Activators Generated By Electron Transfer Research Articles

Copper Nanodrugs by Atom Transfer Radical Polymerization

In this study, some copper catalysts used for atom transfer radical polymerization (ATRP) were explored as efficient anti‐tumor agents. The aqueous solution of copper‐containing nanoparticles with uniform spheric morphology was in situ prepared through a copper‐catalyzed activator generated by electron transfer (AGET) ATRP in water. Nanoparticles were then directly injected into tumor‐bearing mice for antitumor chemotherapy. The copper nanodrugs had prolonged blood circulation time and enhanced accumulation at tumor sites, thus showing potent antitumor activity. This work provides a novel strategy for precise and large‐scale preparation of copper nanodrugs with high antitumor activity.

Copper Nanodrugs by Atom Transfer Radical Polymerization.

In this study, some copper catalysts used for atom transfer radical polymerization (ATRP) were explored as efficient anti-tumor agents. The aqueous solution of copper-containing nanoparticles with uniform spheric morphology was in situ prepared through a copper-catalyzed activator generated by electron transfer (AGET) ATRP in water. Nanoparticles were then directly injected into tumor-bearing mice for antitumor chemotherapy. The copper nanodrugs had prolonged blood circulation time and enhanced accumulation at tumor sites, thus showing potent antitumor activity. This work provides a novel strategy for precise and large-scale preparation of copper nanodrugs with high antitumor activity.

Novel Copper-Based Catalytic Systems for Atom Transfer Radical Polymerization of Acrylonitrile

Atom Transfer Radical Polymerization (ATRP) is an effective catalytic process leading to well-defined polymers with desired properties. This process based on reversible deactivation of propagating chains has a lower rate in comparison with conventional radical polymerization, especially in the case of obtaining polymers with high molecular weights. Thus, the increase of the rate of this process with preserving control over molecular weight distribution is a challenging task. In this work, novel catalytic systems for Activators Generated by Electron Transfer (AGET) ATRP of acrylonitrile based on copper (II) bromide complexes were proposed. It was found that Rochelle salt (potassium sodium tartrate tetrahydrate) may be used as a reducing agent for regeneration of copper-based catalysts to increase the rate of the process. The provided UV-vis spectroscopy experiments have confirmed the reducing ability of tartaric anion. It was found that the use tandem catalytic system based on two copper complexes with different ligands also increases the polymerization rate. The performed experiments allowed us to develop a catalytic system for rapidly obtaining polyacrylonitrile polymers with desired molecular weights exceeding 100 kDa.

Thermally Stable Copolymers with Pendant “N-Arylimide” Groups Via Reversible Deactivation Radical Polymerization Technique

This paper reports the synthesis of copolymers of N-arylitaconimides (NAI) and methyl methacrylate (MMA) with random architecture via activator generated electron transfer atom transfer radical polymerization (AGET-ATRP) method, resulting in N-arylimide as pendant group.The AGET-ATRP is a versatile and famous reversible deactivation radical polymerization technique used to synthesize the well defined polymers. The structural characterizations of obtained copolymers were done using FT-IR, 1H-NMR spectroscopy and elemental analysis. The molecular weights of copolymers were in the range 8,000-20,000 g/ mol with a narrow polydispersity index i.e. 1.2-1.3. Thermal characterization of Poly(NAI-ran-MMA) copolymers were done using differential scanning calorimetry (DSC) and thermogravimetric analysis (TG/ DTG). DSC scans show 60-117% enhancements in the glass transition temperature (Tg), as compared to Poly(methyl methacrylate). The rate of copolymerization, molecular weight and Tg were observed to increase with increase in electron releasing nature of the substituent on aromatic ring of the pendant group.

Novel Amphiphilic Polyfluorene-Graft-(Polymethacrylic Acid) Brushes: Synthesis, Conformation, and Self-Assembly.

Novel polyfluorene polymer brushes with polymethacrylic acid side chains were obtained by atom transfer radical polymerization (ATRP) and activator generated by electron transfer (AGET) ATRP of tert-butyl methacrylate on polyfluorene multifunctional macroinitiator, followed by protonolysis of the tert-butyl groups of the side chains. Kinetics of polymerization and molecular weights were fully characterized. These polymer brushes luminesce in the blue region of the spectrum with high quantum yields (0.64–0.77). It was shown that the luminescence intensity of polymer brushes is higher than the luminescence intensity of the macroinitiator (0.61). Moreover, due to their amphiphilic nature, they can form unimolecular micelles when an alcohol solution of the polymer brush is injected into water. These properties can potentially be used in drug delivery and bioimaging.

