Living Radical Polymerization in Dispersed Systems: An

Review pubs.acs.org/CR

Controlled/Living Radical Polymerization in Dispersed Systems: An Update Per B. Zetterlund,*,† Stuart C. Thickett,†,⊥ Sébastien Perrier,‡,§ Elodie Bourgeat-Lami,∥ and Muriel Lansalot∥

Downloaded by UNIV OF NEBRASKA-LINCOLN on August 29, 2015 | http://pubs.acs.org Publication Date (Web): August 27, 2015 | doi: 10.1021/cr500625k

†

Centre for Advanced Macromolecular Design (CAMD), School of Chemical Engineering, The University of New South Wales, Sydney, NSW 2052, Australia ‡ Department of Chemistry, The University of Warwick, Coventry CV4 7AL, U.K. § Faculty of Pharmacy and Pharmaceutical Sciences, Monash University, Melbourne, VIC 3052, Australia ∥ Laboratory of Chemistry, Catalysis, Polymers and Processes (C2P2), LCPP group, Université de Lyon, Université Lyon 1, CPE Lyon, CNRS, UMR 5265, 43, Boulevard du 11 Novembre 1918, F-69616 Villeurbanne, France 4.6. Iodine Transfer Polymerization in Emulsion 5. Microemulsion Polymerization 5.1. General Considerations 5.2. Microemulsion NMP 5.3. Microemulsion ATRP 5.4. RAFT Microemulsion Polymerization 6. CLRP in Dispersed Systems Involving CO2 6.1. General Considerations 6.2. NMP 6.3. ATRP 6.4. RAFT 6.5. CO2-Induced Miniemulsions 7. Dispersion and Precipitation Polymerization 7.1. NMP 7.1.1. Dispersion Polymerization 7.2. ATRP 7.2.1. Dispersion Polymerization 7.2.2. Precipitation Polymerization 7.3. RAFT 7.3.1. Dispersion Polymerization 7.3.2. Precipitation Polymerization 7.4. Other CLRP Techniques 8. Morphological Aspects 8.1. General Considerations 8.2. Morphological Control via CLRP 8.2.1. General Considerations 8.2.2. Morphological Control via Dispersion Polymerization 8.2.3. Morphological Control via Emulsion Polymerization 9. Organic/Inorganic Hybrid Particles 9.1. General Considerations 9.2. Miniemulsion Polymerization Approaches 9.3. Emulsion Polymerization Approaches 10. Surface-Initiated Polymerization 10.1. General Considerations 10.2. Surface-Initiated ATRP 10.3. Surface-Initiated RAFT 10.4. Surface-Initiated NMP 10.5. Surface-Initiated TERP

CONTENTS 1. Introduction 2. CompartmentalizationThe Concept of Nanoreactors 2.1. General Considerations 2.2. CLRP Based on the Persistent Radical Effect 2.3. CLRP Based on Degenerative Transfer 3. Miniemulsion Polymerization 3.1. General Considerations 3.2. NMP in Miniemulsion 3.3. ATRP in Miniemulsion 3.3.1. Surfactants 3.3.2. Inverse Miniemulsion ATRP 3.4. RAFT in Miniemulsion 3.4.1. Polymeric Stabilizers/MacroRAFT Agent 3.4.2. Inverse Miniemulsion RAFT 3.4.3. Miscellaneous Miniemulsion RAFT 4. Emulsion Polymerization 4.1. General Considerations 4.2. Emulsion NMP 4.3. Emulsion ATRP 4.3.1. Emulsion AGET/ARGET ATRP 4.3.2. Miscellaneous Emulsion ATRP 4.4. Emulsion RAFT 4.4.1. Ab Initio RAFT Emulsion Polymerization via Self-Assembly 4.4.2. Miscellaneous RAFT Emulsion Polymerization 4.5. Emulsion TERP © XXXX American Chemical Society

B B B B C D D D E E E F F G G H H H H H I I J K L

L L L L L M N N N N O O O P P P P P Q Q T T T T U U V X Z Z Z AB AG AG AH AI AJ AJ

Received: November 3, 2014

A

DOI: 10.1021/cr500625k Chem. Rev. XXXX, XXX, XXX−XXX

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11. Conclusions Author Information Corresponding Author Present Address Notes Biographies List of Abbreviations References

Review

(nonliving) emulsion polymerization, compartmentalization effects are well-known to occur in so-called “zero-one” systems,25,26 where polymerization occurs in polymer particles of diameter typically less than 100 nm. In such systems, segregation of propagating radicals between particles leads to a reduction in termination rate and, thus, high Rp and high molecular weight. Compartmentalization effects may also play a role when CLRP is implemented in dispersed systems. Compared to a nonliving system, the kinetics in a compartmentalized CLRP system are typically considerably more complex because the deactivator species (e.g., nitroxide in NMP) may also be compartmentalized (in addition to propagating radicals). Compartmentalization in systems based on the persistent radical effect (PRE),27 mainly NMP and ATRP, was thoroughly reviewed by Zetterlund in 2011.28 Compartmentalization effects in both PRE systems and degenerative transfer systems (RAFT) were reviewed in 2008 by Zetterlund et al.1 The present review will focus on theoretical developments since 2011 for NMP/ATRP and since 2008 for RAFT. With regard to experimental evidence of compartmentalization effects, the reader is referred to the 2008 review by Zetterlund et al.1

AJ AJ AJ AJ AJ AJ AL AM

1. INTRODUCTION This review is an extensive update to the comprehensive review on controlled/living radical polymerization (CLRP) in dispersed systems published in 2008.1 A note on nomenclature: we recognize that an IUPAC task group has recommended the use of the term “reversible deactivation radical polymerization” (RDRP);2 however, throughout this review the older term CLRP is used to avoid possible confusion. Several reviews on CLRP (some only covering specific CLRP techniques) in dispersed systems were published before 2009,3−13 and Cunningham and Monteiro14 reviewed the field in 2012 in a nonexhaustive report focusing on prospects of commercial development of CLRP processes in dispersed systems. CLRP is by now well-established in polymer chemistry and has been reviewed extensively.15−18 In short, CLRP enables one to synthesize a wide range of structurally advanced and welldefined macromolecular structures that are inaccessible by nonliving radical polymerization techniques, such as block copolymers, star (co)polymers, and other more complex architectures. Recent developments in CLRP methodology has also paved the way for synthesis of high-order multiblock copolymers,19−22 bringing us closer to realizing control of the monomer sequence distribution along chains. CLRP was initially developed in homogeneous systems (bulk, solution) in the 1980s and 1990s, but it soon became apparent that for these techniques to realize their full potential, they must be made compatible with heterogeneous systems, such as aqueous emulsion polymerization. Aqueous dispersed systems are the industrial methods of choice, and synthesis of nanoparticles and various other polymeric nano-objects typically involve conducting CLRP in a heterogeneous environment. Prior to 2008, the main thrust of the research on CLRP in dispersed systems remained fairly fundamental; significant efforts were devoted to understanding how one can best implement CLRP in various heterogeneous systems while control/livingness and colloidal stability were maintained. Many of the initial issues encountered have now been overcome, although gaps in our understanding remain, and the focus has now shifted toward more applied aspects, such as synthesis of complex nanoobjects of nonspherical morphology with a range of potential applications.

2.2. CLRP Based on the Persistent Radical Effect

The two most well-known CLRP systems that operate based on the PRE are NMP and ATRP, and both have been studied extensively with regard to compartmentalization, especially from a theoretical perspective, by the teams of Zetterlund,28−39 Tobita,40−46 Cunningham,47 and Reyniers.48 The main features of compartmentalization in these systems are as follows (Figure 1):28 (i) The confined space effect on deactivation (later

Figure 1. Schematic illustrations of (a) the segregation effect and (b) the confined space effect in a compartmentalized reaction system. Reprinted with permission from ref 1. Copyright 2008 American Chemical Society.

referred to as “single molecule concentration theory” by Tobita), whereby deactivation occurs more rapidly in smaller particles, primarily leading to lower Rp and narrower MWD;29 (ii) The segregation effect on termination (later referred to as “isolation effect” by Tobita), whereby physical separation of propagating radicals reduces the termination rate, leading to higher Rp, broader MWD, and increased livingness;29 and (iii) The fluctuation effect, whereby an uneven distribution of deactivator species between particles leads to an increase in Rp, broadening of the MWD, and decrease in livingness. These features have been described in detail in the papers cited above and in a 2011 review by Zetterlund.28 Typically, particle diameters lower than 200 nm are required for compartmen-

2. COMPARTMENTALIZATIONTHE CONCEPT OF NANOREACTORS 2.1. General Considerations

Compartmentalization refers to the physical confinement of reactants to a very small space. Depending on a number of factors, this may alter reaction rates compared to the corresponding noncompartmentalized system. Ultimately, one wishes to understand and exploit such effects to tweak reactions and polymerizations to optimize yields and/or increase rates, not only in the field of polymer chemistry.23,24 In conventional B


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Figure 2. Simulated conversion−time data for NMP of styrene using St-TEMPO initiator at 125 °C without (blue, broken−dotted lines) and with (black, solid lines) exit and entry of TEMPO at particle diameters of 10 (left), 40 (center), and 70 nm (right) ([St]0/[St-TEMPO]0 = 8.71/0.02). The red, broken lines denote simulated bulk NMP. Reprinted with permission from ref 53. Copyright 2012 American Chemical Society.

