RAFT Agent Research Articles

AB/ABC/ABCD supramolecular block copolymers from Hamilton wedge and barbiturate-functionalized RAFT agents

Two RAFT agents bearing respectively a Hamilton receptor (HR) and barbiturate (Ba) recognition units have been designed and proven to selectively associate. Polymerizations mediated by these CTAs afforded high molar mass tailor-made H-bonding homopolymers and block copolymers. The capacity of the resulting macromolecular building blocks to form sextuple H-bonded complexes allowed for the straightforward preparation of original AB, ABC and ABCD supramolecular block copolymers with relatively high binding constants (Kassoc ∼ 1.59 to 1.95 × 105 M−1 in toluene at 25 °C).

The scope for synthesis of macro-RAFT agents by sequential insertion of single monomer units

The scope for synthesis of new macro-RAFT agents (Z–C(S)S–(M)–R) by sequential insertion of monomers (M) ‘one at a time’ into an initial RAFT agent (Z–C(S)S–R) has been explored. The process is illustrated with the preparation of a styrene-N-isopropylacrylamide (NIPAM) co-dimer macro-RAFT agent [(CH3)3C(CN)–CH2CH(Ph)–CH2CH(CONHiPr)–SC(S)–S-alkyl] by successive single unit monomer insertions into a cyanoisopropyl trithiocarbonate. Critical factors for success are a high transfer constant for the RAFT agent and a high rate of addition of the radical (R·) to monomer relative to further propagation. With these conditions satisfied, the rate of reaction is largely determined by the rate of R· adding to monomer. Initiator-derived by-products (Z–C(S)S–(M)–I) become an issue when R· is different from the initiator-derived radical (I·).

Solution Processable Phosphorescent Red Luminescent Polymer for OLED Devices

This study reports on the synthesis of red phosphorescent, solution processable chain-end functional, mid-chain- and three-arm star polymers from a functionalized styryl monomer host and a RAFT agent contain- ing a tris-cyclometalated Ir(III) complex phosphorescent group (dopant). The polymerization was carried out in toluene at 120 ˚C, and the resulting polymers showed a narrow molecular weight distribution (- D<1.3) and con- tained approximately 6-11 mol% of the Ir(piq)3 complex. All polymers showed good solubility in non-polar organic solvents and exhibited red emission. Of these polymers, the three-arm star polymer showed better energy trans- fer (in film) compared to the midchain functional and end chain functional polymers. No significant difference in optical properties and energy levels was found for the end functional vs the mid-chain and three-arm star poly- mers. Preliminary device evaluation of the end functional Ir(piq)3 poly(host) showed a current efficiency of 0.4 cd/A at 10 mA/cm 2 and a voltage of 10.5 V with color CIE 1931 coordinate (0.68, 0.31).

Host–guest driven supramolecular assembly of reversible comb-shaped polymers in aqueous solution

We report an original strategy towards supramolecular assembly of reversible comb-shaped polymers in aqueous solution through β-cyclodextrin–adamantane (β-CD–Ada) host–guest inclusion. Ada-functionalized poly(acrylic acid) grafts were generated by RAFT polymerization mediated by an adamantane-α-functionalized RAFT agent. A β-CD-grafted backbone was obtained by a two-step procedure: alkyne-functionalized backbones were first generated by RAFT polymerization of trimethylsilyl propargyl methacrylate and subsequently converted in a host system by CuAAC with azide-functionalized β-CD. The self-assembly between a β-CD-grafted polymer backbone and Ada-functionalized grafts was highlighted by 1H 2D NOESY NMR in D2O and by DLS. The reversible character of the host–guest association between the complementary macromolecular blocks was demonstrated by DLS through the addition of competing free β-CD.

Dispersion polymerization of styrene using poly(4-vinylpyridine) macro-RAFT agent under UV radiation

The dispersion polymerization of styrene using a poly(4-vinylpyridine) (P4VP) macromolecular RAFT (macro-RAFT) agent as both a macro-initiator and a colloidal stabilizer under UV radiation was investigated for the first time. The P4VP macro-RAFT agent (M n,GPC=49,000 g/mol, PDI=1.14) was prepared by the RAFT polymerization of 4-vinylpyridine using 2-cyanoprop-2-yl dithiobenzoate as a chain transfer agent. The resulting polystyrene (PSt) particles had hairy P4VP chains, which could successfully immobilize very small Au nanoparticles on the surface of the PSt particles. It was found that hairy polymeric particles could be produced by photo-initiated dispersion polymerizations of vinyl monomers using macro-RAFT agents that are susceptible to UV radiation as both macro-initiators and colloidal stabilizers.

