5848
Langmuir 2007, 23, 5848-5851
Preparation of Novel Fluoroalkyl-End-Capped 2-Acrylamido-2-methylpropanesulfonic Acid Cooligomeric Nanoparticles Containing Adamantane Units Possessing a Lower Critical Solution Temperature Characteristic in Organic Media Masaki Mugisawa,† Keiichi Ohnishi,‡ and Hideo Sawada*,† Department of Frontier Materials Chemistry, Faculty of Science and Technology, Hirosaki UniVersity, Bunkyo-cho, Hirosaki 036-8561, Japan, and Asahi Glass Company, Ltd., Yurakucho, Chiyoda-ku, Tokyo 100-8405, Japan ReceiVed July 15, 2006. In Final Form: February 6, 2007 Fluoroalkyl-end-capped 2-acrylamido-2-methylpropanesulfonic acid cooligomers containing adamantyl segments were prepared by reaction of fluoroalkanoyl peroxide with 2-acrylamido-2-methylpropanesulfonic acid (AMPS) and 3-hydroxy-1-adamantyl acrylate (Ad-HAc). These obtained fluorinated AMPS-Ad-HAc cooligomers were found to form nanometer-size-controlled fine particles not only in water but also in a large variety of traditionally organic solvents. In addition, these fluorinated cooligomeric nanoparticles showed a good dispersibility in these solvents. Interestingly, the size of these fluorinated nanoparticles is extremely sensitive to solvent changes, and an increase of the particle size was observed in the solvents, in which the dielectric constant is higher or lower. More interestingly, these fluorinated AMPS-Ad-HAc cooligomeric nanoparticles exhibited a lower critical solution temperature around 52 °C in an organic medium (tert-butyl alcohol).
Introduction There has hitherto been a great interest in temperature-sensitive polymers such as poly(N-isopropylacrylamide) (poly-NIPAM) and its copolymers from the viewpoints of pharmaceutical and biomedical applications.1 It is well-known that poly-NIPAM exhibits a lower critical solution temperature (LCST) around 30-34 °C in aqueous solutions, indicating that it is water soluble below the LCST and precipitates above the LCST. In general, the LCST is related to the hydrophilic-hydrophobic balance in the polymer, and an increase in the number of hydrophobic moieties in the NIPAM-based copolymers would decrease the LCST of the homopolymer.2 In general, a thermally induced phase separation of poly-NIPAM can be observed above the LCST only in aqueous media due to the interaction between the hydrophilic and hydrophobic characteristics.3 From this point of view, there have hitherto been no reports on the LCST behavior in organic media by the use of a large variety of polymers including poly-NIPAM and its analogues. It is well-known that organofluorine compounds containing longer fluoroalkyl groups have strong oleophobic and hydrophobic characteristics toward a * To whom correspondence should be addressed. Phone: +81-172-393578. Fax: +81-172-39-3541. E-mail address:
[email protected]. † Hirosaki University. ‡ Asahi Glass Co., Ltd. (1) (a) Hoffman, A. S. J. Controlled Release 1987, 6, 297-305. (b) Peppas, N. A. J. Bioact. Compat. Polym. 1991, 6, 241-246. (c) Chen, G.; Imanishi, Y.; Ito, Y. Macromolecules 1998, 31, 4379-4381. (2) (a) Tanaka, T.; Nishio, I.; Sun, S.; U.-Nishio, S. Science 1982, 218, 467469. (b)Ricka, J.; Meewes, M.; Quellet, C.; Binkert, T. Prog. Colloid Polym. Sci. 1993, 91, 156-157. (c) Neradovic, D.; Hinrichs, J.; K.-van den Bosch, J. J.; Hennink, W. E. Macromol. Rapid Commun. 1999, 20, 577-581. (d) Kujawa, P.; Raju, B.: Winnik, F. M. Lamgmuir 2005, 21, 10046-10053. (e) Wang, C.; Flynn, N. T.; Langer, R. AdV. Mater. 2004, 16, 1074-1079. (f) Chen, B.; Gao, C. Macromol. Rapid Commun. 2005, 26, 1657-1663. (g) Zhang, J.-T.; Huang, S.W.; Gao, F.-Z.; Zhuo, R.-X. Colloid Polym. Sci. 2005, 283, 461-464. (h) Cui, Y.; Tao, C.; Zheng, S.; He, Q.; Ai, S.; Li, J. Macromol. Rapid Commun. 2005, 26, 1552-1556. (3) (a) Hirokawa, Y.; Tanaka, T. J. Chem. Phys. 1984, 81, 6379-6380. (b) Schild, H. G. Prog. Polym. Sci. 1992, 17, 163-249. (c) Miyazaki, H.; Kataoka, K. Polymer 1996, 37, 681-685. (d) Mueller, K. F. Polymer 1992, 33, 34703476. (e) Taylor, L. D.; Cerankowski, L. D. J. Polym. Sci., Polym. Chem. Ed. 1975, 13, 2551-2569.
