Fragmentation Chain Transfer Polymerization Research Articles

RAFT-Polymerized N-Cyanomethylacrylamide-Based (Co)polymers Exhibiting Tunable UCST Behavior in Water.

In this present work, the synthesis of a new family of upper critical solution temperature (UCST)-thermoresponsive polymers based on N-cyanomethylacrylamide (CMAm) is reported. It is demonstrated that the thermally initiated reversible addition fragmentation chain transfer (RAFT) polymerization of CMAm conducted in N,N-dimethylformamide (DMF) is well controlled. The homopolymer presents a sharp and reversible UCST-type phase transition in pure water with a very small hysteresis between cooling and heating cycles. It is demonstrated that the cloud point (TCP ) of poly(N-cyanomethylacrylamide) (PCMAm) is strongly molar mass dependent and shifts toward lower temperatures in saline water. Moreover, the transition temperature can be tuned over a large temperature range by copolymerization of CMAm with acrylamide or acrylic acid. The latter copolymers are both thermoresponsive and pH responsive. Interestingly, by this strategy sharp and reversible UCST-type transitions close to physiological temperature can be reached, which makes the copolymers extremely interesting candidates for biomedical applications.

Synthesis of a Diapocynin Prodrug for Its Prolonged Release from Zwitterionic Biodegradable Nanoparticles

AbstractToday, neurodegenerative diseases are affecting more and more individuals. A typical therapeutic target to treat the progression of the symptoms related to these diseases is the proinflammatory microglia. Diapocynin, the dimeric version of apocynin, is often the drug of choice. However, suitable carriers for its controlled delivery are currently lacking in the clinics. In fact, its high hydrophilicity hampers the development of a formulation enabling its sustained release in a biological environment. In this work, the possibility of modifying diapocynin is explored in order to synthesize a prodrug that can be chemically incorporated into biodegradable zwitterionic polymer nanoparticles (NPs). These NPs are synthesized via combination of ring opening polymerization and reversible addition–fragmentation chain transfer (RAFT) polymerization, allowing the incorporation of the desired number of diapocynin units into the carrier and thus to set the drug dosage a priori. The chemical binding of diapocynin avoids its premature release compared to its physical loading inside similar nanovectors. With this strategy, sustained diapocynin release can be achieved for more than 9 days, thus paving the way to a therapy with low number of repeated administrations.

Photo-Enhanced Antimicrobial Activity of Polymers Containing an Embedded Photosensitiser.

This work presents the synthesis of a novel photosensitive acrylate monomer for use as both a self-catalyst in the photoinduced electron/energy transfer-reversible addition fragmentation chain transfer (PET-RAFT) polymerisation process and a photosensitiser (PS) for antibacterial applications. Hydrophilic, cationic, and antimicrobial formulations are explored to compare the antibacterial effects between charged and non-charged polymers. Covalent attachment of the catalyst to well-defined linear polymer chains has no effect on polymerisation control or singlet oxygen generation. The addition of the PS to polymers provides activity against S. aureus for all polymer formulations, resulting in up to a 99.99999 % killing efficacy in 30 min. Antimicrobial peptide mimetic polymers previously active against P. aeruginosa, but not S. aureus, gain significant bactericidal activity against S. aureus through the inclusion of PS groups, with 99.998 % killing efficiency after 30 min incubation with light. Thus, a broader spectrum of antimicrobial activity is achieved using two distinct mechanisms of bactericidal activity via the incorporation of a photosensitiser monomer into an antimicrobial polymer.

Photo‐Enhanced Antimicrobial Activity of Polymers Containing an Embedded Photosensitiser

AbstractThis work presents the synthesis of a novel photosensitive acrylate monomer for use as both a self‐catalyst in the photoinduced electron/energy transfer–reversible addition fragmentation chain transfer (PET‐RAFT) polymerisation process and a photosensitiser (PS) for antibacterial applications. Hydrophilic, cationic, and antimicrobial formulations are explored to compare the antibacterial effects between charged and non‐charged polymers. Covalent attachment of the catalyst to well‐defined linear polymer chains has no effect on polymerisation control or singlet oxygen generation. The addition of the PS to polymers provides activity against S. aureus for all polymer formulations, resulting in up to a 99.99999 % killing efficacy in 30 min. Antimicrobial peptide mimetic polymers previously active against P. aeruginosa, but not S. aureus, gain significant bactericidal activity against S. aureus through the inclusion of PS groups, with 99.998 % killing efficiency after 30 min incubation with light. Thus, a broader spectrum of antimicrobial activity is achieved using two distinct mechanisms of bactericidal activity via the incorporation of a photosensitiser monomer into an antimicrobial polymer.