Separation and quantification of dead species in styrene RAFT polymerization by gradient polymer elution chromatography

In living polymerization, the inevitable dead chain impurities, due to bimolecular termination and side reactions, are not only an obstacle for the synthesis of pure block copolymers but also an impairment in the application performance of the resulting polymer materials. In this paper, a simple separation and quantification method based on gradient polymer elution chromatography (GPEC) was developed to experimentally investigate the dead species in RAFT polymerization of styrene. The RAFT-prepared polystyrene (PSt) was extended with methyl acrylate in a specially-designed chain extension reaction, in which the living PSt chains were extended and transformed into block copolymer, but the remaining dead PSt chains (D-PSt) will remain constant and can be separated and quantified by GPEC. The systematic experimental investigation of the effect of various polymerization parameters on the mass fraction of dead species (fD-PSt) in RAFT-prepared polystyrene (PSt) was implemented. The results clearly demonstrated the initiator concentration and RAFT agent concentration can exhibit a linear and inversely proportional dependence on fD-PSt, respectively. In addition, the dead chains were found to be formed throughout the entire RAFT process. These unambiguous experimental data confirmed the previous theoretical calculation and model prediction, which may be beneficial to understand RAFT processes, optimize polymerization conditions and to minimize dead polymer contaminations. Moreover, the method based on GPEC proposed here was able to fractionate and quantify the dead and living species, which can serve as a powerful tool in the mechanistic study of the living radical polymerizations.

Facile synthesis of highly pure block copolymers by combination of RAFT polymerization, click reaction and de-grafting process

A facile strategy for synthesizing highly pure block copolymers with polymeric segments such as polystyrene, polyacrylamides and polyacrylates was described. The methodology involves a grafting reaction by tandem RAFT polymerization and azide–alkyne cycloaddition reaction and a subsequent de-grafting reaction via aminolysis or radical-induced addition-fragmentation reaction. S-methoxycarbonylphenylmethyl S′-propynyloxycarbonylethyltrithiocarbonate was used to synthesize Z-alkyne-functionalized macro chain transfer agents, and silica particles grafted with well-defined “living” block copolymers were obtained by simultaneous RAFT process and click reaction using clickable RAFT agents and azido-functionalized silica particles as raw materials. This approach afforded grafted polymers with polydispersity typically lower than 1.2 and silica–polymer hybrids with grafting density in the range of 0.020–0.091 chains nm−2 as the grafted chains had molecular weights between 4920 and 26 300 g mol−1. Highly pure block copolymers with terminal functionalities such as thiol, methyldithio, carboxyl, hydroxyl and halogen were obtained by a de-grafting process and postmodification, and azido-functionalized silica particles were efficiently recovered. The cycles of grafting and de-grafting reactions could be applied many times, and no significant decrease in grafting density was noted, indicating the versatility and generality of this approach for surface modification, synthesis of high-purity block copolymers and recycling of clickable solid substrate.

Synthesis and self-assembly of amphiphilic gradient copolymer via RAFT emulsifier-free emulsion polymerization

The amphiphilic gradient copolymers of 2,2,2-trifluoroethyl methacrylate (TFEMA) and acrylic acid (AA) have been synthesized by using amphiphilic RAFT agent via emulsifier-free emulsion polymerization with a starved feed method of adding TFEMA. Different cosolvents are added into polymerization system to inhibit AA’s homopolymerization of in aqueous phase. RAFT polymerization kinetics under different reaction conditions are discussed in detail. 1H NMR results indicate that the obtained copolymer has a chain structure with AA segments gradually changing to TFEMA segments. The copolymer latexes exhibit good pH stability (pH value from 5 to 14) and Ca2+ stability. The self-assembly behavior of gradient copolymers in selective solvents are observed and studied by transmission electron microscopy. All the copolymers can form spherical micelles, but the homogeneity and size of micelles are different.

