© Copyright 2007 American Chemical Society
JULY 17, 2007 VOLUME 23, NUMBER 15
Letters Formation of Tethered Polyacrylic Acid Loops in Core-Shell Micelles Michael R. Whittaker, Carl N. Urbani, and Michael J. Monteiro* Australian Institute of Bioengineering and Nanotechnology, School of Molecular and Microbial Sciences, UniVersity of Queensland, Brisbane QLD 4072, Australia ReceiVed March 12, 2007. In Final Form: May 9, 2007 Well-defined amphiphilic four-arm star P(AA-b-STY) block copolymers have been dispersed in water to form core-shell micelles in which the shell consists of tethered PAA loops. The entropic penalty for having such loops resulted in a less densely packed PSTY core when compared to linear diblock copolymers of the same arm length. The surface of the shell is irregular because of the tethering points, but when cleaved the PAA chains extend to form a regular and relatively uniform corona.
Introduction In this letter, we demonstrate a nonintuitive strategy to tether hydrophilic polymer loops upon micellization of well-defined amphiphilic four-arm star block copolymers. The four-arm stars consist of four poly(acrylic acid-block-styrene), P(AA-b-STY), arms attached to a core molecule in which the PAA blocks are located in the interior and PSTY is located at the exterior of the star (Scheme 1). Micellization of these star polymers in water results in core-shell polymer nanostructures that produce unusual PAA architectures (i.e., tethered loops) in the shell (Scheme 1). The micelles have been characterized using dynamic light scattering (DLS) and asymmetric field flow fractionation (FFF) to obtain information about the hydrodynamic diameter, radius of gyration, aggregation number, and polydispersity of the aggregates. The tethered loops are easily cleaved to produce diblock copolymers of PAA-PSTY, and the resulting changes in micelle characteristics have been also studied. The micellization of complex architectures has attracted great attention, especially miktoarm block copolymers,1,2 graft co* Author to whom correspondence should be sent. E-mail: m.monteiro@ uq.edu.au. (1) Hadjichristidis, N.; Iatrou, H.; Behal, S. K.; Chludzinski, J. J.; Disko, M. M.; Garner, R. T.; Liang, K. S.; Lohse, D. J.; Milner, S. T. Macromolecules 1993, 26, 5812-5815.
polymers,3,4 dendrimers,5 and stars.6-8 The latter have the potential to form unimolecular micelles in water.7 Recently, we showed that core-shell micelles consisting of amphiphilic four-arm star block copolymers (where PSTY was in the interior and PAA was at the exterior of the star) were formed in which approximately 15 stars aggregated to form a micelle.8 It was proposed that because of the restricted movement of the arms tethered to the core molecule in the star, the PAA segments in the shell were not fully extended. Only after the addition of piperidine to the micelle solution, which cleaved the arms from the core molecule, did PAA became fully extended. In most described cases, the hydrophilic polymer is located at the exterior of the polymer particle, which results in different types of nanostructures in water, ranging from micelles to vesicles to rods. However, there are only a few examples where the micellization process itself was used to form new polymer architectures. The use of BAB block copolymers (where B is a hydrophobic block and A is a (2) Pispas, S.; Hadjichristidis, N.; Potemkin, I.; Khokhlov, A. Macromolecules 2000, 33, 1741-1746. . (3) Ma, Y.; Cao, T.; Webber, S. E. Macromolecules 1998, 31, 1773-1778. (4) Eckert, A. R.; Webber, S. E. Macromolecules 1996, 29, 560-567. (5) Tomalia, D. A.; Berry, V.; Hall, M.; Hedstrand, D. M. Macromolecules 1987, 20, 1164-1167. (6) Chen, X.; Smid, J. Langmuir 1996, 12, 2207-2213. (7) Heise, A.; Hedrick, J. L.; Frank, C. W.; Miller, R. D. J. Am. Chem. Soc. 1999, 121, 8647-8648. (8) Whittaker, M. R.; Monteiro, M. J. Langmuir 2006, 22, 9746-9752.
