Reversible Deactivation Radical Polymerization Research Articles

Stimuli-sensitive polymer prodrug nanocarriers by reversible-deactivation radical polymerization.

Polymer prodrugs are based on the covalent linkage of therapeutic molecules to a polymer structure which avoids the problems and limitations commonly encountered with traditional drug-loaded nanocarriers in which drugs are just physically entrapped (e.g., burst release, poor drug loadings). In the past few years, reversible-deactivation radical polymerization (RDRP) techniques have been extensively used to design tailor-made polymer prodrug nanocarriers. This synthesis strategy has received a lot of attention due to the possibility of fine tuning their structural parameters (e.g., polymer nature and macromolecular characteristics, linker nature, physico-chemical properties, functionalization, etc.), to achieve optimized drug delivery and therapeutic efficacy. In particular, adjusting the nature of the drug-polymer linker has enabled the easy synthesis of stimuli-responsive polymer prodrugs for efficient spatiotemporal drug release. In this context, this review article will give an overview of the different stimuli-sensitive polymer prodrug structures designed by RDRP techniques, with a strong focus on the synthesis strategies, the macromolecular architectures and in particular the drug-polymer linker, which governs the drug release kinetics and eventually the therapeutic effect. Their biological evaluations will also be discussed.

Enhancing photothermal depolymerization with metalloporphyrin catalyst

AbstractThe ability to revert polymers to their original monomers represents a crucial chemical recycling technique, promoting sustainability and offering the chance to convert used materials into valuable products. In recent years, numerous studies have explored the use of polymers synthesized via reversible deactivation radical polymerization (RDRP) techniques to facilitate efficient depolymerization reactions. Herein, we report the use of a photocatalyst, zinc tetraphenylporphyrin (ZnTPP), along with light irradiation to accelerate depolymerization of polymers prepared by reversible addition‐fragmentation chain transfer (RAFT) polymerization. We explore various parameters affecting depolymerization efficiency, including solvents, reaction temperature (80, 100, and 120°C), the presence of photocatalysts (ZnTPP and Eosin Y), and the type of RAFT end‐groups, namely trithiocarbonate, dithiobenzoate, and 1H‐pyrazole‐1‐carbodithioate. For instance, when PMMA was diluted to 25 mM in 1,4‐dioxane and heated to 120°C under green light irradiation in the presence of ZnTPP (200 ppm), rapid depolymerization exceeding 70% occurred within 1 h. Without ZnTPP, under similar conditions, the reaction required over 8 h to achieve a slightly lower yield. Furthermore, this method confers moderate oxygen tolerance to the system, enabling depolymerization to proceed without the need of deoxygenation, albeit at a lower rate and consequently lesser monomer recovery (31%).

Robust Miniemulsion PhotoATRP Driven by Red and Near-Infrared Light.

Photoinduced polymerization techniques have gathered significant attention due to their mild conditions, spatiotemporal control, and simple setup. In addition to homogeneous media, efforts have been made to implement photopolymerization in emulsions as a practical and greener process. However, previous photoinduced reversible deactivation radical polymerization (RDRP) in heterogeneous media has relied on short-wavelength lights, which have limited penetration depth, resulting in slow polymerization and relatively poor control. In this study, we demonstrate the first example of a highly efficient photoinduced miniemulsion ATRP in the open air driven by red or near-infrared (NIR) light. This was facilitated by the utilization of a water-soluble photocatalyst, methylene blue (MB+). Irradiation by red/NIR light allowed for efficient excitation of MB+ and subsequent photoreduction of the ATRP deactivator in the presence of water-soluble electron donors to initiate and mediate the polymerization process. The NIR light-driven miniemulsion photoATRP provided a successful synthesis of polymers with low dispersity (1.09 ≤ Đ ≤ 1.29) and quantitative conversion within an hour. This study further explored the impact of light penetration on polymerization kinetics in reactors of varying sizes and a large-scale reaction (250 mL), highlighting the advantages of longer-wavelength light, particularly NIR light, for large-scale polymerization in dispersed media owing to its superior penetration. This work opens new avenues for robust emulsion photopolymerization techniques, offering a greener and more practical approach with improved control and efficiency.

