Reducing Agent Atom Transfer Radical Research Articles

Synthesis and characterization of polystyrene-b-poly(vinyldipicolinic acid) pH-responsive core-shell nanoparticles

The self-assembly of a new series of amphiphilic polystyrene-b-poly(4-vinyldipicolinic acid) PS-b-PVDPA diblock copolymers in aqueous solution is reported in order to obtain core–shell nanoparticles composed of a PS core and a PVDPA shell. Diblock copolymers were synthesized by Supplemental Activation Reducing Agent-Atom Transfer Radical Polymerization (SARA-ATRP) with a degree of polymerization (DP) of the PS block in the range 112–260 and a DP of PVDPA block of 10, 30 or 50. Anionic latex nanoparticles of PS-b-PVDPA were prepared by solvent displacement methods. All the nanoparticle suspensions had a narrow size distribution (0.014 ≤ PDI ≤ 0.144) with zeta potential in the range −27 mV to −38 mV indicating electrostatic repulsions due to carboxylate anions and therefore high colloidal stability. DLS was used to determine nanoparticle size, with SEM and TEM used to determine and confirm both size and spherical shape. All three methods found the size for these nanoparticles to be in the range 75–120 nm. Using fluorimetry and DLS methods, Critical Aggregation Concentration (CAC) for each type of nanoparticle was determined to be within the range of 33–69 mg/L. Micelles were pH-responsive with stability in aqueous conditions for pH > 3.5. Micelles were stable at pH 5.5 for up to 40 days and at temperature up to 60 °C.

Replacing organics with water: Macromolecular engineering of non-water miscible poly(meth)acrylates via interfacial and ion-pair catalysis SARA ATRP in miniemulsion

The paper presents the possibility to synthesize immiscible with water, well-defined poly(meth)acrylates via supplemental activation and reducing agent atom transfer radical polymerization (SARA ATRP) in a miniemulsion environment, using a copper wire (Cu0) as reducing agent and supplemental activator. This is the first example of interfacial and ion-pair catalysis presented for Cu0-mediated ATRP carried out in heterogeneous media. In addition, scanning electron microscopy (SEM) was used for further analysis of the occurring processes and miniemulsion droplets were characterized by dynamic light scattering (DLS). Particular attention was paid to the selection of optimum reaction conditions and the applicability of the developed system for a wide range of monomers. For the sake of the environment, the advantages of the presented polymerization technique in the context of sustainable development of the chemical industry were analyzed and highlighted by calculating the green metrics (environmental factors – E-factors) for the synthesized polymers.

Where is the induction from? Effect of disproportionation and comproportionation in Cu(0)-mediated reversible deactivation radical polymerization

There is a controversial debate about the mechanism of reversible deactivation radical polymerization (RDRP) in the presence of Cu(0). Two mechanism models have been proposed - supplemental activator and reducing agent atom transfer radical polymerization (SARA ATRP) and single-electron transfer living radical polymerization (SET-LRP), however, they are contradictory to each other, and neither of them are able to fully explain experimental phenomenon in the Cu(0)-mediated RDRP process, especially a period of slow addition i.e., induction period occurs under certain reaction conditions. In this work, the induction phenomenon and its underlying mechanism was explored and clarified by using different catalyst systems (CuI, Cu(0), Cu(0)&CuII) and different initiator systems i.e., EBriB (ethyl α-bromoisobutyrate), EBrP (ethyl 2-bromopropionate), MBrP (methyl 2-bromopropionate) and MClP (methyl 2-chloropropionate). New insights on the roles of different copper species and their mutual conversion kinetics were provided. It is proved that the appearance/absence of the induction period is due to the difference in the relative concentrations of CuI and CuII accumulated at the early stage of the reaction. Moreover, the disproportionation and comproportionation co-exist in the Cu(0)-mediated RDRP system and play an essential role in establishing the equilibrium among different copper species (Cu0, CuI and CuII) at the early reaction stage.