of particles contain no propagating radicals and no nitroxide, and consequently, exit of TEMPO from a particle where an activation event has occurred produces a particle with one sole propagating radical, resulting in uncontrolled propagating. These findings are anticipated to also apply to other NMP and ATRP systems, depending on the partitioning characteristics of the deactivator. Bentein et al.48 investigated the system styrene/SG1/123 °C initiated by a low molecular weight alkoxyamine, also using Smith-Ewart equations accounting for compartmentalization of propagating radicals and nitroxide as well as nitroxide exit/entry. For a particle diameter of 70 nm, nitroxide partitioning did not result in any strong effects on the kinetics of the system, except for a minor increase in Rp. Given the high NMP equilibrium constant of this system, coupled with the relatively large particles, there was a high number of free nitroxide species per particle (∼40), and as such exit/entry of nitroxide does not have as pronounced an effect as in the system investigated by Sugihara and Zetterlund.53 It is of course desirable to “detect”, and ultimately exploit,55 compartmentalization effects experimentally.50,56−63 This is, however, a great challenge, as reviewed in detail by Zetterlund,28 mainly because a number of other effects may play a role simultaneously (e.g., partitioning, interface effects,64−67 enhanced spontaneous radical generation68,69). Moreover, in most cases, the corresponding homogeneous experiments have not been conducted, and thus, direct comparison between homogeneous and heterogeneous systems is not possible. Perhaps the most convincing experimental evidence to date is the work by Cunningham’s team on styrene miniemulsion NMP using TEMPO56 and miniemulsion reverse ATRP of n-butyl methacrylate58,61,70

talization effects to be significant in CLRP, but this depends very much on the particular system. The typical scenario when compartmentalization effects are operative (based on simulations) is that both the control (narrower MWD) and livingness are increased, but this is at the expense of a lower Rp (compared to the corresponding noncompartmentalized case). It has also been shown that for the styrene/TEMPO and styrene/TIPNO systems at 125 °C, simultaneous improvement in both control and livingness cannot be achieved by simply diluting or adding extra free nitroxide to the corresponding bulk system.39 With the exception of the theoretical work by Thomson and Cunningham dealing with a specific ATRP system,47 all cases investigated to date show that it is not possible to obtain a simultaneous increase in control/livingness and Rp as a result of compartmentalization effects.28 Prior to 2012, compartmentalization of both propagating radicals and deactivator [nitroxide in NMP, Cu(II) complex in ATRP] had not been modeled simultaneously with the exit/ entry of deactivator. Typically, it had been assumed that the deactivator is confined to the dispersed phase (or is freely mobile in the system49), although effects of deactivator partitioning in compartmentalized systems had been considered.34,40,50 However, in the typical NMP system styrene/ TEMPO, it is known that TEMPO does in fact partition to some extent to the continuous aqueous phase.51,52 To investigate this, Sugihara and Zetterlund53 modified the twodimensional Smith−Ewart equations29,54 to also account for nitroxide exit/entry for the system styrene/TEMPO/125 °C initiated by a low molecular weight alkoxyamine. Exit/entry of TEMPO was modeled using a previously developed theory25 using the experimentally obtained partitioning coefficient of TEMPO between styrene/water at 135 °C ([TEMPO]St/ [TEMPO]water = 98.8).51 It turns out that even for the relatively hydrophobic nitroxide TEMPO, the exit/entry of TEMPO has a major effect on the polymerization. Relative to the corresponding bulk system, Rp increases, the livingness increases, but the MWD becomes broader. This is in sharp contrast to when the exit/entry of TEMPO is not accounted for (in which case Rp decreases and both control and livingness are improved). The influence of TEMPO exit/entry on Rp is illustrated in Figure 2, which displays conversion−time plots with and without exit/entry and the corresponding bulk system. For a compartmentalized NMP system, the very vast majority

2.3. CLRP Based on Degenerative Transfer

Degenerative transfer systems, such as RAFT polymerization, are intrinsically different from PRE systems with regard to compartmentalization in the sense that the deactivation step is typically unaffected by compartmentalization [because the deactivator (the RAFT agent) concentration is generally too high]. RAFT polymerization in dispersed systems can be influenced by a number of factors (that are interrelated to compartmentalization effects), such as RAFT agent partitioning, “RAFT-induced” exit,71−73 and chain-length-dependent termination,74−76 as reviewed in detail in 2008 by Zetterlund et al.1 The focus here will be on developments since 2008, which have mainly been theoretical work in the area of compartmenC



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reduce the extent of this effect. It would appear that the MCV effect is of a general nature; i.e., it should apply also to other CLRP systems, as well as nonliving systems. The reason that Rp in fact decreases as the diameter is reduced beyond a certain minimum diameter is that the MCV effect becomes stronger than the segregation effect, reducing the bimolecular termination rate.45 Note that the confined space effect on deactivation is not operative in a typical RAFT system due to the RAFT agent concentration being too high.1 The MWDs are also influenced by compartmentalization.78,83 In short, in the low to intermediate conversion range, the MWDs broaden if the particles are small enough due to different levels of conversion between particles (MCV effect). A higher initiation rate mitigates this, instead leading to generation of a greater number of dead chains overall, manifested in broader MWD at high conversion. Smaller particles lead to a higher Rp, and as such, fewer dead chains are generated over a shorter polymerization time. In RAFT polymerization, the number of dead chains formed by termination corresponds exactly to the number of radicals generated by initiator decomposition during the polymerization time (with adjustment made for termination by combination vs disproportionation).20,22 As discussed previously,1 xanthates are suitable as RAFT agents for implementation of ab initio RAFT emulsion polymerization due to their low reactivity. Gomes and coworkers91,92 investigated the kinetics and compartmentalization effects in such systems, also using semibatch processes with a view to improve the overall level of control over MWD and particle size distribution. Monteiro and co-workers93 synthesized star polymers in miniemulsion using a tetrafunctional RAFT agent, exploiting compartmentalization to reduce the level of bimolecular termination (including star−star coupling).

talization effects on RAFT polymerization in idealized miniemulsion systems in the absence of phase transfer effects.41,45,77−83 The precise RAFT mechanism remains under debate, in particular with regard to the exact role of intermediate RAFT adduct radicals.84−87 In the case of dithiobenzoates in homogeneous systems, the presence of a RAFT agent leads to a reduction in Rp. This has been rationalized via two main schools of thought:63,65 (i) slow fragmentation of the adduct radical88 or (ii) cross-termination between a propagating radical and an adduct radical.89 Thus, when trying to understand RAFT compartmentalization effects via modeling and simulations, one must first make a choice as to what basic model to adopt. Tobita and Yanase41,45,77 used Monte Carlo simulations to demonstrate that model ii leads to an increase in Rp with decreasing particle diameter (down to a certain minimum diameter), whereas Rp according to model i is independent of particle size. For model ii, a rate increase is only observed for smaller particles if the lifetime of a propagating radical is sufficiently high relative to that of an adduct radical, as given by an “active radical period” (ϕA) of greater than approximately 0.01 ϕA =

K K + [XP]

(1)

where [XP] denotes the RAFT end group concentration and K is the RAFT equilibrium constant as defined by K = k1/k2, with k1 and k2 being the rate coefficients for fragmentation and addition of propagating radical to RAFT moiety, respectively (note that K is, unlike here, typically defined as k2/k1). This is consistent with the case of conventional radical polymerization (in the absence of RAFT agent) where a rate increase is typically observed, in which case ϕA = 1. The fact that the two models for retardation (slow fragmentation model and crosstermination model) respond differently to a change in particle size provides a means of elucidation of the true origin of retardation.82 Suzuki et al.81,83 showed that experimentally Rp increases with decreasing particle size (as seen also in many other studies1), thus providing strong support for the crosstermination model. Simulations by Tobita79,80 showed that increasing the RAFT agent concentration leads to retardation in zero−one systems, regardless of whether cross-termination occurs or not; crosstermination does not influence Rp under such conditions. This predicted retardation in a zero-one system on increasing the RAFT agent concentration is consistent with earlier work by Luo et al.,90 which showed that the presence of a RAFT agent means that some of the particles that are “1” (i.e., containing one radical species) are inactive due to the radical being a RAFT adduct radical. An additional feature of compartmentalized RAFT systems is the so-called monomer concentration variation (MCV) effect,45,77,79 which refers to a reduction in Rp due to the monomer concentrations being different in different particles (compared to the average monomer concentration of the whole system applying to all particles) for systems with sufficiently small particle size (diameter 2 in most cases). These results may be explained by the coexistence of conventional and controlled/living radical polymerization, as the amount of RAFT agent was quite low compared to that of the photoinitiator. This resulted in a complex nucleation step leading to a bimodal PSD, eventually narrowing to one single population at the end of the process (Figure 11). The influence of various parameters (RAFT agent structure and concentration and concentration of Darocur 1173, PVP, and MMA) was subsequently studied in more detail, leading systematically to highly monodisperse particles with, however, poor control of the polymerization. 362 This approach was nevertheless extended with success to the synthesis of cross-linked or functional particles.361 The particle surface was tailored further by replacing PVP with different trithiocarbonate macroRAFT agents, namely, poly(oligo(ethylene oxide) methyl ether acrylate) (POEGA), P(OEGA-co-AA), PAA, and P(OEGA-co-

7.3. RAFT

7.3.1. Dispersion Polymerization. The very first studies on RAFT dispersion polymerization were carried out using low molecular weight RAFT agents.340,353−357 Except for the work of Barner and co-workers,353 they all relied on the two-stage dispersion method developed by Song and Winnik.340 Narrow PSD was ensured, but with mixed results in regard to the level Q



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initially fully soluble in the polymerization medium, but PEVA being thermoresponsive, the increase of the temperature to start the polymerization of styrene led to the self-assembly of the macroRAFT agent. The presence of these micelles greatly shortened the induction time very often observed with other macroRAFT agents, which corresponds to the time needed for the block copolymers to self-assemble. This system behaved like a seeded dispersion, with no need for nucleation. The central PEVA sensitive block enables the modification of the particle structure (PEVA part of the corona below its LCST, part of the core above). In closely related work, PSt-bPDMAAm macroRAFT agents, after micellization in water/ ethanol in the presence of styrene, were used as seeds for styrene RAFT dispersion polymerization.375 The active chain end being carried by the PDMAAm solvophilic block, the growth of the second PS block led to flowerlike nanoparticles stabilized by the central block of PDMAAm. A great deal of work has also been dedicated to the synthesis of nanogels and core cross-linked star (CCS) polymers, using a cross-linker during the polymerization of the core-forming block. It is noteworthy that all the nanogel studies described below also incorporate the synthesis of amphiphilic block copolymer particles first carried out in the absence of crosslinker. This field was pioneered by An et al.,376 who used PDMAAm-based macroRAFT agents for the aqueous microwave-assisted polymerization of NIPAM in the presence of BIS. The living character of the nanogels was shown by using them as seeds for the copolymerization of N-isopropyl methacrylamide (NIPMAM) and BIS, leading to the formation of nanogels (size 90%) led to CCS polymers.385 Various CCS polymers have been synthesized by An’s group. PDMAAm and POEGMA macroRAFT agents were used for the synthesis in water of CCS polymers of P(NIPAM-co-BIS) (with high NIPAM/BIS ratio, typically 5), which were revealed to be efficient stabilizers for Pickering emulsions.387 Heteroarm CCS polymers of P(nBA-co-HDDA) were formed in water/ ethanol using at the same time PDMAAm and PMEA macroRAFT agents. The Dh of the CCS in acetone was 13.9 nm, but it increased to ca. 45 nm in water, indicating the formation of aggregates.388 In a closely related study, either homoarm or heteroarm CCS polymers of PHDDA were prepared with the same macroRAFT agents. CCS polymers with tunable polarity could be formed and used as stabilizer of an O (oil)/W (water) emulsion or even multiple O/W or W/O emulsions.389 Following the same strategy, high internal phase emulsions (HIPE) were produced using CCS polymers with PDMAEMA arms and PHDDA core.390 More recently, CCS polymers meant to be used as pH-sensitive 19F magnetic resonance imaging (MRI) contrast agents have been reported.391 POEGMA-b-P(DMAEMA-co-TFEMA) (providing pH sensitivity and MRI signal) was used in the RAFT dispersion of bis(2-methacryloyl)oxyethyl disulfide, affording a cross-linked core degradable via the addition of reducing agents. Finally, macroRAFT (co)polymers have also been evaluated as reactive stabilizers, the goal being to covalently anchor the macroRAFT agent onto the particle surface, via the in situ

