Perspective pubs.acs.org/Macromolecules
Polymer Nanoparticles via Living Radical Polymerization in Aqueous Dispersions: Design and Applications Michael J. Monteiro*,† and Michael F. Cunningham*,‡ †
Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane QLD 4072, Australia Department of Chemical Engineering, Queen’s University, Kingston, Ontario, Canada K7L 3N6
‡
ABSTRACT: In the past decade, living radical polymerization (LRP) has revolutionized academic research in the fields of free-radical polymerization and materials design. Sophisticated macromolecular architectures, designed for a variety of applications and end-use properties, can now be synthesized using relatively simple LRP chemistries that do not require stringent oxygen or moisture free environments, subzero reaction temperatures, or highly purified reagents. Publications abound not only in the fundamentals of LRP but also its use in designing tailor-made polymers and polymer−hybrid composites. Corporate research organizations have also been actively involved in LRP, with numerous patents being issued annually. Despite the intense research interest, however, comparatively few products have been commercialized, with high process costs being a primary factor. Most commercial free-radical polymerizations are conducted in aqueous dispersions due to significantly lower process costs compared to bulk or solution polymerizations. Successful widespread commercialization of LRP will be advantaged by the development of waterborne processes yielding aqueous dispersions of nanoparticles. Conducting LRP within nanoparticles (i.e., using nanoscale particles as self-contained chemical reactors or “nanoreactors”) enables faster reaction times and if harnessed properly will provide better control over the polymer livingness; it also has the potential in the control of the particle mesostructure and microstructure. Recent progress in LRP dispersions is presented with a discussion of outstanding issues and challenges as well as the outlook for adoption of LRP dispersions by industry.
■
INTRODUCTION In the early and mid-1990s, “living” radical polymerization techniques were introduced, initiating a surge of interest in research on free-radical polymerization (a field that was widely considered mature at that time) and revolutionizing our ability to control polymer chain microstructure and synthesize complex architectures with facile processes under routine experimental conditions. Until the advent of living radical polymerization (LRP), also referred to as “controlled radical polymerization”, fine microstructure control and complex architectures were only accessible using ionic polymerization techniques, typically requiring high purity materials, reaction environments free of oxygen and moisture, and very low reaction temperatures (∼−50−80 °C). Ionic polymerizations were also not amenable to a wide variety of monomers, whereas LRP has proven to be quite versatile and suitable for most free radically polymerized monomers. (A few important monomers, such as vinyl acetate, have proven to be challenging, in large part due to their inherent kinetics, such as high rates of transfer to monomer and/or polymer.) In the ensuing years, there has been an intensive LRP research effort, in both industry and academia, with industrial efforts aimed at developing commercial products. Despite the intensity and duration of these efforts, however, there are relatively few commercial products available. Destarac has provided a summary of commercially available products.1 © XXXX American Chemical Society
Given the initial expectations and extensive resources poured into LRP research and development over the past decade, it is rather surprising and disappointing that commercialization of LRP products has been so limited. This situation begs the question: what are the obstacles to widespread commercialization of LRP, and why has the marketplace not embraced LRP to the extent many thought it would? There are multiple considerations to the question of why LRP has been so slow to be commercialized. The simplest and most direct answer is that companies, including LRP proponents within those companies, have had difficulty building a sound economic case for commercializing LRP polymers. A potentially new product requires a product niche in the marketplace but also needs to compete economically with existing manufacturing processes. Moderate improvement in properties compared to an existing product will likely not justify the expenditure and risk of new process development and commercialization. While some companies have found that LRP can deliver some improvement in properties, often similar property improvements can be obtained with innovative polymer reaction engineering approaches. A primary challenge is that LRP products will require new manufacturing processes and the accompanying investment in process development and Received: January 22, 2012 Revised: April 5, 2012
A
dx.doi.org/10.1021/ma300170c | Macromolecules XXXX, XXX, XXX−XXX
Macromolecules
Perspective
hydrophobe, thereby alleviating the VOC issue. Another challenge for LRP in emulsions is the scale-up from 5% to 10% solids content usually prepared in most academic formulations to over 50% solids required in industrial formulations, in which colloidal stability becomes a critical issue. With a better understanding of the mechanisms in emulsion LRP and the use of alternative methods, these obstacles are slowly being overcome. If LRP products are to achieve widespread commercialization, it will most likely require development of processes based on aqueous dispersions. While aqueous dispersion are more “green” than bulk or solution processes and therefore have that appeal, this factor alone is insufficient to warrant investment in commercializing an LRP process based on aqueous dispersions. The objective of this Perspective is to elaborate on the role and importance of LRP in aqueous dispersions in future development of commercially viable LRP products, particularly at larger scale and for product markets with large volumes. (Small volume, high value added products tend to have a high cost tolerance, so there is less need to develop processes using aqueous dispersions.) We review the current status of dispersed phase LRP, highlighting recent achievements (particularly those that will facilitate commercial development) and identifying unresolved issues and challenges. Being a Perspective, this is not intended to be an exhaustive review. Recent reviews on LRP in aqueous dispersed systems are available in the literature.10−18 Therefore, we do not detail all LRP approaches but rather focus on those most pertinent to the issue of commercializability. We present a comparison of alternative process options (e.g., emulsion vs miniemulsion) and discussion of other advantages that may be attainable by performing LRP in aqueous dispersions (e.g., better livingness and/or control, control of mesostructure such as particle morphology), including the potential benefits of compartmentalization. Finally, we address the question of whether LRP is likely to see widespread adoption by industry or whether it will remain as a valuable research tool but lacking commercial significance.
perhaps capital expenditure. Without a significantly different or preferably unique product, this requirement usually precludes commercialization. Dispersed phase polymerizations, such as emulsion and suspension polymerization, in which the product is polymer particles dispersed in an aqueous medium, are the preferred processes for free-radical polymerizations.2−4 They are used for products in which the final desired state is a dispersion of particles (e.g., coatings, adhesives, sealants, paints) and when a bulk polymer resin is desired. In the latter case, the dispersion is coagulated and the coagulum is then isolated and usually pelletized. Emulsion (∼50−1000 nm diameter particles) and suspension polymerization (∼20−2000 μm diameter particles) are distinguished by their inherent mechanisms and by their final particle size. Emulsion is generally preferred over suspension because of the ease of handling smaller particle dispersions, particularly for soft polymers where suspension beads tend to coalesce. Aqueous dispersions are the preferred manufacturing process because they feature low viscosity reaction mixtures that are easily mixed, with excellent heat transfer, ease of addition of formulation components (e.g., comonomers, initiators, chain transfer agents) during polymerization, and ease of transfer of the dispersion to other vessels following polymerization. Furthermore, they do not require organic solvent, and residual monomer can be removed much easier than for high viscosity polymer solutions, thereby giving low VOC products. Homogeneous processes also require solvent removal and capture steps and high viscosity processing equipment. These factors result in the overall economics of aqueous dispersions, especially emulsion polymerization, being strongly favored over most alternate routes such as bulk or solution polymerization. There are several critical differences between performing LRP in an emulsion-based system (emulsion or miniemulsion polymerization) compared to bulk/solution polymerization. These include partitioning of all