Reversible Addition-fragmentation Chain Research Articles

Polymerization-Induced Self-Assembly for the Synthesis of Polyisoprene-Polystyrene Block and Random Copolymers: Towards High Molecular Weight and Conversion.

In this study, reversible addition-fragmentation chain- transfer (RAFT) polymerization combined with the polymerization-induced self-assembly (PISA) technique is used to synthesize polyisoprene (PI)-based block and random copolymers with polystyrene (PS), aiming for high molecular weight and monomer conversion. The focus is to optimize the polymerization conditions to overcome the existing challenge of cross-linking and Diels-Alder reactions during the polymerization of isoprene, which typically constrain the reaction conversion and molecular weight of the final polymers. Using a poly(methacrylic acid) (PMAA) macroRAFT agent synthesized in ethanol at 80°C, random and block copolymers of PS-PI with a target molecular weight of 50000gmole-1 and a high monomer conversion of ≈80% are achieved under optimized conditions in water-emulsion at 35°C. 1H nuclear magnetic resonance (NMR) verified the successful synthesis as well as the high content of 1,4 microstructure in polyisoprene. The thermal analysis via differential scanning calorimetry indicated distinct glass transitions for the microphase-separated PI-PS block copolymer, while a single transition for PI-PS random copolymer, indicating no microphase separation. Furthermore, dynamic light scattering analysis together with transmission electron microscopy provided further insight into the self-assembled emulsion nanoparticles of the polymers indicating a particle size in the range 70 to 130nm.

Water-Soluble and Degradation-Resistant Curcumin Copolymers from Reversible Addition–Fragmentation Chain (RAFT) Copolymerization

Water-Soluble and Degradation-Resistant Curcumin Copolymers from Reversible Addition–Fragmentation Chain (RAFT) Copolymerization

Synergistic effect of folate-conjugated polymers and 5-fluorouracil in the treatment of colon cancer

BackgroundIn recent years, targeted drug delivery strategies have received special attention from the scientific world due to advantages such as more effective therapy and reduction of side effects. The principle of operation is delayed excretion from the bloodstream of the drug delivery system compared to the drug itself, as well as facilitated penetration into diseased cells thanks to the use of ligands recognized by appropriate receptors. Particularly interesting drug carriers are amphiphilic copolymers that form nano-sized micelles with a drug, which can release the drug at a specific place in the body under the influence of appropriate stimuli.ResultsWe describe the synthesis of the diblock polymer, poly(2-hydroxyethyl acrylate)-b-poly(N-vinylcaprolactam) using RAFT/MADIX (Reversible Addition-Fragmentation chain Transfer/MAcromolecular Design by Interchange of Xanthate) controlled polymerization affording polymers with good dispersity according to SEC (Size-Exclusion Chromatography). Some post-modifications of the polymer with folic acid were then performed as evidenced by NMR (Nuclear Magnetic Resonance), UV–Vis (UltraViolet–Visible) and FT-IR (Fourier-Transform Infrared) spectroscopy, and TGA (ThermoGravimetric Analysis). The formation of stable micellar systems from polymers with and without the drug, 5-fluorouracil, was confirmed by DLS (Dynamic Light Scattering) and zeta potential measurements, and TEM (Transmission Eelectron Microscopy) imaging. Finally, the cloud point of the polymers was investigated, which turned out to be close to the temperature of the human body. Most importantly, these micellar systems have been explored as a drug delivery system against colon cancer, showing increased cytotoxicity compared to the drug alone. This effect was achieved due to the easier cellular uptake by the interaction of folic acid and its receptors on the surface of cancer cells.ConclusionsThe presented results constitute a solid foundation for the implementation of a nano-sized drug delivery system containing folic acid for practical use in the treatment of drug-resistant cancer, as well as more effective therapy with fewer side effects.Graphical

