Controlled bimodal molecular-weight-distribution polymers: facile synthesis by RAFT polymerization

The RAFT agents RAFT-1 and RAFT-2 were used for RAFT polymerization to synthesize well-defined bimodal molecular-weight-distribution (MWD) polymers. The system showed excellent controllability and "living" characteristics toward both the higher- and lower-molecular-weight fractions. It is important that bimodal higher-molecular-weight (HMW) polymers and block copolymers with both well-controlled molecular weight (MW) and MWD could be prepared easily due to the "living" features of RAFT polymerization. The strategy realized a mixture of higher/lower-molecular-weight polymers at the molecular level but also preserved the features of living radical polymerization (LRP) of the RAFT polymerization.     

Rate Optimization in Controlled Radical Emulsion Polymerization Using RAFT

Summary: Means of improving rates in RAFT‐mediated radical emulsion polymerizations are developed, by setting out strategies to minimize the inhibition and retardation that always are present in these systems. These effects arise from the RAFT‐induced exit of radicals, the desorption of the RAFT‐reinitiating radical from the particles, and the specificity of the reinitiating radical to the RAFT agent. Methods for reducing the inhibition period such as using a more hydrophobic reinitiating radical are predicted to show a significant improvement in the inhibition periods. The time‐dependent behavior of the RAFT adduct to the entering radical and the RAFT‐induced exit (loss) of radicals from particles are studied using a previously described Monte Carlo model of RAFT/emulsion particles. It is shown that an effective way of reducing the rate coefficient for the exit of radicals from the particles is to use a less active RAFT agent. Techniques for improving the rate of polymerization of RAFT/emulsion systems are suggested based upon the coherent understanding contained in these models: the use of an oligomeric adduct to the RAFT agent, a less water‐soluble RAFT re‐initiating group, and a less active RAFT agent.

Populations of the different types of particles (left axis) along with the concentration of the initial RAFT agent, D_R (right axis), as a function of time.     

Carbazyl RAFT agents synthesized by an improved aqueous phase method and their applications in RAFT polymerization

A series of carbazyl dithiocarbamates as RAFT agents, i.e. benzyl 9H-carbazole-9-carbodithioate (B), 1-phenylethyl 9H-carbazole-9-carbodithioate (C), cumyl 9H-carbazole-9-carbodithioate (D) and tert-butyl 9H-carbazole-9-carbodithioate (E), were successfully synthesized by an improved aqueous phase method based on a nucleophilic substitution reaction between sodium carbazole-9-carbodithioate (A) and alkyl halides at room temperature. Furthermore, the optimum reaction conditions and synthetic technology were sought. Compared with the traditional oil-phase method, the expected high-purity RAFT agents were obtained in the form of crystal that was precipitated and separated from the aqueous solution, so that vast organic solvents for purification were avoided. The activities of the carbazyl dithiocarbamates obtained as RAFT agents for the polymerizations of both styrene and methyl methacrylate were determined. The results show that all of the RAFT agents above mentioned are of significant activity in the RAFT polymerization of styrene, but only D has obvious activity in the RAFT polymerization of methyl methacrylate. Therefore, both the novel synthetic method and the carbazyl dithiocarbamates obtained possess potential application in the RAFT polymerization.     

Parametric Analysis of the Intermediate Concentration in a RAFT Polymerization and its Influence upon the Polymerization Kinetics

Summary: A kinetic analysis of living/controlled radical polymerizations in bulk mediated by RAFT is presented. The main objective is to show how the kinetics of the RAFT process and, in particular, of the RAFT intermediate radical is affecting the overall polymerization rate. Namely, three different cases are analyzed: (i) slow fragmentation of the RAFT intermediate; (ii) cross‐termination of the RAFT intermediate with other radicals; and (iii) slow re‐initiation of the RAFT agent leaving group. Simplified analytical formulas are derived for the time‐dependent concentrations of the involved species as well as for conversion. They are supported by numerical simulations and are qualitatively compared to literature experimental findings. Criteria are also given to judge the influence of the RAFT reaction kinetic rate constants on the different phenomena observed experimentally in RAFT polymerization, namely inhibition and retardation. Since these criteria are given by using non‐dimensional groups, they can be readily applied to a broad spectrum of experimental conditions.