species and especially mediating agent between the aqueous and organic phases, the common use of surfactant in emulsions (which may cause problems with control of the polymerization, as with ATRP using anionic surfactants5), the spontaneous tendency for hydrophilic mediating agents or monomers to preferentially locate near the particle interface, the possibility of radical exit/ re-entry, the possibility of exited radicals terminating or deactivating in the aqueous phase, and the complexity of particle nucleation in the case of emulsion polymerization or the need for a droplet/particle formation step in the case of miniemulsion polymerization. The droplet formation step has been a particularly troublesome concern with attempting to scale up LRP miniemulsions as the equipment required at large scale (e.g., microfluidizers, piston homogenizers) are often wellsuited for this purpose; however, recent work has demonstrated that miniemulsions can be produced using only static mixers, thereby presenting a solution to this problem.6 Furthermore, the use of in situ surfactants (in which organic acid and base are added to different phases to create surfactant at the droplet interface)7,8 in combination with low shear mixing has proven to be amenable to LRP.9 Miniemulsion polymerizations also require a hydrophobe to preserve droplet stability through retardation of Ostwald ripening. It is sometimes perceived this is a disadvantage because common hydrophobes (e.g., hexadecane) are VOC’s, but it is now common practice to use a few percent of a hydrophobic monomer (long chain acrylate or methacrylate) as the
■
THEORY OF LIVING RADICAL POLYMERIZATION (LRP) IN SOLUTION AND BULK This section will describe the general features of the most commonly used LRP techniques,19−24 with a greater emphasis on those techniques used in water-based dispersion polymerization.10,13,16,25 The general mechanistic pathways will also be discussed in terms of the kinetic parameters that govern the rate of polymerization, degree of polymerization (or polymer chain length), chain-end fidelity and functionality, and molecular weight distribution (MWD). A “living” radical polymerization is commonly thought to be defined by a linear increase in the degree of polymerization (or number-average molecular weight, Mn) with conversion and narrow MWDs (i.e., polydispersity indexes, PDI, below 1.1). A more comprehensive definition is that termination through radical− radical bimolecular termination and transfer to monomer or other species that produces dead polymer has a low concentration compared to that of the dormant species. This means that even a polymer with a PDI of 2 can be classed as following “living” radical behavior should the previous statement hold true26a more detailed discussion will follow below. Understanding LRP in solution and bulk provides some insight into the application of LRP techniques to emulsion or miniemulsion polymerizations; although emulsion and miniB
dx.doi.org/10.1021/ma300170c | Macromolecules XXXX, XXX, XXX−XXX
Macromolecules
Perspective
radicals at or close to diffusion-controlled rates to form alkoxyamines (Scheme 1)32 and represent an important class of
emulsions have the added complexities of compartmentalization, partitioning of monomer and reagents in the various phases, and entry, exit, and re-entry of radicals into and between growing polymer latex particles. Polymer chains made by free-radical polymerization mediated by a living agent can be classified into three major categories: dormant chains, dead chains (formed through transfer or termination reactions and that can no longer be chain extended), and polymeric radicals. The latter, polymeric radicals, is usually of such a low concentration that it is considered to be negligible. The other two, dormant and dead chains, and their ratio determine whether the polymer formed follows the above definition of living behavior. The general equations used to define the change in number-average molecular weight (Mn) with conversion are as follows: Mn =
Scheme 1. Generalized Mechanism for Nitroxide-Mediated Polymerization (NMP)
radical deactivators.24 At elevated temperatures, the C−O bond within the alkoxyamine homolytically cleaves to form back the nitroxide and carbon-centered radicals.33 This reversible termination provides an avenue for the monomer to propagate with the radical, resulting in the growth of the polymer chain. The equilibrium between dormant and active chains (i.e., P−T and P•, where P• and T• represent a polymeric chain and nitroxide, respectively) determines the “livingness” of the system. As the termination of polymeric radicals with nitroxides is diffusion controlled and therefore largely independent of temperature, the rate coefficient for homolytic cleavage of P−T governs the rate of polymerization, amount of dead polymer, and degree of livingness. Radical−radical termination (an irreversible reaction) results in an increase in the concentration of nitroxide and as a consequence a decrease in the rate of radical−radical termination. This phenomenon is known as the persistent radical effect (PRE).34,35 The PRE results in the selfregulation between the active and dormant polymer, and the rate of polymerization will slow down as the PRE becomes dominant. The PRE has the desired effect of producing polymers with a narrow MWD or low PDI values and high chain-end functionality. Nitroxide-mediated polymerizations can be initiated by starting with a small molecule alkoxyamine at high temperatures in the presence of monomer. In the case of styrene polymerizations at high temperatures, the rate can be maintained through the production of external radicals from the thermal self-initiation of styrene monomer.36−38 These additional radicals overcome the rate retardation caused by the PRE, allowing high conversions to be reached. A conventional free-radical initiator and nitroxide in the presence of monomer is an alternative method to the one described above. However, this method is not as effective in controlling the polymer MWD as the alkoxyamine and relies on a rapid decomposition of initiator to form the alkoxyamines.24,39,40 It was apparent from early studies the importance of nitroxide design in obtaining an equilibrium rate constant (K = kd/kc, where kd and kc are the rate coefficients for homolysis of the alkoxyamine and crosscoupling between T and P•, respectively) that allowed the production of well-defined polymers at lower temperatures. These more versatile nitroxides39,41−44 made available a much wider range of monomers to be polymerized and greatly expanded the utility of NMP. Alpha-hydrido nitroxides are acyclic nitroxides that are now able to control a wider range of monomers (including styrenics, acrylates, and dienes) than cyclic nitroxides such as TEMPO, and often at lower temperatures than TEMPO due to the decreased stability of their alkoxyamines. It also provided translation of NMP to
[M]xM w,mon ([living agent]0 − [living agent]t ) + [radicals] (1)
where [M] is the initial concentration of monomer, x is conversion, Mw,mon is the molecular weight of the monomer unit, and [living agent]0 and [living agent]t represent the initial concentration and concentration at time, t, of the living agent, respectively (e.g., RAFT agent, alkyl halide in copper-catalyzed polymerization, or alkoxyamine in NMP). This equation can be used to demonstrate that should the living agent be less reactive and the polymerization produce a low amount of dead polymer compared to dormant polymer, then one will not observe a linear increase in Mn with x, and the PDIs will be much greater than 1.1. If the living agent is consumed within the first few percent conversion and the dormant polymer is far greater than dead polymer, then eq 1 can be simplified to the well-known eq 2.26 Mn =
[M]xM w,mon [living agent]0
(2)
Should the amount of dead polymer be small compared to the dormant species following eq 1, then the polymer can be chain extended with a different monomer to form a AB diblock copolymers. In this case, there should be a linear increase of Mn with conversion regardless of living agents reactivity,27 and one can predict the polydispersity of block B using the following equation if the PDIs of block A and the diblock AB are known:28 PDIdiblock − 1 = (PDIA − 1)wA 2 + (PDIB − 1)wB 2
(3)
where wA and wB are the weight fractions of A and B in the diblock (i.e., wA = 1 − wB). This equation can also be used when coupling two polymer of know PDI and is a useful equation to determine coupling efficiencies, especially in “click” type reactions in polymer systems.29−31 There are two main classes of LRP techniques: reversible termination that includes NMP, metal-catalyzed mediated polymerization and reversible chain transfer that includes RAFT and degenerative chain transfer mediated polymerizations. There are many comprehensive reviews on all these LRP techniques,19−24 and therefore we will only attempt to give a general overview and highlight important parameters that will affect the translation of these techniques to aqueous dispersion polymerization. Nitroxide-Mediated Polymerization (NMP). Nitroxides are stable radicals that can terminate with carbon-centered C
dx.doi.org/10.1021/ma300170c | Macromolecules XXXX, XXX, XXX−XXX
Macromolecules