Reversible-Addition Fragmentation Chain Transfer Step-Growth Polymerization.

Reversible-addition fragmentation chain transfer (RAFT) polymerization has been widely explored since its discovery due to its structural precision, versatility, and efficiency. However, the lack of tunability of the polymer backbone limits some applications. Herein, we synergistically combine RAFT and step-growth polymerization mechanisms, by employing a highly selective insertion process of a single monomer with a RAFT agent, to achieve RAFT step-growth polymerization. A unique feature of the RAFT step-growth polymers is that each backbone repeat unit bears a pendant RAFT agent, which can subsequently graft side chains in a second polymerization step and afford molecular brush polymers. Enabled by cleavable backbone functionality, we demonstrate transformation of the resulting brushlike polymers into linear chains of uniform size upon a stimulus.

Fabrication and characterization of glutathione‐responsive nanoparticles from the disulfide bond‐bridged block copolymer

AbstractThe purpose of this paper is to fabricate novel nanoparticles (NPs) from a single disulfide bond‐bridged block copolymer poly(hydroxyethyl methacrylate)‐S‐S‐polycaprolactone (PHEMA‐S‐S‐PCL). The novel biomaterial was synthesized by ring‐opening polymerization and reversible addition–fragmentation chain transfer polymerization. The cargo‐free NPs were fabricated with the solvent evaporation method, and studies on NPs' characterizations were carried out. The hydrogen nuclear magnetic resonance (1H NMR) and Fourier transform infrared spectroscopy spectra confirmed the synthesis of PHEMA‐S‐S‐PCL copolymer. Thermo‐gravimetric analysis curves indicated that the obtained PHEMA‐S‐S‐PCL copolymer had good thermostability. Transmission electron microscopy and dynamic light scatter results suggested that the cargo‐free NPs were in round shapes with an average diameter of 103.6 ± 0.12 nm. The low critical micelle concentration of cargo‐free NPs (7.9 × 10−4 mg/ml) indicated that these NPs would keep their spherical shapes after being attenuated by abundant liquid (e.g., blood or body fluid). Furthermore, these NPs showed high stability at the presence of bovine serum albumin. Therefore, it could be speculated that these NPs would not be absorbed by proteins in blood, and they could be used as a candidate carrier for drug delivery.

Experimental Design in Polymer Chemistry—A Guide towards True Optimization of a RAFT Polymerization Using Design of Experiments (DoE)

Despite the great potential of design of experiments (DoE) for efficiency and plannability in academic research, it remains a method predominantly used in industrial processes. From our perspective though, DoE additionally provides greater information gain than conventional experimentation approaches, even for more complex systems such as chemical reactions. Hence, this work presents a comprehensive DoE investigation on thermally initiated reversible addition–fragmentation chain transfer (RAFT) polymerization of methacrylamide (MAAm). To facilitate the adaptation of DoE for virtually every other polymerization, this work provides a step-by-step application guide emphasizing the biggest challenges along the way. Optimization of the RAFT system was achieved via response surface methodology utilizing a face-centered central composite design (FC-CCD). Highly accurate prediction models for the responses of monomer conversion, theoretical and apparent number averaged molecular weights, and dispersity are presented. The obtained equations not only facilitate thorough understanding of the observed system but also allow selection of synthetic targets for each individual response by prediction of the respective optimal factor settings. This work successfully demonstrates the great capability of DoE in academic research and aims to encourage fellow scientists to incorporate the technique into their repertoire of experimental strategies.