Logarithmic non‐dimensional concentration for the radicals (r) and intermediate radicals (q) versus the non‐dimensional polymerization time ( ).     

<Emphasis Type="Italic">In situ</Emphasis> synthesis of block copolymer nano-assemblies by polymerization-induced self-assembly under heterogeneous condition

Controlled synthesis of amphiphilic block copolymer nanoparticles in a convenient way is an important and interest topic in polymer science. In this review, three formulations of polymerization-induced self-assembly to in situ synthesize block copolymer nanoparticles are briefly introduced, which perform by reversible addition-fragmentation chain transfer (RAFT) polymerization under heterogeneous conditions, e.g., aqueous emulsion RAFT polymerization, dispersion RAFT polymerization and especially the recently proposed seeded RAFT polymerization. The latest developments in several selected areas on the synthesis of block copolymer nano-assemblies are highlighted.     

Waterborne RAFT polymers

A recently invented novel family of RAFT (Reversible Addition-Fragmentation chain Transfer) agents having a common formula Z-C(S)-S-CR₂COOR¹ where Z = -SR, -NR₂, or -OR, and R¹ represents H or a variety of functional groups allows for tailoring their hydrophilicity-hydrophobicity balance. A limited hydrophilicity of the RAFT agents can be achieved which is sufficient for their diffusion through water, yet the agents are hydrophobic enough to phase-separate out of water. Thus, the limited hydrophilicity of otherwise hydrophobic agents allows them to be at the loci of polymerization making them suitable for the emulsion polymerization mechanism. With several RAFT agents, good control over molecular weight was demonstrated for a broad variety of ab initio acrylic emulsion polymers. For methyl methacrylate, a portion of RAFT did not engage, resulting in less than the theoretical number of polymer chains. It was found, however, that as little as ∼10 wt% of an acrylic monomer slowed down polymerization enough to engage all RAFT agent molecules and yield predicted molecular weights. A broad variety of colorless and odorless telechelic acrylic and methacrylic emulsion polymers were synthesized.Microemulsion and solution-dispersion techniques produced clean colloidally stable RAFT dispersions. These two techniques did not require RAFT agents with tailored hydrophilicity-hydrophobicity.The UV spectra and photooxidative stability of the RAFT polymers were studied. The RAFT fragment in polymers appeared to have no impact on their photooxidative stability.     

Reversible Addition‐fragmentation Chain Transfer Polymerization Grafted from Silicon Surface to Prepare Poly(methyl methacrylate) Brushes

通过共价键锚固链转移剂4-氰基-4-二硫代苯甲酰基戊酸琥珀酯于硅片表面,然后采用可逆加成-断裂链转移（RAFT）自由基聚合方法制备了聚甲基丙烯酸甲酯（PMMA）高分子刷. 聚合动力学研究表明,在反应进行2小时后,PMMA的厚度随聚合时间的增大而几乎呈线性增大,具有明显的活性聚合特征. 用椭圆偏光仪、X-光电子能谱（XPS）、原子力显微镜（AFM）及接触角测试对硅片表面的PMMA高分子刷进行了表征.     

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 × 10⁻² mol · L⁻¹ and the RAFT agent concentration was varied between 0.0 mol · L⁻¹ and 2.4 × 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.

