Hydrogen Transfer Polymerization Research Articles

Synthesis and characterization of amphiphilic Poly(2-hydroxyethyl acrylate-g-α-Methyl-β-Alanine) by Nitroxide-Mediated Polymerization Using “grafting through” approach

Oligomeric poly(α-methyl-β-alanine)with vinyl end-group (PmBA) was synthesized via base-catalyzed hydrogen-transfer polymerization (HTP) of molten methacrylamide (MAm) in the presence of sodium tert-butoxide (t-BuONa). The PmBA was used as a comonomer in the synthesis of amphiphilic poly(2-hydroxyethyl acrylate-g-α-methyl-β-alanine) (PHEA-g-PmBA)via nitroxide-mediated polymerization (NMP)and "grafting through" approach.The graft copolymer formation was confirmed byproton nuclear magnetic resonancespectroscopy (1H-NMR), Fourier-transform infrared spectroscopy (FT-IR), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), and static light scattering (SLS)measurements. Thermogravimetric analysis of the amphiphilicPHEA-g-PmBAexhibited a multi-step decomposition curve corresponding to the α-methyl-β-alanine and the 2-hydroxyethyl acrylate blocks at about 306, 369, and 403 °C.DSC curve of the copolymer has a baseline shift at −12.87 °C attributed to the glass transition temperature. SLS analysis of the final product resulted in a weight average molecular weight of 83.6 kDa. The spectroscopic and thermal analyses proved that amphiphilicPHEA-g-PmBA was successfully synthesized through HTP and NMP.

Preparing Degradable Polymers with Promising Mechanical Properties by Hydrogen Transfer Polymerization

Preparing Degradable Polymers with Promising Mechanical Properties by Hydrogen Transfer Polymerization

Hydrophobicity Regulates the Cellular Interaction of Cyanine5-Labeled Poly(3-hydroxypropionate)-Based Comb Polymers.

An in-depth understanding of the effect of physicochemical properties of nanocarriers on their cellular uptake and fate is crucial for the development of novel delivery systems. In this study, well-defined hydrophobic carboxylated poly(3-hydroxypropionate)-based comb polymers were synthesized. Two oligo(3-hydroxypropionate) (HPn) of different degrees of polymerization (DP; 5 and 9) bearing α-vinyl end-groups were obtained by an hydrogen transfer polymerization (HTP)-liquid/liquid extraction strategy. 2-Carboxyethyl acrylate (CEA), representing the DP 1 analogue of HPn, was also included in the study. (Macro)monomers were polymerized via reversible addition-fragmentation chain-transfer (RAFT) polymerization and fully characterized by 1H NMR spectroscopy and size exclusion chromatography. All polymers were non-hemolytic and non-cytotoxic against NIH/3T3 cells. Detailed cellular association and uptake studies of Cy5-labeled polymers by flow cytometry and confocal laser scanning microscopy (CLSM) revealed that the carboxylated water-soluble PCEA, the polymer with the shortest side chain, efficiently targets mitochondria. However, increasing the side-chain DP led to a change in the intracellular fate. P(HP5) was trafficked to both mitochondria and lysosomes, while P(HP9) was exclusively found in lysosomes. Importantly, FLIM-FRET investigation of P(HP5) provided initial insight into the mitochondria subcompartment location of Cy5-labeled carboxylated polymers. Moreover, intracellular uptake mechanism studies were performed. Blocking scavenger receptors by dextran sulfate or cooling cells to 4 °C significantly affected the cell association of hydrophobic carboxylated polymers with an insignificant response to membrane-potential inhibitors. In contrast, water-soluble carboxylated polymers' cellular association was substantially inhibited in cells treated with compounds depleting the mitochondrial potential (ΔΨ). Overall, this study highlights hydrophobicity as a valuable means to tune the cellular interaction of carboxylated polymers and thus will inform the design of future drug carriers based on Cy5-modified carboxylated polymers.

