RAFT Agent Research Articles

Poly(N‐vinyl imidazole) grafted silica nanofillers: Synthesis by RAFT polymerization and nanocomposites with polybenzimidazole

ABSTRACTIn this report, we synthesized poly(N‐vinyl imidazole) (PNVI) grafted silica nanoparticles (SiNP) by using RAFT polymerization through grafting‐from approach to demonstrate that the self‐assembled structure of SiNP is the key diving force in improving physical properties of SiNP based nanocomposites. In a multistep synthetic process, well‐defined PNVI chains with tunable molecular weights and surface chain densities were grown from the RAFT agent anchored SiNP surface using N‐vinyl imidazole (NVI) as a monomer. Spectroscopic and thermal analysis confirmed surface grafting of PNVI on SiNP surface and the amount of grafted PNVI chins were also quantified. The mean diameter of the PNVI grafted SiNP (PNVI‐g‐SiNP) particles altered between 50 and 100 nm with the variation of PNVI chain lengths. The present approach is metal‐catalyst free, straight forward, and provides PNVI functionalized SiNP in a simple manner in comparison to the reported methods. Further, these PNVI‐g‐SiNP particles were used as a nanofiller to prepare nanocomposites with Poly(4,4′‐diphenylether‐5,5′‐bibenzimidazole) (OPBI). These nanocomposites displayed significantly higher mechanical, proton conductivity and less acid leaching properties than the pristine OPBI. The anisotropic self‐assembled ordered structure formation of nanofillers in the nanocomposites believed to be the driving force for the enhanced physical properties. © 2017 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2018, 56, 365–375

Toward Sulfur-Free RAFT Polymerization Induced Self-Assembly.

Polymerization induced self-assembly (PISA) using methacrylate-based macromonomers as RAFT agents is an unexplored, attractive route to make self-assembled colloidal objects. The use of this class of RAFT-agents in heterogeneous polymerizations is however not trivial, because of their inherent low reactivity. In this work we demonstrate that two obstacles need to be overcome, one being control of chain-growth (propagation), the other monomer partitioning. Batch dispersion polymerizations of hydroxypropyl methacrylate in the presence of poly(glycerol methacrylate) macromonomers in water showed limited control of chain-growth. Semicontinuous experiments whereby monomer was fed improved results only to some extent. Control of propagation is essential for PISA to allow for dynamic rearrangement of colloidal structures. We tackled the problem of monomer partitioning (caused by uncontrolled particle nucleation) by starting the polymerization with an amphiphilic thermoresponsive diblock copolymer, already "phase-separated" from solution. TEM analysis showed that PISA was successful and that different particle morphologies were obtained throughout the polymerization.

Improved antiviral properties of chain end lipophilic fucoidan-mimetic glycopolymers synthesized by RAFT polymerization

Sulfated polysaccharides and synthetic glycopolymers are promising candidates as antiviral drugs but have failed in clinical trials most likely due to lack of virucidal activity. However, studies have shown that incorporation of lipophilic end groups to oligosaccharide chains is a mean to gain the desired virucidal properties. Here, we describe the introduction of lipophilic end groups to sulfated α-l-fucoside-pendant polymethacrylamides, also known as fucoidan-mimetic glycopolymers, by RAFT polymerization. RAFT agents bearing octadecyl, dioctadecyl and cholesteryl groups were used to synthesize lipoglycopolymers of different chain lengths. Short lipoglycopolymers bearing lipophilic end groups showed an improved ability to block viral entry and infection of cells compared to glycopolymers without lipophilic end groups. Short lipoglycopolymers bearing octadecyl or dioctadecyl end groups, also completely stopped the spreading of the viral infection. However, these lipoglycopolymers did not show actual virucidal properties. Nevertheless, we have described a first step towards obtaining virucidal synthetic glycopolymers for clinical use.

