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Langmuir 2003, 19, 3198-3201
Spontaneous Vesicle Formation of Short-Chain Amphiphilic Polysiloxane-b-Poly(ethylene oxide) Block Copolymers Guido Kickelbick,*,† Josef Bauer,† Nicola Hu¨sing†, Martin Andersson,‡ and Anders Palmqvist‡ Institut fu¨ r Materialchemie, Technische Universita¨ t Wien, Getreidemarkt 9/165, A1060 Wien, Austria, and Department of Applied Surface Chemistry, Chalmers University of Technology, SE-412 96 Go¨ teborg, Sweden Received October 28, 2002. In Final Form: January 20, 2003 Short-chain amphiphilic diblock copolymers composed of polysiloxane and poly(ethylene oxide) segments show a spontaneous vesicle formation in water. The surfactants were formed with high yields and purity by a hydrosilation coupling reaction between the Si-H-functionalized polysiloxane and the allyl-modified poly(ethylene oxide) block. The phase behavior of the resulting macromolecules was investigated with cryogenic transmission electron microscopy. Depending on the composition of the block copolymer and its concentration in water, the spontaneous formation of vesicles and their transition to lamellar structures were observed.
Introduction Amphiphilic block copolymers have attracted much interest recently due to their tendency to self-assemble and to their compatibilizing properties. Polymers based on hydrophilic poly(ethylene oxide) (PEO) blocks and hydrophobic poly(propylene oxide) (PPO) blocks are the most widely studied class of amphiphilic block copolymers, but many other types have been investigated as well. The solution behavior of the block copolymers depends strongly on their different solubilities and on the weight ratio of the hydrophilic and the hydrophobic blocks. The PEOPPO block copolymers at low concentration in water normally form micelles, with the PPO blocks forming the hydrophobic core and the PEO blocks protruding out into the water. At higher concentration surfactant liquid crystals, i.e., mesophases with distinct order over larger distances but with short-range disorder, form. The surfactant liquid crystalline phases may coexist with water. Examples of such mixtures are cubosomes, i.e., dispersions of a cubic phase in water,1,2 hexosomes, i.e., dispersions of a hexagonal phase in water,3 and liposomes, i.e., dispersions of a lamellar phase in water. Liposomes are also referred to as vesicles. Cubosomes and hexosomes (particularly dispersions of a reverse hexagonal phase in water) are usually made by the use of a surface-active polymer as emulsifier. Liposomes are usually prepared without any external emulsifier. Much interest has been devoted to vesicles, partly because of their stability in water and partly due to the possibility to use them for drug delivery applications.4 Most vesicular solutions are not thermodynamically stable, but the phase separation into water and a lamellar phase may take weeks or months. * To whom correspondence should be addressed. Fax: (+43)158801-15399. E-mail:
[email protected]. † Technische Universita ¨ t Wien. ‡ Chalmers University of Technology. (1) Andersson, S.; Jacob, M.; Ladin, S.; Larsson, K. Z. Kristallogr. 1995, 210, 315. (2) Nakano, M.; Sugita, A.; Matsuoka, H.; Handa, T. Langmuir 2001, 17, 3917. (3) Neto, C.; Aloisi, G.; Baglioni, P.; Larsson, K. J. Phys. Chem. B 1999, 103, 3896. (4) Langer, R. Science 1990, 249, 1527.
Polysiloxane-based block copolymers show amazing properties such as high hydrophobicity and flexibility, optical transparency, biocompatibility, etc. These characteristics make polysiloxanes interesting as blocks for the preparation of amphiphiles with properties different from those of many other purely organic polymers. The remarkable surface-active properties of polysiloxanes have already been shown by the investigation of the so-called “superspreaders” based on trisiloxanes.5,6 Two properties of the dimethylsiloxane chain, its flexibility and low cohesive energy, are responsible for the unusual properties of siloxane surfactants. Our aim was the investigation of the vesicle formation of short-chain poly(dimethylsiloxane) (PDMS) block copolymers and the comparison with the behavior of pure organic block copolymers7-17 that often exhibit long hydrophobic chains. An advantage of the reported approach is the increased hydrophobicity