Chain Transfer Process Research Articles

PH-labile and photochemically cross-linkable polymer vesicles from coumarin based random copolymer for cancer therapy

The stability of a drug payload inside a nanocarrier at physiological environment and the release of the said drug at specific tumor cells in a sustainable manner are the two most important factors that determine the efficiency of a smart targeted drug-delivery system. In this work, 2-hydroxyethyl methacrylate and a coumarin-based methacrylate monomer containing β-thiopropionate moiety were copolymerized via reversible addition-fragmentation chain transfer (RAFT) process, followed by characterization using NMR and GPC. The said copolymer self-assembled at physiological pH to form vesicular nano-aggregates which was confirmed using DLS, TEM and by fluorescence measurements. These vesicles were further stabilized by photochemical crosslinking via coumarin (2π + 2π) cycloaddition reaction. These cross-linked vesicles (CVs) exhibited a 38% reduction in premature drug leakage as compared to the uncross-linked vesicles (UCVs) at physiological pH. Additionally, a slow hydrolysis of the β-thiopropionate moieties under mildly acidic conditions prevalent in tumor cells resulted in disassembly of the vesicles, thereby releasing the loaded drug in a sustainable manner. Studies related to in vitro toxicity, efficiency of cellular uptake and pH-responsive antineoplastic activity of doxorubicin (DOX) loaded in the cross-linked vesicles (CVs) toward cancer cell lines were undertaken. A significant reduction in IC50 was noticed for DOX-loaded CVs in comparison to free DOX toward MG63 cancer cell lines, making these vesicles as potent nanocarrier systems for cancer therapy.

Catalytic living ring-opening metathesis polymerization with Grubbs' second- and third-generation catalysts.

In a conventional living ring-opening metathesis polymerization (ROMP), an equal number of ruthenium complexes to the number of polymer chains synthesized are required. This can lead to high loadings of ruthenium complexes when aiming for shorter polymers. Here, a reversible chain-transfer agent was used to produce living ROMP polymers from norbornene derivatives using catalytic amounts of Grubbs' ruthenium complexes. The polymers obtained by this method showed all of the characteristics of a living polymerization (that is, good molecular weight control, narrow molecular weight dispersities and the ability to form block copolymers). Monomers carrying functional moieties such as ferrocene, coumarin or a triisopropylsilyl-protected primary alcohol could also be catalytically polymerized in a living fashion. The method presented follows a degenerative chain-transfer process and is more economical and environmentally friendly compared with previous living ROMP procedures as it utilizes only catalytic amounts of costly and toxic ruthenium complexes.

One‐Pot Synthesis of Block Copolymers by a Combination of Living Cationic and Controlled Radical Polymerization

Front Cover: The in-situ switch between different controlled/living polymerization methods remains a challenging but powerful tool to expand the wealth of well-defined functional block copolymers. In article number 1800398, Ulrich S. Schubert and co-workers present an approach that bridges the gap between cationic ring-opening polymerization of 2-oxazolines and the reversible addition-fragmentation chain transfer process for the controlled synthesis of vinyl monomers in a straightforward manner and without the need for tedious purification steps.

Extended Exposure to Stiff Microenvironments Leads to Persistent Chromatin Remodeling in Human Mesenchymal Stem Cells.

Bone marrow derived human mesenchymal stem cells (hMSCs) are a promising cell source for regenerative therapies; however, ex vivo expansion is often required to achieve clinically useful cells numbers. Recent results reveal that when MSCs are cultured in stiff microenvironments, their regenerative capacity can be altered in a manner that is dependent on time (e.g., a mechanical dosing analogous to a chemical one). It is hypothesized that epigenomic modifications are involved in storing these mechanical cues, regulating gene expression, and ultimately leading to a mechanical memory. Using hydrogels containing an allyl sulfide cross‐linker and a radical‐mediated addition‐fragmentation chain transfer process, in situ softened hMSC‐laden hydrogels at different time points are achieved and the effects of short‐term and long‐term mechanical dosing on epigenetic modifications in hMSCs are quantified. Results show that histone acetylation and chromatin organization adapt rapidly after softening and can be reversible or irreversible depending on time of exposure to stiff microenvironments. Furthermore, epigenetic modulators are differentially expressed depending on the culture history. Collectively, these experiments suggest that epigenetic remodeling can be persistent and might be a memory keeper.