Toughness improvement of epoxy thermosets with cellulose nanocrystals

AbstractWe report the toughness improvement of epoxy thermosets by the use of cellulose nanocrystals (CNCs). Pristine CNCs were functionalized via surface‐initiated reversible addition–fragmentation chain transfer/macromolecular design via interchange of xanthates (RAFT/MADIX) polymerization. The pristine CNCs were first surface‐treated with 4‐cyano‐4‐(isopropoxycarbonothioylthio)pentanoic chloride and then poly(N‐vinylpyrrolidone)‐grafted CNCs (CNC‐PVPy) were synthesized with the xanthate‐functionalized CNCs as chain transfer agent. Notably, the as‐obtained CNC‐PVPy can be dispersed into epoxy thermosets in the form of single fibrous nano‐objects, i.e. the nanocomposites of epoxy with CNCs were successfully obtained. The uniform dispersion of CNCs in epoxy matrix is attributable to the compatibilizing effect of PVPy chains. The introduction of CNCs markedly improved the toughness of epoxy thermosets. When the mass fraction of CNC‐PVPy was 30 wt%, the nanocomposites displayed the maximum critical stress intensity factor (K1C) and critical fracture energy (G1C) of 1.76 MN m−3/2 and 0.66 kJ m−2, respectively. The toughening of epoxy thermosets is mainly attributed to the plastic deformation of epoxy matrix, which is initiated from CNCs. © 2021 Society of Industrial Chemistry.

Reversible addition fragmentation chain transfer‐mediated bioconjugated amphiphilic graft‐block copolymer using dextran, poly (N‐isopropylacrylamide), and poly (vinyl acetate)

AbstractRAFT polymerization is a well‐known approach to develop amphiphilic copolymer with less heterogeneity and narrow dispersity. Herein, an amphiphilic bioconjugated graft‐block copolymer (Dextran‐g‐(PNIPAAm‐b‐PVAc)) using dextran, N‐isopropyl acrylamide and vinyl acetate has been developed through RAFT polymerization. The chain length of the PVAc block has been varied to obtain the copolymers with different hydrophobic segments. The lower critical solution temperature, critical micelle concentration, and micellar stability of the synthesized copolymers have been studied in details. in‐vitro cytotoxicity, as well as the in vitro release of a hydrophobic drug have been carried out to explore its suitability in the field of biomedical science. The synthesized copolymer has been found to have controlled molecular weight with narrow dispersity. It is cytocompatible toward Human cervical cancer cell line cell lines, can efficiently load a hydrophobic drug‐norfloxacin, and subsequently, release in the sustained manner as manifested from in vitro release study.

Development of a graphene oxide-poly lactide nanocomposite as a Smart Drug Delivery System

In this study, a nanoscale graphene oxide polymer composite drug delivery system was synthesized and investigated for possible oral delivery of doxorubicin. A doxorubicin-loaded nanocomposite composed of graphene oxide/poly(2-hydroxyethylmethacrylate)-g-poly(lactide)-b-polyethyleneglycol-b-poly(2-hydroxyethylmethacrylate)-g-poly(lactide) GO/(PHEMA-g-PLA)-b-PEG-b-(PHEMA-g-PLA) was synthesized via reversible addition fragmentation chain (RAFT) and ring open polymerization (ROP). The GO/(PHEMA-g-PLA)-b-PEG-b- (PHEMA-g-PLA) nanocomposites was characterized by scanning electron microscopy (FE-SEM), thermogravimetry (TG), ultraviolet-visible (UV–Vis) spectroscopy, and dynamic light scattering (DLS). Doxorubicin was successfully loaded into the nanocomposite with a small particle size of 51 nm and an encapsulation efficiency (EE) of 82% ±1.12%. The results showed that DOX was attached to the graphene surface via hydrophobic interactions and π-π stacking. DOX release took place under neutral and acidic conditions, reaching 24.7% and 41.2% respectively after 72 h. Cytotoxicity experiments on 4T1 murine breast cancer cells demonstrated the antitumor activity of the DOX@GO nanocomposite. Biocompatibility, cell uptake, DAPI staining, Annexin V/PI double staining, intracellular reactive oxygen species (ROS) assay, and scratch healing assay were measured. The DOX@graphene nanocomposite system could be promising for breast cancer therapy.

