Atom Transfer Radical Polymerization (ATRP): Current Status and

Perspective pubs.acs.org/Macromolecules

Atom Transfer Radical Polymerization (ATRP): Current Status and Future Perspectives Krzysztof Matyjaszewski Department of Chemistry, Carnegie Mellon University, 4400 Fifth Avenue, Pittsburgh, Pennsylvania 15213, United States ABSTRACT: Current status and future perspectives in atom transfer radical polymerization (ATRP) are presented. Special emphasis is placed on mechanistic understanding of ATRP, recent synthetic and process development, and new controlled polymer architectures enabled by ATRP. New hybrid materials based on organic/inorganic systems and natural/synthetic polymers are presented. Some current and forthcoming applications are described.

■

INTRODUCTION Conventional radical polymerization (RP) is employed to produce annually ca. 100 million tons of polymers, with thousands of different compositions. However, the architectural control in these polymers is very limited. Therefore, the advent of controlled radical polymerization (IUPAC recommends a term reversible-deactivation radical polymerization (RDRP) or controlled reversible-deactivation radical polymerization to describe the procedures and discourages using a term “living radical polymerization”)1 has opened new avenues to various advanced materials with precisely controlled molecular architecture.2 For a long time, control of molecular architecture in a RP was considered impossible at a level similar to other living ionic systems because two radicals always terminate at a very fast, diffusion-controlled rate.3 Although living radical polymerization cannot be realized in the purist’s sense, when the concept of dynamic equilibrium was introduced to radical polymerization,4 it revolutionized this field and gave access to polymers with precisely controlled molecular weight, relatively low dispersities (Mw/Mn < 1.1), and controlled molecular architecture in terms of chain topology (stars, cycles, combs, brushes, regular networks), composition (block, graft, alternating, gradient copolymers), and diverse functionality. Under appropriate conditions, the proportion of terminated chains could be sufficiently small (typically between 1 and 10 mol %) that it does not interfere with the designed architecture.3 The formation of the required dynamic equilibria in RDRP’s can be accomplished in two ways. One approach employs reversible deactivation of propagating radicals to form dormant species that can be intermittently reactivated either in a catalytic manner, as in atom transfer radical polymerization, ATRP,5 or spontaneously, as in stable radical mediated polymerization, SRMP (with aminoxyl radicals or organometallic species).6 The kinetics of an ATRP generally follows a persistent radical effect.7 The second approach employs degenerate transfer between propagating radicals and a dormant species. Typical examples of degenerative transfer radical polymerization, DTRP, include © 2012 American Chemical Society

reversible addition−fragmentation chain-transfer polymerization, RAFT,8 or iodine transfer radical polymerization, ITRP.9 Generally, for DTRP, an external source of radicals is necessary, but the dormant species can also be activated internally by Cu-based catalyst, without generation of new chains.10 RDRP is among the most rapidly developing areas of polymer science since it is a versatile synthetic tool that enables preparation of new (co)polymers with controlled architecture and materials for various advanced technologies and biomedicine. Figure 1 presents the cumulative number of papers

Figure 1. Results of SciFinder search on various RDRP systems as of December 30, 2011. A detailed explanation of terms is provided in the text.

published during the past 15 years on overall RDRP processes (using terms controlled radical polymn or living radical polymn, “SUM CRP”) and on more specific systems, ATRP or atom transfer (radical) polymn (“SUM ATRP”; this search does not Received: January 22, 2012 Revised: March 25, 2012 Published: April 11, 2012 4015

dx.doi.org/10.1021/ma3001719 | Macromolecules 2012, 45, 4015−4039

Macromolecules

Perspective

equilibrium constant and the concentration of dormant species, activators, and deactivators, as shown in eq 1.

include terms such as metal mediated or metal catalyzed (living) radical polymerization), NMP or SFRP or nitroxide mediated polymn or stable f ree polymn (“SUM SFRP”), and RAFT (“SUM RAFT”). The latter two terms were respectively refined with terms radical polymn and polymer or polymn, since the search coincides with other common chemical terms such as N-methylpyrrolidone or raft-associated proteins. In summary, over 18 000 papers have been published on various RDRP systems since 1995 and more than 11 000 on ATRP. Figure 1 also shows that recently more papers are published on specific RDRP methods rather than on a generic CRP or LRP. The growth in the number of publications in all areas of RDRP reflects the increasing interest in this field, although now many papers do not use term related to RDRP in titles, abstract, or keywords, as they become well-known “classic” terms in polymer science. Each of three major RDRP techniques has certain advantages and limitations. A common feature of all of them is that they all have typical signatures of radical processes, including specific chemo-, regio-, and stereoselectivities, such as specific reactivity ratios, limited tacticity control, and unavoidable radical termination. However, ATRP, SMRP, and DTRP each have their own peculiarities, expressed by the range of polymerizable monomers, available initiators, reaction conditions, techniques for preparation of polymers with complex architecture, hybrids, functional surfaces, etc. This Perspective will be focused on copper-mediated ATRP and will present a summary of the present state-of-the-art and future perspectives focusing on mechanistic aspects, synthetic procedures, formation of copolymers with complex architectures, preparation functional materials, and applications.

⎛ [P X][Cu I/L][M] ⎞ ⎟⎟ R p = k p[M][P*n] = k pKATRP⎜⎜ n II ⎝ [X−Cu /L] ⎠

(1)

The structure of the ligand and monomer/dormant species as well as reaction conditions (solvent, temperature, and pressure) can strongly influence the values of the rate constants, kact12 and kdeact,13 and their ratio, KATRP.7a,13b Rates of ATRP increase with catalysts activity (KATRP) but under some conditions may decrease, due to radical termination and a resulting low [CuI/L]/[ X−CuII/L] ratio, due to buildup in the concentration of deactivator via the persistent radical effect.7b Equation 2 shows how, in the ideal case for fast initiation and no chain termination or chain transfer, the dispersity of molecular weight (MW) (Mw/Mn) of polymers prepared by ATRP is affected by the concentration of dormant species (PnX) and deactivator (X−CuII), the rate constants of propagation (kp) and deactivation (kdeact), and monomer conversion (p).14 ⎞⎛ 2 ⎛ ⎞ k p[PnX] Mw 1 ⎟⎟⎜ − 1⎟ =1+ + ⎜⎜ II Mn DPn ⎝ kdeact[X−Cu /L] ⎠⎝ p ⎠

(2)

Thus, for the same monomer, a catalyst that deactivates the growing chains faster will result in smaller kp/kdeact and will produce polymers with a lower Mw/Mn value and a narrower MW distribution, MWD. This value can be decreased by increasing the concentration of deactivator, reducing the concentration of the dormant species (targeting higher MW), and attaining higher conversion. Rates of ATRP and Chain End Functionality. Chain growth in all RDRP processes, including ATRP, occurs via radical intermediates that exchange with dormant species. These radicals are not only intermittently formed and propagate but also continuously terminate. At the first approximation (without taking into account the chain length dependent termination coefficient), the same polymerization rate indicates the same concentration of propagating radicals in any RP (also in RDRP) and, consequently, the same concentration of terminated chains. However, in conventional RP, at any time essentially all chains are dead (except ppm amounts of growing chains that are constantly formed and terminate after ca. 1 s growth time). Conversely, in RDRP, the fraction of terminated chains is significantly smaller (1−10%) because of a large pool of dormant species that are intermittently activated. If initiation is sufficiently fast, this process results in the concurrent growth of essentially all chains (except for the small fraction of dead chains). A new paradigm of ATRP (and other RDRP processes) relies on extending life of propagating chains from about 1 second in conventional RP to more than 1 day, by inserting dormant periods of ∼1 minute after each ∼1 ms activity. Thus, the 1 second of radical activity is expanded, like an accordion, to several hours with hundreds intermediate dormancy periods. This would be like extending human life from 70 years to 2000 years, much more than in a classic Rip van Winkle story − if each day of our active life would be followed by one month of a dormant state. Nevertheless, in all RDRP, termination always occurs, and it is important to know how many chains lost functionality and cannot be further chain extended or functionalized. Understanding how the different reaction conditions can affect chain end functionality is equally important. Assuming predominant

