Evolution of Multicompartment Micelles to Mixed Corona Micelles

Sep 13, 2008 - Miktoarm star triblock copolymers μ-[poly(ethylethylene)][poly(ethylene oxide)][poly(perfluoropropylene oxide)] self-assemble in dilut...
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Langmuir 2008, 24, 12001-12009

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Evolution of Multicompartment Micelles to Mixed Corona Micelles Using Solvent Mixtures Chun Liu,† Marc A. Hillmyer,*,† and Timothy P. Lodge*,†,‡ Department of Chemistry, and Department of Chemical Engineering and Materials Science, UniVersity of Minnesota, Minneapolis, Minnesota 55455-0431 ReceiVed July 21, 2008. ReVised Manuscript ReceiVed August 21, 2008 Miktoarm star triblock copolymers µ-[poly(ethylethylene)][poly(ethylene oxide)][poly(perfluoropropylene oxide)] self-assemble in dilute aqueous solution to give multicompartment micelles with the cores consisting of discrete poly(ethylethylene) and poly(perfluoropropylene oxide) domains. Tetrahydrofuran is a selective solvent for both the poly(ethylethylene) and poly(ethylene oxide) blocks, and thus in tetrahydrofuran mixed corona micelles are favored with poly(perfluoropropylene oxide) cores. The introduction of tetrahydrofuran into water induces an evolution from multicompartment micelles to mixed corona [poly(ethylethylene) + poly(ethylene oxide)] micelles, as verified by dynamic light scattering and nuclear magnetic resonance spectroscopy. A mixed solvent containing 60 wt % tetrahydrofuran corresponds to the transition point, as verified by analysis of a poly(ethylethylene)poly(ethylene oxide) diblock copolymer in the same solvent mixtures. Furthermore, cryogenic transmission electron microscopy suggests that, as the poly(ethylethylene) block transitions from the core to the corona, the micelle morphologies evolve from disks to oblate ellipsoid micelles (with some vesicles), with worms and spheres evident at intermediate compositions.

Introduction The self-assembly of multiblock copolymers into multicompartment micelles whose cores are subdivided into distinct nanodomains is an exciting area of polymer science due to potential applications in biomedicine, pharmacy and biotechnology.1,2 The concept of multicompartment micelles first emerged from the idea of imitating eukaryotic cells in biological systems.3 Diblock copolymers are incapable of forming such complex micelles since they can only be divided into “core” and “corona” domains. Triblock terpolymers, on the other hand, with three mutually immiscible components serve as the simplest model to create discrete subdomains within one core.4 Some initial progress toward this goal has already been made with linear triblock polymers.5-8 However, the linear architecture normally favors a core-shell-corona structure due to the sequential linkage of each block.9 In contrast, mikto(mixed)arm star terpolymers suppress the formation of core-shell–corona micelles by the mandatory convergence of three immiscible blocks at a single juncture. Previously we obtained multicompartment micelles from selfassembly of µ-[poly(ethylethylene)][poly(ethylene oxide)][poly(perfluoropropylene oxide)] (µ-EOF) in dilute aqueous * To whom correspondence should be addressed. E-mail: hillmyer@ umn.edu (M.A.H.); [email protected] (T.P.L.). † Department of Chemistry. ‡ Department of Chemical Engineering and Materials Science.

(1) Laschewsky, A. Curr. Opin. Colloid Interface Sci. 2003, 8, 274. (2) Lutz, J. F.; Laschewsky, A. Macromol. Chem. Phys. 2005, 206, 813. (3) Ringsdorf, H.; Lehmann, P.; Weberskirch, R. Book of Abstracts, 217th National Meeting of the American Chemical Society, Anaheim, CA, March 21-25, 1999. (4) Lodge, T. P.; Hillmyer, M. A.; Zhou, Z.; Talmon, Y Macromolecules 2004, 37, 6680. (5) Kubowicz, S.; Baussard, J. F.; Lutz, J. F.; Thu¨nemann, A. F.; von Berlepsch, H; Laschewsky, A. Angew. Chem., Int. Ed. 2005, 44, 5262. (6) Thu¨nemann, A. F.; Kubowicz, S.; von Berlepsch, H.; Mo¨hwald, H. Langmuir 2006, 22, 2506. (7) Cui, H.; Chen, Z.; Zhong, S.; Wooley, K. L.; Pochan, D. J. Science 2007, 317, 647. (8) Mao, J.; Ni, P.; Mai, Y.; Yan, D. Langmuir 2007, 23, 5127. (9) Zhou, Z.; Li, Z.; Ren, Y.; Hillmyer, M. A.; Lodge, T. P. J. Am. Chem. Soc. 2003, 125, 10182.

