Reversible Addition-fragmentation Chain Transfer Technique Research Articles

Evaluation of a temperature-responsive magnetotocosome as a magnetic targeting drug delivery system for sorafenib tosylate anticancer drug

In this investigation, a polymeric fusion of chitosan (CS) and thermosensitive poly (N-isopropyl acrylamide) - PNIPAAm - encapsulated a magnetotocosome, biocompatible nanocarrier. This encapsulation strategy demonstrated improved drug entrapment efficiency, achieving up to 98.8 %. Additionally, it exhibited extended stability, optimal particle dimensions, and the potential for industrial scaling, thus facilitating controlled drug delivery of sorafenib tosylate to cancerous tissue. Reversible Addition-Fragmentation Chain Transfer (RAFT) techniques were employed to synthesize PNIPAAm. The effects of polymer molecular weight and polydispersity index on the lower critical solution temperature (LCST) were evaluated. The resulting polymeric amalgamation, involving the thermosensitive PNIPAAm synthesized using RAFT techniques and CS that coated the magnetotocosome (CS-Raft PNIPAAm-magnetotocosome) with an LCST approximately at 45 °C, holds the potential to enhance drug bioavailability and enable applications in hyperthermia treatment, controlled release, and targeted drug delivery.

RAFT-Based Polymers for Click Reactions.

The parallel development of reversible deactivation radical polymerization and click reaction concepts significantly enriches the toolbox of synthetic polymer chemistry. The synergistic effect of combining these approaches manifests itself in a growth of interest to the design of well-defined functional polymers and their controlled conjugation with biomolecules, drugs, and inorganic surfaces. In this review, we discuss the results obtained with reversible addition–fragmentation chain transfer (RAFT) polymerization and different types of click reactions on low- and high-molar-mass reactants. Our classification of literature sources is based on the typical structure of macromolecules produced by the RAFT technique. The review addresses click reactions, immediate or preceded by a modification of another type, on the leaving and stabilizing groups inherited by a growing macromolecule from the chain transfer agent, as well as on the side groups coming from monomers entering the polymerization process. Architecture and self-assembling properties of the resulting polymers are briefly discussed with regard to their potential functional applications, which include drug delivery, protein recognition, anti-fouling and anti-corrosion coatings, the compatibilization of polymer blends, the modification of fillers to increase their dispersibility in polymer matrices, etc.

Synthesis of an amphiphilic copolymer using biopolymer-dextran via a combination of ROP and RAFT techniques

Ring-opening polymerization (ROP) and reversible addition–fragmentation chain-transfer (RAFT) polymerization are efficient synthetic approaches to develop self-assembled copolymers with narrow dispersity (Đ).

Synthesis and Characterization of Poly (2-hydroxyethyl methacrylate) Homopolymer at Room Temperature via Reversible Addition–Fragmentation Chain Transfer (RAFT) Polymerization Technique

Synthesis and characterization of Poly (2-hydroxyethyl methacrylate) (PHEMA) by RAFT technique at room temperature was first reported in this study. In this context, molecular weight, monomer conversion and semi-logarithmic kinetic curves of the RAFT polymerization, which is one of the controlled-living polymerization techniques, were determined by ATR-FTIR and NMR at certain time intervals. Linear change of molecular weight and monomer conversion with time, semi-logarithmic kinetic curve to the first degree kinetics of the synthesized PHEMA shows that the growth of polymer chains in a controlled manner. PHEMA polymers synthesized by RAFT technique at room temperature without the use of catalyst and metal types have the potential to be easily used in bio applications. It is also important for peptide and protein adsorption that this polymer has functional properties due to the carboxylic acid at the end of the RAFT agent.