Table 1. RAFT Dispersion Polymerization Using Various MacroRAFT Agents (Systems Yielding Spherical Particles) macroRAFT

solvent

Core

ref

PSt

cyclohexane

PEO P2EHA

chloroform isododecane

P4VP P(4VP-coDVB) P(St-co-MAn) PMA

364

PNIPAM P(mPEGV)/PDMAAm PMAA PDMAAm PKSPMA PNIPAM-b-PDMAEMA PDMAEMA-b-PNIPAM P(mPEGV)-b-PNIPAM PDMAAm-b-PEVA (seed above PEVA LCST) PSt-b-PDMAAm (seed after micellization in selective solvent)

ethanol/water ethanol/water methanol water water methanol/water

PSt PSt PnBA PNIPAM PHPMA PSt

365 366, 367 360 368 369 370 371 372

methanol/water methanol/water

PSt PSt

373 374

ethanol/water

PSt

375

presence of PEGDMA, to synthesize biocompatible, thermosensitive (tunable by the ratio MEO2MA/OEGMA), and antifouling nanogels.381,382 The synthesis of P(MEA-coPEGA) thermosensitive nanogels stabilized by a PDMAAm hairy layer was also reported.383 The thermoresponsive behavior of PDMAEMA was also used for the aqueous synthesis of PEG-stabilized nanogels of P(DMAEMA-coBIS).384 Thermoresponsive PDEAAm nanogels were obtained by Rieger, Charleux, and co-workers using double hydrophilic S


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Figure 12. Evolution of the hydrodynamic diameter (Dh) versus temperature for cross-linked PDMAAm/P(MEA-co-OEGA) (a) and PDMAAm/ PNIPAM (b) nanogels. Reprinted with permission from ref 380. Copyright 2014 American Chemical Society.

sis,410−412 drug delivery device,413 chemical sensor,414 and chiral selector for HPLC415).

formation of an amphiphilic/diblock copolymer, without seeking the control over the radical polymerization of the core-forming polymer. This approach has been described for the synthesis of PSt particles using macroRAFT agents of PMAA,392 P4VP,393 or PVAc-b-P4VP.394 PnBA, PMA, and PAN particles have also been reported using macroRAFT agents of PNAM,395 P2-EHA,396 and PEG-b-PAN,397 respectively. 7.3.2. Precipitation Polymerization. Barner and coworkers were the first to report on RAFT precipitation polymerization. 3 5 3 , 3 9 8 , 3 9 9 Quite polydisperse poly(divinylbenzene) (PDVB) microspheres were synthesized in acetonitrile using various RAFT agents, with however no direct evidence of the control of the polymerization. The RAFT end groups contained inside and on the particle surface were further used to graft various polymer chains [PS,353 PnBA and PDMAAm,399 and poly(ε-caprolactone)398]. In more recent work, RAFT precipitation polymerization has mainly been used for the synthesis of MIP microspheres, and Zhang and co-workers have, like they did in the area of ATRP, largely contributed to the field.400 2,4-D-imprinted microspheres with a narrow PSD were obtained via the RAFT precipitation polymerization of 4VP and EGDMA in the presence of cumyl dithiobenzoate (CDB).401 These MIP microspheres showed improved performances compared to their analogues prepared in the absence of CDB. Just like in the case of the PDVB particles, there was no evidence of the controlled/living nature of the polymerization. The formation of water-compatible402 and also thermosensitive403 MIP microspheres was then achieved via the surface-initiated RAFT polymerization of HEMA or NIPAM, respectively. The grafting onto approach was also investigated.404 The use of PNIPAM,405 PEG,405 or PHEMA406 macroRAFT agents (together with CDB) during the MIP synthesis offered an elegant alternative to introduce polymer chains on the surface of the particles. Multiresponsive particles were also produced.407 Indeed, an azobenzene-containing MIP shell (photoresponsive) was first formed on the cross-linked core, and a pH-sensitive and thermosensitive hairy layer of P(NIPAM-coDMAEMA) was then grown via surface-initiated RAFT. Again, similar particles could be obtained via a one-pot process using a PHEMA macroRAFT agent.408 Some of the MIP detailed above were intended for use in real biological samples (river water, milk, bovine serum) for specific recognition of small molecules.406,408 Following similar procedures, different kinds of MIP microspheres (with or without a polymer layer) have been developed by others for various purposes (food industry,409 environmental analy-

7.4. Other CLRP Techniques

The two-stage dispersion strategy proved to be also efficient in ITP dispersion. Song and Winnik340 successfully used C6F13I in the two-stage dispersion polymerization mentioned above using RAFT molecular agent. After optimization, narrow, micronsized particles could be obtained in ethanol/water (95/5) with a reasonable control of the polymerization up to 70% conversion.

8. MORPHOLOGICAL ASPECTS 8.1. General Considerations

One of the earliest demonstrations of the feasibility of CLRP in dispersed systems was the use of spherical polystyrene nanoparticles (prepared by conventional emulsion polymerization) as a seed for the subsequent polymerization of St mediated by a dithioester RAFT agent, which was incorporated into the particle interior by a solvent transport method.416 This initial work was soon followed by the development of what ultimately became known as the “RAFT-in-emulsion” process,128,129,181 whereby a short hydrophilic block [typically poly(acrylic acid) (PAA)] prepared by RAFT was used to control the starve-feed polymerization of a second hydrophobic monomer (e.g., St, nBA) in water, yielding spherical polymer micelles at a critical degree of polymerization of the second block via self-assembly. Further polymerization and growth ultimately resulted in spherical polymer nanoparticles of tunable size, consisting of polymer with relatively narrow MWD. The initial development of CLRP in dispersed systems quickly saw the preparation of spherical polymer nanoparticles where the MWD of the polymer is well-defined become a mature field of research.1,3,9−11,16,417−419 In order to minimize surface free energy, the generation of spheres is essentially the “default” morphology with respect to polymer nanoparticle synthesis, and initially, little attention was paid to alternative particle morphologies. There is, however, an intense interest in the preparation of nonspherical polymeric objects due to their unique properties and potential applications:420 polymeric objects with high aspect ratios (rods, fibers) have applications as unique viscosity modifiers compared to equivalent spherical objects,421 while polymer vesicles have potential applications in drug or biomolecule encapsulation and delivery,422,423 in addition to numerous other applications of these materials in the solid state, such as in coatings,424,425 membranes,426 and lithography.427 The focus of this section is to highlight the use T


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Table 2. Composition of the Solvophilic Block, Solvophobic Block, Solvent and Observed Morphologies for CLRP Dispersion Polymerization Systems


solvophilic block

solvophobic block

St methacrylic POSS mPEGV-St DMAEMA 4VP

4VP-co-DVB St

OEOMA MAA MPC KSPMA-co-HEMA KSPMA-mix-HEMA KSPMA-co-GMA KSPMA-mix-GMA GMA QDMAEMA-co-GMA QDMAEMA-mix-GMA PEG GMA DMAEMA MPC DMAEMA HPMA LMA

St-co-VBA St-alt-NMI HPMA (co-EDGMA) HPMA

cyclohexane octane ethanol/water, 85/15 methanol methanol toluene methanol ethanol/dioxane, 50/50 water water

observed morphologiesa 364

S S/W/V/PP450 S/W/V451 S/W/V/LCV433 S/W/V/D/L,183 S/W/V448 S/V/LCV452 S/W/V423 S/W/L453 S/W/V,435 S/LR454 S/V371

S/V,455 S/W/J/V,434 W456 S/W/V457 S/W/V/OLV458 S/W/V459

BzMA

ethanol, methanol

S/W/V460 S/W/J/V461 S/W/V462 S/W463 S/W464

BzMA-b-TFEMA Chol-TEGMA

ethanol ethanol, isopropanol heptane dodecane ethanol/water (varying composition) dioxane/water (varying composition) ethanol ethanol/water, 95/5

PEMA

ethanol

S/W/V466

MAA-co-OEOMA MAA AA-co-OEOA MAA-co-OEOMA DMAEMA

solvent

S/W/V465 F-LC437

a

Morphological abbreviations: S = spheres, W = worms/rods, V = vesicles, L = lamellae, LR = lumpy rods, LCV = large compound vesicles, F-LC = liquid crystalline fibers, J = jellyfish, OV = oligolamellar vesicle, D = doughnuts, PP = porous particles.

the surfactant “headgroup” and the solvophobic blocks selfassemble into structures of varying morphology, which are dependent on factors such as the volume fraction of each block,433−436 monomer concentration,434,435 total molecular weight, and interactions between the two blocks and between each block and the solvent,437 in addition to pH and salt effects in aqueous systems.436,438−442 Numerous approaches exist with respect to the preparation of polymeric nano-objects via the self-assembly of A−B BCPs in solution. One of the most traditional approaches is the technique pioneered by Eisenberg and co-workers,440−444 whereby a BCP is dissolved in a good solvent for both blocks, followed by the slow addition of a block-selective solvent and subsequent dialysis against that solvent (e.g., dissolution of PStb-PAA in DMF, followed by the slow addition of water and then dialysis). Spherical, rodlike, and vesicular morphologies are attainable by this approach; however, this method is usually conducted in dilute solution (less than 1% w/v), which is undesirable from a processing perspective. This problem has been extensively addressed in the past 5−10 years through the use of CLRP in two dispersed systems, namely, dispersion and emulsion polymerization, to yield dispersions of solids (up to 25% w/v) of both controllable and predictable morphology. Termed polymerization-induced self-assembly (PISA),182−184,187 the technique utilizes the livingness of growing polymer chains in a typical CLRP system, whereby a solvophilic block is first

of CLRP techniques in dispersed systems to create such morphologies, which has become an area of recent intense research. We restrict our focus to these “external” morphologies and how they are realized; the preparation of particles via CLRP that have complex “internal” morphologies, such as hollow, core−shell, Janus, and multicompartment structures, are not discussed here. For discussion on these topics, we direct the reader to several excellent reviews.418,428−430 8.2. Morphological Control via CLRP

