Predictive Phase Diagrams for RAFT Aqueous Dispersion

Jun 13, 2012 - The final copolymer morphology in such PISA syntheses depends on just three parameters: the mean degree of polymerization (DP) of the...
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Predictive Phase Diagrams for RAFT Aqueous Dispersion Polymerization: Effect of Block Copolymer Composition, Molecular Weight, and Copolymer Concentration A. Blanazs,* A. J. Ryan, and S. P. Armes* Dainton Building, Department of Chemistry, The University of Sheffield, Brook Hill, Sheffield, South Yorkshire S3 7HF, U.K. S Supporting Information *

ABSTRACT: Polymerization-induced self-assembly (PISA) of poly(glycerol monomethacrylate)−poly(2-hydroxypropyl methacrylate) (PGMA−PHPMA) diblocks is conducted using a RAFT aqueous dispersion polymerization formulation at 70 °C. Several PGMA macromolecular chain transfer agents (macroCTAs) are chain-extended using a water-miscible monomer (HPMA): the growing PHPMA block becomes increasingly hydrophobic and hence drives in situ self-assembly. The final copolymer morphology in such PISA syntheses depends on just three parameters: the mean degree of polymerization (DP) of the PGMA stabilizer block, the mean DP of the PHPMA core-forming block, and the total solids concentration. Transmission electron microscopy is used to construct detailed diblock copolymer phase diagrams for PGMA DPs of 47, 78, and 112. For the shortest stabilizer block, there is essentially no concentration dependence: spheres, worms, or vesicles can be obtained even at 10% w/w solids simply by selecting the DP of the PHPMA block that gives the appropriate molecular curvature. For a PGMA DP of 78, the phase diagram is rich: and the copolymer morphology depends strongly on the total solids concentration. There is also a narrow region where spheres, worms, and vesicles coexist, which may be due to the effect of polydispersity. For a PGMA112 macro-CTA, the phase diagram is dominated by spherical morphologies. This is probably because the longer core-forming block DPs required to reduce the molecular curvature are significantly more dehydrated and hence less mobile, which prevents the in situ evolution of morphology from spheres to higher order morphologies. This hypothesis is supported by the observation that addition of ethanol to aqueous PISA syntheses conducted using the longer macro-CTAs allows access to diblock copolymer worms or vesicles, since this cosolvent solvates the core-forming PHPMA chains and hence increases their mobility at 70 °C. Elucidation of such phase diagrams is vital to ensure reproducible targeting of pure phases, rather than mixed phases.

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alcoholic dispersion polymerization.41,42 Optimized formulations allow efficient polymerizations (>99% within 2 h) and relatively low final copolymer polydispersities (Mw/Mn < 1.20).35,40 In each case the water-soluble steric stabilizer block is prepared first, with the subsequent growth of the waterinsoluble block driving the in situ phase separation. This “convergent growth” strategy ensures good colloidal stability for the final diblock copolymer nanoparticles due to a steric stabilization mechanism.43 Moreover, producing the diblock copolymer chains in the form of nanoparticles ensures much lower viscosities than for solution polymerizations, which is an important consideration for scale-up syntheses. Recently, Sugihara et al.34 demonstrated that the final particle morphology in such PISA-based syntheses is dictated by two parameters: the copolymer concentration and the block copolymer composition. In this regard, the AB diblock copolymer chains behave similarly to small molecule surfactants,44−46 for which it is well-known that self-assembly is dictated by the molecular curvature.47,48 Assuming that there is sufficient amphiphilic character, this

INTRODUCTION It is well-known that amphiphilic molecules undergo spontaneous self-assembly in aqueous solution.1 Indeed, this inherent property is fundamental to life itself since it enables the construction of cell membranes from phospholipid-based surfactants.2 Amphiphilic surfactants have been utilized as emulsifiers, for pigment dispersion and for latex stabilization.3−5 In the case of amphiphilic block copolymers, a remarkably wide range of nanostructures can be accessed, including spherical micelles, 6 worm-like micelles, 7,8 rod-like micelles, 9−11 vesicles,6,12−19 nanotubes,20,21 and toroids.22 Classically, such block copolymer self-assembly involves careful processing in dilute aqueous solution via either a solvent switch (often achieved by dialysis 6 ), a pH switch, 17,23 or thin film rehydration.14,24 However, recent advances in polymerizationinduced self-assembly (PISA) via reversible addition−fragmentation chain transfer (RAFT) polymerization25−27 have enabled AB diblock copolymer to be prepared directly in water in the form of spheres, worms, or vesicles at relatively high solids (10− 25%). This has been achieved using formulations based on either aqueous dispersion polymerization28−37 or aqueous emulsion polymerization,38−40 with closely related work involving © 2012 American Chemical Society