Introduction of 3‐Hydroxypropionate Moieties to Polystyrene by “Graft Through” Strategy

Abstract3‐hydroxypropionate moieties grafted polystyrene [poly(S‐g‐3HP)] was prepared by sequentially applying the hydrogen‐transfer polymerization (HTP) and the free‐radical polymerization (FRP) via “grafting through” strategy. For this purpose, oligomeric poly(3‐hydroxypropionate) with vinyl end‐group (P3HP) was prepared via HTP of acrylic acid in the presence of tNaBuO as an alkaline catalyst. Then, the oligomeric P3HP was used as a comonomer in the FRP of styrene yielding the poly(S‐g‐3HP) copolymer, namely chemically modified polystyrene. 1H‐NMR, FTIR, DSC, TGA, GPC, and MALDI MS techniques were applied to confirm the structures of both the oligomer and modified polystyrene. Glass transition temperatures of the modified polystyrene samples were found to be decreased from 103 to 84 °C depending upon the amount of 3‐hydroxypropionate (3HP) moieties. Solution‐cast films were prepared by the polystyrene homopolymer and modified polystyrenes. The contact angle values were determined to decrease gradually from 87.5 to 53.7° with increasing the amount of the 3HP moiety grafted polystyrene.

Synthesis and characterization of novel poly(α-methyl β-alanine-b-lactone)s through hydrogen-transfer and ring-opening polymerization

Abstract A series of novel poly(α-methyl β-alanine-b-lactone)s were prepared by a combination of hydrogen-transfer polymerization (HTP) of methacrylamide (MAm) and anionic ring-opening polymerization (AROP) of β-propiolactone (BPL), β-butyrolactone (BBL), and δ-valerolactone (DVL). For this purpose, poly(α-methyl β-alanine) (PmBA) having a living anionic end-group for a further extension was obtained via HTP of MAm. The anionic end-group on PmBA chains were used as initiation sites for AROP of BPL, BBL, and DVL. Fourier Transform Infrared Spectroscopy (FTIR) and Proton Nuclear Magnetic Resonance Spectroscopy (1H-NMR) confirmed the existence of both ester and α-methyl β-alanine (mBA) units in the final products. MALDI-MS analysis revealed that the poly(α-methyl β-alanine-b-lactone)s with average molar masses of several thousand g·mol−1 were obtained. DSC and TGA thermograms of each copolymer showed that the copolymers comprised the mBA and the corresponding ester units.

Synthesis of Novel Aba-Type Amphiphilic Copolymers Including 2-Hydroxypropyl Propionate and N-Isobutoxymethyl Β-Alanine by Peg-Dialkoxide Initiated Hydrogen-Transfer Polymerization

Novel ABA-type amphiphilic copolymers were prepared using end-groups activated poly (ethylene glycol) (PEG) as an initiator of hydrogen-transfer polymerization (HTP). For this purpose, PEG with 1450 Da (PEG-1450) was treated with the equivalent amount of sodium hydride to synthesize PEG with dialkoxide end-groups, namely PEG-dialkoxide. Using the PEG-dialkoxide as a macroinitiator, base-catalysed HTP of 2-hydroxypropyl acrylate (HPA), and N-isobutoxymethyl acrylamide (BMA) were performed to achieve the novel ABA-type block copolymers. The copolymers were obtained with relatively high yields. Characterization of the ABA-type amphiphilic copolymers was carried out using FTIR and MALDI mass spectrometry. FTIR spectra of the copolymers exhibited some characteristic bands assigning to the functional groups arising from the mechanism of HTP. Molar mass distributions of the copolymers from the MALDI mass study pointed out that chain extensions by mass in each copolymer were almost equal. Hence, the MALDI mass spectra of the copolymers revealed that chain extensions of PEGs by HPA, and BMA units were successfully fulfilled.

Novel ABA–type Block Copolymers from Telechelic PEG–initiated Hydrogen–transfer Polymerization

ABSTRACT Novel ABA-type block copolymers were prepared using end-groups activated poly(ethylene glycol) (PEG) as an initiator for hydrogen transfer polymerization (HTP). For this purpose, PEG with average molar mass of 1450 Da (PEG-1450) was firstly treated with the equivalent amount of sodium hydride to synthesize PEG with dialkoxide end-groups, namely PEG-dialkoxide. Using the PEG-dialkoxide as a macroinitiator, base-catalyzed HTP of acrylamide, N-methoxypropyl acrylamide, and 2-hydroxyethyl acrylate were then performed to achieve the novel ABA-type block copolymers. The copolymers were obtained with high yields of about 90%. Characterization of the ABA-type copolymers was carried out using Fourier Transform Infrared Spectroscopy (FTIR spectroscopy) and Matrix Assisted Laser Desorption Ioizaton (MALDI) mass spectrometry. FTIR spectra of the copolymers exhibited some characteristic bands assigned to the functional groups arising from the mechanism of HTP. Molar mass distributions of the copolymers from the MALDI mass study pointed out that chain extensions by mass in each copolymer were almost equal. Hence, the MALDI mass spectra of the copolymers revealed that chain extensions of telechelic PEGs by β-alanine, 2-hydroxyethyl acrylate, and N-methoxypropyl β-alanine units were successfully fulfilled.