10.1021/la700724h CCC: $37.00 © 2007 American Chemical Society Published on Web 05/19/2007
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Letters Scheme 1
Table 1. Molecular Weight Data for the Synthesis of Star Block Copolymers in Toluene at 60 °C Using RAFT-Mediated Polymerizationa entry
block copolymer
time (min)
fract. conv. (x)
Mn star (theory)
Mn (SEC)
PDI (SEC)
1 2 3 4 5 6 7 8 9
(PSTY153)4d (PSTY153-tBA33)4 (PSTY153-tBA87)4 (PSTY153-tBA175)4 (PSTY153-tBA234)4 (PSTY153-tBA33)e (PSTY153-tBA87)e (PSTY153-tBA175)e (PSTY153-tBA234)e
1290 120 240 360 480
0.66 0.065 0.181 0.381 0.527
69 359 (61 388)f 81 749 (71 288)f 109 371 (96 504)f 154 970 (127 864)f 184 916 (138 808)f
65 160b 65 320b 71 310b 85 460b 86 850b 17 530c 23 840c 31 680c 34 410c
1.04 1.04 1.13 1.19 1.25 1.23 1.6 1.26 1.31
a [PSTY-macroRAFT] ) 0.65 Mmol/L; [AIBN]) 0.73 mM). b Determined from light scattering. c Determined from RI detection. d Polymerization was carried out at 110 °C with thermal initiation using a RAFT concentration of 8.84 mmol/L. e Star-block polymers were cleaved to the arms using piperidine. f Mn ) 4 × Mn of arm.
hydrophilic block) has been shown to form loops of block A in the micelle shell9,10 (Scheme 1). However, once these loops are bound to a solidlike (or kinetically frozen) micelle core, they cannot be opened. The aim of this work was to use the micellization process to produce complex polymer architectures in which the loops are tethered together and easily opened when desired, leading to possible applications in host-guest devices11 for drug and gene
delivery. The strategy used in this work is nonintuitive and relies on the micellization of block star copolymers in which the hydrophilic polymer is located at the interior and the hydrophobic polymer is located at the exterior of each star molecule. It would be expected that the hydrophobic polymer would shield the hydrophilic polymer from stabilizing the micelle, but conditions were found in this work where the block length of PAA was sufficiently high to produce stable micelles.
(9) Booth, C.; Attwood, D. Macromol. Rapid Commun. 2000, 21, 501-527. (10) Zhou, Z.; Chu, B.; Nace, V. M.; Yang, Y.-W.; Booth, C. Macromolecules 1996, 29, 3663-3664. (11) Meier, M. A. R.; Gohy, J.-F.; Fustin, C.-A.; Schubert, U. S. J. Am. Chem. Soc. 2004, 126, 11517-11521.
Synthesis of Four-Arm Star Block Copolymers. The approach to preparing amphiphilic four-arm star-block copolymers was by the Z-group RAFT methodology with a tetrafunctional RAFT agent12 (Scheme 1). First, PSTY was grown from
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Langmuir, Vol. 23, No. 15, 2007 7889
Table 2. Characterization of Linear and Four-Arm Star Amphiphilic Diblock Copolymer Micelles in DMF, Toluene, and Water water entry
DMF DH (nm)
1. poly(STY153-AA33) 2. poly(STY153-AA87) 3. poly(STY153-AA175) 4. poly(STY153-AA234)
4.7 5.0 6.2 6.3
5. poly(STY153-AA33)4 6. poly(STY153-AA87)4 7. poly(STY153-AA175)4 8. poly(STY153-AA234)4
5.9 8.4 8.9 7.9
toluene DH (nm)
DH (nm)
Linear Diblock Copolymers 24.9 39.2 55 42.5 91 44.5 79
Rg
Mw × 106
PDI
aggregation number (Z)a
23.8 30.0 29.2
7.4 7.5 4.56
1.03 1.08 1.07
400 (100) 348 (87) 176 (44)
4.6 5.2
1.05 1.12
53 58
4.0 5.0
1.02 1.10
188 (47) 224 (56)
Four-Arm Star Diblock Copolymers 16.8 28.8 32.4 88 66.3 29.7 97 40.3 Arm Cleavage of Stars with Piperidine
9. poly(STY153-AA33) 10. poly(STY153-AA87) 11. poly(STY153-AA175) 12. poly(STY153-AA234) a
69 85
29.4 30.4
Z values in parentheses are the four-arm star equivalents.