Perspective
water-based dispersion polymerizations, which are usually carried out between 50 and 90 °C. Nitroxide coupling can be combined with copper catalysis (see below) as a reaction with “click” type attributes.45−47 Complex polymer architectures can be produced using this method.48,49 Metal-Catalyzed “Living” Radical Polymerization. There are now many “living” radical polymerizations catalyzed using a range of transition metals.23,50−52 In this section, we will concentrate on copper-mediated polymerizations. Copper is a metal that is relatively cheap and readily available and thus has attracted considerable industrial interest in producing advanced polymeric materials. The most commonly used method is atom transfer radical polymerization (ATRP) as shown in Scheme 2.53 The copper source used in ATRP is Cu(I) usually
Scheme 3. Proposed Mechanism for Single Electron Transfer−Living Radical Polymerization (SET-LRP)a
a
Self-regulated systems driven by disproportionation of Cu(I) to Cu(0) and Cu(II).76
Scheme 2. Generalized Mechanism for Atom Transfer Radical Polymerization (ATRP)
disproportionation of Cu(I) to the active Cu(0). The application of AGET to aqueous-based dispersion polymerizations produced well-defined polymer.71,77−79 However, SET has not been applied to dispersions, as it requires a highly polar solvent that is usually miscible with water. Reversible Addition−Fragmentation Chain Transfer (RAFT) Polymerization. As with copper-catalyzed living radical polymerization, RAFT-mediated polymerization80,81 has grown in popularity with academic researchers for the synthesis of polymers for use in biomedical applications. The reason for this is the ability of RAFT to control the polymerization of monomers that have biologically relevant side groups and a wide range of functional and nonfunctional water-soluble monomers.20,21,82 The mechanism of RAFT (Scheme 4) originates from degenerative chain transfer, in which the functional group is transferred from dormant to active species. The simplest form of degenerative chain transfer involves the transfer of iodine; however, this technique has a low transfer constant, Ctr (= ktr/kp, where ktr is the transfer rate coefficient for exchange between the halide and radical and kp is the rate coefficient for propagation of the monomer), resulting in polymers with broad MWDs.83,84 The reactivity for the exchange of halide toward active species determines the MWD, and can be predicted, should the Ctr value be first determined for the chain transfer agent (CTA), using the two sets of analytical equations.85 γ0x or M n xn = 1 − (1 − α)(1 − x)β γ0x M0 = 1 − (1 − α)(1 − x)β (4)
coordinated with nitrogen-based ligands and has the additional advantage that the halide end-groups on the polymer can be easily transformed or reacted using a variety of “click” reactions54,55 to produce a wide range of complex polymer architectures.29,31,56−64 This has expanded the synthetic capabilities to produce designer molecules and thus advanced polymeric materials for a broad range of applications, with greater emphasis in the biomedical area.65 Similar to NMP, the PRE and the value of KATRP (=kact/ kdeact) in ATRP determines the MWD of the resulting polymer. Chain-length dependent termination66 also plays a role in the PRE.67 The combination of ligand, solvent and monomer(s) should be chosen carefully67 since KATRP can alter by orders of magnitude by changing either the ligand and/or solvent for a particular monomer(s) system. Considerable work68,69 has been dedicated to obtaining these KATRP values, and has provided a framework to judiciously choose the most favorable ligand, monomer and initiator combination that result in the production of well-defined polymers. Narrow MWDs (i.e., PDIs < 1.1) are predicated on the rapid consumption of initiator in the first few percent conversion, and one can, through the choice of initiator, prepare polymers with PDIs greater than 1.1 and with high chain-end halide functionality (vide supra). However, for copper-catalyzed polymerizations to produce polymers on an industrial scale and become commercially attractive, the levels of copper should be low as large quantities would be toxic to the environment. The more recent methods to significantly reduce the amount of copper down to ppm levels and still maintain control over the MWD are activators generated by electron transfer (AGET),70,71 initiators for continuous regeneration (IGAR),72 activators regenerated by electron transfer (ARGET),73,74 and single electron transfer−living radical polymerization (SETLRP)75,76 (see Scheme 3). The mechanistic principle of all these techniques is the regeneration of the active copper catalyst using either external reducing agents for Cu(II) or via
PDI =
⎤ 2α(1 − α) β−1 1 1⎡ + ⎢2 + (2 − x)⎥ − ⎦ x⎣ γ0x α−β (β − α )x [1 − (1 − x)1 + β / α ]
(5)
where M0 is the monomer molar mass, γ0 = [M]0/[CTA]0, x is fractional conversion, α = [P•]/[CTA] (with [P•] the concentration of propagating radicals), and β = Cex (where Cex equals Ctr for a RAFT system). These equations can be used for reversible chain transfer where termination, transfer to monomer, and all other side reactions are neglected. In most cases, these equations do not account for the influence of dead polymer on the Mn or PDI, D
dx.doi.org/10.1021/ma300170c | Macromolecules XXXX, XXX, XXX−XXX
Macromolecules
Perspective
Scheme 4. Generalized Mechanism for Reversible Addition−Fragmentation Chain Transfer (RAFT) Polymerizationa
a
Additional pathways (e.g., intermediate radical termination, IRT) are not included.
the additional advantage that carrying out the polymerization in a compartmentalized system would theoretically provide better control over the MWD as termination would be significantly reduced due to exclusion of the radicals in different particles. The attractiveness of RAFT from an industrial perspective was that re-engineering of the reactors or processes for emulsion and miniemulsions was not required, as the RAFT agent could simply replace the conventional chain transfer agents. This would then allow polymers using RAFT to be made feasible on an industrial scale. Although this has been the case for the low reactive RAFT agents (including the xanthates), unfortunately, the use of the highly reactive RAFT agents resulted in many unforeseen problems due to different thermodynamic and kinetic controlling factors in a RAFT-mediated polymerization, which will be discussed below. It took over 10 years to successfully control the MWD and particle size, in which a polymer particle could be designed with a specific MWD and made with a specific particle size.90 In this section, we will describe how the understanding of the complex kinetics of RAFT and the effect of thermodynamic parameters in aqueous dispersion allowed us to achieve such control in MWD and particle size. We will not give a review of RAFT in aqueous dispersion, including ab initio and seeded emulsions, miniemulsion, self-assembly, and surfactant-free polymerizations. The topic has been comprehensively reviewed elsewhere.11,16,25,91,92 This section will focus on the knowledge gained from the kinetic and thermodynamic precepts to provide a framework to successfully produce polymer latex particles with controlled MWDs and PSDs using RAFT. In addition, we will provide a description of a new, exciting, and emerging area of RAFT-mediated emulsion polymerization to produce thermodynamic and kinetically trapped three-dimensional structures (e.g., cylinders, donuts, vesicles) at high polymer solids.
and the more comprehensive kinetic simulations through solving all the differential equations provides an accurate determination of the conversion, Mn, and PDI with time.26 Such simulations also provide insight into block formation.27 Equations 4 and 5, however, do provide an accurate description even for RAFT-mediated polymerizations (Scheme 4) only when the dead polymer is below 5% to that of the dormant species. To accomplish this in a RAFT-mediated polymerization, the concentration of initiator (in reality the amount of initiator decomposed to active radicals) should be significantly lower than the initial concentration of RAFT agent (or CTA). At low Ctr values of the CTA (e.g., Ctr = 1), the Mn reaches its maximum value at low conversions and remains constant over the conversion range.26 An increase in the Ctr value results in polymerizations that trend toward a linear increase in Mn and a decrease in PDI with conversion. Only when the Ctr is greater than 10 can we expect to produce polymer with a very narrow MWD. It should be recognized that the number of chains and the chain-end fidelity consisting of a RAFT agent are the same regardless of the Ctr value at 100% conversion. Therefore, if a highly reactive RAFT agent (e.g., cumyl dithiobenzoate, Ctr ∼ 6000)86 or a low reactive RAFT agent (xanthates in which the polymerization was denoted as MADIX,87,88 Ctr between 0.7 and 4)89 is used in styrene polymerizations, the only difference between the two resultant polymers is the breath of the MWD. In addition, the polymers made by either cumyl dithiobenzoate or xanthate could be chain extended to form diblock copolymers with the same efficiency. The PDI for the xanthate diblock polymerization can be predicted using eq 3.