Received: May 24, 2012 Published: June 13, 2012 5099

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Scheme 1. Synthesis of the Various Poly(glycerol monomethacrylate)−Poly(2-hydroxypropyl methacrylate) (Gx−Hy) Diblock Copolymers via RAFT Aqueous Dispersion Polymerization

analysis of the HPMA monomer indicated a dimethacrylate impurity of around 0.10 mol %. In the case of the CPDB, the manufacturer’s stated purity was 97%, but 1H NMR analysis indicated a somewhat lower (and variable) purity of 75−90%. The actual purity of each CPDB batch was taken in account when calculating the target degree of polymerization for the PGMA block. Deuterated methanol (CD3OD) was purchased from Goss Scientific (Nantwich, UK). All solvents were of HPLC quality and were purchased from Fisher Scientific (Loughborough, UK). PGMAx Macro-CTA Synthesis. A typical protocol for the synthesis of PGMA47 is given below: CPDB RAFT agent (1.50 mmol, 0.330 g, purchased from Sigma-Aldrich with 80% purity as judged by 1H NMR spectroscopy) and GMA monomer (89.6 mmol, 14.35 g) were weighed into a 50 mL round-bottomed flask and purged under N2 for 20 min. ACVA initiator (0.30 mmol, 83.7 mg, CTA/ACVA molar ratio = 5.0) and anhydrous ethanol (21.6 mL, to afford a 45% w/w GMA solution), which had been purged with N2 for 30 min, were then added, and the resulting red solution was purged for a further 10 min. The sealed flask was immersed into an oil bath set at 70 °C for 80 min (final GMA conversion = 57% as judged by 1H NMR; see Figure S1), and the polymerization was subsequently quenched by immersion in liquid nitrogen. Methanol (50 mL) was added to the reaction solution, followed by precipitation into a ten-fold excess of cyclohexane (1 L). The precipitated PGMA macro-CTA was washed three times with cyclohexane and then dialyzed against methanol overnight (with three changes of methanol) using semipermeable cellulose tubing. 1H NMR analysis indicated a mean degree of polymerization of 47 for this PGMA macro-CTA. Its Mn and Mw/Mn were 14 100 g mol−1 and 1.13, respectively, as judged by GPC using DMF eluent, a refractive index detector, and a series of near-monodisperse poly(methyl methacrylate) calibration standards. RAFT Aqueous Dispersion Polymerization of PGMA47− PHPMA200. A typical protocol for the synthesis of PGMA47− PHPMA200 is as follows: PGMA47 macro-CTA (0.150 g, 0.019 mmol) and HPMA monomer (0.5578 g, 3.9 mmol; target DP = 200) were weighed into a 25 mL round-bottomed flask and purged with N2 for 20 min. ACVA was added (1.80 mg, 0.0063 mmol, CTA/ACVA molar ratio = 3.0) and purged with N2 for a further 5 min. Deionized water (6.4 mL, producing a 10.0% w/w aqueous solution), which had been previously purged with N2 for 30 min, was then added and the solution was degassed for a further 5 min prior to immersion in an oil bath set at 70 °C. The reaction solution was stirred overnight (16 h) to ensure complete HPMA monomer conversion and quenched by exposure to air. For the sake of brevity, we denote the PGMA and PHPMA blocks as simply G and H in the rest of this article. For example, the above PGMA47−PHPMA200 diblock is referred to as G47−H200. Polymer Characterization. 1H NMR Spectroscopy. All NMR spectra were recorded using a 400 MHz Bruker Avance-400 spectrometer (64 scans averaged per spectrum). Gel Permeation Chromatography (GPC). Copolymer molecular weights and polydispersities were determined using a DMF GPC setup operating at 60 °C and comprising two Polymer Laboratories PL gel 5 μm Mixed-C columns connected in series to a Varian 390-LC multidetector suite (refractive index detector only) and a Varian 290-