Table 1. Molecular Parameters of EO Diblock and µ-EOF Star Triblock Polymers19,28 sample IDa EO(2-9) µ-EOF(2-9-3) µ-EOF(2-9-5) µ-EOF(2-13-3)

Mnd NPEEb NPEOb NPFPOb fPEEc fPEOc fPFPOc (kDa) PDIe 31 31 31 31

197 197 197 285

20 31 20

0.22 0.19 0.17 0.14

0.78 10.6 1.11 0.66 0.15 14.0 1.27 0.61 0.22 15.9 1.24 0.74 0.12 17.9 1.08

a The numbers in parentheses denote the molecular weight of each block in kDa. b Calculated via 1H NMR and 19F NMR spectra. c The volume fractions were calculated using the molecular weight from NMR spectroscopy and the amorphous density at room temperature: F(PEE) ) 0.815 g/cm3 F(PEO) ) 1.12 g/cm3, F(PFPO) ) 1.9 g/cm3. d Calculated from NMR spectra. e Polydispersity (PDI) was obtained from SEC using PS standards and THF as eluent at 40 °C.

solution.10 These micelles are composed of oblate disk-like poly(perfluoropropylene oxide) (PFPO) cores with the top and bottom surrounded by a poly(ethylethylene) (PEE) shell with emanating poly(ethylene oxide) (PEO) chains that contact the water and screen the most unfavorable PFPO/hydrated PEO interactions. We further demonstrated that two incompatible agents could be separately and simultaneously stored in the discrete PEE and PFPO subdomains of these “hamburger-like” micelles with independent solubilization efficiencies,11 a feature desirable for drug delivery vehicles.12 As for laterally nanostructured vesicles, the combination of high toughness13 and controllable bilayer structure offers an intriguing possibility to mimic the properties of natural cell membranes.14 Previous investigations on diblock copolymers have established that an efficient strategy to manipulate micelle morphology is to vary the copolymer composition.15-18 As the ratio of (10) Li, Z; Kesselman, E.; Talmon, Y.; Hillmyer, M. A.; Lodge, T. P. Science 2004, 306, 98. (11) Lodge, T. P.; Rasdal, A.; Li, Z.; Hillmyer, M. A. J. Am. Chem. Soc. 2005, 127, 17608. (12) Kwon, G. S.; Forrest, M. L. Drug DeV. Res. 2006, 67, 15. (13) Discher, B. M.; Won, Y. Y.; Ege, D. S.; Lee, J. C. M.; Bates, F. S.; Discher, D. E.; Hammer, D. A. Science 1999, 284, 1143. (14) Li, Z.; Hillmyer, M. A.; Lodge, T. P. Nano Lett. 2006, 6, 1245. (15) Shen, H.; Eisenberg, A. Macromolecules 2000, 39, 2561.

10.1021/la802336k CCC: $40.75  2008 American Chemical Society Published on Web 09/13/2008

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case of poly(styrene)-b-poly(isoprene) (PS-PI) and PS-b-poly(dimethylsiloxane) (PS-PDMS).21,22 Furthermore, morphological changes in poly(styrene)-b-poly(acrylic acid) (PS-PAA) in dioxane-water mixtures could be reversed, consistent with thermodynamic equilibration.23 Similar transitions can also occur for triblock polymers.24-27 In this paper we report the self-assembly behavior of µ-EOF miktoarm stars in mixtures of THF and water; THF is good solvent for both PEE and PEO blocks and a poor solvent for the PFPO block. Two major effects are expected to occur upon the incorporation of THF into the aqueous media. On the one hand, the solvent becomes more selective for the PEE block as the THF content increases, thereby inducing the transition of the PEE block from the core to the corona and the consequent evolution from multicompartment micelles to mixed corona micelles. On the other hand, selective swelling of the PEE block changes the overall volume ratio of the solvophilic block(s) to the solvophobic block(s), resulting in micelle structural changes similar to those achieved by variation of copolymer composition.

