Reversible-Deactivation Radical Polymerization in the Presence of

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Reversible-Deactivation Radical Polymerization in the Presence of Metallic Copper. A Critical Assessment of the SARA ATRP and SETLRP Mechanisms Dominik Konkolewicz,† Yu Wang,† Mingjiang Zhong,† Pawel Krys,† Abdirisak A. Isse,‡ Armando Gennaro,‡ and Krzysztof Matyjaszewski*,† †

Center for Macromolecular Engineering, Department of Chemistry, Carnegie Mellon University, 4400 Fifth Avenue, Pittsburgh, Pennsylvania 15213, United States ‡ Department of Chemical Sciences, University of Padova, via Marzolo 1, 35131 Padova, Italy S Supporting Information *

ABSTRACT: Reversible-deactivation radical polymerization (RDRP) in the presence of Cu0 is a versatile technique that can be used to create well-controlled polymers with complex architectures. Despite the facile nature of the technique, there has been a vigorous debate in the literature as to the mechanism of the reaction. One proposed mechanism, named supplemental activator and reducing agent atom transfer radical polymerization (SARA ATRP), has CuI as the major activator of alkyl halides, Cu0 acting as a supplemental activator, an inner-sphere electron transfer occurring during the activation step, and relatively slow comproportionation and disproportionation. In SARA ATRP slow activation of alkyl halides by Cu0 and comproportionation of CuII with Cu0 compensates for the small number of radicals lost to termination reactions. Alternatively, a mechanism named single electron transfer living radical polymerization (SET-LRP) assumes that the CuI species do not activate alkyl halides, but undergo instantaneous disproportionation, and that the relatively rapid polymerization is due to a fast reaction between alkyl halides and “nascent” Cu0 through an outer-sphere electron transfer. In this article a critical assessment of the experimental data are presented on the polymerization of methyl acrylate in DMSO with Me6TREN as the ligand in the presence of Cu0, in order to discriminate between these two mechanisms. The experimental data agree with the SARA ATRP mechanism, since the activation of alkyl halides by CuI species is significantly faster than Cu0, the activation step involves inner-sphere electron transfer rather than an outer-sphere electron transfer, and in DMSO comproportionation is slow but occurs faster than disproportionation, and activation by CuI species is much faster than disproportionation. The rate of deactivation by CuII is essentially the same as the rate of activation by CuI, and the system is under ATRP equilibrium. The role of Cu0 in this system is to slowly and continuously supply CuI activating species and radicals, by supplemental activation and comproportionation, to compensate for CuI lost due to the unavoidable radical termination reactions. With the mechanistic understanding gained by analyzing the experimental data in the literature, the reaction conditions in SARA ATRP can be tailored toward efficient synthesis of a new generation of complex architectures and functional materials.

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INTRODUCTION

with complex architectures, since it can be applied to a wide variety of monomers under mild conditions.13−17 In ATRP control over the structure of the polymer is gained through an activation−deactivation equilibrium, where a transition metal complex in the lower oxidation state, most often CuI/L, activates an alkyl halide, through an inner-sphere electron transfer (ISET) process, to generate a radical and the transition metal complex in a higher oxidation state. This radical can propagate with monomer before reacting with the higher oxidation state complex to return to the alkyl halide, as

In the past two decades polymer chemistry has been revolutionized by reversible-deactivation radical polymerization (RDRP) techniques.1−3 These RDRP techniques give similar control over polymer architecture as traditional ionic living polymerizations,4,5 but they offer tolerance to reaction conditions and functionalities similar to conventional radical polymerizations.1 The three most commonly used RDRP methods are nitroxide-mediated polymerization (NMP),6,7 reversible addition−fragmentation chain transfer polymerization (RAFT),8−10 and atom transfer radical polymerization (ATRP).11−13 ATRP was developed in 1995, and it is a particularly useful tool for synthesizing functional materials © XXXX American Chemical Society

Received: June 16, 2013 Revised: August 15, 2013

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dx.doi.org/10.1021/ma401243k | Macromolecules XXXX, XXX, XXX−XXX

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metallic copper as a reducing agent in ATRP systems was first realized in 1997 although it was also used as a direct activator in the presence of suitable ligands.33,49 Subsequently, several papers reported use of metallic copper in polymer or organic synthesis.46,50−57 The most important historical developments in metal-mediated RDRP, including those involving Cu0, are shown in Scheme 3. They include first use of Cu0, very active ligands such as tris(2-(dimethylamino)ethyl)amine (Me6TREN), and also polar solvents in ATRP of acrylates, such as methyl acrylate (MA), as well as key mechanistic studies .12,20,32,33,49,50,53,57−69 Polymerizations using Cu0 and the ligand Me6TREN were implemented as components of ATRP systems in 1997.33 In 2006, the Cu-mediated RDRP of MA was reinvestigated, using the same components as previously reported (Cu0, Me6TREN, polar solvents), but a very different mechanism, single electron transfer living radical polymerization (SET-LRP), was postulated.50 Dormant alkyl halides were proposed to be exclusively activated by Cu0, via outer-sphere electron transfer (OSET) process, and CuI was postulated to instantaneously and completely disproportionate back to Cu0 and CuII.50 The radicals were proposed to be deactivated by CuII to re-form alkyl halides and CuI, the latter of which would again instantaneously disproportionate to Cu0 and CuII, as shown in Scheme 3.50 In an earlier paper the SET-LRP mechanism was criticized as violating the principle of microscopic reversibility (PMR) and neglecting comproportionation, such that the process should resemble an ARGET process.53 In order to recognize the direct activation by Cu0 as well as comproportionation, the term supplemental activator and reducing agent (SARA) ATRP was subsequently introduced to describe the RDRP of monomers such as MA in polar solvents using Cu0 and ligands such as Me6TREN.32,66 In SARA ATRP, the activation of radicals by CuI and deactivation of radicals by CuII are at the core of the process, and Cu0 acts as a supplemental activator and reducing agent. This is because the contribution of Cu0 to the activation process is 99% of all activations occur with CuI, and Cu0 can reduce excess CuII through comproportionation.66−69 In SARA ATRP, the activation of alkyl halides by either CuI or Cu0 proceeds by inner-sphere electron transfer (ISET) and not by OSET. Thus, in the literature there are two mechanisms explaining how the copper-mediated RDRP proceeds in the presence of Cu0, in polar media such as dimethyl sulfoxide (DMSO), using active ligands such as Me6TREN. The key reactions involving alkyl halides, alkyl radicals, and Cu0, CuI, and CuII species are given in Scheme 4, with the SARA ATRP mechanism given in Scheme 6 and the SET-LRP mechanism given in Scheme 5. Because of the conflicting assumptions in SET-LRP and SARA ATRP, a vigorous debate has proceeded about the mechanism of copper-mediated RDRP in the presence of Cu0.50,53,70 This debate is sparked because the two competing models, SARA ATRP and SET-LRP, actually use exactly the same components, although the proposed mechanisms are completely different in terms of their kinetic contributions. This article first discusses the features, possibilities, and limitations of RDRP in the presence of Cu0, including the complex architectures that can be synthesized by this technique. Subsequently, the mechanistic assumptions in SARA ATRP and SET-LRP are discussed in detail. A critical analysis of experimental data is presented, with a focus on DMSO and MA/DMSO based systems, with the conclusion that the kinetic

shown in Scheme 1. ATRP is subject to the persistent radical effect (PRE), where unavoidable radical termination reactions Scheme 1. Mechanism of ATRPa

Pn−X is an alkyl halide which is the (macro)initiator, CuI/L is the activator, Pn• is the (macro)radical, and X-CuII/L is the deactivator. The dashed arrow represents the relatively low contribution of termination reactions by combination or disproportionation compared to the other reactions. a

cause a buildup of the deactivator complex, or “persistent radical”, decreasing the rate of polymerization but suppressing the rate of termination, as shown at the bottom of Scheme 1.18,19 Various strategies have been developed to diminish the concentrations of Cu catalyst needed.20 In all cases the excess of CuII deactivator is reduced back to the CuI activator complex, as shown in Scheme 2.21 In addition to applying a Scheme 2. Mechanism of ATRP with Low Catalyst Concentrationsa

Pn−X is an alkyl halide which is the (macro)initiator, CuI/L is the activator, Pn• is the (macro)radical, and CuIIX/L is the deactivator.

a

reducing potential,22−24 or photochemically reducing the CuII complex,25−27 chemical reducing agents such as conventional thermal initiators,20 SnII species, glucose,28,29 ascorbic acid,30 hydrazine,20 sulfites,31 and zerovalent metals,32 including Cu0,33 have been used. This process of continually reducing the CuII deactivator to regain the CuI activator is termed activators regenerated by electron transfer (ARGET) ATRP,28 and when a conventional initiator is used, the system is called initiators for continuous activator regeneration (ICAR) ATRP.20,34,35 The kinetics and thermodynamics of ATRP can be tuned by the ligand,36−38 initiator,36 temperature,39,40 pressure,41 and solvent polarity.39,42 These systems with low catalyst concentrations have been used to create well-controlled polymers with complex architectures, and functional materials in various media, ranging from hydrophobic aromatic solvents to water.29,43−45 An industrially viable reducing agent is metallic copper, due to its simple removal, relatively low cost, and compatibility with inexpensive ligands.46 In addition, the reaction can be performed in a copper tube in a continuous flow manner, facilitating large scale implementation.47,48 The potential of B


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Scheme 3. Major Historical Developments in Cu-Mediated RDRP, Relevant to Polymerizations in the Presence of Cu0

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SCOPE, ADVANTAGES, AND LIMITATIONS OF RDRP IN THE PRESENCE OF Cu0 RDRP in the presence of Cu0 is attractive due to its relative simplicity, mild conditions, tolerance to air, and relatively fast polymerization (for acrylates), allowing it to be used in various materials applications.71 In the majority of cases, RDRP in the presence of Cu0 is used to polymerize acrylic monomers. The RDRP of acrylates in the presence of Cu0 gives well-controlled polymers, with specific end-groups and high end-group functionality.72−74 Acrylates are attractive monomers since a wide range of functional groups can be introduced due to the ester linkage. Additionally, acrylic monomers have high propagation rate coefficients (kp) relative to their termination rate coefficient (kt),75−77 giving the resulting polymer high chain-end functionality (CEF), even when they are rapidly polymerized. To highlight this, under ideal radical polymerization conditions, less than 1 min is needed to polymerize methyl acrylate with 90% retained end-group functionality at 90% conversion, when targeting DP = 100, whereas 17 h are needed for methyl methacrylate and 3.5 days are needed for styrene, all at 80 °C.78 These values were determined from the ratio of the propagation to termination rate coefficients and

Scheme 4. Reactions Possible between the Various Forms of Copper as Well as between Alkyl Halides and Copper and Radicals and Copper

experiments agree with SARA ATRP not with SET-LRP in DMSO-based systems. Finally, key experimental findings, experimental phenomena, guidelines for well-controlled reactions, and an outlook for the process are presented. C


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Scheme 5. The SET-LRP Mechanisma

to more challenging monomers such as acrylamides84,122 and copolymers containing methacrylic acid.81 One advantage of RDRP in the presence of Cu0 is that the reaction is heterogeneous in its nature due to the presence of metallic Cu0 in the form of a wire, turnings, or powder. Since only the surface of Cu0 is available for reaction, this feature implies that the reaction rate can be tuned simply by varying the surface area of Cu0 powder or wire.66,123 Furthermore, after the polymerization, the unused Cu0 can be physically removed from the polymer solution and used again in a new reaction.65 In most cases, the polymerization after the use of Cu0 has relatively low residual metal concentrations, typically in the order of 100 ppm, as highlighted in Figure 1, which shows the

a

Bold arrows indicate dominating reactions, thin solid arrows indicate contributing reactions, and dashed arrows indicate reactions that have minimal contribution and can be neglected. In the originally proposed SET-LRP mechanism,50 the dashed arrows of radical deactivation by CuI, alkyl halide activation by CuI were completely neglected from the mechanism.

Scheme 6. The SARA ATRP Mechanisma

Figure 1. (a) Color of the polymerization solution RDRP in the presence of Cu0 after 4 h of reaction under the conditions [MA]0: [MBrP]0:[Me6TREN]0 = 200:1:0.1, with 1 cm of Cu0 wire (d = 0.25 mm) in 10 mL of MA/DMSO = 1/1 (v/v) after 4 h reaction (left), (b) 100 ppm of CuBr2/Me6TREN in MA/DMSO = 1/1 (v/v), and (c) 1000 ppm of CuBr2/Me6TREN in MA/DMSO = 1/1 (v/v) (right). Note that ca. 7 mL of the reaction mixture (a) was removed after polymerization to match the solvent levels.

color of a typical polymerization mixture after 4 h of reaction as well as 100 and 1000 ppm of CuBr2/Me6TREN in MA/DMSO = 1/1 (v/v). This highlights the low concentrations of Cu species in the solution. Other advantages include that the polymerization can be performed in a tubular continuous flow reactor made of Cu0 47 and the reaction compatibility with inexpensive ligands, 46 facilitating its use in industrial applications. These features make the RDRP of acrylates in the presence of Cu0 one of the simplest and most attractive methods of synthesizing well-controlled polyacrylates. Some particularly elegant implementations of the method are the syntheses of multiblock copolymers initially with 6 distinct blocks,62 and ultimately with up to 10 different blocks,98 or multiarm star polymers with 5 blocks.106 In these cases, each block was relatively short, and monomer was essentially consumed before the addition of the next monomer. Figure 2 shows the evolution of molecular weight distribution for 10 blocks, of either 10 blocks of poly(methyl acrylate) or the multiblock poly(methyl acrylate-b-ethyl acrylate-b-n-butyl acrylate-b-tertbutyl acrylate-b-methyl acrylate-b-ethyl acrylate-b-n-butyl acrylate-b-tert-butyl acrylate-b-methyl acrylate-b-ethyl acrylate). Although the molecular weight distributions of both polymers show some tailing toward low molecular weight, caused by termination reactions, the overall yield of the desired polymer was high, at 90% by weight and 54% by number.98 A significant limitation of the RDRP in the presence of Cu0 is that there is continuous increase in the concentration of soluble copper species. Since radical termination is unavoidable, any termination event leads to a loss of halogen chain end

a

Bold arrows indicate dominating reactions, thin solid arrows indicate contributing reactions, and dashed arrows indicate reactions that have minimal contribution and can be neglected.

therefore are valid for any RDRP process, where termination by radical−radical coupling is the dominant radical loss mechanism.78 These RDRP reactions in the presence of Cu0 have been used to create well-defined small molecules,54−56 homopolymers,50,52,79−92 block copolymers,62,93−98 polymers with complex architectures, 93, 94,96, 99−106 functional polymers,73,107−110 functionalized surfaces,111,112 and bioconjugates.113 RDRP reactions in the presence of Cu0 proceed through a radical mechanism, regardless of whether the SARA ATRP or SET-LRP mechanism is assumed. This implies that the process can be applied to similar functionalities, with tolerance to small amounts of impurities and under conditions similar to other homogeneous copper-mediated radical polymerizations. 114−117 The polymerization of acrylates,46,50,53,72,73,99 methacrylates,52,88,118−120 and styrene89,97,121 has been successful, although the method has also been applied D


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concentration of soluble Cu should be 0.83 mM (110 ppm). If less than 100 ppm catalyst concentrations were desired, then ICAR or ARGET ATRP methods could be used.