■

ATRP MECHANISM ATRP is controlled by an equilibrium between propagating radicals and dormant species, predominately in the form of initiating alkyl halides/macromolecular species (PnX). The dormant species periodically react with the rate constant of activation (keact) with transition metal complexes in their lower oxidation state, Mtm/L, acting as activators (Mtm represents the transition metal species in oxidation state m and L is a ligand; the charges of ionic species and counterions are omitted here) to intermittently form growing radicals (Pn•), and deactivatorstransition metal complexes in their higher oxidation state, coordinated with halide ligands X−Mtm+1/L (Scheme 1). Scheme 1. ATRP Equilibrium

The deactivator reacts with the propagating radical in a reverse reaction (kdeact) to re-form the dormant species and the activator. ATRP is a catalytic process and can be mediated by many redox-active transition metal complexes (CuI/L and X−CuII/L has been the most often used transition metal but other studied metals include Ru, Fe, Mo, Os, etc.).11 The rate of an ATRP depends on the rate constant of propagation and on the concentrations of monomer and growing radicals. The radical concentration depends on the ATRP 4016


Macromolecules

Perspective

Table 1. Minimal Time Required for Polymerization of MA, MMA, and St with Preserved 90% Functionality (DCF = 10%)a DPT = 500 M MA MMA St

DPT = 100

kp (M−1 s−1)b

kt (M−1 s−1)b

p = 60%

p = 90%

p = 60%

p = 90%

47400 1300 665

1.10 × 10 9.00 × 107 1.10 × 108

37 s 13.3 h 2.8 days

234 s 83.9 h 17.5 days

7s 2.7 h 0.6 days

47 s 16.8 h 3.5 days

8

Conditions: 80 °C, [M]0/[R−X]0 = DPT, bulk polymerization. bkp and kt values from literature data.16 The value for kt is the sum of ktc (the combination rate constant) and ktd (the disproportionation rate constant). a

by Cu complexes, resulting in a small fraction of terminated chains. Although nonradical active species were proposed in ATRP,18 there is abundant evidence that ATRP operates via a radical mechanism. This includes cross-propagation kinetics and reactivity ratios,19 regioselectivity and stereoselectivity,19c,20 tacticity,21 racemization, chemoselectivity with various traps and transfer agents,22 radical termination products, and kinetic isotope effects;23 all have values similar to those in conventional RP. In addition, propagating radicals have been observed directly by EPR in the polymerization of dimethacrylates,24 and EPR revealed the presence of X−CuII species resulting from the persistent radical effect in ATRP.25 Nevertheless, the multiple competing equilibria involved in RDRP with intermittent activation can result in some differences in cross-propagation kinetics or branching from those in a standard RP.25g,26 ISET vs OSET. ATRP is a radical-based process and radicals can be formed from dormant species by several pathways. Mechanistically, halogen atom transfer from alkyl halide to CuI complex can occur via either the outer-sphere electron transfer (OSET) or the inner-sphere electron transfer (ISET), i.e., atom transferpassing through a Cu−X−C transition state, which is formally also a single electron transfer process. OSET can proceed via a stepwise manner with radical anion intermediates or in a concerted process with simultaneous dissociation of alkyl halide to a radical and anion. According to Marcus analysis of electron transfer processes (Figure 2), OSET has an energy barrier ∼15 kcal/mol higher than what is experimentally measured, i.e., OSET is ∼1010 times slower than ISET.27 The differences are much greater than any computational or experimental errors, and consequently, it must be concluded that a copper-catalyzed ATRP occurs via concerted homolytic dissociation of the alkyl halide via ISET, i.e., an atom transfer process. Energetically least favorable is the two-step process via the radical anion intermediates.28 This mechanistic feature should apply to ATRP systems catalyzed by other transition metal complexes, as the main reason for slow OSET process is a very slow electron transfer to alkyl halides, the dormant species in an ATRP. The electron transfer between transition metal complexes may be relatively fast.29 Structure−Reactivity Correlation in ATRP. Equilibrium constants in ATRP depend on the structure of the catalysts and alkyl halides (i.e., monomer) and also on the reaction medium. Generally, ATRP equilibrium constants increase strongly with solvent polarity, by stabilization of more polar CuII species, and also with temperature. Deactivation rate constants are usually very high and may approach diffusion control limits (kdeact > 107 M−1 s−1). They are less influenced by the structure of the involved reagents than the activation rate constants.13a Figures 3 and 4 illustrate variation of the values of kact with the alkyl halides and ligand structure. Alkyl Halides. Reactivities of alkyl halides in ATRP depend on the structure of the alkyl group and transferable (pseudo)halogen. It is important to select a sufficiently reactive species

termination by disproportionation with the rate coefficient of termination, kt, the dead chain fraction (DCF, defined as a ratio of concentration of terminated chains, T, to initial concentration of initiator, R−X) depends on targeted degree of polymerization (DPT, i.e., ratio of [M]0 to [R−X]0), monomer conversion (p), propagation and termination rate constants (kp, kt), and reaction time, t. Equation 3 indicates that DCF decreases for slower rates of polymerization (longer t), lower monomer conversion (smaller p), lower targeted DPT, and higher initial monomer concentration (larger [M]0) and for rapidly propagating monomers (lower kt/(kp)2 value). DCF =

2DPTk t[ln(1 − p)]2 [T] = [R−X]0 [M]0 k p2t

(3)

Faster polymerization always leads to more termination. In RP, termination is often a diffusion-controlled process and kt values for different monomers are similar. However, propagation rate constants depend strongly on monomer structure. For example, at 80 °C, the kp of styrene (St) is approximately half that of MMA but nearly 2 orders of magnitude smaller than that of methyl acrylate (MA). Table 1 shows corresponding rate constants and values for 10% DCF (90% preserved chain end functionality) for these three monomers.15 For example, it is possible to prepare poly(methyl acrylate) (PMA) with 10% DCF targeting a DPT = 500 at 60% conversion in 37 s. However, as highlighted by boldface entries in Table 1, the same level of control requires 13 h for PMMA and 2.8 days for polystyrene (PSt)! Italic entries show the effect of DPT = 500 and 100 for PMA at 90% conversion. The former requires 4 min but the latter only 1 min. Also, boldface-italic entries show that the same DCF = 10% for PSt and DPT = 100 requires 3.5 days at 90% but only 0.6 days at 60% conversion. Although the required rate of polymerization for sufficiently low DCF depends primarily on the type of monomer, there are some possibilities to decrease kt/(kp)2 by tuning reaction conditions. For example, higher temperatures increase kp much more than kt due to lower activation energy of termination, as compared to that of propagation. However, there is a limit in the ability to increase temperature due to chain transfer (e.g., acrylates), self-initiation (St), depropagation (e.g., methacrylates), and other side reactions involving mediating agents. Pressure is another important parameter.16b Radical propagation has a negative volume of activation while termination has a positive one, and higher pressure not only enhances kp but also reduces kt. This strategy has been successfully applied to synthesize high-MW polymers and hybrids by ATRP.17 Other strategies involve compartmentalization in dispersed media, confined space, charge repulsion, complexation, etc. All these strategies are important as they allow increasing retention of chain end functionality. Radicals as Propagating Species. The “living” nature of ATRP originates in fast initiation, concurrent growth of all chains via intermittent activation of dormant species catalyzed 4017


Macromolecules

Perspective

Figure 2. Comparison of the free energies during an ISET and OSET process for the reaction of bromoacetonitrile with CuI/TPMA catalyst in acetonitrile at 25 °C. Reprinted with permission from ref 27.