of PDMS, combining it with a simple synthetic procedure. Nonionic polysiloxane ABA and comblike block copolymers have already shown their potential to aggregate in aqueous solutions.18-21 In this paper we present the synthesis and the spontaneous vesicle formation in water of short-chain amphiphilic diblock copolymers composed of short-chain (5) Rosen, M. J.; Wu, Y. Langmuir 2001, 17, 7296. (6) Wu, Y.; Rosen, M. J. Langmuir 2002, 18, 2205. (7) Zhang, L.; Eisenberg, A. Science 1995, 268, 1728. (8) Zhang, L.; Yu, K.; Eisenberg, A. Science 1996, 272, 1777. (9) Yu, K.; Eisenberg, A. Macromolecules 1996, 29, 6359. (10) Yu, Y.; Zhang, L.; Eisenberg, A. Langmuir 1997, 13, 2578. (11) Yu, Y.; Eisenberg, A. J. Am. Chem. Soc. 1997, 119, 8383. (12) Cornelissen, J. J. L. M.; Fischer, M.; Sommerdijk, N. A. J. M.; Nolte, R. J. M. Science 1998, 280, 1427. (13) Kabanov, A. V.; Bronich, T. K.; Kabanov, V. A.; Yu, K.; Eisenberg, A. J. Am. Chem. Soc. 1998, 120, 9941. (14) 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. (15) Shen, H.; Eisenberg, A. J. Phys. Chem. B 1999, 103, 9473. (16) Shen, H.; Eisenberg, A. Angew. Chem., Int. Ed. 2000, 39, 3310. (17) Luo, L.; Eisenberg, A. Angew. Chem., Int. Ed. 2002, 41, 1001. (18) Gradzielski, M.; Hoffmann, H.; Robisch, P.; Ulbricht, W.; Gru¨ning, B. Tenside, Surfactants, Deterg. 1990, 27, 366. (19) Hill, R. M.; He, M.; Lin, Z.; Davis, H. T.; Scriven, L. E. Langmuir 1993, 9, 2789. (20) Lin, Z.; Hill, R. M.; Davis, H. T.; Scriven, L. E.; Talmon, Y. Langmuir 1994, 10, 1008. (21) Stu¨rmer, A.; Thuning, C.; Hoffmann, H.; Gru¨ning, B. Tenside, Surfactants, Deterg. 1994, 31, 90.
10.1021/la026763c CCC: $25.00 © 2003 American Chemical Society Published on Web 03/11/2003
Spontaneous Vesicle Formation of PDMS-PEO Copolymers
PDMS as the hydrophobic component and PEO as the hydrophilic component.
Langmuir, Vol. 19, No. 8, 2003 3199 Scheme 1
Experimental Section Measurements. Relative size exclusion chromatography (SEC) measurements in THF were performed using a Waters system including a 515 HPLC pump, a 717 autosampler, a 2410 differential refractive index detector, and Styragel columns (HR 0.5, 3, and 4, linear) at 40 °C at a rate of 1 mL/min, applying linear polystyrene standards. Molecular weight analysis was calculated with Waters Millennium32 software including the GPC/V option and related to an internal standard (diphenyl ether). NMR spectra were recorded on a 300 MHz DRX Avance Bruker instrument working at 300, 75.43, and 59.6 MHz for 1H, 13C, and 29Si, respectively. GC/MS measurements were performed on a Finnigan Voyager instrument equipped with a CPSil-8 column (CHROMPACK). Materials. THF used for synthesis was distilled from solid KOH. Benzene and toluene were distilled from sodium. THF used as the solvent in polymerization experiments was additionally refluxed over potassium for 24 h and distilled under an argon atmosphere prior to use. Following purification all solvents were stored under an argon atmosphere. Hexamethylcyclotrisiloxane (D3) (Aldrich) was dissolved in benzene and stirred over calcium hydride overnight at reflux under argon. The solvent was removed by trap-to-trap distillation at reduced pressure. The monomer was then sublimed into another flask and stored at room temperature under argon. The purity of the monomer was checked by gas chromatography (GC/MS) and was found to be 99.8%. Dimethylchlorosilane (Wacker) was distilled under an argon atmosphere before use. Poly(ethylene oxide methyl ether) (ACROS) was purified by precipitation in MeOH before use, and allyl bromide (Aldrich) was distilled and stored under an argon atmosphere at 4 °C. Synthesis of Butylpoly(dimethylsiloxane)-Dimethylhydrosilylsiloxane. General Procedure. D3 was dissolved in THF at room temperature, forming a clear solution. n-BuLi was added to initiate the anionic ring-opening polymerization. After 3 h of the solution being stirred at room temperature, the reaction was quenched with dimethylchlorosilane. The organic phase was extracted three times with water. The phases were separated, the organic phase was dried over Na2SO4, and the solvent was evaporated. The products were analyzed by 1H NMR and SEC. Synthesis of Allyl-Terminated PEO Polymers. This synthesis was carried out according to a literature procedure.22 Preparation of PDMS-b-PEO Copolymers. A solution of Si-H-functionalized polysiloxanes and allyl-functionalized PEO blocks (1 mol/mol Si-H groups) was stirred at room temperature under an argon atmosphere. The polymers were coupled by a hydrosilation reaction, applying 10-4 mol/mol double bond Pt(0) catalyst (Karstedt catalyst). The solution was stirred for 10 h at room temperature and additionally for 24 h at 70 °C. After completion of the hydrosilation reaction (determined by 1H NMR and SEC), the excess silane and solvent were evaporated under reduced pressure at elevated temperature (40-50 °C). The products were purified by precipitation into dry methanol. 