Nitroxide mediated controlled radical polymerization of α‐Methylene‐γ‐Butyrolactone

AbstractThe controlled polymerization of α‐methylene‐γ‐butyrolactone (MBL, a naturally occurring sesquiterpene lactone found in tulips) was performed by nitroxide mediated polymerization (NMP) using the alkoxyamine Dispolreg 007 as the initiating system at 80 °C in 50 wt% DMSO. Features of a reversible‐deactivation radical polymerization (RDRP) were observed with a linear growth of the macro‐radical with conversion and a relatively low dispersity (Ð ≤ 1.45). The P(MBL) homopolymer chain ends were mostly re‐activatable as the chain extensions with styrene (S) and glycidyl methacrylate (GMA) in DMSO were successful. Interestingly, the polymerization of MBL initiated by 2‐methyl‐2‐[N‐tert‐butyl‐N‐(1‐diethoxyphosphoryl‐2,2‐dimethylpropyl)‐aminoxy]‐N‐propionyloxysuccinimide (known as NHS‐BlocBuilder) under various experimental conditions did not produce well‐defined P(MBL), possibly due to an excessively high equilibrium constant. However, the bulk copolymerization of MBL with 10–21 mol% of β‐myrcene (Myr, another renewable monomer from the terpene family) initiated by NHS‐BlocBuilder at 100–110 °C led to all the features of a controlled system. The SG1 chain end fidelity of the resulting P(MBL‐co‐Myr) copolymer was confirmed via 31P NMR and by re‐initiating successfully the copolymer chains with a mixture of GMA and Myr monomers at 120 °C in DMSO.

BaTiO3 catalyzed ultrasonic driven piezoelectric induced miniemulsion atom transfer radical polymerization (Piezo-miniATRP)

Compared with other stimulus such as light and heat, ultrasonic possesses much deeper penetration into tissues and organs and has lower scattering in heterogeneous systems as a noninvasive stimulus, and has already been used as the external stimulus to initiate reversible-deactivation radical polymerization (RDRP). However, the development of efficient ultrasonic drive RDRP in aqueous dispersed media remains a challenge. Here in this work, ultrasonic driven piezoelectric induced miniemulsion atom transfer radical polymerization (Piezo-miniATRP) was performed, with tetragonal BaTiO3 (BTO) nanoparticles as the piezoelectric catalyst. The Piezo-miniATRP exhibited features of controllable and livingness, such as linear increase of molar mass and narrow molar mass distributions (Mw/Mn < 1.30). The effect of different polymerization parameters on the polymerization reaction was investigated, including the amounts of surfactant, CuBr2 and BTO dosages. Excellent temporal control of the polymerization and the chain fidelity of polymers were illustrated by “ON and OFF” experiment and chain extension, separately. This novel BTO catalyzed Piezo-miniATRP process could also be extended to other aqueous dispersion RDRP systems.

Using RAFT Polymerization Methodologies to Create Branched and Nanogel-Type Copolymers.

This review aims to highlight the most recent advances in the field of the synthesis of branched copolymers and nanogels using reversible addition-fragmentation chain transfer (RAFT) polymerization. RAFT polymerization is a reversible deactivation radical polymerization technique (RDRP) that has gained tremendous attention due to its versatility, compatibility with a plethora of functional monomers, and mild polymerization conditions. These parameters lead to final polymers with good control over the molar mass and narrow molar mass distributions. Branched polymers can be defined as the incorporation of secondary polymer chains to a primary backbone, resulting in a wide range of complex macromolecular architectures, like star-shaped, graft, and hyperbranched polymers and nanogels. These subcategories will be discussed in detail in this review in terms of synthesis routes and properties, mainly in solutions.

Grafting Block Copolymer Nanoparticles to a Surface via Aqueous Photoinduced Polymerization-induced Self-Assembly at Room Temperature.

The creation of well-defined surface nanostructures is important for a diverse set of applications such as cell adhesion, superhydrophobic coating, and lithography. In this study, we describe a robust bottom-up method for surface functionalization that involves surface-initiated reversible deactivation radical polymerization (RDRP) and the grafting of block copolymer nanoparticles to material surfaces via aqueous photoinduced polymerization-induced self-assembly (photo-PISA) at room temperature. Using silica nanoparticles as a model substrate, colloidal mesoscale hybrid assemblies with various morphologies were successfully prepared. The morphologies can be easily tuned by changing the lengths of macromolecular chain transfer agents and parameters of the silica nanoparticles. The surface-initiated photo-PISA approach can also be employed for other large-scale substrates such as silicon wafer. Taking advantage of mild reaction conditions of this method (room temperature, aqueous medium, and visible light), enzymatic deoxygenation was introduced to develop oxygen-tolerant surface-initiated photo-PISA that can fabricate well-defined nanostructures on large-scale substrates under open-to-air conditions.

