Single Electron Transfer-living Radical Polymerization Research Articles

PH and thermo dual-responsive starch-g-P(DEAEMA-co-PEGMA): Synthesis via SET-LRP, self-assembly and drug release behaviors

A novel pH and thermo dual-responsive graft copolymer, starch-graft-poly(N,N-diethyl aminoethyl methacrylate-co-poly(ethylene glycol) methyl ether methacrylate) [starch-g-P(DEAEMA-co-PEGMA)], was successfully synthesized through single-electron transfer living radical polymerization (SET-LRP). The structure and molecular weight of the grafted chains were confirmed by 1H NMR. These graft copolymers can self-assemble into micelles with starch backbone and PDEAEMA as the core and PPEGMA as the corona in water at pH 7.4. The critical micelle concentration (CMC) of the graft copolymers varied between 0.0313 and 0.1364 mg/mL, decreasing with an increase in the molecular weight of the grafted chains and the ratio of PDEAEMA and PPEGMA segments. The pH and thermo dual-responsive behaviors of starch-g-P(DEAEMA-co-PEGMA) micelles were investigated by DLS and TEM. As the pH decreasd from 8.0 to 5.5, the micelle sizes continued to increase due to the protonation of the PDEAEMA segments, and as the pH decreased to below 5.5, the micelles began to disassemble, which was verified by TEM observations. Upon heating, the size of the micelles decreased because of the shrinkage of the PDEAEMA segments. The pH and thermo dual-responsive behaviors of the starch-g-P(DEAEMA-co-PEGMA) micelles are reversible. Doxorubicin (DOX), a hydrophobic drug, was encapsulated in the micelles, and in vitro release from the drug-loaded micelles displayed good pH-responsive behavior.

Polymer Brush Graft-Modified Starch-Based Nanoparticles as Pickering Emulsifiers.

We study biosourced core-shell particles with a starch-based core and thermo-responsive polymer brush shell using surface-initiated single-electron transfer living radical polymerization (SI-SET-LRP) as a Pickering stabilizer. The shell endows the Pickering stabilizer with reversible emulsification/demulsification of oil and water properties. The initiator attached to the starch-based nanosphere (Br-SNP) core particle was first fabricated using the precipitation method. Subsequently, dense poly( N-isopropylacrylamide) (PNIPAM) brush graft-modified starch-based nanoparticles (SNP- g-PNIPAM) were obtained via the SI-SET-LRP process. Interfacial properties of the resultant particles were analyzed by interfacial tensiometer measurements, as were the effects of the grafted polymer chain length and temperature on the interfacial activity. Pickering emulsion was obtained using SNP- g-PNIPAM particles as the stabilizer. The effect of the concentration of the Pickering stabilizer on the size of emulsion droplets was analyzed. The emulsification/demulsification process of the Pickering emulsion can be reversed and easily repeated by changing the temperature.

Polyacrylates Derived from Biobased Ethyl Lactate Solvent via SET-LRP.

The precise synthesis of polymers derived from alkyl lactate ester acrylates is reported for the first time. Kinetic experiments were conducted to demonstrate that Cu(0) wire-catalyzed single electron transfer-living radical polymerization (SET-LRP) in alcohols at 25 °C provides a green methodology for the LRP of this forgotten class of biobased monomers. The acrylic derivative of ethyl lactate (EL) solvent and homologous structures with methyl and n-butyl ester were polymerized with excellent control over molecular weight, molecular weight distribution, and chain-end functionality. Kinetics plots in conventional alcohols such as ethanol and methanol were first order in the monomer, with molecular weight increasing linearly with conversion. However, aqueous EL mixtures were found to be more suitable than pure EL to mediate the SET-LRP process. The near-quantitative monomer conversion and high bromine chain-end functionality, demonstrated by matrix-assisted laser desorption ionization time-of-flight analysis, further allowed the preparation of innovative biobased block copolymers containing rubbery poly(ethyl lactate acrylate) poly(ELA) sequences. For instance, the poly(ELA)- b-poly(glycerol acrylate) block copolymer self-assembled in water to form stable micelles with chiral lactic acid-derived block-forming micellar core as confirmed by the pyrene-probe-based fluorescence technique. Dynamic light scattering and transmission electron microscopy measurements revealed the nanosize spherical morphology for these biobased aggregates.