Remote Performance Modulation of Ultrafiltration Membranes by Magnetically and Thermally Responsive Polymer Chains.

Ultrafiltration membranes, that respond to an external magnetic field and local temperature have been developed. Surface-initiated activator-generated electron transfer (AGET) atom transfer radical polymerization (ATRP) has been used to graft poly(N-isopropylacrylamide) (PNIPAm) from the surface of 300 kDa regenerated cellulose membranes. The polymerization initiator was selectively attached to the entire membrane surface, only the outer membrane surface or only the inner pore surface. A superparamagnetic nanoparticle was attached to the end of the polymer chain. The DI water flux as well as the flux and rejection of bovine serum albumin were investigated in the absence and presence of a 20 and 1000 Hz oscillating magnetic field. In an oscillating magnetic field, the tethered superparamagnetic nanoparticles can cause movement of the PNIPAm chains or induce heating. A 20 Hz magnetic field maximizes movement of the chains. A 1000 Hz magnetic field leads to greater induced heating. PNIPAm displays a lower critical solution temperature at 32 °C. Heating leads to collapse of the PNIPAm chains above their Lower Critical Solution Temperature (LCST). This work highlights the versatility of selectively grafting polymer chains containing a superparamagnetic nanoparticle from specific membrane locations. Depending on the frequency of the oscillating external magnetic field, membrane properties may be tuned.

Kinetics of MMA Atom Transfer Radical Polymerization Initiated by Reducing Agent in Stirred Batch Emulsion Reactor

AbstractAb initio emulsion atom transfer radical polymerization (ATRP) differs from regular emulsion polymerization because the kinetic and thermodynamic aspects of each process are very unlikely alike. This paper presents a kinetic analysis of activator generated by electron transfer (AGET) ATRP of methyl methacrylate (MMA) in a stirred emulsion reactor. The focus of the study is to assess the variation of the monomer content in the organic phase and the rate polymerization for different reaction temperatures, as well as the impact of surfactant content and stirring speed on latex stability. Poly(methyl methacrylate) (PMMA) polymer samples are analyzed by means of gravimetry, dynamic light scattering, gel permeation chromatography, and HNMR techniques to determine monomer conversion, polymer particle diameter, molecular weight distribution, and polymer molecular structure, respectively. The results show the production of PMMA of narrow polydispersity index (Ð) and low molar mass (Mn) for MMA conversion around 60% and detect two‐regions instead of a three‐regions trend of rate of polymerization (Rp) as conventional emulsion polymerization. The reaction rate increases during the nucleation stage and then flattens over an invariant trend which confirms a living feature of the AGET ATRP polymerization. The average number of radicals per latex particle (ñ) is also debated.

Construction of macroinitiators labeled magnetic spheres as a notable signal amplification system for biosensing

Here we report macroinitiators labeled magnetic spheres (MSs) as a notable signal amplification system for biosensing. The macroinitiators as labels with multiple initiators on each polymer backbone facilitate the polymerization process for fluorescent signal amplification, while the carriers of micro-sized MSs are beneficial to reaction kinetics and could be rapidly read via flow cytometer in a high-throughput way. By utilizing an optimal two-step activators generated electron transfer for atom transfer radical polymerization (AGET ATRP) reaction, our proposed macroinitiators labeled MSs strategy exhibits a significantly superior fluorescent signal amplification effect when compared to conventional dye-labeled MSs, indicating the promising potential for biosensing in diagnostic fields.

Controlling gelation time of in situ polymerization of gel system through AGET ATRP principle

To better control the gelation time of in situ polymerization of gel system in reservoir, an activator regenerated by AGET (activator generated by electron transfer) ATRP (atom transfer radical polymerization) initiating system was developed. The AGET ATRP initiating system was composed of an initiator 1,2-dibromoethane, a catalyst ferric chloride and a reducing agent vitamin C, and the effects of these three component proportions on the gelation time and gel viscosity were systematically investigated. Results of bottle tests indicated that the gelation time can even be more than 20 h at 60 °C at optimal concentration ratios. Moreover, the viscosity decreased and the gelation time increased with the increase of salinity and temperature. The gelation time of the core test was 1.5 times or even longer in comparison with that of the bottle test owing to the influences of dilution, adsorption, and rock skeleton isolation. It was also confirmed that the AGET ATRP initiating system can initiate the cross-link gelation of monomers in the core. The enhanced oil recovery result indicated that the oil recovery increased by 9.17% after the gelation of the gelling solutions, and final oil recovery was 40.05%. This research provided a brand-new method to control the gelation time of the in situ polymerization of gel system.