Visible light‐induced RAFT polymerization of methacrylates with benzaldehyde derivatives as organophotoredox catalysts

ABSTRACTThe benzaldehyde derivatives, such as 2,4‐dimethoxy benzaldehyde (PC1) and p‐anisaldehyde (PC2), were successfully used as photoredox catalysts (PCs) in combination with typical RAFT agent 4‐cyano‐4‐(phenylcarbonothioylthio)pentanoic acid (CTP) for the controlled photoinduced electron transfer RAFT polymerization (PET‐RAFT) of methyl methacrylate (MMA) and benzyl methacrylate (BnMA) at room temperature. The kinetics of the polymerizations showed first order with respect to monomer conversions. Besides, the average number molecular weights (Mn) of the produced polymers increased linearly with the monomer conversions and kept relatively narrow polydispersity (PDI = Mw/Mn). For example, the Mn of PMMA increased from about 3400 to 17,300 g mol−1 with the increasing in monomer conversion from 11% to 85%, and the PDI maintained around 1.36. The living features of polymerizations with the PC1 and PC2 as catalysts have also been further supported by chain extension and synthesis of PMMA‐b‐PBnMA diblock copolymer. As a result, the simplicity and efficiency of benzaldehyde derivatives catalyzed PET‐RAFT polymerization have been demonstrated under mild conditions. © 2017 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2018, 56, 229–236

Systematic comparison of single-walled carbon nanotube/poly(vinyl acetate) graft-to reactions

The covalent grafting of polymers to single-walled carbon nanotubes (SWCNTs) is widely used to improve solvent compatibility, as well as composite and functional performance. Here, three different graft-to strategies are directly compared, using azide, diazonium, and bromide terminated polymers, over four different molecular weights (oligomeric to 10 kDa) using specifically synthesized low polydispersity, end-group controlled poly(vinyl acetate) (PVAc) prepared by polymerisation using a bespoke protected-amine RAFT agent. Coupling of the bromo-polymer to reduced SWCNTs led to higher degrees of functionalisation (grafting ratios up to 68.9%) than the azide and diazonium grafting reactions, attributed to better initial dispersion of the pre-grafted SWCNTs. The use of higher molecular weight polymers led to a decrease in the total weight of polymer grafted, as the increase in per-polymer weight is more than offset by steric occlusion on the SWCNT surface. For these graft-to reactions, the dispersibility of grafted SWCNTs was found to depend most strongly on the polymer molecular weight, not total weight of grafted polymer or grafting chemistry, with an intermediate Mn∼5757 PVAc giving the best dispersibilities, at up to 118 mg L−1.

Designing catechol‐end functionalized poly(DMAm‐co‐NIPAM) by RAFT with tunable LCSTs

ABSTRACTProviding catechol‐end functionality to controlled structure lower critical solution temperature (LCST) copolymers is attractive, given the versatility of catechol chemistry for tethering to nanostructures. Controlled polymer chain lengths with catechol RAFT end groups are of interest to provide tunable LCST behavior to nanoparticles, although these polymerizations are relatively unexplored. Herein, the reactivity ratios for the RAFT copolymerization of N,N‐dimethylacrylamide (DMAm) and N‐isopropylacrylamide (NIPAM) pairs based on catechol‐end RAFT agents using an in situ NMR technique were first determined. Several catechol‐end poly(DMAm‐co‐NIPAM) samples were then prepared using the RAFT agent to provide copolymer. The reactivity ratios for the DMAm‐NIPAM pair were rDMAm = 1.28–1.31 and rNIPAM = 0.48–0.51. All the poly(DMAm‐co‐NIPAM) samples were found to have Mn values ≤ 26 kDa and Ð < 1.08 with LCST values ranging from 31 to 92°C, while maintaining a short range of glass transition temperature (Tg = 118–137°C). The difference in LCST values for the catechol functionalized poly(DMAm‐co‐NIPAM) based on 0.5 wt% aqueous buffered solutions at pH 5.5 and 8.5 was found to be <3.0°C. These conditions are suitable for subsequent catechol‐induced coordination and nucleophilic addition chemistry for covalent and noncovalent linkages during subsequent post‐modification. © 2017 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2017, 55, 4062–4070