Self-Assembly and Temperature-Driven Chirality Inversion of Cholesteryl-Based Block Copolymers

Block copolymers (BCPs), comprising a poly(methyl methacrylate) (PMMA) block and a poly(cholesteryloxyhexyl methacrylate) (PChMA) block, were synthesized via reversible addition–fragmentation chain transfer polymerization. The self-assembly of the liquid crystalline BCPs was characterized by differential scanning calorimetry, polarized optical microscopy, and synchrotron-based small/wide-angle X-ray scattering. The results indicate the formation of both tilted and nontilted chiral smectic (SmC* and SmA*) phases. A phase transition from the SmA* to SmC* phase on cooling was observed for BCPs but not for PChMA homopolymers. The layer spacing (5.00 ± 0.18 nm) between those can be controlled to maintain the number of ChMA units while varying the lengths of the PMMA block, thus introducing systematically the SmC* phase. Furthermore, BCPs with the short PMMA block showed inversion of chirality at specific temperatures; however, for PChMA attached with the long PMMA block, no chirality inversion was observed. This mode of chirality switching, investigated by circular dichroism, NMR, and theoretical studies, is associated with the methyl substituents in the backbone affecting the packing of the polymers. The basic rules, described here, have the potential to be implemented for the design of a wide range of functional materials, where helix–helix conversion is of use.

Synthesis and characterization of well-defined end-chain functional macrophotoinitiators of polystyrene and polyacrylonitrile by RAFT/MADIX polymerization

An alternative approach for the synthesis of well-defined macrophotoinitiators of polystyrene and polyacrylonitrile with an end-chain photofunctional group via reversible addition-fragmentation chain transfer/macromolecular design via the interchange of xanthate (RAFT/MADIX) polymerization has been described. For this purpose, a novel photoreactive chain transfer agent (CTA-PI), namely S-benzyl O-(2-oxo-1,2-diphenylethyl) carbonodithioate, was prepared with an efficient one-pot, two-step synthesis by first reacting benzoin photoinitiator (PI) with CS2 in the presence of NaH and then reacting this intermediate with benzyl bromide in THF. The structure of CTA-PI was determined by FT-IR, 1H NMR, and 13C NMR spectroscopy and confirmed by elemental analysis. Here, we used this xanthate based CTA in conjunction with 4,4′-azobis(4-cyanovaleric acid) (ACVA), as the initiating species, to investigate RAFT/MADIX polymerization of styrene (St), acrylonitrile (AN), methyl methacrylate (MMA), the so-called more activated monomers (MAMs), and vinyl acetate (VAc), one of the less activated monomers (LAMs). While RAFT/MADIX polymerization of styrene and acrylonitrile progressed in a controlled manner producing well-defined macrophotoinitiators with benzoin end-chain functional group, polymerization of methyl methacrylate proceeded uncontrollably. Polymerization of vinyl acetate under the same reaction conditions, on the other hand, did not occur at all. Spectroscopic and GPC measurements indicated that syntheses of polystyrene and polyacrylonitrile macrophotoinitiators bearing a photoreactive benzoin end group, PSt-PI and PAN-PI, respectively, with well-defined structures were achieved. These unique macrophotoinitiators were then used as prepolymers in photoinitiated free radical promoted cationic polymerization of cyclohexene oxide (CHO) and butyl vinyl ether (BVE) monomers to obtain PSt-PCHO, PSt-PBVE, PAN-PCHO, and PAN-PBVE di-block copolymers.

Polyhedral oligomeric silsesquioxane-capped poly(N-vinyl pyrrolidone) amphiphiles: synthesis, self-assembly, and use as porogen of nanoporous poly(vinylidene fluoride)

In this contribution, we reported the synthesis of polyhedral oligomeric silsesquioxane (POSS)-capped poly(N-vinyl pyrrolidone) (PVPy) via reversible addition-fragmentation chain transfer/macromolecular design via interchange of xanthate (RAFT/MADIX) polymerization. First, a POSS macromer bearing xanthate moiety was synthesized and was then used as the chain transfer agent to mediate the radical polymerization of N-vinylpyrrolidone (NVP). By controlling the mass ratios of the POSS-CTA to NVP, a series of the POSS-capped PVPy amphiphiles were successfully synthesized with various molecular weights. It was found that in bulks, the POSS-capped PVPy was microphase-separated and the POSS end groups were self-organized into the spherical microdomains with the size of 10~100 nm in diameter. In the solvent selective for PVPy (e.g., water), the POSS-capped PVPy was capable of self-assembling into the spherical micelles with an average diameter of 20~50 nm as evidenced by dynamic laser scattering (DLS) and transmission electron microscopy (TEM). Owing to the amphiphilicity, POSS-capped PVPy also displayed the self-assembly behavior in poly(vinylidene fluoride) (PVDF), in which the POSS cages were aggregated into 10~30 nm microdomains. In the nanocomposites of PVDF with POSS-capped PVPy, the spherical POSS microdomains were readily etched by using hydrofluoric acid, leaving the nanopores in the materials.