Coenzyme−catalyzed electroinitiated reversible addition fragmentation chain transfer polymerization for ultrasensitive electrochemical DNA detection

Ultrasensitive detection of biomarkers at an early stage is generally limited by external influence factors such as high reaction temperature, complex operations, and sophisticated instruments. Here, we circumvent these problems by using nicotinamide adenine dinucleotide (NAD+) to control electroinitiated reversible addition fragmentation chain transfer (electro−RAFT) polymerization for biosensing that enables the detection of a few molecules of target DNA. In this coenzyme−catalyzed electro−RAFT polymerization, numerous ferrocenylmethyl methacrylate (FCMMA) as monomer with electrochemistry signal were linked to the biomarker on Au electrode. Afterwards, a strong oxidation peak appears at the potential of about 0.3 V that represents a typical oxidation potential of FCMMA. The sensitivity of this methodology was presented by detecting DNA from 10−1 to 104 fM concentration and detection limit (LOD) being down to 4.39 aM in 10 μL samples. This is lower by factors than detection limits of most other ultra−sensitive electrochemical DNA assays.

Nanozymes based on coassembly of albumin and photosensitizer for photocontrolled RAFT polymerization

Photoactive enzymes have been proposed as promising catalysts in photocontrolled reversible addition–fragmentation chain transfer (RAFT) polymerization. However, only a few enzymes have the photoactive properties suitable for initiating RAFT polymerization. Herein, we synthesize nanozymes with uniform and well-defined nanostructures through coassembly of albumin and photosensitizer. The resulting nanozymes feature the absorption bands of the monomeric photosensitizer, facilitating efficient light capture and electron transfer, which lead to high conversion efficiencies in photocontrolled RAFT polymerization. Importantly, the nanozymes show good reusability in multiple rounds of polymerizations and precise controllability of activation and deactivation of the reactions. This work represents the first realization of photoactive nanozymes that can be used for photocontrolled RAFT polymerization and thus will conceivably promote the rational design and catalytic applications of functional nanozymes.

Reversible addition–fragmentation chain transferbased copolymers of acrylonitrile and alkyl acrylates as possible precursors for carbon fibers: synthesis and thermal behavior during stabilization

AbstractCopolymers of acrylonitrile and alkyl acrylates with various alkyl substituents (methyl, ethyl, butyl, 2‐ethylhexyl and lauryl) were synthesized via reversible addition–fragmentation chain transfer polymerization in dimethylsulfoxide. It is demonstrated that reactivity of alkyl acrylate in copolymerization decreases with increase of the length of the alkyl substituent. The molar fractions of homodiads and homotriads of acrylonitrile and the number‐average sequence length of acrylonitrile units decreases with a decrease in the acrylate content in the copolymer or with an increase in the length of the alkyl substituent in the acrylate. The copolymer composition was held constant throughout copolymerization in all the studied systems resulting in the formation of copolymers with high compositional homogeneity. Additionally the reversible addition–fragmentation chain transfer mechanism provides low dispersity of the copolymers. Both factors enable the effect of the alkyl substituent in alkyl acrylate on the thermal behavior of acrylonitrile copolymers to be carefully revealed. Being inert in the cyclization reaction, alkyl acrylates have no effect on the activation energy of the reaction. However, increase of the length of the alkyl substituent is followed by a slower evolution of the ladder structure. In contrast, in conditions of oxidative stabilization, the stabilization index increases in the order of increase of the number‐average sequence length of the acrylonitrile units in the copolymers. Thus, the use of alkyl acrylates with longer alkyl substituents provides an increase of chain flexibility and the formation of an enhanced ladder structure during oxidative stabilization which is profitable for carbon fiber production. © 2021 Society of Industrial Chemistry.

Dispersion of Few-Layer Black Phosphorus in Binary Polymer Blend and Block Copolymer Matrices

Exfoliated black phosphorus (bP) embedded into a polymer is preserved from oxidation, is stable to air, light, and humidity, and can be further processed into devices without degrading its properties. Most of the examples of exfoliated bP/polymer composites involve a single polymer matrix. Herein, we report the preparation of biphasic polystyrene/poly(methyl methacrylate) (50/50 wt.%) composites containing few-layer black phosphorus (fl-bP) (0.6–1 wt.%) produced by sonicated-assisted liquid-phase exfoliation. Micro-Raman spectroscopy confirmed the integrity of fl-bP, while scanning electron microscopy evidenced the influence of fl-bP into the coalescence of polymeric phases. Furthermore, the topography of thin films analyzed by atomic force microscopy confirmed the effect of fl-bP into the PS dewetting, and the selective PS etching of thin films revealed the presence of fl-bP flakes. Finally, a block copolymer/fl-bP composite (1.2 wt.%) was prepared via in situ reversible addition–fragmentation chain transfer (RAFT) polymerization by sonication-assisted exfoliation of bP into styrene. For this sample, 31P solid-state NMR and Raman spectroscopy confirmed an excellent preservation of bP structure.

