Free Nitroxide Research Articles

Nitroxide mediated controlled synthesis of glycidyl methacrylate-rich copolymers enabled by SG1-based alkoxyamines bearing succinimidyl ester groups

The controlled nitroxide-mediated copolymerization of glycidyl methacrylate (GMA) and styrene (S) with varying GMA molar feed fractions (fGMA,0 = 0.12–0.94) was accomplished by using a SG1-based alkoxyamine initiator bearing a N-succinimidyl ester group (NHS-BlocBuilder) in 50 wt% 1,4-dioxane solution at 90 °C. Copolymerizations indicated linear evolution of number average molecular weight Mn with respect to conversion up to approximately 50% and narrow molecular weight distributions with Mw/Mn = 1.22–1.44 and GMA incorporation into copolymer (FGMA) as high as 0.92. No additional SG1 free nitroxide was required to control polymerizations, even at high fGMA,0. Chain extensions of poly(GMA-ran-S) macroinitiators with S at 110 °C yielded a high fraction of block copolymer in most cases (except at the highest FGMA), as clear, monomodal shifts in Mn using gel permeation chromatography (GPC) were observed, thereby suggesting the poly(GMA-ran-S) macroinitiators were substantially “living”.

Effect of the nature of a solvent on pseudoliving free-radical polymerization of styrene mediated by TEMPO

The kinetics and mechanism of the pseudoliving free-radical polymerization of styrene are studied for the first time under the conditions of reversible inhibition by TEMPO nitroxides. An abnormal decline in the reduced rate of polymerization, which is inconsistent with a decrease in the concentration of the monomer, and an increase in the steady-state concentration of the free nitroxide are discovered. The main quantitative characteristics of the pseudoliving process are determined, namely, the rate constants of reinitiation and reversible recombination, and the constant of pseudoliving equilibrium between dormant and growing chains. It is shown that the polarity of a medium and the concentration of the monomer determine the character of polymerization in a solution: With an increase in the polarity of the solvent, the pseudoliving equilibrium constant increases, the reduced rate of styrene polymerization decreases, and the molecularmass-distribution of the polymer formed at initial conversions narrows. The smaller the concentration of styrene in the reaction system, the more pronounced the above differences associated with the solvent nature.

Nitroxide‐Mediated Radical Polymerization of Butyl Acrylate Using TEMPO: Improvement of Control Exploiting Nanoreactors?

AbstractCompartmentalization effects in the nitroxide‐mediated radical polymerization of butyl acrylate in a dispersed system using the nitroxide 2,2,6,6‐tetramethylpiperidine‐N‐oxyl (TEMPO) at 130 °C have been examined by means of modeling and simulations employing modified Smith–Ewart equations that account for compartmentalization effects on both propagating radicals and free nitroxide species. TEMPO‐mediated acrylate polymerization is known to be problematic, speculated to be mainly related to excessive accumulation of free TEMPO with increasing conversion. The present theoretical results indicate that it may be possible to at least partially overcome this difficulty by careful exploitation of compartmentalization effects in nanoreactors.magnified image

Free radical and nitroxide mediated polymerization of hydroxy-functional acrylates prepared via lipase-catalyzed transacylation reactions

3-Hydroxypropyl acrylate, 4-hydroxybutyl acrylate, 2-methyl-3-hydroxypropyl acrylate, 2-hydroxypropyl acrylate, neopentyl glycol acrylate, glyceryl acrylate, and dihydroxyhexyl acrylate were prepared via transacylation reaction of methyl acrylate with diols and triols catalyzed by Candida antarctica lipase B. After removal of the enzyme by filtration and the methyl acrylate by distillation, the monomers were polymerized via free radical polymerization (FRP) with azobisisobutyronitrile as initiator and nitroxide mediated polymerization (NMP) employing Blocbuilder™ alkoxyamine initiator and SG-1 free nitroxide resulting in hydroxy functional poly(acrylates). The NMP kinetics are discussed in detail. In addition, the polymers obtained by FRP and NMP are compared and the results are related to the amount of bisacrylates that are present in the initial monomer mixtures resulting from the transacylation reactions. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 48: 2610–2621, 2010

Inclusion Complexes of Nitroxides of Pyrrolidine and Imidazoline Series with Cucurbit[7]uril

