Synthesis of New Glycine-Based Polymers and their Thermoresponsive Behavior in Water.

In this work, new glycine-derived polymers are developed that exhibit thermoresponsive properties in water. Therefore, a series of monomers containing one, two, or three amide functional groups and one terminal cyanomethyl group is synthesized. The resulting homopolymers, obtained by free radical polymerization (FRP) and reversible addition fragmentation chain transfer (RAFT) polymerization, display a sharp and reversible upper critical solution temperature (UCST)-type phase transition in water. Additionally, it is shown that the cloud point (TCP) can be adjusted over more than 60 °C by the number of glycyl groups present in the monomer structure and by the polymer's molar mass. These novel thermoresponsive polymers based on cyanomethylglycinamide enrich the range of nonionic UCST polymers and are promising to find applications in various fields.

Unimer Exchange Is not Necessary for Morphological Transitions in Polymerization-Induced Self-Assembly.

Polymerization-induced self-assembly (PISA) has established itself as a powerful and straightforward method to produce polymeric nano-objects of various morphologies in (aqueous) solution. Generally, spheres are formed in the early stages of polymerization that may evolve to higher order morphologies (worms or vesicles), as the solvophobic block grows during polymerization. Hitherto, the mechanisms involved in these morphological transitions during PISA are still not well understood. Combining a systematic study of a representative PISA system with rheological measurements, we demonstrate that-unexpectedly-unimer exchange is not necessary to form higher order morphologies during radical RAFT-mediated PISA. Instead, in the investigated aqueous PISA, the monomer present in the polymerization medium is responsible for the morphological transitions, even though it slows down unimer exchange.

RAFT-Polymerized N-Cyanomethylacrylamide-Based (Co)polymers Exhibiting Tunable UCST Behavior in Water.

In this present work, the synthesis of a new family of upper critical solution temperature (UCST)-thermoresponsive polymers based on N-cyanomethylacrylamide (CMAm) is reported. It is demonstrated that the thermally initiated reversible addition fragmentation chain transfer (RAFT) polymerization of CMAm conducted in N,N-dimethylformamide (DMF) is well controlled. The homopolymer presents a sharp and reversible UCST-type phase transition in pure water with a very small hysteresis between cooling and heating cycles. It is demonstrated that the cloud point (TCP ) of poly(N-cyanomethylacrylamide) (PCMAm) is strongly molar mass dependent and shifts toward lower temperatures in saline water. Moreover, the transition temperature can be tuned over a large temperature range by copolymerization of CMAm with acrylamide or acrylic acid. The latter copolymers are both thermoresponsive and pH responsive. Interestingly, by this strategy sharp and reversible UCST-type transitions close to physiological temperature can be reached, which makes the copolymers extremely interesting candidates for biomedical applications.

Biobased Amphiphilic Block Copolymers by RAFT-Mediated PISA in Green Solvent.

Biobased amphiphilic diblock copolymers are prepared thanks to the combination of reversible addition-fragmentation transfer (RAFT) polymerization and polymerization-induced self-assembly (PISA) in an eco-friendly solvent mixture. First, the formation of a poly(acrylic acid) macroRAFT agent (PAA-TTC) is performed in water at 70 °C. Then, in a series of experiments, the PAA-TTC macroRAFT agent is used directly, without purification, as both chain transfer agent and stabilizing agent in the RAFT-PISA of menthyl acrylate (MnA) in dispersion in an ethanol/water mixture. The polymerizations of MnA are fast with high final conversions and well-controlled amphiphilic diblock copolymers are synthesized. Stable, sub-micrometric spherical particles composed of the diblock copolymers are formed. The influence of the monomer concentration and the length of the solvophobic block on the diameter of the self-assemblies is studied by means of dynamic light scattering and cryogenic transmission electron-microscopy.

RAFT-Mediated Polymerization-Induced Self-Assembly.

After a brief history that positions polymerization-induced self-assembly (PISA) in the field of polymer chemistry, this Review will cover the fundamentals of the PISA mechanism. Furthermore, this Review will also give an overview of some of the features and limitations of RAFT-mediated PISA in terms of the choice of the components involved, the nature of the nanoobjects that can be obtained and how the syntheses can be controlled, as well as some potential applications.