parameter depends primarily on the relative volume fractions of the A and B blocks. Unlike surfactants, block copolymers are more likely to form kinetically frozen (nonergodic) nanostructures, particularly for higher molecular weight chains. This is due to much slower exchange kinetics between the colloidal aggregates and the individual copolymer chains.49−55 In PISA syntheses, it has been demonstrated that the copolymer morphology can evolve from spheres to worms to vesicles during the in situ polymerization.34,35,40,42 This is attributed to the gradual reduction in molecular curvature for the copolymer chains as the core-forming block grows from the (fixed) stabilizer block and is mediated by the unreacted monomer solvating the core-forming chains. Furthermore, in the case of PHPMAcontaining formulations, the chains are only weakly hydrophobic and are also partially swollen/plasticized by water.56,57 The bound water molecules were found to reduce the effective Tg from 95 °C for rigorously dried PHPMA to 47 °C for watersoaked PHPMA.35 Recently, careful sampling of PISA reaction solutions combined with electron microscopy studies has revealed remarkable jellyfish intermediates.35 This study has shed new light on the mechanism of the worm-to-vesicle transition for block copolymers which is believed to be generic, rather than specific to PISA formulations. As far as we are aware, there has only been a single report of just one phase diagram for PISA syntheses of block copolymer nanoparticles.34 Herein we have elucidated detailed phase diagrams for a prototypical RAFT aqueous dispersion polymerization formulation described earlier.30,35 Such phase diagrams are vital for the development of PISA-based syntheses, since they enable pure (rather than mixed phase) block copolymer morphologies to be targeted with good reproducibility. For a target AB diblock copolymer comprising a water-soluble poly(glycerol monomethacrylate) (PGMA) block and a waterinsoluble poly(2-hydroxypropyl methacrylate) (PHPMA) block, we show that the final copolymer morphology is dictated by the mean degree of polymerization (DP) of the core-forming block and the copolymer concentration. More importantly, we also demonstrate for the first time that the degree of polymerization of the stabilizer block profoundly af fects the PISA phase diagram.

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EXPERIMENTAL SECTION

Materials. Glycerol monomethacrylate (GMA; 99.8%) was kindly donated by Cognis Performance Chemicals (Hythe, UK) and used without further purification. 2-Hydroxypropyl methacrylate (HPMA, 97%), 2-cyano-2-propyl dithiobenzoate (CPDB), 4,4′-azobis(4-cyanopentanoic acid) (ACVA; V-501; 99%) D2O, anhydrous ethanol (99%), and dialysis tubing (SPECTRA/POR; molecular weight cutoff = 1000) were purchased from Sigma-Aldrich UK and used as received. HPLC 5100

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LC pump injection module. The GPC eluent was HPLC grade DMF containing 10 mM LiBr at a flow rate of 1.0 mL min−1. DMSO was used as a flow-rate marker. Calibration was conducted using a series of ten near-monodisperse poly(methyl methacrylate) standards (Mn = 625− 618 000 g mol−1). Chromatograms were analyzed using Varian Cirrus GPC software (version 3.3). Dynamic Light Scattering (DLS). Intensity-average hydrodynamic diameters of the dispersions were obtained by DLS using a Malvern Zetasizer NanoZS instrument, which detects backscattered light at 173°. Aqueous copolymer dispersions of 0.20% w/v were analyzed using plastic disposable cuvettes, and all data were averaged over three consecutive runs. Transmission Electron Microscopy (TEM). Aggregate solutions were diluted fifty-fold at 20 °C to generate 0.20% w/w dispersions. Copper/ palladium TEM grids (Agar Scientific, UK) were surface-coated inhouse to yield a thin film of amorphous carbon. The grids were then treated with a plasma glow discharge for 30 s to create a hydrophilic surface. Each aqueous diblock copolymer dispersion (0.20% w/w, 12 μL) was placed onto a freshly treated grid for 1 min and then blotted with filter paper to remove excess solution. To stain the deposited nanoparticles, a 0.75% w/w aqueous solution of uranyl formate (9 μL) was placed via micropipet on the sample-loaded grid for 20 s and then carefully blotted to remove excess stain. Each grid was then carefully dried using a vacuum hose. Imaging was performed at 100 kV using a Phillips CM100 instrument equipped with a Gatan 1 k CCD camera.

Figure 1. DMF gel permeation chromatograms obtained for a series of G47−Hx (where x = 90, 150, and 200) diblock copolymers synthesized at either (a) 25% w/w or (b) 10% w/w and the corresponding G47 macroCTA.