     

Well-defined higher-molecular-weight polyacrylonitrile via RAFT technique in the presence of disulfide compounds as a source of chain transfer agent

Well-defined polyacrylonitrile with a higher number-average molecular weight () up to 200,000 and a lower polydispersity index (PDI, 1.7-2.0) was firstly obtained via reversible addition-fragmentation chain transfer (RAFT) process. This was achieved by selecting a stable, easy way to prepare disulfide compound intermediates including bis(thiobenzoyl) disulfide (BTBDS) and bis(thiophenylacetoyl) disulfide (BTPADS) to react with azobis(isobutyronitrile) to directly synthesize RAFT agents in situ. The polymerization of acrylonitrile (AN) displays the characteristics of controlled/living radical polymerization as evidenced by pseudo first-order kinetics of polymerization, linear evolution of molecular weight with increasing monomer conversion, and narrow PDIs. The polymerization rate and the efficiency for producing RAFT agent of BTPADS system are obviously higher than those of BTBDS system, whereas the control of the latter over the polymerization is superior to that of the former. ¹H NMR analysis has confirmed the dithioester chain-end functionality of the resultant polymer. The RAFT copolymerizations of AN and the comonomers including methyl acrylate, itaconic acid, methyl methacrylate, n-butyl acrylate, 2-hydroxyethyl acrylate, and acrylamide were also successfully carried out using the same polymerization system.     

Combining Steric and Electrostatic Stabilization Using Hydrophilic MacroRAFT Agents in an Ab Initio Emulsion Polymerization of Styrene

Hydrophilic (co)polymers carrying a thiocarbonyl thio end group such as poly(dimethylaminoethyl methacrylate), poly(ethylene oxide), and poly(ethylene oxide)‐block‐poly(dimethylaminoethyl methacrylate) have been evaluated as precursors of stabilizers in batch ab initio emulsion polymerization of styrene under acidic conditions to form electrosterically stabilized polystyrene latex particles. As a mixture of P(DMAEMA/H⁺Cl⁻)‐RAFT and PEO‐RAFT failed to give satisfactory results, PEO‐RAFT was used as a control agent for the RAFT polymerization of DMAEMA, and the resulting block copolymer was successfully used in ab initio styrene emulsion polymerization.

     

Living Free Radical Polymerization of Cyclodextrin Host‐Guest Complexes of Styrene via the Reversible Addition Fragmentation Chain Transfer (RAFT) Process in Aqueous Solution

Summary: Host‐guest complexes of styrene and randomly methylated β‐cyclodextrin (m‐β‐CD) were polymerized in aqueous medium via the reversible addition fragmentation chain transfer (RAFT) process. 3‐Benzylsulfanylthiocarbonylsulfanylpropionic acid (TTC) was used as trithiocarbonate‐type RAFT agent. The results indicate a controlled character of the polymerization of the styrene complexes as the number‐average molecular weight, , increases linearly with monomer to polymer conversion; however, the molecular weights of the obtained polystyrenes deviate to higher values than those theoretically predicted. Nevertheless, the molecular weights can be controlled by variation of the initial RAFT agent concentration. The polystyrenes produced in this system exhibited narrower polydispersities (1.23 < < 2.36) than those produced without RAFT agent (5.24 < < 9.21) under similar conditions. The present contribution represents the first example of RAFT polymerization of a m‐β‐CD‐complexed hydrophobic vinylmonomer (styrene) from homogenous aqueous solution.

Schematic presentation of complexation and RAFT polymerization of m‐β‐CD‐complexed styrene with TTC as RAFT agent and evolution of the full molecular weight distributions in the CD‐mediated styrene free radical RAFT polymerization.     

A novel strategy for synthesis of amphiphilic π-shaped copolymers by RAFT polymerization

The amphiphilic π-shaped copolymers with narrow molecular weight distribution (M_w/M_n = 1.04-1.09) based on polystyrene (PSt) and poly(ethylene glycol) have been synthesized successfully. The reversible addition-fragmentation transfer (RAFT) polymerization of St in the presence of dibenzyl trithiocarbonate and N,N′-azobis(isobutyronitrile) (AIBN) yielded macro RAFT agent PSt-SC(S)S-PSt, subsequent reaction with excess maleic anhydride (MAh) at 80 °C in tetrahydrofuran afforded the PSt-MAh-SC(S)S-MAh-PSt. It was used as RAFT agent in the RAFT polymerization of St, and finally the amphiphilic π-shaped copolymers were obtained by the reaction of MAh with hydroxyl-terminated poly(ethylene glycol methyl ether) at 90 °C for 48 h. Their structures were confirmed by FT-IR and ¹H NMR spectra, and their molecular weight and molecular weight distribution were measured by gel permeation chromatography.     