Core-shell polymeric nanoparticles comprising BODIPY and fluorescein as ultra-bright ratiometric fluorescent pH sensors.

A new ratiometric fluorescent pH nanosensor is presented. It is based on ultrabright nanoparticles containing two spatially separated fluorophores: BODIPY covalently linked to the polystyrene core and fluorescein grafted to the nanoparticle shell. The nanoparticles comprise a large number (≥2500) of both fluorescent moieties. Their spectroscopic characteristics were studied at different pH and ionic strength. They could successfully be used to determine the solution pH between 5.5 and 7.5 by measuring the fluorescence intensity ratio of the sensor molecule (fluorescein) relative to the reference dye (BODIPY).

Beyond Simple AB Diblock Copolymers: Application of Bifunctional and Trifunctional RAFT Agents to PISA in Water.

The influence of the macromolecular reversible addition-fragmentation chain transfer (macro-RAFT) agent architecture on the morphology of the self-assemblies obtained by aqueous RAFT dispersion polymerization in polymerization-induced self-assembly (PISA) is studied by comparing amphiphilic AB diblock, (AB)2 triblock, and triarm star-shaped (AB)3 copolymers, constituted of N,N-dimethylacrylamide (DMAc = A) and diacetone acrylamide (DAAm = B). Symmetrical triarm (AB)3 copolymers could be synthesized for the first time in a PISA process. Spheres and higher order morphologies, such as worms or vesicles, could be obtained for all types of architectures and the parameters that determine their formation have been studied. In particular, we found that the total DPn of the PDMAc and the PDAAm segments, i.e., the same overall molar mass, at the same Mn (PDMAc)/Mn (PDAAm) ratio, rather than the individual length of the arms determined the morphologies for the linear (AB)2 and star shaped (AB)3 copolymers obtained by using the bi- and trifunctional macro-RAFT agents.

Templated PISA: Driving Polymerization-Induced Self-Assembly towards Fibre Morphology.

Dispersions of block copolymer fibres in water have many potential applications and can be obtained by polymerization-induced self-assembly (PISA), but only under very restricted experimental conditions. In order to enlarge this experimental window, we introduced a supramolecular moiety, a hydrogen-bonded bis-urea sticker, in the macromolecular reversible addition fragmentation chain transfer (RAFT) agent to drive the morphology of the nano-objects produced by RAFT-mediated PISA towards the fibre morphology. This novel concept is tested in the synthesis of a series of poly(N,N-dimethylacrylamide)-b-poly(2-methoxyethyl acrylate) (PDMAc-b-PMEA) diblock copolymers prepared by dispersion polymerization in water. The results prove that the introduction of the templating bis-urea stickers into PISA greatly promotes the formation of fibres in a large experimental window.

Use of Primary and Secondary Polyvinylamines for Efficient Gene Transfection.

Gene transfection with polymeric carrier remains a challenge; particularly, high transfection levels combined with low toxicity are hard to achieve. We herein revisit polyvinylamines, an old and neglected family of cationic polymers. They can be readily obtained by controlled hydrolysis of polyvinylamides prepared through (controlled) radical polymerization. A series of tailor-made and well-defined polyvinylamines bearing primary amino groups, and poly(N-methylvinylamine) bearing secondary amines, were evaluated for the transfection of cells with pDNA as a function of their molar mass, molar mass distribution, and degree of deacetylation. Unexpected high transfection levels, in combination with low cytotoxicity were recorded for both series. Surprisingly, a great impact of the molar mass was observed for the primary amine polyvinylamine series, whereas the results were mostly independent of molar mass or dispersity for the polymer bearing secondary amine. It was further established that a certain percentage of acetamide groups increased the transfection level, while maintaining low cytotoxicity. These results highlight for the first time the real potential of polyvinylamines as gene carriers, and make these polymers very attractive for further development in gene therapy.

Amphiphilic polyoxometalates for the controlled synthesis of hybrid polystyrene particles with surface reactivity.

