initio RAFT emulsion polymerization of butyl acrylate mediated by poly(acrylic acid) trithiocarbonate

We describe a very simple and straightforward strategy towards self-stabilized poly(acrylic acid)-block-poly(butyl acrylate), PAA-b-PBA, block copolymer particles via an ab initio RAFT-controlled emulsion polymerization. Latexes were obtained at 23 wt% solids without the use of additional surfactants, thus avoiding any diffusion issues occurring during film formation. It was possible to reach in a controlled manner PAA-b-PBA diblock copolymers with high molar masses up to 100 kg mol−1. In contrast to previous studies, it was possible to reduce the weight percent of the hydrophilic polymer to 1.2 wt% (with respect to PBA). The block lengths of both PAA and PBA were varied in order to demonstrate the robustness of the system. Ammonium hydroxide was used as a volatile base to adjust the pH of the polymerization medium. Besides improving the polymerization control, ammonium hydroxide is particularly appealing for coating applications, as it can be easily removed during film formation by evaporation. Finally, using these latexes as seeds for the emulsion polymerization of styrene, it was possible to prepare novel nanostructured particles composed of PAA-b-PBA-b-PS triblock copolymers.

Study of poly(N,N-diethylacrylamide) nanogel formation by aqueous dispersion polymerization of N,N-diethylacrylamide in the presence of poly(ethylene oxide)-b-poly(N,N-dimethylacrylamide) amphiphilic macromolecular RAFT agents

The formation of thermoresponsive poly(N,N-diethylacrylamide) (PDEAAm) nanogels via an aqueous dispersion polymerization process in the presence of poly(ethylene oxide)-b-poly(N,N-dimethylacrylamide) macromolecular reversible addition–fragmentation chain transfer agents (macroRAFT agents) was studied. The latter exhibit a hydrophobic trithiocarbonate reactive group with a dodecyl substituent, and had previously proved to act simultaneously as control agents and stabilizers in such a synthesis process (Rieger et al., J. Polym. Sci. Part A: Polym. Chem., 2009, 47, 2373). The nanogel size and stability were found to depend strongly on the chain length of the macroRAFT agents, but also on the crosslinker (N,N′-methylene bisacrylamide) and monomer concentrations. The aim of the present work was to better understand the mechanisms that govern the nanogel formation in such heterogeneous polymerization conditions performed under RAFT control, with special emphasis on the role of the macroRAFT agents. In the first part, the aqueous solution properties of the macroRAFT agents in the conditions of the dispersion polymerizations were studied by light scattering and fluorescence spectroscopy and it was found that they self-assemble to form star micelles. In the second part, the nanogel formation at different DEAAm and crosslinker concentrations was monitored by dynamic and static light scattering, and by size exclusion chromatography. It appeared that at low monomer conversion the calculated number of chains per nanogel particle was close to the aggregation number, Nagg, of the macroRAFT agent micelles. With increasing conversions, however, the number of chains clearly increased and exceeded the initial Nagg. Higher monomer concentrations hardly influenced the formation process and thus the gel particle size, whereas enhanced crosslinker concentration had a strong impact on the latter. These results strongly suggest that precursor particles are formed very rapidly at the polymerization onset and then aggregate with each other to form complex inter-crosslinked particles.

Synthesis and characterization of a thermoresponsive polyoxometalate-polymer hybrid.

We report the synthesis of the first organo-POM with thermoresponsive properties. Our concept will provide chemists with a new tool to design POMs whose solubility is reversibly controllable through an external stimulus. POM-polymer TBA(7)[POM]-poly(N,N-diethylacrylamide) (POM-PDEAAm), was prepared by grafting PDEAAm-NH(2) (obtained by RAFT polymerization) onto the activated Dawson acyl-POM, α(2)-[P(2)W(17)O(61)SnCH(2)CH(2)C(=O)](6-). Extensive MS analysis was used to monitor the chain-functionalization steps and to confirm the formation of the hybrid. Aqueous solutions of the (NH(4))(7)[POM-PDEAAm] exhibited a LCST of 38 °C. Thus, the solubility/aggregation of the hybrid was reversibly controlled by changing the temperature. Above 38 °C, the solution became cloudy, and cleared again upon cooling. Dynamic light scattering (DLS) revealed the formation of small aggregates in the range 100 nm. We assumed that the charged POM head units prevented the formation of the larger-scattering aggregates that are usually observed for PDEAAm, and promoted the formation of micelle-like structures. The conjugate exhibited a temperature transition, which was different from that of the polymer and depended on the counterions associated with the POM. This result demonstrates the potential for merging organic (in this case, polymer) and inorganic structures to afford materials that exhibit new properties.

Synthesis by nitroxide-mediated aqueous dispersion polymerization, characterization, and physical core-crosslinking of pH- and thermoresponsive dynamic diblock copolymer micelles

Diblock copolymers consisting of a poly(acrylic acid) (PAA) segment and a LCST-type poly(N,N-diethylacrylamide) (PDEAAm) block were obtained by nitroxide-mediated polymerization in aqueous dispersion using a water-soluble macroalkoxyamine. The influence of several parameters on the polymerization (temperature, initial free nitroxide or macroalkoxyamine concentrations, and solids content) was evaluated in terms of kinetics, macromolecular control, and colloidal features. As determined by dynamic light scattering (DLS), stable dispersions of monodisperse particles could be obtained for solids content as high as 39 wt% without the need for any additional surfactant via a polymerization-induced self-assembly mechanism. Rendered possible by the use of a controlled/living polymerization process, the effective semi-batch incorporation of hydrophobic units (styrene) in the growing chains during the polymerization allowed the formation of physically crosslinked nanogels. The pH and temperature sensitivity were proved by means of DLS and high-sensitivity differential scanning calorimetry (HSDSC) measurements. Due to the formation of aggregates observed by size-exclusion chromatography in N,N-dimethylformamide, accurate molar masses could not be determined directly but deconvoluted hydrodynamic volume distributions suggested a good control of the polymerization.