variety of solvents including water. The introduction of both longer fluoroalkyl and oleophilic groups into polysoaps is of particular interest from the developmental viewpoint of novel temperature-sensitive polymers, which should exhibit the LCST characteristic in organic media. Now, we have found that fluoroalkyl-end-capped 2-acrylamido-2-methylpropanesulfonic acid cooligomers containing adamantyl segments could exhibit an LCST in an organic medium (tert-butyl alcohol, t-BuOH) around 52 °C. To the best of our knowledge, our finding is the first example of the LCST behavior in organic media. These results will be described herein. Experimental Section NMR spectra and Fourier-transform infrared (FTIR) spectra were measured using a JEOL JNM-400 (400 MHz) FT NMR system (Tokyo, Japan) and a Shimadzu FTIR-8400 FT-IR spectrophotometer (Kyoto, Japan), respectively. Dynamic light scattering (DLS) measurements were measured using an Otsuka Electronics DLS7000 HL instrument (Tokyo, Japan). Transmission electron microscopy (TEM) images were obtained using a JEOL JEM-121 electron microscope (Tokyo, Japan). Ultraviolet-visible (UV-vis) spectra were measured using a Shimadzu UV-1600 UV-vis spectrophotometer (Kyoto, Japan). The following is a typical procedure for the preparation of fluoroalkyl-end-capped 2-acrylamido-2-methylpropanesulfonic acid cooligomer containing adamantyl segments. Perfluoro-2,5-dimethyl3,6-dioxanonanoyl peroxide (1.9 mmol) in AK-225 (1:1 mixed solvents of 1,1-dichloro-2,2,3,3,3-pentafluoropropane and 1,3dichloro-1,2,2,3,3-pentafluoropropane, 25 g) was added to an aqueous solution (50%, w/w) of 2-acrylamido-2-methylpropanesulfonic acid (AMPS; 7.7 mmol) and a mixture of 3-hydroxy-1-adamantyl acrylate (Ad-HAc; 9.7 mmol) and AK-225 (200 g). The heterogeneous mixture was stirred at 45 °C for 5 h under nitrogen. After removal of the solvent, the obtained crude products were reprecipitated from ethanol-acetone to give an R,ω-bis(perfluoro-1,4-dimethyl-2,5dioxaoctyl)ated AMPS-Ad-HAc cooligomer [RF(AMPS)x(AdHAc)yRF; RF ) CF(CF3)OCF2CF(CF3)OC3F7] (1.2 g). This cooligomer exhibited the following spectral characteristics: IR (ν/cm-1) 3371 (OH, NH), 2920 (CH), 1732 (CO), 1650 [C(dO)N+H2-], 1308 (CF3), 1250 (CF2); 1H NMR (CD3OD) δ 1.05-1.80 (CH, CH2,
10.1021/la062060+ CCC: $37.00 © 2007 American Chemical Society Published on Web 04/25/2007
Letters
Langmuir, Vol. 23, No. 11, 2007 5849 Scheme 1
Table 1. Dispersibility and Size of RF(AMPS)x(Ad-HAC)yRF Cooligomeric Nanoparticles in a Variety of Solvents runa
H2O
MeOH
EtOH
i-PrOH
t-BuOH
THF
AK-225
DMSO
DMF
acetone
CH2ClCH2Cl
1
4b (395)e 4 (624)e 4 (643)e
Oc (122) O (82) O (11)
O (12) O (10) O (11)
O (11) O (11) O (11)
O (13) O (12) O (10)
4 (458) ∆ (446) ∆ (452)
×d
O (83) O (55) O (11)
O (80) O (83) O (82)
×
4 (93) 4 (89) 4 (83)
2 3
e
× ×
× ×
a Each different from those of Scheme 1. b 4 indicates a turbid solution. c O indicates a transparent solution. d × indicates an insoluble mixture. Size (nm) of the nanoparticles detemined by DLS.
