Reversible Addition Fragmentation Research Articles

Synthesis of lipase polymer hybrids with retained or enhanced activity using the grafting-from strategy

We report the synthesis of new polymer-protein conjugates using a grafting-from method employing photoinduced electron transfer reversible addition-fragmentation chain transfer (PET-RAFT) polymerization. Lipase, an industrially important enzyme, was modified with a reversible addition-fragmentation (RAFT) chain transfer agent (CTA) using activated ester chemistry. To study the effects of polymer composition and molecular weight on the enzyme activity, a hydrophilic and hydrophobic polymer were grafted at three different polymer lengths. We found a significant impact of polymer composition on enzyme activity with hydrophobic polymer substantially increasing enzyme activity.

Synthesis of Poly(lactic acid)-block-poly(N,N-dimethylaminoethyl methacrylate) Copolymers with Controllable Block Structures via Reversible Addition Fragmentation Polymerization from Aminolyzed Poly(lactic acid)

Poly(lactic acid)-block-poly(N,N-dimethylaminoethyl methacrylate) (PLA-PDMAEMA) copolymers were synthesized from aminolyzed PLA via reversible addition fragmentation (RAFT) polymerization. PLA undergoes aminolytic degradation with ethylenediamine (EDA). The kinetics of the aminolysis reaction of PLA at different temperatures and EDA concentrations was investigated in detail. The molar masses of products rapidly decreased in the initial stage at low aminolytic degree. Meanwhile, reactive –NH2 and –OH groups were introduced to the end of shorter PLA chains and used as sites to further immobilize the RAFT agent. PLA-PDMAEMA block copolymers were synthesized. A pseudo-first-order reaction kinetics was observed for the RAFT polymerization of PDMAEMA at a low conversion. By controlling the aminolysis reaction of PLA and RAFT polymerization degree of DMAEMA, the length distributions of the PLA and PDMAEMA blocks can be controlled. This method can be extended to more systems to obtain block copolymers with controllable block structure.

Self‐Healable and Tough Thermoplastic Materials from Metal–Thioether Block Polymers

AbstractThioether‐based acrylate block polymers are conveniently prepared via reversible addition–fragmentation chain‐transfer polymerization, and further combined with the merit of reversible metal–thioether coordination to fabricate a new type of “smart” thermoplastic materials. This metal/polymer hybrid architecture imparts extraordinary mechanical performance to the product materials, exhibiting an excellent ductility (breaking strain ≈ 1000%) as well as a relatively high breaking stress (1–5 MPa). Notably, it is facile to thermally process these materials into desired shapes (e.g., dog‐bone specimens, films, disks, etc.). Most importantly, these thermoplastic materials are endowed with the smart characteristic of being self‐healable under ambient conditions. To the authors' knowledge, it is the first report on thermally processable, self‐healing, and mechanically tough thermoplastic materials based on thioether polymers. These discoveries not only provide a pioneering route to design and construct self‐healing thermoplastics, but also elucidate the pathway toward a large portfolio of new hybrid materials built on the platform of organosulfur chemistry.

Use of short isobornyl methacrylate building blocks to improve the heat and oil resistance of thermoplastic elastomers via RAFT emulsion polymerization

ABSTRACTTriblock copolymer (TCP)‐based thermoplastic elastomers (TPEs) were designed via reversible addition–fragmentation chain‐transfer emulsion polymerization. Short isobornyl methacrylate (IM) building blocks in the two ends of molecular chain were incorporated to guarantee the mechanical properties of the TPEs at high temperature (i.e., heat resistance) because of the high glass‐transition temperature (Tg) of poly(isobornyl methacrylate) (PIM; ∼180 °C). The microphase separation, tensile properties at different temperatures, dynamic mechanical properties, oil resistance, and thermal stability of the TPEs were extensively characterized. The TPEs had distinct microphase separation with a wide inter‐Tg interval (150–185 °C). The tensile strength and elongation at break of the TPEs decreased with increasing temperature from 25 to 100 °C because of the reduced interactions in the phase domain. Even so, the TPEs had a high elongation at break beyond 200% and little change in the tensile strength even at 100 °C together with a wide quasi‐platform stage between the Tg values in dynamic mechanical analysis; this indicated good heat resistance. Meanwhile, the TPEs had an enhanced oil resistance and a thermal stability higher than 300 °C. These TCP‐based TPEs with heat and oil resistance broaden the application potential in practical fields. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017, 134, 45379.