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such asymmetric amphiphiles, the post mortem diblock copolymer morphology (obtained at full monomer conversion) has essentially no concentration dependence, at least over the range investigated. Thus, higher order morphologies (i.e., worms or vesicles) can be readily accessed when conducting RAFT syntheses at just 10% w/w solids. Moreover, there is no evidence for any mixed phase regions (i.e., spheres plus worms or worms plus vesicles). Hence this phase diagram differs qualitatively from that recently reported by us for the synthesis of M25−Hx diblocks, where M = poly(2-(methacryloyloxy)ethylphosphorylcholine).34 In this latter system, the vesicle phase could only be accessed by conducting the synthesis at 22−25% solids while also targeting a relatively high DP for the core-forming block (375− 400). The characteristic dimensions of the diblock copolymer “nano-objects” estimated by TEM in both studies are comparable to a good first-order approximation; i.e., the mean spherical diameter is fairly close to both the mean worm width and the mean vesicle membrane thickness. In principle, the worm width should always be greater than the spherical diameter since, for a fixed PGMA stabilizer DP, a longer core-forming block is required for the anisotropic phase. In practice, this will only be true if the degree of dehydration of the core-forming block remains constant. Similarly, the vesicle membrane thickness might be expected to be a little less than the mean worm width due to the well-known interdigitation effect.24 Previously, we have demonstrated that careful sampling of a G47−H200 10% w/w formulation reveals the in situ evolution in diblock copolymer morphology during the growth of the coreforming block.35 This is due to a gradual reduction in the molecular curvature of the diblock copolymer chains.48 Thus spheres become first worms, and ultimately vesicles, via a remarkable hemi-vesicle (jellyfish-like) intermediate.35 To a good approximation, this corresponds to traversing a vertical line on the phase diagram at 10% w/w and hence accounts for the various morphologies. It is also noteworthy that no diblock nanoparticles are observed by TEM for core-forming DPs of less than around 90. Under these conditions, the diblock copolymer chains are simply dissolved in the aqueous solution since the core-forming block is not sufficiently hydrophobic to induce micellar nucleation.

RESULTS AND DISCUSSION Scheme 1 outlines the RAFT aqueous dispersion polymerization formulation utilized to synthesize the various diblock copolymer nanoparticle dispersions for this study. Three poly(glycerol monomethacrylate) (PGMAx) macro-CTAs (where x = 47, 78, and 112) were first synthesized via RAFT solution polymerization in anhydrous ethanol at 70 °C. In order to preserve RAFT end-group PGMA fidelity, each polymerization was quenched at around 50−70% GMA conversion. It was found empirically that using anhydrous ethanol was beneficial in such syntheses since this ensured more consistent kinetics: low levels of water increase the rate of GMA polymerization, which result in higher DPs being obtained in a given time than those targeted in the absence of any water. An even more important strategy was to prepare a single large batch (at least 15 g) of each PGMA macro-CTA for the elucidation of each phase diagram, since producing precisely the same actual degree of polymerization (and blocking efficiency) from two or more such macro-CTA syntheses is highly problematic. Thus, utilizing a single batch of PGMA macro-CTA for each phase diagram eliminates such systematic errors. Figure 1 shows the GPC data obtained for a series of G47−Hx diblock copolymers synthesized at a total solids concentration of (a) 25% w/w and (b) 10% w/w with total HPMA monomer conversions above 99% (as calculated by 1H NMR). For a fixed DP of the stabilizer (G) block, systematic variation of the target DP of the core-forming (H) block leads to a monotonic increase in the GPC molecular weight of the diblock copolymer, as expected. Moreover, essentially the same molecular weight distribution is obtained for a given targeted diblock composition, regardless of whether the RAFT synthesis is conducted at 10 or 25% w/w or whether the final diblock copolymer morphology is spheres, worms, or vesicles (or a mixed phase). Similar results were also obtained for three series of G78−H200, G78−H400, and G112−H800 diblock copolymers prepared at up to five different concentrations (see Figures S1−S3 in the Supporting Information). A phase diagram for a series of G47−Hx diblock copolymer “nano-objects” determined by TEM is shown in Figure 2. For 5101

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Figure 2. Representative TEM images and the corresponding phase diagram for a series of G47−Hx copolymers synthesized by aqueous RAFT dispersion polymerization at 10 and 25% w/w. S = spherical micelles, W = worms, BW = branched worms, and V = vesicles.