The investigation of butyl acrylate grafting using model alkyds

Four model alkyds (stearic, oleic, linoleic, and linolenic model alkyds) were copolymerized with butyl acrylate (BA) in the presence of AIBN or BPO. 1H and 2D gHMQC NMR, Soxhlet extraction, and gas chromatography were used to characterize model alkyd–BA systems. It was found that mechanisms of grafting BA onto model alkyds were dependent on the structure of fatty acids in the model alkyds. In stearic model alkyd hybrid systems, BA homopolymer was the predominate pathway with minimal grafting via hydrogen abstraction from polyol backbone followed by termination with propagating BA radicals. Oleic model alkyd–BA systems improved the degree of grafting by direct addition of the BA free radical to the double bonds. Severe retardation of BA polymerization was observed in both linoleic and linolenic model alkyd–BA systems due to the presence of double allylic sites. A chain transfer process subsequently dominates the other free radical pathways leading to a high degree of grafting.

One-Pot Synthesis of Ion-Containing CO2-Based Polycarbonates Using Protic Ionic Liquids as Chain Transfer Agents

An analysis of the construction of ion-containing CO2-based polycarbonates via metal-catalyzed immortal copolymerization of propylene oxide (PO) and carbon dioxide in the presence of protic ionic liquids (ILs) as chain transfer agents is described. The reactions were catalyzed by the binary (salen)CoO2CCF3/onium salt system in the absence of added solvent. On the basis of the results of this study, which includes 1H NMR and MALDI-TOF-MS data, it is clear that the role of the protic IL in this process is dominated by its anion. When the anion of the protic ionic liquid is nucleophilic, such as chloride, the protic ionic liquid acts as a cocatalyst in the reaction system for epoxide ring opening, and the chain transfer reaction initiated by the cation is completely suppressed. However, when the anion of the protic ionic liquid is non-nucleophilic, such as BF4–, the protic ionic liquid acts as an effective chain transfer agent to afford IL-based polycarbonates by rapid and reversible chain transfer processes...

Facile one-pot synthesis and solution behavior of poly(acrylic acid)-block-polycaprolactone copolymers

A metal-free protocol to obtain poly(acrylic acid)-block-polycaprolactone diblock copolymers (PAA-b-PCL) by a one-pot method involving simultaneous Reversible Addition-Fragmentation Chain Transfer (RAFT) and Ring Opening Polymerization (ROP) processes is reported. The strategy is based on the use of diphenyl phosphate (DPP) as catalyst and a bifunctional compound that acts as both chain transfer agent (CTA) in the acrylic acid RAFT polymerization process and co-initiator in the ε-caprolactone (ε-CL) ROP process. PAA-b-PCL diblock copolymers were obtained with near quantitative conversions of both monomers in a relatively short period of time. In aqueous solutions, PAA-b-PCL diblock copolymers self-assembled into pH- and ionic strength- responsive micellar structures.

One-Pot Synthesis of Block Copolymers by a Combination of Living Cationic and Controlled Radical Polymerization.

The reversible addition-fragmentation chain-transfer (RAFT) process represents a sophisticated polymerization technique for the preparation of tailored and well-defined polymers from acrylates, acrylamides, and (meth)acrylates. The direct switching from other methods, such as cationic polymerizations, without the need for tedious functionalization and purification steps remains challenging. Within this study, it is demonstrated that poly(2-oxazoline) (P(Ox)) macro chain-transfer agents (macro-CTAs) can be prepared through the quenching of the cationic ring-opening polymerization with a carbonotrithioate salt. The end-functionalization of the P(Ox)s is observed to be almost quantitative and the macro-CTAs could be directly used for RAFT polymerization without further purification. This one-pot procedure could be extended to a variety of (multi)block copolymers consisting of different 2-oxazolines and acrylates with good-to-excellent control. Kinetic studies revealed the controlled polymerization of block copolymers, which are further accessible for α- and ω-end-functionalization. The simplicity and versatility of the approach promise a straightforward access to block copolymers from cationic and controlled radical polymerizations.