RAFT‐mediated graft polymerization of glycidyl methacrylate in emulsion from polyethylene/polypropylene initiated with γ‐radiation

ABSTRACTThe successful reversible addition‐fragmentation (RAFT)‐mediated graft polymerization of glycidyl methacrylate (GMA) in emulsion phase from polyethylene/polypropylene nonwoven fabric using 4‐cyano‐4‐[(phenylcarbonothioyl)thio]pentanoic acid under γ‐irradiation at ambient condition is reported. While conventional graft polymerization in emulsion phase yielded grafted materials with low of grafting (Dg) values [<7.5% at 10% (wt/wt) GMA], addition of RAFT agent to the graft polymerization system allowed the synthesis of polyethylene/polypropylene‐g‐poly(GMA) with more tunable Dg (8% ≤ Dg ≤ 94%) by controlling the grafting parameters. Relatively good control (PDI ∼1.2 for selected grafting conditions) during polymerization was attained at 100:1 monomer‐to‐RAFT agent molar ratio. The number average molecular weight of free poly(glycidyl methacrylate) (PGMA) increased as a function of monomer conversion. NMR analyses of the free PGMA homopolymers indicate the presence of dithiobenzoate group from 4‐cyano‐4‐((phenylcarbonothioyl)thio) pentanoic acid on the polymer chain. The reactive pendant oxirane group of the grafted GMA can be modified for various environmental and industrial applications. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017, 134, 45270.

Synthesis of Discrete Oligomers by Sequential PET‐RAFT Single‐Unit Monomer Insertion

AbstractUniform synthetic polymers with precisely defined molar mass and monomer sequence (primary structure) have many potential high‐value applications. However, a robust and versatile synthetic strategy for these materials remains one of the great challenges in polymer synthesis. Herein we describe proof‐of‐principle experiments for a modular strategy to produce discrete oligomers by a visible‐light‐mediated radical chain process. We utilize the high selectivity provided by photo‐induced electron/energy transfer (PET) activation to develop efficient single unit monomer insertion (SUMI) into reversible addition–fragmentation chain‐transfer (RAFT) agents. A variety of discrete oligomers (single unit species, dimers, and, for the first time, trimers) have been synthesized by sequential SUMI in very high yield under mild reaction conditions. The trimers were used as building blocks for the construction of uniform hexamers and graft copolymers with precisely defined branches.

PH-Degradable Mannosylated Nanogels for Dendritic Cell Targeting.

We report on the design of glycosylated nanogels via core-cross-linking of amphiphilic non-water-soluble block copolymers composed of an acetylated glycosylated block and a pentafluorophenyl (PFP) activated ester block prepared by reversible addition-fragmentation (RAFT) polymerization. Self-assembly, pH-sensitive core-cross-linking, and removal of remaining PFP esters and protecting groups are achieved in one pot and yield fully hydrated sub-100 nm nanogels. Using cell subsets that exhibit high and low expression of the mannose receptor (MR) under conditions that suppress active endocytosis, we show that mannosylated but not galactosylated nanogels can efficiently target the MR that is expressed on the cell surface of primary dendritic cells (DCs). These nanogels hold promise for immunological applications involving DCs and macrophage subsets.