Morphologies and dielectric properties of epoxy thermosets containing poly(N-vinylcarbazole), fullerene-C60 and their charge transfer complex nanophases

Both poly(ethylene oxide)-block-poly(N-vinylcarbazole) (PEO-b-PVK) diblock copolymer and fullerene-capped poly(ethylene oxide) (PEO-C60) were synthesized in this work. The former was obtained via reversible addition-fragmentation chain transfer/macromolecular design via the interchange of xanthate process whereas the latter via click reaction of azido-capped poly(ethylene oxide) with fullerene-C60. Both of the amphiphiles were incorporated into epoxy to obtain the nanostructured thermosets. It was found that the PVK-C60 charge transfer complexes were formed in the ternary thermosetting blends of epoxy, PEO-b-PVK and PEO-C60. The nanostructured epoxy thermosets containing PVK or/and fullerene displayed the enhanced dielectric constants whereas the dielectric loss remained almost unchanged. Nonetheless, the dielectric constants were significantly decreased while both PEO-b-PVK and PEO-C60 were simultaneously incorporated into the thermosets. The depression in dielectric constant is attributable to the formation of the charge transfer complexes of PVK with fullerene-C60. It was found that the dielectric constants can be modulated with the contents of the PVK-C60 charge transfer complexes.

Synthesis of narrow molecular weight distribution polyvinyl acetate by gamma–rays initiated RAFT/MADIX miniemulsion polymerization

Abstract For the first time, conventional and controlled miniemulsion polymerization of vinyl acetate (VAc) was performed using gamma radiation as alternative source of initiation. Reversible addition-fragmentation chain transfer/macromolecular design via interchange of xanthates (RAFT/MADIX) technique was applied to control the polymerization process. For this purpose, S-2-cyano-2-propyl-O-ethyl xanthate ( C TA) was used as chain transfer agent. To illustrate the advantages of using gamma radiation instead of other initiation sources, we compared gamma radiation and the 2,2′-azobis(isobutyronitrile) (AIBN) as initiators in the polymerization mediated by RAFT/MADIX technique. Compared with conventional miniemulsion polymerization, the controlled polymerization process allowed obtaining monomodal molecular weight distribution s and a significant control over the molecular weight distribution. The miniemulsions showed colloidal stability during polymerization and stable latices were obtained in a short reaction time with high conversion. Gamma radiation demonstrated to be a better initiator than AIBN for the miniemulsion polymerization of VAc, mediated by RAFT/MADIX.

Organic–inorganic poly(N‐vinylpyrrolidone) copolymers with double‐decker silsesquioxane in the main chains: Synthesis, glass transition, and self‐assembly behavior

ABSTRACTAn organic–inorganic copolymer with polyhedral oligomeric silsesquioxane (POSS) and xanthate moieties in the main chain was synthesized via the polycondensation between 3,13‐di(2‐bromopropionate)propyl double‐decker silsesquioxane (DDSQ) and 1,4‐di(xanthate potassium)butane. This hybrid copolymer was used as the macromolecular chain transfer agent to obtain the organic–inorganic poly(N‐vinylpyrrolidone) (PVPy) copolymers via a reversible addition fragmentation chain transfer/macromolecular design via the interchange of xanthates (RAFT/MADIX) polymerization approach; the polymerization behavior of N‐vinyl pyrrolidone was investigated by means of gel permeation chromatography. It was found that the polymerization was in a living and controlled manner. Transmission electron microscopy (TEM) showed that the organic–inorganic PVPy copolymers with DDSQ in the main chains were microphase‐separated in bulks. Compared to plain PVPy, the organic–inorganic PVPy copolymers displayed the decreased glass transition temperatures (Tgs); the decreased Tgs are attributable to the effect of the introduced DDSQ cages on the packing of PVPy chains as evidenced by means of Fourier transform infrared spectroscopy (FTIR). In water, the organic–inorganic PVPy copolymers can self‐assemble into the spherical nano‐objects with the size of 20–50 nm in diameter. In the self‐assembled nano‐objects, the aggregates of the hydrophobic DDSQ constituted the cores of the polymeric micelles whereas the PVPy chains between the DDSQ behaved as the coronas of the polymeric micelles. © 2016 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2016, 54, 2949–2961