Visible light-induced photo-radical ring-opening copolymerization of thionolactone and acrylates

Radical ring-opening (co)polymerization (RROP) provides an accessible method for synthesizing main chain degradable vinyl polymers. Although the applications of reversible deactivation radical polymerization (RDRP) into RROP have been reported, the use of photo-mediated RDRP methods has received less attention than the thermal process. Here, photo-RROP of the thionolactone dibenzo [c,e]-oxepine-5(7H)-thione (DOT) and methyl acrylate (MA) was studied using photo-iniferter (PI) reversible addition-fragmentation (chain) transfer (RAFT) polymerization at ambient temperature without external radical initiators or photocatalysts. Despite the occurrence of some side reactions including desulfurization-oxygenation and O–S isomerization of DOT promoted by photoexcited thiocarbonyl groups, polymers with thioester linkages in the backbone were prepared, which degraded in the presence of amines and bleach.

Xolography for the Production of Polymeric Multimaterials

AbstractThree‐dimensional (3D) printed multimaterials have quickly grown in interest as researchers aim to mimic the material chemistry and geometric complexity of natural materials. While some exceptional multimaterial 3D printing systems have been developed, there is still a shortfall in the scope and production of these materials. More recently, the introduction of xolography as a single‐step, auxiliary‐free additive manufacturing approach has enabled rapid production of materials with geometries inaccessible via other additive manufacturing techniques. However, previous systems required resins with high transparency for effective material formation, and multimaterial formation has not been demonstrated. In this work, reversible deactivation radical polymerization is used and resin composition, viscosity, and processing parameters are explored to develop new resins capable of application to visible light‐mediated xolography. After optimization, non‐transparent resins containing thiocarbonylthio species are applied to xolography to manufacture geometrically complex, auxiliary‐free materials. The resulting 3D printed polymer network materials can be functionalized via the embedded thiocarbonylthio moieties to impart new functionality to the printed materials. Finally, the unique 3D printing capabilities of xolography are demonstrated to manufacture multimaterials featuring chemically disparate domains with high 3D‐spatial control. This two‐step overprinting approach is operationally simple and provides a new avenue for manufacturing polymeric multimaterials via 3D printing.

The renaissance and evolving design of radical polymerization

Abstract During the 49th World Polymer Congress held 17–21 July 2022 in Winnipeg, Canada, Graeme Moad presented the Stepto Lecture Award [1], describing the mechanism and terminological evolution of reversible deactivation radical polymerization (RDRP) [2, 3, 4], including more recent intricate designs through the use of light and electrical propulsion.

Synthesis of phosphate hydrogels with excellent swelling behavior prepared by ascorbic acid -mediated ARGET ATRP

This manuscript explores the synthesis of hydrogels through reversible deactivation radical polymerization (RDRP) methods, specifically, activators regenerated by electron transfer atom transfer radical polymerization (ARGET ATRP) and Cu0-mediated ATRP. These techniques are known to offer improved control over polymer network structures due to their slow polymerization kinetics. However, these methods have historically been challenging to apply to stimuli-responsive polymers, such as those with acidic or basic moieties. In this study, the direct synthesis of poly(2-(methacryloyloxy) ethyl phosphate) (PMOEP), a phosphate-pendant hydrogel, was investigated in aqueous media by both ascorbic acid (AsA)-mediated ARGET ATRP and Cu0-mediated ATRP. 2-(methacryloyloxy) ethyl phosphate (MOEP) was utilized as the active monomer with tris(2-pyridylmethyl) amine (TPMA) as the ligand. A unique feature of this work is that the diene moiety inherently present in the commercial monomer, bis[2-(methacryloyloxy) ethyl] phosphate (BMOEP), served as the crosslinking agent to obtain the novel PMOEP hydrogel. Formulations were tuned to optimize the swelling characteristics of the hydrogels, with the restriction that the hydrogels should swell homogeneously without fracture. Importantly, using AsA as the reducing agent in the ARGET ATRP reaction resulted in improved homogeneity and enhanced swelling properties of the hydrogel. Furthermore, tuning the target degree of polymerization (Dp) ([monomer]:[initiator]) had a significant impact on swelling characteristics. Specifically, PMOEP hydrogels synthesized via ARGET ATRP with a target Dp of 300 and 1 mM CuII catalyst demonstrated outstanding water absorption capacity of more than 2500% (relative to the dry mass) in phosphate buffer solution (PBS) at pH 7.4 and over 6000% in pure water. The morphology of these hydrogels was imaged using field emission environmental scanning electron microscopy (FE-ESEM) and the chemical composition was examined using Fourier transform infrared (FTIR) spectroscopy. Furthermore, nuclear magnetic resonance (NMR) analysis was performed to investigate the conversion rate of monomer during Cu0-mediated ATRP. To the authors’ knowledge, the synthesis of a 100% phosphate-pendant hydrogel using AsA-mediated ARGET ATRP and an internal phosphodiester crosslinking moiety without dilution or comonomer, has not been reported previously. This facile method for synthesizing and controlling phosphate-based hydrogel properties also provides an opportunity to include additional functional groups and holds significant promise for applications in biomedical engineering, agriculture, and membrane separations.