Selective ethylene tetramerization with iron-based metal−organic framework MIL-100 to obtain C8 alkanes

Metal-organic framework MIL-100(Fe) evacuated under different temperatures were used as catalysts for selective ethylene tetramerization with alkylaluminum cocatalysts in a laboratory slurry reactor to obtain C8 alkanes, possibly as gasoline additives contributing to octane number. Depending on evacuation temperature, the surface area, the content of FeII and FeIII coordinatively unsaturated sites of MIL-100(Fe) both changed, which were found to be three main factors affecting oligomerization performance. MIL-100(Fe) evacuated at 250 °C with intact pore structure and high rate of FeII sites reached the maximal catalytic activity of 1.26 × 105 g/(molFe·h), and more than 80% of products were C8 mainly comprising branched and ringed alkanes. The high C8 selectivity was not attributed to the steric hindrance of the pore structure of MIL-100(Fe) but the nature of metal sites. The cocatalysts had obvious influence on oligomerization performance via scavenging capacities rather than chain transfer processes through alkylation.

Blood‐Catalyzed RAFT Polymerization

AbstractThe use of hemoglobin (Hb) contained within red blood cells to drive a controlled radical polymerization via a reversible addition‐fragmentation chain transfer (RAFT) process is reported for the first time. No pre‐treatment of the Hb or cells was required prior to their use as polymerization catalysts, indicating the potential for synthetic engineering in complex biological microenvironments without the need for ex vivo techniques. Owing to the naturally occurring prevalence of the reagents employed in the catalytic system (Hb and hydrogen peroxide), this approach may facilitate the development of new strategies for in vivo cell engineering with synthetic macromolecules.

From Tree to Tape: Direct Synthesis of Pressure Sensitive Adhesives from Depolymerized Raw Lignocellulosic Biomass.

We report a new and robust strategy toward the development of high-performance pressure sensitive adhesives (PSAs) from chemicals directly obtained from raw biomass deconstruction. A particularly unique and translatable aspect of this work was the use of a monomer obtained from real biomass, as opposed to a model compound or lignin-mimic, to generate well-defined and nanostructure-forming polymers. Herein, poplar wood depolymerization followed by minimal purification steps (filtration and extraction) produced two aromatic compounds, 4-propylsyringol and 4-propylguaiacol, with high purity and yield. Efficient functionalization of those aromatic compounds with either acrylate or methacrylate groups generated monomers that could be easily polymerized by a scalable reversible addition–fragmentation chain-transfer (RAFT) process to yield polymeric materials with high glass transition temperatures and robust thermal stabilities, especially relative to other potentially biobased alternatives. These lignin-derived compounds were used as a major component in low-dispersity triblock polymers composed of 4-propylsyringyl acrylate and n-butyl acrylate (also can be biobased). The resulting PSAs exhibited excellent adhesion to stainless steel without the addition of any tackifier or plasticizer. The 180° peel forces were up to 4 N cm–1, and tack forces were up to 2.5 N cm–1, competitive with commercial Fisherbrand labeling tape and Scotch Magic tape, demonstrating the practical significance of our biomass-derived materials.

Oxygen Tolerant and Room Temperature RAFT through Alkylborane Initiation.

A reversible addition-fragmentation chain transfer (RAFT) process was developed capable of being performed at room temperature and in the presence of oxygen by initiating polymerization through an alkylborane-amine complex. This air-stable alkylborane-amine complex was chemically deblocked with carboxylic acid or isocyanate functionalities to liberate a reactive trialkylborane that consumes oxygen and generates radicals to mediate RAFT. Alkylborane-initiated RAFT (AI-RAFT) was demonstrated to allow the synthesis of a wide range of polymer molecular weights with narrow distributions. Rapid polymerization was also possible within minutes under an ambient environment without any prior deoxygenation. Optimal conditions were investigated revealing that carboxylic acids are required in larger excess to alkylborane versus isocyanates and that deblocker functionality can have an impact on polymerization kinetics, achievable molecular weight, and dispersity. Living chain-ends were confirmed by synthesizing block copolymers using AI-RAFT-derived macro-chain transfer agents. In this preliminary study, a chemically induced RAFT process is introduced without requirement of any thermal, photochemical, electrical, or mechanical stimulus capable of polymerizing acrylamide, acrylate, and methacrylate monomers in limited amounts of oxygen at room temperature.

RAFT Polymerization of Tert-Butyldimethylsilyl Methacrylate: Kinetic Study and Determination of Rate Coefficients.