Core–shell particles of poly(methyl methacrylate)‐block‐poly(n‐butyl acrylate) synthesized via reversible addition–fragmentation chain‐transfer emulsion polymerization and the polymer's application in toughening polycarbonate

ABSTRACTPoly(methyl methacrylate) (PMMA) block copolymer is interesting because it is compatible with many polymers. A series of poly(methyl methacrylate)‐b‐poly(n‐butyl acrylate) (PMMA‐b‐PnBA) diblock copolymers with various compositions was synthesized via reversible addition–fragmentation chain‐transfer (RAFT) emulsion polymerization with the amphiphilic oligo(methacrylic acid41‐b‐methyl methacrylate8) RAFT agent as both the polymerization mediator and surfactant. The molecular weights of the block copolymers agreed well with the theoretical prediction, although the polydispersity indices were relatively broad. The resulting core [poly(n‐butyl acrylate)]–shell (PMMA) particles of PMMA‐b‐PnBA were found to be very effective impact modifiers for polycarbonate (PC). The diblock copolymer was well dispersed in 100–300‐nm particles in the PC matrix, and the dispersed particle size was highly dependent on the block copolymer compositions. PMMA250‐b‐PnBA550 (the subscripted number signifies the designed degree of polymerization), which was dispersed into 100‐nm particles, presented the best capability for improving the impacting properties. Compared with the neat PC, the notched impact strength of PC toughened by 5 wt % PMMA250‐b‐PnBA550 was increased by four times to 62.81 kJ/m2 with the same yield strength, a slightly decreased modulus, an increased elongation at break, and an increased tensile strength. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016, 132, 42833.

Multifunctional Hybrid Silica Nanoparticles with a Fluorescent Core and Active Targeting Shell for Fluorescence Imaging Biodiagnostic Applications

AbstractWe prepared hybrid nanoparticles with a brightly fluorescent silica core and a biocompatible thermoresponsive polymer shell containing tumor‐targeting folic acid (FA) groups. The silica core has a perylenediimide fluorescent dye anchored covalently to the structure for traceability and bioimaging applications. The polymeric shell was synthesized by reversible addition–fragmentation chain‐transfer (RAFT) polymerization to guarantee the homogeneous size of the particle shell. The shell is composed of copolymer chains with one block of oligo(ethylene glycol)methacrylate and 2‐(2′‐methoxyethoxy)ethylmethacrylate with another block of the reactive monomer N‐acryloxysuccinimide (NAS). The NAS groups were used to covalently attach a large amount of amino‐functionalized FA to the particle shells to provide active targeting properties towards cancer cells and tissues. The targeting capability of the folate‐containing nanoparticles was evaluated against NCI‐H460 tumor cells, which overexpress folate receptors. The nanoparticles with FA show a higher uptake efficiency compared to that of the equivalent nanoparticles without FA. This result validates the imaging capabilities and active targeting efficiency of our nanoparticles, an important step towards the goal of developing vehicles for precision drug delivery systems that combine therapeutic and diagnostic (theranostic) functionalities with large drug payloads, active targeting, and stimuli‐activated drug release.

Poly(Lactic Acid) Hemodialysis Membranes with Poly(Lactic Acid)-block-Poly(2-Hydroxyethyl Methacrylate) Copolymer As Additive: Preparation, Characterization, and Performance

Poly(lactic acid) (PLA) hemodialysis membranes with enhanced antifouling capability and hemocompatibility were developed using poly(lactic acid)-block-poly(2-hydroxyethyl methacrylate) (PLA-PHEMA) copolymers as the blending additive. PLA-PHEMA block copolymers were synthesized via reversible addition-fragmentation (RAFT) polymerization from aminolyzed PLA. Gel permeation chromatography (GPC) and (1)H-nuclear magnetic resonance ((1)H NMR) were applied to characterize the synthesized products. By blending PLA with the amphiphilic block copolymer, PLA/PLA-PHEMA membranes were prepared by nonsolvent induced phase separation (NIPS) method. Their chemistry and structure were characterized with X-ray photoelectron spectroscopy (XPS), scanning electron microscope (SEM) and atomic force microscopy (AFM). The results revealed that PLA/PLA-PHEMA membranes with high PLA-PHEMA contents exhibited enhanced hydrophilicity, water permeability, antifouling and hemocompatibility. Especially, when the PLA-PHEMA concentration was 15 wt %, the water flux of the modified membrane was about 236 L m(-2) h(-1). Its urea and creatinine clearance was more than 0.70 mL/min, lysozyme clearance was about 0.50 mL/min, BSA clearance was as less as 0.31 mL/min. All the results suggest that PLA-PHEMA copolymers had served as effective agents for optimizing the property of PLA-based membrane for hemodialysis applications.