Figure 3. Representative TEM images and the corresponding phase diagram for a series of G78−Hx copolymers synthesized by aqueous RAFT dispersion polymerization at various concentrations ranging between 10 and 25% w/w. S = spherical micelles, W = worms, and V = vesicles.

A detailed phase diagram obtained for the G78−Hx diblock copolymer series is shown in Figure 3. This has many features in common with that previously reported for the M25−Hx system mentioned above.34 Thus the final copolymer morphology is strongly concentration-dependent, with lower concentrations favoring the formation of spheres. DLS studies corroborate this

observation (see Figure 4). Hence G78−H400 forms spherical micelles with an intensity-average diameter of 65 nm at 10% w/ w. If G78−H400 is synthesized at higher solids, a larger intensityaverage diameter is obtained due to the gradual formation of a vesicle phase, as confirmed by TEM studies; this is because DLS is strongly biased toward larger nano-objects. For example, the 5102

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solids and x = 275−300) that contains all three morphologies (spheres, worms, and vesicles). At first sight, this seems rather counterintuitive, since the molecular curvature required for spheres is greater than that for worms, which in turn exceeds that required for vesicles. Thus, although sphere/worm and worm/ vesicle boundaries are expected, it is difficult to envisage the coexistence of these three morphologies for a given diblock copolymer composition (e.g., G78H300-13%, G78H300-15%, or G78H275-15%). However, given that this three-phase window is very narrow, a likely explanation may be the diblock copolymer polydispersity. Although this is relatively low (e.g., Mw/Mn = 1.14 for G78H300 at 15%), there is no doubt that there is significant compositional heterogeneity. Thus the fraction of copolymer chains that are more PGMA-rich should tend to form spheres, while PHPMA-rich copolymer chains should favor vesicles and copolymer chains of intermediate composition should produce worms. Comparing Figures 2 and 3, it is apparent that the phase diagram is very sensitive to the stabilizer (G) block DP as well as that of the core-forming (H) block. This is because, for a longer stabilizer DP (i.e., a fixed “headgroup” area), a correspondingly longer core-forming block (and hence more voluminous tail) is required to produce the same molecular curvature. However, longer core-forming chains are increasingly hydrophobic and hence more dehydrated. This can significantly reduce their mobility under the reaction conditions and hence inhibits in situ morphological evolution.35,53 This effect can be alleviated by increasing the initial HPMA concentration, as indicated by the increased complexity of the phase diagram shown in Figure 3. At intermediate monomer conversions, unreacted HPMA can act as a cosolvent for the growing PHPMA chains, which facilitates anisotropic fusion of spherical micelles to produce worms (and also aids the subsequent worm-to-vesicle transition).35 Alternatively, an additional cosolvent can be employed to aid

Figure 4. DLS intensity-average diameter distribution and corresponding morphology adopted by G78−H400 diblock copolymer nanoparticles synthesized at 10, 13, 15, 17, and 25% w/w.

“sphere plus vesicle” mixed phase observed for G78−H400 synthesized at either 13 or 15% w/w exhibits intensity-average diameters of 111 or 181 nm, respectively. At 17% w/w or above, a pure vesicular phase is obtained for G78−H400, with an intensityaverage diameter of 260−270 nm. The pure worm phase is relatively narrow (x = 225−250) and is surrounded by two mixed phase regions. Pure vesicles are only obtained above 17% solids and x = 350. Particularly for this formulation, a detailed knowledge of the phase diagram is essential for reproducible syntheses of pure diblock copolymer morphologies. Experimentally, it is relatively easy to access welldefined spheres and vesicles, while the worm phase is more elusive. Unlike the phase diagram reported by Sugihara et al.34 for M25−Hx, there is also a relatively narrow region (at 13−15% w/w

Figure 5. Representative TEM images and the corresponding phase diagram for a series of G112−Hx diblock copolymers synthesized by aqueous RAFT dispersion polymerization at various concentrations ranging between 10 and 25% w/w. S = spherical micelles, W = worms, and V = vesicles. 5103