Experimental Section

Figure 1. Rh distributions as a function of time obtained from dilute dispersions (1 wt %) in water: (a) µ-EOF(2-9-5), (b) µ-EOF(2-9-3). The scattering angle is 90°.

solvophilic block to solvophobic block increases, the micelle morphology transforms from vesicles to worms to spheres. A similar evolution has also been identified for µ-EOF multicompartment micelles, which change from laterally nanostructured vesicles and polygonal bilayers, to segmented or multicompartment worms and finally to hamburger-like micelles as the relative length of the hydrophilic PEO block increases.14,19 On the other hand, an increase of the PFPO block relative to the PEE block drives the micellar structure from hamburger-like micelles or segmented worms to raspberry-like micelles or multicompartment worms due to “double frustration”: the impossibility for the PFPO core to eliminate contact with the PEO corona, arising from their covalent junction, combined with the difficulty for the minority PEE component to screen most of the PFPO block.19 Solvent selectivity is another key parameter that can be used to control micelle morphology.20 As the solvent selectivity increases, interfacial tension increases, leading to the decreased interfacial area per chain and a corresponding morphology change (i.e., from spheres to wormlike micelles to vesicles). One advantage of this strategy is that various micelle morphologies can be achieved from a single block copolymer either in different selective solvents or their mixtures, as shown for example in the (16) Won, Y. Y.; Brannan, A. K.; Davis, H. T.; Bates, F. S. J. Phys. Chem. B 2002, 106, 3354. (17) Jain, S.; Bates, F. A. Science 2003, 300, 460. (18) Zupancich,; J, A.; Bates, F. S; Hillmyer, M. A Macromolecules 2006, 39, 4286. (19) Li, Z.; Hillmyer, M. A.; Lodge, T. P. Langmuir 2006, 22, 9409. (20) Lodge, T. P.; Bang, J.; Li, Z.; Hillmyer, M. A; Talmon, Y. Faraday Discuss. 2005, 128, 1.

Materials and Micelle Dispersions. Midhydroxyl-functionalized poly(ethylethylene)-b-poly (ethylene oxide) diblock copolymers (EO) were synthesized by two successive living anionic polymerizations, and µ-EOF star triblock copolymers were obtained through one coupling reaction between EO and an acid chloride end-functionalized PFPO, as described in detail elsewhere.28 The characteristics of the polymers employed here are summarized in Table 1. µ-EOF micelle solutions were prepared by direct dispersion of solid µ-EOF samples into the respective solvents or solvent mixtures to make 0.1 or 1 wt % dispersions. EO micelle dispersions were prepared using the thinfilm hydration protocol. EO was first dissolved in methylene chloride, the solvent was evaporated to give thin films, and solvents or solvent mixtures were then added to make 0.5 wt % solutions. All the micelle dispersions were stirred in sealed vials at room temperature for at least 2 weeks before analysis. Dynamic Light Scattering (DLS). All micelle dispersions were passed through 0.45 µm microfilters (Millipore) into 1 in. diameter optical glass tubes that were scrupulously dedusted. DLS measurements were carried out at 25 °C using a home-built photometer equipped with an electrically heated silicon oil bath, a Lexel 75 Ar+ laser operating at 488 nm, a Brookhaven BI-DS photomultiplier, and a Brookhaven BI-9000 correlator.29 The intensity autocorrelation functions, g2(t), were recorded at six angles ranging from 45° to 120°, and accepted when the baseline differences (calculated vs measured) were less than 0.1%. The cumulant expression eq 1 was used to fit the autocorrelation functions to extract the mean decay rate, Γ.

(

g2(t) - 1 ) A exp(-2Γ · t) 1 +

µ2 2 µ3 3 t - t +· · · 2! 3!