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MECHANISTIC FEATURES OF SARA ATRP AND SET-LRP Both SARA ATRP and SET-LRP were proposed to explain the relatively rapid polymerization of monomers such as methyl acrylate in polar solvents such as DMSO in the presence of metallic copper and ligands that form active Cu complexes, although the mechanism used to explain the observed polymerization is vastly different for SET-LRP and SARA ATRP. The main differences between the SARA ATRP and SET-LRP mechanisms lie in (a) relative rates of the activation of alkyl halides by Cu0 and CuI; (b) the nature of the electron transfer associated with the activation process; (c) relative rates of activation by CuI and disproportionation, i.e., the role of CuI; (d) relative rates of activation by Cu0 and comproportionation, i.e., the role of Cu0; and (e) the dynamics and position of the disproportionation − comproportionation equilibrium. One common feature of both SARA ATRP and SET-LRP is the heterogeneity of the system, which is introduced by Cu0, as opposed to the typically homogeneous ICAR and ARGET ATRP processes. The heterogeneity implies that reactions such as activation by Cu0, comproportionation, and even disproportionation67,68 depend on the surface area of Cu0, relative to the volume of the system. Therefore, rate coefficients measured in one particular reaction can be scaled by the ratio of the surface of Cu0 (S) to the total volume of the solution (V) to give surface-volume-independent rate coefficients. In particular the S/V-independent rate coefficients of activation by Cu0, kapp a0 , app , and disproportionation, k , are comproportionation, kapp comp disp app over app over given by kover a0 = (S/V)ka0 , kcomp = (S/V)kcomp, and, kdisp = (S/ V)kapp disp, where the superscript “over” refers to the fact that these rate coefficients are the overall ones. The superscript “app” refers to the fact that these rate coefficients are based on total CuI, CuII concentrations and Cu0 surface concentration, without reference to specific speciations or complexes.67−69,125 Scheme 4 shows the reactions possible between the various oxidation states of copper, between the metallic species and alkyl halides, as well as the metallic species and propagating radicals. The Cu0 and CuII species can react with each other to comproportionate, with rate coefficient kcomp, and give two CuI species, and the reverse process, i.e. disproportionation of CuI, is also possible with rate coefficient kdisp. The lower oxidation state copper species (Cu0 and CuI) can activate alkyl halides to give the metal in the higher oxidation state and propagating radicals with rate coefficients ka0 and ka1, respectively, which can terminate with rate coefficient kt. The higher oxidation state copper species, CuI and CuII, can deactivate radicals to give the metal in the lower oxidation state and re-form the alkyl halide with rate coefficient kd0 and kd1, respectively. The contributions of these reactions depend on the structure of the reagents such as initiators, ligands, monomers, etc., and also on the medium properties such as the polarity, temperature, and pressure. The SET-LRP mechanism assumes essentially exclusive activation by Cu0 species, typically as colloidal or “nascent” Cu0, with deactivation by CuII. In SET-LRP, the activation by Cu0 is assumed to occur by an outer-sphere electron transfer (OSET), generating a radical anion intermediate. The other key feature in SET-LRP is the instantaneous and complete disproportionation of CuI species. Since SET-LRP is proposed to go through radical species, propagation occurs, but in some

Figure 2. Evolution of molecular weight distributions for decablock (co)polymers of (a) poly(methyl acrylate) and (b) decablock poly(MA-b-EA-b-nBA-b-tBA-b-MA-b-EA-b-nBA-b-tBA-b-MA-b-EA). Reproduced with permission from ref 98.

functionality, and this loss must be compensated by an increase in the concentration of other halogenated species.124 In the case of RDRP in the presence of Cu0, the halogen atoms lost to termination are transformed to soluble CuI and CuII halide species.124 The soluble CuI and CuII species are much more difficult to separate from the polymer than the solid Cu0. Additionally, the heterogeneous nature of the reaction requires the reaction to be well stirred to maintain even polymerization throughout the whole reaction volume. The typical concentration of soluble Cu species for the polymerization of acrylates is in the order of 10−100 ppm, and their concentration increases throughout the whole reaction. This increase in soluble Cu species is due to the activation by Cu0 and comproportionation processes, which have been shown to occur under polymerization conditions in MA/ DMSO mixtures.69 For each activation event from Cu0 and each comproportionation, the concentration of soluble Cu species increases, and there is minimal decrease in the concentration of soluble Cu species since disproportionation has been shown to be very slow in DMSO systems.67 Since radical termination reactions are unavoidable, activation by Cu0 and/or comproportionation are needed to compensate for termination events to maintain a steady radical concentration, implying a continuous increase in the concentration of soluble Cu species. For example, with [MA]0:[MBrP]0:[Me6TREN]0 = 222:1:0.1, in MA/DMSO = 2/1 (v/v), 5 mL total volume, in the presence of Cu0 (length 1 cm, diameter 0.25 mm, surface area of 0.078 cm2) when there are 1% terminated chains, the minimum concentration of soluble Cu should be 0.17 mM (23 ppm to MA); for 5% terminated chains, the minimum E


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formed in conventional radical processes. One feature of any RDRP process where the end group is a halogen species is the principle of halogen conservation. This principle states that all halogen species lost from the polymer chains must be transferred to other species, for instance CuII species, the oxidized product of a chemically added reducing agent, or, in the case of RDRP in the presence of Cu0, the newly formed soluble Cu species.124 This implies that any increase in the CuIBr or CuIIBr2 species in solution is due to a commensurate loss of halogen functionality from the polymer end groups, since the alkyl halide is the only source of halogens in the system. This is highlighted in Scheme 7, since it shows that

cases SET-LRP is proposed to undergo either zero, or essentially zero termination.74,126,127 The key features of the SET-LRP mechanism are outlined in Scheme 5, presented in the same way as in Scheme 4, although some reactions are omitted in SET-LRP schematics, as shown in the middle part of Scheme 3. Therefore, SET-LRP does not include any significant kinetic contributions from alkyl halide activation by CuI. The SARA ATRP mechanism has the traditional CuI−CuIIcatalyzed activation−deactivation ATRP processes at the core. However, there are additional, slower, reaction steps in SARA ATRP, introduced by the presence of Cu0. These additional steps in SARA ATRP arise from the dual role of Cu0, which can act both as a supplemental activator of alkyl halides and as a reducing agent of Cu II . In SARA ATRP the Cu I /Cu II activation/deactivation processes dominate the system and occur with the fastest rate. As in other ATRP processes, the activation occurs through an inner-sphere electron-transfer (ISET) mechanism. In SARA ATRP the CuI species lost to termination are regenerated from the supplemental activator and reducing agent roles of Cu0, which occur with moderate to slow reaction rates. As in all radical polymerizations, propagation occurs with a high rate, and termination also contributes to the process, and in some cases termination occurs faster than conventional radical polymerization due to Cu-induced radical loss.69,128,129 This Cu-induced radical loss can be due to either CuI reacting with the propagating radical, leading to a CuII organometallic species, followed by β−H elimination and regeneration of the CuI species when the CuII hydride reacts with a second radical, or alternatively there can be radical loss caused by reactions between the Cu0 metal in the presence of ligand and the radical.69,128,129 Finally, in SARA ATRP in DMSO, there can be a small, albeit kinetically insignificant, extent of disproportionation of Cu I and deactivation by CuI. Even if disproportionation would be faster than comproportionation, the rates of these reactions should be much slower than the classical ATRP activation/deactivation processes. It is important to note that SARA ATRP, in contrast to SET-LRP, requires that the kinetically favored fate of CuI is to activate alkyl halides, not to disproportionate. These reactions are shown in Scheme 6. Thus, in Scheme 5 and 6 the same chemical reactions are shown but their relative contributions are dramatically different. Therefore, precise kinetic measurements under polymerization relevant conditions are needed to discriminate between SARA ATRP and SETLRP. Despite the differences in the mechanistic assumptions between the two models, there are some similarities, and both models aim to describe exactly the same polymerization conditions. The main similarities are the fast deactivation by CuII species and the negligible deactivation by CuI species. However, SET-LRP is an unusual mechanism since it violates the principle of microscopic reversibility (PMR).53 Previously, our group discussed this issue, since PMR dictates that at equilibrium all chemical reactions follow the same pathway in forward and reverse directions.

Scheme 7. Schematic Illustration of the Principle of Halogen Conservation for RDRP in the Presence of Cu0

whenever a termination event occurs, either a CuIBr/L or CuIIBr2/L is formed irreversibly. Therefore, the buildup of CuII species,68,126 implies that there must be a commensurate loss of chain-end functionality (CEF). In the majority of cases this loss of CEF is relatively small, on the order of a few percent,74 which may have minimal impact on the properties of the final polymer or its utility in further reactions. This decrease of a few percent in chain-end functionality is difficult to measure experimentally by NMR or mass spectrometry but easily measured as the buildup of CuII species by UV−Vis−NIR spectrometry.68 For example, although 100% retention of endgroup functionality was claimed in the literature,74 the UV−Vis spectra showed that under the same conditions more than 1% of CuBr2/Me6TREN was formed with respect to the initiator.126 This shows that at least 2% of the end groups were lost by termination, according to the principle of halogen conservation. Comproportionation and Disproportionation of Cu Species. One of the most significant mechanistic differences between SARA ATRP and SET-LRP is the kinetics of the comproportionation/disproportionation equilibrium between CuI and Cu0 and CuII. The SET-LRP mechanism relies on rapid disproportionation, while SARA ATRP assumes relatively slow rates of comproportionation and disproportionation, and activation by CuI much faster than disproportionation of CuI. In pure DMSO, the disproportionation equilibrium constant of the CuI cation coordinated by solvent only, with no additional ligand, is Kdisp = 1.82 (log Kdisp = 0.26),67,130,131 which implies that the equilibrium favors comproportionation under typical polymerization conditions, involving millimolar concentration of Cu species. However, the equilibrium can also be shifted by the ligand, 132 as seen by a significant shift toward comproportionation when 0.01 M bromide anions are added; the disproportionation equilibrium constant becomes log KBr disp = −9.4.130 Ligands that form active complexes, namely tris(pyridylmethyl)amine (TPMA) and Me6TREN, can also shift the disproportionation/comproportionation equilibrium significantly.66,125,132 The disproportionation/comproportionation reaction and equilibrium between CuIBr/L and CuIIBr2/L species is

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EXPERIMENTAL DATA IN THE CONTEXT OF SARA ATRP AND SET-LRP Radical Reactions and Chain-End Functionality. Both SARA ATRP and SET-LRP have carbon-centered free radicals as their propagating species. This implies that these species propagate and participate in radical coupling or disproportionation reactions with the same rate coefficients as radicals

L K disp

2Cu Br/L HoooI Cu 0 + Cu IIBr2/L + L I

F

(1)


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Figure 3. (a) Comproportionation of [CuIIBr2]0 = 2.5 mM with 2.1 equiv of Me6TREN in the presence of 4 cm of Cu0 wire (d = 1 mm) and (b) disproportionation of [CuIBr]0 = 10 mM with 1.05 equiv of Me6TREN in the presence of 16 cm of Cu0 wire (d = 0.25 mm) (this condition gives identical equilibrium concentrations as that of comproportionation of 5 mM CuIIBr2 with 2.1 equiv of Me6TREN). Both experiments were performed in 4.5 mL of DMSO at 25 °C. Reproduced with permission from ref 67. L Kdisp =

βIIL (βIL )2

Kdisp

the comproportionation and disproportionation reactions. The disproportionation equilibrium constant is KLdisp = 2 × 10−2 in pure DMSO with [Me6TREN]0 = 5.25 mM and [CuBr2]0 = 2.5 mM. Furthermore, when considering the reaction medium consisting of MA/DMSO = 2/1 (v/v), the value decreases by a factor of 20 to KLdisp = 1 × 10−3. An additional important conclusion is that comproportionation is favored with higher ligand concentrations, and since RDRP in the presence of Cu0 is always performed with a relatively large excess of ligand to soluble Cu species that are formed from termination, comproportionation dominates in these polymerization systems, and disproportionation is negligible.67 Although the equilibrium is strongly shifted toward comproportionation in pure DMSO or the polymerization medium MA/DMSO = 2/1 (v/v), there is still a limited amount of disproportionation. This can explain the presence of a relatively small amount of precipitate visually seen in experiments.134 An additional, interesting observation is that when conditions are chosen to favor a limited amount of disproportionation, e.g., using a small amount of ligand vs soluble Cu species, the newly formed or “nascent” Cu0 aggregates or attaches to a pre-existing Cu0 surface.67,135 Nevertheless, it must be stated that under polymerization conditions, such as reactions in MA/DMSO = 2/1 (v/v), with a large excess of ligand, comproportionation completely dominates disproportionation, and therefore disproportionation can be ignored in the reaction kinetics. The very slow rate, and minimal extent of disproportionation, indicate that the rate of formation and contribution of “nascent” Cu0 is very low, since “nascent” Cu0 cannot react faster than it is formed by disproportionation. The data in Figure 3 are obtained for the comproportionation and disproportionation of well-equilibrated solutions. In cases where the ligand is added to a pre-prepared solution of CuIBr in DMSO, the formation of Cu0 and CuII is much faster, since the species CuI without ligand and CuIBr/L react rapidly due to their vastly different redox potentials, although the system will eventually reach the same equilibrium.67,125 This reaction formally is not disproportionation between the same species, but it is a redox reaction between two different species in the same oxidation state. The rate coefficients for comproportionation and disproportionation are kapp comp = 9.0 × −5 cm s−1 in pure DMSO, 10−4 cm s−1 and kapp disp = 2.0 × 10 corrected for the surface-to-volume ratio. These rate

(2)