PH-responsive nanoparticles based on POEOMA-b-PDPA block copolymers for RNA encapsulation, protection and cell delivery

The use of gene-based products, such as DNA or RNA, is increasingly being explored for various innovative therapies. However, the success of these strategies is highly dependent on the effective delivery of these biomolecules to target cells. Therefore, the development of pH-responsive nanoparticles comprises the creation of intelligent delivery systems with high therapeutic efficiency. In this work, the pH-responsiveness of the poly(2-(diisopropylamino)ethyl methacrylate)) (PDPA) block was investigated for the encapsulation and delivery of small RNAs (sRNA) to cancer cells. The pH responsiveness was dependent on the protonation profile of the tertiary amines of PDPA, which directly affected the electrostatic interactions established with RNA. Thus, block copolymers based on poly(oligo(ethylene oxide) methyl ether methacrylate) (POEOMA) and PDPA, POEOMA-b-PDPA, were synthesized by supplemental activator and reducing agent atom transfer radical polymerization (SARA ATRP). The structure of the block copolymers was characterized by size exclusion chromatography and 1H NMR spectroscopy. The copolymers allowed effective complexation of model sRNAs and a pre-miRNA with efficiencies of about 89 % and 91 %, respectively. The characterization by dynamic light scattering revealed that these systems had sizes between 76 and 1375 nm. It was also found that the morphology of the polyplexes depended on the pH, since the preparation at a pH lower than the pKa of the copolymers resulted in spherical but polydisperse particles, while higher pH values resulted in nanoparticles with more homogeneous size, but altered morphology. Moreover, due to pH-responsiveness, it was achieved the release of RNA at pH higher than the pKa of the copolymers, while maintaining its integrity. The polyplexes also showed a high potential to protect RNA from RNases. The transfection of a lung cancer model (A549) and fibroblast cell lines showed that these polyplexes did not cause cell toxicity. In addition, the polyplexes enabled the effective transfection of the A549 cell line with pre-miRNA-29b and miRNA-29b, resulting in a decrease of expression levels of the target DNMT3B gene by approximately 51 % and 47 %, respectively. Overall, the POEOMA-b-PDPA copolymers proved to be a promising strategy for developing responsive delivery systems, that can play a critical role in some diseases, such as cancer, where pH varies between the intra and extracellular environments.

Probing the molecular basis for sulfonamides recognition in surface molecularly imprinted polymers using computational and experimental approaches

The computer-aided design of surface molecularly imprinted polymers (SMIPs) of sulfadimethoxine (SDM) using methacrylic acid (MAA), 4-vinylpyridine (4-VP) or 4-aminostyrene (AS) as functional monomers was performed using Gaussian software, and the corresponding materials were innovatively prepared by surface-initiated supplemental activator and reducing agent atom transfer radical polymerization (SI-SARA ATRP) using an Fe(0)/Cu(II) catalytic system. Sulfonamides were selected as template molecules because of their stable nuclear parent and regular side chain changes, which could help explore the molecular mechanism of imprinting and recognition from the perspective of structural differences. The imprinted systems were calculated using Gaussian software to obtain parameters related to intermolecular interactions. The morphology and physicochemical properties of SMIPs were determined by scanning electron microscope (SEM), oxygen bomb combustion-ion chromatography (OBC-IC) and thermogravimetric analyzer (TGA). The relevant adsorption mechanism was evaluated using the Langmuir–Freundlich (LF) isotherm. The adsorption capacities (Q) of the three SMIPs for nine other sulfonamides were evaluated by experiments, and the weak interaction energy between other sulfonamide molecules and the molecularly imprinted pores generated by SDM was simulated. Compared with the two other functional monomers, MAA demonstrated advantages in Q, pore uniformity, and imprinting factor. Weak interaction energies between the drug and functional monomer, as the main influencing factor, and steric hindrance as a secondary factor, influenced the Q, difficulty of template elution, and selective adsorption of the polymers for the nine other sulfonamides. Quantum chemical calculation data revealed that the number of hydrogen bonds generated, the participation of other weak interactions, and the charge of hydrogen bond donors had great influence on the weak interaction energy.