Figure 3. ATRP activation rate constants for various initiators with CuIX/PMDETA (X = Br or Cl) in MeCN at 35 °C. 3°: red; 2°: blue; 1°: black; isothiocyanate/thiocyanate: left half-filled; chloride: open; bromide: filled; iodide: bottom half-filled; amide: ▼; benzyl: ▲; ester: □; nitrile: ○; phenyl ester: ◇. Reprinted with permission from ref 32.

because it is more sensitive to polar effects rather than to steric effects.2a,30 In RAFT and SRMP, methacrylates are more reactive than acrylonitrile, as result of a delicate balance between polarity and steric effects.2a,30 Thus, the order of block copolymer synthesis in ATRP should follow the order acrylonitrile > methacrylates > acrylates ≈ styrene > acrylamides. Nevertheless, uniquely in ATRP this order can be altered by a halogen exchange process whereby Br-terminated polyacrylates can be efficiently chain extended with methacrylates in the presence of CuCl catalyst complexes, because the resulting chain extended alkyl chlorides are less reactive than the initially added alkyl bromides.31 There is a good correlation between values of ATRP equilibrium constants and bond dissociation energies calculated by high level ab initio computations.27,30 Values of KATRP together with kp can provide information on relative rates of polymerization of various monomers. For example, if, under

for an efficient ATRP initiation for the selected monomer. Reactivity of alkyl halides follows the order of 3° > 2° > 1°, in agreement with bond dissociation energy needed for homolytic bond cleavage. Also, radical stabilization is enhanced by the presence of an α-cyano group which is more activating than either an α-phenyl or ester group. The most active initiator is ethyl α-bromophenylacetate, with combined activation effect of both benzyl and ester species, which is >10 000 times more active than 1-phenylethyl bromide, PEBr, and >100 000 times more active than methyl 2-bromopropionate, MBrP. Alkyl halide reactivities follow the order I > Br > Cl and are higher than those of alkyl pseudohalides. Knowledge of the order of reactivity of different alkyl halides is important for the selection of appropriate initiators, especially for lower targeted DPs, but also for the efficient synthesis of block copolymers. ATRP differs from other RDRP processes 4018


Macromolecules

Perspective

Figure 4. ATRP activation rate constants for various ligands with EtBriB in the presence of CuIBr in MeCN at 35 °C. N2: red; N3: black; N4: blue; amine/imine: solid; pyridine: open; mixed: left-half solid; linear: □; branched: ▲; cyclic: ○. Reprinted with permission from ref 12.

Figure 5. (A) Ligands 1: Cyclam-B; 2: Me6TREN; 3: TPMA; 4: BPED; 5: TPEDA; 6: PMDETA; 7: BPMPA; 8: dNbpy; 9: HMTETA; 10: bpy; 11: N4[3,2,3]; 12: N4[2,3,2]. (B) Initiators 1: MClAc; 2: BzCl; 3: PECl; 4: MClP; 5: EtCliB; 6: BzBr; 7: ClAN; 8: PEBr; 9: MBrP; 10: ClPN; 11: EtBriB; 12: BrPN; 13: EBPA. Reprinted with permission from ref 13a.

catalyst complex being 10 000 times more active than the Et6TREN complex.34 In ATRP, the dynamics of the exchange reactions may be even more important than the overall values of the equilibrium constants. Radicals must be very quickly deactivated, and values of kdeact should be as large as possible. This requires very rapid rearrangement from L/Cu(II)−X to L/Cu(I) species, with minimal complex reorganization as accomplished with branched tetrapodal ligands. Figures 5A,B show the correlation of activation rate constants (kact) and deactivation rate constants (kdeact) with equilibrium constants (KATRP) for various CuIBr/ligand complexes with a standard alkyl halide, ethyl 2-bromoisobutyrate (EtBriB), and for various initiators in the presence of a CuI/TPMA (tris(pyridylmethyl)amine) at 22 °C in MeCN.12,35 The equilibrium constants increase as a consequence of a large increase in kact accompanied by a small decrease in kdeact. The ideal catalyst for ATRP of less reactive monomers or used at lower concentration should have a large value for KATRP (i.e., larger kact) but also preserve very large value of kdeact.

otherwise same conditions, the ATRP of methyl acrylate would require 1 h to reach 90% conversion, the same conversion would be reached for acrylonitrile within 1 s, for styrene within 10 h, and for vinyl acetate 15 years.33 This demonstrates the necessity of choosing an appropriate catalyst and appropriate reaction conditions for each monomer. Transition Metal Complexes. The range of activity of ATRP catalyst complexes covers over 6 orders of magnitude. The general order of Cu complex activity in ATRP for ligands is tetradentate (cyclic-bridged) > tetradentate (branched) > tetradentate (cyclic) > tridentate > tetradentate (linear) > bidentate ligands; i.e., bridged cyclam, tris(2-dimethylaminoethyl)amine (Me6TREN), and tris(2-pyridylmethyl)amine (TPMA) are among most active and pyridineimine and 2,2′-bipyridine least active. The nature of nitrogen atoms in ligands also plays a role in the activity of the Cu complexes and follows the order pyridine ≈ aliphatic amine > imine < aromatic amines.12 Generally, alkyl amines complex to Cu(II) stronger than pyridines. A C2 bridge between N atoms generates complexes with higher activities than C3 and C4. Steric effects around the Cu center are very important, with a Me6TREN 4019


Macromolecules

Perspective

of the Cu(II)−X bond, like water, is challenging, especially at low concentrations of the complex. Detailed speciation studies should be performed in other solvents and temperatures (or pressures) because stability constants are relative to the particular solvent used and depend on other conditions. Recently, electrochemistry was successfully applied to evaluate not only speciation of different species but also activation and deactivation rate constants of ethyl 2-bromoisobutyrate with CuBr/Me6TREN system in MeCN and DMSO. Fast deactivation (kdeact = 107 M−1 s−1) and an extremely fast activation (kact = 4 × 104 and 9 × 104 M−1 s−1, respectively) was reported in both solvents.42 This confirms that ATRP activation process with CuI species is very fast, especially in DMSO. Medium Effects. Solvents have much lower influence on RP than on ionic polymerization. Nevertheless, the choice of polymerization medium may exert a remarkable effect on the ATRP equilibrium and rate constants.43 The main reason is the less polar character of Cu(I) complexes (with weakly coordinated halide that can be considered as neutral complexes) than the cationic Cu(II) complexes which are strongly stabilized in more polar solvents.39 The effect of solvent on KATRP for CuIBr/HMTETA with MBriB was examined38 in terms of Kamlet−Taft parameters for 11 solvents and then extrapolated to cover catalyst activity in a total of 17 additional solvents, including water. The plot of log(KATRP) values against values predicted by the Kamlet−Taft relationship is shown in Figure 7.38

Activation rate constants increase with temperature and activation energy is higher for less reactive alkyl halides and Cu complexes.36 A similar study on the effect of pressure shows negative volume of activation for ATRP systems, an additional reason for the successful ATRP under high pressure.37 The values of equilibrium and rate constants in ATRP scale very well with the electrochemical activity of the complexes, as shown in Figure 6. A complex with 300 mV more negative

Figure 6. Correlation between KATRP and redox potentials of different ATRP active CuBr2/L complexes in MeCN at 25 °C. Reprinted with permission from ref 38.

redox potential is ca. 100 000 times more reactive than the less reducing complex. Speciation. ATRP catalysts formed from Cu with N-based and halides ligands are formed dynamically, and the concentration of catalytic species and their speciation depend on their stability constants and concentration and also on reaction medium.39 Detailed studies were carried out for copper bromides and chlorides with Me6TREN and PMDETA ligands in acetonitrile at 25 °C. Stability constants for ligand/Cu complexes are much larger for the Cu(II) species (log K = 23.3 for PMDETA and log K = 27.3 for Me6TREN) than for the Cu(I) species (log K = 6.5 for PMDETA and log K = 7.3 for Me6TREN). Bromide is strongly associated with Cu(II) (log K = 4.5 for PMDETA and log K = 6.8 for Me6TREN) but also weakly associated with Cu(I) (log K = 1.8 for PMDETA and log K = 2.3 for Me6TREN). The latter interaction is not obvious because Cu(I) species are typically tetracoordinated. The association of halide with Cu(I) species coordinated with tetradentate TPMA ligand was previously observed by X-ray but also deduced from EXAFS studies.40 Stability constants for chloride complexes are generally larger than for bromides. When the fifth coordination site in the Cu(I) complexes is occupied by a halide, it prevents a direct reaction with the alkyl halide and the OSET atom transfer process. Therefore, the halide must first dissociate from the catalyst complex for atom transfer to occur.41 Therefore, the presence of a large excess of halide anions may slow down an ATRP due to the diminished overall reactivity of Cu(I) species. More precisely, halide association reduces the concentration of tetracoordinated Cu(I) species with a site open for atom transfer. The opposite situation is seen for the Cu(II) species. Efficient deactivation requires the presence of a Cu(II)−X bond, and a Cu(II) complex with a dissociated halide cannot deactivate the growing radical. Thus, conducting an ATRP in solvents that decrease the stability

Figure 7. Experimental vs Kamlet−Taft predicted KATRP. Reprinted with permission from ref 38.