KLdisp

where is the disproportionation equilibrium constant for species bound with the ligands L and Br− (eq 1), Kdisp is the disproportionation equilibrium constant for solvated species not bound to any ligand, and βII and βI are the stability constants of CuIIBr2/L and CuIBr/L, respectively. In the literature, experiments have been performed to quantify the kinetics of disproportionation/comproportionation and the position of the equilibrium for copper complexes stabilized by the ligands Me6TREN and TPMA, in DMSO, acetonitrile, and mixtures of the monomer MA and DMSO (MA/DMSO = 2/1 (v/v)).66,67 In a polymerization, the kinetics of comproportionation and disproportionation are more important than the position of the equilibrium. This is because the rate of comproportionation dictates how quickly CuI activators are regenerated after termination reactions, irreversibly leading to CuII species. Similarly, the kinetics of disproportionation will determine whether CuI species primarily participate in the activation of alkyl halides, as in the SARA ATRP mechanism, or if the CuI species disproportionate, as proposed in SET-LRP. Figure 3 shows the results of both a comproportionation and disproportionation experiment of Cu species in the presence of Cu0 and Me6TREN in pure DMSO. As shown in Figure 3, at equilibrium, the vast majority, ca. 90%, of the Cu species are in the form of CuI, not CuII, showing that comproportionation is significantly favored over disproportionation in DMSO. These results were corroborated by the experiments from the literature that found less than 20% of CuIBr/Me6TREN underwent disproportionation in DMSO, when a sufficient amount of ligand relative to Cu was used.133 Furthermore, recent experiments also show that comproportionation dominates disproportionation of CuIBr/Me6TREN in DMSO with 90% conversion of CuII to CuI when using a 6-fold excess of ligand to CuBr2.64 Importantly, Figure 3 shows that the kinetics of both comproportionation and disproportionation are slow, with >4 h hours required to reach equilibrium. These results can be quantified with values of the parameter L Kdisp and also the associated apparent rate constants of app disproportionation and comproportionation, kapp disp and kcomp, where “app” refers to the fact that the precise speciation is neglected and the values stand for the overall rate coefficients of G


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Figure 4. Experimental and simulated data for a reaction between 4 cm of Cu0 wire (S = 1.27 cm2) and 10 mM MBrP in the presence of 15 mM Me6TREN in 7 mL of DMSO (S/V = 0.18 cm−1). Points represent experimental data and lines follow theoretical simulation results. (a) Concentrations of MBrP, CuI, and CuII. (b) Rates of all relevant reactions from 0 to 10 000 s and the inset showing the comproportionation/ disproportionation rates from 0 to 40 000 s. Ra1, Rd1, Ra0, Rt, Rcomp, Rdisp, and Rd0 are the rates of activation by CuI, deactivation by CuII, activation by Cu0, termination, comproportionation, disproportionation, and deactivation by CuI, respectively. Reproduced with permission from ref 68.

for the activation of MBrP by Cu0, in the presence of Me6TREN, were recently performed, although with no nitroxide.68 The rate coefficients of activation by Cu0, in the −4 presence of Me6TREN, was kapp cm s−1 for MBrP, a0 = 1.8 × 10 −4 −1 10 × = 1.0 cm s for Br-capped in pure DMSO, and kapp a0 poly(methyl acrylate) (PMA-Br) in MA/DMSO = 1/1 (v/v). Interestingly, these values are very similar to those measured for EBiB with PMDETA as the ligand,65 indicating that the alkyl halide and ligand seem to have a smaller influence on activation by Cu0 than on activation by CuI. This has been also observed in the literature, that the polymerization rate is of the same order of magnitude when it is initiated by an alkyl chloride, bromide, or iodide.50 This can be explained through the ISET mechanisms proposed for SARA ATRP, since in this case the increase in the bond dissociation energy of the alkyl halide moving from iodide to chloride is offset by the increase in halidophilicity of the Cu moving from iodide to chloride. It is important to quantify the amount of Cu0 in a typical reaction. Small Cu0 particles can be formed by either mechanical scraping of the original Cu0 or the very small extent of disproportionation that occurs in DMSO systems. These small particles can contribute to the total surface area of Cu0 in the system. However, the experiments where the Cu0 wire was lifted out of the polymerization medium showed that the polymerization rate dropped to approximately 10% of the value with Cu0 wire in the mixture.140 By the square root dependence of the polymerization rate on the total surface area,71 this 10-fold decrease in polymerization rate indicates that lifting the Cu0 wire removed 99% of the Cu0 in the system. This indicates that the approximately 99% of the Cu0 surface area is represented by the wire; therefore, particles or “nascent” Cu0 contribute only a small fraction to the total Cu0 activation, and the surface area of the wire is a good approximation to the total surface of Cu0 in the system. Figure 4a shows simulations using experimentally measured parameters which give excellent agreement with the experimentally determined CuII and MBrP concentrations in an activation experiment, performed in DMSO. The data show two distinct regimes. The first one is where the Cu II concentration is increasing, the MBrP concentration is decreasing, and the CuI concentration is almost zero. This regime continues until essentially all the MBrP is consumed,

coefficients correspond to the data in Figure 3, which show that the comproportionation reaction required >4 h to reach equilibrium. In MA/DMSO = 2/1 (v/v) the comproportionation is approximately 3 times faster, but importantly, the disproportionation is almost 10 times slower, since the values −3 −6 cm s−1 and kapp cm s−1. are kapp comp = 3.5 × 10 disp = 3.1 × 10 These results show that disproportionation is slow, and dominated by comproportionation in DMSO systems, consistent with SARA ATRP, not SET-LRP. Activation of Alkyl Halides by Cu0 and CuI. Since the earliest developments of ATRP, CuI has been considered as the primary activator of alkyl halides.12,136 Subsequently, the activation rate coefficients of alkyl halides by CuI species, kapp a1 , app app and the ATRP equilibrium constants, Kapp ATRP = ka1 /kd1 , have been quantified.36,39,40,137−139 In this case, the superscript “app” refers to the fact that these are apparent rate coefficients, measured on the basis of the total CuI and total CuII in the system, rather than those based on the specific associations between the metal ligand and halogen. One of the most active ATRP catalysts, CuIBr/Me6TREN, gave rate coefficients of activation for methyl 2-bromopropionate (MBrP) of 320 M−1 s−1 in DMSO and 200 M−1 s−1 in MA/DMSO = 2/1 (v/v) as measured by stopped flow methods at ambient temperature,68 with values in the same order of magnitude as those measured in acetonitrile,137 not accounting for the specific nature of all CuI species. When measuring the activation of the more active initiator, ethyl α-bromoisobutyrate (EBiB) by electrochemical methods, the CuI/Me6TREN activator complex gave a rate coefficient of almost 105 M−1 s−1 in DMSO.138 Similarly, recent −4 for CuIBr/ measurements of Kapp ATRP gave values of 2.3 × 10 −7 Me6TREN in DMSO and 7.4 × 10 in MA/DMSO = 2/1 (v/ v).39 In addition to measurements of the reaction between alkyl halides and CuI, the activation kinetics of alkyl halides by Cu0 have also been measured. A recent series of experiments reported the activation of EBiB in the presence of Cu0 and the ligand N,N,N′,N″,N″-pentamethyldiethylenetriamine (PMDETA), which typically forms less active CuI catalysts than Me6TREN.65 A value for Cu0 activation of 6.3 × 10−5 s−1 was determined, and if one normalizes this value with Cu0 surface area of 1.42 cm2 and the reaction volume of 5.67 mL,68 this −4 value becomes kapp cm s−1. Similar measurements a0 = 2.5 × 10 H


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followed by a regime where the CuII concentration decreases due to comproportionation, leading to the formation of CuI. The first regime is similar to the recent findings of a continuous buildup of CuII species over time,126 and this is caused by the fact that activation by Cu0 as well as activation by CuI species occurs faster than comproportionation. Therefore, the concentration of CuII species builds up until essentially all the alkyl halide is consumed. Because of the differences in units, it is not simple to directly compare the activation rate coefficients of MBrP or PMA-Br by Cu0 and CuI. However, a comparison of the relative activities of Cu0 and CuI directly in the reaction solution can be obtained using kinetic simulations. Analysis of the rates of reactions in Figure 4b for these two regimes shows that while the MBrP concentration is nonzero, the rate of activation by CuI is 2−3 orders of magnitude higher than the activation rate by Cu0. Interestingly, the rate of activation by CuI matches the rate of deactivation by CuII, meaning that the ATRP equilibrium is maintained, and this allows the radical to be exchanged efficiently between the polymer chains. The inset shows that the disproportionation is slow, since it takes 10 h for it to match the rate of comproportionation. Such systems equilibrating at different times are reminiscent of the competitive equilibria highlighted for the polymerization of acrylates.141 As shown in the previous paragraph, the activation of alkyl halides is typically 3 orders of magnitude faster for CuI than Cu0 in pure DMSO. A similar analysis was performed in MA/ DMSO = 2/1 (v/v), which is the polymerization medium. Instantaneous and cumulative contributions of alkyl halide activation by Cu0 and CuI are given by IFact_0 =

R a0 R a0 + R a1

(3)

IFact_1 =

R a1 R a0 + R a1

(4)

Figure 5. Plot of relative contribution of CuI and Cu0 to activation vs monomer conversion. Inset: zoom-in of the plot at conversion range of 0−1%. Conditions: 25 °C, [MA]0:[MBrP]0:[Me6TREN]0 = 200:1:0.1, MA/DMSO = 2/1 (v/v), V = 4.5 mL, S = 1.27 cm2 (l = 4 cm, d = 1 mm). Data reproduced with permission from ref 69.

(DET): stepwise mechanism involving the intermediate formation of a radical anion and a concerted mechanism in which electron transfer and bond rupture occur in a single step.142 Extensive experimental data on DET to organic halides show that alkyl halides follow the concerted mechanism,143−145 whereas the stepwise mechanism prevails for aromatic halides.145−148 Both outer-sphere and inner-sphere electron transfers are possible in either DET mechanism. In an OSET process the reactants approach each other, exchange one electron without any significant interaction (weak overlap of the relevant electronic orbitals), and float away from each other. In contrast, there is a significant interaction between the reagents in an ISET process. This may be due to the bridging of a ligand, the formation of an adduct, adsorption of a reagent on a surface, and so on. Therefore, while OSET defines a wellcircumscribed reaction, ISET encompasses a plethora of reaction types such as, for example, atom abstraction,149−151 redox reactions evolving through ligand bridging,152 adduct formation,153 charge-transfer complexes,154 and surface-assisted electron transfer processes.148,155,156 The final major difference between SARA ATRP and SETLRP is the nature of the electron transfer. SARA ATRP assumes atom transfer or an ISET process,53,61,157 whereas SET-LRP assumes an OSET process.50,158 Based on assessments of the ISET and OSET processes for the homogeneous reaction between CuI/L and the alkyl halide, atom transfer, or ISET, had an activation energy approximately 15 kcal/mol lower than OSET, which corresponds to the ISET reaction occurring approximately 1010 times faster than OSET.61,159 A scheme of the free energies involved in both mechanisms is given in Figure 6 for CuIBr/TPMA activating bromoacetonitrile, and a one for CuIBr/Me6TREN with MBrP should be similar. A recent study on the reduction of alkyl halides at noncatalytic electrodes reported that radical anions, postulated to be intermediates in SET-LRP, cannot be formed by electron transfer to alkyl halides through OSET, and instead a concerted dissociative electron transfer occurs.160 However, the process requires potentials that are more than 1 V more negative than the standard reduction potential of the alkyl halide, and under such highly reducing conditions, radicals would also be reduced to anions, which is not consistent with the radical mechanism of both SARA ATRP and SET-LRP.160 To determine if the

t

CFact_0 =

∫0 R a0 dt t

t

∫0 R a0 dt + ∫0 R a1 dt

(5)

t

CFact_1 =

∫0 R a1 dt t

t

∫0 R a0 dt + ∫0 R a1 dt

(6)

where Ra0 and Ra1 are the rates of alkyl halide activation by Cu0 and by CuI, respectively. As shown in Figure 5, in the polymerization medium, under typical conditions, CuI contributes almost exclusively to the activation process, except below 0.1% monomer conversion. These results and those in DMSO agree with SARA ATRP, which assumes that CuI is the major activator, not SET-LRP, which assumes exclusive activation by Cu0. As highlighted in an earlier paper, 2000 m of Cu0 wire (d = 0.25 mm) must be used in 10 mL of solvent, to match the activation rate of 1 mM CuI/ Me6TREN.68 Additionally, the rate of disproportionation is so low that over 99.9% of reactions involving CuI are activation of alkyl halide rather than disproportionation. Electron Transfer Process. Regardless of the nature of the electron source, a chemical species in solution, a metal surface, or an electrode, electron transfer to alkyl halides ends up with the fragmentation of a carbon−halogen bond. There are two possible mechanisms for this dissociative electron transfer I


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Figure 6. Comparison of free energies during ISET and concerted OSET processes for the reaction of bromoacetonitrile with CuI/TPMA in acetonitrile at 25 °C. Reproduced with permission from ref 61.

activation of alkyl halides by Cu0 goes via OSET or ISET, it is necessary to examine the reductive cleavage of alkyl halides at a copper electrode. The overall reaction between Cu0 and the alkyl halide in SARA ATRP/SET-LRP can be viewed as a combination of two redox semireactions: one-electron reduction of the alkyl halide and oxidation of Cu0, both occurring at the metal surface. From this perspective, important information on the nature of electron transfer from Cu0 to the alkyl halide can be gained from the reduction of the alkyl halide on a Cu electrode. The voltammetric behavior of MBrP at Cu and glassy carbon electrodes in DMSO containing 0.1 M (Et4)4NBF4 as a background electrolyte is shown in Figure 7. An irreversible

A comparison of the Ep values measured at both electrodes with Eo points out that the heterogeneous electron transfer, ET, involves high overpotentials (0.5−1.0 V), typical of ET processes concerted with bond rupture.160 In addition, Ep at Cu is 0.5 V more positive than Ep at GC, which is often considered to be the best approximation to an outer-sphere donor, i.e., an electrode acting by an OSET mechanism.162 The positive shift of Ep at Cu with respect to GC clearly shows that the metal surface has good catalytic properties, which reduce the large overpotential associated with the concerted ET−bond breaking process. This means that electron transfer to the alkyl halide at a Cu surface occurs by an ISET mechanism with important interactions between Cu0 and the alkyl halide. The activation rate coefficient of MBrP by Cu0 in DMSO in the presence of Me6TREN was found to be ka0 = 1.8 × 10−4 cm s−1. Marcus theory of electron transfer can be applied to the reaction of metallic copper with MBrP to estimate ka0(OSET) for an OSET. This requires knowledge of the Gibbs free energy of the reaction and the possibility of evaluating the activation free energy, ΔG‡. Full details of the analysis are reported in the Supporting Information. This analysis leads to the estimation of a maximum value of activation rate constant, giving ka0(OSET) < 6.8 × 10−14 cm s−1. This value is more than 9 orders of magnitude lower than the experimental ka0, clearly indicating that Cu0 does not react with alkyl halides by an outer-sphere electron transfer mechanism, but instead through an ISET mechanism. Further evidence in favor of ISET against OSET mechanism can be gained by comparing activation of alkyl halides by Cu0 and CuI. Activation of alkyl halides by CuI has been previously shown to occur by ISET with a strong decrease of ΔG‡, resulting in activation rate coefficients up to 10 orders of magnitude greater than predictions by OSET.61,159 The reaction is much faster than predicted by OSET because ET passes through a strongly bonded transition state, which drastically lowers the intrinsic barrier arising from the breaking bond. Also, the intrinsic barrier of MBrP activation by Cu0 is remarkably lowered with respect to OSET by the catalytic activity of the surface. The rate coefficients of MBrP activation by CuIBr/Me6TREN and Cu0 in MA/DMSO are 200 M−1 s−1 and 1.0 × 10−4 cm s−1, respectively, suggesting that under usual experimental conditions, where [CuI] = 10−5−10−4 M and S/V

Figure 7. Cyclic voltammograms of CuIIBr2/Me6TREN and MBrP recorded at a scan rate of 0.2 V/s on copper and glassy carbon electrodes in DMSO + 0.1 M (Et4)4NBF4: (a) 2 mM CuIIBr2/ Me6TREN; (b, c) 2 mM MBrP.

reduction peak is observed at both electrodes. The values of the reduction potential measured at a scan rate of 0.2 V/s are −1.55 and −1.05 V vs SCE for GC and Cu, respectively. These values can be compared with the standard reduction potential of MBrP under the same conditions, which cannot be measured owing to the irreversibility of the reduction process. The standard reduction potentials, SRPs, of alkyl halides used as initiators in ATRP have recently been reported in acetonitrile and dimethylformamide.161 Considering that DMSO and DMF have similar properties, the Eo of MBrP in DMSO should be approximately equal to the value of −0.56 V vs SCE reported in DMF. J


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Scheme 8. Schematic Depiction of the Lifting of Cu0, Which Leads to a 10-fold Decrease in the Polymerization Rate, and Decanting, Which Leads to a Complete Cessation of the Polymerization (Reproduced with Permission from Ref 140. Copyright 2013 the Royal Society of Chemistry)

Figure 8. Contribution of SA and RA in SARA ATRP under various conditions. Conditions: 25 °C, [MA]0:[MBrP]0:[Me6TREN]0:[CuIIBr2]0 = 200:x:0.1:y, MA/DMSO = 2/1 (v/v), V = 4.5 mL, S = 1.27 cm2. (a) x = 1, y = 0; (b) x = 0.1, y = 0.01. Reproduced with permission from ref 69.