1H NMR (CDCl ): δ (ppm) 0.00-0.14 [m, OSi(CH ) O], 0.473 3 2 0.57 [m, PrCH2Si(CH3)2O, OSi(CH3)2CH2CH2CH2O], 0.92 [t, CH3PrSi(CH3)2O, 3J ) 6.7 Hz], 1.26-1.40 [m, CH3CH2CH2CH2Si, OSi(CH3)2CH(CH3)CH2O], 1.52-1.70 [m, OSi(CH3)2CH2CH2CH2O], 3.15 [s, OCH3], 3.30-3.38 [m, OSi(CH3)2CH2CH2CH2O, CH2CH2OCH3], 3.55-3.74 [m, PEO-H]. 13C NMR (CDCl ): δ (ppm) 0.3 [q, BuSi(CH ) O], 0.4 [q, OSi3 3 2 (CH3)2PrO], 0.9-1.6 [m, OSi(CH3)2], 14.0 [q, CH3CH2CH2CH2Si(CH3)2O], 14.7 [t, OSi(CH3)2CH2CH2CH2O], 18.2 [t, PrCH2Si(CH3)2O],24.1[t,OSi(CH3)2CH2CH2CH2O],25.7[t,CH3CH2CH2CH2Si(CH3)2O], 26.6 [t, CH3CH2CH2CH2Si(CH3)2O], 58.9 [q, CH3O], 70.6 [t, OSi(CH3)2CH2CH2CH2O], 70.8-71.1 [t, PEO-C], 72.4 [t, CH3OCH2CH2], 74.2 [t, OSi(CH3)2CH2CH2CH2O]. 29Si NMR (CDCl ): δ (ppm) -21.7 to -20.6 [m, Si(CH ) ], 7.8 3 3 2 [OSi(CH3)2PrO], 7.9 [BuSi(CH3)2O].
Si-H-functionalized PDMS was prepared via anionic ring-opening reactions of hexamethylcyclotrisiloxane quenched with dimethylchlorosilane. Applying hydrosilation with an allyl-functionalized PEO block, a variety of surfactants with different block lengths and, therefore, various relative molar ratios of the blocks were synthesized in high yields (Scheme 1). This preparation method offers the possibility for the large-scale synthesis of PDMS-bPEO diblock copolymers with a high degree of purity at low polydispersity. The purity of the diblock copolymers was proved by SEC and NMR. No homopolymer residues were detected after the purification procedure in the samples as was indicated by a complete shift to lower retention volumes with no signals in the homopolymer range. Table 1 shows the properties of the two block copolymers for which vesicle formation was studied in this paper. Although there are distributions on the EO and DMS chain lengths, the completeness of the hydrosilation reactions, which was determined by 1H NMR experiments, is typically in the range of 95-99%. The spontaneous formation of vesicles was shown by applying two low molecular weight PDMS-b-PEO diblock copolymers. Aqueous solutions of PDMS4-b-PEO12 (4
(22) Mitchell, T. N.; Heesche-Wagner, K. J. Organomet. Chem. 1992, 436, 42.
(23) Gustafsson, J.; Oraedd, G.; Nyden, M.; Hansson, P.; Almgren, M. Langmuir 1998, 14, 4987.
Cryogenic Transmission Electron Microscopy (CryoTEM). Aqueous samples of the PDMS4-b-PEO12 and PDMS10b-PEO12 diblock copolymers in different concentrations were prepared by adding doubly distilled water to the compounds and sonicating them for 5 min. After resting overnight at room temperature, the samples were shaken again, and the cryo-TEM samples were prepared. Specimens for electron microscopy were prepared in a controlled environment vitrification system (CEVS),23 to ensure fixed temperature (301.15 K) and high humidity (saturated with water) to avoid water loss from the solution during sample preparation. In brief, an 8 µL drop of the sample was put on a lacy carbon film, supported by a copper grid. Then, the drop was gently blotted with filter paper, to create a thin liquid film over the grid, and rapidly plunged into liquid ethane at its melting temperature. The technique produces vitrified specimens; i.e., the water is supercooled and does not undergo crystallization during fixation. In this way, the original fluid microstructure is preserved and component segregation and rearrangement are prevented. The vitrified specimens were stored under liquid nitrogen and then transferred to a Phillips CM120 BioTWIN cryo electron microscope using an Oxford CT3500 cryoholder and its workstation. Specimens were kept in the microscope and imaged at a temperature of about 93.5 K. Images were recorded digitally with a CCD camera (Gatan MSC791), and