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morphological evolution even at relatively low monomer concentrations (e.g., 10% w/w); see later. Increasing the stabilizer block length by a further 34 HPMA units generates a relatively homogeneous series of G112−Hx diblock copolymer nanoparticles (see Figure 5). In this case, spheres are the predominant phase. Worms and vesicles are observed only as mixed phases (i.e., contaminated by spheres), even when targeting PHPMA-rich copolymers at relatively high concentrations. Vesicles (and spheres) are only formed above 20% w/w solids when targeting a PHPMA DP of at least 600, whereas worms (and spheres) are only observed for G112−H500 at 25% w/w. This lack of morphological complexity is attributed to kinetic trapping of spherical micelles due to reduced mobility of the relatively hydrophobic core-forming chains. Whether this is viewed as a problem or an opportunity depends on which phase is of interest. Thus restricting G112−Hx syntheses to only 10% w/ w enables systematic variation of the mean spherical diameter from around 40 nm (x = 200) to 100 nm (x = 1000), see Figure 6. At these relatively high DPs, the copolymer chains must be highly frustrated within their spherical domains.

Figure 7. Phase diagram summarizing the various morphologies observed for the three series of G112−Hx, G78−Hx, and G47−Hx diblock copolymers synthesized by RAFT aqueous dispersion polymerization at 10% w/w. Increasing the mean degree of polymerization (DP) of the PGMA macro-CTA from 47 to either 78 or 112 leads to the exclusive generation of spherical diblock copolymer nanoparticles under these conditions. S = spherical micelles, W = worms, BW = branched worms, and V = vesicles.

interfacial tension between the G and H blocks as there is a distribution of water molecules across the core and corona regions. A similar phase diagram constructed for the same G112− Hx, G78−Hx, and G47−Hx copolymer series prepared at 25% w/w is shown in Figure S4 (see Supporting Information). As we have shown, using a relatively long PGMA78 macroCTA leads to exclusively spherical morphologies at 10% solids (see Figures 3 and 7). One question that arises here is whether this is simply due to a kinetic effect. To test this hypothesis, these RAFT syntheses were repeated in the presence of a relatively small volume of water-miscible cosolvent (ethanol). This cosolvent was expected to plasticize the core-forming PHPMA chains, hence conferring greater mobility than that obtained in purely aqueous formulations. In principle, this should allow higher order morphologies to be accessed. Figure 8 depicts TEM images obtained for four G78−H500 diblock copolymers prepared at 10% w/w in the presence of 0, 10, 15, and 20 mass % ethanol. In the absence of ethanol, only spheres are observed, as expected (see Figures 3 and 7). For 10% ethanol, a mixed phase comprising spheres and vesicles is obtained, while predominantly vesicles are observed at 15% ethanol. We interpret these changes in morphology to be due to the ethanol acting as a cosolvent for the PHPMA chains, which is equivalent to the role played by the unreacted HPMA monomer in diblock copolymer syntheses at higher solids. Finally, a mixture of vesicles and worms is formed at 20% ethanol. This is because the ethanol concentration is now so high that it destabilizes the vesicular phase, since it substantially swells the PHPMA chains and hence reduces the interfacial tension between the two blocks. DLS size distributions were obtained for the various diblock copolymer nanoparticles prepared in the presence of ethanol cosolvent. For these measurements, the final 10% w/w diblock copolymer dispersions in ethanol were diluted fifty-fold with water to generate 0.20% w/w dispersions with final ethanol contents below 0.04%, which has a negligible effect on the solution viscosity. As shown in Figure 8e, increasing the ethanol

Figure 6. DLS intensity-average diameter distribution for spherical nanoparticles formed by G112−Hx synthesized at 10% w/w. As expected, an increase in the targeted DP of the core-forming PHPMA chains results in a monotonic increase in the hydrodynamic diameter.

Figure 7 shows an overall phase diagram for the G112−Hx, G78−Hx, and G47−Hx copolymer series prepared at a fixed solids concentration of 10% w/w: these data emphasize the effect of varying the mean DP of the stabilizer chains and the mole fraction of the core-forming chains. The mole fraction was chosen to allow meaningful comparison between diblock copolymers of differing overall molecular weights. For a given copolymer composition, the molecular curvature of the copolymer chain is fixed. However, it is clear that, under the specific reaction conditions used in these PISA syntheses, higher order morphologies (i.e., worms or vesicles) can only be accessed for lower molecular weight diblock copolymers. As a corollary, higher molecular weight copolymer chains with approximately the same spontaneous curvature can only form frustrated spheres if synthesized at relatively low concentration (e.g., 10% solids). Again, this is because of the significant reduction in mobility of the longer core-forming PHPMA chains (see above). Since the copolymer chains are compressed normal to the sphere surface, their intrinsic frustration is likely to be mediated by the low 5104

