Macromolecular Chain Transfer Agent Research Articles

Multiple Pickering emulsions stabilized by surface-segregated micelles with adaptive wettability.

Surface-segregated micelles (SSMs) with adaptive wettability have considerable potential for application in Pickering emulsions and bioanalytical technology. In this study, spherical SSMs were prepared via polymerization-induced self-assembly co-mediated with a binary mixture of macromolecular chain transfer agents: pH-responsive poly(2-(dimethylamino) ethyl methacrylate) and hydrophobic polydimethylsiloxane. Using these SSMs as the sole emulsifier, we adjusted the pH to successfully produce both water-in-oil-in-water (W/O/W) and oil-in-water-in-oil (O/W/O) multiple emulsions through a single-step emulsification process. Moreover, we demonstrated that multiple emulsion systems with adjustable pH are suitable for the development of an efficient and recyclable interfacial catalytic system. Multiple emulsion microreactors increase the area of the oil-water interface and are therefore more efficient than the commonly used O/W and W/O emulsion systems.

RAFT Emulsion Polymerization of Styrene Using a Poly((N,N-dimethyl acrylamide)-co-(N-isopropyl acrylamide)) mCTA: Synthesis and Thermosensitivity.

Thermoresponsive poly((N,N-dimethyl acrylamide)-co-(N-isopropyl acrylamide)) (P(DMA-co-NIPAM)) copolymers were synthesized via reversible addition−fragmentation chain transfer (RAFT) polymerization. The monomer reactivity ratios were determined by the Kelen–Tüdős method to be rNIPAM = 0.83 and rDMA = 1.10. The thermoresponsive properties of these copo-lymers with varying molecular weights were characterized by visual turbidimetry and dynamic light scattering (DLS). The copolymers showed a lower critical solution temperature (LCST) in water with a dependence on the molar fraction of DMA in the copolymer. Chaotropic and kosmotropic salt anions of the Hofmeister series, known to affect the LCST of thermoresponsive polymers, were used as additives in the aqueous copolymer solutions and their influence on the LCST was demonstrated. Further on, in order to investigate the thermoresponsive behavior of P(DMA-co-NIPAM) in a confined state, P(DMA-co-NIPAM)-b-PS diblock copolymers were prepared via polymerization induced self-assembly (PISA) through surfactant-free RAFT mediated emulsion polymerization of styrene using P(DMA-co-NIPAM) as the macromolecular chain transfer agent (mCTA) of the polymerization. As confirmed by cryogenic transmission electron microscopy (cryoTEM), this approach yielded stabilized spherical micelles in aqueous dispersions where the PS block formed the hydrophobic core and the P(DMA-co-NIPAM) block formed the hydrophilic corona of the spherical micelle. The temperature-dependent behavior of the LCST-type diblock copolymers was further studied by examining the collapse of the P(DMA-co-NIPAM) minor block of the P(DMA-co-NIPAM)-b-PS diblock copolymers as a function of temperature in aqueous solution. The nanospheres were found to be thermosensitive by changing their hydrodynamic radii almost linearly as a function of temperature between 25 °C and 45 °C. The addition of kosmotropic salt anions, as a potentially useful tuning feature of micellar assemblies, was found to increase the hydrodynamic radius of the micelles and resulted in a faster collapse of the micelle corona upon heating.

Recoverable Thermo-Responsive Polymeric Surfactants for the Synthesis of Bulk Plastics from Latexes

Free-radical emulsion polymerization (eFRP) is widely adopted in industries due to the great advantages that this technique offers in terms of a high polymerization rate, good heat management, and conduction in a non-toxic solvent like water. On the other hand, eFRP requires surfactants to stabilize the produced polymer nanoparticles (NPs). At the same time, the recovery of a bulk material from a NP suspension needs the addition of salts or alkali for the destabilization of the emulsion and the precipitation of the polymer. These can contaminate the final product and affect its properties. For this reason, alternative strategies able to coagulate the NP latex avoiding the addition of exogenous compounds are needed. In this work, we synthesized thermo-responsive polymeric surfactants that are able to promote the NP formation during the eFRP and to allow the recovery of the bulk polymer by simply increasing the environment temperature. Surfactants with a tunable hydrophilic–lipophilic balance were produced through reversible-addition fragmentation chain transfer (RAFT) emulsion polymerization by chain-extending a polyethylene glycol-based macromolecular chain transfer agent with butyl methacrylate, in order to obtain a series of block copolymers with high blocking efficiency, controlled molecular weight distribution, and well-defined thermo-responsive behavior. Then, the RAFT agent was removed to avoid the further extension of the block copolymers, and the surfactants were tested in the eFRP of different monomers (i.e., butyl methacrylate, methyl methacrylate, and styrene) to produce stable NP latexes. Finally, the possibility of triggering the NP aggregation and of guaranteeing the recovery of both surfactants and bulk material by simply changing the temperature of the system was assessed.