Hydrophobic modification of fir wood surface via low ppm ATRP strategy

Wood-polymer hybrid material was prepared using an easily scalable supplemental activator and reducing agent atom transfer radical polymerization (SARA ATRP) concept with low ppm catalyst concentration. Polymers with hydrophobic characteristics – poly (n-butyl acrylate) (PnBA), poly (tert-butyl acrylate) (PtBA) and poly (methyl methacrylate) (PMMA) were grafted from the fir wood surface in a controlled manner, proved by linear first-order kinetics of polymerization in solution and low dispersity (Mw/Mn = 1.12) of the polymers formed in the reaction mixture. Moreover, the thickness of the polymer brushes grafted from the wood surface was estimated based on the measurements performed for brush decorated silicon wafers that were placed in the reaction mixture. Scanning electron microscopy (SEM) proved successful coverage of the wood by a covalently attached polymer layer, going from sharp-edged untreated wood surface with clearly visible wood cell wall structural elements, to full coverage rough texture with no visible structural components. Water contact angle (Θ) measurements indicated excellent hydrophobic properties of the prepared biohybrid material (Θ ~138°) without notable changes after 120 s of water droplet exposure. Water and acid solution uptake tests confirmed a significant improvement in resistance for absorption of wood samples after modification with polymers.

Smart, Naturally-Derived Macromolecules for Controlled Drug Release.

A series of troxerutin-based macromolecules with ten poly(acrylic acid) (PAA) or poly(2-dimethylaminoethyl methacrylate) (PDMAEMA) homopolymer side chains were synthesized by a supplemental activator and reducing agent atom transfer radical polymerization (SARA ATRP) approach. The prepared precisely-defined structures with low dispersity (Mw/Mn < 1.09 for PAA-based, and Mw/Mn < 1.71 for PDMAEMA-based macromolecules) exhibited pH-responsive behavior depending on the length of the polymer grafts. The properties of the received polyelectrolytes were investigated by dynamic light scattering (DLS) measurement to determine the hydrodynamic diameter and zeta potential upon pH changes. Additionally, PDMAEMA-based polymers showed thermoresponsive properties and exhibited phase transfer at a lower critical solution temperature (LCST). Thanks to polyelectrolyte characteristics, the prepared polymers were investigated as smart materials for controlled release of quercetin. The influence of the length of the polymer grafts for the quercetin release profile was examined by UV–VIS spectroscopy. The results suggest the strong correlation between the length of the polymer chains and the efficiency of active substance release, thus, the adjustment of the composition of the macromolecules characterized by branched architecture can precisely control the properties of smart delivery systems.

Catalytic Halogen Exchange in Supplementary Activator and Reducing Agent Atom Transfer Radical Polymerization for the Synthesis of Block Copolymers.

Synthesis of block copolymers (BCPs) by catalytic halogen exchange (cHE) is reported, using supplemental activator and reducing agent Atom Transfer Radical Polymerization (SARA ATRP). The cHE mechanism is based on the use of a small amount of a copper catalyst in the presence of a suitable excess of halide ions, for the synthesis of block copolymers from macroinitiators with monomers of mismatching reactivity. cHE overcomes the problem of inefficient initiation in block copolymerizations in which the second monomer provides dormant species that are more reactive than the initiator. Model macroinitiators with low dispersity are prepared and extended to afford well-defined block copolymers of various compositions. Combined cHE/SARA ATRP is therefore a simple and potent polymerization tool for the copolymerization of a wide range of monomers allowing the production of tailored block copolymers.

Rapid SARA ATRP of Methyl Acrylate in Polyethylene Glycol Mediated by a Mixed Sulfite/CuBr2 Catalytic System

Supplemental activator and reducing agent atom transfer radical polymerization (SARA ATRP) of methyl acrylate was successfully performed in inexpensive, eco-friendly polyethylene glycol solvents and catalyzed by a mixed sulfite/CuBr2 system at room temperature. The presence of polyethylene glycol in the reaction mixtures allowed fast and controlled polymerizations throughout the whole reaction time. Remarkably, a fast polymerization can be achieved with a monomer conversion reaching 90% in only 50 min using PEG 200 as the reaction solvent. The controlled character of the ATRP of methyl acrylate was confirmed by the linear increase in molecular weight with monomer conversion, the narrow molecular weight distributions (Mw/Mn = 1.15) and the results of chain extension experiments. 1H NMR analysis also confirmed the molecular structure and chain-end functionality of the obtained polymers, and the effects of PEG molecular weight and inorganic sulfites on the polymerization behavior were investigated.