■
LIVING RADICAL POLYMERIZATION (LRP) IN HETEROGENEOUS AQUEOUS SYSTEMS RAFT in Heterogeneous Aqueous Systems. It was originally thought that it would be easy to translate RAFT from solution or bulk to aqueous dispersion polymerization and have E
dx.doi.org/10.1021/ma300170c | Macromolecules XXXX, XXX, XXX−XXX
Macromolecules
Perspective
Thermodynamic Precepts for RAFT in Dispersion Polymerizations (Superswelling Theory). The first ab initio RAFT-mediated emulsion polymerizations using surfactant micelles as the locus of polymerization gave very poor control over the MWD and particle size distribution (PSD) and instability of the latex.93 Miniemulsions using conventional ionic surfactants, similar to an ab initio emulsion, also gave latex instability and broad MWDs and PSDs.94,95 It was evident that transportation of the unreacted RAFT agent from monomer droplets or unnucleated miniemulsion droplets was too slow to reach the growing particles. Prescott et al.96,97 used a seeded emulsion polymerization, transported all the RAFT agent to the particles using acetone, and then removed the acetone using rotovaporation to localize the RAFT in the seed particles. Polymerizations using this method showed the classical increasing of Mn with conversion with PDIs below 1.4 when the polymer from the seed was subtracted. It was the realization by Luo, Tsavalas, and Schork98 that the kinetics alone could not explain the instability of the latex particles during the polymerization and the resultant formation of a red monomer layer resting on top of the emulsion mixture (see discussion below on the kinetics of RAFT in dispersion polymerization). They proposed the “superswelling” theory, based from the original work of Ugelstad et al.,99−101 describing the influence of molecular weight on the monomer swelling capacity of the polymer latex particles using a modified Morton equation. The thermodynamics of swelling dictate that oligomers will have a much greater capacity to induce swelling of the monomer in the particles than polymers with high molecular weight. The diffusion of monomer in this system is governed by the monomer’s chemical potential difference between droplets and particles. Ugelstad and co-workers101 showed that polymer particles can swell up to 5 times their unswollen volume in the presence of small hydrophobic molecules. They also showed100,101 that polymer particles consisting of oligomers can swell as much as 100 times their volume. In conventional free-radical polymerization, oligomers and high molecular weight polymer form continuously throughout the polymerization, and thus swelling is governed primarily by the high molecular weight polymer. In a “living” radical polymerization in which there is a linear increase in Mn with conversion, the oligomers formed at early conversions (or early polymerization times) are the dominant species. This should result in a large amount of monomer transfer from droplets (high monomer chemical potential) to oligomeric particles (low monomer chemical potential), giving rise to the colloidal instability and ultimately loss of molecular weight control observed experimentally. Luo, Tsavalas, and Schork also showed using Ugelstad’s equations that the superswelling equilibrium will be affected to some extent by the costabilizer concentration and length, initial droplet size, interfacial tension, and RAFT agent concentration.98,102 The “superswelling” theory is becoming more widely accepted as the thermodynamic reason for poor control in RAFT-mediated aqueous dispersion polymerizations and was used by Urbani et al.103 to describe their results. (While the superswelling phenomena has not been explicitly well studied for NMP and metal-catalyzed polymerizations, the thermodynamic basis is the same as for RAFT polymerizations, and therefore the same issues should exist in NMP and metalcatalyzed polymerizations. For example, the appearance early in the reaction of a monomer layer on the surface of NMP and metal-catalyzed polymerizations is common.) The authors
commented that by utilizing a nonionic surfactant such as Brij98 “superswelling” could be avoided due to the surfactant’s lower efficiency104 (i.e., it can stabilize a larger surface area than for example SDS) and also hinder monomer transportation.98 Luo and Cui105 used the “superswelling” theory to aid in the experimental design to produce well-defined polymer using RAFT in the presence of high amounts of SDS and initiator. However, deviation from theory was observed when high molecular weights were targeted analogous to Urbani et al.103 results. In this case, although Mn increased linearly with conversion and was close to that calculated, the PDI values ranged between 1.5 and 1.8. The authors suggested that the high PDI values were not a result of the colloidal stability but were most probably a result of a heterogeneous distribution of RAFT agent among the particles formed at different nucleation times. Therefore, according to the “superswelling” theory, an increase in the nucleation rate should lead to lower PDIs, which was found by Urbani et al.103 The rates of nucleation (i.e., stinging the particles with radicals) and the rates of monomer and RAFT agent diffusion through the water phase will greatly influence the establishment of the superswelling state. If nucleation is slow and monomer diffusion fast (relative to initiation) through the water phase, then superswelling would be increased due to the few number of particles being formed. If nucleation is fast, superswelling will be suppressed due to the formation of greater numbers of particles. Superswelling can be used advantageously to produce an ideal RAFT-mediated aqueous dispersion polymerization, in which the molecular weight PDI is 100), the simulations (not shown here) show an inhibition time that increased with increasing RAFT concentration. Successful RAFT Aqueous Dispersion Polymerizations. The understanding of kinetics and thermodynamic factors when using RAFT in aqueous dispersions allowed researchers to circumvent the issues of transportation and other issues by redesigning the system. The main aim for all these systems (e.g., miniemulsions,94,121 nanoprecipitation,122,123 selfassembly,124 and nanoreactors90,125) was to colocalize the RAFT agent and monomer together to avoid transportation issues and provide some control of the particle size. In this section, we will discuss the self-assembly and nanoreactor techniques as they form the basis of creating 3D polymer structure in water. Charleux and co-workers126−131 showed that diblock amphiphilic copolymers could function to stabilize conventional ab initio emulsion polymerizations. Hawkett and coworkers124,132 developed the synthesis of “latex” particle via a self-assembly process. The initiator (4,4′-azobis(4-cyanopentonoic acid)) was added to a solution of poly(acrylic acid) (PAA) macro-RAFT agent in water. The mixture was brought to the reaction temperature and butyl acrylate fed into the reaction to maintain the monomer concentration below the saturation concentration of butyl acrylate (BA) in the water phase. The BA units were added to the PAA macro-RAFT agent to form a diblock copolymer, and when the number of BA units was great enough, the diblock would self-assemble into small PAA stabilized nanoparticles, where the core consisted of PBA. The monomer would then swell the hydrophobic PBA region and polymerization would continue with growth of the particles. There was a linear increase in Mn with conversion, and the PDI increased from approximately 1.25 (10% conversion) to 1.5 (70% conversion). The increase in PDI with conversion for the higher molecular weight polymerizations could possibly be explained by the “superswelling” phenomenon or the heterogeneous distribution of RAFT agent among the particles formed at different nucleation times. A new nanoreactor approach has been used to produce polymer latex particles with narrow MWDs and PSDsa significant advance on previous systems. A diblock copolymer consisting of poly(N-isopropylacrylamide-b-dimethylacrylamide) (P(DMA49-b- NIPAM106)) was used to construct the nanoreactor.103,125,133 At room temperature the diblock was water-soluble, and when the reaction mixture, including monomer, MacroCTA (PNIPAM18-SC(S)SC4H9), and initiator, was heated above the LCST of PNIPAM block (∼32 °C) to the polymerization temperature of 70 °C, nanoparticles instantaneously formed with the MacroCTA located inside (see Scheme 5). Polymer chains were formed rapidly with the predicted molecular weights and with very narrow molecular weight distributions (polydispersity indexes below 1.1). In addition, the particle size distribution was very narrow, and by altering the weight ratio of monomer to MacroCTA, the final particle size could be predetermined by controlling the size of the nanoreactor and the amount of styrene to be encapsulated in the nanoreactor (Scheme 6). This
(DR) of the radical, its partition coefficient (q) between the oil and water phases, and the radius of the swollen particle (rs) and is given as follows:114 kexit =
3DR qrs
(7) •
These exited R radicals can either terminate in the aqueous phase or re-enter a micelle or particle with rate coefficient k re‐entry = 4πDR NArs
(8)
and therefore ρre‐entry = k re‐entry[R•]aq
(9)
•
