Reversible Chain Transfer Agent Research Articles

A single-step extraction and immobilization of soybean lipolytic enzymes by using a purpose-designed copolymer of styrene and maleic acid as a membrane lysis agent

Approaches aiming to recover proteins without denaturation represent attractive strategies. To accomplish this, a membrane lysis agent based on poly(styrene-alt-maleic acid) or PSMA was synthesized by photopolymerization using Irgacure® 2959 and carbon tetrabromide (CBr4) as a radical initiator and a reversible chain transfer agent, respectively. Structural elucidation of our in-house synthesized PSMA, so-called photo-PSMA, was performed by using NMR spectroscopy. The use of this photo-PSMA in soybean enzyme extraction was also demonstrated for the first time in this study. Without a severe cell rupture, energy input or any organic solvent, recovery of lipolytic enzymes directly into nanometric-sized particles was accomplished in one-step process. Due to the improved structural regularity along the photo-PSMA backbone, the most effective protective reservoir for enzyme immobilization was generated through the PSMA aggregation. Formation of such reservoir enabled soybean enzymes to be shielded from the surroundings and resolved in their full functioning state. This was convinced by the increased specific lipolytic activity to 1,950 mU/mg, significantly higher than those of sodium dodecyl sulfate (SDS) and the two commercially-available PSMA sources (1000P and 2000P). Our photo-PSMA had thus demonstrated its great potential for cell lyse application, especially for soybean hydrolase extraction.

Synthesis and modification of copolymers of stearyl methacrylate and maleic anhydride and study of their effect on low-temperature characteristics of diesel fuel

Polymer-analogous transformations have been used to modify copolymers of stearyl methacrylate with maleic anhydride synthesized under radical polymerization conditions using reversible chain transfer agents of various structures. It has been established that copolymer of stearyl methacrylate with maleic anhydride modified by 25% with octanol-1 has a high depressant effect for a pour point of minus 19°С and at the same time significantly reduces both the cloud point values and the maximum filterability temperature of diesel fuel. In this regard, the obtained modified copolymers may be of interest in terms of their practical use as fuel additives.

Cationic β‐Scission of C−H and C−C Bonds for Selective Dimerization and Subsequent Sulfur‐Free RAFT Polymerization of α‐Methylstyrene and Isobutylene

AbstractA series of exo‐olefin compounds ((CH3)2C(PhY)−CH2C(=CH2)PhY) were prepared by selective cationic dimerization of α‐methylstyrene (αMS) derivatives (CH2=C(CH3)PhY) with p‐toluenesulfonic acid (TsOH) via β‐C−H scission. They were subsequently used as reversible chain transfer agents for sulfur‐free cationic RAFT polymerization of αMS via β‐C−C scission in the presence of Lewis acid catalysts such as SnCl4. In particular, exo‐olefin compounds with electron‐donating substituents, such as a 4‐MeO group (Y) on the aromatic ring, worked as efficient cationic RAFT agents for αMS to produce poly(αMS) with controlled molecular weights and exo‐olefin terminals. Other exo‐olefin compounds (R−CH2C(=CH2)(4‐MeOPh)) with various R groups were prepared by different methods to examine the effects of R groups on the cationic RAFT polymerization. A sulfur‐free cationic RAFT polymerization also proceeded for isobutylene (IB) with the exo‐olefin αMS dimer ((CH3)2C(Ph)−CH2C(=CH2)Ph). Furthermore, telechelic poly(IB) with exo‐olefins at both terminals was obtained with a bifunctional RAFT agent containing two exo‐olefins. Finally, block copolymers of αMS and methyl methacrylate (MMA) were prepared via mechanistic transformation from cationic to radical RAFT polymerization using exo‐olefin terminals containing 4‐MeOPh groups as common sulfur‐free RAFT groups for both cationic and radical polymerizations.

Cationic β-Scission of C-H and C--C Bonds for Selective Dimerization and Subsequent Sulfur-Free RAFT Polymerization of α-Methylstyrene and Isobutylene.