the RAFT agent, and t-butyl acrylate (tBA) was then copolymerized to obtain a four-arm block copolymer star consisting of (PSTY-PtBA)4. The monomers were inserted via the core, and the arms were grown outward, resulting in a PSTY shell and a PtBA core. The PtBA block was then hydrolyzed with trifluoroacetic acid to PAA to form the desired product (i.e., PSTY at the exterior and PAA in the interior of the star). This coregrowth RAFT methodology has the advantage that it produces only linear dead polymer and “living” star-block copolymers; no star-star coupling occurs because the RAFT moieties are always at the center of the star.12 The evolution of the molecular weight of the star-block copolymer is given in Table 1. The numberaverage molecular weight (Mn) of the starting (PSTY153)4 is close to theory, and its polydispersity (PDI) is low (1.04), suggesting that there is little linear dead polymer in the system. Chain extension with tBA results in star polymers with a low PDI (below 1.25). To determine the molecular weight distribution of the arms on the star, piperidine was used to cleave the linkage between the block arms and trithiocarbonate core molecule. The cleavage of the trithiocarbonate linkages with piperidine is quantitative as determined from the loss of absorption in the UV-vis spectrum at 310 nm (which corresponds to trithiocarbonate).8 The Mn of the arms multiplied by 4 (values given in parentheses in Table 1) shows good agreement with theoretical Mn values of the stars, confirming that well-defined star structures have been synthesized. It can be seen that there is a systematically higher PDI for the linear arms than for the star diblock copolymers. The reason for this is that the coupling of two or more polymers with a broad distribution via a random process will lead to a resulting distribution that is narrower than the original starting polymer distributions, termed the random coupling process.13 Micellization of Stars. The characterization of amphiphilic linear diblocks (PSTY-PAA) and stars ((PSTY-PAA)4) in various solvents was carried out using dynamic light scattering (DLS). The number-average hydrodynamic diameter (DH) in DMF, toluene, and water is given in Table 2. In DMF, a good solvent for both blocks, the diameter is small (5.9 nm, entry 5) but increases with the number of monomer units of AA (7.9 nm, entry 8). The linear diblock copolymers (entries 1-4 in Table (12) Mayadunne, R. T. A.; Jeffery, J.; Moad, G.; Rizzardo, E. Macromolecules 2003, 36, 1505. (13) Tanaka, T.; Omoto, M.; Inagaki, H. J. Macromol. Sci. Phys. 1980, B17, 211.