Inclusion of nitroxides into the cavity of molecular nanocontainers may prevent or significantly retard nitroxide reactions with cellular reductans and increase nitroxide lifetime. This paper is aimed at studying possible applications of cucurbit[7]uril (CB7) as a molecular nanocontainer for pH-sensitive nitroxides probes. Inclusion complexes of CB7 with different nitroxides--3-aminomethyl-proxyl (AMP), 3-hydroxymethyl-proxyl (HMP), 4-amino-2,2,5,5-tetramethyl-2,5-dihydroimidazole-1-oxyl (ATI), and 2,2,4,5,5-pentamethyl-2,5-dihydroimidazole-1-oxyl (MTI)--were studied. It was found that reversible formation of inclusion complexes AMP@CB7, AMPH(+)@CB7, HMP@CB7, ATIH(+)@CB7, and MTIH(+)@CB7 is accompanied by a decrease of hyperfine interaction (HFI) constant on nitrogen of the nitroxide group and by a 5-7-fold increase of rotational correlation time monitored by electron paramagnetic resonance (EPR). The binding constants of nitroxide@CB7 complexes were determined, and the influence of alkali metal ions and pH on the equilibrium between free and encapsulated nitroxides was studied. The EPR spectra of CB7 mixtures with protonable nitroxides were found to be more sensitive to pH changes than the spectra of pure nitroxides, and the apparent pK of these mixtures was found to increase with CB7 concentration. The nitroxide@CB7 complexes showed higher resistance to chemical reduction with ascorbic acid compared to free nitroxides. Thus, CB7 can be used for the improvement of functional properties of nitroxides.

Nitroxide-Mediated Radical Polymerization in Nanoreactors: Can Dilution or Increased Nitroxide Concentration Provide Benefits Similar to Compartmentalization?

Compartmentalization of a nitroxide-mediated radical polymerization system can lead to improved levels of both control and livingness, but at the cost of a reduced polymerization rate. Improved control is a result of the confined space effect on deactivation, whereas improved livingness stems from the segregation effect on bimolecular termination. Modelling and simulations have been carried out for the systems styrene/2,2,6,6-tetramethylpiperidine-N-oxyl (TEMPO) and styrene/2,2,5-trimethyl-4-phenyl-3-azahexane-3-oxy (TIPNO) using the respective nitroxide-based polystyrene macroinitaitors (alkoxyamines) at 125°C to elucidate whether similar benefits can be obtained in the corresponding bulk polymerizations by merely diluting the systems or by addition of extra free nitroxide. The results have shown that neither approach leads to simultaneous improvement in control and livingness relative to the corresponding bulk systems, thus accentuating the merits of compartmentalization in nanoreactors.

Nitroxide‐Mediated Copolymerization of 2‐Hydroxyethyl Acrylate and 2‐Hydroxypropyl Acrylate: Copolymerization Kinetics and Thermoresponsive Properties

Poly(2-hydroxyethyl acrylate) (PHEA) is an interesting biomaterial with similar biocompatibility as the widespread used poly(2-hydroxyethyl methacrylate). Poly(2-hydroxypropyl acrylate) (PHPA) is a less frequently studied polymer that exhibits thermoresponsive behavior in water. Therefore, copolymers of HEA and HPA are interesting thermoresponsive polymers to evaluate as potential biomaterials. Here, we report the copolymerization kinetics of HEA and HPA by nitroxide-mediated polymerization, employing Blocbuilder® initiator and SG-1 free nitroxide, revealing an ideal random copolymerization. Furthermore, the thermoresponsive properties of the resulting copolymers are discussed, whereby the cloud points are related to both polymer composition as well as polymer concentration.

Kinetic Modeling of Nitroxide‐Mediated Polymerization: Conditions for Living and Controlled Polymerization

AbstractSimulations of conversion versus time, molecular weight ($\overline M _{\rm n}$), polydispersity index (PDI), and living fractions versus conversion plots are performed using the PREDICI software, to study the influence of several kinetic parameters on the living and controlled character of nitroxide‐mediated polymerization (NMP). In particular, the crucial role of the main equilibrium represented by both kd and kc (the rate coefficients respectively of dissociation and recombination) is highlighted. On the other hand, the importance of the initiation step, the targeted $\overline M _{\rm n}$ value, and the initial excess of free nitroxide are also demonstrated. It is further proved that side reactions, such as disproportionation and transfer to solvent, have a strong impact on the polymerization characteristics.magnified image

Synthesis and evaluation of a new polar, TIPNO type nitroxide for “living” free radical polymerization

The bromine–magnesium exchange of 2-bromopyridine provides an easy access to a new versatile TIPNO type nitroxide. The synthesis of four functionalized alkoxyamines have been achieved. Polymerizations of styrene and n-butyl acrylate mediated with this new nitroxide exhibited all the expected features of a controlled system. Because of its increase of polarity, this pyridine nitroxide is more efficient than TIPNO for the acrylate polymerization as no added free nitroxide is required, that confirms the strong influence of the polarity of the nitroxide on the efficiency of nitroxide-mediated radical polymerization, result already observed in the case of the polar SG1 nitroxide. Different block copolymers were synthesized. Polystyrene, poly(n-butyl acrylate) and poly(tert-butyl acrylate) blocks were successfully used as macroinitiators for the synthesis of various diblock and triblock copolymers. A representative example of such architecture is given by polystyrene-b-poly(n-butyl acrylate)-b-poly(tert-butyl acrylate) with a PDI of 1.2!