The re-entry of R into a micelle of ∼3 nm would occur quite rapidly due to the great number of micelles but would also rapidly re-escape due to their very small size (limit 3 in emulsion polymerizationtermination within the particle is rate-determining2). This situation will change if they enter the larger polymer particles (∼20−40 nm) as exit decreases by an order of magnitude (cf. eq 7). The R• radicals have a much higher probability to propagate due to the higher monomer concentration in the particles compared to micelles (cf. the Morton equation115) or undergo termination if the particles contain a polymeric or other radical species. Therefore, exited radicals play an important role in emulsion systems where the size of the particles are small and have found to retard the rate of polymerization in seeded and ab initio emulsion polymerizations with similar RAFT agents used in this work.106,116,117 Similar to the derivation by Butte et al.118 for the Smith− Ewart equations in two dimensions for NMP119 and Luo et al.120 for RAFT (but where j represents the intermediate radical concentration in their derivation of the Smith−Ewart equation), we derive an equation for RAFT.107 The reactivity of the RAFT agent (i.e., Ctr,RAFT) and the rate of formation of R• radicals is the dominant kinetic process in determining the influence of RAFT in a growing particle. As shown in Scheme 5, after the addition of polymeric or oligomeric radicals to the RAFT agent produce R• radicals that can react with monomer or exit a particle.107 Figure 1 shows the kinetic simulations of swollen micelles of 20 nm and the influence of two RAFT agents with different C tr,RAFT values at varying CTA concentrations on conversion with time and the rate at which micelles are nucleated. The first set of simulations show that a RAFT agent with Ctr,RAFT value of 0.7 (similar to that found for xanthates)89,117 gave a significant retardation in rate with increasing CTA concentration (Figure 1A). This suggests that these exited R• radicals act to reduce the number of active growing radicals within the particles through exit and reentering particles to terminate with the growing radical. However, exit and re-entry play an important role to sting (or nucleate) all micelles in the system (Figure 1B). Most micelles are nucleated after only a few percent conversion using a high CTA concentration. In contrast, in a conventional freeradical emulsion polymerization (i.e., without RAFT) the number of micelles nucleated is very small even at full conversion (curve a in Figure 1B). The second set of simulations, for a CTA with Ctr,RAFT value of 3.5,107 shows that the more reactive RAFT agent generates conversion−time profiles with a much greater extent of retardation (Figure 1C). The simulations suggests that with a greater extent of exit early in the polymerization the rate is retarded until all the CTA has been consumed. The consequence of a higher Ctr,RAFT value is H
dx.doi.org/10.1021/ma300170c | Macromolecules XXXX, XXX, XXX−XXX
Macromolecules
Perspective
Scheme 6. Designer Thermoresponsive Nanoreactors for the Template “Living” Radical Polymerization of Styrene To Obtain Monodisperse Nanoparticles with Independent Control over Particle Size and Molecular Weight133
represents the first successful RAFT heterogeneous polymerization where the molecular weight and particle size distributions were narrow and importantly can be controlled independently of each other.125,133 This nanoreactor system takes advantage of superswelling to produce this outcome. It was found that at the beginning of the polymerization only a small fraction of monomer could swell into the nanoreactors. After a few percent conversion and through “superswelling” of the small oligomers the rest of the monomer swell into the nanoreactors, representing a 6-fold volume increase over the theoretical swelling volume according to the Morton equation.115 Producing 3D Structures in Situ Using RAFT Aqueous Dispersion Polymerization. The traditional method for producing three-dimensional polymer structures in water was through the self-assembly of amphiphilic block copolymers consisting of AB,134 ABC,135 or more complex polymer architectures.136,137 The block copolymers can form a wide range of attractive structures, including spherical micelles,134 worm or cylinders,138−141 vesicles or polymersomes,142 toroids,143 and many other structures.144 This traditional way of forming these 3D structures usually relied on first dissolving the block copolymer in a good solvent for all the blocks and then slowly adding water over a long period to drive the structures to their thermodynamic equilibrium. The very low weight fractions (∼1 wt %) of polymer and the long time to form these structures in water restrict the use nanostructures to only a few potential applications. There are only a few reports for the polymerization-induced self-assembly using aqueous dispersion with RAFT.145−149 This method can produce 3D structures at significantly high polymer solids (>10 wt %) in a few hours. The concept relies on forming an amphiphilic AB diblock copolymer in situ and,
depending on the chain length of both the starting hydrophilic A block and the newly formed hydrophobic B block at conversion x, produces 3D structures that are dependent on the same parameters (i.e., free energy) as for the same diblock selfassembled by traditional means. This means that during the RAFT-mediated aqueous polymerization, the 3D structure can change as the chain length of block B increases. Block A consists of a water-soluble MacroCTA that is chain extended in water to form a AB diblock, collapsing into particles when the hydrophobic B block is of sufficient length. At this length superwelling of monomer into the particles should occur, resulting in monomer swollen spherical micelles. The monomer will plasticize the hydrophobic block allowing the diblock to be driven toward it equilibrium structure. At higher conversions and thus higher chain lengths of B, the structures can transform from spherical to either cylindrical or vesicles. The use of a special monomer, 2-hydroxypropyl methacrylate (HPMA), also resulted in the production of a wide range of 3D structures.148,149 The monomer HPMA was water-miscible (up to 13% w/v at room temperature) but when formed into a polymer became hydrophobic. As the HPMA (block B) was copolymerized in situ with the hydrophilic MacroCTA (i.e., A block), the resultant AB diblock collapsed, following the same process as described above. There is the suggestion that the HPMA could swell the hydrophobic polymer region, thus allowing the polymerization to reach high conversions. Armes and co-workers150 constructed a phase diagram as a function of B chain length and solids content. They found that as the solids and chain length of PHPMA increased, the structures transformed from spheres to worm to vesicles. They could also observe with conversion how worms transformed into vesicles. The worms started to aggregate to form an octopi I
dx.doi.org/10.1021/ma300170c | Macromolecules XXXX, XXX, XXX−XXX
Macromolecules
Perspective
Scheme 7. SG1-Based Alkoxyamine BlocBuilder MA in Ionized (a) and Nonionized (b) Forms and (c) the Difunctional DIAMA
behaviors of TEMPO- and SG1-mediated polymerizations, the following discussion will consider each nitroxide separately. TEMPO-Mediated Miniemulsion Polymerization. Miniemulsion polymerization is a widely used and robust process for preparing NMP dispersions. TEMPO is well suited to the homopolymerization of styrenics and copolymerization of styrenics with acrylates. TEMPO-mediated miniemulsions polymerizations require relatively high reaction temperatures (∼130−135 °C), and therefore vessels pressurized to about 3 atm are needed. Operating under pressure is not technically difficult, but from a practical industrial perspective it is disadvantageous as changes in operating procedures would be required, and even modest pressures require different equipment specifications than reactors designed to operate at ambient pressure. Use of tubular reactors152−154 provides a simple and inexpensive alternative to TEMPO-mediated miniemulsions, as the pressure required is easily accommodated in a tube. The important role of thermal polymerization in TEMPOmediated styrene miniemulsions gives rise to unexpected kinetic behavior. Most surprisingly, rates have been found to be nearly independent of nitroxide water solubility, even for nitroxides with very different partition coefficients (e.g., TEMPO and 4-hydroxy-TEMPO).155 The expected result, seen with SG1, is that increased nitroxide partitioning into the aqueous phase should lead to higher rates, poor control, and increased termination.156 Strategies have been developed to increase the typically low reaction rates in TEMPO-mediated polymerizations, including for miniemulsions. TEMPO-scavenging additives have been used in bulk and solution polymerizations, but aqueous dispersions offer the advantage of a low viscosity continuous phase that facilitates addition of water-soluble rate enhancers. Low aqueous phase viscosity also allows addition throughout the polymerization, unlike in bulk where high viscosity prevents effective mixing at moderate−high conversions. Semibatch addition of ascorbic acid is particularly effective in enhancing the polymerization rate, allowing high conversions to be achieved in ∼3 h while maintaining good control.157,158 Interestingly, because the overall reaction time is reduced, loss of livingness through disproportionation is reduced, thereby resulting in an overall increase in chain livingness even with a faster rate. Carefully controlled addition of ascorbic acid can even allow the polymerization temperature with TEMPO to be reduced to as low as ∼100 °C.159 Although the