CH3), 1.85-2.15 (CH2), 2.15-2.35 (CH). The molecular weight of this cooligomer could not be determined by SEC due to the formation of nanoparticles. Other fluoroalkyl-end-capped AMPS-Ad-HAc cooligomers and RF(NAT)x(Ad-HAc)yRF cooligomers were prepared under similar conditions. The NMR spectra and molecular weight of RF(NAT)x(Ad-HAc)yRF cooligomers were not measured due to gelling (or insolubility) of the samples. The lower critical solution temperatures (LCSTs) of RF(AMPS)x(Ad-HAc)yRF cooligomeric nanoparticles in tert-butyl alcohol were measured by a turbidity method. A UV-vis spectrophotometer equipped with a temperature controller was used to trace the phase transition by monitoring the transmittance of the light at a wavelength of 500 nm as a function of temperature. The concentration of the cooligomeric nanoparticle solutions used was 6 g/dm3, and the temperature of the solutions was raised from 25 to 85 °C. The LCST was defined as the temperature where the transmittance was 50%. A procedure for studying the gel-formation ability was based on a method reported by Hanabusa et al.4 Briefly, weighted RF(NAT)x(Ad-HAc)yRF cooligomer was mixed with water in a tube. The mixture was treated under ultrasonic conditions until the solid was dissolved. The resulting solution was kept at 30 °C for 1 h, and gelation was checked visually. The gel was stable, and the tube could be inverted without the shape of the gel being changed.
Results and Discussion The reactions of fluoroalkanoyl peroxide with AMPS and Ad-HAc were carried out at 45 °C for 5 h under nitrogen. The process is outlined in Scheme 1. Fluoroalkanoyl peroxide was found to react with AMPS and Ad-HAc under mild conditions to afford fluoroalkyl-end-capped 2-acrylamido-2-methylpropanesulfonic acid cooligomers containing adamantyl segments [RF(AMPS)x(Ad-HAc)yRF] in 21-46% isolated yields. These results are also shown in Scheme 1. The yields of RF(AMPS)x(Ad-HAc)yRF cooligomers obtained are in general dependent upon the molar ratios of AMPS and Ad-HAc employed, increasing with greater molar ratios of Ad-
HAc in Ad-HAc-AMPS. This finding would be due to the higher radical polymerizable characteristic of Ad-HAc toward fluoroalkanoyl peroxide. Previously, we reported that fluoroalkyl-endcapped AMPS homooligomers [RF(AMPS)nRF] can form gels not only in water but also in organic polar solvents such as methanol, ethanol, N,N-dimethyformamide (DMF), and dimethyl sulfoxide (DMSO) due to the synergistic interaction between the aggregations of end-capped fluoroalkyl segments and the ionic interactions of the amide cations and sulfonate anions.5 Our present RF(AMPS)x(Ad-HAc)yRF cooligomers were not able to form such gels in these solvents; however, interestingly, we observed the formation of fluorinated cooligomeric nanoparticles in these solvents. These results are shown in Table 1. As shown in Table 1, RF(AMPS)x(Ad-HAc)yRF cooligomers were insoluble in fluorinated solvents (AK-225) and acetone; however, it was demonstrated that these cooligomers could exhibit a good dispersibility in water, MeOH, EtOH, 2-propanol (iPrOH), t-BuOH, tetrahydrofuran (THF), DMSO, DMF, and 1,2dichloroethane (DE) to form fluorinated cooligomeric nanoparticles. Of particular interest, it was demonstrated that