The multivariable linear regression allowed the extrapolation of ATRP catalyst activity to cover complexes that span over 7 orders of magnitude in activity, from 10−11 in fluoroalcohols to nearly 10−4 in water. The latter is 1000 times higher than in DMSO and 10 000 times higher than in acetonitrile, as recently confirmed experimentally.44 Future Perspectives: Mechanisms. Profound mechanistic understanding is needed not only for optimization of the ATRP process but also to expand the range of polymerizable monomers, reduce the amount of catalyst, and allow synthesis of better defined polymers. The previous sections illustrated how the structure of ligands, resulting catalyst complexes and reaction medium (solvent, 4020


Macromolecules

Perspective

temperature and pressure), can affect the dynamics and kinetics of an ATRP equilibrium. These relationships confirm certain trends and allow scaling from one system to another. On one side, it is important to expand these studies to include new alkyl halides, especially pseudohalides such as dithioesters, as they can be used in concurrent ATRP/RAFT processes, but it is also important to develop more reducing and more halidophilic transition metal complexes. According to the excellent correlation of KATRP with redox potentials, shown in Figure 6, the preparation of complexes with 400 mV more negative E1/2 values should result in a million times larger KATRP and could potentially be suitable for vinyl acetate. How could such complexes be prepared? There are several cyclam derivatives with a sufficiently negative redox potential, but they are not efficient in ATRP because they exchange very slowly between X−Cu(II)/L to Cu(I)/L state. So, not only thermodynamics but also kinetics/dynamics is very important. Branched or bridged tetradentate ligands are the best performing ligands so far. Can electronic effects be additionally employed to increase their activity? Indeed, it has been recently demonstrated that electron-donating substituents in pyridine rings can dramatically increase catalysts activity and a Cu complex with bpy having two p-Me2N substituents has a redox potential comparable to Me6TREN complex, one of the most active ATRP catalysts.45 Or perhaps could one entirely change the nature of the ligands from multiamine to metallocene, charged anionic ligands, or carbenes, etc.? There are many possibilities, especially taking into account other transition metal complexes. In fact, complexes of Os, Ru, and some other more halidophilic metals already exhibit much larger ATRP activity than anticipated from their redox properties. Potential side reactions in ATRP with much more active Cu(I) complexes are that they may dimerize or strongly bind with halides and reduce their activity. They may also start to form a direct bond with alkyl radicals entirely changing mechanism from intermittent activation with halides to an organometallic RP, or they could start participating in catalytic chain transfer processes. There are also other challenges for ATRP catalysts that currently limit the application of ATRP to acidic monomers and dienes. Acidic monomers can protonate ligands and destroy the catalyst complexes and dienes, or sometimes even (poly)acrylamides can competitively displace ligands and generate less redox-active complexes. These competitive complex formation processes are especially important for low ppm Cu processes. To overcome these issues, it is necessary to prepare more stable complexes (speciation) but with preserved activity and dynamics. Furthermore, less basic ligands could survive in acidic media. Thus, one should make a thorough correlation for various alkyl halides and complexes, as it was already successfully accomplished for reactions of various electrophiles and nucleophiles.46 Unfortunately, range of reactivities in radical processes is much smaller than in ionic reactions; nevertheless, an example of a linear free energy relationship (LFER) for kact in ATRP systems is shown below in Figure 8. The following equation was applied to correlate the activation rate constants with catalyst activities (C) and alkyl halide initiators (I) that are characterized by catalysts specific slopes (sc).

Figure 8. Correlation between ATRP rate constants of activation for various initiators and CuBr/L complexes in MeCN at 35 °C.

complexes with Me6TREN were most active (C = +2.3) and those with HMTETA least active (C = −1.3). The specific slopes for different catalysts were very similar and varied only from 0.84 (Me6TREN) to 1.09 (Me4Cyclam). Such LFER should be expanded to other systems, also other solvents, to provide a good estimate for values not yet measured. A potential loss of correlation could point toward a mechanism change. As stated earlier, ATRP proceeds through the same radical intermediates and has the same chemo-, regio-, and stereoselectivities as other RPs. However, involvement of multiple equilibria that can compete one with another can lead to altered apparent reactivity ratios in copolymerization and even a different fraction of branching in polyacrylates.26b,c It will be very interesting to explore to a deeper level the concept of modifying interactions between multiple equilibria and use it as a tool for additional architectural control.

■

ATRP PROCESSES ATRP processes have evolved significantly during the past 15 years. The original “normal” ATRP starting with roughly equivalent concentration of R−X and a catalyst with the transition metal in a lower oxidation state (Mtn/L)5a,21b was carried out in bulk or in organic solvents. Subsequently, a “reverse” ATRP was developed that started by addition of the transition metal complex in its higher oxidation state, X−Mtn+1/L, which was then converted to the activator (Mtn) by reaction with a standard free radical initiator.47 This development permitted starting ATRP with oxidatively stable but more reactive complexes that were reduced to the activator state in situ. However, this process could only be used for the preparation of homopolymers and not for block copolymers or systems with a more complex architecture. Simultaneous reverse and normal initiation (SR&NI) ATRP was developed to take advantage of the ability to use more active catalyst complexes with addition of a relatively larger amount of alkyl halide initiator concurrently with a small amount of radical initiators. A limitation of SR&NI was the formation of a small fraction of polymer chains initiated by the added free radical initiator. This also happens in systems based on degenerative transfer, such as RAFT, as new chains are always continuously generated. SR&NI evolved into activators generated by electron transfer (AGET) where the added deactivator was activated by various

log kact = sc × I + C

Activities of alkyl halides increase from I = −3.5 for methyl chloroacetate to I = +0.8 for 2-bromopropionitrile. CuBr 4021


Macromolecules

Perspective

reducing agents48 including Mt0 species49 rather than a radical initiator. The added reducing agents should be selected so that they not form any additional initiating species but only generate activators by electron transfer. Low ppm Cu ARGET and ICAR ATRP Systems. AGET was a precursor to activator regenerated by electron transfer (ARGET) ATRP in which small amount of catalyst is continuously regenerated by a reducing agent to account for unavoidable levels of radical termination. ARGET is a “green” procedure that uses ppm of the catalyst in the presence of appropriate reducing agents such as FDA-approved tin(II) 2-ethylhexanoate (Sn(EH)2), glucose,50 ascorbic acid,51 phenol,48b hydrazine, phenylhydrazine,52 excess inexpensive ligands,53 nitrogen-containing monomers,48e or Cu0. Since the reducing agents allow starting an ATRP with the oxidatively stable CuII species, the reducing/reactivating cycle can be also employed to eliminate air, or other radical traps, in the system. For example, styrene was polymerized by the addition of 5 ppm of CuCl2/Me6TREN and 500 ppm of Sn(EH)2 to the reaction mixture, resulting in preparation of a polystyrene with Mn = 12 500 (Mn,th = 12 600) and Mw/Mn = 1.28 without removal of inhibitors or deoxygenation.50a An additional advantage of ARGET ATRP is that catalystinduced side reactions are diminished. Therefore, it is possible to prepare copolymers with higher molecular weight while retaining chain end functionality.54 The initiators for continuous activator regeneration (ICAR) procedure could be considered as a “reverse” ARGET ATRP (as shown in Scheme 2). In ICAR ATRP, a source of organic