structure that coalesced to form a jellyfish structure that transformed into vesicles at high conversions (∼99%). The nanoreactor approach of Monteiro and co-workers151 provides a very different approach to make 3D structures. This technique produces 3D structures at high polymer solids, rapidly, reproducibly from well-defined, low polydispersity (PDI) polymers, with excellent stability in solution, and the ability to be freeze-dried and rehydrated without a change in structure. The latter two points are important for stability and sterilization when using these structures in biological applications. The concept relies on the use of a MacroCTA consisting of the thermoresponsive poly(N-isopropylacrylamide) (PNIPAM) in the presence of monomer, ionic surfactant (sodium dodecyl sulfate, SDS), ionic initiator in water. The polymerization mixture heated from room temperature (i.e., below the LCST of the MacroCTA) to 70 °C, resulting in small hydrophobic PNIPAM nanoparticles stabilized by SDS. After polymerization, diblock spherical nanoparticles of P(NIPAM-bSTY) formed with very low PDI values (∼5.5, although an initial pH ∼ 8 seems to give better overall performance), as occurs in conventional emulsion polymerization. The first process step involves preparation of a low molecular weight seed latex, which can then be swollen with monomer and polymerized to yield final latex particles. Using a seed latex eliminates monomer droplet formation early in the polymerization and therefore prevents droplet polymerization and consequent colloidal instability.164−166 This process is very similar to that used in industrial emulsion polymerization processes, where an initial seed latex is made using ∼2−5% of the total monomer charge and the remainder of the monomer is then fed to the reactor over a period of hours. A difunctional alkoxyamine, DIAMA, which is easily synthesized, has also been used in emulsion.165,166 The presence of two charged groups enhances colloidal stability, allowing a significant reduction in particle size and narrower distribution compared to latexes prepared using the monofunctional BlocBuilder MA. Water-soluble macroalkoxyamines comprised of a methacrylic acid-co-sodium styrenesulfonate block terminated with SG1 have recently been shown to be effective in emulsion polymerization.167−169 Using MMA and styrene monomer, an
polydispersities are higher than those at higher temperatures, polymer livingness is good. TEMPO-Mediated Emulsion Polymerization. Inadequate colloidal stability and coagulum formation characterized early attempts to conduct TEMPO-mediated emulsion polymerizations.12,13 Researchers shifted to the more successful and robust miniemulsion NMP, although an emulsion NMP process would still be preferable. The fundamental reasons for the failure of emulsion NMP were shown to be the unavoidable polymerization in monomer droplets occurring concurrently with polymerization in particles, which results in the formation of large (>1 μm particles) and compromises colloidal stability.160,161 When polymerization in the monomer droplets (but not the particles) was inhibited using hydrophobic 4stearoyl-TEMPO, coagulum-free latexes were obtained. A nanoprecipitation technique also gave stable latexes, but the need to use solvent evaporation negates much of the benefit of an aqueous dispersion.122 The prospect for commercially viable TEMPO-mediated emulsion polymerization appears poor. Process modifications can give a reasonably successful outcome, but the additional expense and effort will probably not be justified. hSG1-Mediated Aqueous Dispersions. Because of its versatility in the polymerization of styrenics, acrylates, and even methacrylates (when copolymerized with a small amount of styrene), N-tert-butyl-N-(1-diethylphosphono-2,2-dimethylpropyl) nitroxide, or SG1, has become the most popular and commonly used nitroxide for aqueous dispersions, in both emulsion and miniemulsion. It is available as an alkoxyamine under the trade name “BlocBuilder MA”, from the Arkema Group (Scheme 7). Unfortunately, the nitroxide itself is no longer available from Arkema. Blocbuilder MA dissociates at relatively low temperatures (∼70 °C), making it well-suited as an initiator. Even more advantageous for emulsion polymerization, the carboxylic acid group is ionized at pH > ∼5.5, thereby giving a water-soluble alkoxyamine. SG1-Mediated Polymerization in Miniemulsion. Prior to the availability of BlocBuilder, which can be made watersoluble and is therefore well-suited to emulsion polymerization, earlier studies were conducted in miniemulsion using either monomer-soluble SG1-based alkoxyamines or even two component initiating systems (free radical initiator with SG1).162,163 While the SG1-based miniemulsion process functions effectively, miniemulsions are still slightly more complex (and therefore costly) processes than emulsion polymerization due K
dx.doi.org/10.1021/ma300170c | Macromolecules XXXX, XXX, XXX−XXX
Macromolecules
Perspective
highly living polymer with monomodal particle size distributions. BlocBuilder in its ionized state was used as the watersoluble initiator. The oligomeric chains produced in the aqueous phase also functioned as surfactant. The same onepot, differential monomer addition process was also conducted with surfactant. Interestingly, and in contrast to Charleux’ results discussed above using an amphiphilic macroinitiator, SG1-mediated polymerization of MMA-co-styrene in the presence of surfactant above the cmc yielded monomodal particle size distributions. However, with BMA-co-styrene in the presence of surfactant above the cmc, bimodal particle size distributions were observed, likely due to the occurrence of both micellar and aggregative nucleation. Counterintuitively, converting to a surfactant-free process gave better control over the particle size distribution as well as affording the advantages of eliminating surfactant that can be deleterious to product performance. Recent work has further improved the macroalkoxyamine route developed in the Charleux group. The amphiphilic poly(methacrylic acid-co-styrene)-SG1 macroinitiator was prepared in solution, thereby facilitating a one-pot process.176 Morphology control was also shown to be possible by varying the mass of the hydrophobic block, and the particle morphology can be varied to form spheres, vesicles, or nanofibers.177 Surfactant Choice in Nitroxide-Mediated Aqueous Dispersions. Suitable surfactants for NMP aqueous dispersions include sulfonates such as sodium dodecyl benzenesulfonate (SDBS) and DOWFAX 8390, which exhibit excellent hydrolytic stability at the required elevated temperatures (100− 140 °C). Sulfates, although commonly used in conventional emulsion polymerization, are more prone to hydrolysis at higher temperatures. Caution should be exercised when selecting surfactant concentration, as the rate may be influenced by [SDBS],178,179 possibly due to additional radical generation.180 Metal-Catalyzed “Living” Radical Polymerization in Aqueous Systems. Metal-mediated dispersed aqueous polymerizations can be considerably more challenging than their homogeneous counterparts due to catalyst partitioning and potential poisoning of the catalyst by aqueous phase components (e.g., anionic surfactants). Catalyst partitioning is of particular concern since the deactivator Cu(II) species are usually more water-soluble than the Cu(I) species which activate dormant chains, and therefore even slight partitioning can result in loss of control and excessive termination. The chosen ligand should be highly hydrophobic (e.g., EHA6-TREN or BPMODA, Scheme 9) to minimize catalyst partitioning; however, this also precludes the facile use of conventional emulsion polymerization which requires the mediator to be able to diffuse through the aqueous phase from monomer droplets to particles. A further restriction for metal-mediated polymerizations in aqueous dispersions is that the catalyst/ligand complexes must be fully soluble in monomer, unlike bulk or solution processes where heterogeneous catalysts are commonly used. ATRP in Emulsion Polymerization. Performing ATRP in emulsion polymerization is not straightforward since aqueous phase transport of highly hydrophobic catalyst from monomer droplets to particles is ineffective. (Use of less hydrophobic catalyst results in poor control and increased termination.) Severe colloidal problems were often encountered in early emulsion ATRP studies using alkyl halide initiators with Cu(I)/