Phenanthroline Derived N-Doped Carbon Dots as Robust Metal-Free Photocatalysts for PET-RAFT Polymerization and Polymerization-Induced Self-Assembly.

Metal-free organic photocatalysts for photo-mediated reversible deactivation radical polymerization (photo-RDRP) are witnessed to make increasing advancement in the precise synthesis of polymers. However, challenges still exist in the development of high-efficiency and environmentally sustainable carbon dots (CDs)-based organocatalysts. Herein, N-doped CDs derived from phenanthroline derivative (Aphen) are prepared as metal-free photocatalysts for photoinduced electron transfer reversible addition-fragmentation chain transfer (PET-RAFT) polymerization. The introduction of phenanthroline structure enhances the excited state lifetime of CDs and expands the conjugated length of their internal structure to enable the light-absorption to reach green light region, thereby enhancing photocatalytic activity. The as-designed CDs exhibit unprecedented photocatalytic capacity in photopolymerization even in large-volume reaction (100mL) with high monomer conversion and narrow polymer dispersity (Mw/Mn < 1.20) under green light. The photocatalytic system is compatible with PET-RAFT polymerization of numerous monomers and the production of high molecular weight polyacrylate (Mn >250000) with exquisite spatiotemporal control. Above results confirm the potential of CDs as photocatalyst, which has not been achieved with other CDs catalysts used in photo-RDRP. In addition, the construction of fluorescent polymer nanoparticles using CDs as both photocatalyst and phosphor through photoinitiated polymerization-induced self-assembly (Photo-PISA) technology is successfully demonstrated for the first time.

Research progress in highly efficient reversible deactivation radical polymerization of vinylidene fluoride

Research progress in highly efficient reversible deactivation radical polymerization of vinylidene fluoride

Reversible Thiyl Radical Addition−Fragmentation Chain Transfer Polymerization

AbstractDeveloping reversible‐deactivation radical polymerization (RDRP) methods that could directly control the thiyl radical propagation is highly desirable yet remains challenging in modern polymer chemistry. Here, we reported the first reversible thiyl radical addition‐fragmentation chain transfer (SRAFT) polymerization strategy, which utilizes allyl sulfides as chain transfer agents for reversibly deactivating the propagating thiyl radicals, thus allowing us to directly control a challenging thiyl radical chain polymerization to afford polymers with well‐defined architectures. A linear dependence of molecular weight on conversion, high chain‐end fidelity, and efficient chain extension proved good controllability of the polymerization. In addition, density functional theory calculations provided insight into the reversible deactivation ability of allyl sulfides. The SRAFT strategy developed in this work represents a promising platform for discovering new controlled polymerizations based on thiyl radical chemistry.

Reversible Thiyl Radical Addition-Fragmentation Chain Transfer Polymerization.

Developing reversible-deactivation radical polymerization (RDRP) methods that could directly control the thiyl radical propagation is highly desirable yet remains challenging in modern polymer chemistry. Here, we reported the first reversible thiyl radical addition-fragmentation chain transfer (SRAFT) polymerization strategy, which utilizes allyl sulfides as chain transfer agents for reversibly deactivating the propagating thiyl radicals, thus allowing us to directly control a challenging thiyl radical chain polymerization to afford polymers with well-defined architectures. A linear dependence of molecular weight on conversion, high chain-end fidelity, and efficient chain extension proved good controllability of the polymerization. In addition, density functional theory calculations provided insight into the reversible deactivation ability of allyl sulfides. The SRAFT strategy developed in this work represents a promising platform for discovering new controlled polymerizations based on thiyl radical chemistry.

