Radical Ring-opening Polymerization Research Articles

Degradable N-Vinyl Copolymers through Radical Ring-Opening Polymerization of Cyclic Thionocarbamates.

A thiocarbonyl radical ring-opening polymerization approach was implemented with cyclic thionocarbamates to generate degradable copolymers with N-vinyl monomers. The rigid structures of cyclic N-substituted thionocarbamates have been revealed by X-ray crystallography and NMR spectroscopy. The corresponding copolymers show incorporation of the thiocarbamates within the carbon backbone of polyvinylpyrrolidone influenced by acyl substituents through radical ring-opening copolymerization. The phenyl-substituted cyclic thionocarbamate copolymerized with N-vinyl carbazole and N-vinyl caprolactam, while little to no incorporation occurred with tBu acrylate and styrene, respectively. Further, these copolymers can undergo hydrolytic degradation under mild conditions. A new family of cyclic thionocarbamates capable of radical ring-opening copolymerization with N-vinyl monomers has been established.

Fast and Selective Main-Chain Scission of Vinyl Polymers Using the Domino Reaction in the Alternating Sequence for Transesterification.

This communication reports on vinyl polymers capable of selective and fast main-chain scission (MCS). The trick is the domino reaction in an alternating sequence of methyl 2-(trimethylsiloxymethyl)acrylate and 5,6-benzo-2-methylene-1,3-dioxepane, a cyclic ketene acetal for radical ring-opening polymerization. Removal of the trimethylsilyl group using Bu4N+·F- readily led to MCS via irreversible transesterification of the ester backbone, affording a five-membered lactone fragment. The molar mass decreased drastically within 5 min, and no side reactions were observed. Control experiments suggest that the formation of a five-membered ring via a domino reaction is critical for fast and selective MCS. The terpolymers with methyl methacrylate and styrene also exhibited a large decrease in molar mass within 5 min. In addition, MCS was also observed for the heterogeneous reaction system in acidic aqueous media; treatment of the binary copolymer in a 50 wt % acetic acid solution resulted in a significant decrease in molar mass after 30 min. These results suggest efficient construction of degradable sites using a binary monomer system corresponding to the pendant trigger and ester backbone. Because this molecular design using a binary monomer system provides selective and fast MCS for terpolymers containing other vinyl monomers, it can provide various degradable vinyl polymers.

Plenty of Space in the Backbone: Radical Ring-Opening Polymerization.

Radical polymerization is the most widely applied technique in both industry and fundamental science. However, its major drawback is that it typically yields polymers with non-functional, non-degradable all-carbon backbones-a limitation that radical ring-opening polymerization (rROP) allows to overcome. The last decade has seen a surge in rROP, primarily focused on creating degradable polymers. This pursuit has resulted in the creation of the first readily degradable materials through radical polymerization. Recent years have witnessed innovations in new monomers that address previous design limitations, such as ring strain and reactivity ratios. Furthermore, advances in integrating rROP with reversible deactivation radical polymerization (RDRP) have facilitated the incorporation of complex, customizable chemical payloads into the main polymer chain. This short review discusses the latest developments in monomer design with a focused analysis of their limitations in a broader historical context. Recently evolving strategies for compatibility of rROP monomers with RDRP are discussed, which are key to precision polymer synthesis. The latest chemistry surveyed expands the horizon beyond mere hydrolytic degradation. Now is the time to explore the chemical potential residing in the previously inaccessible polymer backbone.

Visible light-driven organocatalyzed radical ring-opening polymerization of Bicyclo[1.1.0]butanes

Radical ring-opening polymerization (rROP) offers an essentially practical strategy to introduce a broad scope of functional groups in the polymer backbone. While suitable cyclic monomers mostly possess a vinyl group to facilitate the radical addition step, we herein present an efficient rROP of highly strained bicyclo[1.1.0]butane (BCB)-derived monomers through radical addition to bridge σ-carbon–carbon bond by photoinduced electron/energy transfer reversible addition−fragmentation chain transfer (PET-RAFT) polymerization technique, producing poly(BCBs) with relatively predictable molecular wight and low to moderate dispersity. Spatiotemporal control over the polymer chain-growth was achieved and high chain-end fidelity was imparted to access intriguing random and block copolymers with complex structures.