Activator Generated Electron Transfer Combined Atom Transfer Radical Polymerization (AGET-ATRP) for Controlled Grafting Location of Glycidyl Methacrylate on Regenerated Cellulose Ultrafiltration Membranes

This investigation indicates the ability to selectively graft glycidyl methacrylate (GMA) only from the external surface of regenerated cellulose (RC) ultrafiltration (UF) membranes using activator generated electron transfer (AGET) atom transfer radical polymerization (ATRP). This controlled polymerization resulted in epoxy functionalized polymer brush ends. Further reaction of the terminal epoxy groups provides a flexible platform to introduce desired functionalities either by electrophilic or nucleophilic epoxy ring opening. Selective grafting from the external membrane surface was achieved by using an appropriate pore filling solvent prior to modification. A high viscosity pore filling solvent that is immiscible with the reactive monomer solution used during surface modification was the most effective in supressing grafting from the internal pore surface. The effects of grafting on membrane performance were evaluated by determining water permeability and protein rejection.

Epoxy functionalized polymer grafted magnetic nanoparticles by facile surface initiated polymerization for immobilization studies of Candida Antarctica lipase B

Immobilization of Candida Antarctica lipase B (CalB) was done on the epoxy functionalized polymer (EFP) grafted magnetic nanoparticles (MNPs) via covalent attachment with the active epoxy groups. The EFP brushes were grafted on iron-oxide based MNPs by a facile surface-initiated atom transfer radical polymerization (ATRP) using activators generated by electron transfer (AGET) of glycidyl methacrylate (GMA). Each step of the surface modification, polymer grafting, and enzyme immobilization process on the polymer grafted MNPs was studied using Fourier transform infrared spectroscopy (FTIR). A thermogravimetric analysis (TGA) calculated the amount of engineered organic components, a transmission electron microscopy (TEM) visualized the core-shell formation of the MNPs, and a vibrating sample magnetometer (VSM) validated their magnetic properties at various modification stages. The lipase immobilization efficiency was described as a function of immobilization time, as well as, enzyme amount. The activity was characterized within a range of pH, temperature, kinetic parameters, resusability and storage stability, for both the free and immoblized Cal-B enzyme. The results of this study suggested that poly(GMA) grafted MNPs can be successfully used for the immobilization of Cal-B with improved efficiencies compared to those obtained with free soluble lipase. The reported enzyme immobilization method appears to be reproducible and scalable for industrial production.

Atom transfer coupling reactions performed with benign reducing agents and radical traps

ABSTRACTMonobrominated polystyrene (PSBr) was prepared by ATRP, and the resulting chain ends were activated in the presence of radical traps to induce chain end‐coupling. In atom transfer radical coupling (ATRC) with radical trap assistance, to achieve significant coupling requires excess metal catalyst, ligand, and a reducing agent that is often additional metal. In this work, activators generated by electron transfer (AGET) and radical trap assistance are used in the ATRC sequence to successfully lead to chain‐end coupling without the need for the oxidatively unstable copper (I) and with environmentally friendlier agents in place of copper metal. High extents of coupling (Xc) were achieved using ascorbic acid (AA) as the reducing agent and copper(II) bromide as the oxidized version of the catalyst, and when combined with AGET ATRP to prepare the PSBr precursor, only a fraction of the total metal was required compared to traditional atom transfer reactions, while still retaining similar Xc values. © 2019 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2019, 57, 2113–2120

Experimental Design and Statistical Analysis of AGET ATRP of MMA in Emulsion Polymer Reactor

AbstractThis study investigates atom transfer radical polymerization (ATRP) of methyl methacrylate (MMA) using activators generated by electron transfer (AGET) as the initiation technique in an emulsion well‐mixed 2L stirred tank reactor. The performance of the AGET ATRP of MMA is analyzed for five key independent variables, namely temperature, catalyst complex (CuBr2/dNbpy), initiator (EBiB), reducing agent (ascorbic acid), and surfactant (Brij 98). The reaction is carried out based on a two‐step polymerization procedure. A resolution 5 fractional factorial design technique is employed to assess the influence of the five independent variables on the monomer conversion, polymer average molecular weights, and polydispersity index (PDI). An input–output model is constructed from the data of 21 designed experimental tests. A statistical analysis of the results shows that the temperature is the most influential variable for the three output process responses. The initiator strongly affects the poly(methyl methacrylate) (PMMA) molecular weights. It is the least important key variable affecting MMA conversion and PDI, and the surfactant is the least one affecting PMMA Mn. On assessing the independent interactions effect, the interactions of temperature‐surfactant on conversion, and temperature‐initiator for PMMA Mn are considered. Process simulation in 3D mapping has demonstrated that model predictions agree well with experimental data.