= 0.02 cm−1 (such as those in Figure 15), the rate of the homogeneous reaction is approximately 3−4 orders of magnitude faster than heterogeneous one. If, however, one compares the reactivity of CuI and Cu0 at a molecular level, i.e., a molecule of CuIBr/Me6TREN in solution versus one atom of Cu0 on the metal surface, the two copper species have similar reactivity: 5.3 × 10−22 s−1 for CuI and 9.4 × 10−23 s−1 for Cu0.68 Since the reactivity of CuI is ca. 10 orders of magnitude greater than expected if the reaction were OSET, the fact that Cu0 has a similar reactivity as CuI may be interpreted in two ways: Cu0 follows an OSET mechanism, but its intrinsic reactivity is much higher (ca. 10 orders of magnitude) than that of OSET by CuI; alternatively, the two metal species have similar intrinsic reactivity, but both react by an ISET mechanism. To help distinguish between these possibilities, we may evaluate the relative reducing abilities of CuI and Cu0 or, in other words, the difference between the standard potentials of the CuII/CuI and CuI/Cu0 couples. The equilibrium constant of reaction 1 can be expressed as Kdisp = L exp[(E°CuI/Cu0 − E°CuII/CuI)F/RT] and then rearranged to give E°CuII/CuI − E°CuI/Cu0 ≈ 0.1 V, using Kdisp = 2.2 × 10−2 in L DMSO. E°CuI/Cu0 is only slightly more negative than E°CuII/CuI, which means Cu0 as a reducing agent is only slightly stronger than CuI. Assuming exclusive OSET activation, this small difference in reducing ability cannot explain the 1010-fold faster process for alkyl halide activation by Cu0 compared to the

OSET process for alkyl halide activation by CuI. Instead, to explain the activities, per atom, of Cu0 and CuI in activating alkyl halides, the activation by both species should occur by ISET, as proposed in SARA ATRP, not OSET, as proposed in SET-LRP. It should be stressed that CuI and Cu0 activate alkyl halides by the ISET mechanisms, although this does not imply that the two metal species follow identical reaction pathways. Finally, if Cu0 were able to reduce alkyl halides by OSET, as proposed in SET-LRP, it should reduce CuII complexes by OSET even faster, since their redox potentials dictate that CuII is much more easily reduced than the alkyl halides used in ATRP.36,160,163 In the specific case of MBrP, the standard reduction potential of CuIIBr2/Me6TREN (−0.36 V vs SCE) is ca. 0.7 V more positive than the reduction potential of the alkyl halide on Cu (Figure 7). With this difference in reduction potentials, the reduction of Cu II Br 2/Me 6 TREN by Cu0 (comproportionation) should be many orders of magnitude faster than the reduction of MBrP by Cu0 (activation by Cu0), if both occur by OSET. This would indicate that comproportionation, not disproportionation as proposed in SET-LRP, should dominate if Cu0 acts as an activator by OSET. Summary of Experimental Data. The data from the literature are in agreement with the SARA ATRP mechanism, not the SET-LRP mechanism. As discussed earlier, comproportionation dominates disproportionation in DMSO systems, and the rate of activation by CuI is much higher than the rate of K


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RDRP methods over conventional radical methods.164 In the case of methacrylates, the polymerization could also be controlled,52,88,119,120 but in most cases with a certain amount of CuII added at the start of the reaction. Finally, in the case of styrene, higher temperatures were required89 to achieve an acceptable rate of polymerization. Recently water-soluble acrylates, acrylamides, and methacrylamides have also been studied.90,91,122 Solvents. In the vast majority of cases DMSO71 or other polar solvents such as DMF are used as the reaction medium. The success of DMSO lies primarily in a high ATRP equilibrium constant,42 not in disproportionation. As shown in the earlier parts of this paper, disproportionation is slow and minimal in pure DMSO and negligible in mixtures of MA/ DMSO = 2/1 (v/v). However, in DMSO and its mixtures with monomers, ATRP equilibrium constant are high,39,42 which implies a low ratio of CuI/CuII. This low ratio of CuI/CuII improves the control and minimizes the extent of CuI promoted radical loss reactions,128,129 which enhances the end-group functionality and reaction rate. In addition, the lower rate of CuI catalyzed radical loss leads to lower concentrations of Cu in the final polymer by the principle of halogen conservation.124 Another interesting feature of using DMSO is that a biphasic system can be created if less polar acrylic monomers are used. When the nonpolar monomer n-butyl acrylate is polymerized in DMSO, a biphasic system forms during the polymerization with the majority of CuII in the DMSO phase, facilitating removal of Cu from the product.166 Solvents such as acetonitrile and toluene do not perform as well for RDRP in the presence of Cu0. There are several reasons for the poorer control in these solvents. Both solvents have lower values of the ATRP equilibrium constant than DMSO, which implies a higher ratio of CuI/CuII, which could lead to a higher rate of CuI-catalyzed radical loss.128,129 In addition, the value of the rate coefficient of Cu0-catalyzed radical loss is expected to be higher for acetonitrile than for DMSO,68 leading to an even greater loss of chain-end functionality in acetonitrile compared to DMSO. One final difference between DMSO and acetonitrile is that comproportionation occurs faster in acetonitrile than in DMSO. Although a slow rate of comproportionation can compensate for radical termination, if the rate is too high, there should be a continuous buildup of radicals, leading to higher rates of termination. The rates of comproportionation for both Me6TREN and TPMA ligands are illustrated in Figure 9. Toluene was also used as a solvent for the polymerization of acrylates, methacrylates, and styrene.63,74,88,89,167 Typically, in

activation by Cu0, and both occur by ISET. Lifting experiments (cf. Scheme 8) indicate that there is very little Cu0 that is not attached to the Cu0 wire, showing the minimal contribution of “nascent” Cu0 to the reaction.140 Thus, CuI is the major activator of alkyl halides, and Cu0 acts as a supplemental activator and reducing agent (SARA). The instantaneous and cumulative contributions of these processes are given by R comp

IF0_comp =

IF0_act =

R comp + R a0

(7)

R a0 R comp + R a0

(8)

t

CF0_comp =

∫0 R comp dt t

t

∫0 R comp dt + ∫0 R a0 dt

(9)

t

CF0_act =

∫0 R a0 dt t

t

∫0 R comp dt + ∫0 R a0 dt

(10)

Figure 8 shows that under typical conditions the supplemental activator (SA) component is larger than the reducing agent (RA) component, since the concentration of alkyl halides is higher than the concentration of CuII, because CuII only accumulates due to radical termination, by the persistent radical effect. Depending on the reaction conditions, the fraction of SA and RA can be altered, as shown in Figure 8. Figure 8a illustrates a typical polymerization of acrylates in the presence of Cu0.69 However, RA can dominate, if the alkyl halide concentration is lower and if CuII is added to the reaction mixture, as shown in Figure 8b. One interesting conclusion from the above analysis is that RDRP in the presence of Cu0 is well controlled only because the supplemental activation and reduction by Cu0 are relatively slow.69 Consequently, superactive Cu0 species would lead to very high radical concentrations and low chain-end functionality. Overall, the body of model experiments and polymerizations agree well with the SARA ATRP mechanism and lie in direct opposition to the SET-LRP mechanism. Therefore, the process of RDRP in the presence of Cu0 should be described by the SARA ATRP terminology, rather than SET-LRP, since SARA ATRP accurately describes the mechanism.

■

FEATURES OF RDRP IN THE PRESENCE OF Cu0 The following section aims to describe the key features of RDRP in the presence of Cu0. In particular, the monomer variety, solvents, and trends in terms of experimental variables, such as Cu0 surface area, ligand concentration, and added CuIIBr2, will be discussed. Monomers. The monomers that are most commonly used for RDRP in the presence of Cu0 are acrylates,71 although methacrylates52,88 and styrene89 have also been polymerized using this method. The main advantage of using acrylic monomers by the RDRP in the presence of Cu0 is the higher rate coefficient of propagation relative to that of termination.78 This implies that a fast polymerization of acrylates can be performed, with the vast majority of polymers retaining a Br end group. The main limitation of using acrylates is transfer reactions, which can lead to branching,164,165 although transfer is relatively slow at room temperature and is also reduced using

Figure 9. Kinetics of comproportionation in different solvents with different ligands. [CuIIBr2]0 = 2.5 mM; [ligand]0 = 5.25 mM; 4 cm of Cu0 wire (d = 1 mm); in 4.5 mL of solutions at 25 °C. When using MA/DMSO mixture as a solvent, the ratio was MA/DMSO = 2/1 (v/ v). Reproduced with permission from ref 66. L


Macromolecules

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toluene the rate of polymerization of acrylates is lower and the chain-end functionality is poorer than in DMSO, suggesting enhanced catalyzed radical loss due to either Cu0 or CuI. In addition, the solubility of Cu salts in toluene is rather low, indicating that the equilibrium between CuI and CuII could be distorted due to solubility issues. Therefore, polar solvents such as DMSO are desirable for the RDRP in the presence of Cu0, given the high ATRP equilibrium constant, relatively low rates of comproportionation, compared to activation by Cu0, and good solubility of Cu species. Recently solvents such as water or mixtures of water and other polar solvents such as alcohols have received some attention.90−92,122,168 Aqueous systems are subject to high ATRP equilibrium constants and very fast activation of alkyl halides by CuI.23,42,139 However, the activation of alkyl halides by Cu0 in ethanol and water mixtures is slower than in DMSO.65 The comproportionation/disproportionation equilibrium favors disproportionation more in ethanol and water mixtures than in DMSO; 65 however, the kinetics of comproportionation process is slow. Therefore, the CuI species formed by alkyl halide activation by Cu0 or radical deactivation by CuII will preferentially activate an alkyl halide rather than disproportionate, since the activation should still be much faster than disproportionation. Furthermore, the high activity of CuI implies that only a small amount of CuI is sufficient to efficiently exchange the radical center among the polymer chains, assuming the concentration of CuII deactivator complexes is high enough. Therefore, the actual ratio of CuI/ CuII during polymerization may be lower than that dictated by the comproportionation/disproportionation equilibrium. This indicates that some comproportionation may occur even in aqueous systems and that Cu0 may retain its role as a supplemental activator and reducing agent and that SARA ATRP not SET-LRP may govern these aqueous systems. More experiments are needed to accurately describe the kinetics of aqueous RDRP in the presence of Cu0. Cu0 and Other Zerovalent Metals. Cu0, as well as other zerovalent metals,32 can be used in these polymerizations to generate radicals and compensate for excess CuII species in solution. In all cases, the zerovalent metal is a heterogeneous catalyst, and therefore the kinetics depend on the ratio of the surface area of the heterogeneous catalyst (S) to the volume of the solution (V). Therefore, the S/V ratio is the appropriate way to characterize the “concentration” of the zerovalent metal in solution. Various experiments32,65,71,123 showed that the rate of the polymerization scales as the square root of the surface area of Cu0 or S/V ratio. An example of the scaling of the polymerization rate with the Cu0 surface area is given in Figure 10 for the RDRP in the presence of Cu0, using either Me6TREN or TPMA as the ligand. This can be explained by Cu0 acting as both a supplemental activator of alkyl halides and a reducing agent of CuII. As mentioned in the literature,63 the supplemental activator role of Cu0 has kinetic similarities to the role of the conventional radical initiator in ICAR ATRP. Since ideal ICAR ATRP has a square root dependence of the polymerization rate with the conventional initiator concentration,20,21 the supplemental activator component of SARA ATRP should also have a square root dependence on the Cu0 surface area. Additionally, since Cu0 likewise acts as a reducing agent for CuII, the kinetics should also follow a square root dependence with the concentration of the reducing agent, where the concentration here is the surface area of the Cu0, as

Figure 10. Scaling of the polymerization rate with the surface area of Cu0 wire for Me6TREN and TPMA based systems in 4.5 mL of solvent. Reproduced with permission from ref 66. Me6TREN (red broken line) data taken from ref 71.

in ARGET ATRP processes.43 However, this requires that the concentration of CuII remain fairly constant throughout the polymerization, which is easily achieved by adding a few hundred ppm of CuII to the system; otherwise, the RA contribution should increase with time, since the concentration of CuII will increase appreciably over the reaction.65 Therefore, the combined SARA process, with either the supplemental activator contribution being dominant or a sufficiently high initial concentration of CuII so that the reducing agent contribution does not change over the reaction, should have an overall square root dependence of the reaction rate with the Cu0 surface area, as observed in experiments, simulations, and analytic models.65,69 However, as highlighted by simulations,69 in the majority of cases, the supplemental activator role of Cu0 is dominant, implying that the square root dependence is primarily due to the role of Cu0 as a supplemental activator of alkyl halides. As for any radical polymerization, a compromise must be reached between the rate of polymerization and the rate of radical termination, since both increase with higher Cu0 surface area. If high surface area Cu0 sources are used, such as Cu0 powders, the rate of polymerization will be faster, and high conversion can be reached in less than 1 h for MA, but the chain-end functionality will be lower. In contrast, if a low surface area, such as 1 cm of Cu0 wire with diameter 0.5 or 0.25 mm is used, the reaction will be slower, but the chain-end functionality could exceed 95% at 90% conversion. Therefore, the optimal surface area used should depend on the application. If rate is the primary focus, a high surface area powder could be used, whereas if chain-end functionality is the primary focus, a short length of thin Cu0 wire should be used. In addition, other metals, including iron, can be used in a similar capacity as a supplemental activator and reducing agent.32 One interesting observation was that the RDRP in the presence of Cu0 required continuous contact with the metal to maintain the polymerization rate. When the Cu0 wire was lifted out of the reaction mixture, the polymerization rate decreased by a factor of 10, whereas when the reaction mixture was carefully decanted to remove all Cu0, the reaction almost completely ceased.140 These two experiments are shown in Scheme 8. When the Cu0 wire was lifted out of the solution, small particles not attached to the wire were left behind.140 This M


Macromolecules

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Figure 11. Simulated kinetics: (a) removing Cu0 at 20 min and reinserting at 110 min; (b) removing Cu0 at 60 min and reinserting at 150 min in an interrupted SARA ATRP polymerization. Conditions: [MA]0:[MBrP]0:[Me6TREN]0 = 222:1:0.1, MA/DMSO = 2/1 (v/v), in 4.5 mL total (S = 0.19 cm2, S/V = 0.042 cm−1). Experimental data taken from ref 140 with permission from the Royal Society for Chemistry.