(e.g., RAFT and ATRP), since ATRP can be conducted with an expanding range of radically transferable groups, including alkyl pseudohalides based on dithioesters, xanthates, dithiocarbonates, or trithiocarbonates.57 An advantage of initiating an ATRP with an alkyl pseudohalide as the transferable group over conducting a standard RAFT polymerization is that no new chains are formed by added radical initiators and higher molecular weight copolymers can be prepared. A similar process also allowed preparation of block copolymers with vinyl acetate.58 Zerovalent Metals as Reducing Agents (and Supplemental Activators). Metals such as Cu, Fe, Mg, or Zn can also be used as the reducing agent for X−CuII/L species.59 In addition to acting as a reducing agent, they can act as supplemental activators by a direct reaction with alkyl halides. However, transition metal complexes other than Cu or Fe are generally relatively poor deactivators. ATRP with Cu0 can be considered as a special case because, in the presence of ligand, it produces in situ the efficient activating/deactivating species. Cu0 and Fe0 in a form of “a powder, a turning, a wire, a mesh, a film and an electrode” (claim 19 in ref 60a and claim 24 in ref 60b) were used alone with ATRP ligands and also together with CuII/ligands and FeIII/ligands (including polar DMF) to catalyze ATRP of acrylates, methacrylates, and styrene already in 1997.49a,60 The role of Cu0 and the effect of polar solvents on the kinetics of an ATRP were discussed in detail.38,49,61 Nevertheless, in 2006 it was proposed that the high activity observed in an ATRP conducted in the presence one of the most powerful ligands, Me6TREN and Cu0 (one of several possible reducing agents), in polar solvents indicated a change in mechanism62 rather than reflecting the repercussions of a change in reaction conditions.27,59b The alternative mechanistic proposal for the ATRP of methyl acrylate in DMSO in the presence of Cu0 and Me6TREN was named SET LRP (single electron transfer living radical polymerization).62a The proposed mechanism involves an outer-sphere electron transfer (OSET) from Cu0 to the alkyl halide to form the CuI species and radical anions, although as was already discussed ISET is much faster than OSET and the probability of radical anion formation is very low.28 The resulting CuI species was assumed to “instantaneously” and completely disproportionate back to Cu0 and CuII species. The intermediate radical anions were proposed to cleave, forming propagating radicals and anions that associate with the CuII species. Growing radicals were postulated to be trapped exclusively by CuII species to form the dormant species and a CuI complex that instead of activating the dormant species “instantaneously” disproportionated. Detailed kinetic and mechanistic studies show that alkyl halides preferentially react with the soluble CuI/Me6TREN complex due to its very high ATRP activity,41,42 rather than with solid Cu0 that has a relatively small surface area. The Cu0 serves as a reducing agent and preferentially comproportionates with Cu(II), formed as a “persistent radical” in the radical termination process. Cu0 also slowly reacts directly with alkyl halides, acting as a supplemental activator.59 With typical amounts of ligand, only ∼10% of CuBr/Me6TREN disproportionates in pure DMSO, and this degree of disproportionation is even lower in mixtures containing the less polar methyl acrylate monomer.61 Disproportionation/comproportionation is a relatively slow process rather than “instantaneous”, and since disproportionation is only partial in most systems, comproportionation dominates. CuI is always present in the system and is the predominant activator. The faster rate of polymerization in DMSO is due to the

Scheme 2. ARGET and ICAR ATRP

free radicals is employed to continuously regenerate the CuI activator, which would otherwise be consumed in termination reactions, when catalysts are used at very low concentrations. With this technique, controlled synthesis of polystyrene and poly(meth)acrylates (Mw/Mn < 1.2) can be conducted with catalyst concentrations between 5 and 50 ppm, levels at which removal or recycling of the catalyst complex could be avoided for some applications. The reaction is driven to completion with addition of low concentrations of standard free radical initiators.52a The rate of ICAR ATRP is governed by the rate of decomposition of the added free radical initiator, as in RAFT, while the degree of control, the rate of deactivation, and MWD are controlled by KATRP, as in ATRP.7a,52a,54c,55,56 Indeed, components of RAFT and ICAR ATRP are quite similar. In addition to (co)monomers and radical initiators (AIBN), RAFT includes addition of alkyl dithioesters (often made from alkyl bromides) while ICAR utilizes the same alkyl bromides and ppm amounts of Cu catalyst. These similarities remove the clear distinction between the classic RDRP systems 4022


Macromolecules

Perspective

fact that the ATRP equilibrium constant is larger in DMSO than in other organic solvents.38 Moreover, the OSET process is much slower than the ISET process due to very slow electron transfer to alkyl halides,28,59 and the proposed SET-LRP mechanism is not viable, since it violates the principle of microscopic reversibility.59b ATRP in the presence of Cu0 and ligands that form catalyst complexes that do not disproportionate such as TPMA have the same kinetic features as with Me6 TREN where some disproportionation occurs.61 Thus, it is recommended to avoid using SET-LRP terminology and instead use ARGET ATRP or SARA (supplemental activators and reducing agents) ATRP terms as these terms do describe the fundamentals of the occurring reactions. Nevertheless, the use of Cu(0) as a reducing agent, and supplemental activator, has some advantages due to relatively facile handling and removal of solid Cu(0), control of the rate of reduction by surface area, and atom economy since one Cu(0) atom can take two Br atoms to form CuBr2 species. One limitation of the procedure is that it introduces more transition metal into the reaction mixture. Electrochemical ATRP. In all ARGET and ICAR processes, reducing agents are oxidized, generating some side products: new chains in ICAR, copper halides in SARA, dehydroascorbic acid, and tin(IV) species, etc., in ARGET. These oxidized species might be less benign than the original reducing agents. Therefore, it would be of interest to avoid using chemicals as reducing agents and replace them by electrons, specifically electrical current. This is the concept of electrochemically mediated ATRP (eATRP) in which the ratio of the concentration of activator to deactivator is precisely controlled by electrochemistry. Several parameters, such as applied current, potential, and total charge passed, can be controlled in eATRP to allow selection of the desired concentration of the redox-active catalytic species. The mechanism of ATRP mediated through electrochemical control over the ratio of CuI/CuII and (re)generation of activators is shown in Scheme 3.

Figure 9. Conversion (solid circles) and applied potential (dashed line) with respect to time, in MA polymerization at two different applied potentials. Reprinted from with permission from ref 63. Copyright 2011 AAAS.

under different Eapp increased linearly with conversion and narrow molecular weight distributions were attained.63 Since electrochemistry permits a lower oxidation state catalyst (CuIBr/Me6TREN) to be reverted back to its original higher oxidation state by simply shifting Eapp to more positive values, the procedure provides a means to rapidly deactivate an ongoing polymerization. In Figure 9, switching the applied Eapp values between −0.69 and −0.40 V vs Ag+/Ag standard electrode, respectively, in a polymerization conducted in 50% (v/v) MA in MeCN at 25 °C resulted in changing between “on” and “off” states for the polymerization. Figure 9 shows that the polymerization reaction stopped soon after changing Eapp and started again when Eapp was reduced. The molecular weight of the formed polymer increased regularly with conversion, and there was no change in the “livingness” of the formed polymer during the enforced dormant state. ATRP in Aqueous Systems. Water is an inexpensive environmentally friendly solvent with high thermal capacity. It is an attractive medium for exothermic RP, particularly since both solution polymerization of water-soluble monomers and biphasic polymerization of hydrophobic monomers in latexes are presently being used in industrial scale processes. Polymer latexes and solid particles can be prepared in a wide range of size, nanometers to millimeters, by employing the wide range of aqueous dispersed media: suspension, dispersion, precipitation, emulsion, miniemulsion, microemulsion, and inverse miniemulsion systems.64,65 The resulting segregation of active radicals through compartmentalization can prevent macroscopic gelation when preparing copolymers from multifunctional initiators. A suitable ligand should be selected for a controlled ATRP in aqueous systems.22d,66 Conditions should be adjusted from those applied in homogeneous systems to account for lower complex stability that may lead to disproportionation, very large equilibrium constants, 10 000 times larger than in MeCN,38,44 and potential hydrolysis of CuII−X and Pn−X bonds. In heterogeneous systems, the catalyst complexes should be sufficiently hydrophobic to be preferentially located in organic phase and the choice of surfactant is important. Conventional amphiphilic surfactants have been recently replaced by polymerizable reactive surfactants or dual reactive surfactants that are anchored to particle surface and provide better stability and also selected surface functionality.67 Emulsion, miniemulsion, microemulsion, dispersion, precipitation, and inverse miniemulsion polymerization were successfully carried out by ATRP.68 The latter procedure provided a new