A series of exo-olefin compounds ((CH3)2C(PhY)-CH2C(=CH2)PhY) were prepared by selective cationic dimerization of α-methylstyrene (αMS) derivatives (CH2=C(CH3)PhY) with p-toluenesulfonic acid (TsOH) via β-C-H scision. They were subsequently used as reversible chain transfer agents for sulfur-free cationic RAFT polymerization of αMS via β-C-C scission in the presence of Lewis acid catalysts such as SnCl4. In particular, exo-olefin compounds with electron-donating substituents, such as a 4-MeO group (Y) on the aromatic ring, worked as efficient cationic RAFT agents for αMS to produce poly(αMS) with controlled molecular weights and exo-olefin terminals. Other exo-olefin compounds (R-CH2C(=CH2)(4-MeOPh)) with various R groups were prepared by different methods to examine the effects of R groups on the cationic RAFT polymerization. A sulfur-free cationic RAFT polymerization also proceeded for isobutylene (IB) with the exo-olefin αMS dimer ((CH3)2C(Ph)-CH2C(=CH2)Ph). Furthermore, telechelic poly(IB) with exo-olefins at both terminals was obtained with a bifunctional RAFT agent containing two exo-olefins. Finally, block copolymers of αMS and MMA were prepared via mechanistic transformation from cationic to radical RAFT polymerization using exo-olefin terminals containing 4-MeOPh groups as common sulfur-free RAFT groups for both cationic and radical polymerizations.

Versatile Production of Multivariate, Hyperdimensional End Group and Main Chain Functionalized Polyolefins.

The (stereoselective) living coordinative copolymerization of 1-alkenes with 4-aryl-1,6-heptadienes, in both the absence and presence of multiple equivalents of a reversible chain transfer agent, is established as a highly versatile strategy for production of multivariate hyperdimensional functionalized semi-crystalline or amorphous polyolefins that optionally possess either mono- or difunctionalized (telechelic) end-groups in combination with a programmable level of incorporation of orthogonal functional groups within the main-chain. The non-conjugated diene comonomers are readily obtained from a diverse range of aryl carboxaldehyde precursors through a one-step bis-allylation process. These results serve to provide a new platform for exploring the science and technology of a vast new landscape of functionalized classes of polyolefins that are now accessible in practical and scalable quantities.

Versatile Production of Multivariate, Hyperdimensional End Group and Main Chain Functionalized Polyolefins

AbstractThe (stereoselective) living coordinative copolymerization of 1‐alkenes with 4‐aryl‐1,6‐heptadienes, in both the absence and presence of multiple equivalents of a reversible chain transfer agent, is established as a highly versatile strategy for production of multivariate hyperdimensional functionalized semi‐crystalline or amorphous polyolefins that optionally possess either mono‐ or difunctionalized (telechelic) end‐groups in combination with a programmable level of incorporation of orthogonal functional groups within the main‐chain. The non‐conjugated diene comonomers are readily obtained from a diverse range of aryl carboxaldehyde precursors through a one‐step bis‐allylation process. These results serve to provide a new platform for exploring the science and technology of a vast new landscape of functionalized classes of polyolefins that are now accessible in practical and scalable quantities.

Multi-signal amplification electrochemiluminescence biosensor based on GO-CDTPA-AuNPs composites and PET-RAFT for ultrasensitive detection of KRAS G12C mutation