Figure 12. (a) Dependence of the polymerization rate on the ligand concentration for Me6TREN and TPMA based systems. Reproduced with permission from ref 66, with Me6TREN data taken from ref 169. (b) Simulated rates of polymerization with variable CuBr2 species under the conditions: 25 °C, [MA]0:[MBrP]0:[Me6TREN]0 = 200:1:0.1, MA/DMSO = 2/1 (v/v), V = 4.5 mL. Reproduced with permission from ref 69.

“lifting” experiment indicates that the surface area of Cu0 that remained in solution was 100 times smaller than that of the original wire, due to the square root dependence of the polymerization rate on the surface area of Cu0.68 Thus, the surface area of small particles or “nascent” Cu0 is on the order of 1% of the surface area of the Cu0 wire, consistent with the slow rate and small extent of disproportionation in DMSO, or mechanical scraping of the Cu0 wire. Kinetic simulations of SARA ATRP were performed for removal of all the Cu0, i.e., the decanting experiments, using the scheme and rate coefficients described in the Supporting Information. The lifting experiments were not simulated since the exact surface area, and the size distribution, of the Cu0 particles left in solution are not known. In one simulation, the reaction mixture was decanted, leaving 0% of the original Cu0 surface area in solution at 20 min, and then reinserted at 110 min. In the other simulation, the Cu0 was removed (or decanted) at 60 min and reinserted at 150 min. The kinetic results are shown and compared to the experimental data140 in Figure 11a and Figure 11b, respectively. These simulations accurately describe the “interrupted” polymerization of MA, since SARA ATRP is subject to the persistent radical effect. With the low concentrations of soluble Cu in SARA ATRP, a small number of terminated chains leads to a large decrease in

polymerization rate. Assuming 50 ppm of soluble Cu, with 10% CuI and 90% CuII, consistent with the simulation data, this equates to 5 ppm of CuI with respect to monomer. With a ratio of monomer to alkyl halide of 200 to 1, or DP = 200, this corresponds to a ratio alkyl halide to CuI of [CuI]/[RX]0 = [CuI]/[M]0 × DP = 5 × 10−6 × 200 = 0.1%. Therefore, if 0.1% of the chains terminate, all the CuI should be converted to CuII, and the reaction completely ceases. Effect of the Ligand Concentration. The final crucial component needed to perform RDRP in the presence of Cu0 is the ligand. In these reactions a certain minimal amount of ligand must be available; otherwise, the polymerization will be very slow.169 This trend has been observed for both TPMA and Me6TREN ligands, as shown in Figure 12a66 and also in model reactions.68 In the literature,65 this has been explained as Eley− Rideal kinetics, where a certain amount of ligand is needed to coat the Cu0, to promote activation of alkyl halides by Cu0, with further increases of the ligand concentration yielding minimal improvement in the kinetics, since the Cu0 surface is already saturated. Since the activation of alkyl halides by Cu0 is the key step controlling the rate of polymerization, or the ratedetermining step, any decrease in the rate of alkyl halide activation by Cu0 will decrease the polymerization rate. N


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Effect of CuII Added to the Reaction Mixture. One of the attractive features of RDRP in the presence of Cu0 is that the polymerization can be performed with only monomer, ligand, solvent, initiator, and Cu0. However, in these systems the control over the reaction is poor until the concentration of CuII halide deactivator species builds up after the loss of a small fraction of halogen end groups, by the principle of halogen conservation. Alternatively, the control over all chains can be improved by adding CuBr2 to the reaction mixture, negating the need for termination reactions to build up CuII. As highlighted by simulations in Figure 12b, the polymerization rate is not strongly affected by the addition of CuBr2, and this is confirmed by experiments.66,84,167 This technique removes the high molecular weight fraction observed at low conversion and can be used to create better controlled homo- or multiblock copolymers,62,66,88,89,98,167,170 although in this case the total concentration of soluble Cu species increases.126 The added CuII improves the control over the polymer structure, as measured by the Mw/Mn value, particularly at low conversion. Is Disproportionation Important? It has been claimed in the literature that perfect chain-end functionality is retained in the presence of disproportionation of CuI species.74 The small amounts of precipitate in disproportionation experiments in nonpolar media such as methyl methacrylate or toluene reported134 could be due to the limited solubility of CuII. Precipitation of CuII should then further shift the equilibrium toward disproportionation products (Cu0 and CuII). A similar concept is used in a Finkelstein reaction, where more stable alkyl chlorides or alkyl bromides are converted to alkyl iodides, because potassium iodide is soluble in acetone, while potassium chloride or bromide are not.171 Figure 13a shows the small amount of fine Cu0 powder generated by adding 35 mM of Me6TREN to 20 mM of CuIBr

added slowly to a ligand solution in DMSO, the disproportionation of the in situ generated CuIBr/Me6TREN complex was very slow, requiring hours to reach equilibrium.67 Figure 13b shows the reaction mixture 30 min after adding 2 mL of MA to the 1 mL of DMSO to generate the typical polymerization medium of MA/DMSO = 2/1 (v/v). The solution in Figure 13b is colorless, and there are no visible Cu0 particles, indicating almost complete comproportionation and essentially 100% CuIBr/Me6TREN. The comproportionation was relatively fast due to the high surface area of the Cu0 powder. Figure 13c shows the green solution, formed 10 min after the addition of 40 mM of MBrP, indicating the presence of CuII, formed by the activation of MBrP by CuI, followed by the termination of the generated radicals. The monomer conversion was 69%, yielding a well-controlled polymer with Mn = 11 000 and Mw/Mn = 1.04, in excellent agreement with the theoretical value of Mn = 11 100. Since the experimental data showed that there was essentially no Cu0, CuI must have been responsible for polymerization. A similar process was reported in DMSO,140 except in that publication there was also approximately 10% of the Cu in the form of small amount of Cu0 particles. Therefore, in ref 140 and in Figure 13 the rapid activation of the alkyl halide and formation of CuII must be primarily due to CuI, since disproportionation is slow and limited. A second argument against the necessity of disproportionation in these polymerizations is that the same kinetic features are observed when either Me6TREN or TPMA was used as a ligand. As highlighted in the literature, Me6TREN gives CuI complexes that undergo a limited extent of disproportionation, whereas TPMA gives complexes that undergo virtually no disproportionation, due to its strong binding to both CuI and CuII.125,132 However, the kinetic trends observed when either TPMA or Me6TREN was used as the ligand were the same, implying that disproportionation is not a necessary condition for good control over the polymerization.66 Preservation of Chain-End Functionality. One of the key features of RDRP in the presence of Cu0 is the high endgroup functionality that can be attained,74 giving the technique access to polymers with complex architectures such as multiblock copolymers or stars.62,98,106 This is possible for acrylic polymers due to their high rate coefficient of propagation, relative to the rate coefficient of termination, as highlighted in the monomers section.32 In all cases, a relatively small amount of CuIIBr2 is formed, typically in the order of 100 ppm, with respect to monomer.68,124,126 This implies that a minimum of [T] = 200 ppm of chains have terminated, estimated by the principle of halogen conservation, because all the bromide ligands for the CuII species must have come from polymer end groups, since the bromine end groups are the only source of halogens in this polymerization.124 Assuming a target DP = 200, this 200 ppm of chain end loss, corresponds to T% = [T]/[RX]0 = ([M]0/[RX]0) × ([T]/[M]0) = DP × [T]/[M]0 = 200 × 200 × 10−6 = 4% loss of chain-end functionality, which might be below the detection limits of some techniques used to measure the end-group functionality, such as NMR, mass spectrometry, or chain extension by GPC. A strong argument for Cu0- and CuI-catalyzed radical terminations is provided by the analysis of end-group functionality by mass spectrometry.170 In a typical RDRP of MA in the presence of Cu0, there were 6% dead chains, including 4% hydrogen-terminated chains and 2% unsaturated chains, and essentially no coupled product. Since radicals formed in the

Figure 13. Photographs of (a) 20 mM CuIBr with 35 mM Me6TREN in 1 mL of DMSO after 20 min, (b) 30 min after diluting 1 mL of the 20 mM CuIBr and 35 mM Me6TREN with 2 mL of MA, and (c) 10 min after adding 40 mM MBrP. T = 25 °C in all cases.

in DMSO. In order to form Cu0, ligand was added to CuIBr solution. The CuIBr then quickly reacted with newly formed CuIBr/Me6TREN due to a large difference in their redox potentials, followed by slow comproportionation. This is not a formal disproportionation reaction because it involves two different species. However, when CuIBr solution in DMSO was O


activation by Cu I via ISET 1010 times faster than via OSET;61 approximately the same behavior for activation by Cu0 (activation via ISET >1010 times faster than via OSET, this paper) CuIIBr2/Me6TREN ca. 0.7 V more easily reduced than MBrP, implying activation of MBrP by Cu0 through OSET should be many orders of magnitude slower than comproportionation; excellent electrocatalytic activity of Cu for the reduction of MBrP electron transfer to alkyl halides with no stable radical anion intermediates159,160

activation via ISET for both Cu0 and CuI 13,53,157

CuI predominantly involved in activation and not in disproportionation slow comproportionation, with even slower disproportionation53

activation by Cu0 via OSET, through a radical anion intermediate50

CuI involved only in disproportionation and not in activation

instantaneous disproportionation dominating comproportionation

P

faster polymerizations with higher radical concentrations, resulting in more dead chains69 in all cases, a buildup of CuII species, due to a loss of Br end groups68,124,126

limited amount of termination124 number of dead chains increases with polymerization rate

ultrafast polymerization, giving ultrahigh molecular weight polymers,50 with 100% chain-end functionality at full conversion74

differences in kinetics due to the higher KATRP in DMSO compared to less polar solvents39

relative concentration of CuI , CuII governed by ATRP equilibrium, not by slow comproportionation/disproportionation activation of alkyl halides as the dominant reaction involving CuI rather than disproportionation69

solvents promoting disproportionation needed50,70,74

kinetics of polymerization comparable for Me6TREN, with limited disproportionation, and TPMA, which does not disproportionate66

comproportionation is slow, but dominates, under typical polymerization conditions and in pure DMSO64,67,133

rate of activation by CuI ∼ 108 times faster than rate of disproportionation

2000 m of Cu0 wire, with diameter 0.25 mm, needed in 10 mL of DMSO to match the activity of 1 mM CuI/ Me6TREN68 Cu0 particles in solution have only a small fraction (ca. 1%) of the surface area of Cu0 wire, according to the lifting experiments140 alkyl halides rapidly activated by CuI complexes according to: stopped flow;68,137 electrochemical methods;138 CuI/Me6TREN responsible for more than 99% of all activation events68

observations

CuI as the major activator of alkyl halides53

Cu0 much less active than CuI

no activation of alkyl halides by CuI complexes140,175

SARA ATRP claims Cu0 as a supplemental activator of alkyl halides53,66

alkyl halides activated by Cu0 and nascent Cu0 particles50,175

SET-LRP claims

Table 1. Claims and Observations on RDRP in the Presence of Cu0

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Figure 14. (a) Kinetics, (b) Mn, (c) Mw/Mn, and (d) CEF for polymerization of MA. Conditions: (blue squares) targeted DP = 60: [MA]0:[MBrP]0: [Me6TREN]0 = 60:1:1; (red circles) targeted DP = 200: [MA]0:[MBrP]0:[Me6TREN]0 = 200:1:1; in both cases MA/DMSO = 1/1 (v/v), T = 25 °C, 1 cm of Cu0 (d = 0.5 mm, S = 0.16 cm2) in 10 mL of solvent, S/V = 0.016 cm−1.

kinetics.65 Once the majority of the ligand is depleted, the polymerization rate decreases significantly, which could explain why polymerizations in solvents such as acetonitrile show nonlinear semilogarithmic plots, whereas in DMSO semilogarithmic kinetic plots are typically linear.53,70

polymerization of acrylates terminate preferentially by coupling,172 these disproportionation-like products, in a non 1:1 ratio, indicate radical loss reactions other than the radical coupling. This can include Cu0- and CuI-catalyzed radical terminations,69,129 and also reactions with a ligand such as transfer,173 or quaternization of the alkyl halide with excess Me6TREN ligand.174 A sufficient amount of ligand is needed to maintain an acceptable rate of polymerization, and if the ligand concentration is too low, the polymerization is slow or would stop at a certain conversion. This is because the ligand determines the maximum number of terminated chains, since the soluble Cu species, accumulated due to termination, cannot exceed the ligand concentration. Additionally, the loss of end-group functionality cannot be more than 2 times the ligand concentration assuming the majority of soluble Cu is in the CuII form, by the principle of halogen conservation. This also explains the nonlinear first-order kinetics observed when solvents such as acetonitrile are used in the polymerization of MA compared to the more linear first-order kinetics observed under similar conditions in DMSO.53,70 As described earlier, the Cu-catalyzed radical termination reactions in acetonitrile are faster than in DMSO,68 indicating that a larger amount of the Cu0 and ligand must be consumed to reach the same conversion in acetonitrile, due to the higher rate of termination and greater loss of chain-end functionality. Thus, at a certain monomer conversion, the majority of the free ligand will be consumed in acetonitrile due to a commensurate loss of chainend functionality, whereas in DMSO there will be still a larger excess of ligand available. As shown in the literature, a certain minimal amount of ligand is needed;169 otherwise, the rate of the polymerization will be low, as explained by Eley−Rideal

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CLAIMS AND OBSERVATIONS Table 1 highlights some claims made regarding RDRP in the presence of Cu0 and how those claims can be explained, together with relevant experimental observations regarding each claim.