8.2.1. General Considerations. For the development of nonspherical “external” particle morphologies, such as rods and vesicles, we briefly consider the influence of the molecular shape of amphiphiles with respect to their self-assembly. One of the most convenient descriptions used for small molecule surfactants is the packing parameter (p),431 which is defined as v p= (2) la where a is the area of the surfactant headgroup, and v and l are the volume and length, respectively, of the surfactant “tail”. When p < 1/3, spherical objects are formed, but as p increases, objects with lower radii of curvature begin to form: cylinders (1/3 < p < 1/2), vesicles (1/2 < p < 1), and ultimately lamellae.432 The same behavior is true for A−B-type diblock copolymers (BCPs) that possess chemically distinct and immiscible blocks; in solution, the solvophilic block acts as U


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Figure 13. Drying and redispersion of PSt prepared via RAFT-mediated DP in methanol, utilizing a trithiocarbonate-capped P4VP block as the solvophilic segment. The TEM image on the right demonstrates the successful re-establishment of the original nanorod morphology after redispersion in methanol. Reproduced with permission from ref 183. Copyright 2009 Royal Society of Chemistry.

crucially in the presence of a large excess of monomer.183,433,448,449 Initially using a trithiocarbonate-terminated P4VP macroRAFT agent (Mn = 10 400 g/mol, Đ = 1.08), the polymerization of St was performed at 80 °C using a macroRAFT:St:initiator (AIBN) molar ratio of 10:50 000:1.183,448 At such a high loading of monomer, St additionally acts as a cosolvent, improving the solubility of the growing PSt block in the reaction medium. The polymerization solution quickly became translucent and ultimately opaque, indicating in situ self-assembly, which was verified by the observation of spherical micelles, short rodlike micelles, vesicles, and lamellae by TEM during the polymerization. Impressively, these morphologies were reobtained after the solvent was removed and the dried polymer redispersed in fresh solvent (Figure 13). Only spherical micelles were observed when a 10-fold reduction in monomer concentration was used, which was attributed to the self-assembled morphology being “locked” due to the solvophobic chains being below their Tg, with insufficient monomer present to plasticize the system, swell the core, and promote reorganization. Similar behavior was observed when a dithiobenzoate-terminated PDMAEMA (Mn = 10 600 g/mol, Đ = 1.12)433 and a trithiocarbonate-terminated PAA [average degree of polymerization (by 1H NMR) = 61, Đ = 1.13]449 were used to mediate the polymerization of St (in large excess) in methanol, yielding morphological transitions from spheres, polymer “strings”, and vesicles as the polymerization proceeded. The elegance of the approach adopted by Pan and coworkers suffers the drawback of the very low rate of polymerization of St to form the solvophobic block in these systems, resulting in low conversion of monomer to polymer (typically 30−70% conversion after 48 h polymerization). From an industrial perspective, the need to remove unreacted monomer at the conclusion of polymerization is highly undesirable. This problem was overcome by work from Armes’ group, who performed CLRP under DP conditions using benzyl methacrylate (BzMA) as the second monomer,459−461,465 which possesses similar solubility characteristics to styrene (including an aromatic group) but has a much higher propagation rate coefficient (approximately 5 times greater than St at 70 °C).467−469 In alcoholic solvents, the RAFT DP of BzMA routinely reaches greater than 95% conversion after 24 h at 70 °C, resulting in minimal residual monomer while enabling access to numerous higher-order morphologies. Polymerization of BzMA as the solvophobic block has been demonstrated using macroRAFT agents such as PDMAEMA (Mn = 6000 g/ mol, Đ = 1.16;459 Mn = 5500 g/mol, Đ = 1.22; and Mn = 11 300 g/mol, Đ = 1.19460) in ethanol, poly(methacrylic acid) (PMAA, Mn = 9000 g/mol, Đ = 1.19)459,465 and poly(glycerol methacrylate) (PGMA, Mn = 17 000 g/mol, Đ = 1.16)459 in

polymerized followed by the growth of a solvophobic block. The system starts in a fully soluble state, and self-assembly occurs at a critical point during the growth of the solvophobic block. Most importantly, as the length of the solvophobic block increases during the polymerization, the composition of the BCP is continually altered: the length and volume of the macromolecular “tail” both increase, which leads to morphological changes in the self-assembled state. We consider both dispersion and emulsion approaches in detail below. 8.2.2. Morphological Control via Dispersion Polymerization. A dispersion polymerization (DP) is a polymerization system where the monomer is soluble in the continuous phase but the polymer is insoluble.445,446 DP is traditionally used in radical polymerization to yield large (often >1 μm diameter), spherical polymer particles, e.g., the dispersion polymerization of St in low molecular weight alcohols such as methanol and ethanol. Typically, a polymeric stabilizer [e.g., poly(N-vinylpyrrolidone), PVP] is used to both facilitate particle nucleation and provide colloidal stability.447 For the implementation of CLRP in DP systems, colloidal stability is provided via a solvophilic block with an active chain end; the second monomer is soluble in the reaction medium, but the growing second block is insoluble, resulting in in situ self-assembly. Examples of morphological control via CLRP in DP systems are summarized in Table 2 and are discussed in detail below. The first examples of self-assembly and morphology control in a DP system were reported by Pan and co-workers.183,364,433,448,449 Their first report was the demonstration of the influence of solvent on the RAFT polymerization of 4vinylpyridine (4VP) using a macroRAFT agent consisting of differing-length PSt blocks (Mn varying between 2460 and 11 200 g/mol, all Đ < 1.11) possessing a dithiobenzoate end group.364 The polymerization rate and molecular weight evolution in THF (a good solvent for P4VP) were approximately linear over time, yet in cyclohexane (a poor solvent for P4VP) the polymerization proceeded in two intervals: a fast initial polymerization rate followed by a rapid decrease after a few hours of polymerization. Analysis by MALLS indicated that there was a significant change in Mw of the system, indicating aggregation of growing chains and the formation of polymer micelles; the onset of aggregation occurred at the same time as the decrease in the polymerization rate. The copolymerization of 4VP with DVB enabled the formation of micelles with a loosely cross-linked core, as determined by the large Rg/Rh values (1.2−1.3) and the presence of signals from the P4VP core polymer in 1H NMR spectra of the micellar solution. Pan’s group developed the concept of morphological control in DP systems further via the RAFT polymerization of St in methanol, using various types of macroRAFT agents but V



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Figure 14. Representative phase diagram demonstrating the evolution of particle morphologies during the polymerization process for a DP system under RAFT control. Shown is the change in morphology from spheres to worms to vesicles, via intermediate mixed phases, for the DP of BzMA in ethanol at 65 °C, utilizing a trithiocarbonate-capped PHPMA solvophilic block. Reprinted with permission from ref 461. Copyright 2013 American Chemical Society.

the total solids concentration, with distinct regions of “pure” phases (e.g., spheres, worms, vesicles) separated by regions of mixed phases (e.g., spheres and worms, worms and vesicles; see Figure 14). The degree of polymerization of the stabilizing block (Xstab) is of pronounced importance to the final particle morphology; in the PHPMA-stabilized RAFT DP of BzMA reported by Zehm et al.,461 increasing Xstab from 48 to 63 dramatically alters the nature of the phase diagram, yielding only spherical particles or a combined mixed phase. The longer stabilizing block, which is the equivalent of a small-molecule surfactant with a larger headgroup, prevents efficient fusion of spheres to form worms. The highly influential nature of the volume fraction of the stabilizing block was also demonstrated when poly(lauryl methacrylate) (PLMA) macroRAFT agents were used to mediate the polymerization of BzMA in heptane;462 spheres, worms, and vesicles were formed when Xstab = 17, yet only spheres were observed when Xstab = 37. Due to the long alkyl side group of LMA, the volume fraction of the stabilizing block was greater than other polymeric stabilizers with an equivalent degree of polymerization, ensuring that efficiently stabilized spheres was the only possible morphology. The thermally reversible phase transition between worms and spheres at high weight fraction (20% w/w solids) was also recently demonstrated using PLMA-stabilized nano-objects in dodecane;463 an initially soft free-standing “worm gel” at 20 °C was able to degelate upon heating, forming isotropic spherical nanoparticles.

ethanol and methanol, and poly(2-hydroxypropyl methacrylate)461 (PHPMA, Mn = 10 400 g/mol, Đ = 1.25 and Mn = 13 000 g/mol, Đ = 1.22) and poly(2-hydroxyethyl methacrylate)461 (PHEMA, Mn = 14 400 g/mol, Đ = 1.17) in ethanol and 2-propanol. PHPMA proved to be one of the most effective macroRAFT agents due to the greater colloidal stability in alcohols provided by the solvophilic block;461 in mixed solvents (ethanol/water and dioxane/water of varying composition) BzMA has also been polymerized under DP conditions using trithiocarbonate-based macroRAFT agents consisting of 50 mol % MAA and 50 mol % poly(ethylene oxide) monomethyl ether methacrylate (PEOMA) (Mn = 16 900 g/mol, Đ = 1.14).464 Recently, Pei and Lowe demonstrated similar morphological control with a structurally similar monomer, 2-phenylethyl methacrylate, in RAFT-mediated DP in ethanol using PDMAEMA macroRAFT agents of varying composition.466 The development of CLRP in DP systems has enabled the creation of detailed morphological phase diagrams based on the effect of BCP composition, polymer molecular weight, total solids content, and solvent type.434,435,453,459−462,470 In general, the degree of polymerization (Xn) of the solvophobic block is the most influential factor in governing nanoparticle morphology; at a given total solids concentration, increasing the Xn of the solvophobic block reduces the curvature of the interface between the solvophilic and solvophobic blocks, which favors the formation of higher-order morphologies, such as rods/ worms and vesicles,471 as discussed above. In most reported phase diagrams, phase transitions are relatively insensitive to W