The detection of the Kirsten Rat Sarcoma (KRAS) G12C point mutation plays an important role in the early diagnosis and individualized treatment of non-small cell lung cancer (NSCLC). Herein, a novel electrochemiluminescence (ECL) biosensor for the detection of KRAS G12C mutation via GO-CDTPA-AuNPs composites and photo-induced electron/energy transfer reversible addition-fragment chain transfer (PET-RAFT) multi-signal amplification strategy was fabricated for the first time. In this work, gold nanoparticles (AuNPs) were loaded onto the graphene oxide (GO) surface to form a luminol electrochemiluminescence enhanced composite by simple amide reaction and electrostatic adsorption. Specifically, in the presence of KRAS G12C mutation DNA, i.e. target DNA (tDNA), self-assembled hairpin DNA (hDNA) on the biosensor electrode surface was activated after hybridization with the tDNA to expose a 3′-terminal amino group, that could be further linked to GO-CDTPA-AuNPs composites. To increase luminol-based ECL, GO-CDTPA-AuNPs composites contained a lot of photo-induced electron/energy transfer reversible addition-fragment chain transfer (PET-RAFT) agent loaded onto GO surface. PET-RAFT polymerization of N-acryloxysuccinimide (NAS) monomer was initiated to form polymer chains containing multiple binding sites for luminol. Due to the amplification of luminol attachment sites, very high quantities of luminol could be introduced onto the biosensor electrode surface, resulting in significantly amplified ECL signal intensity. Under optimal biosensor fabrication conditions, a good linear relationship between ECL signal intensity and the logarithm of tDNA concentration was observed over the range of 1 fM to 10 nM with a 0.12 fM limit of detection. Moreover, this strategy exhibited high selectivity and excellent applicability for KRAS G12C mutation detection in the clinical human serum samples. Thus, the fabricated biosensor has great potential for application in the clinical diagnosis.

Covalent functionalization of Sb2S3 with poly(N-vinylcarbazole) for solid-state broadband laser protection.

An optimized complex multi-component nanomaterial system would help greatly enhance the optical limiting performance and applicability of 2D nanomaterials. By using antimony sulfide-[S-1-dodecyl-S'-(α,α'-dimethyl-α''-acetic acid)trithiocarbonate] (Sb2S3-DDAT) as a reversible addition fragmentation chain transfer (RAFT) agent, a highly soluble poly(N-vinylcarbazole)-covalently modified Sb2S3 (Sb2S3-PVK) was synthesized in situ and embedded into a non-optically active poly(methylmethacrylate) (PMMA) matrix producing a PMMA-based film with good optical quality. In contrast to both the Sb2S3/PMMA and Sb2S3:PVK blends/PMMA films, the Sb2S3-PVK/PMMA film exhibits more superior optical limiting performance. After annealing in N2 at 200 °C for 30 minutes, the achieved nonlinear absorption coefficient and limiting threshold are changed from 411.79 cm GW-1 and 1.93 J cm-2 at 532 nm and 242.79 cm GW-1 and 4.17 J cm-2 at 1064 nm before annealing to 478.04 cm GW-1 and 1.70 J cm-2 at 532 nm and 520.92 cm GW-1 and 1.40 J cm-2 at 1064 nm after annealing, respectively. These advantages make Sb2S3-PVK one of the potential promising candidates for a broadband laser protector in both the visible and near-infrared ranges.

Dual Function of β-Hydroxy Dithiocinnamic Esters: RAFT Agent and Ligand for Metal Complexation.

The reversible addition-fragmentation chain-transfer (RAFT) process has become a versatile tool for the preparation of defined polymers tolerating a large variety of functional groups. Several dithioesters, trithiocarbonates, xanthates, or dithiocarbamates have been developed as effective chain transfer agents (CTAs), but only a few examples have been reported, where the resulting end groups are directly considered for a secondary use besides controlling the polymerization. Herein, it is demonstrated that β-hydroxy dithiocinnamic esters represent a hitherto overlooked class of materials, which are originally designed for the complexation of transition metals but may as well act as reversible CTAs. Modified with a suitable leaving group (R-group), these vinyl conjugated dithioesters indeed provide reasonable control over the polymerization of acrylates, acrylamides, or styrene via the RAFT process. Kinetic studies reveal linear evolutions of molar mass with conversion, while different substituents on the aromatic unit has only a minor influence. Block extensions prove the livingness of the polymer chains, although extended polymerization times may lead to side reactions. The resulting dithiocinnamic ester end groups are still able to form complexes with platinum, which verifies that the structural integrity of the end group is maintained. These findings open a versatile new route to tailor-made polymer-bound metal complexes.