Amphiphilic organo-polyoxometalates (POMs) used in the radical emulsion polymerization of styrene allowed the preparation in aqueous medium of stable 50-100 nm polystyrene-POM composite latexes. Thanks to the presence of a trithiocarbonate group in the POM amphiphile, POMs could be covalently linked to the polymer particle surface. The chemical and catalytic integrity of the POMs was confirmed, and the POM-mediated surface photoactivity of the latexes was demonstrated by the spatially controlled nucleation of silver nanoparticles at the periphery of the composites.

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, characterization and applications of a perdeuterated amphipol.

Amphipols are short amphipathic polymers that can substitute for detergents at the hydrophobic surface of membrane proteins (MPs), keeping them soluble in the absence of detergents while stabilizing them. The most widely used amphipol, known as A8-35, is comprised of a polyacrylic acid (PAA) main chain grafted with octylamine and isopropylamine. Among its many applications, A8-35 has proven particularly useful for solution-state NMR studies of MPs, for which it can be desirable to eliminate signals originating from the protons of the surfactant. In the present work, we describe the synthesis and properties of perdeuterated A8-35 (perDAPol). Perdeuterated PAA was obtained by radical polymerization of deuterated acrylic acid. It was subsequently grafted with deuterated amines, yielding perDAPol. The number-average molar mass of hydrogenated and perDAPol, ~4 and ~5 kDa, respectively, was deduced from that of their PAA precursors, determined by size exclusion chromatography in tetrahydrofuran following permethylation. Electrospray ionization-ion mobility spectrometry-mass spectrometry measurements show the molar mass and distribution of the two APols to be very similar. Upon neutron scattering, the contrast match point of perDAPol is found to be ~120% D2O. In (1)H-(1)H nuclear overhauser effect NMR spectra, its contribution is reduced to ~6% of that of hydrogenated A8-35, making it suitable for extended uses in NMR spectroscopy. PerDAPol ought to also be of use for inelastic neutron scattering studies of the dynamics of APol-trapped MPs, as well as small-angle neutron scattering and analytical ultracentrifugation.

Soft nanostructured films with an ultra-low volume fraction of percolating hard phase.

In this study, aqueous emulsion polymerization of n-butyl acrylate is performed in batch conditions without surfactants using a poly(acrylic acid)-trithiocarbonate macro-RAFT agent to control the polymerization and to stabilize the emulsion. According to the polymerization-induced self-assembly (PISA) approach, well-defined amphiphilic PAA-b-PBA diblock copolymers form and self-assemble during synthesis to yield highly stable core-shell particles with an extremely thin hard PAA shell. For the first time, we report here the specific properties of films obtained from these particular latexes. After drying the aqueous dispersion, tough and transparent films are obtained. Although the films are not chemically cross-linked, they do not dissolve in good solvents for PBA. Moreover, they remain transparent even after immersion in water. Rheology shows that the films are both stiff and ductile, thanks to the nanostructured but very low volume fraction (less than 3 wt%) of PAA forming a percolating network in the soft PBA. Compared with conventional core-shell-based films, this approach affords for the first time a route to a thin percolating honeycomb nanostructure with a sharp and strong interface between the two phases. The versatility of the synthetic procedure opens perspectives for a large range of functional materials.

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.

One-pot synthesis of pegylated fluorescent nanoparticles by RAFT miniemulsion polymerization using a phase inversion process.

Water-soluble and fluorescent core-shell nanoparticles (FNP) are synthesized in a miniemulsion reversible addition-fragmentation transfer (RAFT) polymerization and are shown to respond to pH. The particles are obtained from a hydrophilic PEO-b-PAA macromolecular RAFT agent which is block-extended with styrene and a fluorescent BODIPY monomer. A miniemulsion is then formed with the residual hydrophobic monomers. After completion of the polymerization, FNP of ≈ 60 nm in diameter are obtained. The fluorescence of the BODIPY dye in the particles is found to remain (0.2 quantum yield). The particles can be precipitated in acidic pH and redispersed upon addition of base without loss of their integrity or noticeable rearrangement.

