A convenient synthesis of functionalized alkoxyamines as initiators for living free radical polymerization

Summary 2,2,6,6-Tetramethylpiperidine- 1-oxyl (TEMPO) was reacted with ethylbenzene (la), 1-bromo-4-ethylbenzene (lb), and 4-ethylphenyl acetate (lc), respectively, using tert-BuOOWCo(OAc)·4H₂O in acetonitrile at room temperature. The reactions produced the respective TEMPO-adducts (2a, 2b, and 2c) in the yields of 37, 44, and 45 %, which were based on TEMPO. Similarly, TEMPO was reacted with 4-ethylphenyl 2,3,6,2',3',4',6'-hepta-O-acetyl-β-D-cellobioside (1d) to afford the glycoconjugated TEMPO-adduct (2d) in 45 5% yield, which was based on 1d. These results indicated that the reaction has the potential to become an easy and also safe strategy, which provided various functionalized alkoxylamines. Received 20 November 2002/Revised Version: 5 December 2002/ Accepted: 7 December 2002 Correspondence to Naoya Sugimoto     

Probing the reaction kinetics of vinyl acetate free radical polymerization via living free radical polymerization (MADIX)

Living free radical polymerization technology (macromolecular design via the interchange of xanthates (MADIX)) was applied to give accesses to chain length and conversion dependent termination rate coefficients of vinyl acetate (VAc) at 80 °C using the MADIX agent 2-ethoxythiocarbonylsulfanyl-propionic acid methyl ester (EPAME). The kinetic data were verified and probed by simulations using the PREDICI^® modelling package. The reversible addition-fragmentation transfer (RAFT) chain length dependent termination (CLD-T) methodology can be applied using a monomer reaction order of unity, since VAc displays significantly lower monomer reaction orders than those observed in acrylate systems (ω(VAc, 80 °C)=1.17±0.05). The observed monomer reaction order for VAc is assigned to chain length dependent termination and a low presence of transfer reactions. The α value for the chain length regime of log(i)=1.25−3.25 (in the often employed expression ) reads 0.09±0.05 at low monomer to polymer conversion (10%) and increases significantly towards larger conversions (α=0.55±0.05 at 80%). Concomitantly with a lesser amount of midchain radicals, the chain length dependence of k_t is significantly less pronounced in the VAc system than in the corresponding acrylate systems under identical reaction conditions. The RAFT(MADIX)-CLD-T technique also allows for mapping of k_t as a function of conversion at constant chain lengths. Similar to observations made earlier with methyl acrylate, the decrease of k_t with conversion is more pronounced at increased chain lengths, with a strong decrease in k_t exceeding two logarithmic units from 10 to 80% conversion at chain lengths exceeding 1800.     

Application of living free radical polymerization for nucleic acid delivery

Therapeutic gene delivery can alter protein function either through the replacement of nonfunctional genes to restore cellular health or through RNA interference (RNAi) to mask mutated and harmful genes. Researchers have investigated a range of nucleic acid-based therapeutics as potential treatments for hereditary, acquired, and infectious diseases. Candidate drugs include plasmids that induce gene expression and small, interfering RNAs (siRNAs) that silence target genes. Because of their self-assembly with nucleic acids into virus-sized nanoparticles and high transfection efficiency in vitro, cationic polymers have been extensively studied for nucleic acid delivery applications, but toxicity and particle stability have limited the clinical applications of these systems. The advent of living free radical polymerization has improved the quality, control, and reproducibility of these synthesized materials. This process yields well-defined, narrowly disperse materials with designed architectures and molecular weights. As a result, researchers can study the effects of polymer architecture and molecular weight on transfection efficiency and cytotoxicity, which will improve the design of next-generation vectors. In this Account, we review findings from structure-function studies that have elucidated key design motifs necessary for the development of effective nucleic acid vectors. Researchers have used robust methods such as atom transfer radical polymerization (ATRP), reverse addition-fragmentation chain transfer polymerization (RAFT), and ring-opening metastasis polymerization (ROMP) to engineer materials that enhance extracellular stability and cellular specificity and decrease toxicity. In addition, we discuss polymers that are biodegradable, form supramolecular structures, target specific cells, or facilitate endosomal release. Finally, we describe promising materials with a range of in vivo applications from pulmonary gene delivery to DNA vaccines.     