Raft approach to the copolymerisation of methyl methacrylate based polymeric micelles

In this study, copolymer micelles were synthesised via free radical RAFT bulk polymerisation and RAFT dispersion polymerisation of methyl methacrylate. 4-CPDB-PDMS was used as the macro- RAFT agent, leading to the formation of the micellar nanostructures. Copolymer micelles obtained from the bulk polymerisation were used as macro RAFT agents in the dispersion polymerisation of methyl methacrylate in hexane, at 70 o C. Characterisation of the various polymeric products was carried out using gel permeation chromatography (GPC), nuclear magnetic resonance spectroscopy(NMR), fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), scanning electron microscopy (SEM) and dynamic light scattering (DLS) analyses. The results show that the molecular weights of the copolymers in the bulk are controlled. The block copolymers in the dispersion have broad polydispersity indices (PDI) and the kinetic study indicates a deviation from ‘pseudo first order’ kinetics at higher conversions. Keywords: RAF; polymerisation; methyl methacrylate; micelles

Functionalized Chitosan for Pharmaceutical Applications

Background: Chitosan structure versatility toward a change in an external stimulus represents a “must have” for the pharmaceutical applications, especially for the pharmaceutical formulations. Chemical modification can open new ways to obtain materials with tailored properties. Despite the great interest for conventional graft modifications, controlled/living free radical polymerizations (i.e. RAFT, ATRP, etc.) and advanced chemistry techniques (i.e. click chemistry) seem more attractive nowadays and involve facile and fast procedure, high regioselectivity, quantitative yield, mild reaction conditions without generation of by-products. Objective: The present review provides a detailed state of art of the chemical modification of chitosan i.e. tailored side-chain functionalization using RAFT polymerization and click chemistry for specific applications within pharmaceutical formulations taking into account the applicative aspect regarding the need of pharmaceuticals. Conclusion: The review showed the routes of current approaches for side chain modification of chitosan including graft, block copolymers or other structural variations. The esterification of RAFT agents on chitosan by using carbonyl activating reagents enables producing chitosan graft and block copolymers with controlled architectures while the development of protection/ deprotection chemistry of chitosan made possible the regioselective modification of chitosan or other polysaccharides. Although these developments increased the potential of chitosan, still the chemical functionality and architectural diversity of the derivatives are limited. Application of modern techniques e.g. RAFT polymerization, “click” chemistry has opened new “doors” for the science of controlled and chemoselective synthesis of well- tailored derivatives with unique and superior properties.

Development of a Robust PET-RAFT Polymerization Using Graphitic Carbon Nitride (g-C3N4)

The metal-free semiconductor, graphitic carbon nitride (g-C3N4), was introduced into RAFT polymerization for the first time. The production of linear polyacrylate and polyacrylamide has been achieved via PET-RAFT polymerization using g-C3N4 as a photoactive organocatalyst without prior deoxygenation. The resulting polymers display controlled molecular weights, narrow polymer dispersities, and high end-group fidelity as exemplified by 1H NMR analysis, MALDI-TOF-MS measurement, and chain extension experiment. Temporal control is illustrated by intermittent light and dark cycles, with polymer growth arrested in the absence of irradiation. The effects of changing RAFT agents (i.e., trithiocarbonates), solvents, catalyst concentrations, and degrees of polymerization in this system have been investigated. The successful polymerization of nonpurified monomer (i.e., still containing radical inhibitors) demonstrates the robust nature of the presented PET-RAFT system.