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.

Unexpected thermo-responsiveness of bisurea-functionalized hydrophilic polymers in water.

HYPOTHESIS: Thermoresponsive polymers are important materials for various applications. However, the number of polymers that exhibit this property in the temperature range of interest remains limited. The development of novel rational design strategies through the understanding of the thermal transition's origin is therefore of utmost importance. EXPERIMENTS: Bisurea-functionalized water-soluble polymers were synthesized by RAFT polymerization. After direct dissolution in water, the supramolecular assemblies were analyzed by cryo-TEM and SANS. Their temperature-dependent water-solubility was characterized by various techniques, namely DLS, SANS, DSC, IR, to understand the origin of the temperature sensitivity. FINDINGS: The supramolecular assemblies exhibit an unexpected temperature-dependent solubility. For instance, a cloud point of only 39 °C was measured for poly(N,N-dimethylacrylamide) assemblies. This property is not restricted to one specific polymer but is rather a general feature of bisurea-functionalized polymers that form supramacromolecular bottlebrushes in water. The results highlight the existence of two distinct transitions; the first one is a visually perceptible cloud point due to the aggregation of individual micelles, presumably driven by the hydrophobic effect. The second transition is related to the dissociation of intermolecular bisurea hydrogen bonds. Finally, we show that it is possible to widely tune the cloud point temperature through the formation of co-assemblies.

Synthesis and Characterization of Temperature-Responsive N-Cyanomethylacrylamide-Containing Diblock Copolymer Assemblies in Water.

We have previously demonstrated that poly(N-cyanomethylacrylamide) (PCMAm) exhibits a typical upper-critical solution temperature (UCST)-type transition, as long as the molar mass of the polymer is limited, which was made possible through the use of reversible addition-fragmentation chain transfer (RAFT) radical polymerization. In this research article, we use for the first time N-cyanomethylacrylamide (CMAm) in a typical aqueous dispersion polymerization conducted in the presence of poly(N,N-dimethylacrylamide) (PDMAm) macroRAFT agents. After assessing that well-defined PDMAm-b-PCMAm diblock copolymers were formed through this aqueous synthesis pathway, we characterized in depth the colloidal stability, morphology and temperature-responsiveness of the dispersions, notably using cryo-transmission electron microscopy (cryo-TEM), dynamic light scattering (DLS), small angle X-ray scattering (SAXS) and turbidimetry. The combined analyses revealed that stable nanometric spheres, worms and vesicles could be prepared when the PDMAm block was sufficiently long. Concerning the thermoresponsiveness, only diblocks with a PCMAm block of a low degree of polymerization (DPn,PCMAm < 100) exhibited a UCST-type dissolution upon heating at low concentration. In contrast, for higher DPn,PCMAm, the diblock copolymer nano-objects did not disassemble. At sufficiently high temperatures, they rather exhibited a temperature-induced secondary aggregation of primary particles. In summary, we demonstrated that various morphologies of nano-objects could be obtained via a typical polymerization-induced self-assembly (PISA) process using PCMAm as the hydrophobic block. We believe that the development of this aqueous synthesis pathway of novel PCMAm-based thermoresponsive polymers will pave the way towards various applications, notably as thermoresponsive coatings and in the biomedical field.

Fluorescent Copolymers for Bacterial Bioimaging and Viability Detection.

Novel fluorescent labels with high photostability and high biocompatibility are required for microbiological imaging and detection. Here, we present a green fluorescent polymer chain (GFPC), designed to be nontoxic and water-soluble, for multicolor bioimaging and real-time bacterial viability determination. The copolymer is synthesized using a straightforward one-pot reversible addition-fragmentation chain-transfer (RAFT) polymerization technique. We show that GFPC does not influence bacterial growth and is stable for several hours in a complex growth medium and in the presence of bacteria. GFPC allows the labeling of the bacterial cytoplasm for multicolor bacterial bioimaging applications. It can be used in combination with propidium iodide (PI) to develop a rapid and reliable protocol to distinguish and quantify, in real time, by flow cytometry, live and dead bacteria.