Synthesis of poly(N-vinyl carbazole)-based block copolymers by sequential polymerizations of RAFT–ATRP

Poly(N-vinylcarbazole) (PNVK) is one of the extensively studied photoconductive polymers because of its wide ranges of applications. Through the reversible addition-fragmentation chain transfer/macromolecular design via the interchange of xanthates (RAFT/MADIX) polymerizations, in this study we investigated the syntheses of PNVK-based block copolymers (BCPs) with styrene (St) and methyl methacrylate (MMA). A variety of difunctional haloester-xanthate inifers were prepared and subjected to sequential polymerizations through RAFT and ATRP. In the presence of small amounts of bromoxanthate inifers, the 1H NMR spectra showed nearly complete consumption of the NVK monomer, but without formation of PNVK. The bromoxanthate inifer could act as acidic moieties that protonated the highly basic NVK monomer. Through 1H NMR and MALDI-TOF spectroscopic analyses, the structures of byproducts were indentified and a plausible mechanism for their formation was proposed. Alternatively, RAFT/MADIX polymerizations of NVK with two chloroxanthate inifers S-[1-methyl-4-(6-chloropropionate)ethyl acetate] O-ethyl dithiocarbonate and S-[1-methyl-4-(6-chloroisobutyrate)ethyl acetate] O-ethyl dithiocarbonate) provided first-order kinetic plots and well-controlled PNVK-Cl MIs (Mn ≈ 6000–40,000; Mw/Mn < 1.35). Using a suitable ATRP-initiating groups and optimization of the reaction conditions, the BCPs PNVK-b-PSt (Mn ≈ 4900–12,800; Mw/Mn < 1.5) and PNVK-b-PMMA (Mn ≈ 46,000–100,000; Mw/Mn < 1.35) were obtained.

Cyclopolymerization of α,ω‐heterodifunctional monomers containing styrene and maleimide moieties

ABSTRACTA series of α,ω‐heterodifunctional monomers with styrene (St) and maleimide moieties bridged by a varied length of oligo‐ethylene glycol (OEG) linkers were synthesized. Cyclopolymerizations of these monomers through reversible addition–fragmentation chain transfer‐mediated alternating radical copolymerization between intramolecular St and maleimide moieties were investigated. For the monomers with three or more ethylene glycol (EG) units, their cyclopolymerizations can be realized properly in low monomer feeding concentrations, affording well‐defined cyclopolymers with crown ether encircled in their main chains. Importantly, the cyclopolymerizations of monomers with six or seven EG units in the presence of KPF6 could be enhanced by the supramolecular effects between the OEG linkers and the potassium metal ion. Thus, the monomer feeding concentration could be largely improved, which may benefit preparation of the cyclopolymers with high degrees of copolymerization. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2014, 52, 330–338

Formation of Nanophases in Epoxy Thermosets Containing Amphiphilic Block Copolymers with Linear and Star-like Topologies

In this work, we investigated the effect of topological structures of block copolymers on the formation of the nanophase in epoxy thermosets containing amphiphilic block copolymers. Two block copolymers composed of poly(ε-caprolactone) (PCL) and poly(2,2,2-trifluoroethyl acrylate) (PTFEA) blocks were synthesized to possess linear and star-shaped topologies. The star-shaped block copolymer composed a polyhedral oligomeric silsesquioxane (POSS) core and eight poly(ε-caprolactone)-block-poly(2,2,2-trifluoroethyl acrylate) (PCL-b-PTFEA) diblock copolymer arms. Both block copolymers were synthesized via the combination of ring-opening polymerization and reversible addition-fragmentation chain transfer/macromolecular design via the interchange of xanthate (RAFT/MADIX) process; they were controlled to have identical compositions of copolymerization and lengths of blocks. Upon incorporating both block copolymers into epoxy thermosets, the spherical PTFEA nanophases were formed in all the cases. However, the sizes of PTFEA nanophases from the star-like block copolymer were significantly lower than those from the linear diblock copolymer. The difference in the nanostructures gave rise to the different glass transition behavior of the nanostructured thermosets. The dependence of PTFEA nanophases on the topologies of block copolymers is interpreted in terms of the conformation of the miscible subchain (viz. PCL) at the surface of PTFEA microdomains and the restriction of POSS cages on the demixing of the thermoset-philic block (viz. PCL).