Enhancing the incorporation of 2-methylen-1,3-dioxepane (MDO) into industrial monomers by the addition of crotonate comonomers

Environmental concerns are pushing towards more sustainable materials such as degradable or bio-based polymers. 2-methylen-1,3-dioxepane (MDO) is a cyclic ketene acetal monomer that when reacts by radical ring opening polymerization can introduce degradable ester groups in the polymer backbone, but it is generally challenging to incorporate it uniformly with other industrially relevant vinylic monomers such as styrenics, methacrylics, acrylics and vinylics. In this work, we explore the use of butyl crotonate as termonomer to enhance the incorporation of MDO into common industrial monomers taking advantage of the particular reactivities of MDO and crotonate. Styrene is found not suitable for terpolymerization, as it just homopolymerized. With methyl methacrylate, the incorporation of MDO is substantially enhanced due to the presence of BCr, but the terpolymer is not homogeneous, and MDO is primarily incorporated in the closed form, which only partially enhanced the degradability. In the terpolymerization with ethyl acrylate high MDO incorporation is achieved (up to 80 %) and most of it is incorporated in to the open formed (80 %). Therefore, the obtained terpolymer shows complete degradation in 28 days. Last, the terpolymerization of vinyl acetate is the most successful, as almost total conversion of all monomers is achieved in short times, including (100 % conversion of MDO). Furthermore, the obtained terpolymers are highly homogeneous and degraded completely in few hours. The addition of crotonate monomer in formulations where MDO or other cyclic ketene acetal could bring new insights as it is shown that not only the incorporation of cyclic ketene acetals is enhanced but also that it favors the incorporation into the open form, which substantially enhanced the degradability of common polymers produced by radical polymerization.

Radical ring-opening polymerization towards degradable polymer as chain extender for polylactic acid

Degradable polymer materials have gained considerable research efforts nowadays. However, widely utilized polymeric chain extenders for degradable polymer materials are mainly nondegradable, where their degradability is ignored. Here, degradable polymeric chain extender for polylactic acid is designed via versatile radical ring-opening polymerization (rROP), by facilely incorporating of labile ester group into main chain of polymeric chain extender. Through reversible addition-fragmentation chain transfer rROP of cyclic ketene acetal as comonomer, a series of epoxy group-containing degradable polymers are synthesized. Further systematic investigations on these degradable polymeric chain extenders for polylactic acid are carried out, which enable polylactic acid with improved viscosity and modulus properties. This work therefore expands the molecular design of degradable polymeric chain extender and the application fields of degradable polymers via rROP, which might cause inspirations to the fields of polymer chemistry, processing and engineering.

From health supplement to versatile monomer: Radical ring-opening polymerization and depolymerization of α-lipoic acid

The radical ring-opening polymerization (rROP) of α-lipoic acid (LA) and its derivatives represents a synthetically accessible, efficient, and scalable strategy to impart degradability into functional copolymers. This review highlights recent advances in the design of sustainable materials containing LA through rROP driven by heat and/or light.

Oxygen-initiated radical ring-opening polymerization of macrocyclic allylic sulfides under ambient conditions

Although radical ring-opening polymerization (ROP) is a powerful approach for synthesizing polymers with diverse backbone structures, the intrinsic oxygen sensitivity of radicals challenges the ability to perform these polymerizations under air conditions. Here, we reported a novel oxygen-initiated radical ROP of macrocyclic allylic sulfides that can efficiently proceed under an air atmosphere, enabling the construction of sulfur-containing polymers with moderate to high molecular weights. The versatility of this approach was further demonstrated by copolymerizing macrocyclic allylic sulfides with vinyl monomers to create degradable vinyl polymers under ambient conditions. Density functional theory calculations revealed that the quenching of radicals by oxygen in the chain-growth process was kinetically disfavored, thereby allowing the polymerization to be compatible with oxygen. This work will further advance applications of radical ROP in diverse fields by enhancing its tolerance towards oxygen.

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.

Degradable Alternating Copolymers by Radical Copolymerization of 2-Methylen-1,3-dioxepane and Crotonate Esters.