Statistical and Block Copolymers of Ethylene and Vinyl Acetate via Reversible Addition-Fragmentation Chain Transfer Polymerization.

A dithiocarbamate chain transfer agent (CTA) based on Z-group substituted with a diphenyl amine (-NPh2 ) moiety is selected for the synthesis of statistical and diblock copolymers of ethylene and vinyl acetate via reversible addition-fragmentation chain transfer polymerization. Benefiting from the good chain growth control of polyethylene (PE), poly(vinyl acetate) (PVAc), and poly(ethylene-co-vinyl acetate) (EVA) achieved with this CTA, linear diblock copolymers of the type EVA-b-PE, EVA-b-EVA, and PVAc-b-EVA are successfully synthesized. A three-arm EVA star is additionally obtained starting from a trifunctional dithiocarbamate CTA.

Direct Access to Polysaccharide-Based Vesicles with a Tunable Membrane Thickness in a Large Concentration Window via Polymerization-Induced Self-Assembly.

Polymersomes are multicompartmental vesicular nano-objects obtained by self-assembly of amphiphilic copolymers. When prepared in the aqueous phase, they are composed of a hydrophobic bilayer enclosing water. Although such fascinating polymeric nano-objects have been widely reported with synthetic block copolymers, their formation from polysaccharide-based copolymers remains a significant challenge. In the present study, the powerful platform technology known as polymerization-induced self-assembly was used to prepare in situ pure vesicles from a polysaccharide-grafted copolymer: dextran-g-poly(2-hydroxypropyl methacrylate) (Dex-g-PHPMA). The growth of the PHPMA grafts was performed with a dextran-based macromolecular chain transfer agent in water at 20 °C using photomediated reversible addition fragmentation chain transfer polymerization at 405 nm. Transmission electron microscopy, cryogenic electron microscopy, small-angle X-ray scattering, atomic force microscopy, and dynamic light scattering revealed that amphiphilic Dex-g-PHPMAX=100-300 (X is the targeted average degree of polymerization, Xn̅, of each graft at full conversion) exhibit remarkable self-assembly behavior. On the one hand, vesicles were obtained over a wide range of solid concentrations (from 2.5% to 13.5% w/w), which can facilitate posterior targeting of such rare morphology. On the other hand, the extension of Xn̅ induces an increase in the vesicle membrane thickness, rather than a morphological evolution (spherical micelles to cylinders to vesicles).

RAFT Synthesis of Reactive Multifunctional Triblock‐Copolymers for Polyplex Formation

AbstractReversible addition–fragmentation chain transfer polymerization with a low‐temperature initiator can be used to synthesize multifunctional block copolymers for polyplex formation. Utilizing three methacrylate monomers (triethylene glycol methyl ether methacrylate (MEO3MA), pyridyldisulfideethyl methacrylate (PDSM), N,N‐dimethylethylenediamine methacrylate (DMAEMA)) and an azide bearing chain transfer agent for polymerization, the resulting triblock‐copolymers possess two orthogonally reactive functionalities (a block with reactive disulfide side chains and an azide end‐group) and two additional functional blocks for i) solubilization and ii) polyplex formation. Thereby, the MEO3MA block provides solubility in aqueous media and the DMAEMA block, having a tertiary amine in the side chain, allows polyplex formation with polyanionic biomacromolecules like DNA or RNA. Due to the reactive disulfide block the polyplexes can be (reversibly) crosslinked with dithiols. Because of the manifold of possibilities to modify the pDNApolyplexes, this polymers system is an interesting candidate for active‐targeting and codelivery approaches.