Block Copolymers From Living Emulsion Polymerization: Reactor Operating Strategies and Blocking Efficiency

AbstractDiblock copolymers are generated using xanthate‐based RAFT agents in conjunction with emulsion polymerization via stage‐wise operations. First, emulsion polymerization is conducted for styrene, methyl acrylate, and butyl acrylate monomers to obtain polymers of specified molar mass. At the second stage, polymers undergo chain extension to produce block copolymers. Linear growth of molecular weight with respect to conversion establishes the living characteristics of the process. Under batch conditions, partly homopolymers are produced. Semi‐batch operation produces copolymers of higher purity with low polydispersity. The choice of blocking sequence is crucial for reducing the influence of the terminated chains on the distribution sequence of copolymers produced.magnified image

Experimental Validation of Intermediate Termination in RAFT Polymerization with Dithiobenzoate via Comparison of Miniemulsion and Bulk Polymerization Rates

AbstractTo understand if either of two controversial models for the retardation by RAFT agents is applicable, styrene polymerization using dithiobenzoate as the RAFT agent is carried out in both bulk and miniemulsion systems with the same rates of radical generation and the same RAFT agent concentrations. Miniemulsion polymerization with average diameters of the miniemulsion droplets of ≈107 nm is by far faster than in bulk, and the obtained rate of polymerization agrees well with the calculated results assuming a bimolecular termination between propagating radical and intermediate radical, generated by the addition reaction of propagating radical to the RAFT agent, which shows that the intermediate termination is the major reason for rate retardation by the RAFT agent.magnified image

Novel Malachite Green- and Rhodamine B-labeled cationic chain transfer agents for RAFT polymerization

Two novel cationic RAFT agents have been synthesized, one labeled with a Malachite Green (MG) dye and another with a Rhodamine B (RhoB) dye. MG-labeled dithiobenzoate (MGEDBA) was prepared in a straightforward manner after synthesis of MG-ethylammonium chloride that reacted with a precursor dithiobenzoate bearing an activated ester function. However, the analogous reaction with RhoB amino derivative led to a mixture of dithiobenzoate and thioamide derivatives. An alternative approach yielded the RhoB-labeled RAFT agent (RhoBEDBA) with complete conversion. The purification of these dye-labeled RAFT agents was very challenging because of their dual nature (aromatic and ionic). Both MGEDBA and RhoBEDBA were efficient RAFT chain transfer agents to control the polymerization of N,N-dimethylacrylamide (DMA). The resulting α-end-labeled MG- and RhoB-PDMA samples presented low dispersities ( Đ<1.2) and both chain-ends were preserved. Finally, we showed that the attachment of RhoB and MG to the PDMA polymer chain-end did not influence the photophysical properties of these dyes. Therefore, these new dye-labeled RAFT agents can be used to prepare various labeled polymers and especially water-soluble ones, to study their conformation and dynamics in solution or at interfaces using fluorescence methods, or as labeled probes for imaging and/or diagnosis purposes.

Heparin‐Like Macromolecules for the Modification of Anticoagulant Biomaterials

A heparin-like structured macromolecule (HLSM) is synthesized by RAFT polymerization using carboxyl-terminated trithiocarbonate as the RAFT agent. The HLSM can be directly blended with PES in DMAC to prepare flat-sheet membrane by means of a liquid-liquid phase separation technique. The synthesized polymeric material retard blood clotting and the modified membrane exhibits good anticoagulant ability due to the existence of the important functional groups SO(3) H, COOH and OH. The anionic groups on the membrane surface may bind coagulation factors and thus improve anticoagulant ability. The results indicate that the HLSM has potential to improve the anticoagulant properties of biomaterials and to be applied in blood purification including hemodialysis and bioartificial liver supports.

Dependence of Thermal Stability on Molecular Structure of RAFT/MADIX Agents: A Kinetic and Mechanistic Study