Scheme 3. Proposed Mechanism for Electrochemical Control over an ATRP

A targeted amount of the air-stable CuIIBr2/Me6TREN catalyst complex can be electrochemically reduced to CuIBr/ Me6TREN activators to start a controlled polymerization. In the absence of mass transport limitations, the rate of reduction is dictated by the applied potential (Eapp), enabling fine-tuning the polymerization rate by the generated ratio of [CuI]: [CuII].63 The rate of an eATRP can be controlled by changing the applied potential (Eapp). A more negative potential induces an increase in the [CuIBr/Me6TREN]/[ CuIIBr2/Me6TREN] ratio, resulting in a faster rate of polymerization. The molecular weight of the polymer formed in three reactions conducted 4023


Macromolecules

Perspective

In addition, the catalysts should not be involved in any side reactions. An interesting approach may come from bioinspired catalysis. For example, the successful ATRP of NIPAM catalyzed by horseradish peroxidase was recently reported.84 Some other enzymes or modified enzymes could be applied to ATRP. Then, could it be possible to extend these systems to Br and Cl? It would also be beneficial to replace transition metal complexes by organic catalysts. Some derivatives of phenols, phosphines, and amines have been successfully used for ATRP with alkyl iodides, under the name of reversible chain transfer catalyzed polymerization, RCTCP.85a Another challenge is the development of new reducing agents. An excellent approach in that direction is eATRP, where reduction is accomplished by an electrical current, but eATRP requires sufficient conductivity of the reaction mixture and the presence of a counter electrode and may have some transport limitations at high conversion. Thus, a range of new reducing agents is needed. They could be either homogeneous or heterogeneous and ideally should act as reversible “halogen sponges” that reduce X−Cu(II)/L species to Cu(I)/L by abstracting halogens without concurrent formation of any side products. It is also possible to mediate ATRP photochemically.85b,c Reducing agents could be added continuously, like in an eATRP.86 Plausibly, after the reaction they could be regenerated to the original state and release halogens that could be used for synthesis of initiators. Currently used sugars, ascorbic acid, metals, Sn(II) derivatives, and other species produce some side products, are used only once, and are not regenerated. Media. A deeper understanding of medium effects and judicious adjustment of reaction conditions is needed. The use of organic solvents should be reduced. They can be replaced by water, homogeneous or heterogeneous systems; the reaction could be run in bulk and ideally to high conversion or to a limited conversion with recovery of unreacted monomer. The effect of temperature and pressure should be fully evaluated to optimize reaction conditions, speed up the rate of an ATRP, avoid vitrification, and at the same time diminish contribution of side reactions. Catalyst Removal. This problem has been partially resolved by using low ppm Cu processes, but further exploration of most efficient and economic ways to remove and reclaim residual Cu is needed; they may include special absorbents, smart systems responsive to external stimuli, electrodeposition, and other as yet unexplored techniques.

method for synthesis and functionalization of well-defined watersoluble/cross-linked polymeric particles.69 Stable colloidal nanoparticles of well-controlled water-soluble poly(oligo(ethylene glycol) monomethyl ether methacrylate) (P(OEOMA)) homopolymers and copolymers were synthesized by inverse miniemulsion AGET ATRP at ambient temperatures.70 Well-defined microgels/nanogels with narrow size distribution, a high degree of chain end functionality, a uniform cross-linked network, and targeted properties (i.e., swelling ratio, degradation behavior and colloidal stability) made by ATRP in inverse miniemulsion66c were superior to microgels prepared by conventional RP.71 Removal of Copper. As noted above, one limitation of the “early” ATRP procedures was associated with the relatively high concentration of catalyst, often equimolar to initiator. This high concentration of catalyst was required to overcome radical termination reactions.72,73 Purification methods included passing the polymer solution through silica or neutral alumina columns,74 stirring with an ion-exchange resin,75 clay,76 precipitation of polymers into a nonsolvent,77 or the use of a heterogeneous catalyst that could be isolated after polymerization.78 The development of higher activity catalysts and polymerization procedures (ARGET, ICAR, SARA, eATRP) involving continuous regeneration of the deactivator (formed by termination reactions) reduced the amount of copper down to ppm levels. These novel activation procedures can be conducted in the presence of limited amounts of air, and the final products obtained from these techniques are essentially colorless.79 However, for certain applications, e.g., electronic and biomedical, it may be necessary to further reduce the catalyst concentration to below 1 ppm levels.80 The techniques developed earlier can be now supplemented by electrochemically controlled ATRP that could facilitate the electrodeposition of Cu to remove it from an ATRP.81 Future Perspectives: ATRP Process. ATRP has been used industrially for several years with commercial products being manufactured in the US, Japan, and Europe. Some fundamental processes based on low ppm Cu should soon be introduced to commercial processes, but further scale-up will require synergistic input from process engineering, converting batch systems to continuous processes, accounting for complex stabilities, transport phenomena, etc.82 Further advancements in chemistry to reach these goals are needed and will be briefly summarized below. Toward Lower ppm Cu Processes. ICAR, ARGET (or SARA), and eATRP can be performed at 100 000 000 and can be visualized by AFM as individual molecules. When deposited on surfaces, they adopt highly chain extended conformation and show many unusual and interesting properties.104 They can change conformation depending on the surface energy, they can move on low-energy surfaces, but deposition on a high-energy surface can introduce a tremendous degree of tension on the backbone that might result in a backbone cleavage.105 The cleavage kinetics can be additionally tuned by incorporating into the backbone weaker bonds such as disulfide.106 The rupture of S−S bond can be accelerated in the presence of reducing agents such as dithiotreithol.107 Bottlebrush molecules were successfully prepared by the first two procedures used for stars (grafting from and grafting onto),108 whereas grafting through was generally less successful due to large steric effects at the propagating site preventing formation of long backbones, unless very “thin” macromonomers such as those based on poly(ethylene oxide) were used.109 The structural distinction between brushes and stars with a linear core is quite subtle. Formally, the backbone of a bottlebrush should be much longer than side chains; conversely, in stars the stem should be much shorter than the arms. Nevertheless, sometimes densely grafted copolymers with a backbone shorter than arms are also named as bottlebrushes.

under high dilution, it can form a functional nanogel that can serve as multifunctional core to grow the arms of stars.96 If the cross-linker is added after a significant degree of polymerization of monomer, such that relatively long macroinitiators are formed, well-defined star polymers are formed in a core forming cross-linking reaction.97 The addition/incorporation of the same amount of cross-linker at low monomer conversion could lead to the formation of a macroscopic gel or hairy nanoparticles at higher monomer conversion. As indicated above, starlike polymers can be formed in several ways. The core first approach, starting from a multifunctional core and a progressive ATRP growth of the arms, can generate well-defined stars and even star-block copolymers. Alternatively, in a grafting-to approach, functional macroinitiators can react with a core containing several complementary functionalities. The “click” reaction between alkyne and azides was successfully used to form star polymers this way.98 This process may have some limitations for stars with larger number of arms, especially using sterically congested cores. As shown in Scheme 7, the arm-first method using similar macroinitiators that are copolymerized with divinyl cross-linkers is generally more efficient, because it generates a less congested core. In this approach the core preserves ATRP functionality and can be used to grow a second generation of arms in a grafting from procedure, resulting in a miktoarm star structure. The efficiency of the second step depends on the nature of monomers, arm length, and core compactness and can vary between 10% and 50%.99 The three general methods of star synthesis are presented in Scheme 7. The concentration of cross-linker typically exceeds 10−20 times that of arms. A larger excess of cross-linker can lead to star− star coupling and gelation. It is possible to avoid cross-linking by substituting macroinitiators (MI) with macromonomers (MM) and then form the star core in the presence of cross-linker and a small amount of low molar mass ATRP initiator.100 Essentially quantitative yields (98%) of stars were obtained under such 4026