Synthesis of ultra‐high molecular weight core cross‐linked star (CCS) polymer using high molecular weight spherical nanoparticles and arm‐first method

AbstractP (N,N‐Dimethylacrylamide) ‐b‐P (2‐methoxyethyl acrylate) (PDMA‐b‐PMEA) and Poly (poly (ethylene glycol) methyl ether methacrylate) ‐b‐P (2‐methoxyethyl acrylate) (PPEGMA‐b‐PMEA) di‐block copolymer nanoparticles are prepared by RAFT dispersion polymerization in water at 35°C. By changing the degree of polymerization (DP) of PMEA and the solid content of the reaction solution, only spherical nanoparticles are obtained. Using PDMA and PPEGMA as macromolecular chain transfer agents (Macro‐CTA), the actual DP of PMEA block can be up to 11,520 and 17,000, respectively, the size of the obtained spherical nanoparticles can be close to 600 nm, and the molecular weight of the block copolymer can reach 106. Such large spheres may serve as model sterically stabilized particles for analytical centrifugation studies. In the mixed solvent of ethanol and water (1:1, v/v), we synthesize ultra‐high molecular weight CCS polymer by the arm‐first method. Star polymer with such high molecular weight and small particle size can be used for emulsification.

Expanding the Scope of Polymerization‐Induced Self‐Assembly: Recent Advances and New Horizons

Over the past decade or so, polymerization-induced self-assembly (PISA) has become a versatile method for rational preparation of concentrated block copolymer nanoparticles with a diverse set of morphologies. Much of the PISA literature has focused on the preparation of well-defined linear block copolymers by using linear macromolecular chain transfer agents (macro-CTAs) with high chain transfer constants. In this review, a recent process is highlighted from an unusual angle that has expanded the scope of PISA including i) synthesis of block copolymers with nonlinear architectures (e.g., star block copolymer, branched block copolymer) by PISA, ii) in situ synthesis of blends of polymers by PISA, and iii) utilization of macro-CTAs with low chain transfer constants in PISA. By highlighting these important examples, new insights into the research of PISA and future impact these methods will have on polymer and colloid synthesis are provided.

Direct Access to Polysaccharide-Based Vesicles with a Tunable Membrane Thickness in a Large Concentration Window via Polymerization-Induced Self-Assembly.

Polymersomes are multicompartmental vesicular nano-objects obtained by self-assembly of amphiphilic copolymers. When prepared in the aqueous phase, they are composed of a hydrophobic bilayer enclosing water. Although such fascinating polymeric nano-objects have been widely reported with synthetic block copolymers, their formation from polysaccharide-based copolymers remains a significant challenge. In the present study, the powerful platform technology known as polymerization-induced self-assembly was used to prepare in situ pure vesicles from a polysaccharide-grafted copolymer: dextran-g-poly(2-hydroxypropyl methacrylate) (Dex-g-PHPMA). The growth of the PHPMA grafts was performed with a dextran-based macromolecular chain transfer agent in water at 20 °C using photomediated reversible addition fragmentation chain transfer polymerization at 405 nm. Transmission electron microscopy, cryogenic electron microscopy, small-angle X-ray scattering, atomic force microscopy, and dynamic light scattering revealed that amphiphilic Dex-g-PHPMAX=100-300 (X is the targeted average degree of polymerization, Xn̅, of each graft at full conversion) exhibit remarkable self-assembly behavior. On the one hand, vesicles were obtained over a wide range of solid concentrations (from 2.5% to 13.5% w/w), which can facilitate posterior targeting of such rare morphology. On the other hand, the extension of Xn̅ induces an increase in the vesicle membrane thickness, rather than a morphological evolution (spherical micelles to cylinders to vesicles).