Producing backbone degradable copolymers via free-radical copolymerization is a promising, yet challenging method to develop more sustainable materials for many applications. In this work, we present the copolymerization of 2-methylen-1,3-dioxepane (MDO) with crotonic acid derivative esters. MDO can copolymerize by radical ring-opening polymerization incorporating degradable ester moieties in the polymer backbone, although this can often be difficult due to the very unfavorable reactivity ratios. Crotonic acid derivatives, on the other hand, can be easily produced completely from biomass but are typically very difficult to (co)polymerize due to low propagation rates and very unfavorable reactivity ratios. Herein, we present the surprisingly easy copolymerization between MDO and butyl crotonate (BCr), which shows the ability to form alternating copolymers. The alternating nature of the copolymer was characterized by MALDI-TOF and supported by the reactivity ratios calculated experimentally (rMDO = 0.105 and rBCr = 0.017). The alternating nature of the copolymers favored the degradability that could be achieved under basic conditions (in 2 h, all chains have molar masses smaller than 2 kg/mol). Last, the work was expanded to other crotonate monomers to expand the portfolio and show the potential of this copolymer family.

Degradable Nanohydroxyapatite-Reinforced Superglue for Rapid Bone Fixation and Promoted Osteogenesis.

Bone glue with robust adhesion is crucial for treating complicated bone fractures, but it remains a formidable challenge to develop a "true" bone glue with high adhesion strength, degradability, bioactivity, and satisfactory operation time in clinical scenarios. Herein, inspired by the hydroxyapatite and collagen matrix composition of natural bone, we constructed a nanohydroxyapatite (nHAP) reinforced osteogenic backbone-degradable superglue (O-BDSG) by in situ radical ring-opening polymerization. nHAP significantly enhances adhesive cohesion by synergistically acting as noncovalent connectors between polymer chains and increasing the molecular weight of the polymer matrix. Moreover, nHAP endows the glue with bioactivity to promote osteogenesis. The as-prepared glue presented a 9.79 MPa flexural adhesion strength for bone, 4.7 times that without nHAP, and significantly surpassed commercial cyanoacrylate (0.64 MPa). O-BDSG exhibited degradability with 51% mass loss after 6 months of implantation. In vivo critical defect and tibia fracture models demonstrated the promoted osteogenesis of the O-BDSG, with a regenerated bone volume of 75% and mechanical function restoration to 94% of the native tibia after 8 weeks. The glue can be flexibly adapted to clinical scenarios with a curing time window of about 3 min. This work shows promising prospects for clinical application in orthopedic surgery and may inspire the design and development of bone adhesives.

Quantitative, Regiospecific, and Stereoselective Radical Ring-Opening Polymerization of Monosaccharide Cyclic Ketene Acetals.

Cyclic ketene acetals (CKAs) are among the most well-studied monomers for radical ring-opening polymerization (rROP). However, ring-retaining side reactions and low reactivities in homopolymerization and copolymerization remain significant challenges for the existing CKAs. Here, we report that a class of monosaccharide CKAs can be facilely prepared from a short and scalable synthetic route and can undergo quantitative, regiospecific, and stereoselective rROP. NMR analyses and degradation experiments revealed a reaction mechanism involving a propagating radical at the C2 position of pyranose with different monosaccharides exhibiting distinct stereoselectivity in the radical addition of the monomer. Furthermore, the addition of maleimide was found to improve the incorporation efficiency of monosaccharide CKA in the copolymerization with vinyl monomers and produced unique degradable terpolymers with carbohydrate motifs in the polymer backbone.

PH-Controlled Reversible Folding of Copolymers via Formation of β-sheet Secondary Structures.

Protein functions are enabled by their perfectly arranged 3D structure, which is the result of a hierarchical intramolecular folding process. Sequence-defined polypeptide chains form locally ordered secondary structures (i.e., α-helix and β-sheet) through hydrogen bonding between the backbone amides, shaping the overall tertiary structure. To generate similarly complex macromolecular architectures based on synthetic materials, a plethora of strategies have been developed to induce and control the folding of synthetic polymers. However, the degree of complexity of the structure-driving ensemble of interactions demonstrated by natural polymers is unreached, as synthesizing long sequence-defined polymers with functional backbones remains a challenge. Herein, we report the synthesis of hybrid peptide-N,N-Dimethylacrylamide copolymers via radical Ring-Opening Polymerization (rROP) of peptide containing macrocycles. The resulting synthetic polymers contain sequence-defined regions of β-sheet encoding amino acid sequences. Exploiting the pH responsiveness of the embedded sequences, protonation or deprotonation in water induces self-assembly of the peptide strands at an intramacromolecular level, driving polymer chain folding via formation of β-sheet secondary structures. We demonstrate that the folding behavior is sequence dependent and reversible.