Synthesis and characterization of poly(α-methyl β-alanine)-poly(ε-caprolactone) tri arm star polymer by hydrogen transfer polymerization, ring-opening polymerization and "click" chemistry

Synthesis and characterization of poly(α-methyl β-alanine)-poly(ε-caprolactone) tri arm star polymer by hydrogen transfer polymerization, ring-opening polymerization and "click" chemistry

Synthesis and characterization of novel ABA type poly(Ester-ether) triblock copolymers

Oligomers of poly(3-hydroxypropionate) (P3HP) were synthesized via hydrogen transfer polymerization of acrylic acid. Olefinic end-group of the oligomers were modified through epoxidation and bromination to obtain activated oligomers with epoxy and bromide end-groups, respectively. Terminally hydroxyl oligomeric poly(ethylene glycol) (PEG-1450) was also converted to sodium alkoxide of PEG-1450 through reaction with sodium hydride. Novel ABA type P3HP-b-PEG-b-P3HP triblock copolymers were successfully obtained through simple nucleophilic addition reactions between alkoxy and epoxy/alkyl bromide. Water uptake measurements of the triblock copolymers were calculated. Characterization of the modified oligomers and the triblock copolymers was performed by using FT-IR, 1H-NMR and MALDI-MS analyses. Thermal transitions and degradation features of the copolymers were investigated by using DSC and TGA methods. Spectroscopic and thermal analyses revealed that both end-group modifications and coupling reactions were successfully achieved.

Enhancement of scaffolding properties for poly(3-hydroxybutyrate): blending with poly-β-alanine and wet electrospinning

Poly-β-alanine (PBA), and its derivatives poly(α-methyl-β-alanine) and poly[N-(3-methoxypropyl-β-alanine) were synthesized by hydrogen transfer polymerization (HTP). Porous 3 D matrices of poly(3-hydroxybutyrate) (P3HB) reinforced with PBA/its derivatives were obtained via lyophilization and wet electrospinning. However, mechanical properties of the porous matrices prepared by wet electrospinning were found to present superior performance for tissue engineering applications. Cell culture study was performed by using wet electrospun P3HB matrices doped with 10% (w/w) PBA which show better manipulation ability, chemical and mechanical properties. Scaffolds of P3HB-PBA (10% w/w) blend was determined to demonstrate better cell attachment and proliferation compared to the scaffolds of pure P3HB.

Synthesis and characterization of amphiphilic triblock copolymers including β-alanine/α-methyl-β-alanine and ethylene glycol by “click” chemistry

Terminally azide poly-β-alanine (PBA-Az) was directly obtained by hydrogen transfer polymerization of acrylamide in the presence of sodium azide as an initiator. However, terminally azide poly(α-methyl β-alanine) (PmBA-Az) was synthesized by the reaction between terminally bromo poly(α-methyl β-alanine) and sodium azide. Dipropargyllated polyethylene glycol (PEG-di-Pr) was synthesized by using the reaction of PEGs with different molecular weights and propargyl bromide. Synthesis of poly(β-alanine-b-ethylene glycol-b-β-alanine) and poly(α-methyl β-alanine-b-ethylene glycol-b-α-methyl β-alanine) amphiphilic ABA triblock copolymers was achieved via “click” chemistry of PBA-Az or PmBA-Az and PEG-di-Pr with different molecular weight. “Click” reaction parameters such as concentration and time were assessed. Macromonomers and the amphiphilic triblock copolymers were characterized by using 1H-NMR, FT-IR, MALDI-MS, TGA, and elemental analysis techniques. The multi-instruments studies of the obtained amphiphilic triblock copolymers reveal that the copolymers easily formed as a result of “click” chemistry.