Understanding the Role of ω-End Groups and Molecular Weight in the Interaction of PNIPAM with Gold Surfaces

Modification of nanoparticle surfaces by adsorption or grafting of polymers allows fine control of hybrid materials properties for diverse applications. To obtain such a control, it is of paramount importance to understand the impact of the polymer structure on the nature and strength of its interaction with the nanoparticle. We investigated here a simple model of hybrid materials made of poly(N-isopropylacrylamide) of different molar masses and end groups interacting with gold surfaces. A series of poly(N-isopropylacrylamide) with number-average molar masses ranging from 3700 to 10000 g·mol–1 were synthesized by reversible addition–fragmentation chain transfer/macromolecular design by interchange of xanthates (RAFT/MADIX). The terminal xanthate group was then reduced into either a thiol or a hydrogen group. Quartz crystal microbalance adsorption/desorption experiments demonstrated that the polymer termini have a strong impact on the mechanism of polymer adsorption on flat gold surfaces. These differences in polymer structure have, in return, a strong influence on the colloidal stability and growth mechanism of nanoparticles when directly synthesized in polymer solution. For those properties, the effect of xanthate group compared very favorably to the conventional thiol moiety. Interestingly, the properties of nanohybrids were poorly affected by the molar mass of the polymer.

Novel pH‐responsive mixed‐charge copolymer brushes based on carboxylic acid and quaternary amine monomers

AbstractIn this study, we report on the fabrication of tunable mixed‐charged copolymer brushes consisting of negatively charged carboxylic acid monomer (4‐vinylbenzoic acid, VBA) and positively charged quaternary amine monomer ((ar‐vinylbenzyl)trimethylammonium chloride) via reversible addition–fragmentation chain transfer‐mediated polymerization. The copolymer brushes have negative charge under neutral and basic conditions, and are positively charged under acidic conditions owing to the protonation of the carboxylate groups. The copolymer brushes revealed a unique reversible wetting behavior with pH. The reversible properties of the copolymer brushes can be employed to regulate the adsorption of charged biomacromolecules such as DNA and proteins. © 2013 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2013

Investigation of the influence of the architectures of poly(vinyl pyrrolidone) polymers made via the reversible addition–fragmentation chain transfer/macromolecular design via the interchange of xanthates mechanism on the stabilization of suspension polymerizations

AbstractLinear, star, and block copolymers based on poly(vinyl pyrrolidone) (PVP) were synthesized with the macromolecular design via the interchange of xanthates (MADIX) process for use as potential stabilizers in suspension polymerization. The design of the leaving group of the dithioxanthate‐based transfer agent was shown to be key to the successful preparation of well‐defined PVP architectures. A linear correlation of the monomer conversion and molecular weight was found in the synthesis of star polymers, whereas the molecular weight distribution remained narrow (polydispersity index &lt; 1.3). Significant side reactions, which typically broaden the molecular weight distribution when R‐designed MADIX agents are used, were absent. The living behavior of the PVP polymerization was furthermore confirmed via chain extension with vinyl acetate, which resulted in the formation of PVP–PVAc block copolymers [where PVAc is poly(vinyl acetate)]. The prepared polymers were used as stabilizers in suspension polymerization to prepare crosslinked poly(vinyl neodecanoate)/ethylene glycol dimethacrylate microspheres. The ratio of the interfacial tension of the aqueous and monomer phases and the overall viscosity were found to have an effect on the diameter of the particles, with PVP star polymers as stabilizers resulting in smaller particles. A smaller interfacial tension, measured when star polymers and block copolymers were used, resulted in the appearance of smaller particles, probably because of more breakup events of the monomer droplets and the enhanced stabilization of the particle surface area. © 2006 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 44: 4372–4383, 2006