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kinetically trapped lamellae were formed; the higher-curvature vesicle phase was not observed in this system. In a similar vein, Zhang et al.437 demonstrated lamellae-like behavior via the polymerization of a monomer that forms a liquid crystalline (LC) core block via RAFT DP in a 95/5 ethanol/water mixture. The solvophobic polymer in the reported system was a cholesteryl-based (meth)acrylate with a tetra(ethylene glycol) spacer between the (meth)acrylate and the cholesteryl moiety; upon polymerization and self-assembly, long fibers with flattened cross sections were formed, which possessed lamellar order as determined by X-ray scattering and SANS. Finally, Warren et al. demonstrated the preparation of an oligolamellar vesicular (OLV) phase via the RAFT DP of HPMA in aqueous media using a poly(ethylene-glycol) (PEG)-based dithiobenzoate,458 prepared via the reaction of an amine-functional PEG (Xn = 113) with a dithiobenzoate containing a succinimide group. The OLV phase was only achievable at high solids content (20% w/w) and was attributed to the stacking of lamellae in solution. 8.2.3. Morphological Control via Emulsion Polymerization. Emulsion polymerization (EP) fundamentally differs from DP systems due to the fact that both the monomer and polymer are insoluble in the continuous phase, which is typically water. The absence or minimization of organic solvents is highly desirable from an industrial perspective; however, the mechanisms that govern EP systems are complicated by interfacial processes, including the presence of monomer droplets.26 With respect to CLRP in EP systems, the first reported particle morphologies were always spherical,128,129 which can be rationalized by examining the experimental conditions: the solvophilic blocks (macroRAFT agents) used were typically short PAA chains with 5 < Xstab < 20, fully deprotonated via the addition of base; in addition, the solvophobic monomer was typically introduced under starvefeed conditions to circumvent the formation of monomer droplets. Using the same geometric considerations of BCPs discussed in section 8.2.1, the strong electrostatic repulsion between solvophilic blocks and the lack of excess monomer to promote exchange and mobility of self-assembled BCPs prevented the formation of low-curvature morphologies. The majority of reported EP systems using CLRP employ either RAFT or NMP to control the resultant polymer architecture (refs 50, 128, 129, 191, 216, 218, 228, 230, 337, 421, 436, 438, 439, 464, and 474−479). The first implementations of NMP in EP used a water-soluble PAA macroalkoxyamine (utilizing SG1 nitroxide or MONAMS alkoxyamine) to polymerize St,50 n-BA,50,475 and diethyl acrylamide (DEAAm)/N,N′-methylenebis(acrylamide) 337 (technically a dispersion polymerization as the monomers are soluble in water) to produce stable latexes (spherical nanoparticles) up to 20% w/w solids content. The initiating efficiency of the macroalkoxyamine in these systems was, however, low, requiring very high reaction temperatures for the polymerization of the solvophobic monomer. The use of P(MAA-co-St)191 or P(MAA-co-4SS)476,479 (4SS = 4-styrenesulfonate) macroalkoxyamines with small amounts (1 μm) vesicles. This was due to the higher ionic strength of divalent salts, in addition to the ability for Ca2+ ions to chelate two carboxylic acid groups, which reduced the volume of the hydrophilic block. At very high divalent salt concentrations, control over molecular weight was lost (Mn > Mn,th and Đ values >2.3). This phenomenon was attributed to particle nucleation via the “conventional” radical EP mechanism (control via aqueous phase growth 26), which dominates at high electrolyte concentration. The influence of the nature of the leaving group on the RAFT EP of St was studied by Zhang et al.436,478 by preparing all-methacrylic versions of the macroRAFT agents described above, i.e., trithiocarbonate-capped P(MAA-co-POEOMA) [OEOMA = oligo(ethylene oxide) methyl ether methacrylate] of varying molecular weight and composition. The presence of a tertiary radical leaving group, when compared to the secondary radical of the all-acrylic equivalent, afforded enhanced molecular weight control with dispersities 50) and to determine their viscoelastic properties;421 at high concentrations, the motion of the nanofibers was no longer Brownian in nature, with interactions between neighboring fibers resulting in temporary elasticity, such as in entangled polymers. The viscoelastic properties of the material were shown to be independent of their chemical composition. Two final examples of morphology control and morphology transformation in EP systems involve the polymerization of styrene utilizing thermoresponsive poly(N-isopropylacrylamide) (PNIPAM) “seeds” of differing composition.482,483 Zhou et al.482 first prepared poly(N,N′-dimethylacrylamide) via trithiocarbonate-mediated RAFT polymerization (Mn = 8200 g/mol, Đ = 1.12), which were used as the “arms” of CCS polymers prepared by the further polymerization of NIPAM and N,N′-methylenebis(acrylamide) (BIS) in a 2:1 mol ratio in water at 70 °C. These CCS systems were then used as a “seed” (hydrodynamic diameter =12 nm) for the EP of styrene at 80 °C. Due to the highly cross-linked nature of the seed, asymmetric growth of the initially spherical particles is observed, resulting in elongated spheres that fuse together, forming long polymeric clusters and fibers. Another elegant example of morphology control using NIPAM/St systems is demonstrated by Jia et al.,483 whereby a PNIPAM trithocarbonate macroRAFT agent (Mn typically ∼4000 g/mol, Đ ∼ 1.1 in all cases) was prepared and added to the EP of styrene in the presence of a traditional ionic surfactant (SDS) at 70 °C. At the reaction temperature, the PNIPAM chains are hydrophobic and chain extension occurs within spherical hydrophobic particles of diameter 210 nm. However, upon cooling to 15 °C and the addition of a small molecule plasticizer (toluene), a temperature-directed morphology transition (TDMT) takes place, yielding polymeric “worms” with high aspect ratio. These worms were also able to be cut into “nanorods” via ultrasonication to a length of approximately 100−150 nm.

9.2. Miniemulsion Polymerization Approaches

The general features of miniemulsion polymerization make it particularly well adapted to the synthesis of polymer/inorganic hybrid particles, as previously reviewed by Landfester,97,492,493 and more recently by Qi et al.494 and Asua.495 Indeed, unlike in conventional emulsion polymerization, miniemulsion droplets can be regarded as independent nanoreactors that can be converted into particles of similar size and composition after polymerization. Hence, if inorganic particles can be suspended in the monomer droplet phase prior to polymerization, it is possible to physically entrap them in the resulting polymer particles. A large variety of inorganic compounds have been successfully encapsulated using this technique, but only a few reports have combined CLRP and miniemulsion polymerization for the synthesis of hybrid particles. As inorganic particles are usually not compatible with nonpolar organic liquids like hydrophobic monomers, their surface needs to be pretreated with compatibilizers to improve their dispersibility. Various CLRP techniques have been used for this purpose. The first report along these lines was published by Bailly et al.,496 who prepared PS-tethered silica particles by surface-initiated NMP (SI-NMP), which could then be dispersed in styrene nanodroplets to generate silica/PS core−shell particles after miniemulsion polymerization. A few years later, Mičušik et al.497 used a similar strategy to encapsulate montmorillonite (MMT) clay platelets into poly(n-butyl methacrylate-co-methyl methacrylate) latexes. The MMT sheets were rendered hydrophobic by grafting of poly(BA-co-MMA) copolymer chains from the clay layers in bulk using a previously anchored SG1-based macroalkoxyamine initiator carrying quaternary ammonium side groups (Scheme 5).

9. ORGANIC/INORGANIC HYBRID PARTICLES 9.1. General Considerations

Organic/inorganic hybrids have attracted considerable interest in the last 2 decades owing to their improved or unusual features arising from the combination of the properties of their organic and inorganic constituents.484,485 The properties of hybrid materials are not simply a sum of the individual contributions of both phases but are also strongly influenced by their nanostructure and the interfacial area. Thus, controlling the morphology of hybrid particles is key in mastering their final properties. With the advent of CLRP, it has become possible to directly synthesize well-defined functional polymers in a variety of media. These functional polymers can be further introduced on the surface of preformed inorganic particles after synthesis or via in situ polymerization.486−490 The resulting polymer-grafted composite particles are playing a major role in the development of advanced functional nanomaterials, often Z


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(higher reaction rates and better colloidal stability).498 An increase of the clay loading led, as expected, to a decrease of the molecular weights and dispersities of the tethered chains, due to the higher RAFT agent concentration, in agreement with a controlled process. This resulted in a change of the composite morphology from semiexfoliated for low clay contents (i.e., for high molecular weights) to intercalated for high clay contents (i.e., for low molecular weights), as further confirmed by SAXS and thermo-mechanical analyses.499 Unfortunately, however, the morphology of the final particles could not be firmly assessed, as the clay platelets were not visible in the TEM images. Only when the dried latex was embedded in an epoxy resin could it be visualized within ultramicrotomed cross sections. Using a similar strategy, Esteves et al.500 reported the successful synthesis of quantum dots (QDs)/polymer nanocomposites by RAFT polymerization in miniemulsion. The RAFT agent was incorporated on the QD surface via ligand exchange using a trialkylphosphine-derivatized chain transfer agent obtained through esterification of tris(3-hydroxypropyl)phosphine with 4-cyano-4-(thiobenzoyl sulfanyl)pentanoic acid (CPDB). The RAFT-functionalized QD nanocrystals were trapped within the polystyrene particles in the form of small clusters and retained their structural integrity and luminescent properties. Although graphite oxide (GO) is not inorganic, it is worth mentioning that the RAFT process was also used to encapsulate GO sheets into polystyrene latexes.501 GO modification was carried out via esterification of the surface hydroxyl groups with dodecyl isobutyric acid trithiocarbonate (DIBTC). The RAFT-grafted GO was dispersed in water; mixed with the oil phase composed of the monomer (styrene), the initiator (AIBN), and the hydrophobe (HD); and sonicated to allow effective swelling of the GO platelets with styrene. The oily phase was then diluted with an aqueous solution of SDBS and sonicated further to form a miniemulsion before polymerizing at 75 °C. TEM showed the formation of stable monodisperse PS/GO composite latexes with encapsulated GO sheets. SEC analysis of the PS chains after cleavage from the GO surface showed a good control of the polymerization (Đ ranging from 1.6 to 1.2) with better control attained at the highest GO (and therefore RAFT) content. The resulting polymer/GO nanocomposites presented enhanced mechanical and thermal properties compared to the neat polymer. Similar GO/polymer nanocomposites have also been prepared in (mini)emulsion by exploiting the amphiphilic properties of GO

Scheme 5. Chemical Structure of the SG1-Based Macro Alkoxyamine Initiator with Quaternary Ammonium Side Chains Used To Modify MMT Plateletsa


a

Reprinted with permission from ref 497. Copyright 2012 Elsevier Ltd.