Crosslinked Polydicyclopentadiene Nanoparticles via Ring-Opening Metathesis Polymerization-Induced Self-Assembly Approach.

In this communication, the preparation of crosslinked polydicyclopentadiene (PDCPD) nanoparticles via ring-opening metathesis polymerization (ROMP)-induced self-assembly approach is reported. For the ROMPs, the macromolecular chain transfer agents (Macro-CTAs) are synthesized via the ring-opening polymerization (ROP) of ε-caprolactone (CL) with cis-2-butene-1,4-diol as the initiator. The ROMPs are performed with chloroform, tetrahydrofuran, toluene, 1,4-dioxane, and N,N-dimethylacetamide as the solvents, respectively, which are catalyzed with Grubbs second generation catalyst. It is found that the crosslinked PDCPD nanoparticles are obtained with spherical, cylindrical to planar morphologies, depending on the molecular weights of Macro-CTAs, the concentrations of DCPD and the natures of solvents. The polymerization induced self-assembly (ROMPISA) by the use of a non-norbornene-based macromolecular chain transfer agent provides a new and efficient approach to prepare crosslinked polymer nanoparticles.

Nano-fluorophores prepared by polymerization-induced self-assembly and its application in cell imaging

In this work, we report a nano-fluorophore prepared by polymerization-induced self-assembly (PISA) method based on reversible addition-fragmentation chain transfer polymerization. The macromolecular chain transfer agent was polyethylene glycol-based trithiocarbonate, and the monomer was a chalcone derivative terminated with ethylene group. The reaction/assembly was conducted in dioxane, where nanoparticles with extremely uniform size (~200 nm) was formed. The nanoparticles were transferred into aqueous solution, and shrank to ~100 nm with excellent dispersion. The nanoparticles showed fluorescence emission at around 570 nm, and after being transferred to aqueous solution, the emission intensity was significantly enhanced. Being covered with hydrophilic polyethylene glycol, the nano-fluorophores possess excellent biocompatibility, and was successfully applied to label HeLa cells for fluorescent imaging. This study presents a novel avenue for including fluorescent dyes into polymeric nanoparticles with narrow size-distribution, tailorable solubility and biocompatibility.

Nanostructured Polymer Composite Electrolytes with Self-Assembled Polyoxometalate Networks for Proton Conduction

Nanostructured Polymer Composite Electrolytes with Self-Assembled Polyoxometalate Networks for Proton Conduction

Synthesis of Lignin-Based MMA-co-BA Hybrid Resins from Cornstalk Residue via RAFT Miniemulsion Polymerization and Their Characteristics.

The conversion of cornstalk lignin derived from the co-product of bio-refinery into value-added products such as polymeric material has remarkable environmental and economic potential. A novel bio-based methyl methacrylate copolymerized with butyl acrylate (MMA-co-BA) hybrid resin in our research was prepared by the reversible addition–fragmentation chain transfer method using lignin-graft-polyacrylamide (lignin-g-PAM) as a bio-derived macromolecular chain transfer agent. The molecular architecture of lignin-g-PAM and the lignin-based MMA-co-BA hybrid resin was elucidated using 1H nuclear magnetic resonance and attenuated total reflectance–Fourier transform infrared. The thermal behavior and mechanical performance of the resultant lignin-based MMA-co-BA hybrid resins were also investigated through thermogravimetric analysis, differential scanning calorimetry, and a stress–strain test, respectively. The lignin-based acrylate resins system exhibited structure-related thermal and mechanical properties. Compared with pure MMA-co-BA resin, the incorporation of lignin into various lignin-based MMA-co-BA graft copolymers resulted in an improved tensile strength and a higher Young’s modulus. This research could provide not only a new avenue to utilize waste biomass for high-value applications, but also a reference for designing new materials for coatings or adhesives.