Solvent effect on TEMPO-mediated living free radical dispersion polymerization of styrene

Living free radical dispersion polymerization of styrene in the presence of 2,2,6,6-tetramethylpiperidin-1-oxyl (TEMPO) and 2,2-azobisisobutyronitrile (AIBN) was conducted in various glycol media having different solubility parameters. Genuine heterogeneous polymerization nature was observed from the initial stage of the reaction. The solubility parameter of the media was found to significantly influence the living characteristics of the polymerization including the polymerization kinetics and the molecular weight evolution at a fixed concentration of TEMPO. A grafting of stabilizer molecules onto monomer and a possible partitioning of TEMPO between the continuous medium and particle phase were postulated for the deviation of the experimentally obtained molecular weight from the calculated value. For a poor medium for styrene, such as diethylene glycol, the living nature was achieved by increasing the amount of TEMPO. The polystyrene (PS) microsphere was well obtained in all tested glycol media and the average size was increased with enhanced affinity of the media to styrene and with decreasing concentration of TEMPO.     

Lithographic results of electron beam photoresists prepared by living free radical polymerization

Summary A new family of random copolymers composed of chloromethylstyrene and a silicon based styrenic monomer was prepared using living radical polymerization. The lithographic efficiency of the resulting electron beam resists was examined. A pronounced improvement on the lithographic resolution and image quality of resists with a narrow molecular mass distribution was observed and is described. Received: 20 April 1999/Revised version: 11 June 1999/Accepted: 17 June 1999     

Photochemically initiated free radical promoted living cationic polymerization of isobutyl vinyl ether

A new photoinitiating system for living cationic polymerization of vinyl ethers such as isobutyl vinyl ether (IBVE) has been reported. The photoinitiating system comprises free radical photoinitiators such as 2,2-dimethoxy-2-phenyl acetophenone (DMPA), benzophenone or thioxanthone, together with an onium salt, such as diphenyliodonium chloride and zinc bromide. In the first step, photochemically generated free radicals are oxidized to the corresponding carbocations which subsequently react with vinyl ether monomer to yield an adduct. In the presence of zinc salt, this adduct initiates living cationic polymerization of IBVE.     

Synthesis of polymeric nanofiber and polymeric nanosphere by living free radical polymerization

Living free radical polymerizations are employed to synthesize the polystyrene copolymer. The applications of those copolymer in nanomaterials are elucidated in this research. It involves the copolymerization of styrene with 2‐hydroxyethyl methacrylate. The copolymers are reacted with cinnamoyl chloride, and then irradiated with UV light. The polymeric nanofibers are formed by solvent splitting. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 101: 3550–3558, 2006     

Twin screw extruders as polymerization reactors for a free radical homo polymerization

The bulk polymerization of n-butylmethacrylate was investigated in a counter-rotating twin screw extruder. It appeared that the gel effect, occurring with bulk polymerizations, affected the polymerization progress very strongly. Due to this effect the conversion of the reaction is independent of the rotation speed of the screws. The reactive extrusion diagram, presented in this paper, indicates how the different phenomena interact with each other and helps to understand the influences of extruder parameters and reaction parameters on the process.     

Quinolineimidazopyridinium derivatives as visible-light photoinitiators of free radical polymerization

Several dyes containing Quinolineimidazopyridinium moiety (QIPD) have been synthesized and evaluated as photoinitiators for free radical polymerization induced with the visible emission of a commercial dental lamp. The tested dyes were tested as photoinitiators in the presence of selected electron donors. Different substituents introduced into both the pyridine ring and quinoline moieties of the dyes influence photophysical properties of the investigated systems. Several different groups were tested including heavy atoms (–Cl, –Br, –I) and electron accepting (–NO₂) group. Analysis of the properties of the tested dyes allows one to conclude that there is a significant heavy atom effect on their photoinitiation efficiency. The type of the applied counter-ion has no effect on the overall performance of the photoinitiating system. QIPDs possess broad structured spectra with long-wavelength part located at the boundary of visible and UV parts of light spectrum. This makes QIPDs good candidates for the use as photoinitiating systems for dental restorative materials.     