Although the polymerization was poorly controlled, wideangle X-ray diffraction (WAXD), TEM, and elemental analyses (EA) showed that the polymer chains effectively grew from the clay surface, resulting in clay exfoliation. The organoclays were then suspended in a mixture of MMA and BA, miniemulsified, and polymerized using Dowfax 2A1 as anionic surfactant, stearyl acrylate as hydrophobe, and KPS as radical initiator. A stable latex was obtained only when the highly miscible chainextended MMT platelets were used, whereas the less compatible macroinitiator-modified MMT led to latex destabilization. This highlights the importance of surface compatibilization to ensure not only successful encapsulation but also good colloidal stability of the resulting composite latex particles. Figure 16 illustrates the overall process. Following a related approach, Samakande et al.498,499 reported the RAFT miniemulsion copolymerization of styrene and n-BA using two CTA-modified clays (a trithiocarbonate and a dithiobenzoate), both of which contained a quaternary ammonium group for anchoring to the clay surface through cation exchange. The surface-tethered RAFT agents led to an increase of the hydrophobic nature of the clay sheets, allowing their successful dispersion in the monomer phase. Contrary to the findings of Mičušik et al., the authors did not encounter any colloidal stability problems, which can likely be attributed to the different nature of the RAFT molecules and also possibly to the RAFT mechanism. The presence of the RAFT agent on the clay surface strongly affected the polymerization process

Figure 16. General procedure for preparation of poly(BA-co-MMA)/MMT nanocomposites through miniemulsion polymerization according to Mičušik et al. Reprinted with permission from ref 497. Copyright 2012 Elsevier Ltd. AA



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Figure 17. General procedure for preparation of poly(n-butyl acrylate)/silica nanocomposites reported by Bombalski et al. The inset shows an AFM image of the resulting silica/PnBA hybrid particles. Reprinted with permission from ref 508. Copyright 2007 American Chemical Society. Note that a very similar process was used the same year by Esteves et al.509 for the encapsulation of CdS nanocrytals (see the text).

nanosheets.502−506 As a final example, Ma et al.507 performed RAFT miniemulsion polymerization of MMA in the presence of [3-(methacryloxy)propyl]trimethoxysilane-grafted silica particles. The growth of the polymer chains was well-controlled, as indicated by the good agreement between theoretical and experimental molecular weights and the narrow molecular weight distributions (Đ < 1.4). However, the poor quality of the TEM micrographs did not facilitate a precise idea of the final particles’ morphology. AGET ATRP has also proven to be a very efficient tool for the preparation of polymer brushes on surfaces and was successfully implemented for the elaboration of hybrid colloids through miniemulsion polymerization. In a typical AGET ATRP system, a transition-metal complex in its higher oxidation state, such as the Cu(II) complex, is used as a catalyst instead of the Cu(I) complex used in normal ATRP systems. A small amount of the Cu catalyst is used together with an appropriate reducing agent. This agent reduces Cu(II) to Cu(I) but is also responsible for scavenging oxygen and radical inhibitors, imparting a degree of oxygen tolerance to the reaction. These advantages potentially make it a more robust and industrially attractive technique due to its compatibility with aqueous-phase polymerizations, notably miniemulsion. Bombalski et al.508 performed AGET ATRP to encapsulate silica nanoparticles through miniemulsion polymerization (Figure 17). The ATRP-anchored initiator molecules were obtained by reacting the silanol groups of silica with (chlorodimethylsilyl)propyl 2-bromoisobutyrate. The resulting silica particles were dispersed in n-butyl acrylate (BA) in the presence of Cu(II), ascorbic acid as reducing agent, bis(2pyridylmethyl)octadecylamine (BPMODA) as ligand, Brij98 as surfactant, and HD as hydrophobe. Under these conditions, the miniemulsion remained stable throughout the course of the polymerization, and the final particle sizes were very close to the starting droplet size (220 nm), indicating the absence of Ostwald ripening or secondary nucleation. In addition, the evolution of molecular weight with conversions showed good agreement between the experimental and theoretical values, indicating a high initiation efficiency, and polymers with low dispersities were obtained (Đ < 1.3). AFM analysis performed after dispersion of the dried particles in tetrahydrofuran showed individualized core−shell silica particles, indicating successful encapsulation. Confinement of the polymerization reaction within the miniemulsion droplets avoided the problem of

macroscopic gelation commonly observed in bulk polymerization due to bimolecular terminations and also resulted in a higher reaction rate. Esteves and co-workers509 described the synthesis of core− shell cadmium sulfide (CdS)/poly(n-butyl acrylate) composite latexes in miniemulsion through AGET ATRP using a previously anchored chlorine-based ATRP initiator. QDs nanocrystals are known to oxidize in the presence of free radicals, leading to deterioration of their optical properties. AGET ATRP prevented the CdS QDs from extensive degradation during polymerization, as attested by absorption spectroscopy, which is an obvious advantage of this process. Following a related strategy, Khezri et al.510 reported the synthesis of poly(styrene-co-methyl methacrylate)/MMT nanocomposites. By appropriately choosing a hydrophobic ligand soluble in the monomer phase and a cationic surfactant less sensitive to temperature, uniform clay-loaded miniemulsion droplets with a diameter of about 200 nm were successfully obtained and polymerized via AGET ATRP to form polymer/ clay composite latexes. Increasing the clay content resulted in a decrease in both molecular weights and conversion and a broader molecular weight distribution. The resulting composite materials showed enhanced thermal properties and an exfoliated morphology. A similar study511 was conducted using a reverse ATRP approach, which was subsequently extended to styrene,512 MMA,513 and a mixture of styrene and BA,514 giving very similar results. Finally, it is worth mentioning the work of Hatami and co-workers515,516 on the synthesis of poly(styrene-co-butyl acrylate)/clay nanocomposites by miniemulsion AGET ATRP. The presence of nanoclay again strongly affected the polymerization process by decreasing the reaction rate and the polymer chain length. It was hypothesized that the clay sheets limited the rate of diffusion of the growing macroradicals through steric hindrance and also likely promoted polymer chain termination via transfer reactions. 9.3. Emulsion Polymerization Approaches

During the last 10 years, significant progress has been made in adapting CLRP techniques to emulsion polymerization systems. Among the recent advances, the PISA process has proved to be a very effective method for the elaboration of polymer latex particles through ab initio emulsion polymerization.182 As described earlier, the PISA process involves chainextending a hydrophilic polymer precursor prepared via CLRP AB


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Figure 18. (a) Scheme illustrating the overall process used to encapsulate pigment particles via macroRAFT-mediated emulsion polymerization and (b) TEM image of encapsulated TiO2 pigments. Reprinted with permission from ref 517. Copyright 2008 American Chemical Society.


Table 3. Chemical Structures of the MacroRAFT Agents Employed in the Literature for the Polymer Encapsulation of TiO2 Pigments, Quantum Dots, Metal Oxides, Metals, Clays, and Carbon Nanotubes

AC


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Table 4. Chemical Structures of the MacroRAFT Agents Used in the Literature for the Synthesis of Organic/Inorganic Hybrid Particles through Emulsion Polymerizationa

a

These macroRAFT copolymers either failed to encapsulate the inorganic particles and/or were used for some other purposes than to encapsulate the inorganic particles.

Claverie,518 utilizes living (co)polymers adsorbed on the inorganic particles to encourage the emulsion polymerization to occur at the particle surface, thereby encapsulating the inorganic particles. These (co)polymers (macroRAFT agents) possess a RAFT functionality that can facilitate rapid transfer of hydrophobic polymer growth between the chains, allowing the formation of a homogeneous polymer shell around the entire particle surface. In addition, their relative hydrophilicity provides stability to the formed objects in water dispersion. The overall process involves two steps, as schematically illustrated in Figure 18 for the case of titanium dioxide encapsulation: (i) macroRAFT agent adsorption on the inorganic particles in aqueous suspension and (ii) emulsion polymerization of hydrophobic monomers under batch or

with hydrophobic monomer(s) to form amphiphilic chains that self-assemble into spherical nano-objects or more complex morphologies, depending on reaction conditions. The notable advantages of this process are the absence of low molecular weight surfactant in the suspension, the simplicity of a one-pot aqueous process applicable to a wide range of monomers, and the ability to achieve a variety of morphologies at high solids content without the aid of an organic cosolvent. Most of the hydrophilic polymer precursors used in the PISA process are also capable of interacting with inorganic compounds. They have therefore been used as both coupling agents and stabilizers to encapsulate a variety of inorganic particles and/or organic pigments. This method, pioneered almost simultaneously by Nguyen et al.517 and Daigle and AD


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Figure 19. Cryo-TEM images of (a) CeO2/poly(St-co-MA) and (b) CeO2/P(MMA-co-nBA) hybrid latexes obtained using (a) P(nBA7.5-co-AA10)DBTTC and (b) P(BA11-co-AA11)-CTTPA macroRAFT copolymers (see Table 4). Although both macroRAFTs have similar molecular weights and compositions, they resulted in significantly different particle morphologies, which can be attributed to the nature of the particles surface leading to different adsorption mechanisms. Reprinted with permission from ref 528. Copyright 2013 Wiley-VCH Verlag GmbH & Co.