An acid-triggered porphyrin-based block copolymer for enhanced photodynamic antibacterial efficacy

Bacterial infection, especially multidrug-resistant (MDR) bacterial infection has threatened public health drastically. Here, we fabricate an “acid-triggered” nanoplatform for enhanced photodynamic antibacterial activity by reducing the aggregation of photosensitizers (PSs) in bacterial acidic microenvironment. Specifically, a functional amphiphilic block copolymer was first synthesized by using a pH-sensitive monomer, 2-(diisopropylamino) ethyl methacrylate (DPA) and porphyrin-based methacrylate (TPPC6MA) with poly(oligo(ethylene glycol) methyl ether methacrylate) (POEGMA) as the macromolecular chain transfer agent, and POEGMA-b-[PDPA-co-PTPPC6MA] block copolymer was further self-assembled into spherical nanoparticles (PDPA-TPP). PDPA-TPP nanoparticles possess an effective electrostatic adherence to negatively charged bacterial cell membrane, since they could rapidly achieve positive charge in acidic bacterial media. Meanwhile, the acid-triggered dissociation of PDPA-TPP nanoparticles could reduce the aggregation caused quenching (ACQ) of the photosensitizers, leading to around 5 folds increase of the singlet oxygen (1O2) quantum yield. In vitro results demonstrated that the “acid-triggered” PDPA-TPP nanoparticles could kill most of MDR S. aureus (Gram-positive) and MDR E. coli (Gram-negative) by enhanced photodynamic therapy, and they could resist wound infection and accelerate wound healing effectively in vivo. Furthermore, PDPA-TPP nanoparticles could well disperse the biofilm and almost kill all the biofilm-containing bacteria. Thus, by making use of the bacterial acidic microenvironment, this “acid-triggered” nanoplatform in situ will open a new path to solve the aggregation of photosensitizers for combating broad-spectrum drug-resistant bacterial infection.

Polycarbonate-block-polycycloalkenes via epoxide/carbon dioxide copolymerization and ring-opening metathesis polymerization

Aliphatic polycarbonate (APC) macromolecular chain-transfer agents (macro-CTAs) with an allyl end group were successfully synthesized by cobalt-catalyzed epoxide/carbon dioxide copolymerization in the presence of allyl alcohol as a chain-transfer agent. The ring-opening metathesis polymerization of cycloalkene monomers using the obtained APC macro-CTAs yielded the corresponding APC-block-polycycloalkene copolymers. Thermal degradation temperatures of the APC blocks were found to be slightly higher (≈20 oC) than those of the block copolymers containing APC and vinyl-polymer blocks we have previously reported. Aliphatic polycarbonate (APC) macromolecular chain-transfer agents (macro-CTAs) with an allyl end group were successfully synthesized by cobalt-catalyzed epoxide/carbon dioxide copolymerization in the presence of allyl alcohol as a chain-transfer agent. The ring-opening metathesis polymerization of cycloalkene monomers using the obtained APC macro-CTAs yielded the corresponding APC-block-polycycloalkene copolymers.

Poly[di(ethylene glycol) vinyl ether]-stabilized poly(vinyl acetate) nanoparticles with various morphologies via RAFT aqueous emulsion polymerization of vinyl acetate

Reversible addition fragmentation chain transfer (RAFT) aqueous emulsion polymerization of vinyl acetate (VAc) is performed using poly[di(ethylene glycol) vinyl ether] (PDEGV) macromolecular chain transfer agents (macro-CTAs) including RAFT end-unfunctionalized PDEGV (up to 32%). Emulsion polymerization directly induces PDEGV-b-PVAc diblock copolymer assemblies in water. This facile formulation enables the production of various particle morphologies, such as spheres, rods (ellipsoids), and vesicles, depending on the composition of the block copolymer. Many other examples of RAFT emulsion polymerization syntheses only result in the formation of kinetically trapped spheres, even when targeting highly asymmetric diblock compositions. However, despite being stabilized only by homopolymer PDEGV macro-CTAs, including PDEGV, PVAc-based nanoparticles with various morphologies can be obtained as PDEGV-b-PVAc assemblies. RAFT aqueous emulsion polymerization owes its success to recent RAFT polymerizations of hydroxy-functionalized vinyl ethers. We investigated the RAFT polymerization of DEGV, analyzed the kinetics of PDEGV-b-PVAc nanoparticle formation, and observed the morphology of resultant particles in detail. We also developed a phase diagram for this RAFT aqueous emulsion polymerization formulation that reliably predicts the precise block compositions associated with well-defined particle morphologies. RAFT aqueous emulsion polymerization of vinyl acetate (VAc) was performed using poly[di(ethylene glycol) vinyl ether] (PDEGV) macromolecular chain transfer agents. The emulsion polymerization directly induced PDEGV-b-PVAc diblock copolymer assemblies in water. Owing to the characteristic PDEGV as a highly hydrophilic steric stabilizer, this facile formulation enables the production of various particle morphologies, such as spheres, rods (ellipsoids), and vesicles, depending on the composition of the block copolymer. Each morphology change in the nanoparticles via RAFT aqueous emulsion polymerization owes its success to the recent RAFT polymerizations of vinyl ethers.