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observed in these cosolvent experiments is fully consistent with the various phase diagrams described for block copolymers prepared in the absence of any cosolvent. These results are also consistent with observations made by van Stam et al., who found that the addition of dioxane cosolvent to polystyrene−poly(sodium methacrylate) diblock copolymer micelles led to a greatly enhanced rate of unimer−micelle exchange.53 Finally we note that, in view of the above discussion, our recent observation58 of a thermoreversible worm-to-sphere transition for a G54−H140 diblock copolymer may have been somewhat fortuitous, since this phenomenon is most likely restricted to a fairly narrow range of block copolymer compositions (i.e., relatively short PGMA and PHPMA blocks).

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CONCLUSIONS It is shown for the first time that the final diblock copolymer morphology obtained via polymerization-induced self-assembly (PISA) conducted under aqueous dispersion polymerization conditions using living radical polymerization chemistry depends strongly on the mean degree of polymerization of the stabilizer block, as well as that of the core-forming block and the total solids concentration. The detailed phase diagrams elucidated herein are both of fundamental scientific interest and also practical utility, since they allow reproducible targeting of pure (rather than mixed) diblock copolymer morphologies in such syntheses. PISA clearly offers enormous scope for the rational design of welldefined diblock copolymer nano-objects based on cheap vinyl monomers in concentrated aqueous solution using scalable chemistry. In forthcoming papers, we will describe specific applications for such bespoke organic nanoparticles.

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ASSOCIATED CONTENT

S Supporting Information *

DMF GPC traces of the Gx−Hy diblock copolymers synthesized at increasing concentrations, DMF GPC traces of the G78−H500 diblock copolymers synthesized in the presence of ethanol, an additional phase diagram summarizing the nano-objects formed for the Gx−Hy diblock copolymers at 25% w/w, and TEM images of the nanostructures generated when synthesizing G112−H800 in the presence of different amounts of ethanol. This material is available free of charge via the Internet at http://pubs.acs.org.

Figure 8. Representative TEM images illustrating the effect of adding ethanol cosolvent to the synthesis of G78−H500 diblock copolymers by RAFT aqueous dispersion polymerization at 10% w/w: (a) no ethanol, (b) 10% ethanol, (c) 15% ethanol, (d) 20% ethanol. (e) Corresponding DLS intensity-average diameter distributions obtained for the same G78−H500 diblock copolymer dispersions.

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AUTHOR INFORMATION

Corresponding Author

*E-mail: [email protected] (A.B.); s.p.armes@sheffield. ac.uk (S.P.A.).

content of the RAFT formulation generates nano-objects with broader size distributions. This is consistent with the aforementioned TEM studies, indicating a transition from spheres to vesicles (and ultimately the formation of a vesicle plus worm mixed phase) as the proportion of ethanol cosolvent is increased. DMF GPC studies of the G78−H500 diblock copolymers (see Figure S5 in the Supporting Information) confirm that the addition of ethanol has relatively little effect on the molecular weight distribution, although slightly lower conversions are obtained due to the reduced local concentration of HPMA monomer within the growing nanoparticles. Nevertheless, conversions of more than 95% were obtained within 2 h at 70 °C in all cases (as judged by 1H NMR). Similar observations have also been made for the addition of ethanol during the synthesis of G112−H800 copolymers (see Figure S6 in the Supporting Information). Thus the evolution of morphology

Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS EPSRC is acknowledged for postdoctoral support of A.B. (Platform grants EP/E012949/1 and EP/J007846/1). REFERENCES

(1) Israelachvili, J. N. Intermolecular & Surface Forces, 2nd ed.; Academic Press: London, 1991; Vol. 1. (2) Alberts, B.; Johnson, A.; Lewis, J.; Raff, M.; Roberts, K.; Walter, P. Molecular Biology of the Cell, 4th ed.; Garland Science: New York, 2002. (3) Garrett, H. E. Surface Active Chemicals, 1st ed.; Pergamon Press: Oxford, 1972. (4) Hunter, R. J. Foundations of Colloid Science, 1st ed.; Oxford University Press: Oxford, 1987; Vol. 1. 5105

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