1) are smaller in size (4.7-6.3 nm) but increase with the number of AA units. This size is consistent with unimolecular star micelles with a random coil conformation. When the stars are solubilized in toluene, a good solvent only for PSTY, the size dramatically increases (from 5.9 to 16.8 nm - entry 5), a trend that is observed for stars with a greater number of AA units. This trend is also observed with the linear diblock copolymers (entries 1-4). This suggests that either the unimolecular micelles coagulate to form higher aggregate micelles (Scheme 1) or the PSTY chains extend well into the toluene, stretching the arms to form an inverse micelle. A concentrated solution of linear diblock copolymers (entries 1-4) in DMF has then been dispersed in water through the slow addition of water over a 17 h period. At the lowest number of AA units per arm (entry 1), precipitation occurs, and there is no observation of micelles or other high-order aggregates. The hydrodynamic diameter increases from 55 nm (entry 2) to 91 nm (entry 3) and decreases to 79 nm (entry 4) with the increasing number of AA units per star. The radius of gyration shows the same trend (ranging from 24 to 30 nm), suggesting that as the AA content increases the core size remains relatively constant but the size of the PAA shell increases. The star polymers with 33 and 87 units of AA per arm have precipitated during micellization attempts (entries 5 and 6), and there has been no evidence of micelles or other structures by transmission electron microscopy (TEM) or DLS. Micelles are observed only when the number of AA units is greater than that of 153 units of STY per arm (entries 7 and 8). The size increases from 88 to 97 nm, but Rg decreases from 66.3 to 40.3 nm as the number of AA units per arm increases from 175 to 234. This suggests that the PSTY core is not densely packed as compared to the linear diblocks (entries 3 and 4) and that the entropic penalty of having tethered PAA chains in the shell extends the PSTY chains in the core. The aggregation number for the star micelles is similar (53 and 58 stars per micelle for entries 7 and 8, respectively), which is in a range similar to that of the linear diblocks of 87 and 44 equivalent four-arm stars per micelle. This suggests that the stars have a similar influence on the micellization process to that of the linear diblocks. Negatively stained TEM images of the micelles (entry 8) shows a distinct core-shell morphology (Figure 1A), but with an irregular shell as depicted in Scheme 1. It is believed that the irregularity is due to the formation of tethered loops of PAA to the solid-like PSTY core.
7890 Langmuir, Vol. 23, No. 15, 2007
Figure 1. TEM with negative staining of (A) four-arm star block copolymer (entry 8; scale bar ) 0.2 µm), and (B) after cleavage with piperidine (entry 12; scale bar ) 0.5 µm). The images show classical core-shell morphology.
Micelles in water (entries 7 and 8) have been treated with piperidine to cleave the arms from the trithiocarbonate (-S(CdS)-S-) core molecule. UV-vis spectroscopy shows that after treatment with piperidine there is no absorbance at 310 nm corresponding to the trithiocarbonate moiety, suggesting quantitative cleavage of the arms to form diblock copolymers. The
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hydrodynamic diameter (DH) decreases from 88 to 69 nm (entry 7 vs 11) and also decreases from 97 to 85 nm with an increasing number of AA units (entry 8 vs 12). More importantly, Rg significantly decreases from 66.3 to 29.4 nm for stars with 175 AA units per arm (entries 7 and 11, respectively), and a similar trend is found for 234 AA units per arm in which Rg decreases from 40.3 to 30.4 nm (entries 8 and 12, respectively). The Rg values for the cleaved stars have similar values to those of the linear diblocks. The aggregation numbers do not significantly differ on the basis of equivalent four-arm stars per micelle, suggesting that there is little or no diblock diffusion to other micelles, and the solid-like PSTY core anchors the diblocks to the micelle. These results are significant because they clearly show that cleaving the PAA chains from each other to form linear species reduces the entropic penalty and allows the PSTY core to reorder and become more densely packed, with a packing density similar to that of linear diblocks.14 The TEM of the piperidine-treated micelles (Figure 1B) shows a more uniform and extended PAA shell. In summary, well-defined amphiphilic four-arm star P(AAb-STY) block copolymers have been dispersed in water to form core-shell micelles in which the shell consists of tethered PAA loops. The entropic penalty for having such loops resulted in a less densely packed PSTY core when compared to that of linear diblock copolymers of the same arm length. The surface of the shell is irregular because of the tethering points, but when cleaved, the PAA chains extend to form a regular and relatively uniform corona. Supporting Information Available: Experimental and UVvis spectrum of the loss of trithiocarbonate moieties from the star. This material is available free of charge via the Internet at http://pubs.acs.org. LA700724H (14) Kim, K. H.; Huh, J.; Jo, W. H. J. Chem. Phys. 2003, 118, 8468-8475.