Synthesis and characterization of star-shaped block copolymers composed of poly(3-hydroxy octanoate) and styrene via RAFT polymerization

This study investigated a macro reversible addition fraction chain transfer (RAFT) agent based on three-arm hydroxylated star-shaped poly(3-hydroxy octanoate). The utilization of this star-shaped poly(3-hydroxy octanoate) macro-RAFT agent in the RAFT process resulted in efficient control in the preparation of star-shaped block styrene copolymers. Poly(3-hydroxy octanoate) (PHO) was reacted with diethanol amine (DEA) in order to obtain three-arm hydroxylated poly(3-hydroxy octanoate) (PHO-DEA). A carboxylic acid-functionalized RAFT agent (2-(dodecylthiocarbonothioylthio)-2-methylpropionic acid) was reacted with the PHO-DEA in order to obtain a star-shaped PHO macro-RAFT agent (PHO-R2). A series of AB3 type PHO-polystyrene (PHO-PS) star-shaped block copolymers were obtained via the polymerization of styrene (S) using the PHO-R2 in toluene at 80 °C. The RAFT polymerization was seen to obey the polymerization kinetics of controlled free radical polymerization. The plasticizing effect of the PHO soft segments was influenced by the glass transition temperature (Tg) of polystyrene. This was clearly observed in the block copolymers. Moreover, it was clear that this plasticizing effect disappeared in the block copolymers as a result of the increase in polymerization time. The molar masses of the obtained copolymers increased in parallel with increases in the polymerization time. Structural, physiochemical, and thermal characterization of the obtained products was carried out using size-exclusion chromatography (SEC), proton nuclear magnetic resonance (1H NMR), differential scanning calorimetry (DSC), and thermal gravimetric analysis (TGA) techniques. The polymerization kinetics of the star-shaped block copolymers were also investigated in detail.

Asymmetric Cationic Polymerization of Benzofuran through a Reversible Chain-Transfer Mechanism: Optically Active Polybenzofuran with Controlled Molecular Weights

Benzofuran (BzF) is a prochiral, 1,2-disubstituted, unsymmetric cyclic olefin that can afford optically active polymers by asymmetric polymerization, unlike common acyclic vinyl monomers. Although asymmetric cationic polymerization of BzF was reported by Natta et al. in the 1960s, the polymer structure has not been clarified, and there are no reports on molecular weight control. Herein, we report dual control of the optical activity and molecular weight of poly(BzF) using thioether-based reversible chain-transfer agents for asymmetric cationic polymerization with β-amino acid derivatives as chiral additives and aluminum chloride as a catalyst. This asymmetric moderately living cationic polymerization leads to an increase in molecular weight and specific optical rotation with monomer conversion. In addition, asymmetric block polymers consisting of opposite absolute configurational segments were synthesized using both enantiomers sequentially as chiral additives. Finally, a comprehensive analysis of the polymerization products and the model reaction revealed that the optical activity of poly(BzF) originates from the threo-diisotactic structure, which occurs by regio-, trans-, and enantioselective propagation.

A Photoinduced Dual-Wavelength Approach for 3D Printing and Self-Healing of Thermosetting Materials.

Vat photopolymerization-based 3D printing techniques have been widely used to produce high-resolution 3D thermosetting materials. However, the lack of repairability of these thermosets leads to the production of waste. In this study, reversible addition fragmentation chain transfer (RAFT) agents are incorporated into resin formulations to allow visible light (405 nm) mediated 3D printing of materials with self-healing capabilities. The self-healing process is based on the reactivation of RAFT agent embedded in the thermosets under UV light (365 nm), which enables reformation of the polymeric network. The self-healing process can be performed at room temperature without prior deoxygenation. The impact of the type and concentration of RAFT agents in the polymer network on the healing efficiency is explored. Resins containing RAFT agents enable 3D printing of thermosets with self-healing properties, broadening the scope of future applications for polymeric thermosets in various fields.