Radical ring-opening polymerization of five-membered cyclic ketene acetals with the tetraleucine macromonomer toward preparation of self-assembling peptide-grafted polyesters

Graft copolymers were synthesized via radical ring-opening copolymerization of 2-methylene-1,3-dioxolane and a tetraleucine peptide macromonomer. Density functional theory (DFT) calculations were performed to discuss the copolymerization behavior.

Main chain selective polymer degradation: controlled by the wavelength and assembly.

The advent of reversible deactivation radical polymerization (RDRP) revolutionized polymer chemistry and paved the way for accessing synthetic polymers with controlled sequences based on vinylic monomers. An inherent limitation of vinylic polymers stems from their all-carbon backbone, which limits both function and degradability. Herein, we report a synthetic strategy utilizing radical ring-opening polymerization (rROP) of complementary photoreactive cyclic monomers in combination with RDRP to embed photoresponsive functionality into desired blocks of polyvinyl polymers. Exploiting different absorbances of photoreactive cyclic monomers, it becomes possible to degrade blocks selectively by irradiation with either UVB or UVA light. Translating such primary structures of polymer sequences into higher order assemblies, the hydrophobicity of the photodegradable monomers allowed for the formation of micelles in water. Upon exposure to light, the nondegradable blocks detached yielding a significant reduction in the micelle hydrodynamic diameter. As a result of the self-assembled micellar environment, telechelic oligomers with photoreactive termini (e.g., coumarin or styrylpyrene) resulting from the photodegradation of polymers in water underwent intermolecular photocycloaddition to photopolymerize, which usually only occurs efficiently at longer wavelengths and a much higher concentration of photoresponsive groups. The reported main chain polymer degradation is thus controlled by the irradiation wavelength and the assembly of the polymers.

Development of an Efficient Thionolactone for Radical Ring-Opening Polymerization by a Combined Theoretical/Experimental Approach.

The environmental impact of plastic waste has been a real problem for the past decades. The incorporation of cleavable bonds in the polymer backbone is a solution to making a commodity polymer degradable. When radical polymerization is used, this approach is made possible by radical ring-opening polymerization (rROP) of a cyclic monomer that allows for the introduction of a weak bond into the polymer backbone. Among the various cyclic monomers that could be used in rROP, thionolactones are promising structures due to the efficiency of the C═S bond to act as a radical acceptor. Nevertheless, only a few structures were reported to be efficient. In this work, we used DFT calculations to gain a better understanding of the radical reactivity of thionolactones, and in particular, we focused on the transfer rate constant ktr value and its ratio with the propagation rate constant kp of the vinyl monomer. The closer to 1, the better is the statistical incorporation of the two comonomers into the backbone. These theoretical results were in good agreement with all of the experimental data reported in the literature. We thus used this approach to understand the key parameters to tune the reactivity of thionolactone to prepare random copolymers. We identified and prepared the 7-phenyloxepane-2-thione (POT) thionolactone that led to statistical copolymers with styrene and acrylate derivatives that were efficiently degraded under accelerated conditions (KOH in THF/MeOH, TBD in THF, or mCPBA in THF), confirming the theoretical approach. The compatibility with RAFT polymerization as well as the homopolymerization behavior of POT was established. This theoretical approach paves the way for the in-silico design of new efficient thionolactones for rROP.

Amphiphilic Block Copolymers PEG-b-PMTCs: Synthesis, Self-Assembly, Degradation Properties and Biocompatibility.

As a hydrophilic cyclic ketene acetal (CKA), 2-methylene-1,3,6-trioxocane (MTC) has recently attracted a lot of attention owing to its ability to promote a quicker (bio)degradation as compared to other heavily studied CKAs. Here, we prepared amphiphilic block copolymers based on poly-MTC with varying chain lengths by radical ring opening polymerization. Self-assemblies of these amphiphiles were performed in PBS buffer to generate nanoparticles with sizes from 40 to 105 nm, which were verified by dynamic light scattering, electron microscopy, and static light scattering (Zimm plots). Subsequently, fluorescence spectroscopy was applied to study the enzymatic degradation of Nile red-loaded nanoparticles. By performing a point-by-point comparison of fluorescence intensity decline patterns between nanoparticles, we demonstrated that lipase from Pseudomonas cepacia was very efficient in degrading the nanoparticles. Hydrolysis degradations under basic conditions were also carried out, and a complete degradation was achieved after 4 h. Additionally, cytotoxicity assays were carried out on HEK293 cells, and the results affirmed cell viabilities over 90% when incubated with up to 1 mg/mL nanoparticles for 24 h. These biodegradable and biocompatible nanoparticles hence hold great potential for future applications such as drug release.