Controlled Direct Growth of Polymer Shell on Upconversion Nanoparticle Surface via Visible Light Regulated Polymerization

Lanthanide-doped upconversion nanoparticles (UCNPs) have unique photoluminescent properties that are useful in many biomedical applications. Modification of UCNPs with a polymer layer can confer additional functionality such as biocompatibility, stability in vivo, or drug delivery capability. It is also important that the modification process can be controlled precisely and without having adverse effects on the UCNPs luminescence properties. Herein, a polymer shell was grafted directly from the surface of UCNPs (grafting from) via visible light (λmax = 635 nm, 0.7 mW/cm2) regulated photoenergy/electron transfer–reversible addition fragmentation chain transfer polymerization (PET-RAFT). The polymerization kinetics, grafting density, and thickness of the surface-tethered polymer chains can be tuned precisely by adjusting the monomer and RAFT agent ratio or the light exposure time. This approach also permits temporal control of the polymerization process. That is, the polymerization process can be initiated,...

Simulation studies of the discrete semi-batch RAFT–mediated polymerization of styrene using a RAFT agent with relatively poor leaving group

Simulated RAFT–mediated polymerization of styrene using a RAFT agent with a relatively poor leaving group exhibits good control under semi-batch mode of polymerization compared to batch mode polymerization. For bulk and solution polymerization simulated under batch condition, the dispersity values are ∼1.40, and the corresponding molecular weight distributions display significant tailing on the low molecular weight side. In the case of RAFT–mediated polymerization simulated under discrete semi-batch conditions, narrower molecular weight distributions are obtained, with dispersity values ∼1.2. Simulated conversion and molecular weight data are in good agreement with experimentally determined values. For polymerizations simulated up to ca. 40% overall monomer conversion under batch and discrete semi-batch mode of polymerization, similar fractions of living chains are obtained.

Mechanism and Kinetics of Dithiobenzoate‐Mediated RAFT Polymerization – Status of the Dilemma

Macromol. Chem. Phys. 2014, 215, 9–26 In the above article, some of the values provided in Table 1 are based on incorrect Arrhenius data and the recommended log A values were interchanged in the footnote (a). The revised data do not affect any of the conclusions drawn in the publication. Additionally, the numbers of the structures in the Schemes 4, 5 and 6 are incorrect. Please find the correct table and schemes here: On page 17, in the originally published article, the last paragraph in column 3, relating to the ‘Secondary RAFT reaction hypothesis’ is corrected to read: Li et al.[72] analysed the major products formed from in reactions of various dithiobenzoate with phenylethyl radicals formed from the corresponding alkoxyamine (29). Rate coefficients for addition and fragmentation were estimated with the aid of Monte Carlo Simulation and the assumption of a SF model, an IRT model, and a proposed new model in which the intermediate radical 27 undergoes further reaction with RAFT agent to form a new intermediate 28 as shown in Scheme 6 (Table 2). The latter process, which the authors called a “secondary RAFT reaction, seems unlikely but is, nonetheless, deserving of consideration. The process can be considered as analogous to copolymerization of the RAFT agent, which is observed as a major side reaction during macromonomer RAFT polymerization with monosubstituted monomers such as styrenes and acrylates.[73,74] However, Li et al.[72] provided no evidence for the formation of species 28 beyond their observation of an incomplete mass balance. While, the intermediate 28, If formed, could undergo reactions analogous to those ascribed to other intermediate radicals, the most likely pathway would be reversion to starting materials. The author apologizes for this inconvenience.

Heterofunctional RAFT‐derived PNIPAM via cascade trithiocarbonate removal and thiol‐yne coupling click reaction