Simplifying the Free-Radical Polymerization of Styrene: Microwave-Assisted High-Temperature Auto Polymerizations

We have investigated the combination of the thermally auto-initiated free radical polymerization of styrene and precipitation polymerization in order to develop a fast and environmentally friendly approach to produce polystyrene. To achieve high reaction temperatures in a short period of time, microwave irradiation was utilized as the heating source. Styrene was used without any purification, e.g., without distillation or column filtration. Due to the auto-initiation of styrene at high temperatures no radical initiator was required. Different water- or ethanol-to-styrene ratios were heated far beyond their boiling points and at relatively high pressures for the auto-initiated polymerization of styrene. The obtained molecular weights could be controlled by the ethanol-to-styrene ratio in the case of ethanol as the solvent although the monomer conversions were rather low under the applied conditions. Moreover, the effect of a commercially available stable free nitroxide was investigated on the control over the polymerization. It has been observed that it is possible to control the molecular weight of the polymer by changing the ratio of styrene to free nitroxide (varied from 10:1 to 400:1) and moderate polydispersity indices (PDI = 1.3 to 1.9) could be obtained. Finally, the developed polymerization processes only require a simple purification step due to the precipitation of the polystyrene in the reaction solvent.

Effect of an Acid Protecting Group on the “Livingness” of Poly(acrylic acid-ran-styrene) Random Copolymer Macroinitiators for Nitroxide-Mediated Polymerization of Styrene

Poly(acrylic acid-ran-styrene) (P(AA-r-S)) and poly(tert-butyl acrylate-ran-styrene) (P(tBuA-r-S)) random copolymers previously made with different molar ratios (0, 4.5, and 9 mol %) of additional free nitroxide mediator, N-tert-butyl-N-[1-(diethylphosphono)-2,2-dimethylpropyl]nitroxide (SG1), relative to 2-[[N-tert-butyl-N-[1-(diethylphosphono)-2,2-dimethylpropyl]amino]oxy]-2-methylpropionic acid (BlocBuilder) alkoxyamine unimolecular initiator were used as macroinitiators for styrene chain extension. The reinitiating experiments were performed in the bulk at 115 °C when using P(tBuA-r-S) macroinitiators or 30−50 wt % dioxane solution at 120 °C when using P(AA-r-S) macroinitiators. The P(tBuA-r-S)-containing macroinitiators (number-average molecular weight Mn = 13.4−25.8 kg·mol−1) with polydispersities Mw/Mn = 1.13−1.57 were capable of initiating chains extended with styrene as indicated by monomodal and narrow molecular weight distributions with Mn = 34.6−66.3 kg·mol−1 and Mw/Mn ranging from 1.24 ...

Libraries of Statistical Hydroxypropyl Acrylate Containing Copolymers with LCST Properties Prepared by NMP

The nitroxide-mediated copolymerization of 2-hydroxypropyl acrylate (HPA) with N-acryloylmorpholine (Amor) or N,N-dimethylacrylamide (DMA) was investigated using N-tert-butyl-N-(1′-diethylphosphono-2,2′-dimethylpropyl)-O-(2-carboxyl-prop-2-yl) (BlocBuilder) alkoxyamine initiator and additional free nitroxide (SG-1). Different reaction conditions, such as the concentration of additional SG-1, were tested to optimize the homopolymerizations using a Chemspeed ASW2000 automated parallel synthesizer. Best control for the homopolymerizations (polydispersity indices of 1.2−1.3) of all three monomers was achieved using 20% additional SG-1 (relative to the initiator) at a reaction temperature of 110 °C for 2 M solutions in N,N-dimethylformamide and a monomer/initiator ratio of 100/1. Libraries of P(Amor-stat-HPA) and P(DMA-stat-HPA) were synthesized with 0−100 mol % HPA with 10 mol % increments using the optimized conditions obtained for the homopolymerizations. The resulting polymers had narrow molecular weight d...