Interfacial RAFT Miniemulsion Polymerization: Architectures from an Interface

Directing polymerization from a liquid–liquid interface is an emergent field delivering new insights into polymerization mechanisms, while creating interesting and novel poly­mer architectures. This review aims to explore how reversible addition–fragmentation chain‐transfer (RAFT) polymerization has been utilized in miniemulsion to perform controlled polymerizations at the biphasic liquid–liquid interface. Highlighted herein are the initial investigations that led to a new class of interfacially active macro‐RAFT agents. These are capable of stabilizing emulsions, directing polymer growth from that interface, and subsequently producing capsule‐like architectures. A comprehensive description is provided concerning the various macro‐RAFT agents employed and the importance of performing this under miniemulsion conditions to obtain either nanoparticles, nanocapsules, and/or core–shell morphologies. Finally, a focus on exciting applications of such systems for the production of nanomaterials including delivery vehicles with stimuli‐responsive properties is presented. image

ChemInform Abstract: Living Radical Polymerization of Ethylene: A Challenge Overcome?

AbstractReview: 16 refs.

Cationic RAFT Polymerization Using ppm Concentrations of Organic Acid

AbstractA metal‐free, cationic, reversible addition–fragmentation chain‐transfer (RAFT) polymerization was proposed and realized. A series of thiocarbonylthio compounds were used in the presence of a small amount of triflic acid for isobutyl vinyl ether to give polymers with controlled molecular weight of up to 1×105 and narrow molecular‐weight distributions (Mw/Mn<1.1). This “living” or controlled cationic polymerization is applicable to various electron‐rich monomers including vinyl ethers, p‐methoxystyrene, and even p‐hydroxystyrene that possesses an unprotected phenol group. A transformation from cationic to radical RAFT polymerization enables the synthesis of block copolymers between cationically and radically polymerizable monomers, such as vinyl ether and vinyl acetate or methyl acrylate.

Using controlled radical polymerization to confirm the lower critical solution temperature of an N‐(alkoxyalkyl) acrylamide polymer in aqueous solution

ABSTRACTN‐(3‐Methoxypropyl) acrylamide (MPAM) was polymerized by controlled radical polymerization (CRP) methods such as nitroxide‐mediated polymerization (NMP) and reversible addition–fragmentation chain‐transfer polymerization (RAFT). CRP was expected to yield well‐defined polymers with sharp lower critical solution temperature (LCST) transitions. NMP with the BlocBuilder (2‐([tert‐butyl[1‐(diethoxyphosphoryl)‐2,2‐dimethylpropyl]amino]oxy)‐2‐methylpropanoic acid) and SG1 ([tert‐butyl[1‐(diethoxyphosphoryl)‐2,2‐dimethylpropyl]amino] oxidanyl) initiating system revealed low yields and lack of control (high dispersity, Đ ∼ 1.5–1.6, and inhibition of chain growth). However, RAFT was far more effective, with linear number average molecular weight, , versus conversion, X, plots, low Đ ∼ 1.2–1.4 and the ability to form block copolymers using N,N‐diethylacrylamide (DEAAM) as the second monomer. Poly(MPAM) (with = 13.7–25.3 kg mol−1) thermoresponsive behavior in aqueous media revealed cloud point temperatures (CPT)s between 73 and 92 °C depending on solution concentration (ranging from 1 to 3 wt %). The and the molecular weight distribution were the key factors determining the CPT and the sharpness of the response, respectively. Poly(MPAM)‐b‐poly(DEAAM) block copolymer ( = 22.3 kg mol−1, Đ = 1.41, molar composition FDEAAM = 0.38) revealed dual LCSTs with both segments revealing distinctive CPTs (at 75 and 37 °C for poly(MPAM) and poly(DEAAM) blocks, respectively) by both UV–Vis and dynamic light scattering. © 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2015, 53, 59–67

Synthesis of a poly(methyl methacrylate)‐b‐poly[2‐(N,N‐dimethylamino) ethyl methacrylate] block copolymer and its effects on the surface charges and pH‐responsive properties of poly(vinylidene fluoride) blend membranes