Preparation of starch-graft-poly(methyl methacrylate) via SET-LRP at molecular level and its self-assembly

A series of starch-graft-poly (methyl methacrylate) (S-g-PMMA) copolymers were prepared by single electron transfer living radical polymerization (SET-LRP) at molecular level under mild conditions. The successful grafting polymerization was confirmed by FT-IR and 1H NMR spectroscopies. The hydrolysate of S-g-PMMA via acid-catalyzed hydrolysis proved to be a mixture of 1-arm, 2-arm and 3-arm polymers by MALDI-TOF measurements. Furthermore, the micelles formed by S-g-PMMA copolymers in water were studied at various conditions by SEM, TEM and DLS measurements. The results indicate that the sizes of micelles decreased following the order of the common solvents of 1,4-dioxane, tetrahydrofuran, acetone and acetonitrile, and also increased with the increase of initial copolymer concentrations, addition rate of water and length of grafted chains.

Evolution in the morphological behaviour of a series of fluorine-containing ABC miktoarm star terpolymers

Fluorine-containing amphophilic polymers, as well as star polymers, have shown extremely abundant self-assembled morphologies because of microphase separation within the assemblies. Taking advantage of these characteristics, we prepared a series of ABC miktoarm star terpolymers with poly(ethylene glycol) (PEG) as a hydrophilic block, as well as poly(2-ethylhexylmethacrylate) (PEHMA) as a hydrophobic chain. Poly(1H,1H,5H-octafluoropentylmethacrylate) (POFPMA) was chosen as the third segment of terpolymers because of its super-hydrophobic/oleophobic characteristics. The terpolymers were synthesised via atom transfer radical polymerisation (ATRP), single electron transfer living radical polymerisation (SET-LRP) and azide-alkyne Huisgen cycloaddition (click reaction). Herein, we investigated the self-assembled behaviours of nanoaggregates formed by varying the length of POFPMA and PEHMA chains of the terpolymers in aqueous solution. The tunable miktoarm star polymer favoured the transformation of nanoassemblies, from patchy spherical micelles to patchy spherical aggregates, spherical micelles, egg-like micelles, segmented-worm micelles, shuttle-like micelles and vesicles. Interestingly, special discontinuous aggregations arranged into lines were observed, which has been seldom found before. The independent control of both of the hydrophobic parameters of terpolymers enhanced the nanostructures of polymeric assemblies of ABC miktoarm terpolymers, providing a reliable method to explore the compartmentalisation behaviours of soft matter assemblies.

SET-LRP of Bio- and Petroleum-Sourced Methacrylates in Aqueous Alcoholic Mixtures.

Single-electron transfer-living radical polymerization (SET-LRP) in "programmed" aqueous organic biphasic systems eliminates the judicious choice of solvent and also provides accelerated reaction rates. Herein, we report efforts to expand the monomer scope for these systems by targeting methacrylic monomers and polymers. Various environmentally friendly aqueous alcoholic mixtures were used in combination with Cu(0) wire catalyst, tris(2-dimethylaminoethyl)amine (Me6-TREN) ligand, and p-toluenesulfonyl chloride (Ts-Cl) initiator to deliver well-defined polymethacrylates from methyl methacrylate, butyl methacrylate, and other monomers derived from biomass feedstock (e.g., lactic acid, isosorbide, furfural, and lauric acid). The effect of water on the nature of the reaction mixture during the SET-LRP process, reaction rate, and control of the polymerization is discussed. The control retained under the reported conditions is demonstrated by synthesizing polymers of different targeted molar mass as well as quasi-block AB copolymers by "in situ" chain extension at high conversion. These results highlight the capabilities of SET-LRP to provide sustainable solutions based on renewable resources.