Preparation of Poly(MTZ) n -(DMAEMA) m Micelles and Study on Their Antibacterial Property.

Bacterial infections are the most common type of clinical infection. The abuse of clinical antibiotics has led to the frequent appearance of drug-resistant strains and even some super bacteria. In this study, we synthesized Poly(MTZ)n–(DMAEMA)m polymer micelles with cations on the surface. The synthesis of this novel polymer comes in two steps. First, Poly(MTZ)n was synthesized with metronidazole (MTZ) referred as the macromolecular chain transfer agent and v-501 as the initiator for initiating the polymerization of 4-cyanopentanoic acid dithiobenzoate. Then, novel polymer micelles were synthesized with Poly(MTZ)n referred as the macromolecular chain transfer agent and v-501 as the initiator for initiating the polymerization of the monomer 2-(dimethylamino) ethyl methacrylate, which could adsorb to the negatively charged bacterial surface via electrostatic interaction and enhance bactericidal activity. Scanning electron microscopy showed that the micelles could be accurately targeted to the surface of bacteria, and the zone of inhibition assay confirmed that the micelles could enhance the sensitivity of bacteria to drugs. Hence, Poly(MTZ)n–(DMAEMA)m polymer micelles will have potential use for the clinical treatment of anaerobic infections in the future.

Hydrogen-Bonding UCST-Thermosensitive Nanogels by Direct Photo-RAFT Polymerization-Induced Self-Assembly in Aqueous Dispersion.

Hydrogen-bonding upper critical solution temperature (UCST) thermosensitive nanogels based on poly(N-acryloyl glycinamide) (PNAGA) are synthesized by photo-reversible addition-fragmentation chain transfer mediated polymerization-induced self-assembly (photo-RAFT PISA) in aqueous dispersion using N,N'-methylenebis(acrylamide) as crosslinker and poly(oligo(ethylene glycol) methyl ether acrylate) as both stabilizer and macromolecular chain transfer agent (macro-CTA). Highly stable, spherical nanogels with narrow polydispersity are efficiently produced up to complete monomer conversion within 1 h under UV irradiation at low temperature (3 °C). The thermosensitive behavior of PNAGA-based nanogels, as assessed by dynamic light scattering and UV-vis spectrophotometry, exhibits reversible heating-induced swelling and cooling-induced shrinking corresponding to the expected UCST behavior. The hydrodynamic diameter, swelling ratio, and phase transition temperature of nanogels can be tuned by modifying the initial molar ratio of monomer-to-macro-CTA and the amount of crosslinker in the photo-RAFT PISA of NAGA.

Proteins Conjugated with Sulfoxide-Containing Polymers Show Reduced Macrophage Cellular Uptake and Improved Pharmacokinetics.