ABSTRACTA poly(methyl methacrylate) (PMMA)‐b‐poly[2‐(N,N‐dimethylamino) ethyl methacrylate] (PDMAEMA) block copolymer was successfully synthesized by a reversible addition–fragmentation chain‐transfer method. The resulting copolymer was used to prepare poly(vinylidene fluoride) blend membranes via a phase‐inversion technique. The polymorphism, structure, and properties of the blend membranes were investigated by Fourier transform infrared spectrometry, scanning electron microscopy (SEM), ζ potential analysis, and filtration. The results indicate that PMMA‐b‐PDMAEMA could migrate onto the surface of the membrane during the coagulation process, and more of the β‐crystal phase appeared with the increase of the block copolymer in the membranes. The surface morphology and cross section of the membranes were also affected by the copolymer, as shown by SEM. The ζ‐potential results show that the surface charges of the membrane could be changed from positive to negative at an isoelectric point as the pH increased. The blend membrane also exhibited good pH sensitivity, and its water flux showed a great dependence on pH. The filtration experiment also indicated that the blend membrane had good hydrophilicity and antifouling properties. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014, 131, 40685.

Preparation of antimicrobial polycarboxybetaine‐based hydrogels for studies of drug loading and release

ABSTRACTA series of cationic poly(N‐isopropyl acrylamide) (PNIPAM)‐g‐poly(carboxybetaine ester) (PCBMAE) hydrogels were prepared by reversible addition–fragmentation chain‐transfer polymerization with PCBMAE precursors reacting with N‐isopropyl acrylamide in the presence of N,N′‐methylene bisacrylamide. These hydrogels exhibited excellent antimicrobial activities against Staphylococcus aureus and could switch to nontoxic zwitterionic hydrogels after hydrolysis. Nonionic tetracycline hydrochloride (TCHC) and anionic sodium salicylate (SA) were selected to evaluate the loading capacities and release kinetics of the cationic hydrogels. We found that the loading efficiencies of TCHC in the PNIPAM‐g‐PCBMAE hydrogels were approximately twice as high as those of SA. However, the cumulative release amount of TCHC was lower than that of SA from the corresponding cationic hydrogel at 37°C. In addition, the PNIPAM‐g‐PCBMAE hydrogels exhibited accelerated release rates of both TCHC and SA with increasing content of (2‐carboxymethyl)−3‐acryloxyethyldimethylammonium chloride methyl ester. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014, 131, 39839.

Polymer Prodrug Nanoparticles Based on Naturally Occurring Isoprenoid for Anticancer Therapy

The synthesis of a novel class of polymer prodrug nanoparticles with anticancer activity is reported by using squalene, a naturally occurring isoprenoid, as a building block by the reversible addition-fragmentation (RAFT) technique. The RAFT agent was functionalized by gemcitabine (Gem) as anticancer drug, and the polymerization of squalenyl-methacrylate (SqMA) led to well-defined macromolecular prodrugs comprising one Gem at the extremity of each polymer chain. The amphiphilic nature of the resulting Gem-PSqMA conjugates allowed them to self-assemble into long-term stable and narrowly dispersed nanoparticles with significant anticancer activity in vitro on various cancer cell lines. To confer stealth properties on these nanoparticles, their PEGylation was successfully performed, as confirmed by X-ray photoelectron spectroscopy (XPS) and complement activation assay. It was also shown that the PEGylated nanoparticles could be internalized in cancer cells to a greater extent than their non-PEGylated counterparts.