Guanidine as inexpensive dual function ligand and reducing agent for ATRP of methacrylates

N,N,N′,N′-Tetramethyl guanidine, an inexpensive and commercially available organic base, is used for the first time as ligand without any chemical modification for the supplemental activator and reducing agent atom transfer radical polymerization.

Poly(4-vinylpyridine)-modified silica for efficient oil/water separation

Silica particles were modified with a poly(4-vinylpyridine) (P4VP) for efficient separation of oil-in-water emulsions. Using a 3-(aminopropyl) triethoxysilane (APTES)-based molecule coupled to an appropriate radical initiator, P4VP chains were built from silica surfaces under mild reaction conditions using surface-initiated supplemental activator and reducing agent atom transfer radical polymerization. P4VP-modified silica particles were successfully used as a pH-switchable barrier for oil/water separation and proved to be efficient in removing oil from an oil-in-water nanoemulsion.

The Role of Cu0 in Surface-Initiated Atom Transfer Radical Polymerization: Tuning Catalyst Dissolution for Tailoring Polymer Interfaces

The availability of catalytic/reducing sites at metallic Cu0 sources during supplemental activator and reducing agent atom transfer radical polymerization (SARA ATRP) is regulated by the components of the polymerization mixture, including ligand (L), alkyl halide initiator (R–X), and CuII-based deactivator. Their contributions were analyzed by quantifying the dissolution of Cu species within a quartz crystal microbalance with dissipation (QCM-D), subjecting a Cu0-coated sensor to different polymerization mixtures. The control of catalyst diffusion from Cu0 was subsequently exploited to fabricate structured polymer brushes with diverse compositions, when ATRP was performed from surface-immobilized initiators in the presence of a Cu0 plate, placed at a determined distance (d) from the substrate. Surface-initiated ATRP in the presence of Cu0 (Cu0-SI-ATRP) is compatible with a broad variety of monomers, including oligo(ethylene glycol) acrylate (OEGA), methyl acrylate (MA), and acrylamide (AAm). The kinetics ...

Increasing the Antimicrobial Activity of Amphiphilic Cationic Copolymers by the Facile Synthesis of High Molecular Weight Stars by Supplemental Activator and Reducing Agent Atom Transfer Radical Polymerization

Infections caused by bacteria represent a great motif of concern in the health area. Therefore, there is a huge demand for more efficient antimicrobial agents. Antimicrobial polymers have attracted special attention as promising materials to prevent infectious diseases. In this study, a new polymeric system exhibiting antimicrobial activity against a range of Gram-positive and Gram-negative bacterial strains at micromolar concentrations (e.g., 0.8 μM) was developed. Controlled linear and star-shaped copolymers, comprising hydrophobic poly(butyl acrylate) (PBA) and cationic poly(3-acrylamidopropyl)trimethylammonium chloride) (PAMPTMA) segments, were obtained by supplemental activator and reducing agent atomtransfer radical polymerization (SARA ATRP) at 30 °C. The antibacterial activity of the polymers was studied by varying systematically the molecular weight (MW), hydrophilic/hydrophobic balance, and architecture. The MW was found to exert the greatest influence on the antimicrobial activity of the polymers, with minimum inhibitory concentration values decreasing with increasing MW. Live/dead membrane integrity assays and scanning electron microscopy analysis confirmed the bactericidal character of the synthesized PAMPTMA- (b)co-PBA polymers.

Copolymer-Templated Synthesis of Nitrogen-Doped Mesoporous Carbons for Enhanced Adsorption of Hexavalent Chromium and Uranium

Polyacrylonitrile (PAN) homopolymer and polyacrylonitrile-block-poly(n-butyl acrylate) (PAN-b-PBA) block copolymer were synthesized via supplemental activator reducing agent atom transfer radical polymerization and used as precursors to nitrogen-doped nanocarbons. Carbonization was performed at two different temperatures (500 and 800 °C) to fabricate nanocarbons with different structural properties and nitrogen contents. Copolymer-templated nitrogen-doped carbons (CTNCs) had larger surface area and higher mesoporosity than PAN homopolymer-templated nanocarbons (PANCs), due to the presence of PBA block acting as a sacrificial porogen. Adsorption performances of PANCs and CTNCs for Cr(VI) and U(VI) species were systematically studied. Due to the well-defined structure and larger surface area, CTNCs showed stronger adsorption ability than PANCs. The nitrogen atoms incorporated into the carbon framework led to higher electrostatic attraction for Cr(VI) anions at low pH and complexation with U(VI) cations at h...