Organosilicon sulfides as co-initiators in photoinduced free radical polymerization

Summary Three sulfur-containing silanes (organosilicon sulfides) were investigated as electron donors in photoinduced free radical polymerization, in conjunction with xanthene dye (5,7-diiodo-3-butoxy-6-fluorone, DIBF) as sensitizer. The results were compared with the nonsulfur-containing silane, N-((trimethylsilyl)methyl)aniline (K1) and thiophenoxyacetic acid (TPAA). The kinetic studies clearly showed that the DIBF-organosilicon sulfides exhibit a significant increase in the efficiency of free radical polymerization of TMPTA compared to nonsulfur-containing silane and that the efficiency of all tested electron donors is only slightly dependent on the structure of the sulfur-containing co-initiators.     

Controlled radical polymerization of styrene with an oxazolidinyl-N-oxyl stable free radical

Summary The bulk polymerization of styrene at 110 °C in the presence of 7-oxo-15-azadispiro[5.2.5.1]pentadecanyl-N-oxyl was investigated. The M _n values of poly(St) formed were increased linearly with conversion, and the M _w/M _n values were 1.48–1.54 at 90% conversion. On the basis of the results it was concluded that 1 controlled radical polymerization of St. Received: 19 October 1998/Revised version: 21 November 1998/Accepted: 26 November 1998     

Stable free radical polymerization of styrene with 4-sulphonate-2,2,6,6-tetramethylpiperidine-N-oxyl as mediators

The stable free radical polymerizations of styrene were investigated with five 4-sulphonate-2,2,6,6-tetramethylpiperidine-N-oxyl stable radicals as mediators and benzoyl peroxide (BPO) as initiators at 125 °C. The results indicated that the polymerizations proceeded in a “living”/controlled manner, i.e., the polymerization rates were first-order with respect to the monomer concentrations, molecular weights increased linearly with conversions and the molecular weight distributions were relatively low (M _w/M _n = 1.2–1.4), ¹H NMR analysis of the polymer chain-ends and successful chain extensions. The polymerization rates were faster than that of 4-hydroxyl-2,2,6,6-tetramethylpiperidine-N-oxyl (OH-TEMPO) mediated ones. The effects of steric interference of different substitute groups at four-position of 2,2,6,6-tetramethylpiperidine-N-oxyl (TEMPO), the molar ratios of stable radical to BPO and the temperature on the polymerizations were investigated.     

Synthesis of thermosensitive gel by living free radical polymerization mediated by an alkoxyamine inimer

Thermosensitive gel is synthesized through controlled/“living” free radical copolymerization of styrene and DVB mediated by an alkoxyamine inimer, 2,2,6,6-tetramethyl-1-(1′-phenylethoxy)-4-(4′-vinylbenzyloxy)-piperidine (V-ET). The inimer plays the role of both incorporating “T-shaped” inter-chain linkages and mediating the polymerization. First order kinetics is observed for crosslinking polymerizations before gel point, indicating a constant concentration of propagating radicals. Monomer conversion at the gel point depends on the feed ratio of DVB to V-ET. Higher amount of V-ET results in later gel point due to smaller molecular weight of the primary chains that depends inversely on the concentration of nitroxide. The resulting gel contains permanent and labile crosslinking points formed by DVB units and alkoxyamine moieties, respectively. Therefore, the gels exhibit gel-sol transition within a narrow temperature range. The gel properties, such as the swelling ratio and gel-sol transition temperature, can be controlled by changing the feed ratio of DVB to V-ET. The microenvironments in different gels, or at different temperatures, are investigated by ESR spectroscopy.     

1,3-dioxane methylcoumarin as a novel photoinitiator for free radical polymerization

1,3-Dioxane methylcoumarin (DOMC), a novel photoinitiator (PI) for free radical polymerization, was synthesized and characterized. UV–vis absorption spectroscopy was used to investigate its photochemical behavior during the photophysical process. The photopolymerization kinetics of DOMC was studied by real-time infrared spectroscopy (FTIR). There was an optimum curing rate with the increase in DOMC concentration. Both the polymerization rate and final conversion increased with the increase in light intensity. DOMC was the most efficient PI for tripropylene glycol diacrylate (TPGDA) in different acrylate monomers. The kinetics study of TPGDA photopolymerization showed that DOMC was a more effective PI than benzophenone/ethyl-4-dimethylaminobenzoate. © 2012 Wiley Periodicals, Inc. J Appl Polym Sci, 2012     

Controlled chain branching free radical polymerization manipulate with trithiocarbonates