The thermal decomposition of different classes of RAFT/MADIX agents, namely dithioesters, trithiocarbonates, xanthates, and dithiocarbamates, were investigated through heating in solution. It was found that the decomposition behavior is complicated interplay of the effects of stabilizing Z-group and leaving R-group. The mechanism of the decomposition is mainly through three pathways, i.e., β-elimination, α-elimination, and homolysis of dithiocarbamate (particularly for universal RAFT agent). The most important pathway is the β-elimination of thiocarbonylthio compounds possessing β-hydrogen, leading to the formation unsaturated species. For the leaving group containing solely α-hydrogen, such as benzyl, α-elimination takes place, resulting in the formation of (E)-stilbene through a carbene intermediate. Homolysis occurs specifically in the case of a universal RAFT agent, in which a thiocarbonyl radical and an alkylthio radical are generated, finally forming thiolactone through a radical process. The stabilities of the RAFT/MADIX agents are investigated by measuring the apparent kinetics and activation energy of the thermal decomposition reactions. Both Z-group and R-group influence the stability of the agents through electronic and steric effects. Lone pair electron donating heteroatoms of Z-group show a remarkable stabilizing effect while electron withdrawing substituents, either in Z- or R-group, tends to destabilize the agent. In addition, bulkier or more β-hydrogens result in faster decomposition rate or lower decomposition temperature. Thus, the stability of the RAFT/MAIDX agents decreases in the order where R is (with identical Z = phenyl) −CH2Ph (5) > −PS (PS-RAFT 15) > −C(Me)HPh (2) > −C(Me)2C(═O)OC2H5 (7) > −C(Me)2Ph(1) > −PMMA (PMMA-RAFT 16) > −C(Me)2CN (6). For those possessing identical leaving group such as 1-phenylethyl, the stability decreases in the order of O-ethyl (11) > –N(CH2CH3)2 (13) > –SCH(CH3)Ph (8) > −Ph (2) > −CH2Ph (4) > −PhNO2 (3). These results consort with the chain transfer acitivities measured by the CSIRO group and agree well with the ab initio theoretical results by Coote. In addition, the difference between thermal stabilities of the universal RAFT agents at neutral and protonated states has also been demonstrated.

Facile synthesis of silica-polymer hybrids via simultaneous RAFT process and hydroxyl-alkoxysilane coupling reaction

This study aimed at the synthesis of silica particles grafted with better-defined homopolymers and block copolymers by tandem approach. Z-functionalized S-benzyl S′-(3-trimethoxysilyl)propyltrithiocarbonate (BTPT) was used as a couplable RAFT agent to synthesize the target inorganic-organic hybrids. Simultaneous coupling reaction and RAFT process using silica particles and BTPT as raw materials efficiently afforded homopolymers grafted silica, and RAFT-synthesized macro chain transfer agents with ω-terminal trimethoxysilane moiety were utilized to mediate graft reaction to prepare silica particles grafted with di-, tri- and tetrablock copolymers comprised of polymer segments such as polystyrene, polyacrylamides and polyacrylates. When the grafted chains had molecular weights ranging between 3920 and 24800 g/mol, the molar grafting ratios, which were dependent on reaction conditions and types and compositions of grafted chains, were estimated to be in the range of 15.2–101 μmol/g, and grafted polymers usually had polydispersity indices lower than 1.3, revealing that the grafting process was almost controllable. To the best of our knowledge, this versatile tandem approach is one of the most facile techniques to prepare silica particles grafted with polymeric chains with controlled molecular weight, low polydispersity and precise composition due to its minimal reaction steps, mild conditions, straightforward synthesis and satisfactory controllability.

Effects of Retardation and Variation of Monomer Concentration in RAFT Miniemulsion Polymerization

AbstractThe polymerization kinetics of the RAFT‐mediated radical polymerization inside sub‐µm particles (Dp &lt; 100 nm) is analyzed. The rate retardation by the addition of a RAFT agent in miniemulsion polymerization can be significantly different from that for bulk polymerization. The particle size below which significant rate acceleration occurs can be estimated from a simple equation. It is demonstrated that the reduction of the polymerization rate through the monomer concentration variation effect results from the correlation of concentration variations in monomer and intermediate or, equivalently, monomer and radical.magnified image

Mathematical Modeling of Hyperbranched Water‐soluble Polymers with Applications in Drug Delivery

AbstractAlthough the method of moments has been used to determine the properties of copolymerizations, accounting for branching has either been ignored or required multiple dimensions to simulate. In this work, we extend our previous modeling efforts to account for hyperbranching, a form of polymerization that is particularly useful in the synthesis of targeted delivery vehicles capable of encapsulating drugs for localized therapeutics, without invoking higher dimension moment treatments. Specifically, the case of RAFT polymerization with a polymerizable double bond incorporated into the RAFT agent is modeled. This gives a very highly‐branched material without the complexity of dendrimer synthesis. The model is then used to simulate three copolymerizations that illustrate the power of this model to accurately predict the copolymer properties and illustrate the polydispersity of the individual segments of the hyperbranched polymer, and the overall hyperbranched polymer. This paper models three different hyperbranched copolymer blends: acrylamide–acrylic acid, acrylonitrile–methacrylic acid, and ethylene–styrene. The first case is of specific interest in the development of hyperbranched polymers for drug delivery. The other two are included in order to explore the effects of specific kinetics on branching. magnified image