)

2

(1)

The mutual diffusion coefficient Dm was determined by linear regression of Γ vs q2, where q ) (4πn/λ) sin(θ/2) and n, λ, and θ (21) Bang, J.; Jain, S.; Li, Z.; Lodge, T. P.; Pedersen, J. S.; Kesselman, E.; Talmon, Y. Macromolecules 2006, 39, 1199. (22) Abbas, S.; Li, Z.; Hassan, H.; Lodge, T. P. Macromolecules 2007, 40, 4048. (23) Shen, H.; Eisenberg, A. J. Phys. Chem. B 1999, 103, 9473. (24) Du, H.; Zhu, J.; Jiang, W. J. Phys. Chem. B 2007, 111, 1938. (25) Pochan, D. J; Chen, Z.; Cui, H.; Hales, K.; Qi, K.; Wooley, K. L Science 2004, 306, 94. (26) Zhu, J.; Jiang, W. Macromolecules 2005, 38, 9315. (27) Bhargava, P.; Zheng, J. X.; Li, P.; Quirk, R. P.; Harris, F. W.; Cheng, S. Z. D. Macromolecules 2006, 39, 4880. (28) Li, Z.; Hillmyer, M. A.; Lodge, T. P. Macromolecules 2004, 37, 8933. (29) Pan, C.; Maurer, W.; Liu, Z.; Lodge, T. P.; Stepanek, P.; von Meerwall, E. D.; Watanabe, H. Macromolecules 1995, 28, 1643. (30) Jakes, J. Collect. Czech. Chem. Commun. 1995, 60, 1781. (31) Bellare, J. R.; Davis, H. T.; Scriven, L. E.; Talmon, Y. J Electron Microsc. 1988, 10, 87.

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Figure 2. CryoTEM images obtained from dilute dispersions in water: (a) µ-EOF(2-9-5) (0.1 wt %) at 37 days, (b) µ-EOF(2-9-5) (0.1 wt %) at 117 days, (c) µ-EOF(2-9-3) (1 wt %) at 37 days, (d) µ-EOF(2-9-3) (1 wt %) at 68 days. Scale bars indicate 100 nm.

are the solvent refractive index, laser wavelength and scattering angle, respectively. The hydrodynamic radius (Rh) was obtained via the Stokes-Einstein equation (eq 2),

Rh )

kBT 6πηsDm

(2)

where kB, T, and ηs are the Boltzmann constant, absolute temperature and solvent viscosity, respectively. The hydrodynamic radii distributions were extracted from the decay rate distributions generated through the inverse Laplace transform program REPES.30 Nuclear Magnetic Resonance Spectroscopy (NMR). 1H NMR spectra were recorded on a Varian Inova 500 MHz spectrometer at room temperature. µ-EOF was directly dispersed into deuterated water (D2O), THF(d8)-D2O mixed solvents and THF(d8) to make 0.6 wt % micelle dispersions. All the solutions were stirred for one week before NMR measurements. Cryogenic Transmission Electron Microscopy (CryoTEM). CryoTEM samples were prepared in a controlled environment vitrification system (CEVS) that was saturated with the corresponding solvent or solvent mixture at room temperature.31 The vitreous

samples were prepared by placing a drop of the micelle dispersion (5-10 µL) onto a lacey Formvar carbon-supported grid. The excess solution was blotted with a piece of filter paper to form thin films of 100-300 nm thickness in the holes. After allowing ca. 10 s to relieve the stress produced during the blotting, the sample was plunged into a reservoir of liquid ethane at its melting temperature (-183 °C). In the case of THF solutions, liquid nitrogen was chosen as the cryogen due to the negligible solubility of THF in liquid nitrogen. The vitrified samples were then kept in liquid nitrogen until they were mounted on a cryogenic sample holder (Gatan 626) and examined with a JEOL1210 TEM operating at 120 kV and -178 °C. The images were recorded on a Gatan 724 multiscan CCD, and processed with DigitalMicrographs version 3.3.1. The phase contrast enhancement was achieved at a nominal underfocus of 6-15 µm. The ramp-shaped optical density gradients in the background were digitally corrected. Transmission Electron Microscopy (TEM). Conventional TEM experiments were also performed for µ-EOF in pure THF. The micelle solutions were first diluted to ca. 0.1 wt % prior to sample preparation. Typically, a 2 µL drop of micelle solution was loaded onto a TEM

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Figure 3. Rh distributions obtained from a dilute dispersion (1 wt %) of µ-EOF(2-13-3) in water. The scattering angle is 90°.

grid. Most of the THF evaporated rapidly in a couple of minutes, and thus no blotting process was applied. The sample grids were allowed to dry overnight under ambient conditions. These grids were imaged at ambient temperature using a JEOL1210 TEM operating at 120 kV.