An EPR and NMR Study of Supramolecular Effects on Paramagnetic Interaction between a Nitroxide Incarcerated within a Nanocapsule with a Nitroxide in Bulk Aqueous Media

A 15N-labeled nitroxide was incarcerated into an octa acid nanocapsule, which was confirmed by 1H NMR and EPR spectroscopy. Electron paramagnetic interaction between the 15N-labeled incarcerated nitroxide and a 14N-labeled free nitroxide in the external aqueous solution was observed by EPR spectroscopy. The observation of spin-spin interaction, through the walls of the cancer and is reflected in the simultaneous line-broadening of both the 15N-labeled and 14N-labeled nitroxides. The computer-assisted analysis of the EPR data further provides direct information on the motion and the polarity of both the incarcerated paramagnetic nitroxide and the nitroxides in the external bulk aqueous phase. We also show how communication between an incarcerated guest and molecules in the bulk solvent can be enhanced or inhibited by supramolecular factors such as Coulombic attraction or repulsion between a charged guest@host complex (incarcerated 15N nitroxide) and charged molecules in the aqueous phase.

Styrene/Acrylic Acid Random Copolymers Synthesized by Nitroxide-Mediated Polymerization: Effect of Free Nitroxide on Kinetics and Copolymer Composition

Styrene/acrylic acid (S/AA) mixtures were copolymerized in concentrated 50 wt % 1,4-dioxane solutions at 120 °C at two ratios of additional free nitroxide mediator, N,N-tert-butyl-N-[1′-diethylphosphono-2,2′-dimethylpropyl] nitroxide (SG1), relative to 2-[N-tert-butyl-2,2-(dimethylpropyl)aminooxy]propionic acid (BlocBuilder, Arkema) alkoxyamine unimolecular initiator (4.5 and 9 mol % [SG1]/[BlocBuilder]). Without SG1 at initial acrylic acid monomer feed concentrations fAA,0 > 40 mol %, the apparent rate constants increased sharply, noticeable exotherms were observed, and polydispersities increased from 1.20 at fAA,0 = 0 mol % to 1.48 at fAA,0 = 80 mol %. With 4.5 mol % [SG1]/[BlocBuilder], polymerization rates were slower and not as strongly affected by fAA,0 although exotherms were still noticeable at high fAA,0. Polydispersities remained ∼1.3 and only increased to >1.4 at high conversions for fAA,0 = 80 mol %. Exotherms were rendered nearly negligible when 9 mol % [SG1]/[BlocBuilder] was used, leading to copolymers with much narrower molecular weight distributions and kpK values for comonomer mixtures bracketed between those of styrene and acrylic acid homopolymerizations at 120 °C (kp = propagation rate constant, K = equilibrium constant). Copolymer reactivity ratios estimated for samples produced using 9 mol % [SG1]/[BlocBuilder] by nonlinear least-squares minimization were rAA = 0.25 ± 0.11 and rS = 0.93 ± 0.37, in agreement with previous literature.

Kinetics of in-Situ Formation of Poly(acrylic acid)-b-polystyrene Amphiphilic Block Copolymers via Nitroxide-Mediated Controlled Free-Radical Emulsion Polymerization. Discussion on the Effect of Compartmentalization on the Polymerization Rate

The kinetics of surfactant-free, ab initio, batch emulsion polymerization of styrene mediated by the nitroxide SG1 ((N-tert-butyl-N-1-diethylphosphono-(2,2-dimethylpropyl) nitroxide) in the presence of a poly(sodium acrylate) macroalkoxyamine playing the role of both the initiator and the stabilizer were studied, and the influence of the compartmentalization of the propagating radicals on the monomer conversion rate was discussed. It was pointed out that the local monomer concentration within very small particles has to be considered with great care. The results showed that free nitroxide was not compartmentalized and that the kinetics were not particularly affected by particle size, even for very small particles below 66 nm in diameter.

Styrene/tert-Butyl Acrylate Random Copolymers Synthesized by Nitroxide-Mediated Polymerization: Effect of Free Nitroxide on Kinetics and Copolymer Composition