the cooligomeric nanoparticles in MeOH, EtOH, i-PrOH, t-BuOH, DMSO, and DMF afforded well-dispersed transparent colorless solutions, and the size of these nanoparticles determined by DLS measurements at 30 °C was at the 10 nm level in these solvents except for DMF (see run 3 in Table 1). In contrast, fluorinated cooligomeric nanoparticles in water, DE, and THF afforded turbid solutions, and the size of these nanoparticles was found to increase to the 83-643 nm level. (4) (a) Hanabusa, K.; Tanaka, R.; Suzuki, M.; Kimura, M.; Shirai, H. AdV. Mater. 1997, 9, 1095-1097. (b) Hanabusa, K.; Okui, K.; Karaki, K.; Kimura, M.; Shirai, H. J. Colloid Interface Sci. 1997, 195, 86-93. (5) (a) Sawada, H.; Katayama, S.; Nakamura, Y.; Kawase, T.; Hayakawa, Y.; Baba, M. Polymer 1998, 39, 743-745. (b) Sawada, H.; Katayama, S.; Ariyoshi, Y.; Kawase, T.; Hayakawa, Y.; Tomita, T.; Baba, M. J. Mater. Chem. 1998, 8, 1517-1524.
5850 Langmuir, Vol. 23, No. 11, 2007
Figure 1. Relationship between the size of RF(AMPS)x(Ad-HAc)yRF nanoparticles and the dielectric constant () of solvents: (a) run 1 in Scheme 1; (b) run 2 in Scheme 1; (c) run 3 in Scheme 1.
Figure 2. TEM image of RF(AMPS)x(Ad-HAc)yRF nanoparticles in methanol (see run 1 in Scheme 1).
The relationship between the solvent dielectric constant () and the size of the RF(AMPS)x(Ad-HAc)yRF cooligomeric nanoparticles determined by DLS is summarized in Figure 1. RF(AMPS)x(Ad-HAc)yRF cooligomeric nanoparticles could afford an increase of the particle size in a higher solvent dielectric constant ( ) 78.5) solvent such as water, indicating this behavior is strongly governed by the interaction of the betaine-type segments (the amide cations and sulfonate anions) in the cooligomer with water to increase the size of the nanoparticles. Similarly, RF(AMPS)x(Ad-HAc)yRF cooligomeric nanoparticles could afford an increase of the particle size in a lower solvent dielectric constant ( ) 7.39) solvent such as THF. This finding suggests that the oleophilic-oleophilic interaction between the nonpolar oleophilic adamantyl segments in cooligomers and the lower solvent (THF) should be preferable to the polar interaction with the betaine-type segments to increase the size of the nanoparticles. Therefore, in the other solvents except for water and THF, fluorinated cooligomeric nanoparticles could afford very fine nanoparticles due to the solvophobic interaction imparted by end-capped fluoroalkyl segments in cooligomers. We have obtained TEM photographs of a methanol solution of RF(AMPS)x(Ad-HAc)yRF cooligomeric particles (run 1 in Scheme 1), and the result is shown in Figure 2. The electron micrograph also shows the formation of fluorinated cooligomeric nanoparticles with a mean diameter of 148 nm. The difference in the average sizes determined by DLS and TEM (DLS, ∼122 nm; TEM, ∼148 nm) would be due to the coagulation or agglomeration of the nanoparticles during sample preparation for TEM measurements. Fluoroalkyl-end-capped homooligomers containing triol segments can also cause a gelation, where the aggregations of
Letters
Figure 3. Temperature dependence of transmittance at 500 nm for tert-butyl alcohol solutions of 6 g/dm3 RF(AMPS)x(Ad-HAc)yRF: (O) run 1 in Scheme 1; (4) run 2 in Scheme 1; (2) run 3 in Scheme 1.