Results and Discussions In this report we will focus on two samples µ-EOF(2-9-5) and µ-EOF(2-9-3) (See Table 1) to study self-assembly in THF-H2O mixed solvents, as they access two distinct packing motifs in water determined by whether the majority core component is PFPO or PEE.19 µ-EOF in Aqueous Solutions. DLS was employed to monitor the size distributions of µ-EOF(2-9-5) and µ-EOF(2-9-3) micelles in dilute aqueous media at different time intervals to ensure the achievement of a steady state morphology. Figure 1 illustrates the evolution of the Rh distribution with time at a scattering angle of 90°. After about 12 days a bimodal distribution with peaks at 100 nm and 1 µm is observed in both cases. The former peak corresponds to the multicompartment micelles, while the latter can be attributed to larger aggregates. These aggregates eventually disperse under stirring, and the micrometer-sized peak is no longer observed after 28 days. After that point, only a slight decrease of Rh occurs and no further change is discerned after 60 days. CryoTEM is complementary to DLS, in that it enables the direct visualization of the detailed micelle structures, but only on limited sample volumes. Typical cryoTEM images of µ-EOF(2-9-5) and µ-EOF(2-9-3) micelles in dilute aqueous

Figure 5. Rh distributions obtained from dilute dispersions (1 wt %) in THF: (a) µ-EOF(2-9-5), (b) µ-EOF(2-9-3). The scattering angle is 90°.

solutions are shown in Figure 2 and in Figures S1 and S2. We assign the micelle morphologies observed in Figure 2b and d as disk-like rather than spherical due to their polygonal shape (particularly in Figure 2b) as well as the observation of a few large micelles whose size would exceed the thickness of the vitrified film if they were spherical (Figure S1d). In both cases, the micelle morphologies evolve slowly over time from branched multicompartment or segmented worms with lengths on the order of 100 nm to multicompartment disks with a core radius (major axis) of around 50 nm. The sizes of both the worms and disks

Figure 4. CryoTEM images obtained from a dilute dispersion (1 wt %) of µ-EOF(2-13-3) in water at (a) 14, (b) 120, (c) 410 days. Scale bars indicate 100 nm.

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Figure 6. CryoTEM and TEM images obtained from dilute dispersions (1 wt %) in THF: (a) cryoTEM image of µ-EOF(2-9-5), (b) TEM image of µ-EOF(2-9-5), (c, d) TEM images of µ-EOF(2-9-3). Scale bars indicate 100 nm.

Figure 7. Rh distributions obtained from dilute dispersions (0.5 wt %) of EO(2-9) in THF-H2O mixed solvents as a function of THF content. The scattering angle is 90°.

match the smaller Rh peak at about 100 nm fairly well (Figure 1), and no large aggregates were captured in the cryoTEM, presumably due to their large size. The earlier time micelle morphologies agree well with the previous reports;19 however,

they evidently are metastable, and can transform into disks over longer periods. Therefore, the multicompartment disks are chosen as the reference for comparison with the micelles formed in the THF-H2O mixed solvents and pure THF. To check whether this structural evolution is common for µ-EOF micelles in water, we also examined an aqueous dispersion of µ-EOF(2-13-3) to assess the effect of the PEO block length. DLS results show that the initially bimodal distribution of µ-EOF(2-13-3) micelle sizes is no longer observed within 90 days and a predominant size distribution centered around 40 nm is apparent after extended times (Figure 3). Meanwhile, the micelle structures change from segmented worms and hamburger-like micelles to multicompartment disks and (presumably laterally nanostructured) vesicles (Figures 4 and S3). Thus, both DLS and cryoTEM show that µ-EOF(2-13-3) micelles experience structural evolution similar to µ-EOF(2-9-5) and µ-EOF(2-9-3). However, the longer PEO chains apparently retard the evolution process, as now it takes the worms and hamburgers more than 120 days to complete the transition. Hence, regardless of the initial micelle structures, µ-EOF micelles in water eventually