Controlled RAFT Polymerization in a Continuous Flow Microreactor

Controlled radical polymerization using the reversible addition−fragmentation chain transfer approach (RAFT) was successfully conducted under continuous flow processing conditions, provided that steel tubing was used to prevent quenching of the radical process by oxygen. A series of different monomers, including acrylamides, acrylates, and vinyl acetate, were polymerized to high conversions (between 80 and 100%) at temperatures between 70 and 100 °C using various initiators, solvents, and RAFT agents. Low dispersities, typically between 1.15−1.20, and average molecular weights similar to those of batch RAFT polymerizations were obtained. The methodology provides a facile, alternative scale-up route to conventional batch polymerization, which can be challenging because of the oxygen-sensitive nature of the RAFT process.

Kinetics of UV‐initiated RAFT crosslinking polymerization of dimethacrylates

AbstractThe UV‐initiated RAFT polymerizations of a series of poly(ethylene glycol) dimethacrylates (PEGDMA) were investigated using differential scanning photocalorimetry (DPC) at room temperature. The rate of the RAFT system was much lower than that of a conventional free radical polymerization. A mild autoacceleration occurred as the addition reaction became diffusion controlled. The influence of the spacer length (CH2CH2O)x between the vinyl moieties of the dimethacrylates on the polymerization kinetics was examined. The polymerization rate of PEGDMA decreased with an increased x value from 4 to 9, but it increased with a further increased x value from 9 to 14. Mechanical properties of the resulting polymers were also examined by dynamic mechanical analysis (DMA). It was concluded that the presence of the RAFT agent during polymerization of multifunctional monomers did not have an effect on the heterogeneity of the polymer network. In comparison with three different PEGDMAs, the PEGDMA with the longest spacer formed the most homogeneous networks with a lower crosslinking density. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011

Narrow disperse polymers using amine functionalized dithiobenzoate RAFT agent and easy removal of thiocarbonyl end group from the resultant polymers

AbstractA novel amine functionalized RAFT agent, 2‐cyanoprop‐2‐yl(4‐N,N‐dimethylaminophenyl) dithiobenzoate has been synthesized and used to control the polymerization of vinyl monomers. This dithiobenzoate RAFT agent, although air sensitive, controlled the polymerization of MMA and St very well in an inert atmosphere and the polymerization results obtained were marginally better than using the most popular 2‐cyanoprop‐2‐yl dithiobenzoate RAFT agent. The living nature of these polymerizations was confirmed by kinetics study and chain extension reactions to yield narrow disperse di‐block copolymers. Most importantly, use of this novel RAFT agent simplified the removal procedure of the color causing end thiocarbonyl group from the RAFT derived polymers and thereby leading to polymers with improved appearance. The removal of end group from the polymer was confirmed by 1H NMR and UV‐vis spectroscopic techniques. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011

RAFT Mediated Polymerization of Methyl Methacrylate Initiated by Bergman Cyclization: Access to High Molecular Weight Narrow Polydispersity Polymers

The first RAFT mediated polymerization of methyl methacrylate initiated by diradicals derived from Bergman cyclization was performed employing 3,4-benzocyclodec-3-ene-1,5-diyne (BCDY) as diradical source and cyanoisopropyldithiobenzoate (CPDB) as RAFT agent. The polymerization was conducted in bulk at 80 °C for 3 h. The concentration of the enediyne was kept constant at 3.0 x 10⁻² mol · L⁻¹ and the RAFT agent concentration was varied between 0.0 mol · L⁻¹ and 2.4 x 10⁻¹ mol · L⁻¹. A detailed ESI-MS analysis reveals the absence of intramolecular termination reactions (ring formation) in the RAFT mediated system, which usually makes diradicalic initiation unfavorable. The presence of polymeric chains propagating at both ends could be confirmed. The conversion of the RAFT mediated polymerization was up to more than two times higher than the RAFT free polymerization at identical conditions. Thus, polymers with narrow polydispersities (1.1 ≤ PDI ≤ 1.5) even at very high molecular weights (near 400,000 Da) were obtained within modest reaction times.