On the Absence of Gel Effect in Radical Ring-Opening Polymerization of Ketene Acetals

On the Absence of Gel Effect in Radical Ring-Opening Polymerization of Ketene Acetals

Investigating the potential of degradable poly(vinyl acetate) copolymer microparticles for encapsulation and in vitro release studies

Poly(vinyl acetate) is a well-known polymer synthesized through the free radical polymerization of vinyl acetate (VAc) monomer. However, enhancing the degradability of this polymer is best achieved by copolymerizing cyclic ketene acetal (CKA) with VAc. Despite their potential, the practical use of these degradable polymers remains limited. Therefore, our study aimed to develop a sustainable technology encompassing the synthesis and application of poly(VAc-co-MDO), and environmental biodegradability of poly(vinyl alcohol (VA)). To achieve this, we synthesized a series of degradable copolymers, namely poly(VAc-co-MDO), via free radical ring-opening polymerization (rROP) of 2-methylene-1,3-dioxepane (MDO) with VAc. The number of degradable ester units in the polymer backbone was systematically controlled by varying the initial monomer feed compositions, resulting in a range of 8–85 mol%. To compare their properties, we also synthesized homopolymers, namely poly(VAc) and poly(MDO). Subsequently, we formulated the homo and copolymers into microparticles using the co-solvent evaporation method, which yielded spherical particles with a particle size distribution ranging from 5 to 10 µm. Furthermore, we demonstrated the applicability of these degradable copolymers, exemplified by a poly[VAc(0.92)-co-MDO(0.08)] with 8 mol% MDO in the polymer backbone, in an encapsulation modeling study using curcumin as the active molecule. Successful encapsulation of curcumin into degradable polymer particles was confirmed and quantified via HPLC analysis. The degradability of the copolymers was evaluated through accelerated alkali hydrolysis, resulting in the formation of oligomeric degradation products. Additionally, we investigated the environmental biodegradability of poly(VA-co-MDO) as a proof of concept, revealing a biodegradability of 89% within 28 days for this polymer consisting of 88 mol% poly(VA) and 12 mol% poly(MDO) in the backbone. Preparing stable formulation for applications and performing biodegradability tests for the copolymers or microparticles derived from random poly(VAc-co-MDO) was challenging due to the insolubility of the polymer or instability in the form of sedimentation of the microparticles in the inoculum. Hence, in order to achieve stable formulation, we synthesized random poly(VA-co-MDO) through the selective cleavage of chloroacetyl group (ClAc) from its precursor, poly(VClAc-co-MDO). This method was preferred because obtaining poly(VA-co-MDO) directly from poly(VAc-co-MDO) was hindered by significant ester backbone cleavage, even under mild conditions. Our research assumes significance in light of recent restrictions imposed by various chemical agencies on the use of non-degradable polymers and microparticles in formulations.

Radical Ring Opening Polymerization of Cyclic Ketene Acetals Derived From d-Glucal.

A cyclic ketene acetal (CKA) derived from d-glucal was synthesized, and its polymerization using free radicals has been investigated. NMR analysis of the resulting polymers revealed the formation of polyacetal-polyester copolymers, with up to 78% of ester linkages formed by radical ring-opening polymerization (rROP). Conversely, the polymerization of the monomer-saturated analogue only produced acetal linkages, demonstrating that the alkene functionality within the d-glucal pyranose ring is essential to promote ring-opening and ester formation, likely via the stabilization of an allyl radical. The thermal properties of the polymers were linked to the ratio of the ester and acetal linkages. Copolymerization with methyl methacrylate (MMA) afforded statistically PMMA-rich copolymers (66-98%) with linkages prone to hydrolytic degradation and decreased glass-transition temperatures. The retention of the pseudoglucal alkene function offers opportunities to functionalize further these bioderived (co)polymers.