A polysaccharide-based micelle-hydrogel synergistic therapy system for diabetes and vascular diabetes complications treatment

Various glucose-sensitive drug delivery platforms have been developed recently to treat diabetes. However, there is much less work has been reported on treatment of diabetes and vascular diabetes complications simultaneously. In this work, a novel polysaccharide-based micelle-hydrogel synergistic therapy system was fabricated to address this limitation. Zwitterionic dialdehyde starch-based micelles (SB-DAS-VPBA) were synthesized via single electron transfer-living radical polymerization (SET-LRP). Hydrophilic segment sulfobetaine (SB) and hydrophobic segment 4‑vinylphenylboronic acid (VPBA) were grafted to the dialdehyde starch (DAS) backbones. Then, chitosan/dialdehyde starch derivatives (CS/SB-DAS-VPBA) micelle-hydrogel was synthesized by Schiff-base bonds. Insulin and nattokinase were loaded to obtain the micelle-hydrogel synergistic therapy system. In vitro drug delivery and blood clots dissolution behaviors were determined. Results suggest that the micelle-hydrogel synergistic therapy system not only possesses glucose-responsive insulin delivery property, but also provides good thrombolytic capacity. Thus, this micelle-hydrogel synergistic therapy system can be used as a platform for diabetes and vascular diabetes complications treatment.

Synthesis of an Acrylamide Copolymer Containing Nano-SiO2 by Ex Situ Cu(0)-Mediated SET-LRP

We report herein the synthesis of a novel star-shaped copolymer containing nano-SiO2 by single-electron transfer living radical polymerization (SET-LRP) in aqueous solution. The effects of polymerization conditions, such as the total amounts and molar ratios of the monomer, initiator, catalyst, ligand, and modified nano-SiO2, have been investigated through a series of experiments. The prepared acrylamide copolymers have been characterized by FTIR spectroscopy and 1H NMR spectrometry. The properties of the copolymers have been assessed by viscometry and rheometry. The results confirmed that the nano-SiO2 functional monomer was successfully combined in the SET-LRP. The optimum polymerization conditions were established through orthogonal experiments as a ratio of [AM] : [DMAEMA] : [I] : [CuBr] : [Me6TREN] of 674.4 : 35.5 : 1 : 1 : 2 at a total concentration of [AM] + [DMAEMA] of 2.5 mol/L. The appropriate concentration of the nano-SiO2 functional monomer (NSFM) was 0.5 wt% with respect to AM + DMAEMA. The rheology of the star-shaped copolymer exhibited a shear-thickening property when the shear rate exceeded a critical value (100 s−1). The AM/DMAEMA/NSFM copolymer displayed a higher viscosity than AM/DMAEMA at the same concentration. It was found that AM/DMAEMA/NSFM exhibited better salt and temperature tolerances.

Luminol‐Pendant Chemiluminescent Polymethacrylamide‐Based Polymers for Peroxide Sensing in Live Cell Imaging.

AbstractThe present study aims at the development of luminol pendant functionalized chemiluminescent polymethacrylamides, for sensing and imaging applications. Luminol functionalized poly(methacrylamide) homopolymer was synthesized by the post‐polymerization modification of poly(methacryloyl chloride), (PMC) with luminol. Luminol based methacrylamide monomer (LUME) was synthesized using a simple Schotten‐Baumann type reaction between methacryloyl chloride and luminol. LUME was copolymerized with hydroxyethyl methacrylate (HEMA) using SET‐LRP (Single Electron Transfer‐ Living Radical Polymerization), a controlled radical polymerization technique. Luminol functionalized homo (PML) and copolymer (PHL) were having excellent solubility in basic medium as well as polar solvents like as dimethyl sulfoxide and dimethyl formamide. Basic solutions of both PML and PHL copolymers were tested for their chemiluminescent sensing of hydrogen peroxide using graphene oxide (GO) as a catalyst. Chemiluminescence intensity was found to be varying linearly with an increase in the concentration of hydrogen peroxide for both these polymers. Upto 1 μM of peroxide can be sensed even with a very dilute solution of PML (1.8x10−11M) and PHL (2x10−8M).These chemiluminescent polymethacrylamides were also studied for peroxide sensing in live cells.

Antifouling Microparticles To Scavenge Lipopolysaccharide from Human Blood Plasma.

Currently, one of the most promising treatments of lipopolysaccharides (LPS)-induced sepsis is based on hemofiltration. Nevertheless, proteins rapidly adsorbed on the artificial surface of membranes which leads to activation of coagulation impairing effective scavenging of the endotoxins. To overcome this challenge, we designed polymer-brush-coated microparticles displaying antifouling properties and functionalized them with polymyxin B (PMB) to specifically scavenge LPS the most common endotoxin. Poly[( N-(2-hydroxypropyl) methacrylamide)- co-(carboxybetaine methacrylamide)] brushes were grafted from poly(glycidyl methacrylate) microparticles using photoinduced single-electron transfer living radical polymerization (SET-LRP). Notably, only parts-per-million of copper catalyst were necessary to achieve brushes able to repel adsorption of proteins from blood plasma. The open porosity of the particles, accessible to polymerization, enabled us to immobilize sufficient PMB to selectively scavenge LPS from blood plasma.