Novel hydrophobic macromonomers for potential amphiphilic block copolymers

Oligomers of 2-methyl nylon3 (2mN3) and 3-methyl nylon3 (3mN3) were synthesized by base-catalyzed hydrogen transfer polymerization (HTP) of methacrylamide and crotonamide, respectively. The detailed structural analyses of 2mN3 and 3mN3 were performed using MALDI-MS, 1H-NMR, elemental analysis and several end-group analyses to ascertain polymerization mechanism and exact chemical structures of final products. The structural analyses revealed that (1) base-catalyzed HTP of methacrylamide and crotonamide follows the sequence of: hydrogen abstraction from amide group of monomer by basic catalyst (NatBuO), addition of monomeric units to the anionic center, intramolecular hydrogen migration and finally, termination by hydrogen transfer from protonated catalyst (tBuOH) to anionic end-group, (2) both oligomeric products have olefinic chain-ends resulting from the initiation mechanism. The specific behavior of basic catalyst leads to the formation of olefinic chain-ends that are apt to possible end-group functionalization. Since the functional end-groups of a well-defined macromonomer are of importance in terms of chain extension, grafting, chemical modification, click chemistry, monolayer surface modification, etc., it was aimed to create more reactive functional end-groups by epoxylation and bromination. Disappearance of the signals belonging to the olefinic protons in 1H-NMR spectra of modified oligomers and existence of bromine and epoxy adducts in MALDI MS spectra of the modified oligomers were attributed to end-group modification as intended. Hence, four novel macromonomers of polyamidic backbone with functional chain-ends were synthesized successfully.

MISCIBILITY AND THERMAL DEGRADATION KINETICS OF POLY-β-ALANINE/POLY(3-HYDROXYPROPIONATE) BLENDS

Poly-β-alanine (PBA) and poly(3-hidroxypropionate) (PHP) were synthesized via base-catalyzed hydrogen transfer polymerization (HTP) of acrylamide and acrylic acid, respectively. Blends of PBA/PHP with different composition (PHP content, 5% to 75%) were studied using FTIR, DSC, TGA, XRD and polarized optical microscope to reveal both miscibility and thermal degradation kinetics of PBA/PHP blends. Optical images of blends were transparent and entirely uniform. Characteristic IR bands of both components shifted in higher frequencies with increasing fraction of other component. Melting temperature (T m ), thermal decomposition temperatures (T d ) and enthalpy of fusion (ΔH f ) of PHP decreased with increasing PBA fraction in blends. Thermal degradation kinetics of both components were studied by Freeman-Carroll method. Activation energies of thermal degradations of blend components were determined with a good regression coefficients (at least 0.994). Activation energies of decomposition decreased from 224.14 to 86.125 kJmol -1 with increasing PHP content. XRD spectra of blends exhibited lower peak intensities than those of neat polymers. The spectroscopic, thermal and optic methods revealed that PBA and PHP were miscible with a good compatibility in amorphous phase.

Solvent-Free Anionic Polymerization of Acrylamide: A Mechanistic Study for the Rapid and Controlled Synthesis of Polyamide-3

Mechanistic insights into bulk hydrogen-transfer polymerization of acrylamide initiated by t-BuONa are proposed in this study where attention is particularly given to the initiation and propagation steps. This anionic polymerization methodology led to the synthesis of polyamide-3 with controlled molar masses. NMR, SEC, and MALDI-ToF characterizations are supporting the chemical structures and the macromolecular dimensions of polyamide-3. The polymerization is completed in a few minutes depending on the targeted molar mass as confirmed by a complementary temperature vs time study. DSC and TGA measurements enabled the determination of the glass transition and degradation temperatures at 88 and 357 °C, respectively. Side reactions such as branching, transfer to monomer, and formation of polyacrylamide units were shown to occur and depend on the amount of base added. The formation of imide groups is also observed due to the formation of ammonia in the polymerization medium.

Direct Synthesis of Hyperbranched Poly(acrylic acid-co-3-hydroxypropionate)

Hyperbranched poly(acrylic acid-co-3-hydroxypropionate) (PAcHP) was synthesized by base-catalyzed hydrogen transfer polymerization of acrylic acid through one step. The copolymers obtained through solution and bulk polymerization were insoluble in water and all organic solvents tried. Structural and compositional characterizations of hyperbranched PAcHP were performed by using FTIR, solid13C-NMR, TGA, and titrimetric analysis. Acrylate fraction of the hyperbranched PAcHP obtained via bulk polymerization was determined as 60–65% by comparing TGA curves of hyperbranched PAcHP and pure poly(3-hydroxy propionate) (PHP). However, analytical titration of the same sample revealed that acrylic acid units were about 47.3%. The results obtained from TGA and analytical titration were used to evaluate the chemical structure of the copolymer. Hyperbranched PAcHP exhibited hydrogel properties. Swelling behavior of the copolymer was investigated at a wide pH range and ionic strength. The dynamic swelling profiles of hyperbranched PAcHP exhibited a fast swelling behavior in the first hour and achieved the equilibrium state within 12 h in PBS. Depending on the conditions, the copolymers exhibited swelling ratios up to 2100%. As the copolymer has easily biodegradable propionate and versatile functional acrylic acid units, it can be used as not only biodegradable material in medical applications but also raw material in personal care commodities.