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GUIDELINES FOR RDRP IN THE PRESENCE OF Cu0 The above sections showed the features of RDRP in the presence of Cu0. With the mechanistic understanding gained through years of meticulous research since 1997, the following section aims to describe some guidelines for a well-controlled polymerization. As highlighted above, RDRP in the presence of Cu0 works best for the polymerization of acrylates, due to their high rate coefficients of propagation, relative to termination. This allows relatively rapid polymerizations with high retention of endgroup functionality. Although methacrylates52,88 and styrene89 can be polymerized using this technique, these reactions cannot be carried out at as high a polymerization rate, and they will result in lower end-group functionality. The selection of solvent is important. First, the solvent should dissolve the CuI species, CuII species, polymer, and monomer. Additionally, the solvents should provide a high value of the ATRP equilibrium constant, as is required for all polymerizations with a low concentration Cu catalyst,21 and the solvent should allow for relatively slow rates of CuI and Cu0 Q


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Figure 15. (a) Plot of concentrations of all species vs monomer conversion. (b) Plot of reaction rates vs monomer conversion. Conditions: [MA]0: [MBrP]0:[Me6TREN]0 = 200:1:0.1, MA/DMSO = 2/1 (v/v), T = 25 °C, 1 cm of Cu0 (d = 0.5 mm, S = 0.16 cm2) in 10 mL of solvent, S/V = 0.016 cm−1, rate coefficients given in the Supporting Information. Rp, Ra1, Rd1, Ra0, Rt, Rcomp, Rdisp, and Rd0 are the rates of propagation, activation by CuI, deactivation by CuII, activation by Cu0, termination, comproportionation, disproportionation, and deactivation by CuI, respectively.

induced radical loss.69,129 Finally, the solvent should not lead to very high rates of comproportionation, to avoid the possibility of a runaway reaction caused by comproportionation between Cu0 and CuII forming 2 CuI, which both activate alkyl halides, forming more CuII, which again comproportionate. DMSO is a good solvent for RDRP in the presence of Cu0, since it provides a high equilibrium constant, solubilizes poly(methyl acrylate), and gives an appropriate ratio of rates of supplemental activation to comproportionation.65 DMF is also a good solvent since it has similar properties to DMSO65 and solubilizes a wider variety of polymers. Acetonitrile can also be used, but it gives a lower value of the ATRP equilibrium constant, leading to more CuI in the ATRP equilibrium, which can reduce the end-group functionality by catalytic radical termination. Although toluene can also be used, the lower solubility of copper salts and chain-end functionality in toluene makes it a less desirable solvent for the polymerization. In addition to the monomer and solvent, the surface area of Cu0 used must be chosen carefully. Since the radical concentration and consequently the polymerization and termination rates depend on the square root of the ratio of the Cu0 surface area to the reaction volume (S/V), a balance must be found for a given polymer architecture. If only homopolymers with a narrow molecular weight distribution are desired, a higher surface area, for instance using a length of 4 cm of 1 mm diameter wire in 10 mL volume can be used to reach >85% conversion in 1 h.66 However, if higher end-group functionality is desired, then a slower polymerization should be performed, for instance using a length of just 1 cm of 0.5 mm diameter wire. This polymerization is highlighted in Figure 14, showing that the chain-end functionality is still greater than 96% at >80% conversion for both targeted DP = 200 and targeted DP = 60. The final two components to be considered are the ligand and added CuIIBr2 species. For the RDRP in the presence of Cu0, ligands that form ATRP catalysts with large rate coefficients of activation and deactivation should be used, particularly for acrylates. These ligands include Me6TREN and TPMA as well as other highly active TPMA derivatives.38,66 The high activity ensures that the majority of the soluble Cu is in the CuII deactivator form, which is necessary for wellcontrolled polymers with parts per million of soluble Cu species. As highlighted above, the ratio of ligand to alkyl halide initiator should also be chosen carefully, since if the

concentration of ligand is too low, the polymerization will be too slow, while an excessive concentration of ligand can lead to too many dead chains and other side reactions.174 Generally, a ratio of ligand to alkyl halide initiator of ca. 0.1 gives a good compromise between these two factors. Although not needed for the polymerization, addition of CuIIBr2 at the start of the reaction can improve the control over the polymerization, particularly at low conversion; however, it will lead to a higher concentration of Cu species in the final polymer.

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OVERALL PICTURE OF RDRP IN THE PRESENCE OF Cu0 The RDRP process in the presence of Cu0 is well described by SARA ATRP, as shown in Scheme 6. The concentrations of various species and the rates of all reactions are shown in Figure 15 for a typical RDRP in the presence of Cu0 under the conditions: 25 °C, [MA]0:[MBrP]0:[Me6TREN]0 = 200:1:0.1, MA/DMSO = 2/1 (v/v), 1 cm of Cu0 (d = 0.5 mm, S = 0.16 cm2) in 10 mL of solvent. Details of the simulations may be found in the Supporting Information. Propagation, activation by CuI, and deactivation by CuII are the dominant reactions. The ATRP equilibrium is maintained throughout the whole reaction, implying the rate of activation by CuI matches the rate of deactivation by CuII. This ATRP equilibrium allows efficient exchange of the radicals with the Br-capped chains. The next significant reactions are termination, activation by Cu0 and comproportionation. At the start of the polymerization, under the conditions [MA]0:[MBrP]0:[Me6TREN]0 = 200:1:0.1, MA/DMSO = 2/1 (v/v), 1 cm of Cu0 (d = 0.5 mm, S = 0.16 cm2) in 10 mL of solvent, propagation occurs 1 order of magnitude faster than activation by CuI and deactivation by CuII, and the rate of activation by Cu0 rate is comparable to the termination rate. The propagation rate is 4 orders of magnitude higher than the termination rate, and the rates of activation by CuI and deactivation by CuII are 3 orders of magnitude higher than the rates of activation by Cu0 and termination. Under typical polymerization conditions, comproportionation occurs at a rate 0.5−1 orders of magnitude slower than the rate of activation by Cu0, while disproportionation and deactivation by CuI occur at rates 4 and 6 orders of magnitude slower than activation by Cu0, respectively, or 7 and 10 orders of magnitude slower than activation by CuI, respectively.69 As shown by the above analysis, Cu0 is of moderate activity, and if it were superactive, it R


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would cause a very high rate of comproportionation and alkyl halide activation, which would lead to a high termination rate and low chain-end functionality. Instead, CuI is the major activator of alkyl halides, and Cu0 acts as a supplemental activator and reducing agent, consistent with SARA ATRP. It is the mild conditions, high end-group functionality, and relatively rapid polymerization rate that have made RDRP in the presence of Cu0, or SARA ATRP, an attractive technique for the synthesis of functional polymers. Recent studies63−65,67−69 have established the mechanism of this highly versatile technique to be consistent with SARA ATRP, not SET-LRP.

Perspective

AUTHOR INFORMATION

Corresponding Author

*E-mail: [email protected]. Notes

The authors declare no competing financial interest. Biographies

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CONCLUSIONS Reversible deactivation radical polymerization (RDRP) in the presence of Cu0 is a versatile technique for the synthesis of well-defined polymers with complex architectures. In this article, we have highlighted some of the materials that can be synthesized using this technique, including multisegmented block copolymers and macromolecules with complex architectures such as star and multiblock copolymers. In order to define conditions optimal for a targeted polymer structure, the mechanism of polymerization must be understood. For RDRP in the presence of Cu0, two vastly different mechanisms have been proposed to explain the same polymerizations of monomers such as methyl acrylate in polar solvents such as DMSO, in the presence of Cu0 and ligands, such as Me6TREN, that generate very active catalysts. One mechanismsingle electron transfer living radical polymerization (SET-LRP) assumes instantaneous disproportionation of CuI species, rapid activation of alkyl halides by Cu0 via an outer-sphere electron transfer. The other mechanismsupplemental activator and reducing agent (SARA) ATRPproposes that alkyl halide activation occurs via an inner-sphere electron transfer with CuI as the major activator and Cu0 as a supplemental activator and reducing agent via slow comproportionation between CuII and Cu0; rate of activation by CuI is much faster than that of disproportionation. Thus, the RDRP in the presence of Cu0 is mediated by a typical ATRP equilibrium involving CuI/CuII species and is not mediated by Cu0. This paper critically evaluated the body of experimental and theoretical evidence in the literature, finding that slow comproportionation of Cu species occurs in DMSO based systems, rather than instantaneous disproportionation, that Cu0 acts a supplemental activator, and that CuI is the major activator. This paper showed that the SARA ATRP mechanism can explain all experiments in the literature. These data agree with the assumptions of SARA ATRP and disagree with the assumptions of SET-LRP, and therefore the SET-LRP terminology should not be used to describe the polymerization of acrylates in DMSO or other similar systems. In the future, similar studies should be performed for different solvents, ligands, and monomers to gain a more detailed understanding under various reaction conditions. With the mechanistic insights gained, RDRP in the presence of Cu0 can be optimized to create tailor-made polymers for various materials and biological applications.

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Dominik Konkolewicz studied for his BSc (Hons) at the University of Sydney and received his PhD from the same institution in 2011, under the supervision of Prof. Sébastien Perrier. Presently he is a Visiting Assistant Professor at Carnegie Mellon University, advised by Prof. Krzysztof Matyjaszewski. His research interests span the fields of polymerization mechanisms including that of reversible additionfragmentation chain transfer polymerization (RAFT) and atomtransfer radical polymerization (ATRP); emulsion polymerization; statistical thermodynamics; synthesis and characterization of polymers with complex architectures; and the development of functional materials. He has co-authored over 35 papers in these fields, which have received over 550 citations (current h = 14). He has also received prizes such as an Australian Postgraduate award (2007−2010), Agnes Campbell prize in Organic Chemistry (2010), Surface Coatings Association of Australia Prize (2008, 2010), and the Treloar Prize for Best Oral Presentation at the 2008 Australasian Polymer Symposium, and he was nominated by the Australian Academy of Sciences and accepted by the Japan Society for the Promotion of Science to attend the Second Hope Meeting (2009).

Yu Wang is currently a PhD student advised by Prof. Dr. Krzysztof Matyjaszewski in Department of Chemistry, Carnegie Mellon University. He received his B.S. degree in Polymer Science and Engineering in 2003 from Qingdao University, Qingdao, China. Then he moved to Tinghua University, Beijing, China, to get the MS degree in Material Science and Engineering in 2008. The same year, he joined the current group where his research mainly focused on study of

ASSOCIATED CONTENT

* Supporting Information S

Experimental procedures. This material is available free of charge via the Internet at http://pubs.acs.org. S


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mechanisms and kinetics of atom transfer radical polymerization (ATRP). He will join Prof. Dr. Klaus Müllen’s group in Max Planck Institute for Polymer Research, Mainz, Germany, in October 2013.

Abdirisak Ahmed Isse received his Laurea degree in Industrial Chemistry at the Somali National University, Mogadishu, in 1982. He received his PhD (1989) in Chemical Sciences at the University of Padova. He remained at the same University as a research associate until 2004, when he became researcher at the Department of Chemical Sciences. His research interests are centered in the area of molecular electrochemistry, with particular interest in topics such as electron transfer processes, homogeneous and heterogeneous electrocatalysis, electrosynthesis, electrochemical approach to controlled radical polymerization and cyclization reactions, and environmental electrochemistry.

Mingjiang Zhong received his BS degree in double majors of Chemistry and Mathematics in 2008 at Peking University under the supervision of Prof. Yun-Dong Wu. He is currently a graduate student co-advised by Profs. Krzysztof Matyjaszewski and Tomasz Kowalewski at Carnegie Mellon University. He will join the groups of Profs. Jeremiah A. Johnson and Bradley D. Olsen at the Massachusetts Institute of Technology as a postdoctoral fellow in October 2013. His primary research interests span the subjects of mechanistic study of reversible-deactivation radical polymerization, macromolecular selfassembly, nanocarbon, and soft materials for energy storage and conversion applications. Zhong is a co-author of 26 peer-reviewed papers. He received a variety of honors for his research achievements, including the Astrid and Bruce McWilliams Fellowship (2012), the Chinese Government Award for Outstanding Self-Financed Students Abroad (2012), Guy C. Berry Graduate Research Award (2013), and the Excellent Graduate Student Award, ACS Polymer Division (2013).

Armando Gennaro obtained his Laurea (Master) degree in Chemistry, magna cum laude, at the University of Padova in 1973. He is Professor of Physical Chemistry at the Department of Chemical Sciences of the University of Padova and leader of the “Electrocatalysis and Applied Electrochemistry” group, founded in 1998, which focuses its research activity in the field of electrosynthesis and electrocatalysis, especially the study of the mechanisms of organic electrochemical processes, the development of eco-friendly electrosyntheses for industrial applications, and the development of electrocatalytic materials and/or electrocatalytic processes. The research activity of Armando Gennaro is centered in molecular electrochemistry and is mainly devoted to electrocatalytic properties of electrode materials, electrocatalytic reduction of organic halides, mechanisms of dissociative electron transfers, electrochemistry of controlled radical polymerization, electrochemical activation of carbon dioxide, electrocarboxylation and electrosyntheses of fine chemicals and pharmaceutical compounds, and electrochemical technologies for wastewater treatments.