Hairy Core–Shell Nanoparticles via RAFT: Where are the Opportunities and Where are the Problems and Challenges?

The preparation of hairy core–shell nanoparticles including (crosslinked) micelles, unimolecular micelles such as star polymers with block structures in each arm and surface grafted nanoparticles such as inorganic particles via the RAFT process are discussed. The RAFT process is certainly a highly versatile process. However, it should not be forgotten that RAFT polymerization is a process, i.e., superimposed on a conventional free radical process. Furthermore, the livingness of the process is dependent on the accessibility of the RAFT group, which can be hampered in certain approaches such as star synthesis and surface grafting from nanoparticles. Nevertheless, the RAFT process is a versatile toolbox that offers good solutions to a range of problems in the preparation of hairy nanoparticles.

     

Monolithic poly(ethylhexyl methacrylate-co-ethylene dimethacrylate) column with restricted access layers prepared via reversible addition-fragmentation chain transfer polymerization

The "living"/controlled radical polymerization has provided an opportunity in making a more homogeneous polymer, which is favorable for polymer-based monolithic column fabrication. To study its application in the preparation of separation material, a capillary poly(ethylhexyl methacrylate-co-ethylene dimethacrylate) monolithic column has been synthesized by reversible addition-fragmentation chain transfer (RAFT) polymerization. The correlation between the synthetic conditions and the polymer structures and separation performance was studied. The result indicated RAFT-mediated reaction provides condition for creating polymers with narrower pore size distribution and higher column efficiency compared with traditional polymerization. The "living" property of the RAFT polymerization was further utilized to graft hydrophilic polymer on the surface of poly(ethylhexyl methacrylate-co-ethylene dimethacrylate). The hydrophilic chain modified monolithic column has both abilities of protein exclusion and small hydrophobic compound retention. The result indicated that RAFT polymerization can be used for making multifunctional material. The restricted access monolithic material synthesized by this method can be used in biological sample analysis with HPLC direct injection.     

Preparation of pH- and reductive-responsive prodrug nanoparticles via polymerization-induced self-assembly

pH- and reductive-responsive prodrug nanoparticles are constructed via a highly efficient strategy, polymerization-induced selfassembly (PISA). First, reversible addition-fragmentation chain transfer (RAFT) polymerization of 2-(diisopropylamino) ethyl methacrylate (DIPEMA) and camptothecin prodrug monomer (CPTM) using biocompatible poly(N-(2-hydroxypropyl) methacrylamide) (PHPMA-CPDB) as the macro RAFT agent is carried out, forming prodrug diblock copolymer PHPMA-P (DIPEMA-co-CPTM). Then, simultaneous fulfillment of polymerization, self-assembly, and drug encapsulation are achieved via RAFT dispersion polymerization of benzyl methacrylate (BzMA) using the PHPMA-P(DIPEMA-co-CPTM) as the macro RAFT agent. The prodrug nanoparticles have three layers, the biocompatible shell (PHPMA), the drug-conjugated middle layer (P(DIPEMA-co-CPTM)) and the PBzMA core, and relatively high concentration (250 mg/g). The prodrug nanoparticles can respond to two stimuli (reductive and acidic conditions). Due to reductive microenvironment of cytosol, the cleavage of the conjugated camptothecin (CPT) within the prodrug nanoparticles could be effectively triggered. pH-Induced hydrophobic/ hydrophilic transition of the PDIPEMA chains results in faster diffusion of GSH into the CPTM units, thus accelerated release of CPT is observed in mild acidic and reductive conditions. Cell viability assays show that the prodrug nanoparticles exhibit well performance of intracellular drug delivery and good anticancer activity.     