Soluble, branched (methyl) methacrylate copolymers have been prepared via facile, one‐step, batch solution free radical polymerizations taken to high conversion. Methyl methacrylate (MMA) or methacrylate has been copolymerized with the branching comonomer (BCM) using a trithiocarbonate (TTC) to inhibit gelation. The BCMs employed were tripropylene glycol diacrylate (TPGDA) and trihydroxymethylpropyl triacrylate (TMPTA). Soluble branched copolymers containing unreacted double bonds have been produced and characterized by ¹H‐NMR spectroscopy. These two brancher monomers have been shown to produce regularly branched material with the small molar mass distributions in the presence of TTC. The results of DSC and Mark–Houwink constant α analyses support the production of the branched architectures. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2009     

Thermal characterization of poly(vinyl chloride) samples prepared by living radical polymerization: Comparison with poly(vinyl chloride) prepared by free radical polymerization

Poly(vinyl chloride) (PVC) samples were synthesized by a living radical polymerization (LRP) method and compared with commercial PVC prepared by the conventional free radical polymerization (FRP). The differences were assessed, for the first time, in terms of viscosimetry parameters and thermal analysis. The LRP method used to prepare the PVC‐LRP samples is the only one available to obtain this polymer free of structural defects, being of commercial interest in a view of preparing a new generation of PVC‐based polymer with outstanding performance. The polymerization temperature selected (35°C) to prepare the LRP samples is currently used in the industry to prepare PVC‐FRP grades with moderate to high molecular weight. Since the thermal stability is a direct consequence of the polymer structure, this study is of vital importance to understand the potential of new PVC‐LRP. The thermoanalytical measurements demonstrate an enhanced thermal stability of PVC‐LRP when compared with its FRP counterpart. The PVC‐LRP sample with very low molecular weight reveals a higher thermal stability than the most stable PVC‐FRP sample. It is the first report dealing with thermal analysis of PVC prepared by LRP. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2008     

Percolation analysis on free radical linear polymerization with instantaneous initiation

Summary Free radical linear polymerization with instantaneous initiation was simulated on the simple cubic lattice. The monomer conversion, polydispersity index and average degree of polymerization were predicted by using the percolation model which was based on computer-simulated self-avoiding walks on the lattice. The adjusting parameters such as reactivity, termination modes, coordination number of given lattice were introduced.     

Thiols as chain transfer agents in free radical polymerization in aqueous solution

The behavior of thiophenol and aliphatic thiols of different structure as chain transfer agents in the polymerization of acrylamide and 1-vinyl-2-pyrrolidone in aqueous solution at 25 °C was studied. Addition of millimolar concentrations of thiols to acrylamide polymerization reduced notably the polymer molecular weights, without change of the polymerization rate. Measurements at different pH showed that the reactive species towards the macroradicals is the protonated -SH group. Chain transfer constants, determined from Mayo plots, are only slightly dependent on the thiol structure. Aliphatic thiols and thiophenol react at similar rates. The selectivity is opposite for acrylamide (electron acceptor) and 1-vinyl-2-pyrrolidone (electron donor), pointing to significant charge transfer contributions. The reactions rates of these sulfur compounds with the electrophilic DPPH radical showed higher selectivity, and are not related with the chain transfer constants measured for the acrylamide macroradicals. These results are explained in terms of the different factors that control the reactivity of thiols with macroradicals.     

Synthesis of 4-arms hydroxy-functionalized PMMA-b-PE through combining free radical polymerization with coordination polymerization

The copolymerization of MMA with ethylene was promoted by metallocene complex in the presence of initiator tetra(2,3-epoxy propoxy)silane (I_s), reducing agent Zn and cocatalyst MAO, combining free radical polymerization with coordination polymerization via sequential monomer addition strategy in one-pot to produce 4-arms hydroxy-functionalized PMMA-b-PE. The effects of polymerization conditions such as temperature, time, ethylene pressure and Al/Ti molar ratio on the polymerization performance were investigated. 4-Arms hydroxy-functionalized PMMA-b-PE was obtained by solvent extraction and determined by GPC, MALLS, DSC, FT-IR, WAXD and ¹H(¹³C) NMR. The DSC result indicated that the 4-arms hydroxy-functionalized PMMA-b-PE had one T_g at 87.0 °C and one T_m at 117.0 °C which attributed to T_g of PMMA segment and T_m of PE segment, respectively. The microstructure of 4-arms hydroxy-functionalized PMMA-b-PE was further confirmed by WAXD, FT-IR, and ¹³C NMR analysis. These results demonstrated that the obtained 4-arms block copolymer consisted of PMMA segment and crystalline PE segment.