Well-defined poly(tert-butyldimethylsilyl methacrylate)s (TBDMSMA) were prepared by the reversible addition-fragmentation chain transfer (RAFT) process using cyanoisopropyl dithiobenzoate (CPDB) as chain-transfer agents (CTA). The experimentally obtained molecular weight distributions are narrow and shift linearly with monomer conversion. Propagation rate coefficients (kp) and termination rate coefficients (kt) for free radical polymerization of TBDMSMA have been determined for a range of temperature between 50 and 80 °C using the pulsed laser polymerization-size-exclusion chromatography (PLP-SEC) method and the kinetic method via steady-state rate measurement, respectively. The CPDB-mediated RAFT polymerization of TBDMSMA has been subjected to a combined experimental and PREDICI modeling study at 70 °C. The rate coefficient for the addition reaction to RAFT agent (kβ1, kβ2) and to polymeric RAFT agent (kβ) is estimated to be approximately 1.8 × 104 L·mol−1·s−1 and for the fragmentation reaction of intermediate RAFT radicals in the pre-equilibrium (k-β1, k-β2) and main equilibrium (k-β) is close to 2.0 × 10−2 s−1. The transfer rate coefficient (ktr) to cyanoisopropyl dithiobenzoate is found to be close to 9.0 × 103 L·mol−1·s−1 and the chain-transfer constant (Ctr) for CPDB-mediated RAFT polymerization of TBDMSMA is about 9.3.

PET-RAFT polymerisation: towards green and precision polymer manufacturing.

The necessity of sustainable development in the chemical industry has continuously drawn attention to find safe, environmentally friendly and atom-economic chemical processes, which is defined in the 12 principles of green chemistry. Merging photoredox catalysis and reversible addition-fragmentation chain transfer (RAFT) polymerisation, the photoinduced electron/energy transfer (PET)-RAFT process has opened up a new way of performing reversible deactivation radical polymerisation for well-defined polymer synthesis using light as an external stimulus. While providing an increased level of control (spatiotemporal, wavelength, and intensity control) over the polymerisation, PET-RAFT has many attractive attributes (abundant catalyst availability, catalyst recyclability, selectivity and oxygen tolerance) to be green and sustainable, which is intriguing for precision polymer manufacturing in industry.

A light-mediated metal-free atom transfer radical chain transfer reaction for the controlled hydrogenation of poly(vinylidene fluoride-chlorotrifluoroethylene)

A light-mediated atom transfer radical chain transfer process is proposed for the controlled hydrogenation of P(VDF-CTFE) using metal-free photocatalyst.

The effect of RAFT polymerization on the physical properties of thiamphenicol-imprinted polymer

The necessity to overcome limitation of conventional free radical polymerization, technology has shifted the way to find an effective method for polymer synthesis, called controlled radical polymerization (CRP). One of the most studied controlled radical system is reversible addition-fragmentation chain transfer (RAFT) polymerization. The method relies on efficient chain-transfer processes which are mediated typically by thiocarbonyl-containing RAFT agents e.g., dithioesters. The presented study revealed the potential benefit in applying RAFT polymerization towards the synthesis of molecularly imprinted polymer for thiamphenicol. They were synthesized in monolithic form using methacrylic acid, ethylene glycol dimethacrylate, azobisisobutyronitrile and acetonitrile as a functional monomer, cross-linker, initiator and porogen, respectively. The surface morphology was studied by scanning electron microscopy (SEM), structural characterization by Fourier transformed infrared (FTIR) and pore structures of polymers produced were characterized by nitrogen sorption porosimetry. SEM analysis showed MIPs produced by RAFT have smoother surface while porosity analysis showed the specific surface area was slightly larger compared to conventional polymerization methods. However FTIR showed the same pattern of spectra produced due to the same co-monomers used in the production. The results upon the uses of RAFT polymerization enables the production of imprinted polymers enhanced the physical properties compared to conventional polymerization.

Thermal decomposition of HFO-1234yf through ReaxFF molecular dynamics simulation

The thermal decomposition of HFO-1234yf with O2 was studied by ReaxFF molecular dynamics simulation at the wide temperature ranges of 1900–3500K. The results show that the initial reactions of HFO-1234yf pyrolysis including CC cleavage, CH cleavage and CF cleavage starts at 2100K and then release free radicals (CF3, F and H). The oxidation reaction starts at 2500K and numerous intermediates (H2O, CF3OH and FCOOH) are produced. The main products observed from simulation are HF, COF2 and CO2 and these products agree with the result of related experiments. Ten formation pathways of primary products are observed from ReaxFF. The concentrations of free radicals (FCOO, F, H, HOO and OH) have a great impact on the reaction activity of HFO-1234yf oxidation. The chain transfer process is primarily carried by the conversion from HOO to OH radical. Our work presents the decomposition mechanisms of HFO-1234yf with O2 from the molecule level and provides a reference for the study of the thermal stability of organic working fluids.