Pawel Krys graduated from Wroclaw University of Technology as the best student in Department of Chemistry and received his MSc in 2012 under the guidance of Prof. Andrzej Trochimczuk. He was awarded the scholarship of Minister of Science and Higher Education for academic merits. Currently, he is a graduate student at Carnegie Mellon University, advised by Prof. Krzysztof Matyjaszewski. His research interests cover various areas of polymer science including theoretical and mechanistic studies of atom transfer radical polymerization (ATRP) and synthesis of complex polymer architectures. T


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(3) Matyjaszewski, K.; Davis, T. P. Handbook of Radical Polymerization; John Wiley & Sons, Inc.: Hoboken, NJ, 2002. (4) Szwarc, M. Nature 1956, 178, 1168−9. (5) Hadjichristidis, N.; Pitsikalis, M.; Pispas, S.; Iatrou, H. Chem. Rev. 2001, 101, 3747−3792. (6) Georges, M. K.; Veregin, R. P. N.; Kazmaier, P. M.; Hamer, G. K. Macromolecules 1993, 26, 2987−8. (7) Nicolas, J.; Guillaneuf, Y.; Lefay, C.; Bertin, D.; Gigmes, D.; Charleux, B. Prog. Polym. Sci. 2013, 38, 63−235. (8) Chiefari, J.; Chong, Y. K.; Ercole, F.; Krstina, J.; Jeffery, J.; Le, T. P. T.; Mayadunne, R. T. A.; Meijs, G. F.; Moad, C. L.; Moad, G.; Rizzardo, E.; Thang, S. H. Macromolecules 1998, 31, 5559−5562. (9) Moad, G.; Rizzardo, E.; Thang, S. H. Aust. J. Chem. 2012, 65, 985−1076. (10) Perrier, S.; Takolpuckdee, P. J. Polym. Sci., Part A: Polym. Chem. 2005, 43, 5347−5393. (11) Kato, M.; Kamigaito, M.; Sawamoto, M.; Higashimura, T. Macromolecules 1995, 28, 1721−3. (12) Wang, J.-S.; Matyjaszewski, K. J. Am. Chem. Soc. 1995, 117, 5614−15. (13) Matyjaszewski, K.; Xia, J. Chem. Rev. 2001, 101, 2921−2990. (14) Konkolewicz, D.; Monteiro, M. J.; Perrier, S. Macromolecules 2011, 44, 7067−7087. (15) Matyjaszewski, K.; Tsarevsky, N. V. Nat. Chem. 2009, 1, 276− 288. (16) Matyjaszewski, K. Macromolecules 2012, 45, 4015−4039. (17) Averick, S.; Simakova, A.; Park, S.; Konkolewicz, D.; Magenau, A. J. D.; Mehl, R. A.; Matyjaszewski, K. ACS Macro Lett. 2012, 1, 6− 10. (18) Fischer, H. Chem. Rev. 2001, 101, 3581−3610. (19) Tang, W.; Tsarevsky, N. V.; Matyjaszewski, K. J. Am. Chem. Soc. 2006, 128, 1598−1604. (20) Matyjaszewski, K.; Jakubowski, W.; Min, K.; Tang, W.; Huang, J. Y.; Braunecker, W. A.; Tsarevsky, N. V. Proc. Natl. Acad. Sci. U. S. A. 2006, 103, 15309−15314. (21) Tsarevsky, N. V.; Matyjaszewski, K. Chem. Rev. 2007, 107, 2270−2299. (22) Magenau, A. J. D.; Strandwitz, N. C.; Gennaro, A.; Matyjaszewski, K. Science 2011, 332, 81−84. (23) Bortolamei, N.; Isse, A. A.; Magenau, A. J. D.; Gennaro, A.; Matyjaszewski, K. Angew. Chem., Int. Ed. 2011, 50, 11391−11394. (24) Magenau, A. J. D.; Bortolamei, N.; Frick, E.; Park, S.; Gennaro, A.; Matyjaszewski, K. Macromolecules 2013, 46, 4346−4353. (25) Tasdelen, M. A.; Uygun, M.; Yagci, Y. Macromol. Chem. Phys. 2010, 211, 2271−2275. (26) Mosnácě k, J.; Ilčíková, M. Macromolecules 2012, 45, 5859−5865. (27) Konkolewicz, D.; Schröder, K.; Buback, J.; Bernhard, S.; Matyjaszewski, K. ACS Macro Lett. 2012, 1, 1219−1223. (28) Jakubowski, W.; Min, K.; Matyjaszewski, K. Macromolecules 2006, 39, 39−45. (29) Jakubowski, W.; Matyjaszewski, K. Angew. Chem., Int. Ed. 2006, 45, 4482−4486. (30) Min, K.; Gao, H.; Matyjaszewski, K. Macromolecules 2007, 40, 1789−1791. (31) Abreu, C. M. R.; Mendonça, P. V.; Serra, A. N. C.; Popov, A. V.; Matyjaszewski, K.; Guliashvili, T.; Coelho, J. F. J. ACS Macro Lett. 2012, 1, 1308−1311. (32) Zhang, Y.; Wang, Y.; Matyjaszewski, K. Macromolecules 2011, 44, 683−685. (33) Matyjaszewski, K.; Coca, S.; Gaynor, S. G.; Wei, M.; Woodworth, B. E. Macromolecules 1997, 30, 7348−7350. (34) Pintauer, T.; Matyjaszewski, K. Chem. Soc. Rev. 2008, 37, 1087− 1097. (35) D’Hooge, D. R.; Konkolewicz, D.; Reyniers, M.-F.; Marin, G. B.; Matyjaszewski, K. Macromol. Theory Simul. 2012, 21, 52−69. (36) Tang, W.; Kwak, Y.; Braunecker, W.; Tsarevsky, N. V.; Coote, M. L.; Matyjaszewski, K. J. Am. Chem. Soc. 2008, 130, 10702−10713. (37) Magenau, A. J. D.; Kwak, Y.; Schröder, K.; Matyjaszewski, K. ACS Macro Lett. 2012, 1, 508−512.

Krzysztof (Kris) Matyjaszewski was born in Poland in 1950. Since 1985 he is at Carnegie Mellon University where he is currently J. C. Warner University Professor of Natural Sciences and director of Center for Macromolecular Engineering. He also holds appointments of Adjunct Professor at the University of Pittsburgh and the Polish Academy of Sciences in Lodz. He is the co-editor of “Progress in Polymer Science” and “Central European Journal of Chemistry”. He has served as co-editor-in-chief for 10 volume 2012 “Polymer Science: A Comprehensive Reference”. His main research interests include controlled radical polymerization, catalysis, environmental chemistry, and synthesis of advanced materials for optoelectronic and biomedical applications. He has developed Cu-based atom transfer radical polymerization (ATRP) which has been commercialized in US, Europe and in Japan. Fifty companies have been members of ATRP and CRP Consortia at CMU, and 15 commercial licenses on ATRP have been signed. Matyjaszewski has co-edited 17 books, co-authored 80 book chapters and 800 peer-reviewed publications, cited 60 000 times. He holds 45 US and 130 international patents. Matyjaszewski received numerous awards, including 2012 Marie Sklodowska-Curie Medal from Polish Chemical Society, 2012 Prize from Société Chimique de France, 2011 Wolf Prize in Chemistry (Israel), 2010 Gutenberg Award (University of Mainz, Germany), 2009 Presidential Green Chemistry Challenge Award, 2005 Macro UK Medal for Outstanding Contributions to Polymer Science, and 2004 Prize from Foundation of Polish Science and also from the American Chemical Society (2013 AkzoNobel North America Science Award, 2011 Hermann Mark Award, 2011 Award in Applied Polymer Science, 2002 Polymer Chemistry Award, 1995 Creative Polymer Chemistry Award). He is a member of USA National Academy of Engineering, Polish Academy of Sciences, and Russian Academy of Sciences. He received honorary degrees from from Pusan National University, South Korea, l’Institut Polytechnique, Toulouse, France, University of Athens, Greece, Russian Academy of Sciences, Lodz Polytechnic, Poland, and University of Ghent, Belgium.

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ACKNOWLEDGMENTS We thank Yaozhong Zhang, Chi-How Peng, Saadyah Averick, Nicola Bortolamei, and Andrew Magenau for fruitful discussions. The work was supported by the NSF (CHE 1026060) and NMR instrumentation at CMU was partially supported by NSF (CHE-1039870). We thank members of the CRP consortium for financial assistance.

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REFERENCES

(1) Braunecker, W. A.; Matyjaszewski, K. Prog. Polym. Sci. 2007, 32, 93−146. (2) Goto, A.; Fukuda, T. Prog. Polym. Sci. 2004, 29, 329−385. U


Macromolecules

Perspective

(38) Schröder, K.; Mathers, R. T.; Buback, J.; Konkolewicz, D.; Magenau, A. J. D.; Matyjaszewski, K. ACS Macro Lett. 2012, 1, 1037− 1040. (39) Wang, Y.; Kwak, Y.; Buback, J.; Buback, M.; Matyjaszewski, K. ACS Macro Lett. 2012, 1, 1367−1370. (40) Seeliger, F.; Matyjaszewski, K. Macromolecules 2009, 42, 6050− 6055. (41) Morick, J.; Buback, M.; Matyjaszewski, K. Macromol. Chem. Phys. 2012, 213, 2287−2292. (42) Braunecker, W. A.; Tsarevsky, N. V.; Gennaro, A.; Matyjaszewski, K. Macromolecules 2009, 42, 6348−6360. (43) Matyjaszewski, K.; Dong, H.; Jakubowski, W.; Pietrasik, J.; Kusumo, A. Langmuir 2007, 23, 4528−4531. (44) Konkolewicz, D.; Magenau, A. J. D.; Averick, S. E.; Simakova, A.; He, H.; Matyjaszewski, K. Macromolecules 2012, 45, 4461−4468. (45) Simakova, A.; Averick, S. E.; Konkolewicz, D.; Matyjaszewski, K. Macromolecules 2012, 45, 6371−6379. (46) Kwak, Y.; Magenau, A. J. D.; Matyjaszewski, K. Macromolecules 2011, 44, 811−819. (47) Chan, N.; Cunningham, M. F.; Hutchinson, R. A. Macromol. Rapid Commun. 2011, 32, 604−609. (48) Scherer, M.; Bollinger, J. M.; Cooper, D.; Tillery, L. S.; Woodruff, R. Method for the continuous production of polymer compositions by atom-transfer-radical polymerization. 0238618, 20020516, 2002. (49) Matyjaszewski, K.; Gaynor, S. G.; Coca, S. Controlled atom or group-transfer radical polymerization, coupling of molecules, multifunctional polymerization initiators, and formation of telechelic functional material. 9840415, 19980917, 1998. (50) Percec, V.; Guliashvili, T.; Ladislaw, J. S.; Wistrand, A.; Stjerndahl, A.; Sienkowska, M. J.; Monteiro, M. J.; Sahoo, S. J. Am. Chem. Soc. 2006, 128, 14156−14165. (51) Nicolay, R.; Kwak, Y.; Matyjaszewski, K. Angew. Chem., Int. Ed. 2010, 49, 541−544. (52) Magenau, A. J. D.; Kwak, Y.; Matyjaszewski, K. Macromolecules 2010, 43, 9682−9689. (53) Matyjaszewski, K.; Tsarevsky, N. V.; Braunecker, W. A.; Dong, H.; Huang, J.; Jakubowski, W.; Kwak, Y.; Nicolay, R.; Tang, W.; Yoon, J. A. Macromolecules 2007, 40, 7795−7806. (54) Harrisson, S.; Couvreur, P.; Nicolas, J. Polym. Chem. 2011, 2, 1859−1865. (55) Matyjaszewski, K.; Woodworth, B. E.; Zhang, X.; Gaynor, S. G.; Metzner, Z. Macromolecules 1998, 31, 5955−5957. (56) Kwak, Y.; Nicolaÿ, R.; Matyjaszewski, K. Macromolecules 2009, 42, 3738−3742. (57) Percec, V.; Barboiu, B.; van der Sluis, M. Macromolecules 1998, 31, 4053−4056. (58) Matyjaszewski, K.; Nakagawa, Y.; Jasieczek, C. B. Macromolecules 1998, 31, 1535−1541. (59) Xia, J.; Gaynor, S. G.; Matyjaszewski, K. Macromolecules 1998, 31, 5958−5959. (60) Queffelec, J.; Gaynor, S. G.; Matyjaszewski, K. Macromolecules 2000, 33, 8629−8639. (61) Lin, C. Y.; Coote, M. L.; Gennaro, A.; Matyjaszewski, K. J. Am. Chem. Soc. 2008, 130, 12762−12774. (62) Soeriyadi, A. H.; Boyer, C.; Nyström, F.; Zetterlund, P. B.; Whittaker, M. R. J. Am. Chem. Soc. 2011, 133, 11128−11131. (63) West, A. G.; Hornby, B.; Tom, J.; Ladmiral, V.; Harrisson, S.; Perrier, S. b. Macromolecules 2011, 44, 8034−8041. (64) Guliashvili, T.; Mendonça, P. V.; Serra, A. C.; Popov, A. V.; Coelho, J. F. J. Chem.Eur. J. 2012, 18, 4607−4612. (65) Harrisson, S.; Couvreur, P.; Nicolas, J. Macromolecules 2012, 45, 7388−7396. (66) Zhang, Y.; Wang, Y.; Peng, C.-h.; Zhong, M.; Zhu, W.; Konkolewicz, D.; Matyjaszewski, K. Macromolecules 2012, 45, 78−86. (67) Wang, Y.; Zhong, M.; Zhu, W.; Peng, C.-H.; Zhang, Y.; Konkolewicz, D.; Bortolamei, N.; Isse, A. A.; Gennaro, A.; Matyjaszewski, K. Macromolecules 2013, 46, 3793−3802.

(68) Peng, C.-H.; Zhong, M.; Wang, Y.; Kwak, Y.; Zhang, Y.; Zhu, W.; Tonge, M.; Buback, J.; Park, S.; Krys, P.; Konkolewicz, D.; Gennaro, A.; Matyjaszewski, K. Macromolecules 2013, 46, 3803−3815. (69) Zhong, M.; Wang, Y.; Krys, P.; Konkolewicz, D.; Matyjaszewski, K. Macromolecules 2013, 46, 3816−3827. (70) Lligadas, G.; Rosen, B. M.; Monteiro, M. J.; Percec, V. Macromolecules 2008, 41, 8360−8364. (71) Rosen, B. M.; Percec, V. Chem. Rev. 2009, 109, 5069−5119. (72) Lligadas, G.; Percec, V. J. Polym. Sci., Part A: Polym. Chem. 2007, 45, 4684−4695. (73) Lligadas, G.; Ladislaw, J. S.; Guliashvili, T.; Percec, V. J. Polym. Sci., Part A: Polym. Chem. 2008, 46, 278−288. (74) Nguyen, N. H.; Levere, M. E.; Kulis, J.; Monteiro, M. J.; Percec, V. Macromolecules 2012, 45, 4606−4622. (75) Buback, M.; Kurz, C. H.; Schmaltz, C. Macromol. Chem. Phys. 1998, 199, 1721−1727. (76) Asua, J. M.; Beuermann, S.; Buback, M.; Castignolles, P.; Charleux, B.; Gilbert, R. G.; Hutchinson, R. A.; Leiza, J. R.; Nikitin, A. N.; Vairon, J.-P.; van Herk, A. M. Macromol. Chem. Phys. 2004, 205, 2151−2160. (77) Johnston-Hall, G.; Monteiro, M. J. J. Polym. Sci., Part A: Polym. Chem. 2008, 46, 3155−3173. (78) Zhong, M.; Matyjaszewski, K. Macromolecules 2011, 44, 2668− 2677. (79) Sienkowska, M. J.; Rosen, B. M.; Percec, V. J. Polym. Sci., Part A: Polym. Chem. 2009, 47, 4130−4140. (80) Fleischmann, S.; Percec, V. J. Polym. Sci., Part A: Polym. Chem. 2010, 48, 4889−4893. (81) Fleischmann, S.; Percec, V. J. Polym. Sci., Part A: Polym. Chem. 2010, 48, 4884−4888. (82) Hatano, T.; Rosen, B. M.; Percec, V. J. Polym. Sci., Part A: Polym. Chem. 2010, 48, 164−172. (83) Liu, X. H.; Zhang, G. B.; Li, B. X.; Bai, Y. G.; Li, Y. S. J. Polym. Sci., Part A: Polym. Chem. 2010, 48, 5439−5445. (84) Nguyen, N. H.; Rosen, B. M.; Percec, V. J. Polym. Sci., Part A: Polym. Chem. 2010, 48, 1752−1763. (85) Turan, E.; Caykara, T. J. Polym. Sci., Part A: Polym. Chem. 2010, 48, 5842−5847. (86) Ding, W.; Lv, C. F.; Sun, Y.; Liu, X. J.; Yu, T.; Qu, G. M.; Luan, H. X. J. Polym. Sci., Part A: Polym. Chem. 2011, 49, 432−440. (87) Haridharan, N.; Dhamodharan, R. J. Polym. Sci., Part A: Polym. Chem. 2011, 49, 1021−1032. (88) Hornby, B. D.; West, A. G.; Tom, J. C.; Waterson, C.; Harrisson, S.; Perrier, S. Macromol. Rapid Commun. 2010, 31, 1276− 1280. (89) Tom, J.; Hornby, B.; West, A.; Harrisson, S.; Perrier, S. Polym. Chem. 2010, 1, 420−422. (90) Nguyen, N. H.; Kulis, J.; Sun, H.-J.; Jia, Z.; van Beusekom, B.; Levere, M. E.; Wilson, D. A.; Monteiro, M. J.; Percec, V. Polym. Chem. 2013, 4, 144−155. (91) Nguyen, N. H.; Rodriguez-Emmenegger, C.; Brynda, E.; Sedlakova, Z.; Percec, V. Polym. Chem. 2013, 4, 2424−2427. (92) Leng, X.; Nguyen, N. H.; van Beusekom, B.; Wilson, D. A.; Percec, V. Polym. Chem. 2013, DOI: 10.1039/C3PY00048F. (93) Feng, C.; Shen, Z.; Li, Y.; Gu, L.; Zhang, Y.; Lu, G.; Huang, X. J. Polym. Sci., Part A: Polym. Chem. 2009, 47, 1811−1824. (94) Tang, X.; Liang, X.; Yang, Q.; Fan, X.; Shen, Z.; Zhou, Q. J. Polym. Sci., Part A: Polym. Chem. 2009, 47, 4420−4427. (95) Feng, C.; Li, Y. J.; Yang, D.; Li, Y. G.; Hu, J. H.; Zhai, S. J.; Lu, G. L.; Huang, X. Y. J. Polym. Sci., Part A: Polym. Chem. 2010, 48, 15− 23. (96) Zhang, W. D.; Zhang, W.; Zhang, Z. B.; Cheng, Z. P.; Tu, Y. F.; Qiu, Y. S.; Zhu, X. L. J. Polym. Sci., Part A: Polym. Chem. 2010, 48, 4268−4278. (97) Jing, R. K.; Wang, G. W.; Zhang, Y. N.; Huang, J. L. Macromolecules 2011, 44, 805−810. (98) Boyer, C.; Soeriyadi, A. H.; Zetterlund, P. B.; Whittaker, M. R. Macromolecules 2011, 44, 8028−8033. V