Mechanistic Insights into Oxygen Tolerance of Graphitic Carbon Nitride-Mediated Heterogeneous Photoinduced Electron Transfer-Reversible Addition Fragmentation Chain Transfer Polymerization

Mechanistic Insights into Oxygen Tolerance of Graphitic Carbon Nitride-Mediated Heterogeneous Photoinduced Electron Transfer-Reversible Addition Fragmentation Chain Transfer Polymerization

Effective carbon dioxide sorption by using phyllosilicate anchored poly(quaternary-ammoniumhydroxidemethyl styrene) nanocomposites

ABSTRACT Polymers are highly promising materials for capturing carbon dioxide (CO2), a greenhouse gas. Hence in this work, we prepared phyllosilicate supported mesoporous polymer via reversible addition–fragmentation chain transfer (RAFT) polymerisation, which is the one among the controlled radical polymerisation. The mesoporous material anchored on dodecanethiol trithiocarbonate acts as a chain transfer agent (CTA) for the polymerisation of chloromethyl styrene and further conversion to quaternary ammonium compound which is effective to trap CO2 using tertiary amine. The synthesised porous phyllosilicate/polymer nanocomposites have been characterised by using various analytical tools. The CO2 sorption experiments were carried out by passing CO2 onto the synthesised porous phyllosilicate/polymer nanocomposites. The sorption kinetics was monitored by X-Ray photoelectron spectroscopy (XPS) and Fourier-transform infrared spectroscopy (FT-IR) spectra in the presence of carbonate were obtained by reaction of quaternary ammonium hydroxide and CO2. The phyllosilicate anchored macromolecular CTA (macro-CTA) and the surface-initiated polymer nanocomposites encompassed apparent surface areas of 94.5 and 26.8 m2 g−1, respectively. In addition, the total pore volumes calculated for the macro-CTA and polymer were found to be 0.27 and 0.095 cm3g−1, while the average pore sizes were 14.24 and 11.46 nm, respectively. The CO2 sorption capacity of the phyllosilicate/polymer nanocomposites, monitored at different temperatures, is the fastest for 25°C but slower for the sample treated at 50°C which may due to the dipole and quadrupole interaction.

Perspective on the controlled polymer‐modification of chitosan and cellulose nanocrystals: Towards the design of functional materials

AbstractThe development of reversible deactivation radical polymerization (RDRP) opened a vast number of possibilities for the synthesis of exotic macromolecular architectures with tailored properties for diverse applications. Given the advantages that RDRP provides, it is possible to obtain such architectures with good control over molecular weight distribution, morphology, composition, and functionality. A field of great interest for many research groups is the modification of natural polymers (or polysaccharides) with synthetic polymers via polymer grafting using RDRP approaches, such as atom transfer radical polymerization (ATRP), nitroxide‐mediated polymerization (NMP), and reversible addition–fragmentation chain transfer polymerization (RAFT) since the properties of the resulting materials can be tailored. Two polysaccharides that stand out due to their properties and potential applications after polymer modification are chitosan and cellulose nanocrystals (CNC). Chitosan is a derivative of chitin, desirable for its biocompatibility, degradability, low toxicity, and ability to act as a chelating agent with potential applications in the biomedical and pharmacy fields or wastewater treatment. CNC are well known for their outstanding mechanical properties, such as high specific strength and modulus and high surface area. For both chitosan and CNC, however, their hydrophilic nature makes them incompatible with non‐polar systems, limiting their potential applications. This feature article highlights the most recent development and our personal perspective of polymer grafting techniques on CNC and chitosan via RDRP for the design of different architectures, the design of responsive materials from such polysaccharides, potential water treatment applications, and our opinion of the future of this attractive research field.

Amphiphilic block versus random copolymer nanoparticles with reactive oxygen species responsiveness as berberine vehicles