Controlling external versus internal pore modification of ultrafiltration membranes using surface-initiated AGET-ATRP

The activators generated electron transfer (AGET) method coupled with atom transfer radical polymerization (ATRP) is shown to be a simple and well controlled approach for surface-initiated polymerization of 2-hydroxyethyl methacrylate (HEMA) on regenerated cellulose (RC) membranes. The AGET-ATRP method has been optimized with respect to the initiator concentration, the polymerization reaction time and the reducing agent (activator) concentration. Control of polymer grafting on the external membrane surface versus the internal pore surface of RC ultrafiltration membranes was investigated using different pore filling solvents having a wide range of viscosity and reactivity during ATRP initiator immobilization via acylation of RC hydroxyl groups. The effectiveness of the pore filling solvent in limiting grafting inside the membrane pores was found to depend on both its viscosity and reactivity. Rejection of BSA and dextran was used to probe changes in pore size. Glycerol was found to be the most effective pore filling solvent, indicated by a significant degree of modification of the membrane surface with grafted polyHEMA but only a very minor increase in solute rejection.

A novel polymer-grafted hydrophobic charge-induction chromatographic resin for enhancing protein adsorption capacity

Hydrophobic charge-induction chromatography (HCIC) is a developing technology for antibody purification. To enhance the protein adsorption capacity, a novel polymer-grafted HCIC resin was developed, in which the surface-initiated activator generated by electron transfer (AGET) atom transfer radical polymerization (ATRP) was explored as a controlled polymerization technique to reconstruct matrix structure and ligand distribution. Using poly(glycidyl methacrylate, GMA) as grafting polymer and 2-mercapto-1-methyl-imidazole (MMI) as functional ligand, poly(GMA)-grafted HCIC resins were prepared with series of grafting and ligand densities. Adsorption behaviors of human immunoglobulin G (hIgG) on the prepared resins demonstrated the necessity of controlling grafting and ligand density. Saturated adsorption capacity (Qm) and effective pore diffusivity (De) reached the maximum under medium ligand density when the grafting density was kept constant. The highest Qm and De values were found under the highest grafting density, which were 73% and 7.17times higher than the non-grafted resin, respectively. Column breakthrough tests indicated that the dynamic binding capacity of the resin with optimized grafting density and ligand density was up to 34.6mg/g when linear velocity was 300cm/h, which was 86.3% higher than dextran-grafted resin. The resin was then used to separate hIgG from a protein mixture (hIgG/human serum albumin=1:4), high purity (>99%) and recovery (>90%) of hIgG were found with 50-cycle reuses, which verified the selectivity and robustness of G-MMI resin prepared. In general, the surface-initiated AGET ATRP provides a controlled grafting strategy to improve protein binding capacity for chromatographic separation, and new resins developed have great potential in large-scale protein purification applications.

Synthesis of poly(n‐butyl acrylate) homopolymer and poly(styrene‐b‐n‐butyl acrylate‐b‐styrene) triblock copolymer via AGET emulsion ATRP using a cationic surfactant

ABSTRACTCationic emulsions of triblock copolymer particles comprising a poly(n‐butyl acrylate) (PnBA) central block and polystyrene (PS) outer blocks were synthesized by activator generated by electron transfer (AGET) atom transfer radical polymerization (ATRP). Difunctional ATRP initiator, ethylene bis(2‐bromoisobutyrate) (EBBiB), was used as initiator to synthesize the ABA type poly(styrene‐b‐n‐butyl acrylate‐b‐styrene) (PS‐PnBA‐PS) triblock copolymer. The effects of ligand and cationic surfactant on polymerizations were also discussed. Gel permeation chromatography (GPC) was used to characterize the molecular weight (Mn) and molecular weight distribution (MWD) of the resultant triblock copolymers. Particle size and particle size distribution of resulted latexes were characterized by dynamic light scattering (DLS). The resultant latexes showed good colloidal stability with average particle size around 100–300 nm in diameter. Glass transition temperature (Tg) of copolymers was studied by differential scanning calorimetry (DSC). © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2016, 54, 611–620

Synthesis of multi-functional nanocapsules via interfacial AGET ATRP in miniemulsion for tumor micro-environment responsive drug delivery