NIR Photocontrolled Organotellurium-Mediated Reversible-Deactivation Radical Polymerization by Activation of C–Te Bonds with Organotellurium Radicals

NIR Photocontrolled Organotellurium-Mediated Reversible-Deactivation Radical Polymerization by Activation of C–Te Bonds with Organotellurium Radicals

Synthesis of copolymers of N‐vinylpyrrolidone and 2‐ethylhexyl acrylate by DL‐methionine‐mediated reversible deactivation radical polymerization and their dispersion behavior in preparation of LiFePO4 battery positive slurry with high solid content

AbstractDispersants play a significant role in the formulation of positive battery slurry. Adding a small amount of dispersant can effectively reduce the viscosity of the slurry, which is beneficial for the production of positive batteries. A series of copolymers of N‐vinylpyrrolidone (NVP) and 2‐ethylhexyl acrylate (2‐EHA) with different molar ratios of NVP to 2‐EHA, different polymer molecular weights and different polymer structures are synthesized by dl‐methionine‐mediated reversible deactivation radical polymerization. The ability of these copolymers to disperse LiFePO4 battery positive slurry with a high solid content (57.08%) as dispersants has been evaluated. Research shows that when the ratio of NVP to 2‐EHA is 20 and the polymer molecular weight is 6000, poly(N‐vinylpyrrolidone‐ran‐2‐ethylhexyl acrylate) (NVP‐ran‐2‐EHA) exhibits the strongest dispersing ability to the slurry. This polymer can reduce the viscosity of the slurry by 43.925% and has the longest stabilization time of 3 h, which is better than poly(N‐vinylpyrrolidone) (PVP) and poly(N‐vinylpyrrolidone)‐block‐poly(2‐ethylhexyl acrylate) (PVP‐b‐PEHA) with the same molecular weight.

Ultra-high molecular weight complex coacervates via polymerization-induced electrostatic self-assembly

Advances in reversible-deactivation radical polymerization (RDRP), particularly the recent renaissance of photoiniferter polymerization, have led to new methods to achieve ultra-high molecular weight polymers with high functional-group tolerance.

Precise Synthesis of Tetrablock Copolymers of Different Acrylamide Derivatives via Iterative Aqueous Cu(0)-Mediated Polymerization

The accessibility of specific synthesis of tetrablock copolymers is reported. In a specific synthesis, four acrylamide monomers are gradually added using an iterative aqueous Cu(0)-mediated reversible-deactivation radical polymerization (RDRP) method. Essential to the success of this approach is the ability to design and polymerize ABCD copolymer sequence with no need for immediate purification steps. The simple in-situ sequential polymerization method allowed for essentially perfect control of accurately well-defined tetrablock copolymers, which are composed of four tiny blocks, each of which contains an average of ten functional monomer units of acrylamide derivatives, resulting in a variety of functional groups. While the final molecular weight distributions have very narrow despersities (Đ &lt; 1.10), the efficient successive chain extension polymerization proceeded with high monomer conversions (&gt;99%), delivering excellent block purification in a short period of time. The tetrablock poly(NIPAM-DMA-HEAA-DEA) was characterized by NMR and GPC and showed beneficial end-group fidelity, allowing quantitative monitoring of the system’s alive nature after each synthetic cycle. Importantly, these one-pot syntheses are carried out at a below temperature of 0.0 °C in water as the solvent and can be implemented for applications of molecular biology. We also investigate the potential for a copper-amide complex to develop with acrylamide monomer, which could have an adverse effect on the end group’s functioning. Finally, we believe that this approach makes it easier to create a novel category of advanced polymeric materials.

Surface Modification of 3D‐Printed Micro‐ and Macro‐Structures via In Situ Nitroxide‐Mediated Radical Photopolymerization

AbstractPhoto‐controlled reversible‐deactivation radical polymerization (RDRP) has recently emerged in light‐based 3D printing at macro‐ and micro‐scales, enabling the elaboration of objects with (re‐)configurable surface properties. The authors' previous work exploits nitroxide‐mediated radical photopolymerization (NMP2) in 3D micro‐printing and subsequent surface modification, by employing analkoxyamine‐based photoresist via 3D direct laser writing (DLW). However, this photoresist suffers from its low photosensitivity to wavelengths above 760 nm, limiting its suitability for commercial 3D DLW setups. To tackle these issues, a new strategy—in situ NMP2 based on a photoresist containing acommercial photoinitiator and a photosensitive‐nitroneis proposed. This photoresist is well‐suited for wavelengths commonly used by 3D DLW systems to obtain well‐defined 3D microstructures. Importantly, the in‐situ formation of alkoxyamine during fabrication allows photo‐induced surface modification of microstructures, highlighted by precise and successive surface patterning. Thesurface modification can be conducted at 800 nm or at wavelengths up to 860 nm. Subsequently, the impact of light wavelength and intensity isinvestigated to understand surface modification. The simple preparation of this novel photoresist allows facile adaptation to digital light processing for 3D macro‐printing. This work broadens the scope of photo‐controlled RDRP in 3D printing and greatly facilitates “living” 3D micro‐ and macro‐printing.