Facile Preparation of Epoxide-Functionalized Surfaces via Photocurable Copolymer Coatings and Subsequent Immobilization of Iminodiacetic Acids.

Herein, we report a simple coat/cure preparation of epoxide-functionalized surfaces using a photocurable copolymer technology. The photocurable copolymer, poly(glycidyl methacrylate- co-butyl acrylate- co-4-benzoylphenyl methacrylate) (GBB), was synthesized by single electron transfer-living radical polymerization (SET-LRP). The epoxide content in the copolymer was tuned by controlling the content of glycidyl methacrylate. Three copolymers, GBB(1), GBB(2), and GBB(3), with epoxide contents of 22, 63, and 91 mol %, respectively, were cast onto polypropylene films and photocured by UV-light exposure. Subsequently, iminodiacetic acids (IDA) were immobilized onto the GBB-coated materials via a ring-opening reaction. The IDA-functionalized coatings GBB(1)-IDA, GBB(2)-IDA, and GBB(3)-IDA presented IDA contents of 1.47 ± 0.08, 18.67 ± 1.46, and 49.05 ± 2.88 nmol/cm2, respectively, which increased as the epoxide content increased. The IDA-functionalized GBB coatings exhibited metal chelating capability toward transition metal ions (e.g., iron and copper). The reported photocurable copolymer technology offers a facile and tunable preparation of epoxide-functionalized surfaces, with potential extended applications in biopatterning, active packaging, and nanotechnology.

A novel side-chain ferrocene-containing polymer by combination of Cu(0)-mediated SET-LRP of acrylonitrile and post-modification

Well-defined side-chain ferrocene-containing polymers have been synthesized by post-modification of well-defined polyacrylonitrile (PAN). PAN prepared by Cu(0)-mediated single-electron transfer living radical polymerization was further modified using sodium azide and ammonium chloride (NH4Cl) to yield polymeric materials with vinyltetrazole units. Side-chain ferrocene-containing polymer was prepared by vinyltetrazole units and hydroxymethylferrocene after Mitsunobu reaction. FTIR, 1H NMR, UV–Vis spectroscopy and thermogravimetric analysis were used to identify the structure of the target product. After linked the ferrocene unit, the final polymer showed typical redox property with a more negative redox potential (E1/2).

Synthesis of a double-hydrophilic star-block copolymer by aqueous SET-LRP and its dual-stimuli responses

The synthesis of a well-defined dual-responsive double-hydrophilic star-block copolymer by single-electron-transfer living radical polymerization (SET-LRP) in aqueous solution is reported. Conditions for iterative block formation have been optimized for an N-isopropylacrylamide three-armed star-shaped polymer, which was prepared with DP = 120–360 with full conversion in < 30 min with polydispersity index (Ð) < 1.18. To demonstrate this approach for true block stimuli-responsive copolymer materials, a well-defined block polymer containing N-isopropylacrylamide, dimethylaminoethyl methacrylate, and N-vinylpyrrolidone has been prepared in high purity, with purification only required in the final step. The Ð after each chain extension was below 1.20. The polymer has been characterized by FTIR spectroscopy, 1H NMR spectrometry, and gel permeation chromatography. The responsive behaviors of the block-star copolymer have been studied by turbidity measurements, dynamic light scattering, and transmission electron microscopy. The phase transition temperature of the star-block copolymer increased with decreasing pH. At pH 3.0, the copolymer displayed weak thermo-responsive behavior. At higher pH (8.6 and 10.0), the star-block copolymer showed a strong thermal response and formed spherical micelles and vesicles.

SET-LRP of the Hydrophobic Biobased Menthyl Acrylate.