ABSTRACTAn efficient one‐pot process to functionalize the α‐ and ω‐positions of RAFT‐derived poly(N‐isopropylacrylamide) (PNIPAM) by two inherently different mechanistic pathways is reported. The method relies on the RAFT polymerization of NIPAM using a new alkyne‐based RAFT agent, namely 2‐cyano‐5‐oxo‐5‐(prop‐2‐yn‐1‐ylamino)pentan‐2‐yl dodecyltrithiocarbonate (COPYDC) and the combination of thiol‐yne click chemistry and thiocarbonylthio chain‐end removal reactions. COPYDC was prepared in good yield and used as an efficient chain transfer agent during the RAFT polymerization of NIPAM. Well‐defined polymers with controlled molar masses ( = 7500–14,700 g.mol−1) and narrow dispersities (Đ = 1.18–1.26) are thus obtained. Cascade thiol‐yne click reaction at the alkyne α‐chain end and trithiocarbonate removal at the ω‐chain end are successfully achieved using benzyl mercaptan and excess AIBN. The reported method provides a facile and mild route to heterofunctional telechelic RAFT polymers with predictable molar masses and low dispersities. © 2017 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2017, 55, 3597–3606

Versatile Routes to Functional RAFT Chain Transfer Agents through the Passerini Multicomponent Reaction.

The widespread adoption of RAFT polymerization stems partly from the ease and utility of installing a functional chain transfer agent onto the ends of the generated polymer chains. In parallel, the Passerini multicomponent reaction offers great versatility in converting a wide range of easily accessible building blocks to functional materials. In this work, we have combined the two approaches such that a single, commonly available, RAFT agent is used in Passerini reactions to generate a variety of multifunctional RAFT chain transfer agents containing ester linkages. Reactions to generate the multifunctional RAFT agents took place under mild conditions and in good yields. The resulting Passerini-RAFT agents were able to exert control over radical polymerization to generate materials of well-defined molecular weights and dispersity. Furthermore, the presence in these polymer cores of ester and amide functionality through the Passerini chemistries, provided regions in the materials which are inherently biodegradable, facilitating any subsequent biomedical applications. The work overall thus demonstrates a versatile and facile synthetic route to multi functional RAFT chain transfer agents and biodegradable polymers.

Use of a trithiocarbonyl RAFT agent without modification as (Co)stabilizer in miniemulsion polymerization

ABSTRACTHerein, we demonstrate the effects of using 4‐cyano‐4‐[(dodecylsulfanylthiocarbonyl)sulfanyl] pentanoic acid (CDPA) simultaneously as RAFT chain transfer agent (RAFT‐CTA) and (co)stabilizer in a miniemulsion polymerization process. The novelty of this report includes use this RAFT‐CTA without modification, such as macro‐CTAs, block, or random copolymers. Using an optimized polymerization procedure, it is possible to use distinct formulations and therefore obtain stable latexes comprised of well‐defined spherical nanoparticles. The polymerization kinetics and final polymer properties are directly correlated to the function of the CDPA in the system: RAFT‐CTA and/or (co)stabilizer. Typically, the nanoparticles present average diameters less than 150 nm. The molar mass properties and the kinetic profiles confirm to an expected RAFT process, although some deviations are observable when using the CDPA as only stabilizer. These deviations are a function of the amount of CDPA present within the nano‐droplets, or adsorption on its surface. © 2017 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2017, 55, 1687–1695

Well‐defined polyisoprene‐grafted silica nanoparticles via the RAFT process

ABSTRACTThe preparation of well‐defined polyisoprene‐grafted silica nanoparticles (PIP‐g‐SiO2 NPs) was investigated. Surface initiated reversible addition fragmentation chain transfer (SI‐RAFT) polymerization was used to polymerize isoprene from the surface of 15 nm silica NPs. A high temperature stable trithiocarbonate RAFT agent was anchored onto the surface of particles with controllable graft densities. The polymerization of isoprene mediated by silica anchored RAFT with different densities were investigated and compared to the polymerization mediated by free RAFT agents. The effects of different temperatures, initiators, and monomer feed ratios on the kinetics of the SI‐RAFT polymerization were also investigated. Using this technique, block copolymers of polyisoprene and polystyrene on the surface of silica particles were also prepared. The well‐defined synthesized PIP‐g‐SiO2 NPs were then mixed with a polyisoprene matrix which showed a good level of dispersion throughout the matrix. These tunable grafted particles have potential applications in the field of rubber nanocomposites. © 2017 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2017, 55, 1493–1501