A series of amphiphilic block and random copolymers based on phenylboronic acid pinacol ester were synthesized via reversible addition–fragmentation chain transfer polymerization. The obtained copolymers can self-assemble in aqueous solution into stable block copolymer nanoparticles and random nanoparticles with sizes of 116.1–158.6 and 126.3–187.0 nm, respectively. All nanoparticles showed hydrogen peroxide (H2O2) sensitivity, and the random copolymer nanoparticles presented faster responsiveness to H2O2 than did those derived from block copolymers. Berberine (BBR) can be effectively encapsulated into block and random copolymer nanoparticles with loading capacity of 7.6%–9.1% and 7.3%–8.9%, respectively. The BBR release can be controlled in an H2O2 medium. For the random copolymer nanoparticles, the release rate of BBR was faster and the cumulative release amounts in response to H2O2 were higher over 48 h. The BBR cumulative release amount in the H2O2 medium for the block and random copolymer nanoparticles was 62.2%–70.2% and 68.6%–80.4%, respectively. Moreover, good biocompatibility was observed for the BBR-loaded block and random copolymer nanoparticles. BBR and BBR-loaded nanoparticles can improve Glut4 translocation to the cell membrane and promote glucose transport into cells. BBR-loaded nanoparticles can decrease the blood glucose levels in diabetic rats over 15 days. These results imply that the different chain formulation of block and random copolymers affects the H2O2 responsiveness and that the two kinds of nanoparticles exhibit potential application as novel vehicles for BBR delivery to regulate blood glucose levels.

GSH-sensitive polymeric prodrug: Synthesis and loading with photosensitizers as nanoscale chemo-photodynamic anti-cancer nanomedicine

Precisely delivering combinational therapeutic agents has become a crucial challenge for anti-tumor treatment. In this study, a novel redox-responsive polymeric prodrug (molecular weight, MW: 93.5 kDa) was produced by reversible addition–fragmentation chain transfer (RAFT) polymerization. The amphiphilic block polymer-doxorubicin (DOX) prodrug was employed to deliver a hydrophobic photosensitizer (PS), chlorin e6 (Ce6), and the as-prepared nanoscale system [NPs(Ce6)] was investigated as a chemo-photodynamic anti-cancer agent. The glutathione (GSH)-cleavable disulfide bond was inserted into the backbone of the polymer for biodegradation inside tumor cells, and DOX conjugated onto the polymer with a disulfide bond was successfully released intracellularly. NPs(Ce6) released DOX and Ce6 with their original molecular structures and degraded into segments with low MWs of 41.2 kDa in the presence of GSH. NPs(Ce6) showed a chemo-photodynamic therapeutic effect to kill 4T1 murine breast cancer cells, which was confirmed from a collapsed cell morphology, a lifted level in the intracellular reactive oxygen species, a reduced viability and induced apoptosis. Moreover, ex vivo fluorescence images indicated that NPs(Ce6) retained in the tumor, and exhibited a remarkable in vivo anticancer efficacy. The combinational therapy showed a significantly increased tumor growth inhibition (TGI, 58.53%). Therefore, the redox-responsive, amphiphilic block polymeric prodrug could have a great potential as a chemo-photodynamic anti-cancer agent.

Utilization of Poor RAFT Control in Heterogeneous RAFT Polymerization

Heterogeneous reversible addition–fragmentation chain transfer (RAFT) polymerization exhibits considerable promise in polymer and colloid synthesis. During the research of RAFT polymerization, good RAFT control is always an important goal to achieve while poor RAFT control is considered to be a lack of success. Herein, we develop heterogeneous RAFT polymerization from an unusual angle by deliberately using RAFT agents with poor RAFT controllability. The utilization of poor RAFT control in heterogeneous RAFT polymerization led to the formation of samples contain high-molecular-weight block copolymers, uncontrolled homopolymers, and the unreacted macro-RAFT agent. Remarkably, uniform polymer spheres with precise size could be obtained via heterogeneous RAFT polymerization, although molecular weight distributions of the obtained polymers were broad. In-depth studies of heterogeneous RAFT polymerization mediated by a binary mixture of RAFT agents with different controllability, the RAFT agent with good controllability dominated the polymerization while the RAFT agent with poor controllability was mainly inactivated or unreacted. On the basis of the unique mechanism provided, we have been able to prepare block copolymer assemblies with rich pendant RAFT groups on the surface by one-step heterogeneous RAFT polymerization using a macro-RAFT agent with divergent RAFT end groups. The reactivity of pendant RAFT groups on the surface provides a landscape for further functionalization of block copolymer assemblies. These proof-of-concept experiments demonstrate that the utilization of poor RAFT control in heterogeneous RAFT polymerization is a promising strategy to a variety of polymer particles that are challenging to be prepared by traditional heterogeneous RAFT polymerizations.