The conjugation of hydrophilic polymers to proteins is an effective approach to prolonging their circulation time in the bloodstream and, hence, improving their delivery to the target region of interest. In this work, we report the synthesis of protein-polymer conjugates using a highly water-soluble sulfoxide-containing polymer, poly(2-(methylsulfinyl)ethyl acrylate) (PMSEA), through a combination of "grafting-to" and "grafting-from" methods. Oligomeric MSEA was synthesized by conventional reversible addition-fragmentation chain transfer (RAFT) polymerization and subsequently conjugated to lysozyme to produce a macromolecular chain transfer agent. This was followed by a visible light-mediated chain extension polymerization of MSEA to obtain a lysozyme-PMSEA conjugate (Lyz-PMSEA). It was found that the Lyz-PMSEA conjugate exhibited much reduced macrophage cellular uptake compared with unmodified and PEGylated lysozyme. Moreover, the Lyz-PMSEA conjugate was able to circulate longer in the bloodstream, demonstrating significantly improved pharmacokinetics demanded for pharmaceutical applications.

Ethylene Polymerization-Induced Self-Assembly (PISA) of Poly(ethylene oxide)-block-polyethylene Copolymers via RAFT.

Poly(ethylene oxide) (PEO) with dithiocarbamate chain ends (PEO-SC(=S)-N(CH3 )Ph and PEO-SC(=S)-NPh2 , named PEO-1 and PEO-2, respectively) were used as macromolecular chain-transfer agents (macro-CTAs) to mediate the reversible addition-fragmentation chain transfer (RAFT) polymerization of ethylene in dimethyl carbonate (DMC) under relatively mild conditions (80 °C, 80 bar). While only a slow consumption of PEO-1 was observed, the rapid consumption of PEO-2 led to a clean chain extension and the formation of a polyethylene (PE) segment. Upon polymerization, the resulting block copolymers PEO-b-PE self-assembled into nanometric objects according to a polymerization-induced self-assembly (PISA).

Dextran-covered pH-sensitive oily core nanocapsules produced by interfacial Reversible Addition-Fragmentation chain transfer miniemulsion polymerization

Aiming to prepare oily core pH-sensitive nanocapsules (NCs) for anticancer drugs delivery, the use of a dextran-based transurf (DexN3-τCTAγ) as both stabilizer and macromolecular chain transfer agent in methyl methacrylate/2-(diethylamino)ethyl methacrylate (MMA/DEAEMA) miniemulsion copolymerization was investigated. NCs of about 195 nm with an oily-core of Miglyol 810 (M810) and a dextran coverage covalently linked to the poly(MMA-co-DEAEMA) intern shell have been obtained. Compared to the non-sensitive PMMA-based NCs (prepared in a similar way), these novel objects were shown to swell in acidic media and to trigger Coumarin 1 release in physiological relevant pH range. As a starting point of NCs biological effects, cytotoxicity and NCs-proteins interactions studies were performed with both PMMA and poly(MMA-co-DEAEMA)-based NCs. Finally, free azide functions from dextran-based coverage were successfully exploited to attach fluorescent model dyes to NCs surface. The overall results suggest that this novel NCs platform could be potentially used as drug nanocarriers for intravenous injection.

Synthesis of dextran-based chain transfer agent for RAFT-mediated polymerization and glyco-nanoobjects formulation

Glycopolymers based on dextran are frequently prepared via ATRP, whereas the use of RAFT polymerization is strangely limited due to the difficult synthesis of Dextran-based macromolecular chain transfer agent (DexCTA). The aim of this work is to establish a controlled and reproducible methodology for its preparation. Direct esterification of the hydroxyl dextran functions is the most common method. Our study shows that this latter leads to a very low degree of functionalization. As alternative, we report a reproductible multistep strategy consisting of oxidation, amination, and amidation reactions. Various DexCTAs with tunable degree of substitution (respectively 0.025, 0.045, and 0.06) were successfully prepared. As proof of concept, one of the DexCTAs was involved in the photo-mediated RAFT polymerization of hydroxypropyl methacrylate in DMSO to prepare amphiphilic Dex-g-PHPMA glycopolymers, which can self-assemble in water into monodisperse spherical nano-objects. MTT assays revealed the biocompatibility of all dextran derivatives.

Poly(vinyl acetate-co-ethylene) particles prepared by surfactant-free emulsion polymerization in the presence of a hydrophilic RAFT/MADIX macromolecular chain transfer agent

Poly(vinyl acetate-co-ethylene) latexes are prepared under a broad range of conditions by emulsion polymerization in the presence of a hydrophilic RAFT/MADIX macromolecular chain transfer agent.