Poly(n‐alkyl methacrylate)s as Metallocene Catalyst Supports in Nonpolar Media

AbstractIn this work, poly(alkylmethacrylates) based on poly(n‐alkyl methacrylate)s (PnAMAs), that is, poly(hexyl methacrylate) (PHMA), poly(lauryl methacrylate) (PLMA), and poly(stearyl methacrylate) (PSMA), with similar molar masses (Mn), are synthesized via reversible addition–fragmentation chain transfer technique using a high‐throughput approach. Analyses by dynamic light scattering (DLS) of PnAMAs in nonpolar solvents show the presence of nanoparticles distributions (unimers or single chains). Interactions of methylaluminoxane (MAO) and MAO/metallocene compounds with PnAMA nanoparticles, lead to self‐assembled micellar‐like structures useful as “nanoreactors” for coordination polymerizations of ethylene. The inverse micellar‐like structures of the three kinds of polymethacrylates, formed in the presence of MAO are confirmed by DLS experiments and by transmission electron microscopy using energy dispersive spectrometry analyzer, in dyed PnAMAs/MAO samples. The encapsulation of the metallocene catalyst into the PSMA/MAO nanoparticles reveals stable catalytic systems that have a clear effect on the morphology of the polyethylenes synthesized through this method.

One-Step Synthesis and Characterization of Poly(ε-caprolactone)-b-poly(N-isopropylacrylamide) Thermo-Responsive Block Copolymers via RAFT and ROP Techniques

In this study, well-defined thermo-responsive block copolymers of poly(e-caprolactone)-b-poly(N-isopropylacrylamide) with narrow molecular weight distribution were synthesized in one-step via reversible addition-fragmentation chain transfer (RAFT) polymerization and ring-opening polymerization (ROP) methods using dual RAFT-ROP initiator which was obtained via the reaction of 3-chloro-1,2-propanediol with the potassium salt of ethyl xanthogenate. Thermo-responsive block copolymers were obtained in high yield and high molecular weight. The characterization of the products was accomplished by NMR and FTIR spectroscopy, gel permeation chromatography, thermogravimetric analysis, differential scanning calorimetry. Furthermore, thermo-responsive properties of the copolymers were verified by UV, and fractional precipitation techniques.

Recent Advances in RAFT Polymerization: Novel Initiation Mechanisms and Optoelectronic Applications.

Reversible addition-fragmentation chain transfer (RAFT) is considered to be one of most famous reversible deactivation radical polymerization protocols. Benefiting from its living or controlled polymerization process, complex polymeric architectures with controlled molecular weight, low dispersity, as well as various functionality have been constructed, which could be applied in wide fields, including materials, biology, and electrology. Under the continuous research improvement, main achievements have focused on the development of new RAFT techniques, containing fancy initiation methods (e.g., photo, metal, enzyme, redox and acid), sulfur-free RAFT system and their applications in many fields. This review summarizes the current advances in major bright spot of novel RAFT techniques as well as their potential applications in the optoelectronic field, especially in the past a few years.

Arm-First Approach toward Cross-Linked Polymers with Hydrophobic Domains via Hypervalent Iodine-Mediated Click Chemistry.

In this work, synthesis of two cross-linked polymeric systems through isoxazoline ring formation using nitrile oxide–acrylate click chemistry has been described. In the first system, styrenic block copolymer with oxime-functionalized middle block was synthesized using S,S′-bis(α,α′-dimethyl-α″-acetic acid)trithiocarbonate as chain-transfer agent using reversible addition fragmentation chain-transfer technique. This block copolymer was further utilized to prepare core cross-linked star polymers by reacting with a four-arm acrylic cross-linker by employing environment-friendly, nontoxic PhI(OAc)2-mediated “click reaction” via the formation of isoxazoline ring. In the second system, two linear styrenic block copolymers, one containing oxime and another containing acrylate group, were reacted to form a cross-linked (CS) polymeric system. Formation of cross-linked polymers and isoxazoline ring was confirmed by Fourier transform infrared spectroscopy, gel permeation chromatography, NMR spectroscopy, and dynamic light scattering studies. Later, we also demonstrated that in aqueous medium these CS polymers produced polymeric nanoparticles (NPs), which can be used as potential carriers of hydrophobic drug molecules. The loading capacity of the hydrophobic domains has been investigated using coumarin dyes with varying hydrophobicity through steady-state and time-resolved spectroscopy studies. The polymeric NPs were also shown to successfully encapsulate a hydrophobic drug doxorubicin.