fluoroalkyl segments and the hydrogen-bonding interaction between the triol segments are involved in establishing a physical gel network.6 Therefore, the preparation of fluoroalkyl-endcapped cooligomers containing both adamantyl and triol segments is very interesting from the developmental viewpoint of new fluorinated nanoparticles. In fact, we have prepared fluoroalkylend-capped N-[tris(hydroxymethyl)methyl]acrylamide cooligomers containing adamantyl segments [RF(NAT)x(Ad-HAc)yRF] by the use of fluoroalkanoyl peroxide as a key intermediate. These results are shown in Scheme 2 and Table 2. The expected RF(NAT)x(Ad-HAc)yRF cooligomers were obtained in 4-35% isolated yields. RF(NAT)x(Ad-HAc)yRF cooligomers thus obtained exhibited a solubility behavior quite different from that of RF(AMPS)x(Ad-HAc)yRF cooligomers, and the fluorinated cooligomers in Scheme 2 could not form nanoparticles in a variety of solvents including water. However, RF(NAT)x(Ad-HAc)yRF cooligomers cause a gelation only in water and exhibit no soubility at all in other solvents. Thus, the yields of RF(NAT)x(Ad-HAc)yRF cooligomers in Table 2 are markedly dependent upon the molar ratios of NAT and Ad-HAc employed, increasing with greater molar ratios of NAT in NATAd-HAc. This finding would be due to the higher gelling characteristic related to the NAT segments in RF(NAT)x(AdHAc)yRF cooligomers. We measured the minimum concentrations of RF(NAT)x(Ad-HAc)yRF cooligomers necessary for gelation. The results on the minimum concentration for gelation (Cmin) in water at 30 °C are also given in Table 2. RF(NAT)x(Ad-HAc)yRF cooligomers exhibited a lower gelling ability (higher Cmin value) compared to the corresponding RF(NAT)nRF homooligomer (Cmin ) 25 g/dm3). This finding suggests that the main driving force for gelation is governed by the synergistic interaction with the aggregation of fluoroalkyl segments and intermolecular hydrogen bonding between triol segments. Therefore, the ionic interaction through the betaine-type segments in cooligomers is necessary for the formation of fluoroalkyl-end-capped cooligomeric nanoparticles containing adamantyl segments. In this way, RF(AMPS)x(Ad-HAc)yRF cooligomers were demonstrated to be an interesting polymeric material for the preparation of nanometer-size-controlled cooligomeric particles in a large variety of solvents. In particular, the size of this fluorinated nanoparticle is very sensitive to solvent changes. It is strongly expected that this fluorinated cooligomeric nanoparticle should also become sensitive to temperature changes. We measured the size of this fluorinated cooligomeric nanoparticle (6) Sawada, H.; Nakamura, Y.; Katayama, S.; Kawase, T. Bull. Chem. Soc. Jpn. 1997, 70, 2839-2845.
Letters
Langmuir, Vol. 23, No. 11, 2007 5851 Scheme 2
Table 2. Preparation of RF(NAT)x(Ad-HAC)yRF Cooligomers and Critical Gel Concentration (Cmin) of RF(NAT)x(Ad-HAC)yRF in Water at 30 °C [RF ) CF(CF3)OC3F7] (RFCOO)2 NAT amt Ad-HAc yielda Cminb(gelator/water) (g/dm3) run amt (mmol) (mmol) amt (mmol) (%) 4 5 6 7
4.0 4.0 2.1 2.1
20.0 20.0 4.2 2.1
12.0 20.0 10.4 12.5
34 35 12 4
66 71 68 68
a Yields are based on the decarboxylated peroxide units (R -R ), F F NAT, and Ad-HAc. b Cmin[RF(NAT)nRF] ) 25 g/dm3.