Cu(0) wire-catalyzed single electron transfer-living radical polymerization (SET-LRP) of (-)-menthyl acrylate, a biobased hydrophobic monomer, was investigated at 25 °C in ethanol, isopropanol, ethyl lactate, 2,2,2-trifluoroethanol (TFE), and 2,2,3,3-tetrafluoropropanol (TFP). All solvents are known to promote, in the presence of N ligands, the mechanistically required self-regulated disproportionation of Cu(I)Br into Cu(0) and Cu(II)Br2. Both fluorinated alcohols brought out their characteristics of universal SET-LRP solvents and showed the proper polarity balance to mediate an efficient polymerization of this bulky and hydrophobic monomer. Together with the secondary alkyl halide initiator, methyl 2-bromopropionate (MBP), and the tris(2-dimethylaminoethyl)amine (Me6-TREN) ligand, TFE and TPF mediated an efficient SET-LRP of MnA at room temperature that proceeds through a self-generated biphasic system. The results presented here demonstrate that Cu(0) wire-catalyzed SET-LRP can be used to target polyMnA with different block lengths and narrow molecular weight distribution at room temperature. Indeed, the use of a combination of techniques that include GPC, 1H NMR, MALDI-TOF MS performed before and after thioetherification of bromine terminus via "thio-bromo" click chemistry, and in situ reinitiation copolymerization experiments supports the near perfect chain end functionality of the synthesized biobased hydrophobic polymers. These results expand the possibilities of SET-LRP into the area of renewable resources where hydrophobic compounds are widespread.

Improving Hemocompatibility of Membranes for Extracorporeal Membrane Oxygenators by Grafting Nonthrombogenic Polymer Brushes.

Nonthrombogenic modifications of membranes for extracorporeal membrane oxygenators (ECMOs) are of key interest. The absence of hemocompatibility of these membranes and the need of anticoagulation of patients result in severe and potentially life-threatening complications during ECMO treatment. To address the lack of hemocompatibility of the membrane, surface modifications are developed, which act as barriers to protein adsorption on the membrane and, in this way, prevent activation of the coagulation cascade. The modifications are based on nonionic and zwitterionic polymer brushes grafted directly from poly(4-methyl-1-pentene) (TPX) membranes via single electron transfer-living radical polymerization. Notably, this work introduces the first example of well-controlled surface-initiated radical polymerization of zwitterionic brushes. The antifouling layers markedly increase the recalcification time (a proxy of initiation of coagulation) compared to bare TPX membranes. Furthermore, platelet and leukocyte adhesion is drastically decreased, rendering the ECMO membranes hemocompatible.

One‐Pot Two‐Step (First ROP, Then SET‐LRP) Synthesis of Polycaprolactone‐Polyacrylate Star Block Copolymers

AbstractA one‐pot, two‐step method is applied to the controlled synthesis of polyacrylate‐b‐(polycaprolactone)2 three‐arm AB2‐type star block polymers. First, ring‐opening polymerization (ROP) of ε‐caprolactone is carried out in toluene using either stannous octoate (Sn(Oct)2) or diphenyl phosphate (DPP) as catalyst, and a multifunctional initiator featuring one bromoester and two alcohol groups. Then, single‐electron transfer living radical polymerization (SET‐LRP) of methyl acrylate and isobornyl acrylate is conducted in the same reaction vessel after sequential addition of its typical reactants, apart from the (PCL)2‐Br macroinitiator generated in the first step, in either toluene/toluene + phenol or toluene/dimethyl sulfoxide solvent systems. DPP (the ROP catalyst) from the first step is found to take part in an acid–base reaction with tris[2‐(dimethylamino)ethyl]amine (the SET‐LRP N‐ligand) in the second part, but stoichiometry could be adjusted to avoid interference and keep the controlled nature of the polymerizations. Interestingly, the electrochemically active Sn(Oct)2 ROP catalyst does not interfere with the SET‐LRP process. Well‐defined poly(methyl acrylate)‐b‐(polycaprolactone)2 and poly(isobornyl acrylate)‐b‐(polycaprolactone)2 are thus synthesized through a simple and cost‐effective experimental procedure. The technique also applies to the synthesis of linear block copolymers.