Preparation of well-defined erythromycin imprinted non-woven fabrics via radiation-induced RAFT-mediated grafting

Radiation-induced RAFT polymerization technique was applied to synthesize well-defined molecularly imprinted polymers (MIPs) of erythromycin (ERY). Methacrylic acid (MAA) was grafted onto porous polyethylene (PE)/polypropylene (PP) nonwoven fabrics, under γ-irradiation by employing 2-pheny-2-propyl benzodithioate as the RAFT agent and ethylene glycol dimethacrylate (EGDMA) as the crosslinker. MAA/erythromycin ratios of 2/1, 4/1, 6/1 were tested to optimize the synthesis of MIPs. The highest binding capacity was encountered at a MAA/ERY ratio of 4/1. Non-imprinted polymers (NIPs) were also synthesized in the absence of ERY. The MIPs synthesized by RAFT method presented a better binding capacity compared to those prepared by conventional method where no RAFT agent was employed.

Design of Dithiobenzoate RAFT Agent Bearing Hydroxyl Groups and Its Application in RAFT Polymerization for Telechelic Diol Polymers.

RAFT polymerization is attractive for its reliability, facile operation, and high tolerance to a wide variety of monomers, functional groups, solvents, and temperatures. Herein, we report the RAFT-based synthesis of well-defined polymers bearing hydroxyl groups at two terminals by using various monomers. We found that the molecular weight of obtained polymers was half that of a target value when a trithiocarbonate-type chain transfer agent (CTA) was used, suggesting that the polymers unexpectedly cleaved at the middle of the polymer chain as the reaction was proceeding. To address the problem, we synthesized a novel “dithiobenzoate”-type CTA, 2-[N-(2-hydroxyethyl)carbamoyl]prop-2-yl 4-hydroxydithiobenzoate (HECPHD), which bears hydroxyl groups at both terminals, and we succeeded in RAFT polymerization with various monomers without a cleavage of the polymers.

Trithiocarbonates as intrinsic photoredox catalysts and RAFT agents for oxygen tolerant controlled radical polymerization

In this study, we reported on the discovery that trithiocarbonates (RAFT agents) can act as intrinsic photocatalyst to significantly reduce the oxygen level in a controlled radical polymerization under visible light irridation.

Synthesis of sharply thermo and PH responsive PMA-b-PNIPAM-b-PEG-b-PNIPAM-b-PMA by RAFT radical polymerization and its schizophrenic micellization in aqueous solutions

Sharply thermo- and pH-responsive pentablock terpolymer with a core-shell-corona structure was prepared by RAFT polymerization of N-isopropylacrylamide and methacrylic acid monomers using PEG-based benzoate-type of RAFT agent. The PEG-based RAFT agent could be easily synthesized by dihydroxyl-capped PEG with 4-cyano-4-(thiobenzoyl) sulfanylpentanoic acids, using esterification reaction. This pentablock terpolymer was characterized by 1H NMR, FT-IR, and GPC. The PDI was obtained by GPC, indicating that the molecular weight distribution was narrow and the polymerization was well controlled. The thermo- and pH-responsive micellization of the pentablock terpolymer in aqueous solution was investigated using fluorescence spectroscopy technique, UV–vis transmittance, and TEM. The LCST of pentablock terpolymer increased (over 50 °C) compared to the NIPAM homopolymer (~32 °C), due to the incorporation of the hydrophilic PEG and PMA blocks in pentablock terpolymer (PNIPAM block as the core, PEG the block and the hydrophilic PMA block as the shell and the corona). Also, pH-dependent phase transition behavior shows at a pH value of about ~5.8, according to pKa of MAA. Thus, in acidic solution at room temperature, the pentablock terpolymer self-assembled to form core–shell–corona micelles, with the hydrophobic PMA block as the core, the PNIPAM block and the hydrophilic PEG block as the shell and the corona, respectively.