MMA-co-styrene hydrophobic block is formed at the outset of polymerization, giving amphiphilic block copolymers that undergo self-assembly. By varying the mass of the hydrophobic block, the particle morphology can be varied to form spheres, vesicles, or nanofibers. While there has been comparatively little attention given to particle size control with NMP emulsion polymerization, some studies have been published. Styrene microemulsions mediated by SG1 were shown to be feasible, while TEMPO-mediated microemulsions were very slow.170,171 Particle sizes in the 25− 60 nm range were prepared, with good control of the polymerization. As is common with microemulsion polymerizations, the surfactant to monomer ratios were fairly high (∼2.5−7:1). A significant finding was that compartmentalization effects from the small particle size yielded better control than for an equivalent bulk system. It was recently shown that particle sizes down to ∼25−30 nm with low surfactant loadings and high solids content could be prepared with a wellcontrolled polymerization, even for methacrylates.172 Furthermore, solids contents ∼40% could also be achieved (Scheme 8). Both features represent major advances for potential commercialization of NMP emulsions. The key to achieving these results, which build on the two-step emulsion process first reported by Charleux,166 lies in an in-depth understanding of the particle nucleation in the first stage. The latexes, which were optically translucent, also had very low surfactant to monomer ratios of 0.13−0.28 w/w (most microemulsions have surfactant to monomer ratios >1). The polymerizations exhibited fast reaction rates and yielded relatively high molecular weight polymer (>100 000 g mol−1). The surprisingly good control at such high molecular weights is probably partly due to reduced termination (compartmentalization), which in turn is attributable to the very small particle size. SG1-mediated n-BA microemulsions have been reported.173 Good control was maintained provided the SG1/AIBN ratio was sufficiently high (>1.6); however, the final particle size grew with increasing SG1/AIBN to the range of ∼90−220 nm, probably due to superswelling. Surfactant free NMP SG1mediated emulsions have also been reported. Styrene was polymerized using a bicomponent initiation system (potassium persulfate in the presence of free SG1) in a two-step emulsion procedure.174 Long induction periods were observed prior to polymerization due to the formation of slow growing SG1-terminated styrene oligomers in the aqueous phase prior. Time was required for these oligomers to propagate to a length where they were sufficiently hydrophobic to nucleate particles, but living chains were produced. Surfactant-free MMA (with 4 mol % styrene) emulsion polymerization was performed by first synthesizing an amphiphilic poly(methacrylic acid-co-styrene)SG1 macroinitiator in solution.167 The isolated macroinitiator acted as both surfactant and initiator for the polymerization, giving a well-controlled polymerization although bimodal particle distributions were observed. SG1-mediated emulsion polymerization of n-butyl methacrylate (BMA) with 10 mol % styrene using a one-pot, differential monomer addition technique has more recently been reported.175 (A small amount of styrene comonomer used with methacrylates yields primarily crosspropagation styrene terminal units in the propagating macroradicals and therefore provides control. Methacrylate terminal units lead to high rates of disproportionation with the nitroxide.) This approach does not require a separate macroinitiator synthesis step and yielded L
dx.doi.org/10.1021/ma300170c | Macromolecules XXXX, XXX, XXX−XXX
Macromolecules
Perspective
Scheme 9. Structure of the Hydrophobic ATRP Ligands BPMODA and EHA6-TREN
Scheme 10. Activator Generated by Electron Transfer (AGET) ATRP71
Surfactant Selection in ATRP Aqueous Dispersions. Unfortunately, not all common emulsion polymerization surfactants are suitable for dispersed phase ATRP. Anionic surfactants such as sulfates and sulfonates poison the catalyst. Most published studies have used nonionic surfactants (Brij 98 (polyoxyethylene(20) oleyl ether)79,181,182 or Tween 80 (polyoxyethylene sorbitan monooleate).183−185,192,193 The best results have been obtained with cationic surfactants such as CTAB (cetyltetramethylammonium bromide), which has been shown to give superior colloidal stability, performs effectively at higher temperatures, and yields smaller particles.194
ligand catalyst complexes.181−183 A two-step seeded emulsion polymerization was more successful than ab initio polymerizations since the catalyst could be confined to the seed particles although colloidal stability remained an issue.184,185 The most effective approach has been to use a two-step emulsion polymerization process in which microemulsion-size particles (∼30−40 nm) containing the catalyst are first prepared.186 The particles are then swollen with added monomer to grow the particles to their final desired size. The process has been further improved by incorporating a surface active monomer into an AGET emulsion for n-BMA polymerization process. The surfactant levels are reasonably low (∼5% with respect to monomer) as are the solids contents (>20%).187 The use of an anionic, surface-active initiator (and not a monomer-soluble initiator as is usually used) has recently been reported in AGET emulsion ATRP of fluorinated monomers.188 ATRP in Miniemulsion Polymerization. Miniemulsion polymerization has proven to be the most robust method for preparing aqueous dispersions via ATRP. Conventional (forward) ATRP gives poor control because of the sensitivity of the Cu(I) species to air. (The preparation of the miniemulsion requires high shear mixing such as sonication or microfluidization that entrains air.) Reverse ATRP using Cu(II) is more tolerant of oxygen and yields better control, although molecular weight predictability is often poor because initiator efficiencies are variable.181,182 SNRI (simultaneous normal and reverse initiation) uses less oxygen sensitive Cu(II) species but addresses with alkyl halide as the primary initiator and a small amount of free radical initiator as a secondary initiator. The activating Cu(I) species is generated in situ by reduction of the Cu(II) to Cu(I) as the free radical initiator decomposes.189−191 Unfortunately, the use of free radical initiator in SNRI leads to minor homopolymer formation, thereby preventing high purity blocks. High purity blocks can be prepared using ascorbic acid as a reducing agent in the AGET (activator generated by electron transfer) ATRP process (Scheme 10). AGET eliminates the need for an initiator as well as increasing the system’s tolerance to air by scavenging oxygen.71,79
■
COMPARTMENTALIZATION IN LRP AQUEOUS DISPERSIONS In conventional emulsion polymerization, segregation of the propagating radicals in different particles results in higher reaction rates and higher molecular weights compared to bulk/ solution processes by effectively reducing the termination rate between macroradicals. (Chains terminate primarily as a result of another short radical entering from the aqueous phase.) This phenomenon, known as “compartmentalization”, fundamentally alters the kinetics in conventional emulsion polymerization by influencing the main chain stopping event (termination).2 In NMP and ATRP (both reversible termination systems) the primary chain stopping event is reversible deactivation. (In RAFT and other reversible transfer based forms of LRP, chain transfer is the main chain stopping event.) Termination between propagating radicals is comparatively minor in a well-controlled system. The relevant question now becomes whether the kinetics of living/controlled radical polymerizations are affected by reducing the reaction volume to that of a ∼50−200 nm particle. RAFT in principle behaves quite similarly to a nonliving radical polymerization with regards to compartmentalization. RAFT polymerizations in aqueous dispersions generally exhibit higher rates compared to bulk, although this tendency may be obscured by other effects such as rate retardation arising from radical desorption into the aqueous phase. Initially it was thought that in reversible termination systems (NMP, ATRP) compartmentalization effects did not exist, based on experimental observations that the rates in bulk and miniemulsion polymerizations appeared to be quite similar. However, it has been demonstrated experimentally for both TEMPO-mediated NMP and ATRP miniemulsions that compartmentalization effects do exist under some conditions.195,196 At sufficiently small particles sizes (which depends on the system in question), decreases in polymerization rate are observed, but more importantly control and livingness are improved. Lower rate M
dx.doi.org/10.1021/ma300170c | Macromolecules XXXX, XXX, XXX−XXX
Macromolecules
Perspective
products where profit margins are slim, competitive pressures are high and the tolerance for increased cost is minimal; there is little likelihood of LRP finding commercial use. At the other end of the spectrum, for very high value added items designed for niche markets such as those in the field of biomedical devices, LRP is an excellent candidate for enabling new polymers and devices. While lucrative on a $/kg basis, the downside of this market is that overall volumes are small and are likely to remain small. However, we believe there exists for LRP a potentially highly profitable middle ground between commodity polymers and those targeted at small niche markets. These include polymers for which the molecular design, chain architecture, and possibly mesostructure (morphology) provide tangible performance advantages over polymers made using conventional free radical polymerizations. This market should be considered in dual categories. The first category includes markets where there is a strong base of existing products and where a new polymer made by LRP would displace similar products. This is often quite difficult; the manufacturing processes for existing products have been optimized to minimize cost based on current capital equipment (bought and paid for). Because there is market risk and possibly substantial investment required to launch a new product, replacing a similar existing product requires dramatically lower cost (which is highly improbable with LRP polymers) and/or significantly enhanced end-use