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Figure 8. 1H NMR results obtained from dilute dispersions (0.6 wt %) of µ-EOF(2-9-5) in THF(d8)-D2O mixed solvents with different THF(d8) contents: (a) 1H NMR spectra and (b) the integration area ratios of the PEE peaks to the PEO peak vs the THF content calculated from (a).

adopt morphologies with mostly flat interfaces such as disks or vesicles to minimize the extremely strong repulsion between the PFPO core and the solvated PEO corona, as anticipated for the superstrong segregation regime.4,32,33 µ-EOF in THF. We also investigated the self-assembly of µ-EOF(2-9-5) and µ-EOF(2-9-3) in pure THF. DLS and cryoTEM were again applied to analyze the micelle morphologies at different time intervals. No significant size and morphology changes were observed over time, presumably due to the overall improvement of the solvent quality, which significantly accelerates the dynamics of structural evolution (Figures 5, 6, S4, and S5).34 The average Rh of µ-EOF(2-9-5) micelles in THF is 84 nm (obtained from cumulant analysis), which is nearly twice as large as that of the µ-EOF(2-9-3) micelles (48 nm) (Figure 5). This could be attributed to the longer PFPO chains in µ-EOF(2-9-5), which favor larger micelle size to minimize the total interfacial area, and thus the interfacial energy between the core and the solvated corona. Compared with the aqueous solutions, these micelles have narrower size distributions, indicating that a more well-defined micelle morphology forms in THF. (32) Semenov, A. N.; Nyrkova, I. A; Khokhlov, A. R Macromolecules 1995, 28, 7500. (33) Dormidontova, E. E.; Khokhov, A. R. Macromolecules 1997, 30, 1980. (34) Willner, L.; Poppe, A.; Allgaier, J.; Monkenbusch, M.; Richter, D. Europhys. Lett. 2001, 55, 667.

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The cryoTEM images of these THF dispersions (Figures 6a, S4a-b, and S5a) show that µ-EOF(2-9-5) and µ-EOF(2-9-3) form large sphere-like and ellipsoidal micelles, with sizes consistent with the DLS results. However, we have previously shown that PFPO core prefers a flat interface even in an organic solvent,35 thus we cannot rule out the possibility that the micelles observed in Figure 6a are actually disk-like. The cryoTEM images (Figures 6a and S5a) are not definitive since the confinement into thin films might have induced the micelles to lie along their longest dimension. Furthermore, the contour lengths of the PFPO block are 7.5 nm for µ-EOF(2-9-3) and 11.5 nm for µ-EOF(2-9-5), thus the core size along the thickness direction (vertical to the vitrified film) should not be larger than twice the contour length. Therefore, we conclude that these micelles are oblate rather than spherical. Conventional TEM was employed to confirm this interpretation. The TEM images (Figures 6b-d, S4c-d, and S5b-c) support the formation of oblate ellipsoidal micelles rather than spherical micelles, since most micelles lay onto the grids and collapsed to form elliptical aggregates instead of the spherical aggregates during the TEM sample preparation. Overall, these results are consistent with the formation of µ-EOF micelles with a mixed PEE and PEO corona in THF. µ-EOF in THF-H2O. In water the PEE block is segregated from the PFPO block in the core of the micelles. In THF the PEE block forms a mixed corona with the PEO block. Therefore, there should be a transition of the PEE block from the micelle core to the corona in THF-H2O mixtures. To explore this, we evaluated the micelle morphologies for the µ-EOF samples as a function of THF content. Initially we monitored the time dependence of µ-EOF micelle structure in THF-H2O mixed solvents, but no temporal evolution of structure was observed for THF contents from 30 to 60 wt % (Figures S6-S13). As a reference to assess the changing solvent quality, we explored the self-assembly of a diblock sample EO(2-9) in THF-H2O mixtures. From the DLS results, three regimes could clearly be identified: 0-30 wt % THF, 50-60 wt % THF and greater than about 60 wt % THF (Figures 7 and S15). CryoTEM images show that EO(2-9) forms spherical micelles in dilute aqueous solution (Figure S16), and these spherical micelles are retained in a mixed solvent containing up to 30 wt % THF, but with a smaller average micelle size due to the decreasing aggregation number arising from the improvement of the solvent quality. Upon further increasing the THF content to 50 or 60 wt %, the PEE core is so swollen by THF that the volume ratio of the PEO corona to the PEE core decreases significantly, leading to a transition of the micelle morphology to worms or vesicles which usually have larger micelle size and broader size distribution than spherical micelles.36,37 Beyond 60 wt % THF, the solvent becomes good for both PEE and PEO and thus no EO micelles form (the Rh peak at around 1 nm from the DLS data is due to dissolved EO chains, not micelles.) Therefore, the transition of the PEE block from the core to the corona in miktoarm star micelles is expected to occur around 60 wt % THF. 1H NMR measurements were carried out to confirm the transition of the PEE chains from the core to the corona by examining µ-EOF(2-9-5) in mixtures of THF(d8) and D2O. Figure 8 summarizes the 1H NMR spectra showing the PEE resonances between 0.8 and 1.8 ppm and the PEO resonance at 3.8 ppm, as well as the ratio of the integrated area of the PEE resonances to the PEO resonances vs THF content. (The modest (35) Edmonds, W. F.; Li, Z.; Hillmyer, M. A.; Lodge, T. P. Macromolecules 2006, 39, 4526. (36) He, Y.; Li, Z.; Simone, P.; Lodge, T. P. J. Am. Chem. Soc. 2006, 128, 2745. (37) He, Y.; Lodge, T. P. J. Am. Chem. Soc. 2008, 128, 12666.