A Photoinduced Dual‐Wavelength Approach for 3D Printing and Self‐Healing of Thermosetting Materials

AbstractVat photopolymerization‐based 3D printing techniques have been widely used to produce high‐resolution 3D thermosetting materials. However, the lack of repairability of these thermosets leads to the production of waste. In this study, reversible addition fragmentation chain transfer (RAFT) agents are incorporated into resin formulations to allow visible light (405 nm) mediated 3D printing of materials with self‐healing capabilities. The self‐healing process is based on the reactivation of RAFT agent embedded in the thermosets under UV light (365 nm), which enables reformation of the polymeric network. The self‐healing process can be performed at room temperature without prior deoxygenation. The impact of the type and concentration of RAFT agents in the polymer network on the healing efficiency is explored. Resins containing RAFT agents enable 3D printing of thermosets with self‐healing properties, broadening the scope of future applications for polymeric thermosets in various fields.

Immunopharmacological Properties of Methacrylic Acid Polymers as Potential Polymeric Carrier Constituents of Anticancer Drugs.

Cytostatic chemotherapeutics provide a classical means to treat cancer, but conventional treatments have not increased in efficacy in the past years, warranting a search for new approaches to therapy. The aim of the study was, therefore, to obtain methacrylic acid (MAA) (co)polymers and to study their immunopharmacological properties. 4-Cyano-4-[(dodecylsulfanylthiocarbonyl)sulfanyl] pentanoic acid (CDSPA) and 2-cyano-2-propyl dodecyl trithiocarbonate (CPDT) were used as reversible chain transfer agents. Experiments were carried out in Wistar rats. The MTT assay was used to evaluate the cytotoxic effect of the polymeric systems on peritoneal macrophages. An experimental tumor model was obtained by grafting RMK-1 breast cancer cells. Serum cytokine levels of tumor-bearing rats were analyzed. The chain transfer agents employed in classical radical polymerization substantially reduced the molecular weight of the resulting polymers, but a narrow molecular weight distribution was achieved only with CDSPA and high CPDT concentrations. Toxicity was not observed when incubating peritoneal macrophages with polymeric systems. In tumor-bearing rats, the IL-10 concentration was 1.7 times higher and the IL-17 concentration was less than half that of intact rats. Polymeric systems decreased the IL-10 concentration and normalized the IL-17 concentration in tumor-bearing rats. The maximum effect was observed for a MAA homopolymer with a high molecular weight. The anion-active polymers proposed as carrier constituents are promising for further studies and designs of carrier constituents of drug derivatives.

Tert-Butyl Esters as Potential Reversible Chain Transfer Agents for Concurrent Cationic Vinyl-Addition and Ring-Opening Copolymerization of Vinyl Ethers and Oxiranes.

tert-Butyl esters are demonstrated to function as chain transfer agents (CTAs) in the cationic copolymerization of vinyl ether (VE) and oxirane via concurrent vinyl-addition and ring-opening mechanisms. In the copolymerization of isopropyl VE and isobutylene oxide (IBO), the IBO-derived propagating species reacts with tert-butyl acetate to generate a copolymer chain with an acetoxy group at the ω-end. This reaction liberates a tert-butyl cation; hence, a polymer chain with a tert-butyl group at the α-end is subsequently generated. Other tert-butyl esters also function as CTAs, and the substituent attached to the carbonyl group affects the chain transfer efficiency. In addition, ethyl acetate does not function as a CTA, which suggests the importance of the liberation of a tert-butyl cation for the chain transfer process. Chain transfer reactions by tert-butyl esters potentially occur reversibly through the reaction of the propagating cation with the ester group at the ω-end of another chain.