performance. Modest improvements in properties or performance afforded by design of LRP polymers will not be sufficient to warrant commercialization. The attractiveness of this market segment lies in the current existence of substantial market receptor demand, which means sales of a new product have the potential to be high from the outset of their initial launch. The second market category is the use of LRP in new products for which there are currently no established markets nor similar polymers available from competitors. The comparative lack of competition provides the commercialization incentive for this market, but the absence of established markets is a clear disadvantage. Product sales are difficult to predict, and therefore there is greater risk than when established markets exist. The growth in demand for LRP polymers targeted at this sector tends to be slow, as it often requires cooperative development efforts with customers. However, the potential rewards, market share, and profitability are considerable. In our experience, a leading cause for the poor market penetration of LRP polymers lies in the difficulty companies have had identifying suitable market opportunities. Many companies we know have made intensive efforts in assessing and evaluating LRP polymers in various product lines, and most have reached the decision that there is simply not adequate economic justification to invest in LRP products. In some cases the performance advantages of LRP polymers are recognized for given applications, but the cost is deemed too high. In other cases, creative polymer reaction engineering techniques can sufficiently narrow the performance gap between LRP and conventional polymers such that investment in LRP is no longer attractive. While many factors may contribute to the increased cost of LRP compared to free radical polymerization (Destarac has provided an excellent discussion on this subject1), high process costs are a key issue. For LRP to be attractive based on the commercial constraints discussed above, the “living” agents must be cheap and readily available on a large scale. Copper is the most readily available
in smaller particles results primarily from enhanced deactivation of propagating radicals, which also increase livingness. (Enhanced deactivation refers to an effective increase in reaction rate of two reactants as a result of being confined to a small reaction volume.) Interestingly, compartmentalization was not observed with SG1-mediated emulsion polymerizations, which was attributed to SG1’s greater solubility that allows it to rapidly diffuse between phases to equilibrate its concentration in different particles.197 A powerful example of the benefits of compartmentalization in ATRP is shown in the preparation of high molecular weight polymer.198 Using a redox initiation system that yielded a low number of chains per particle CuBr2/EHA6-TREN catalyst, poly(n-butyl methacrylate) with Mn ∼ 106 g/mol and PDI ∼ 1.25 was produced. Reaction rates were reasonable (conversion >80% in ∼8 h). Evolution of the molecular weight distributions showed excellent livingness, even at Mn > 800 000 g/mol (Figure 2).
Figure 2. SEC traces for the miniemulsion ATRP of butyl methacrylate yielding high to ultrahigh molecular weights. Conversion increasing from right to left: conversion = 11%, Mn = 222 500, PDI = 1.56; conversion = 23%, Mn = 345 000, PDI = 1.47; conversion = 74%, Mn = 859 000, PDI = 1.24; conversion = 83%, Mn = 989 900, PDI = 1.24.194
Small particle size combined with low particle numbers gave conditions where the probability of termination was significantly reduced compared to the bulk case, allowing very high chain lengths to be produced with negligible termination. Modeling studies have provided additional insight into the role of compartmentalization.199−203 For styrene polymerizations with CuX/4,4′-dinonyl-2,2′-dipyridyl (X = Br or Cl) catalyst,199 predicted livingness should be improved because of segregation, while control was predicted to be improved in sufficiently small particles because of the confined space effect. Larger effects were predicted when there were fewer chains per particle (high target Mn). Thomson and Cunningham simulated the high activity catalyst/ligand system (CuBr/ EHA6TREN) system with n-butyl methacrylate, focusing on the PDI and livingness.200 They predicted the existence of a particle size range where the rate was greater than that of bulk polymerization with PDI and termination rates lower than in bulk. They also predicted rate to be controlled by the relative concentration of Cu(I) and Cu(II), which are dependent upon the size of the particles, unlike in bulk ATRP where the rate is controlled by the ratio of Cu(I)/Cu(II). Perspective. Producing a polymer using LRP will add to the final unit manufacturing cost, regardless of how well the chemistry and the process are designed and optimized. For N
dx.doi.org/10.1021/ma300170c | Macromolecules XXXX, XXX, XXX−XXX
Macromolecules
Perspective
been resolved. Other proprietary nitroxides may have the
material and can be added as a solid (as Cu(0) in SET-LRP or Cu(I)/ligand in ATRP). RAFT and nitroxide agents are becoming readily available and should either or both find industrial penetration, the cost and range of these agents will undoubtedly become cheaper. The authors strongly believe that development of emulsion-based processes, with their inherently lower cost structure, will provide a critical economic advantage to LRP polymers in successfully competing in the marketplace.
potential to be used in emulsion, provided they possess similar important properties to SG1, including an appropriate activation temperature range and the ability to be converted to a water-soluble initiating species. Expansion of the range of monomers that can be used in aqueous NMP dispersions is
■
desirable. Further reduction in nitroxide cost and more
ISSUES AND CHALLENGES General Comments. It is often assumed that for an LRP polymer to have commercial value it must have a narrow molecular weight distribution (low polydispersity index). While this is true for some applications, we are aware of several industrial examples where LRP polymers with comparatively broad distributions (PDI ∼ 1.5−2) perform adequately for given applications. In most of these cases, it is possible to achieve a much lower PDI; however, this typically adds to the process cost. By relaxing the requirement for a narrow molecular weight distribution, the process can often be run at a higher rate (increasing reactor productivity) and driven to high conversion with less mediating agent (for ATRP or SETLRP) and no purification of reagents. However, most publications show examples of only well-controlled systems with low PDI, often at only low to moderate conversions. What is largely missing from the published literature is an examination of how sensitive polymer livingness and control are to the imposition of realistic constraints such as shorter reaction times (∼∼95%), reduced use of mediating agent (for ATRP or SET-LRP), use of unpurified reagents, and realistic high-solids formulations. The exploration of these issues in emulsion-based systems will provide the greatest potential impact in terms of realizing commercial potential. Copper-Catalyzed LRP. Major advances have been made in ATRP in both its adaptation to water-based dispersions and to reducing the required catalyst concentrations. It remains difficult to perform emulsion polymerization with ATRP because of issues with transport of the highly hydrophobic catalyst/ligand complex through the aqueous phase, although the two-stage process developed by Matyjaszewski186 offers some promise. Further reduction in copper concentrations is required in ATRP aqueous dispersions, which are currently limited to the moderately high Cu loadings used in the AGET process. (ARGET is not currently feasible with aqueous dispersions.) Reduction of Cu levels is particularly important as removal of the catalyst from latex particles is currently not possible without approaches such as first dissolving the polymer in solvent, which will destroy the colloidal nature of the system and add considerably to overall cost. Alternatively, methods to remove the catalyst from particles would be invaluable. There are currently a limited number of ligands that are effective in ATRP dispersions; development of additional ligands (and commercial availability) would expand the range of monomers and of feasible process conditions. SET-LRP has also drawn considerable industrial interest due to the rapid polymerization rates, high chain-end fidelity, and reduction in copper. The major challenge for SET-LRP is converting this system to emulsion-based polymerization. Perhaps the most significant impact would be development of catalysts based on more environmentally benign metals such as iron. NMP. With the development of SG1-mediated emulsion polymerization processes, many important process issues have
widespread accessibility of commercial alkoxyamines will facilitate commercialization. The major perceived disadvantage for commercial development of NMP dispersions is the elevated temperatures required for polymerization (usually >100 °C). While technically this is not difficult, it does require industry to adopt new operating procedures if current processes are not operated under pressure and may require capital investment. Both disincentives would be eliminated by development of commercial nitroxides that can be used at temperatures