The influence of using sodium dithionite as SARA agent in miniemulsion ATRP

ABSTRACTThe supplemental activator and reducing agent atom transfer radical polymerization (SARA ATRP) of butyl acrylate (nBA) and styrene (Sty) using miniemulsion is reported for the first time. The polymerization was carried out in the presence of Cu(II)Br2‐based catalytic systems using EHA6TREN or BPMODA* and sodium dithionite (Na2S2O4) as SARA agent. Kinetic data revealed a controlled polymerization for both monomers, with a very stringent control over the molecular weight distribution (Ð ≤ 1.2) but low monomer conversion. Reaction conditions were optimized in an attempt to understand the kinetics of polymerization, aiming to increase the final monomer conversion while maintaining the control over the polymerization. Self‐chain extension reactions revealed low chain end fidelity, which corroborate the impossibility of increasing monomer conversion even after the judicious variation of the main polymerization parameters (monomers, surfactant, deactivator, and Na2S2O4 concentrations, and its method of addition). The data presented suggest a particular feature of Na2S2O4 in these polymerization systems involving the significant formation of dead chains ends, which has never been observed for any other reported system using this SARA agent. In contrast, control ARGET miniemulsion experiments under the same reaction conditions and using ascorbic acid as reducing agent allowed to achieve high monomer conversions. © 2018 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2018, 56, 879–888

Synthesis of Poly(N-H benzamide)-b-poly(lauryl methacrylate)-b-poly(N-H benzamide) symmetrical triblock copolymers by combinations of CGCP, SARA ATRP, and SA ATRC

We design a novel ABA type triblock copolymer (triBCP) by performing efficient synthetic methods of chain-growth condensation polymerization (CGCP), supplemental activator and reducing agent atom transfer radical polymerization (SARA ATRP), and styrenics-assisted atom transfer radical coupling (SA ATRC). A well-defined poly(3-(N-(octyloxy)benzyl benzamide) having a 2-bromo-2-phenylacetate effective ATRP initiating site (i.e., POOBBA-BrPA) through CGCP following quantitative chain end modifications, was firstly synthesized. The POOBBA-BrPA macroinitiator then conducted chain extension with lauryl methacrylate (LMA) via SARA ATRP to obtain the POOBBA-b-PLMA-Br diBCP (Mn = 8800 and Mw/Mn = 1.15). This was followed by SA ATRC of POOBBA-b-PLMA-Br with a high extent of coupling (xc = 0.85, Mn = 15300, and Mw/Mn = 1.26). The obtained triBCP was further purified and the selective removal of the protecting group yielded poly(N-H benzamide)-b-poly(lauryl methacrylate)-b-poly(N-H benzamide) (i.e., PNHBA-b-PLMA-b-PNHBA) was conducted. The characterization of these copolymers was performed using 1H NMR, GPC, FT-IR, TGA, DSC, AFM and SAXS.

Deep eutectic solvents (DES): Excellent green solvents for rapid SARA ATRP of biorelevant hydrophilic monomers at ambient temperature

An eco-friendly type III deep eutectic solvent (reline: choline chloride/urea) was used for the supplemental activator and reducing agent atom transfer radical polymerization (SARA ATRP) of different biorelevant hydrophilic monomers (HEA: 2-hydroxyethyl acrylate, HEMA: 2-hydroxyethyl methacrylate and AMPTMA: (3-acrylamidopropyl)trimethylammonium chloride) near room temperature (30 °C). The polymerization of HEA mediated by a safe and inexpensive SARA agent (Na2S2O4) revealed controlled features, with polymers exhibiting low dispersity (Đ ≈ 1.3) throughout the course of the polymerization. Results also showed that typically, a slow and continuous feeding of the SARA agent to the reaction mixture afforded PHEA-Br with higher chain-end functionality and lower dispersity (Đ ≈ 1.1), in comparison to the one obtained without Na2S2O4 feeding. As proof-of-concept, purified PHEA-Br macroinitiators were used for the preparation of different well-defined block copolymers (PHEA-b-PAMPTMA and PHEA-b-PMA).