Styrene/tert-butyl acrylate (S/t-BuA) mixtures were copolymerized using nitroxide-mediated polymerization in bulk at 115 °C using an alkoxyamine unimolecular initiator, 2-[N-tert-butyl-2,2-(dimethylpropyl)aminooxy]propionic acid (BlocBuilder) to observe the effect of additional N-tert-butyl-N-[1-diethylphosphono-(2,2-dimethylpropyl)] nitroxide (SG1) on kinetics and copolymer composition. Polymerizations with 4.5 mol % SG1 relative to BlocBuilder were more controlled with lower polydispersities (from 1.14 to 1.22), and the number-average molecular weight M̄n exhibited linear behavior with conversion up to ∼50%. In contrast, without SG1, apparent rate constants were greater but higher polydispersities were observed, and M̄n vs conversion deviated from the ideal linear relationship at low conversions ∼20%. The value of kpK (kp = propagation rate constant, K = equilibrium constant) for t-BuA at 115 °C was 3.0 × 10-6 s-1 and is lower than other acrylic monomers. The copolymers were richer in t-BuA than the feed composition at low initial t-BuA feed compositions ft-BuA,0 (20 mol %) but became richer in styrene when ft-BuA,0 > 40 mol %. Copolymer reactivity ratios ranged from rt-BuA = 0.09 to 0.12 and rS = 0.40 to 0.49 using Fineman−Ross, Kelen−Tüdos, and nonlinear least-squares fitting methods.

Synthesis of Multisegmented Degradable Polymers by Atom Transfer Radical Cross-Coupling

Multisegmented degradable polymers were successfully synthesized via atom transfer radical cross-coupling of α,ω-dihalogenated polymers prepared by atom transfer radical polymerization with dinitroxides. High molecular weight polymers (Mn> 100 000 g mol-1) with more than 10 cleavable units in the main chain were prepared. These multisegmented polymers were chemically and thermally degraded. Chemical degradation, via basic hydrolysis or disulfide reduction, as well as thermal degradation, by heating in the presence or in the absence of free nitroxides, led to low molecular weight polymers with relatively low polydispersity (2100 g mol-1 ≤ Mn ≤ 15 100 g mol-1; 1.08 ≤ Mw/Mn ≤ 1.46).

Synthesis of star polymers via nitroxide mediated free‐radical polymerization: A “core‐first” approach using resorcinarene‐based alkoxyamine initiators

AbstractThe synthesis of new octafunctional alkoxyamine initiators for nitroxide‐mediated radical polymerization (NMRP), by the derivatization of resorcinarene with nitroxide free radicals viz TEMPO and a freshly prepared phosphonylated nitroxide, is described. The efficiency of these initiators toward the controlled radical polymerization of styrene and tert‐butyl acrylate is investigated in detail. Linear analogues of these multifunctional initiators were also prepared to compare and evaluate their initiation efficiency. The favorable conditions for polymerization were optimized by varying the concentration of initiators and free nitroxides, reaction conditions, etc., to obtain well‐defined star polymers. Star polystyrene thus obtained were further used as macro‐initiator for the block copolymerization with tert‐butyl acrylate. © 2007 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 45: 5559–5572, 2007

Kinetics of nitroxide-controlled radical polymerization during the non-stationary state

The activation–deactivation equilibrium of nitroxide-controlled radical polymerization of styrene at 123°C was investigated. For this purpose the reaction solution was examined time dependently during the initial phase of the polymerization by using an SEC column combination providing a very good separation of the low-molecular weight species. By time-dependent measurement of the alkoxyamine concentration the activation rate of the alkoxyamines PhEt-TIPNO (N-tert-butyl-N-(2-methyl-1-phenyl-propyl)-O-(1-phenyl-ethyl)-hydroxylamine) kact=3.2×10−3s−1 and PhEt-BIPNO (N-tert-butyl-N-(1-isopropyl-2-methyl-propyl)-O-(1-phenyl-ethyl)-hydroxylamine) kact=6.4×10−3s−1 can be determined directly.Considering the Persistent Radical Effect theory, the measurement of the free nitroxide concentration allows to determine the pseudo-equilibrium constant of dissociation/combination between dormant and active species for polystyryl-TIPNO and polystyryl-BIPNO, K=7.5×10−9mol/L and 1.08×10−8mol/L, respectively.

Modeling of Nitroxide‐Mediated Semibatch Radical Polymerization

AbstractA mechanistic model is developed for high‐temperature (138 °C) styrene semibatch thermally and conventionally initiated FRP, as well as NMP with a two‐component initiating system (tert‐butyl peroxyacetate, 4‐hydroxy‐TEMPO). The model, using kinetic coefficients from literature, provides a good representation of the FRP experimental results. Implementation of a gel effect correlation to represent the change in the diffusion‐controlled termination rate coefficient with conversion improves the fit to the thermally initiated system, but is not required to represent the production of low molecular weight material ($\overline M _{\rm n} < 10\,000$ Dalton) by conventionally initiated FRP or NMP. The low initiator efficiency found in NMP is well explained by a reaction network involving combination of free nitroxide with methyl radicals formed from initiator decomposition.magnified image