Novel multi-functional polymeric hollow nanocapsules (PHN) based on the crosslinked poly(tert-butyl acrylate) (PtBA) shells were synthesized in a miniemulsion interfacial polymerization via activator generated electron transfer atom transfer radical polymerization (AGET ATRP) technique with N,N′-bis(acryloyl) cystamine (BACy) as cross-linking agent, CuBr2 as catalyst, ascorbic acid (VC) as reducing agent and hexadecane as inert solvent. In the AGET ATRP, a folate-conjugated block copolymer, folate-poly(ethylene glycol)-b-poly(tert-butyl acrylate) (FA-PEG-tBA-Br), was used as macroinitiator/stabilizer, and the specific amphiphilic nature of the copolymer led the extending inward of polymer chains. The DLS analysis directly showed the PHN with an average diameter of 150nm was obtained. After the PtBA shells were transformed into poly(acrylic acid) (PAA) by hydrolysis, doxorubicin (DOX), as a model drug, was loaded efficiently into the hydrolyzed polymeric hollow nanocapsules (HPHN), then the in vitro release of drug was carried out in phosphate buffer solution (PBS, pH 7.4 or 5.0, with or without DTT or GSH of different concentrations). It showed that the existence of folate group significantly improved pH stimuli-responsive and DOX-loading capacity of the polymeric nanocapsules. An acidic pH (5.0) and presence of GSH would accelerate the DOX release behavior. Thus, these multi-functional polymeric nanocapsules have excellent available properties in the field of targeted and controlled drug delivery for cancer therapy.

Expanded corn starch as a versatile material in atom transfer radical polymerization (ATRP) of styrene and methyl methacrylate

Polymerization of styrene (St) and methyl methacrylate (MMA) was performed by surface initiated (SI) and activator generated by electron transfer (AGET) systems of atom transfer radical polymerization (ATRP) using renewable expanded corn starch (ECS) as a support. This prepared ECS is found to have V type crystallinity with 50m2g−1 surface area (<1m2g−1 for corn starch (CS)) and average pore volume of 0.43cm3g−1 (<0.1cm3g−1 for CS). In SI-ATRP, hydroxyl groups on ECS were converted into macro-initiator by replacing with 2-bromoisobutyryl bromide (BIBB) with a 0.06 degree of substitution determined from NMR. In AGET-ATRP, CuBr2/ligand complex get adsorbed on ECS (CuII/ECS=10wt.%) to catalyze the polymerization. Synthesized PS/PMMA was characterized by SEM, FT-IR, 1H NMR.

Homogeneous Fe-Mediated AGET ATRP of Methyl Methacrylate in PEG-400 in the Presence of Na2CO3

The activator generated by electron transfer (AGET) atom transfer radical polymerization (ATRP) of methyl methacrylate (MMA) was successfully carried out in poly(ethylene glycol) (PEG-400) with CCl4/FeCl3·6H2O/N,N,N′,N′-tetramethyl-1,2-ethanediamine (TMEDA) as the initiating system in the presence of Na2CO3. The living nature of the polymerization was confirmed by kinetic studies, end-group analysis and chain extension. The molecular weight distribution (MWD) of the polymer obtained was quite narrow (MWD = 1.10–1.40). The effects of ligand and temperature on polymerization were investigated. Based on the slope of the plot of ln (kapp) vs. (1/T), the apparent activation energy (Eapp) of 34.1 kJ mol−1 was calculated. The recovering and recycling of PEG-400 were first investigated. After the polymerization and isolation of PMMA, the mixture containing catalysts and PEG-400 was shown to be recoverable and recyclable without further treatment.

Kinetic Studies of Atom Transfer Radical Polymerisations of Styrene and Chloromethylstyrene with Poly(3-hexyl thiophene) Macroinitiator

Poly(3-hexyl thiophene)-b-poly(styrene-co-chloromethylstyrene) copolymers, to be used as a prepolymer for preparing donor-acceptor block copolymers for organic solar cells, have been synthesised by reacting P3HT macroinitiators with styrene and chloromethylstyrene via three types of atom transfer radical polymerisation (ATRP) systems, which are (1) a normal ATRP, (2) activators generated by electron transfer (AGET), and (3) a simultaneous reverse and normal initiation (SR&amp;NI). The kinetics of these ATRP systems were studied as a function of monomers to the macroinitiator molar ratio. It was found that all of the three types of ATRP systems led to first order kinetics with respect to monomers. The highest rate constant (k) of 3.4 × 10−3 s−1was obtained from the SR&amp;NI ATRP system. The molecular weights of the product determined by the GPC were lower than were the theoretical values. The result was discussed in light of the chain transfer reaction to the poly(chloromethylstyrene) repeating units. Morphology of the synthesized block copolymers, examined by an atomic force microscopy (AFM), were also compared and discussed.