Well‐Defined Macromolecules Using Horseradish Peroxidase as a RAFT Initiase

Enzymatic catalysis and control over macromolecular architectures from reversible addition‐fragmentation chain transfer polymerization (RAFT) are combined to give a new method of making polymers. Horseradish peroxidase (HRP) is used to catalytically generate radicals using hydrogen peroxide and acetylacetone as a mediator. RAFT is used to control the polymer structure. HRP catalyzed RAFT polymerization gives acrylate and acrylamide polymers with relatively narrow molecular weight distributions. The polymerization is rapid, typically exceeding 90% monomer conversion in 30 min. Complex macromolecular architectures including a block copolymer and a protein‐polymer conjugate are synthesized using HRP to catalytically initiate RAFT polymerization.

     

The doubly thermo-responsive triblock copolymer nanoparticles prepared through seeded RAFT polymerization

The doubly thermo-responsive triblock copolymer nanoparticles of polystyrene-block-poly(N-isopropylacrylamide)-block-poly[N,N-(dimethylamino) ethyl methacrylate] (PS-b-PNIPAM-b-PDMAEMA) are successfully prepared through the seeded RAFT polymerization in situ by using the PS-b-PNIPAM-TTC diblock copolymer nanoparticles as the seed. The seeded RAFT polymerization undergoes a pseudo-first-order kinetics procedure, and the molecular weight increases with the monomer conversion linearly. The hydrodynamic diameter (D _h) of the triblock copolymer nanoparticles increases with the extension of the PDMAEMA block. In addition, the double thermo-response behavior of the PS-b-PNIPAM-b-PDMAEMA nanoparticles is detected by turbidity analysis, temperature-dependent 1H-NMR analysis, and DLS analysis. The seeded RAFT polymerization is believed as a valid method to prepare triblock copolymer nanoparticles containing two thermo-responsive blocks.     

Accelerated Combinatorial High Throughput Star Polymer Synthesis via a Rapid One‐Pot Sequential Aqueous RAFT (rosa‐RAFT) Polymerization Scheme

Advanced polymerization methodologies, such as reversible addition‐fragmentation transfer (RAFT), allow unprecedented control over star polymer composition, topology, and functionality. However, using RAFT to produce high throughput (HTP) combinatorial star polymer libraries remains, to date, impracticable due to several technical limitations. Herein, the methodology “rapid one‐pot sequential aqueous RAFT” or “rosa‐RAFT,” in which well‐defined homo‐, copolymer, and mikto‐arm star polymers can be prepared in very low to medium reaction volumes (50 µL to 2 mL) via an “arm‐first” approach in air within minutes, is reported. Due to the high conversion of a variety of acrylamide/acrylate monomers achieved during each successive short reaction step (each taking 3 min), the requirement for intermediary purification is avoided, drastically facilitating and accelerating the star synthesis process. The presented methodology enables RAFT to be applied to HTP polymeric bio/nanomaterials discovery pipelines, in which hundreds of complex polymeric formulations can be rapidly produced, screened, and scaled up for assessment in a wide range of applications.

     

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

An 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 (? = 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     

Reversible Addition‐Fragmentation Transfer Polymerization in the Presence of MMT Immobilized Amphoteric RAFT Agent

Summary: A novel reversible addition‐fragmentation transfer (RAFT) agent, 10‐carboxylic acid‐10‐dithiobenzoate‐decyltrimethylammonium bromide (CDDA), was synthesized and intercalated into montmorillonite (MMT). Successively, the CDDA‐intercalated MMT was used as RAFT agent in the in situ RAFT polymerization for preparation of the polystyrene/MMT nanocomposites. After separation of MMT, the polymers obtained have predictable molecular weight and narrow polydispersity. XRD spectra and TEM images of the nanocomposites demonstrated exfoliated structure. Thermal stability of the composites has been noticeably improved.