Antifouling Cellulose Hybrid Biomembrane for Effective Oil/Water Separation.

Oil/water separation has been of great interest worldwide because of the increasingly serious environmental pollution caused by the abundant discharge of industrial wastewater, oil spill accidents, and odors. Here, we describe simple and economical superhydrophobic hybrid membranes for effective oil/water separation. Eco-friendly, antifouling membranes were fabricated for oil/water separation, waste particle filtration, the blocking of thiol-based odor materials, etc., by using a cellulose membrane (CM) filter. The CM was modified from its original superhydrophilic nature into a superhydrophobic surface via a reversible addition-fragmentation chain transfer technique. The block copolymer poly{[3-(trimethoxysilyl)propyl acrylate]-block-myrcene} was synthesized using a "grafting-from" approach on the CM. The surface contact angle that we obtained was >160°, and absorption tests of several organic contaminants (oils and solvents) exhibited superior levels of extractive activity and excellent reusability. These properties rendered this membrane a promising surface for oil/water separation. Interestingly, myrcene blocks thiol (through "-ene-" chemistry) contaminants, thereby bestowing a pleasant odor to polluted water by acting as an antifouling material. We exploited the structural properties of cellulose networks and simple chemical manipulations to fabricate an original material that proved to be effective in separating water from organic and nano/microparticulate contaminants. These characteristics allowed our material to effectively separate water from oily/particulate phases as well as embed antifouling materials for water purification, thus making it an appropriate absorber for chemical processes and environmental protection.

A novel dual stimuli-responsive thiol-end-capped ABC triblock copolymer: synthesis via reversible addition-fragmentation chain transfer technique, and investigation of its self-assembly behavior

A novel dual stimuli-responsive thiol-end-capped ABC triblock copolymer: synthesis via reversible addition-fragmentation chain transfer technique, and investigation of its self-assembly behavior

Poly(glycidyl Methacrylate) Grafted to Carbon Fiber Surface by RAFT Polymerization for Enhancing Interface Adhesion and Mechanical Properties of Carbon Fiber/Epoxy Composites

In this study, we present a novel approach to graft a large number of poly(glycidyl methacrylate) (PGMA) chains onto the carbon fiber (CF) surface through reversible addition-fragmentation chain transfer (RAFT) polymerization. Characterization results of FT-IR, XPS and TGA demonstrated that PGMA was covalently combined with carbon fibers. The CF/epoxy composites were obtained by addition of pristine CF and CF functionalized with poly(glycidyl methacrylate) (CF-PGMA) into epoxy resin. Experiment results revealed that the grafting of PGMA chains on the CF surface could increase significantly roughness and number of active groups of CF, which enhanced interface and mechanical properties of the composites. The compression strength, tensile strength, flexural strength and interfacial shear strength (IFSS) of CF-PGMA/epoxy composites are enhanced by at least 63.1%, 37.9% 55.6% and 122.5%, respectively, compared to pristine carbon fiber/epoxy composites. This enhancement indicates that surface modification of the carbon fibers by RAFT technique is a potential method to preparing CF-reinforced polymer matrix composites with excellent mechanical properties.