particles deficient in macroRAFT agent stabilizers, hence resulting in their aggregation. There have been however two exceptions. Both Daigle and Claverie518 and Zhong et al.523 reported successful encapsulation of various types of inorganic particles and CNTs, respectively, using a PAA macroRAFT agent (Table 3). Although this would warrant further investigations, successful encapsulation can likely be attributed in these cases to a different adsorption mechanism. Indeed, the nature of the particles’ surface is known to greatly affect adsorption. This is also evident from the works of Garnier et al.526,527 and Warnant el al.,528 who attempted the encapsulation of citrate-coated CeO2 particles using various types of amphiphilic macroRAFT agents (Table 4). Although these macroRAFT agents contained hydrophobic BA units, which are beneficial for adsorption, electrostatic repulsion between the negative citrate layer and the anionic monomer units limited interaction with the particles and prevented effective encapsulation. Attempts to increase macroRAFT agent adsorption by replacing the AA units by sulfonic527 or phosphonic528 acid groups, known to display stronger interaction with CeO2, did not improve the situation, as the nanoceria was either not incorporated at all into the latex particles or was located at the polymer/water interface, as observed for the poly(BA-co-AA) macroRAFT agent. In contrast, Zgheib et al.525 reported successful CeO2 encapsulation using similar poly(BA-co-AA) macroRAFT copolymers and bare (i.e., noncoated) positively charged nanoceria (Figure 19). In addition to demonstrating successful encapsulation and stable latexes, the examples in Table 3 also highlight some conditions for avoiding secondary nucleation, which is responsible for producing inorganic-free polymer particles. First, a random distribution of the hydrophilic and hydrophobic units along the chain is required to prevent the macroRAFT (co)polymers from self-assembling into micelles, which inevitably leads to the formation of new particles via micellar nucleation. Second, the random copolymers should display strong interactions with the inorganic surface to encourage polymerization to be localized at this interface. If the total amount of macroRAFT agent exceeds the amount required to cover the inorganic surface, the excess will exist in solution. It appears, however, that a certain quantity of this free macroRAFT agent is necessary to adsorb on the growing surface during encapsulation and to maintain colloidal stability of the formed objects. In contrast, an excessive free macroRAFT concentration encourages free particle formation. The molecular weight is also of paramount importance. For efficient

starve-feed conditions, where the macroRAFT-functionalized particles act as seeds for the nucleation process. The method is extremely versatile and allows the preparation of a large variety of colloidal nanocomposites directly in water with almost no restriction on the type of inorganic particles or organic pigments that can be potentially encapsulated. Furthermore, it does not require any sophisticated chemical surface treatment of the inorganic materials and is easily scalable to high solids contents. Finally, the technique offers the obvious advantage of not requiring a conventional surfactant to stabilize the final latex particles (similar to the PISA process) and is therefore well-aligned with the growing impetus to remove conventional surfactants from latex formulations for environmental and quality-related reasons. Until now, RAFTmediated processes have been exclusively reported, but any CLRP technique could potentially be applied. Given these attractive features, and inspired by the seminal work of Nguyen and co-workers, researchers applied the approach to the encapsulation of gibbsite519 sheets used as models for plateletlike colloidal substrates, cadmium sulfide (CdS)520 and lead sulfide (PbS)521 quantum dots, MMT522 platelets, carbon nanotubes (CNTs),523,524 and cerium dioxide (CeO2)525 nanoparticles. With the exception of the work of Daigle and Claverie,518 and to a lesser extent of that of Zhong et al.,523 all the aforementioned articles share some common features, which can be used to extract important prerequisites for successful encapsulation, and are therefore described here in more detail. Table 3 contains a complete list of the macroRAFT (co)polymers that have been successfully used to form organic/inorganic hybrid particles in this manner, and Table 4 contains those that were unsuccessful. From Table 3, it is evident that amphiphilic living polymers are required in most cases to ensure effective encapsulation. The random incorporation of hydrophobic (i.e., BA or styrene) units in the polymer chains increases the affinity of the hydrophobic monomers for the particle’s environment and promotes encapsulation. In contrast, hydrophilic macroRAFT homopolymers (i.e., PAARAFT)520,525 (Table 4) or macroRAFT copolymers containing too few hydrophobic units519 failed to encapsulate inorganic particles and/or led to latex destabilization. Rather, their high hydrophilicity and preferential localization in the aqueous phase promote secondary nucleation and shift the polymerization locus from the inorganic surface to the aqueous phase. Formation of new particles can additionally favor macroRAFT migration to the newly created interface, leaving the inorganic AE



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Figure 20. (a) TEM image of an ultrathin cross-section of epoxy-embedded laponite/PSt composite latex particles synthesized by macroRAFTmediated ab initio emulsion polymerization of styrene, and (b) evolution of the size exclusion chromatograms with monomer conversion (SEC THF, PS calibration) showing the good livingness of the polymerization. Reprinted with permission from ref 530. Copyright 2014 The Royal Society of Chemistry.

Figure 21. (a) Schematic and (b) graphical representation of the relationship between graft chain length and shell thickness in the swollen state in comparison to the collapsed conformation. The expansion shows how the effective shell size varies with grafting density, modeled for a PSt shell (bulk density 1.05 × 10−21 g nm−3) surrounding a spherical core (diameter 130 nm). The grafting density varies from 0.0625 (light teal curve), 0.125 (blue curve), 0.25 (green curve), and 0.5 (red curve) to 1.0 chains nm−2 (black curve).

encapsulation, the RAFT copolymer should be small enough to give a high number of RAFT end groups per particle. However, the chains must not be too short to provide sufficient colloidal stability of the encapsulated particles. The overall process (i.e., either batch or starve feed) and the hydrophobic monomer feed

composition have also been shown to strongly influence the overall mechanism of encapsulation and the final particles’ morphology. Starve feed is usually preferred to prevent macroRAFT agent partitioning between the monomer and aqueous phases and to promote kinetically trapped morpholAF



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ogies.517 It also enables the formation of an even polymer coating, while batch conditions may result in uneven growth of polymer chains into localized phase-separated domains.523 The hydrophobicity and the glass transition temperature (Tg) of the copolymer shell are also key parameters. High hydrophobicity results in a high interfacial tension, minimizing the surface area and driving the inorganic particles to the polymer/water interface, which may also be facilitated by a low Tg, as shown by Ali et al.519 and Zgheib et al.,525 for gibbsite and CeO2 encapsulation, respectively. Finally, the influence of the controlled character of the polymerization (i.e., the in situ formation of well-defined diblock copolymers with controlled molecular weights and low molecular weight dispersities) on the success of the encapsulation and on the control of particles morphology is not yet completely understood. Both controlled517,519 and uncontrolled (or poorly controlled)518,521,523,528 polymerizations have been reported to generate polymer-encapsulated inorganic particles. It thus appears that the key role of the RAFT agent is its provision of many active sites for chain growth, with its ability to control the polymerization perhaps assuming less importance. The above-depicted macroRAFT-mediated encapsulation strategy has recently been extended to more elaborate systems, such as the synthesis of TiO2/polymer hybrid “nanorattles”.529 The TiO2 pigment was encapsulated in a polymer shell composed of MMA, BA, and MAA, and the hybrid nanorattles were subsequently produced by swelling the polymer coating in a basic solution. Noteworthy also is the very recent work of Rodrigues Guimaraes et al.530 on the elaboration of multihollow laponite-armored latexes by macroRAFT-mediated emulsion polymerization using a PEO macroRAFT agent previously anchored on the clay surface (Table 4). MacroRAFT agent immobilization on the clay surface decreased RAFT partitioning to the monomer phase, which enabled the significant improvement of the controlled/living character of the polymerization. Clay-armored particles with embedded PEO domains were obtained by this process (Figure 20).

coating thickness can be effected easily by adjusting the polymer chain length when grafted at sufficiently high density from planar substrates, the effective graft density decreases dramatically as you move away from a spherical surface, as shown schematically in Figure 21a. Consequently, the grafted polymer chains adopt a collapsed conformation. Even a dramatic increase in molecular weight does not significantly alter the shell thickness, as exemplified in Figure 21b. Since the polymer chains adopt a collapsed state, it becomes more challenging to tune the properties of the core−shell structures. The impact of grafting density on the shell thickness is demonstrated in the expansion in Figure 21b. Controlling the molecular weight, dispersity, functionality, topology, architecture, and grafting density of polymer grafts is essential to the properties and performance of core−shell structures, as these parameters dictate the nature and uniformity of the polymer shell. It has been well-documented, for instance, that the polymer graft length and grafting density impacts the circulation lifetime534 and cytotoxicity532 of administered nanomaterials, as well as the mechanical properties in polymer composites.535 As such, significant research efforts have focused on the synthesis of polymer grafts in a controlled fashion to facilitate precise control over the core− shell structures and, hence, their properties. There are several approaches commonly used to prepare polymer coatings. They can be broadly defined as grafting-to and grafting-from and are depicted in Figure 22. The former approach involves coupling a

10. SURFACE-INITIATED POLYMERIZATION 10.1. General Considerations

A complementary approach to that described in section 9 for the formation of inorganic−organic core−shell nanostructures is the formation of polymer brushes from the surface of inorganic particles. Indeed, the properties of a hybrid material are not only dependent upon the nature of the polymer (i.e., molecular weight, dispersity, functionality, topology, and architecture), the effective coverage, or the ability of the polymer coating to shield the core material from the surrounding environment but also the conformation the polymer adopts on the surface.490 The term polymer brush was first coined by de Gennes531 to denote the extended conformation adopted by polymers end-grafted to a solid support when grafted at a sufficiently high density. Steric repulsion forces the polymers to stretch away from the surface to avoid mutual interference.532 Under this so-called concentrated brush regime, it is possible to precisely tailor the height of the polymer coating by increasing the polymer chain length, achieving a higher degree of control over the hybrid materials properties.533 Below this critical grafting density, the polymer grafts adopt a collapsed state referred to as a pancake or mushroom conformation. While precise control over the

Figure 22. Synthetic approaches to prepare polymer coatings can be broadly defined as grafting-to and grafting-from. The former approach can vary from physical adsorption of polymers or chemically grafting end-functional polymers to complementary groups on the substrate surface (a). The latter approach involves growing the polymer directly from a surface prefunctionalized with initiating sites (b).

reactive site on the surface with a complementary group on a preformed polymer through physical or chemical interactions (Figure 22a). Although it is considered more straightforward synthetically to graft well-defined polymer chains to a surface, there are several notable limitations. For instance, as a consequence of steric crowding caused by previously attached polymers, high grafting densities are difficult to achieve.536,537 Nevertheless, due to the relative simplicity of this approach, several groups have reported the functionalization of nanoAG