Table 3. Size of RF(AMPS)x(Ad-HAC)yRF Cooligomeric Nanoparticles in tert-Butyl Alcohol Solutions Determined by DLS Measurements at 30 and 50 °C size of nanoparticles (nm)
a
runa
30 °C
50 °C
1 2 3
13.2 ( 0.7 12.3 ( 1.2 10.2 ( 1.1
146 ( 29.3 128 ( 28.0 112 ( 24.0
Each different from those of Scheme 1.
by the use of DLS in tert-butyl alcohol at 30 and 50 °C. These results are shown in Table 3. As shown in Table 3, the size of each fluorinated cooligomeric nanoparticle was found to increase with an increase of temperature from 30 to 50 °C, indicating this fluorinated cooligomeric nanoparticle could cause a thermally induced phase transition in an organic medium such as tert-butyl alcohol. In fact, we found that tert-butyl alcohol solutions of RF(AMPS)x(Ad-HAc)yRF cooligomeric nanoparticles showed a cloud point on heating. The LCSTs of tert-butyl alcohol solutions of 6 g/dm3 cooligomeric nanoparticles were measured, and the results are shown in Figure 3. As shown in Figure 3, a phase separation in each fluorinated nanoparticle occurred around 42 °C, where the solubility of these cooligomeric nanoparticles sharply altered. The LCSTs of these nanoparticles were 52 °C (run 1 in Scheme 1), 50 °C (run 2 in Scheme 1), and 57 °C (run 3 in Scheme 1). The LCSTs were found to increase with an increase of the contents of adamantyl segments in cooligomers (except for the run 2 case), indicating that the oleophilic interaction of adamantyl segments with tertbutyl alcohol should be essential for the preparation of transparent
solutions below the LCST. DLS measurements also indicate a dramatic increase of the fluorinated nanoparticle size around the LCST (50 °C; see Table 3) compared to that below the LCST. This finding suggests that the fluorophilic interactions between the end-capped fluoroalkyl segments in cooligomeric nanoparticles toward tert-butyl alcohol should provide the architecture of self-assembled aggregates of cooligomeric nanoparticles to exhibit the LCST in tert-butyl alcohol. This LCST characteristic was observed only in tert-butyl alcohol. In conclusion, we have succeeded in preparing a new type of thermosensitve fluoroalkyl-end-capped AMPS cooligomeric nanoparticles containing adamantyl segments, which exhibited an LCST characteristic in organic media. The size of these fluorinated cooligomeric nanoparticles was extremely sensitive to the solvent dielectric constant and temperature changes. Especially, our present fluoroalkyl-end-capped AMPS cooligomeric nanoparticles were found to exhibit an LCST around 50 °C in an organic medium such as tert-butyl alcohol. Hitherto, it is well-known that block copolymers such as poly(Nisopropylacrylamide)-block-poly(ethylene oxide) exhibit thermosensitive micellization because of the hydrophobic character of the poly(N-isopropylacrylamide) block above its LCST combined with the hydrophilic property of the poly(ethylene oxide) block in aqueous systems.7 However, it is suggested that our present LCST behavior would be mainly related to the oleophilic-oleophobic balance in these cooligomeric nanoparticles corresponding to the oleophilic character from adamantyl segments and the oleophobic character from fluoroalkyl groups. Therefore, our present LCST observation in organic media is strongly due to the oleophobic characteristic imparted by fluoroalkyl groups. Further studies for the preparation and applications of new fluorinated cooligomers possessing the LCST characteristic in organic media are actively in progress. Acknowledgment. This work was partially supported by a Grant-in-Aid for Scientific Research (KAKENHI) on Priority Areas (2005-2009), MEXT, Japan. Thanks are due to Idemitsu Kosan Co., Ltd., Tokyo, Japan, for supplying Ad-HAc. LA062060+ (7) (a) Topp, M. D. C.; Dijksta, P. J.; Talsma, H.; Feijin, J. Macromolecules 1997, 30, 8518-8520. (b) Lin, H.-H.: Cheng, Y.-L. Macromolecules 2001, 34, 3710-3715.