Facile Synthesis of Intelligent Polymers Modified Gold Nanoparticles in Aqueous Solution

This paper describes the synthesis of gold nanoparticles (GNPs) stabilized with intelligent poly(N,N-dimethylaminoethyl methacrylate) (PDMAEMA). First, the dithioester-terminated PDMAEMA was prepared by the reversible addition-fragmentation chain transfer technique. Then, the dithioester-terminated PDMAEMA was reduced to a thiol-terminated polymer PDMAEMA-SH. PDMAEMA coated GNPs (Au@PDMAEMA NPs) were synthesized in situ from HAuCl4 aqueous solution by using NaBH4 as a reductant and thiolated PDMAEMA as a stabilizer through Au–S bond. The optical and physical properties of GNPs were characterized by UV–Vis spectroscopy, transmission electron microscopy, X-ray diffraction as well as thermogravimetric analysis. The size and shape of GNPs could be controlled by tuning both the [PDMAEMA]:[HAuCl4] molar ratio and the solution pH. It is believed that these highly biocompatible GNPs have potential biomedical applications.

Protecting-Group-Free Synthesis of Glycopolymers Bearing Sialyloligosaccharide and Their High Binding with the Influenza Virus.

Glycopolymers having pendant triazole-linked sialyloligosaccharides were successfully synthesized from free saccharides without any protection of the hydroxy and carboxy groups on the saccharides. The glycomonomers were synthesized by the direct azidation of free saccharides using 2-chloro-1,3-dimethylimidazolinium chloride as a condensing agent followed by copper(I)-catalyzed azide-alkyne cycloaddition. The resultant glycomonomers were copolymerized with acrylamide by a reversible addition-fragmentation chain transfer technique. Each of the glycopolymers were obtained and then immobilized on a gold-coated sensor of quartz crystal microbalance to analyze their binding behavior with the lectin. The glycopolymers strongly bound with the corresponding lectin without nonspecific adsorption in aqueous solution. In addition, the glycopolymer bearing a complex-type sialyl N-linked oligosaccharide was found to strongly bind with both human and avian influenza A viruses. The strong binding, observed using the hemagglutination inhibition assay, was attributed to the glycocluster effect of the glycopolymer and the biantennary structure of the N-linked oligosaccharide.

Thermoregulated Formation and Disintegration of Cationic Block Copolymer Vesicles: Fluorescence Resonance Energy Transfer Study

Formation and disintegration of self-assembled nanostructures in response to external stimuli are important phenomena that have been widely explored for a variety of biomedical applications. In this contribution, we report the thermally triggered assembly of block copolymer molecules in aqueous solution to form vesicles (polymersomes) and their disassembly on reduction of temperature. A new thermoresponsive diblock copolymer of poly(N-isopropylacrylamide) poly((3-methacrylamidopropyl)trimethylammonium chloride) (PNIPA-b-PMAPTAC) was synthesized by reversible addition-fragmentation chain transfer technique. The solution properties and self-assembling behavior of the block copolymer molecules were studied by turbidimetry, temperature-dependent proton nuclear magnetic resonance, fluorescence spectroscopy, dynamic light scattering, and transmission electron microscopy. Fluorescence resonance energy transfer studies between coumarin-153 (C-153, donor) and rhodamine 6G (R6G, acceptor) have been performed by steady-state and picosecond-resolved fluorescence spectroscopy to probe the structural and dynamic heterogeneity of the vesicles. The occurrence of efficient energy transfer was evident from the shortening of donor lifetime in the presence of the acceptor. The capability of the vesicles to encapsulate both hydrophobic and hydrophilic molecules and release them in response to decrease in temperature makes them potentially useful as drug delivery vehicles.

Electron Transfer of Myoglobin Immobilized in Au Electrodes Modified with a RAFT PMMA-Block-PDMAEMA Polymer

Myoglobin was immobilized with poly(methyl methacrylate)-block-poly[(2-dimethylamino)ethyl methacrylate]PMMA-block-PDMAEMA polymer synthesized by reversible addition-fragmentation chain transfer technique (RAFT). Cyclic voltammograms gave direct and slow quasireversible heterogeneous electron transfer kinetics between Mb-PMMA-block-PDMAEMA modified electrode and the redox center of the protein. The values for electron rate constant (Ks) and transfer coefficient (α) were0.055±0.01·s−1and0.81±0.08, respectively. The reduction potential determined as a function of temperature (293–328 K) revealed a value of reaction center entropy ofΔS0of351.3±0.0002 J·mol−1·K−1and enthalpy change of-76.8±0.1 kJ·mol−1, suggesting solvent effects and charge ionization atmosphere involved in the reaction parallel to hydrophobic interactions with the copolymer. The immobilized protein also exhibits an electrocatalytical response to reduction of hydrogen peroxide, with an apparentKmof114.7±58.7 μM. The overall results substantiate the design and use of RAFT polymers towards the development of third-generation biosensors.