Effective and Specific Gene Silencing of Epidermal Growth Factor Receptors Mediated by Conjugated Oxaborole and Galactose-Based Polymers.

Oxaborole-based polymers are stimuli-responsive materials that can reversibly interact with diols at pH values higher than their pKa. The strong binding of the oxaborole with cis-hydroxyl groups allow rapid cross-linking of the polymer chains. In this study, we exploited this phenomenon to develop a novel delivery system for the complexation, protection, and delivery of epidermal growth factor receptors (EGFR) siRNA (small interfering RNA). Galactose and oxaborole polymers were first synthesized by the reversible addition-fragmentation chain transfer (RAFT) process, and they were found to show a robust interaction with each other via the oxaborole-diol effect, which allowed the formation of stable polyplexes with siRNA. Although complexes were successfully formed between the neutral galactose and oxaborole-based polymers, these complexes were insufficient in the protection of the siRNA. Therefore, cationic glycopolymers and oxaborole polymers were investigated showing superior complexation with siRNA and exhibiting effective gene silencing in HeLa (cervical) cancer cells, while showing low toxicity. Gene silencing of up to 60% was achieved with these new complexes in the presence and absence of serum. The excellent stability of the complexes under physiological conditions and the observed low cytotoxicity 48 h post-transfection demonstrated the high potential of this new system for gene silencing therapy application in clinics.

Regioselective Carbyne Transfer to Ring-Opening Alkyne Metathesis Initiators Gives Access to Telechelic Polymers.

Regioselective carbyne-transfer reagents derived from (3,3,3-trifluoroprop-1-yn-1-yl)benzene give access to functionalized ring-opening alkyne metathesis polymerization (ROAMP) initiators [R-C6H4C≡Mo(OC(CH3)(CF3)2)3] featuring electron-donating or -withdrawing substituents on the benzylidyne. Kinetic studies and linear free-energy relationships reveal that the initiation step of the ring-opening alkyne metathesis polymerization of 5,6,11,12-tetradehydrobenzo[a,e][8]annulene exhibits a moderate positive Hammett reaction constant (ρ = +0.36). ROAMP catalysts featuring electron-withdrawing benzylidynes not only selectively increase the rate of initiation (ki) over the rate of propagation (kp) but also prevent undesired intra- and intermolecular chain-transfer processes, giving access to linear poly-(o-phenylene ethynylene) with narrow molecular weight distribution. The regioselective carbyne transfer methodology and the detailed mechanistic insight enabled the design of a bifunctional ROAMP-reversible addition-fragmentation chain-transfer (RAFT) initiator complex. ROAMP followed by RAFT polymerization yields hybrid poly-(o-phenylene ethynylene)-block-poly-(methyl acrylate) block copolymers.

Amphiphilic ABA‐type triblock copolymers for the development of high‐performance poly(vinylidene fluoride)/poly(vinyl pyrrolidone) blend ultrafiltration membranes for oil separation

ABSTRACTABA‐type amphiphilic triblock copolymers (TBCs) were synthesized by a reversible addition fragmentation chain transfer (RAFT) process with a telechelic polystyrene macro‐RAFT agent and 4‐[n‐(acryloyloxy)alkyloxy]benzoic acid monomers. Ultrafiltration (UF) membranes were fabricated by a phase‐inversion process with blends of the TBC, poly(vinylidene fluoride) (PVDF), and poly(vinyl pyrrolidone) (PVP) in dimethylformamide. The UF‐fabricated membranes were characterized by scanning electron microscopy, atomic force microscopy, water contact angle measurement, thermogravimetric analysis, and differential scanning calorimetry. Pure water permeation, molecular weight cutoff values obtained by the permeation of different molecular weight polymers as probe solutes, bovine serum albumin (BSA) solution permeate flux, and oil–water emulsion filtration tests were used to evaluate the separation characteristics of the fabricated membranes. The tripolymer blend membranes exhibited a higher flux recovery ratio (FRR) after the membrane was washed with sodium lauryl sulfate (0.05 wt %) solution for a BSA solution (FRR = 88%) and oil–water emulsion (FRR = 95%) feeds when than the PVDF–PVP blend membrane (57 and 80% FRR values for the BSA solution and oil–water emulsion, respectively). The pendant carboxylic acid functional moieties in this ABA‐type TBC have potential advantages in the fabrication of high‐performance membranes. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017, 134, 45132.