Synthesis of Amphiphilic Copolymers of Acrylic Acid and Styrene with the Desired Microstructure and Their Properties

The regularities of the controlled synthesis of amphiphilic copolymers of styrene and acrylic acid mediated by dithiobenzoate and trithiocarbonates as reversible addition fragmentation chain transfer agents in a 1,4-dioxane solution are considered. The influence of the general composition and chain microstructure on the dispersion stability and hydrodynamic sizes of polymer particles of copolymers containing from 40 to 90 mol % of acrylic acid units is studied. It is shown that in dilute aqueous media random copolymers are dispersed to individual compacted coils owing to the intrachain hydrophobic association of styrene units. The addition of two poly(acrylic acid) blocks to such a copolymer improves its dispersibility in water, and the attachment of two polystyrene blocks makes it insoluble in water because of the interchain association of polystyrene units. The synthesized copolymers possess surface activity, and when applied to a hydrophilic glass surface, they moderately hydrophobize it. In general, this synthetic approach opens up broad prospects for obtaining a wide range of new polymer macromolecules with different properties from one pair of traditional monomers.

Effect of Chain-End Chemistries on the Efficiency of Coupling Antibodies to Polymers Using Unnatural Amino Acids.

Novel conjugates that incorporate strategies for increasing the therapeutic payload, such as targeted polymeric delivery vehicles, have great potential in overcoming limitations of conventional antibody therapies that often exhibit immunogenicity and limited drug loading. Click chemistry has significantly expanded the toolbox of effective strategies for developing hybrid polymer-biomolecule conjugates, however, effective systems require orthogonality between the polymer and biomolecule chemistries to achieve efficient coupling. Here, three cycloaddition-based strategies for antibody conjugation to polymeric carriers are explored and show that a purely radical-based method for polymer synthesis and subsequent biomolecule attachment has a trade-off between coupling efficiency of the antibody and the ability to synthesize polymers with controlled chemical properties. It is shown that careful consideration of both coupling chemistries as well as the potential effect of how this modulates the chemical properties of the polymer nanocarrier should be considered during the development of such systems. The strategies described offer insight into improving conjugate development for therapeutic and theranostic applications. In this system, polymerization using conventional and established reversible addition fragmentation chain transfer (RAFT) agents, followed by multiple post-modification steps, always leads to systems with more defined chemical architectures compared to strategies that utilize alkyne-functional RAFT agents.

Linear Coordination Polymer Synthesis from Bis-Catechol Functionalized RAFT Polymers.

Catechol-Fe(III) complexes contain some of the strongest known metal-chelate coordination bonds. Despite this, they have until now not been utilized in (polymeric linker) linear coordination polymer (LCP) synthesis. With the view of generating catechol end-functional polymers, a new, symmetrical bis-catechol functionalized trithiocarbonate reversible addition fragmentation chain transfer (RAFT) agent is synthesized (CatDMAT). Acrylamide (AM) and dimethylacrylamide (DMA) polymerizations are conducted with CatDMAT using direct photoactivation RAFT polymerization to yield bis-catechol end-functionalized homo- and block-copolymers of molecular weight 10-15kDa. Catechol-Fe(III) LCPs are successfully formed from the telechelic catechol polymers by bis-complexation to Fe(III). The tetrahedral bis-complex is detected by UV-vis spectroscopy (λmax = 570nm), while increases in relative viscosity and Mn,GPC over their respective uncomplexed polymers confirm the occurrence of supramolecular polymerization. The catechol-LCPs are shown to undergo oxidation and crosslinking in aqueous solution after 24 h.

Effect of (co)polymers based on methacrylic acid on the state of cells of the immune system

A series of methacrylic acid co(polymers) were obtained using various reversible chain transfer agents. The molecular weight characteristics of the synthesized (co)polymers were determined using gel permeation chromatography. In vitro studies showed the absence of cytotoxicity of the obtained compounds against immune cells (peritoneal macrophages) and the absence of an effect on the functional activity of the cells.

Composites Based on Functionalized Polystyrene and Semiconductor Quantum Dots

A procedure for producing nanocomposites by bonding polystyrene to the terminal carboxyl group and quantum dots based on CdSe and ZnS has been developed. The terminal functional group has been introduced into the polymer by radical polymerization with reversible chain transfer using trithiocarbonate. The effect of the reaction conditions and structure of the reversible chain transfer agent on the content of quantum dots in the nanocomposite has been studied. It has been shown that quantum dots of the CdSe core type and the CdSe/ZnS core/shell type have different activity upon binding to the polymer.