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particles via this route.538−540 The latter approach (Figure 22b), called grafting-from or surface-initiated polymerization (SIP), is the preferred method, allowing the formation of highly dense polymer brushes. Using this approach, the polymer chains are grown directly from initiating sites decorating the surface.536,537,541 A third noteworthy alternative is the so-called grafting-through method, in which a monomer is attached to the surface of the particle and copolymerised in the presence of one or more comonomers. This approach is a hybrid route of the grafting-from and grafting-to methodologies, as the polymer chains both need to diffuse to the surface to react on the monomer functionality, then grow away from it. In that respect, it is far less efficient and has only received limited interest. Surface-initiated CLRP (SI-CLRP) has proven to be the most powerful tool in the preparation of core−shell materials. CLRP techniques allow the precise control over the structural parameters of the tethered polymer chains, taking advantage of the versatility and chemical tolerance of conventional radical polymerization. Significant technological developments have emerged since the introduction of CLRP techniques over the past 20 years. The preparation of well-defined polymers is possible with good fidelity of chain-end functionality and without the demanding reaction conditions needed for traditional living techniques, such as ionic polymerization (which is particularly sensitive to impurities, including water and oxygen, and requires the use of highly pure reagents). The “living” chains are then capable of being reinitiated by the addition of a second monomer to precisely tune the material properties. While conventional free radical polymerization offers ready access to a broad range of acrylate, methacrylate, and styrenic polymers and copolymers without the need for vigorous drying or highly stringent reaction conditions, more complex architectures and topologies, such as the formation of a second block by chain extension, are not feasible.542 The application of CLRP techniques to grow a polymer from initiating sites decorating a solid support has proven an effective route to prepare well-defined thin polymer films.536,543 In the following section, we present the key aspects of the various SICLRP synthetic strategies. For a more in-depth review of the materials obtained by SI-CLRP and their applications, the reader is referred to a number of recent comprehensive reviews.490,491,544−547

Although typical SI-ATRP relies on the tethering of an ATRP initiator to the surface, grafting can also be obtained by attaching a conventional free radical initiator to a surface and mediating the polymerization with a catalyst, introducing the deactivator species at the start of the reaction [typically a Cu(II) halide complex].563 The key difference between solution ATRP and SI-ATRP lies in the initiating and the propagation steps. The need for the monomer to diffuse to the surface-tethered initiator and chainend of the surface tethered polymer (propagation) may limit chain growth and therefore affect the kinetics of polymerization. In addition, since attaching an initiator to a surface leads to lower concentrations in initiator when compared to solution ATRP, the catalyst deactivator species [e.g., Cu(II)] is generated at a lower rate, and irreversible termination reactions dominate over reversible deactivations, thus leading to poor control over polymerization. Control is therefore dramatically improved by the introduction of a sacrificial initiator564 or deactivator,565 which leads to an increase in deactivator concentration. The latter approach is typically preferred, as it allows control over polymerization early in the reaction, while the introduction of free initiator requires the ATRP equilibrium to be established before control is obtained, and also consumption of monomer to form untethered polymeric chains that contaminate the final product. These free chains are, however, convenient, as they can easily be analyzed to inform one of the molecular weight of the grafted chains, as well as the grafting density. It should, however, be noted that the molecular weight of the grafted chain is also affected when the crowding and grafting density increase; thus, free chains might not necessarily be an accurate representation of tethered chains. Simulations and experimental data have shown that this effect varies between systems and with reaction conditions, and it is less pronounced with concave surfaces (particles) compared to flat surfaces.566 Irreversible termination in SI-ATRP only occurs between close neighbor tethered chains when one chain is activated next to an existing radical, via the “migration effect”. The termination rate coefficient is therefore proportional to the catalyst concentration, with high catalyst concentration leading to more termination events.567 Irreversible termination can also occur between interparticle chains and cause macroscopic gelation.568 These events can be reduced by working at high dilution and/or low monomer conversion, but these conditions limit application of the system. An alternative approach is to compartmentalize the particles by using miniemulsion569,570 or by polymerizing under high pressure, where the rate of propagation is increased and the rate of termination is decreased.571 A drawback of ATRP is the use of a catalyst, which may pollute the final product. Traces of (particulate) metals can be particularly difficult to remove from a particle suspension. An elegant approach to reduce the concentration of catalyst for ATRP is the use of reducing agents [e.g., ascorbic acid, tin(II) 2-ethylhexanoate] to continuously restore Cu(I) species by reducing Cu(II). This process permits the use of a much smaller concentration of ATRP catalyst and has been successfully applied to SI-ATRP.509,570,572 Polymerization of acidic monomers is also an issue in ATRP, as the monomer may deactivate the catalyst. However, acidic polymer brushes have been obtained by SI-ATRP via the polymerization of the corresponding sodium salt monomers.573

10.2. Surface-Initiated ATRP

Among the various techniques of SI-CLRP, surface-initiated atom transfer living radical polymerization (SI-ATRP) has by far been the most studied.490 The first report of SI-ATRP from a particle showed the controlled polymerization of acrylamide from benzyl chloride-derivatized silica particles.548 Since this initial work, SI-ATRP has been applied, allowing precise control over the particle brush architectures (grafting density, molecular weight, molecular weight distribution, connectivity, and composition) with monomers as diverse as styrene,549,550 nBA,551,552 MA,550 MMA,552−555 tBA,550,556,557 DMAEMA,558 styrenesulfonate,559,560 etc. Numerous substrates have also been employed,491 among which inorganic particles such as silica, alumina, titanium oxide, iron oxides, gold, germanium, quantum dots, pyrolyzed carbon hard spheres,561 and graphene and graphene oxide562 are the most noteworthy. Among these various substrates, silica is the most commonly encountered, since the Si−OH functionality of silica surface can easily be converted into stable siloxane bonds to attach an initiator. AH


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10.3. Surface-Initiated RAFT

amine-coated silica particles, which focuses on the use of a RAFT agent bearing a latent isocyanate functionality (azide carbonyl) on its R-group.593 The carbonyl azide converts into an isocyanate group as the RAFT agent initiates polymerization, followed by rapid addition of the isocyanate onto the amine and hydroxyl groups of the polydopamine substrate. In the early stage of the polymerization, the mechanism is a hybrid between grafting-to and grafting-from, but the rapid addition of the isocyanate group, formed in situ, to the substrate ensures that the polymerization rapidly follows the traditional graftingfrom route. In addition to the versatility of the approach, which does not require prefunctionalization of the particles with a RAFT agent, the selectivity of the isocyanate reaction with amine (no catalyst required) and hydroxyl (catalyst required) groups enables tuning of the grafting density. A unique feature of the RAFT process is the possibility to grow polymeric chains by attaching the RAFT agent to a surface through its Z-group. In this approach, a propagating polymeric chain has to diffuse to the surface of the particle to undergo degenerative transfer. Thus, despite the fact that the RAFT agent is attached to the surface, the Z-group approach resembles the grafting-to approach, as it relies on the diffusion of preformed polymer chains to the surface in order to obtain a grafted particle. The first example of such a system was provided by Perrier and co-workers, who functionalized Merrifield resin beads and silica particles by attaching a Zsupported dithiobenzoate RAFT agent to mediate methyl acrylate polymerization without the addition of a free CTA.594−597 A noteworthy feature of the Z-group approach is that it produces well-controlled, “pure” living polymeric chains, as each polymer chain bound to the particle is endfunctionalized by the Z-group of the RAFT agent. However, the main drawback of the approach, as in typical grafting-to approaches, is the low grafting density that is obtained due to steric hindrance of the chains diffusing to the surface-anchored Z-group. This drawback was elegantly exploited by Zhao et al., who reacted azide-functionalized silica particles with alkyne Zfunctionalized RAFT agents in a parallel copper-mediated azide alkyne cycloaddition (CuAAC)/RAFT approach. The authors obtained silica−polymer core−shell nanoparticles only partially grafted with polymer chains via reaction with some azide groups. The polymer grafts were then cleaved from the particles and the remaining unreacted azide groups used for subsequent RAFT/CuAAC reactions, permitting one to employ the silica particles as a reusable solid support to generate highly pure living polymers.538 A particularly insightful study to compare R- and Z-group approaches is the work by Ranjan and Brittain, who used CuAAC to attach an alkyne-functionalized RAFT agent onto azide-functionalized silica particles via either its R- or Z-group and demonstrated that a much higher grafting density was accessible via the grafting-from approach when compared to that of the grafting-to method.539,540,598 Similar observations were made by Rotzoll and Vana, who grafted MA loops to silica surfaces using bifunctional RAFT agents anchored via either the R-group or the Z-group.599,600 The authors noted that the molecular weights of polymers grafted with the Z-group attached to the particles were higher than those obtained from a R-group-bound RAFT agent. They rationalize that larger propagating polymer chains are capable of reacting with Zgroup-bound RAFT agents due to the lower steric hindrance caused by low grafting densities.

In SI-RAFT polymerization, grafted polymeric chains can be obtained either by tethering the initiator or the RAFT agent to the substrate, and in the latter case, either the R-group or the Zgroup of the RAFT agent can be used as an anchor. In some studies, tethering a RAFT agent via its Z-group is described as a grafting-to approach rather than the typical grafting-from approach of SI-CLRP. SI-RAFT has grown in popularity over the years and has been used with a number of acrylic, methacrylic, and styrenic monomers.491 The first report of a silica-supported R-group RAFT agent was published by Tsuji et al., who transformed the bromide group of polystyrene chains grafted from a silica particle by ATRP into a dithiobenzoate. The resulting particles were used to mediate the polymerization of styrene under standard RAFT conditions.574 A more direct approach is the synthesis of a RAFT agent that can be directly attach to the solid substrate.575 Control over the polymerization is significantly increased by the introduction of a free RAFT agent, as it favors rapid exchange between surface-bound radicals and free chains, even at high conversions. The system also generates free polymeric chains, the molecular weight and dispersities of which typically reflect those of the grafted chains,574,576 although it has been recently suggested that at a high grafting density of RAFT agent (1.95 RAFT agents/nm2), slow diffusion of species may lead to grafted chains growing via a (uncontrolled) free radical process, thus yielding polymeric chains with a higher molecular weight than that of free chains.577 SI-RAFT polymerization has been used with a variety of substrates, with silica (nano)particles545 being by far the most utilized but also including, for instance, titania,578 CdSe,579 iron oxide,580 gold nanoparticles,581 carbon582−585 and halloysite586 nanotubes, and graphene and graphene oxide.562 Typically, excellent control over the polymerization is achieved, although reactions have to be kept at low monomer conversion (

Living Radical Polymerization in Dispersed Systems: An

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