Macromolecules

Perspective

(99) Whittaker, M. R.; Urbani, C. N.; Monteiro, M. J. J. Polym. Sci., Part A: Polym. Chem. 2008, 46, 6346−6357. (100) Li, L.-Y.; He, W.-D.; Li, J.; Han, S.-C.; Sun, X.-L.; Zhang, B.-Y. J. Polym. Sci., Part A: Polym. Chem. 2009, 47, 7066−7077. (101) Rosen, B. M.; Lligadas, G.; Hahn, C.; Percec, V. J. Polym. Sci., Part A: Polym. Chem. 2009, 47, 3931−3939. (102) Zhang, W.; Zhang, W.; Zhu, J.; Zhang, Z.; Zhu, X. J. Polym. Sci., Part A: Polym. Chem. 2009, 47, 6908−6918. (103) Zhai, S. J.; Wang, B. D.; Feng, C.; Li, Y. J.; Yang, D.; Hu, J. H.; Lu, G. L.; Huang, X. Y. J. Polym. Sci., Part A: Polym. Chem. 2010, 48, 647−655. (104) Vlcek, P.; Raus, V.; Janata, M.; Kriz, J.; Sikora, A. J. Polym. Sci., Part A: Polym. Chem. 2011, 49, 164−173. (105) Voepel, J.; Edlund, U.; Albertsson, A. C.; Percec, V. Biomacromolecules 2011, 12, 253−259. (106) Boyer, C.; Derveaux, A.; Zetterlund, P. B.; Whittaker, M. R. Polym. Chem. 2012, 3, 117−123. (107) Potisek, S. L.; Davis, D. A.; Sottos, N. R.; White, S. R.; Moore, J. S. J. Am. Chem. Soc. 2007, 129, 13808−13809. (108) Fleischmann, S.; Percec, V. J. Polym. Sci., Part A: Polym. Chem. 2010, 48, 2251−2255. (109) Kaur, S.; Singh, G.; Gupta, V. K. J. Polym. Sci., Part A: Polym. Chem. 2008, 46, 7299−7309. (110) Syrett, J. A.; Jones, M. W.; Haddleton, D. M. Chem. Commun. 2010, 46, 7181−7183. (111) Ding, S.; Floyd, J. A.; Walters, K. B. J. Polym. Sci., Part A: Polym. Chem. 2009, 47, 6552−6560. (112) Zoppe, J. O.; Habibi, Y.; Rojas, O. J.; Venditti, R. A.; Johansson, L. S.; Efimenko, K.; Osterberg, M.; Laine, J. Biomacromolecules 2010, 11, 2683−2691. (113) Jones, M. W.; Gibson, M. I.; Mantovani, G.; Haddleton, D. M. Polym. Chem. 2011, 2, 572−574. (114) Haddleton, D. M.; Clark, A. J.; Crossman, M. C.; Duncalf, D. J.; Heming, A. M.; Morsley, S. R.; Shooter, A. J. Chem. Commun. 1997, 0, 1173−1174. (115) Lligadas, G.; Percec, V. J. Polym. Sci., Part A: Polym. Chem. 2008, 46, 3174−3181. (116) Fleischmann, S.; Rosen, B. M.; Percec, V. J. Polym. Sci., Part A: Polym. Chem. 2010, 48, 1190−1196. (117) Jiang, X. A.; Rosen, B. M.; Percec, V. J. Polym. Sci., Part A: Polym. Chem. 2010, 48, 2716−2721. (118) Wang, W.; Zhang, Z.; Zhu, J.; Zhou, N.; Zhu, X. J. Polym. Sci., Part A: Polym. Chem. 2009, 47, 6316−6327. (119) Fleischmann, S.; Percec, V. J. Polym. Sci., Part A: Polym. Chem. 2010, 48, 2236−2242. (120) Fleischmann, S.; Percec, V. J. Polym. Sci., Part A: Polym. Chem. 2010, 48, 2243−2250. (121) Gao, J.; Zhang, Z.; Zhou, N.; Cheng, Z.; Zhu, J.; Zhu, X. Macromolecules 2011, 44, 3227−3232. (122) Zhang, Q.; Wilson, P.; Li, Z.; McHale, R.; Godfrey, J.; Anastasaki, A.; Waldron, C.; Haddleton, D. M. J. Am. Chem. Soc. 2013, 135, 7355−7363. (123) Nguyen, N. H.; Rosen, B. M.; Lligadas, G.; Percec, V. Macromolecules 2009, 42, 2379−2386. (124) Wang, Y.; Zhong, M.; Zhang, Y.; Magenau, A. J. D.; Matyjaszewski, K. Macromolecules 2012, 45, 8929−8932. (125) Bortolamei, N.; Isse, A. A.; Di Marco, V. B.; Gennaro, A.; Matyjaszewski, K. Macromolecules 2010, 43, 9257−9267. (126) Levere, M. E.; Nguyen, N. H.; Percec, V. Macromolecules 2012, 45, 8267−8274. (127) Nguyen, N. H.; Levere, M. E.; Percec, V. J. Polym. Sci., Part A: Polym. Chem. 2012, 50, 860−873. (128) Schröder, K.; Konkolewicz, D.; Poli, R.; Matyjaszewski, K. Organometallics 2012, 31, 7994−7999. (129) Wang, Y.; Soerensen, N.; Zhong, M.; Schroeder, H.; Buback, M.; Matyjaszewski, K. Macromolecules 2013, 46, 683−691. (130) Foll, A.; Le Démezet, M.; Courtot-Coupez, J. J. Electroanal. Chem. 1972, 35, 41−54.

(131) Ahrland, S.; Blauenstein, P.; Tagesson, B.; Tuhtar, D. Acta Chem. Scand., Ser. A 1980, 34, 265−272. (132) Tsarevsky, N. V.; Braunecker, W. A.; Matyjaszewski, K. J. Organomet. Chem. 2007, 692, 3212−3222. (133) Rosen, B. M.; Jiang, X.; Wilson, C. J.; Nguyen, N. H.; Monteiro, M. J.; Percec, V. J. Polym. Sci., Part A: Polym. Chem. 2009, 47, 5606−5628. (134) Levere, M. E.; Nguyen, N. H.; Leng, X.; Percec, V. Polym. Chem. 2013, 4, 1635−1647. (135) Nguyen, N. H.; Sun, H.-J.; Levere, M. E.; Fleischmann, S.; Percec, V. Polym. Chem. 2013, 4, 1328−1332. (136) Wang, J.-S.; Matyjaszewski, K. Macromolecules 1995, 28, 7901− 7910. (137) Pintauer, T.; Braunecker, W.; Collange, E.; Poli, R.; Matyjaszewski, K. Macromolecules 2004, 37, 2679−2682. (138) Bell, C. A.; Bernhardt, P. V.; Monteiro, M. J. J. Am. Chem. Soc. 2011, 133, 11944−11947. (139) Horn, M.; Matyjaszewski, K. Macromolecules 2013, 46, 3350− 3357. (140) Levere, M. E.; Nguyen, N. H.; Sun, H.-J.; Percec, V. Polym. Chem. 2013, 4, 686−694. (141) Konkolewicz, D.; Sosnowski, S.; D’hooge, D. R.; Szymanski, R.; Reyniers, M.-F.; Marin, G. B.; Matyjaszewski, K. Macromolecules 2011, 44, 8361−8373. (142) Savéant, J.-M. In Advances in Electron Transfer Chemistry; Mariano, P. S., Ed.; JAI Press: New York, 1994; Vol. 4, pp 53−116. (143) Andrieux, C. P.; Gallardo, I.; Savaent, J. M.; Su, K. B. J. Am. Chem. Soc. 1986, 108, 638−647. (144) Cardinale, A.; Isse, A. A.; Gennaro, A.; Robert, M.; Savéant, J.M. J. Am. Chem. Soc. 2002, 124, 13533−13539. (145) Isse, A.; Berzi, G.; Falciola, L.; Rossi, M.; Mussini, P.; Gennaro, A. J. Appl. Electrochem. 2009, 39, 2217−2225. (146) Andrieux, C. P.; Blocman, C.; Dumas-Bouchiat, J. M.; Savéant, J. M. J. Am. Chem. Soc. 1979, 101, 3431−3441. (147) Enemaerke, R. J.; Christensen, T. B.; Jensen, H.; Daasbjerg, K. J. Chem. Soc., Perkin Trans. 2 2001, 0, 1620−1630. (148) Isse, A. A.; Mussini, P. R.; Gennaro, A. J. Phys. Chem. C 2009, 113, 14983−14992. (149) Lexa, D.; Saveant, J. M.; Su, K. B.; Wang, D. L. J. Am. Chem. Soc. 1987, 109, 6464−6470. (150) Lexa, D.; Saveant, J. M.; Schaefer, H. J.; Binh, S. K.; Vering, B.; Wang, D. L. J. Am. Chem. Soc. 1990, 112, 6162−6177. (151) Howes, K. R.; Bakac, A.; Espenson, J. H. Inorg. Chem. 1988, 27, 3147−3151. (152) Haim, A. Acc. Chem. Res. 1975, 8, 264−272. (153) Jagannadham, V.; Steenken, S. J. Am. Chem. Soc. 1984, 106, 6542−6551. (154) Kochi, J. K. Acc. Chem. Res. 1992, 25, 39−47. (155) Weaver, M. J.; Anson, F. C. Inorg. Chem. 1976, 15, 1871−1881. (156) Isse, A. A.; Falciola, L.; Mussini, P. R.; Gennaro, A. Chem. Commun. 2006, 344−346. (157) Matyjaszewski, K. Macromolecules 1998, 31, 4710−4717. (158) Guliashvili, T.; Percec, V. J. Polym. Sci., Part A: Polym. Chem. 2007, 45, 1607−1618. (159) Isse, A. A.; Bortolamei, N.; De Paoli, P.; Gennaro, A. Electrochim. Acta 2013, http://dx.doi.org/10.1016/j.electacta.2013.04. 132. (160) Isse, A. A.; Gennaro, A.; Lin, C. Y.; Hodgson, J. L.; Coote, M. L.; Guliashvili, T. J. Am. Chem. Soc. 2011, 133, 6254−6264. (161) Isse, A. A.; Lin, C. Y.; Coote, M. L.; Gennaro, A. J. Phys. Chem. B 2011, 115, 678−684. (162) Gennaro, A.; Isse, A. A.; Bianchi, C. L.; Mussini, P. R.; Rossi, M. Electrochem. Commun. 2009, 11, 1932−1935. (163) Qiu, J.; Matyjaszewski, K.; Thouin, L.; Amatore, C. Macromol. Chem. Phys. 2000, 201, 1625−1631. (164) Ahmad, N. M.; Charleux, B.; Farcet, C.; Ferguson, C. J.; Gaynor, S. G.; Hawkett, B. S.; Heatley, F.; Klumperman, B.; Konkolewicz, D.; Lovell, P. A.; Matyjaszewski, K.; Venkatesh, R. Macromol. Rapid Commun. 2009, 30, 2002−2021. W


Macromolecules

Perspective

(165) Junkers, T.; Barner-Kowollik, C. J. Polym. Sci., Part A: Polym. Chem. 2008, 46, 7585−7605. (166) Boyer, C.; Atme, A.; Waldron, C.; Anastasaki, A.; Wilson, P.; Zetterlund, P. B.; Haddleton, D.; Whittaker, M. R. Polym. Chem. 2013, 4, 106−112. (167) Lligadas, G.; Percec, V. J. Polym. Sci., Part A: Polym. Chem. 2008, 46, 6880−6895. (168) Nguyen, N. H.; Rosen, B. M.; Jiang, X.; Fleischmann, S.; Percec, V. J. Polym. Sci., Part A: Polym. Chem. 2009, 47, 5577−5590. (169) Nguyen, N. H.; Jiang, X.; Fleischmann, S.; Rosen, B. M.; Percec, V. J. Polym. Sci., Part A: Polym. Chem. 2009, 47, 5629−5638. (170) Nyström, F.; Soeriyadi, A. H.; Boyer, C.; Zetterlund, P. B.; Whittaker, M. R. J. Polym. Sci., Part A: Polym. Chem. 2011, 49, 5313− 5321. (171) Streitwieser, A. Chem. Rev. 1956, 56, 571−752. (172) Moad, G.; Solomon, D. H. The Chemistry of Free Radical Polymerization, 2nd ed.; Elsevier: Amsterdam, 2006. (173) Schön, F.; Hartenstein, M.; Müller, A. H. E. Macromolecules 2001, 34, 5394−5397. (174) Anastasaki, A.; Waldron, C.; Wilson, P.; McHale, R.; Haddleton, D. M. Polym. Chem. 2013, 4, 2672−2675. (175) Lligadas, G.; Rosen, B. M.; Bell, C. A.; Monteiro, M. J.; Percec, V. Macromolecules 2008, 41, 8365−8371.

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