Preparation of hydrazine functionalized polymer brushes hybrid magnetic nanoparticles for highly specific enrichment of glycopeptides

Hydrazide chemistry is a powerful technique in glycopeptides enrichment. However, the low density of the monolayer hydrazine groups on the conventional hydrazine-functionalized magnetic nanoparticles limits the efficiency of glycopeptides enrichment. Herein, a novel magnetic nanoparticle grafted with poly(glycidyl methacrylate) (GMA) brushes was fabricated via reversible addition-fragmentation chain transfer (RAFT) polymerization, and a large amount of hydrazine groups were further introduced to the GMA brushes by ring-opening the epoxy groups with hydrazine hydrate. The resulting magnetic nanoparticles (denoted as Fe3O4@SiO2@GMA-NHNH2) demonstrated the high specificity of capturing glycopeptides from a tryptic digest of the sample comprising a standard non-glycosylated protein bovine serum albumin (BSA) and four standard glycoproteins with a weight ratio of 50 : 1, and the detection limit was as low as 130 fmol. In the analysis of a real complex biological sample, the tryptic digest of hepatocellular carcinoma, 179 glycosites were identified by the Fe3O4@SiO2@GMA-NHNH2 nanoparticles, surpassing that of 68 glycosites by Fe3O4@SiO2-single-NHNH2 (with monolayer hydrazine groups on the surface). It can be expected that the magnetic nanoparticles modified with hydrazine functionalized polymer brushes via RAFT technique will improve the specificity and the binding capacity of glycopeptides from complex samples, and show great potential in the analysis of protein glycosylation in biological samples.

Strain state of poly(N‐isopropylacrylamide) in polystyrene‐b‐poly(N‐isopropylacrylamide) block copolymers and binary blends with polystyrene

ABSTRACTThree diblock copolymers of polystyrene‐b‐poly(N‐isopropylacrylamide) (PS‐b‐PNIPAM) were prepared by reversible addition‐fragmentation chain transfer technique (RAFT) with compositions fPS = 0.84, fPS = 0.29, and fPS = 0.33. Block copolymers rich in PNIPAM were blended with polystyrene and its morphological effects were studied. The morphology of thin films was induced by acetone vapor and determined in the dried state by means of TEM. Copolymers with fPS = 0.84 and fPS = 0.29 form hexagonally packed cylinder (HPC) morphologies while that with fPS = 0.33 corresponds to a lamellar structure. In almost all cases where PNIPAM constitutes the continuous phase, a contraction of the PNIPAM blocks with respect to their average unperturbed dimension was observed, contrary to what one expects from the physics of self‐assembly of block copolymers. In contrast, for HPC morphology where PNIPAM is confined in a PS matrix, both blocks are highly extended. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2013, 51, 1368–1376

Preparation and Characterization of PMMA and its Derivative via RAFT Technique in the Presence of Disulfide as a Source of Chain Transfer Agent