Increasing the Bile Acid Sequestration Performance of Cationic Hydrogels by Using an Advanced/Controlled Polymerization Technique.

To investigate the influence of the polymerization technique and the content of hydroxyl groups on the performance of new bile acid sequestrants based on PAMPMTA-co-PHEA (PAMPTMA: poly((3-acrylamidopropyl)trimethylammonium chloride); PHEA: poly(2-hydroxyethyl acrylate)) hydrogels. PAMPMTA-co-PHEA hydrogels were prepared using either free radical polymerization or supplemental activator and reducing agent atom transfer radical polymerization. The chemical structure and composition of the hydrogels was confirmed by both FTIR and ssNMR. The binding of sodium cholate as the model bile salt was evaluated in simulated intestinal fluid using HPLC. The degradation of the polymers was evaluated in vitro in solutions mimicking the gastrointestinal tract environment. The binding showed that an increase of the amount of HEA in the hydrogel lead to a decrease of the binding capacity. In addition, it was demonstrated for the first time that the hydrogels produced by SARA ATRP presented a higher binding capacity than similar ones produced by FRP. Finally, it was observed that copolymers of PAMPTMA-co-PHEA showed no sign of degradation in solutions mimicking both the stomach and the intestine environment. The use of an advanced polymerization technique, such as the SARA ATRP, could be beneficial for the preparation of BAS with enhanced performance.

Surface initiated supplemental activator and reducing agent atom transfer radical polymerization (SI-SARA-ATRP) of 4-vinylpyridine on poly(ethylene terephthalate)

Poly(ethylene terephthalate) (PET) substrates were modified by means of surface-initiated supplemental activator and reducing agent atom transfer radical polymerization (SI-SARA-ATRP) of 4-vinylpyridine (4VP). Substrates were pretreated in order to graft chloromethylbenzene (CMB) units capable of initiating the radical polymerization reaction of 4VP units. Surface characterization techniques, including Water Contact Angle (WCA), Attenuated Total Reflection (ATR), X-ray photoelectron spectroscopy (XPS), Atomic Force Microscopy (AFM) and Time-of-Flight Secondary Ion Mass Spectrometry (ToF-SIMS) showed a successful grafting of a stable, smooth and homogenous layer of p4VP. This process offers the advantages of a rapid, simplified and low cost strategy to chemically modify polymer substrates with covalently bonded layer of the pH responsive p4VP for different applications. Moreover, by using TOF-SIMS profiling, we were able to track a density gradient along the z-axis generated by the interpenetrating phases of the different layers of the final modified surface. Fact that we correlated to the various positions of initiation sites within the polyethylenimine (PEI) used for PET aminolysis prior to CMB grafting. Our strategy will be used in future work to graft other polymers for different applications where industrial scale viable options are needed.

Polyacrylonitrile-b-poly(butyl acrylate) Block Copolymers as Precursors to Mesoporous Nitrogen-Doped Carbons: Synthesis and Nanostructure

A series of polyacrylonitrile-block-poly(butyl acrylate) (PAN-b-PBA) copolymers were prepared by supplemental activator reducing agent atom transfer radical polymerization (SARA ATRP). These copolymers were then used as precursors to pyrolytic nanostructured carbons with the PAN block serving as a nitrogen-rich carbon precursors and the PBA block acting as a sacrificial porogen. The study revealed that while the size of mesopores can be controlled by the size of the porogenic block, the connectivity of pores diminishes with the decrease of the overall molecular weight of the precursor. This partial loss of mesopore connectivity was attributed to the weaker phase segregation between the blocks of shorter lengths inferred from the shape of small-angle X-ray scattering profiles and from the crystallinity of polyacrylonitrile phase.