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Figure 9. CryoTEM images obtained from dilute dispersions (1wt %) of µ-EOF(2-9-5) in THF-H2O mixed solvents at different THF contents: (a) 31 wt % THF, (b) 52 wt % THF, (c) 52 wt % THF, (d) 60 wt % THF. Scale bars indicate 100 nm.

shifts of the PEE and PEO peak positions are due to the variation of the solvent composition.) The PEE block is insoluble in water and is located in the core of the micelles, and no signal is observed due to its extremely long relaxation time. As the THF content increases, the solvent becomes more selective for PEE, leading to the increasing swelling of the PEE block by THF. This accelerates the dynamics of the PEE block, and thus the PEE peak appears in 1H NMR spectroscopy with increasing peak area. At 35 wt % THF, apparently the PEE block is swollen by the THF, but its dynamics are not as fast as the PEO corona, indicated by the smaller PEE/PEO ratio than the theoretical value based on the copolymer composition. Combined with the previous DLS results that show the preservation of spherical EO micelles at 30 wt % THF, we speculate that the PEE block is still embedded in the core, and the multicompartment micelles are formed in the mixed solvent with THF content up to about 30 wt %. When the THF content reaches 50 wt %, the observed PEE/PEO integration ratio is very close to the theoretical value, indicating that the PEE dynamics are too fast to be in the core. The DLS results for EO(2-9) shows that the mixed solvent is still somewhat selective for PEO, thus we speculate that the PEE block does not

behave as if it were completely in the corona. Therefore, the PEE block may be in an intermediate state between the PFPO core and the PEO corona, possibly leading to the formation of approximately core-shell-corona micelles, where the “shell” comprises THF-swollen PEE blocks plus some PEO. Beyond 60 wt % THF, DLS and 1H NMR data are consistent and indicate the formation of mixed corona micelles. The transition of the PEE block from the core to the corona is also indicated by the increasing mobility of the PEE chains with THF content, which results in a narrower full-width at half-maximum (Figure S17).38 In addition to the overall transition from multicompartment to mixed corona micelles, the detailed micelle morphologies are also expected to evolve due to changes in the volume fraction of the solvophilic block(s) and solvophobic block(s). As shown in Figure 9a, when the THF content reaches about 30 wt %, the multicompartment disks still persist for µ-EOF(2-9-5) as expected from the previous DLS and 1H NMR results. The smaller size of these disks could be attributed to the improvement of the (38) Matsuda, K.; Hibi, T.; Kadowaki, H.; Kataura, H.; Maniwa, Y. Phys. ReV. B 2006, 74, 073415.