Poly(methyl methacrylate) (PMMA) were synthesized by using chain transfer agents(CTA), S-1-Dodecyl-S′-(α,α′-dimethyl-α-acetic acid) trithiocarbonate (MTTCD), S,S′-bis (2-hydroxyethyl-2′-dimethylacrylate) trithiocarbonate (BDATC), 2-cyanoprop-2-yl dithiobenzoate (CPDB) respectively, through the reversible addition fragmentation chain transfer (RAFT) polymerization under a range of synthesis conditions. The results indicated that the structure of the end-group of RAFT agents had significant effects on the ability to control polymerization. Compared with MTTCD and CPDB, BDATC can provide better control over the relative molecular mass, distribution and polymerization of PMMA. The derived well-controlled block copolymer PMMA-b-PDMAEMA and PMMA-b-PDMAEA were also successfully prepared by using N, N-dimethylaminoethy acrylate (DMAEA) or N, N-dimethylaminoethyl methacrylate (DMAEMA) as the second monomer. The chemical composition and structure of the products were characterized by FTIR, 1HNMR, XRD and DSC. CO2 and N2 permeation performance of the PMMA-b-PDMAEA/PS composite membranes were tested at different pressure. The results showed that the resulted composited membrane had a CO2 permeation rate of 3.68×10-5cm3 (STP) cm-2s-1cmHg-1, a N2 permeation rate of 1.78×10-7 cm3 (STP) cm-2s-1cmHg-1 and an ideal CO2/ N2 selectivity of 206.6 at a feed gas pressure of 7.6 cmHg and 30 oC.

Fabrication of cell outer membrane mimetic polymer brush on polysulfone surface via RAFT technique

Cell membrane mimetic antifouling polymer brush was grown on polysulfone (PSF) membrane by surface-induced reversible addition–fragmentation chain transfer (RAFT) polymerization of 2-methacryloyloxyethyl phosphorylcholine (MPC). The RAFT agent immobilized PSF substrate was prepared by successive chloromethylation, amination with ethylenediamine (EDA) and amidation of the amine group of grafted EDA with the carboxylic group of 4-cyanopentanoic acid dithiobenzoate (CPAD). The surface RAFT polymerization of MPC was initiated in aqueous solution by 4,4′-azobis-4-cyanopentanoic acid (ACPA). The formation of PMPC brush coating is evidenced by X-ray photoelectron spectroscopy and water contact angle measurements. The degree of polymerization of PMPC and the polymer grafting density were calculated from the high resolution XPS spectra. The platelet adhesion and protein adsorption results showed that the PMPC-grafted PSF surface has excellent antifouling ability to resist platelet adhesion completely and suppress protein adsorption significantly. This biomimetic and bio-friendly surface RAFT polymerization strategy could be promising for a variety of biomedical applications.

Controlled synthesis of branched polystyrene via RAFT technique in the presence of chain transfer monomer p-vinyl benzene sulfonyl chloride

Branched polystyrene was first obtained via a reversible addition-fragmentation chain transfer (RAFT) process in the presence of chain transfer monomer p-vinyl benzene sulfonyl chloride (VBSC) in benzene at 60 °C with 2-(ethoxycarbonyl)prop-2-yl dithiobenzoate as the RAFT agent and 2,2-azobisisobutyronitrile as an initiator. During the RAFT polymerization, VBSC played the role of branching agent. It could not only copolymerized but also acted as a chain transfer agent due to the polymerizable vinyl group and sulfonyl chloride chain transfer group in the VBSC. Gel permeation chromatography (GPC) traces demonstrated that the number-average molecular weights and molecular weight distributions increased along with monomer conversion. Compared with the RAFT process without VBSC, the resulting polymers had broad molecular weight distributions and the sulfonyl functionality of the resultant polymer at the branching point, indicating the formation of branched polystyrene. The structure of the obtained polystyrene was further analyzed by proton nuclear magnetic resonance (1H NMR) spectroscopy. The findings indicated that the branched polystyrene was mainly formed via the RAFT copolymerization of VBSC and styrene firstly to form polystyrene bearing pendant sulfonyl chloride group, and then the pendant sulfonyl chloride group acted as the chain transfer agent to generate the branched structure. In addition, the degree of branching and VBSC unit in copolymer increased along with the VBSC in the feed, implying that composition and structure of the branched polystyrenes could be tuned by the amount of VBSC in the feed. Open image in new window