Macromolecules

Perspective

Scheme 8. Examples of Polymers with Controlled Composition Prepared by ATRP

As will be discussed in the next section on polymer composition, stars and bottlebrushes can be constructed not only from homopolymers but also from gradient, random, and block copolymers, including blocks along the backbone and blocks in side chains forming core−shell structures.110 They show very interesting properties and can be used as templates, porogenic materials, and photonic crystals.111 ATRP was also used for synthesis of some other less common examples of designed polymer topology, including cyclic, dendritic, pom-pom, and other structures.112,113 Polymer Composition. Scheme 8 presents some examples of polymers with controlled composition prepared by ATRP. The list of monomers successfully homopolymerized by ATRP includes various styrenes, acrylates, methacrylates, acrylamides, and acrylonitrile as well as vinyl acetate and vinyl chloride.114 Less reactive monomers such as alkenes without radical stabilizing groups have not yet been homopolymerized but were successfully copolymerized with acrylates.115 The preparation of block copolymers requires following an appropriate sequence of monomer polymerization, one that generally follows ATRP equilibrium constants: acrylonitrile > methacrylates > styrene ∼ acrylates > acrylamides > vinyl chloride > vinyl acetate. This order is different than in RAFT or SRMP and mostly reflects polar effects and less steric effects.2a,30 It is possible to alter this system and switch successfully from polyacrylates to polymethacrylates by using the halogen exchange process.31 Block copolymerization by successive chain extension within the same class of monomers (e.g., acrylates and also their copolymerization with styrene) can be successfully repeated several times, as demonstrated by the preparation of ABCBA pentablocks.116 A recent publication reported efficient crosspropagation carried out 10 times for acrylates, as shown in Figure 10.117

As discussed before, graft copolymers can be prepared by grafting from, grafting onto, and grafting through. Because of the fact that graft density is lower in graft copolymers than in brushes, grafting onto and grafting through with macromonomers has been successful. Nevertheless, incompatibility between the backbone and side chains may reduce the efficiency of grafting onto and grafting through reactions. For example, copolymerization of methyl methacrylate (MMA) with methacrylate-terminated poly(dimethylsiloxane), PDMSMA, resulted in formation of a gradient structures and a higher apparent reactivity ratio of MMA.119 However, when a PDMS macroinitiator was used, a statistical copolymer was formed as a consequence of improved compatibility of PDMS segments. The formation of a graft copolymer with uniformly distributed grafts also resulted in significantly improved mechanical properties with tensile elongation ∼280% vs 30%.26a Similar graft copolymers were prepared using polylactide macromonomers, poly(ethylene oxide) macromonomers, and others.120 In order to prevent issues related to incompatibility between the backbone and side chains, it is recommended to use a grafting from procedure, as the side chains grow they only progressively become incompatible and can reach much higher graft density and uniformity, as has been observed for polyisobutene-graft-PMMA. The reactivity ratios of monomers in ATRP are essentially the same as in conventional RP, but some differences could be observed based on the intermittent activation in ATRP. The differences would include diffusion and compatibility/miscibility, as discussed above for graft copolymers. For example, the concentration of alkene groups in macromonomers may be depleted in the vicinity of growing radicals, resulting in lower rate of consumption and apparently lower reactivity ratios. Another reason for differences in reactivity ratios might be existence of multiple competing equilibria. In conventional RP, the cross-propagation equilibrium (or steady-state concentration of copolymerizing radicals) is established very quickly and maintained during the entire polymerization. However, in ATRP the concentration of radicals is defined not only by cross-propagation but also by the active−dormant species equilibrium. Because ATRP equilibrium constants are very different for e.g. acrylates and methacrylates but the concentration of Cu(I) and Cu(II) species must be the same for both systems, one equilibrium may not be reached quickly, and a steady state in cross-propagation is only reached at higher conversion. This can lead to copolymer composition that differs in ATRP and RP.25g Comonomer pairs with strongly different polarities have strong tendency to alternate. Classic examples include styrene− maleic anhydride and styrene−maleimides. Other comonomers with a weak alternation (e.g., styrene/MMA with reactivity ratios ∼0.5) form statistical copolymers but in the presence of complexing agents such as strong Lewis acids can also lead to alternating incorporation of the monomers.121 Because maleimides have a high tendency to alternation, they can be added at timed intervals and form periodic copolymers with a maleimide moieties incorporated at different spacing.122 Sequence regulation was also reported by a repetitive ABA sequence by double cyclopolymerization of complexed mono-

Figure 10. Evolution of molecular weight during synthesis of decablock copolymer: poly(MA-b-EA-b-nBA-b-tBA-b-MA-b-EA-bnBA-b-tBA-b-MA-b-EA). Reprinted with permission from ref 117.

The formation of block copolymers by ATRP was also successfully used in nonlinear structures, such as stars or brushes.104,110a,118 4027


Macromolecules

Perspective

Scheme 9. Examples of Synthesis of Periodic AB2 and ABC Copolymersa

a

Reprinted with permission from ref 123. Copyright 2011 Wiley-VCH. Reprinted with permission from ref 124. Copyright 2010 Nature Publishing Group.

mers;123 another option is a step-growth radical polymerization of inimers with lower reactivity comonomers (Scheme 9).124 Gradient copolymers form a new class of copolymers with a composition continuously changing along the chain length that arose with the advent of controlled radical copolymerization. Interest in gradient copolymers originates in their unique properties such as blend compatibilizers and surfactants due to their specific critical micellar concentrations, broad glass transition temperature, and vibration and noise dampening properties.19d Two requirements should be fulfilled to synthesize gradient copolymers: continuous and concurrent growth of all chains (a controlled/living process) and different rate of incorporation of comonomers. For comonomers with sufficiently different reactivity ratios this can be accomplished by simultaneous copolymerization, resulting in a spontaneous gradient defined by the composition of the initial reaction mixture and reactivity ratios. For comonomers with similar reactivity ratios, a forced gradient copolymer can be obtained by continuous feeding of one comonomer, typically the more reactive, to the ongoing polymerization. ATRP was successfully used to prepare several spontaneous and forced gradient copolymers under both homogeneous and heterogeneous conditions.125 Also, gradient molecular bottlebrushes were prepared this way.110b Another interesting possible pathway to gradient copolymers is solvolysis of methacrylates concurrent to their incorporation to the backbone (Scheme 10).

Since monomer solvolysis is much faster than that of polymeric segments, this leads to gradient copolymers with a composition dependent upon solvolysis rate.126 Tacticity can be considered as another structural parameter related to composition. Stereochemical control in radical polymerization is inferior to that achieved in coordination polymerization. Nevertheless, some success has been reported in polymerization of acrylamides in the presence of Lewis acids such as Y(OTf)3 and Yb(OTf)3. The meso dyad content increased from 50% to >90% in homopolymers of dimethylacrylamide, and the first stereoblock copolymers with atactic and isotactic segments were prepared in a continuous ATRP by addition of the Lewis acid at an intermediate conversion.127 Interestingly, gradient stereocopolymers were prepared using a similar concept.128 Polymer Functionality. Scheme 11 shows some examples of polymers with functional groups placed in different positions. They include polymers with one functional group (this group could be also a polymerizable group as in macromonomers) but also with two groups, as in telechelics with the same or different functionalities. They can be extended to prepare multifunctional polymers, with either regular structure such as in stars and brushes or a less regular structure as in those based on hyperbranched structures. It is possible to place functionality at a specific site of a macromolecule, generally in a center or a branch point but potentially also in a specific position, e.g., by incorporating aforementioned maleimides.122b Functional groups in ATRP can originate from the initiator or from a comonomer but can also be incorporated by replacing end terminal halogens via another functionality, as shown in Scheme 12.2b,129 For example, the use of functional 2-bromoisobutyrates as ATRP initiators can contain protected or unprotected carboxylic acid, hydroxy or cyano group, epoxides, alkene and alkyne, azide, trichloro or trialkoxysilyl group, amino groups, or more complex functionality. There are also many macroinitiators available for ATRP. They were

Scheme 10. Synthesis of Gradient Copolymers with a Composition Dependent upon Solvolysis Ratea

a

Reprinted with permission from ref 126.