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Figure 10. CryoTEM images obtained from dilute dispersions (1 wt %) of µ-EOF(2-9-3) in THF-H2O mixed solvents at different THF contents: (a) 31 wt % THF, (b) 31 wt % THF, (c) 52 wt % THF, (d) 60 wt % THF. Scale bars indicate 100 nm.

solvent quality, which decreases the average micelle aggregation number. Figure 10a reveals the emergence of some nanostructured vesicles for µ-EOF(2-9-3) in addition to multicompartment disks (see, for example, Figure 10b). In particular, some vesicles share parts of the flat walls (Figure 10a), possibly representing an intermediate state between disks and vesicles. Upon further increasing the THF content to 50-60 wt %, the cryoTEM images show the formation of the short worms and spheres (Figures 9b-d and 10c-d), possibly with a core-shell-corona structure as indicated by the previous DLS and 1H NMR results. This morphological change can be understood in terms of the increasing volume fraction of the solvophilic blocks (PEE+PEO) to the solvophobic block (PFPO), since the swollen PEE chains are now able to shield the PFPO core to some extent. The significant swelling of the PEE+PEO “shell” by THF reduces the contrast difference between the shell and the vitrified film, and thus the shell could not readily be observed by cryoTEM and thus some of the wormlike structures appear to be “discontinuous”, resembling a string of spheres (Figure 9c). In addition, the central parts of some spheres in Figure 9b-c exhibit reverse contrast

caused by beam damage, as the vitrified organic materials are very sensitive to the electron beam (Figure S14).39,40 Overall, the µ-EOF micelle morphology evolves from the disks and vesicles to the mixture of worms and spheres in THF-H2O mixed solvents with increasing THF content. A more detailed discussion of the various factors that dictate the structure of micelles formed from miktoarm star terpolymers has been given previously.19

Conclusions We have systematically investigated the structural evolution of µ-EOF(2-9-5) and µ-EOF(2-9-3) micelles in H2O, THF and mixtures of THF and H2O, as summarized in Figure 11. DLS and cryoTEM measurements show that these miktoarm stars self-assemble into multicompartment disk-like micelles in dilute aqueous solutions. In mixtures of THF and H2O, DLS results on EO(2-9) and 1H NMR spectra of µ-EOF(2-9-5) consistently (39) Kesselman, E.; Talmon, Y.; Bang, J.; Abbas, S.; Li, Z.; Lodge, T. P. Macromolecules 2005, 38, 6779. (40) Simone, P. M.; Lodge, T. P. Macromol. Chem. Phys. 2007, 208, 339.

Multicompartment Micelles to Mixed Corona Micelles

Langmuir, Vol. 24, No. 20, 2008 12009

Figure 11. Schematic cartoons and illustrative cryoTEM and TEM images of the micelle structural evolution described in the text.

indicate that the structures formed by µ-EOF evolve from multicompartment micelles to core-shell-corona micelles to mixed corona micelles as THF content increases. The micelle morphology evolves upon addition of THF due to the increasing volume faction of the solvophilic block(s) relative to the solvophobic block(s) arising from the swelling of the PEE chains. At 30 wt % THF, the multicompartment disks persist but are smaller in size. Upon further increasing THF content to 50-60 wt %, µ-EOF forms worm-like and spherical micelles with an approximately core-shell-corona structure. The transition of the PEE block from the core to the corona is completed near 60 wt % THF, and thus mixed corona elliptical oblate micelles are obtained from self-assembly of µ-EOF in pure THF. Collectively, these results demonstrate how micelle structure evolves and can be controlled by controlling solvent composition.

Acknowledgment. This work was supported by the MRSEC program of the National Science Foundation under Award No. DMR-0212302 at the University of Minnesota. Parts of this work were carried out in the University of Minnesota I.T. Characterization Facility, which receives partial support from NSF through the NNIN program. We thank Dr. Zhibo Li for providing the polymer samples, and John Zupancich and Peter Simone for initial help with the cryoTEM experiments and fruitful discussions. Supporting Information Available: Complementary DLS and H NMR results, cryoTEM and TEM images of µ-EOF and EO micelles in H2O, THF-H2O mixed solvents and THF (Figures S1-S17). This material is available free of charge via the Internet at http://pubs.acs.org. 1

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