Degradation Behavior and Biocompatibility of PEG/PANI-Derived Polyurethane Co-polymers

A series of polyurethane (PU) co-polymers with designable molecular weight between cross-linking dots was synthesized by a hydrogen transfer polymerization route from polyaniline (PANI), poly(ethylene glycol) (PEG), various curing agents and chain extenders using dibutyltin dilaurate as a catalyst. Their swelling, hydrophilicity, degradation and biocompatibility were inspected and assessed based on different degrees of polymerization of PANI and PEG, and their component proportion. Fourier transformation infrared spectrometry (FT-IR), 1H-NMR spectroscopy, scanning electron microscopy (SEM), gel-permeation chromatography (GPC) and goniometry were used to characterize the structure and surface morphology of the synthesized PEG/PANI-based PU co-polymers, PU residues after degradation and degraded polymers at different time periods of hydrolysis. The thermal properties, aggregate structure and surface microstructure were examined by differential scanning calorimetry (DSC), wide-angle X-ray diffraction (WAXD) and atomic force microscopy (AFM). Hemolysis, static platelet adhesion, dynamic clotting measurements and MTT assays were adopted to evaluate the hemo- or cytocompatibility. The experimental results indicated that these polymers exhibit various degrees of micro-phase separation, depending on the concentration and degree of polymerization of PANI, molecular weight of PEG, type of curing agent and chain extender, which further influence their swelling, hydrophilicity, degradable properties and biological performances in vitro. The incorporation of PANI and PANI* in co-polymers led to decreased thermal stability but slower decomposition rates than typical PEG-based PUs. The stress–strain tests showed that the as-prepared PU co-polymers possessed increased tensile strength and modulus, and decreased toughness in comparison with the blank PEG-based PU. These co-polymers are expected to find specific applications in tissue engineering or controlled drug release.

ナトリウム触媒によるアクリルアミドおよびその誘導体の水素移動重合

ナトリウム触媒によるアクリルアミドおよびその誘導体の水素移動重合

Hydrogen-transfer polymerization behavior ofN-acylacrylamide

The anionic polymerization of the N-acylacrylamide derivatives 1 and 2 was carried out at 120 °C for 24 h in N,N-dimethylformamide by lithium tert-butoxide (t-BuOLi, 3 mol %) as an initiator to obtain polymers 3 and 4 in moderate yields. The obtained polymers selectively were composed of the hydrogen-transfer polymerization unit.

Stereospecific Anionic Polymerization and Novel Hydrogen-Transfer Polymerization of α-(Aminomethyl)acrylates Having Unprotected Amino Group

Anionic polymerization of α-(aminomethyl)acrylates (2—8) having an unprotected amino proton was carried out using lithium reagents at −78°C. Acrylates except for 4 and 8 afforded the polymers in good yields. The polymerization of ethyl α-[N-(diphenylmethyl)aminomethyl]acrylate (3) with n-BuLi or the Ph2NLi-N,N,N′,N′-tetramethylethylene-diamine (TMEDA) complex in toluene afforded a polymer with a normal vinyl polymer structure and high isotacticity. Hydrogen-transfer of the amino proton hardly occurred in the polymerization process. The anionic polymerizations of ethyl α-[N-(1-phenylethyl)aminomethyl]acrylate (2) using lithium reagents in toluene and tetrahydrofuran (THF) proceeded with hydrogen-transfer reaction. CH carbon generated by hydrogen-transfer in the main chain was detected by DEPT NMR measurement of poly(2). The CH-containing unit in the polymer increased up to nearly 40% when THF was used as a solvent. Monomers 4 and 8 showed low polymerizability.

Hydrogen-transfer polymerization of vinyl monomers derived from p-tolyl isocyanate and acrylamide derivatives

The anionic polymerization of N-acryloyl- N′- p-tolylurea ( 1) was carried out at 80°C in N, N-dimethylformamide (DMF), dimethylsulfoxide (DMSO), acetonitrile or toluene containing N-phenyl-β-naphthylamine (1 mol.%) as a radical inhibitor for 24 h using t-BuOK or 1,8-diazabicyclo[5,4,0]undec-7-ene (DBU) (3 mol.%) as an initiator. It was found that 1 undertook selectively the hydrogen-transfer polymerization in the case of t-BuOK as an initiator but both hydrogen-transfer and vinyl polymerization proceeded in the case of DBU.