Scheme 11. Examples of Polymers with Functional Groups Placed in Different Positions

4028


Macromolecules

Perspective

Scheme 12. Examples of Functional Polymers Prepared from Functional Initiators, Monomers, and by End Group Transformationa

a

Reprinted from with permission from ref 2b. Copyright 2009 NPG.

bonding, π−π stacking, ionic interactions, or weak covalent bonding. Additionally, some functional groups can be sensitive to temperature, light, redox, or pH, leading to smart responsive materials.104 These groups can be part of monomers and end groups but can also be incorporated after polymerization, via click (reaction of azides with alynes catalyzed by Cu) or thiol− ene reactions.22g Polymer Architecture: Future Directions. Since the seminal discovery of anionic living polymerization by Szwarc in 1956, many previously poorly controlled polymerization processes have been converted to “living” systems. Indeed, over the past 50 years, one of the main targets of synthetic polymer chemistry was to prepare macromolecules with precisely controlled architecture in terms of narrow molecular weight distribution, exact topology, including controlled welldefined branching, well-defined monomer sequence distribution, tacticity, and functionality. Such macromolecules were successfully used by physical chemists and physicists to establish a comprehensive correlation between molecular structure and macroscopic properties. This also helped theoreticians develop new models and verify their theories on development of properties in polymer science. Evidently, many macroscopic properties depend not only on molecular structure but also on processing conditions, i.e., thermal history, mechanical stresses, or solvent used. Nevertheless, control over molecular structure could be considered as a prerequisite

synthesized by anionic, cationic, coordination, ring-opening (including metathesis), polycondensation, and even conventional free-radical polymerization. Sometimes they can be part of an inorganic support or biomolecule. In a similar way functional groups can be part of polymerizable monomers, including also salts and even peptide or nucleobase groups. The halogen present on the active chain end can be replaced by nucleophilic substitution in polyacrylates and polystyrene; however, this procedure is less efficient for tertiary polymethacrylates. Reaction with tertiary amines and phosphines generates the corresponding onium salts.129 Reaction with (meth)acrylic acid in the presence of a base provides macromonomers. Perhaps the most efficient postpolymerization functionalization is the reaction with azide anions forming azido terminal polymers, subsequently used for many click reactions.130 It is also possible to replace halogen under atom transfer radical addition conditions and prepare polymers with hydroxy or epoxy groups. Halogens from polystyrenes can be also replaced using electrophilic addition reactions. Epoxy functionality, incorporated e.g. via (co)polymerization of glycidyl (meth)acrylates, can be converted to many useful functionalities as shown in the Scheme 13, including hydroxides, thiols, amines, acids, chlorides, and also azides.131 Functional groups can modify the polymers properties but can also be used for cross-linking, chain extension, and supramolecular assembly based on weaker interactions via hydrogen 4029


Macromolecules

Perspective

Scheme 13. Examples of Transformation of Glycidyl Groups into Other Functional Groups

for controlling polymer morphology and, ultimately, many “predictable” properties. ATRP has offered unprecedented control over macromolecular architecture using many commercially available reagents under undemanding reaction conditions. This could be the main reason for the widespread use of ATRP in academic and industrial laboratories. As presented in this section, various aspects of chain uniformity, topology, composition, including tacticity to a limited extent, and functionality can be well controlled by ATRP. Molecular brushes, stars, multisegmented block copolymers, and end functional polymers were prepared with high chain end fidelity and precisely controlled structure. However, synthesis of such tailored made polymers often requires long reaction times, special catalysts, and higher purity of all reagents. Advent of new low catalyst ATRP systems (ICAR, ARGET, SARA, eATRP) offers more environmentally benign and industrially scalable reaction conditions for the synthesis of similar polymers but also with designed dispersity, defined by the catalyst content. This can be considered as a new concept of controlled heterogeneity.132 In terms of dispersity, it provides avenues to materials with broader, but controlled, molecular weight distributions and with new stable morphologies.83a In terms of composition, it provides access to novel gradient copolymers,19d and in terms of chain topology, materials with variable branching.95b Both topological and compositional heterogeneity broadens the spectrum of relaxation times and can lead to new specialty materials. Controlled heterogeneity will also allow preparation of materials with more tolerant processing windows for the (co)polymers and should reduce the cost and improve cost−performance relationship. Thus, two orthogonal directions can be anticipated in the area of polymer architecture. On one side, the preparation of polymers with even more complex and precisely controlled architecture, as illustrated in Scheme 14, where some elements of chain composition, topology, and functionality can be combined to prepare brushes with gradient or blocky side

Scheme 14. Complex Architectural Control Based on Combination of Several Individual Structural Featuresa

a

Reprinted from with permission from ref 132. Copyright 2011 AAAS.

chains, with pom-pom and block cyclic gradient structures or with multifunctional miktoarm stars that can specifically assemble under external stimuli and generate smart, perhaps self-repairing materials.133 Alternatively, materials with controlled incorporation of imperfections and controlled heterogeneity become progressively more interesting.

■

HYBRID MATERIALS Hybrid materials, in the broadest sense, constitute two or more segments prepared by different methods, connected at a molecular level, typically by covalent bonds. They include organic polymers linked to inorganic substrates or synthetic polymers attached to natural products but could also comprise segmented copolymers prepared by different polymerization mechanisms. For example, the end groups in polymers prepared by ionic, coordination, metathesis, ring-opening, conventional free radical polymerization, and step growth polymerization techniques can be easily transformed to ATRP 4030


Macromolecules

Perspective

macroinitiators and subsequently chain extended to generate “mechanistic hybrids”.134 It is also possible to grow two or more segments concurrently by different mechanisms (ROP or ROMP and ATRP). In fact, the AGET ATRP process with tin(II) octoate was discovered while attempting concurrent ATRP of methacrylates with ROP of ε-caprolactone using hydroxyethyl 2-bromoisobutyrate as a dual initiator.48c,135 Hybrid graft copolymers can be prepared by “grafting-onto”, “grafting-from”, or “grafting-through” methods. In order to attach a preformed polymer (“grafting-onto”) or an initiator (“grafting-from) to an inorganic or (bio)organic building block, functional groups complementary to those present on the targeted component should be present in the polymer or initiator. Each process has some advantages and limitations. Grafting-onto can involve well-defined ATRP copolymers with end functionality complementary to that on an inorganic substrate or natural product. Incompatibility between these systems and a relaxed coiled polymer conformation limit graft density and may also complicate separation of unreacted polymers, used often in large excess, from the resulting hybrid materials.136 On the other hand, the grafting-from procedure can provide much higher grafting density, approaching 1 chain/ nm2, but may cause gelation due to interparticle radical termination reactions between the large number of intermittently active chains concurrently grown from inorganic or natural product substrate. To prevent macroscopic gelation, ATRP is often run slowly to low conversion and under high dilution. Alternatively, one could use miniemulsion to provide compartmentalization or apply high pressure.17b,137 Although separation of hybrid material from unreacted monomer is much simpler than from the preformed functional polymer, the ATRP catalytic system should be sufficiently inert not to directly interact with the inorganic substrates or natural products.86 ATRP polymers were covalently attached to a variety of biomolecules such as proteins, nucleic acids, sugars, etc.138 Biological molecules have accessible carboxylate, amine, hydroxy, or thiol groups that can be functionalized in a straightforward way. Also, the advancement of “click” chemistry techniques,86,139 including thiol−ene reactions,140 provides a convenient way to attach polymers or initiators with either azide or alkyne group to biomolecules. Nevertheless, conducting a grafting from ATRP is challenging, particularly if it should be carried out under biologically relevant conditions: ambient temperature, low organic content (

Atom Transfer Radical Polymerization (ATRP): Current Status and

Recommend Documents