Preparation of Reinforced poly (BisGMA-UDMA) Graphene-Based Nanocomposites Via Moderate in Situ SET-LRP

ABSTRACTIn the present study, cross-linked poly (dimethacrylate- urethane dimethacrylate) [poly (BisGMA-UDMA)] functionalized-graphene oxide nanosheets were prepared via single-electron transfer living radical polymerization (SET-LRP) using the ‘grafting from’ strategy, under mild conditions. This method first involves the covalent attachment of Br-containing groups onto the surface of grapheme sheets to give the initiating-groups-containing graphene (G-Br). After that, the succeeding SET-LRP polymerization in DMSO in the presence of a Cu wire/Me6TREN catalytic system at room temperature leads to the grafting of poly (BisGMA-UDMA) chains onto the graphene surface. The resulting graphene-poly (dimethacrylate- urethane dimethacrylate) (G-PDMA-UDMA) nanocomposites were characterized using FT-IR, XRD, DSC, AFM, FE-SEM, and TEM analysis techniques. It was proved that polymer chains were successfully introduced to the surface of the graphene planes. After grafting with poly (BisGMA-UDMA), the dispersibility of the modified GO sheets significantly improved. When compared to G-PDMA, the resulting G-PDMA-UDMA nanocomposite revealed around 75%, 97%, and 65%, increase in compressive strength, Young's modulus and toughness, respectively. Such smart graphene-based nanocomposites can be used as promising biomaterials in orthopaedic and dental applications with the desired mechanical properties.

Surface modification and drug delivery applications of MoS2 nanosheets with polymers through the combination of mussel inspired chemistry and SET-LRP

Abstract Mussel inspired chemistry is a promising surface modification tool, which has attracted great research attention for different applications owing to its universality and interest properties. In this work, a rather simple and efficient method for the surface modification of MoS2 nanosheets with copolymers was achieved through the combination of mussel inspired chemistry and single-electron transfer living radical polymerization (SET-LRP) using 2-methacryloyloxyethyl phosphorylcholine (MPC) and itaconic acid (IA) as the monomers. The obtained MoS2-PDA-poly(MPC-IA) nanocomposites were ascertained by a series of characterization techniques, such as nuclear magnetic resonance spectroscopy, transmission electron microscopy, Fourier transform infrared spectroscopy, thermogravimetric analysis and X-ray photoelectron spectroscopy. Moreover, the MoS2-PDA-poly(MPC-IA) nanocomposites showed enhanced dispersbility and great biocompatibility. The results implied that the MoS2-PDA-poly(MPC-IA) nanocomposites showed great potential in the field of biomedical science. In this work, the drug loading capability and controlled drug release behavior towards CDDP have been investigated. The drug loading in MoS2-PDA-poly(MPC-IA) composites is as high as 55.26%. All of these above results suggested that the combination of mussel inspired chemistry and SET-LRP is a facile and efficient strategy for fabrication of MoS2 based polymer nanocomposites with great potential application in biomedical fields.

Sequence Controlled Polymers from a Novel β-Cyclodextrin Core.

In this work the synthesis and use of a novel β-cyclodextrin-based single electron transfer-living radical polymerization (SET-LRP) initiator are reported. Three different approaches toward the synthesis of this initiator, based on several "click"-like reactions (copper(I)-catalyzed azide-alkyne cycloaddition, nucleophilic thiol-ene reaction, and radical thiol-ene reaction), are explored and discussed. Synthesis via radical thiol-ene proves to be most successful in achieving this. The β-cyclodextrin-based initiator is subsequently used for the polymerization of several acrylates in a controlled fashion, yielding 7-arm multiblock copolymers. The achieved sequence-controlled polymers exhibit low dispersities (≤1.12) and are completed under 6.5 h at high monomer conversion (≥95%) for each block.

Single-Electron Transfer Living Radical Polymerization Platform to Practice, Develop, and Invent.

The most fundamental aspects of single-electron transfer (SET) principles are presented. They are discussed according to different definitions used by expert practitioners and are applied to SET living radical polymerization (SET-LRP) according to the definition of the division of organic chemistry of IUPAC that relies on principles elaborated by Taube, Eberson, Chanon, and Kochi. Additional definitions are also discussed to help clarify for the nonexpert contradictory literature reports. Subsequently, the principles and evolution of SET-LRP together with the methodologies currently available to practice it are discussed. It is expected that this Perspective will be able to help experts and nonexperts practice, develop, and invent new concepts and methodologies for SET-LRP to advance its status and the status of other living radical polymerization methods to the level of the most precise living polymerization methods.