One‐pot synthesized poly(vinyl pyrrolidone‐co‐methyl methacrylate‐co‐acrylic acid) blended with poly(ether sulfone) to prepare blood‐compatible membranes

ABSTRACTIn this study, a random copolymer of poly(vinyl pyrrolidone‐co‐methyl methacrylate‐co‐acrylic acid) was synthesized via a one‐pot reaction with the reversible addition–fragmentation chain‐transfer method and was then blended with poly(ether sulfone) (PES) to prepare flat‐sheet membranes that were expected to have anticoagulant and antifouling properties. The synthesized copolymer was characterized by Fourier transform infrared (FTIR) and NMR spectroscopy. The molecular weights and molecular weight distributions were determined by gel permeation chromatography. Elemental analysis was used to calculate the molar ratios of vinyl pyrrolidone (VP), methyl methacrylate (MMA), and acrylic acid (AA) in the copolymer. A liquid–liquid phase‐inversion technique was used to prepare the copolymer‐blended PES membranes. X‐ray photoelectron spectroscopy and attenuated total reflectance–FTIR spectroscopy were used to investigate the copolymer on the membrane surfaces. Compared with the pristine PES membrane, the modified PES membranes showed improved hydrophilicity, low hemolysis ratios, decreased protein adsorption, and suppressed platelet adhesion. Furthermore, the thrombin time and activated partial thromboplastin time indicated that the blood compatibility of the modified PES membranes were improved. The results of the 3‐(4,5‐Dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) assay and the cell morphology suggested that the cytocompatibility increased. In addition, the modified membranes showed good protein antifouling properties. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 130: 4284–4298, 2013

Well-Defined Aminooxy Terminated N-(2-Hydroxypropyl) Methacrylamide Macromers for Site Specific Bioconjugation of Glycoproteins

Syntheses and characterization of aminooxy terminated polymers of N-(2-hydroxyproyl) methacrylamide (HPMA) of controlled molecular weight and narrow molecular weight distribution are presented here. Design of a chain transfer agent (CTA) containing N-tert-butoxycarbonyl (t-Boc) protected aminooxy group enabled us to use reversible addition-fragmentation (RAFT) polymerization technique to polymerize the HPMA monomer. An amide bond was utilized to link the aminooxy group and the CTA through a triethylene glycol spacer. As a result, the aminooxy group is linked to the poly(HPMA) backbone through a hydrolytically stable amide bond. By varying the monomer to initiator ratios, polymers with targeted molecular weights were obtained. The molecular weights of the polymers were determined by gel permeation chromatography (GPC) and mass spectrometry (ESI and MALDI-TOF). The t-Boc protecting group was quantitatively removed to generate aminooxy terminated poly(HPMA) macromers. These macromers were converted to rhodamine B terminated poly(HPMA) by reacting N-hydroxysuccinimide (NHS) ester of the dye with the terminal aminooxy group to form a stable alkoxyamide bond. Utility of these dye-labeled polymers as molecular probes was evaluated by fluorescence microscopy by studying their intracellular uptake by renal epithelial cells. These aminooxy terminated poly(HPMA) were also tested as biocompatible carriers to prepare chemoselective bioconjugates of proteins using transferrin (Tf) as the protein. Oxidation of the sialic acid side chains of Tf generated aldehyde functionalized protein that was reacted with aminooxy terminated poly(HPMA), which resulted in protein-polymer bioconjugates carrying oxime linkages. These bioconjugates were characterized by gel electrophoresis and MALDI-TOF mass spectrometry.

Thermally amendable tailor-made functional polymer by RAFT polymerization and “click reaction”

This investigation reports the preparation and char- acterization of thermally amendable functional polymer bearing furfuryl functionality via reversible-addition fragmentation and chain transfer (RAFT) polymerization and Diels-Alder (DA) reac- tion. In this case, furfuryl methacrylate (FMA) was polymerized using 4-cyano-4-((dodecylsulfanylthiocarbonyl)sulfanyl) penta- noic acid as RAFT reagent and 4,4 0 -azobis(4-cyanovaleric acid) as thermal initiator. 1 H NMR, 13 C NMR, and matrix-assisted laser desorption ionization time-of-flight mass spectrometry analysis showed that furfuryl group in poly(furfuryl methacrylate) (PFMA) was not affected during RAFT polymerization and the tailor-made polymer had RAFT end group. The DA reaction was successfully carried out between the reactive furfuryl functional- ity of PFMA and different bismaleimides. The thermoreversible property of these DA polymers was characterized by FT-IR and DSC analysis. V C 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2013, 51, 3365-3374