© Copyright 2007 American Chemical Society
MARCH 27, 2007 VOLUME 23, NUMBER 7
Letters Particulation of Hyperbranched Aromatic Biopolyesters Self-Organized by Solvent Transformation in Ionic Liquids Dongjian Shi, Tatsuo Kaneko,† and Mitsuru Akashi* Department of Applied Chemistry, Graduate School of Engineering, Osaka UniVersity, 2-1 Yamadaoka, Suita, Osaka 565-0871, Japan ReceiVed NoVember 8, 2006. In Final Form: January 29, 2007 Hyperbranched copolymers were prepared by the heat transesterification of 4-hydroxycinnamic acid (4HCA) and 3,4-dihydroxycinnamic acid (DHCA) with a high 4HCA composition dissolved in trifluoroacetic acid (TFA). The nanoparticles were formed after two homogeneous copolymer solutions were mixed in DMF and TFA, which are both good solvents for the copolymer P(4HCA-co-DHCA). We confirmed that the driving force for particulation was solvent interactions that produce ion pairs, which elevate the polarity of the solvent too much to solubilize the copolymers.
Introduction Polymeric nanoparticles have attracted increasing interest in the last two decades because of their well-defined structures and colloidal dispersions.1 Such particles have great potential applications in fields such as drug delivery,2,3 diagnosis,3,4 microreactors,5 and separation technology.6 Self-organization was widely used as an efficient and rapid method to prepare nanoscale materials. The driving force for self-organization is polymer chain exclusion from the solution using special sol* To whom correspondence should be addressed. E-mail: akashi@ chem.eng.osaka-u.ac.jp. Tel: +81-6-6879-7356. Fax: +81-6-6879-7359. † Current affiliation: School of Materials Science, Japan Advanced Institute of Science and Technology, 1-1 Asahidai, Nomi, Ishikawa 923-1292, Japan. (1) (a) Kaneko, T.; Hamada, K.; Kuboshima, Y.; Akashi, M. Langmuir 2005, 21, 9698-9703. (b) Bhatt, K. H.; Velev, O. D. Langmuir 2004, 20, 467-476. (c) Chen, M. Q.; Zhang, K.; Kaneko, T.; Liu, X. Y.; Cai, J.; Akashi, M. Polym. J. 2005, 37, 118-125. (d) Zhang, J. X.; Qiu, L. Y.; Zhu, K. J. Macromol. Rapid Commun. 2005, 26, 1716-1723. (2) Kataoka, K.; Harada, A.; Nagasaki, Y. AdV. Drug DeliVery ReV. 2001, 47, 113-131. (3) Patil, G. V. Drug DeV. Res. 2003, 58, 219-247. (4) Trubetskoy, V. S.; Frank-Kamenetsky, M. D.; Whiteman, K. R.; Wolf, G. L.; Torchilin, V. P. Acad. Radiol. 1996, 3, 232-238. (5) Chiu, D. T.; Wilson, C. F.; Karlson, A.; Danielson, A.; Lundqvist, A.; Stroembery, F.; Ryttsen, M.; Davidson, F.; Nordholm, S.; Orwar, O.; Zare, R. N. Chem. Phys. 1999, 247, 133-139. (6) Nagarajan, R.; Barry, M.; Ruckenstein, E. Langmuir 1986, 2, 210-215.
vents,7 which is sometimes accompanied by hydrogen bonding between polymers and solvents.8 Additives such as salts, ions, and homopolymers9 effectively form nanoparticles as well as temperature and/or pH changes.10 When nanoparticles are formed at room temperature, a solvation inhibitor is often added to the homogeneous solution. However, the particulation behavior depends on the addition conditions, which affect the homogeneity of the additive dispersion.11 If the combination of two good solvation conditions of the polymers would induce selforganization, then nanoparticles may be easily prepared. However, there is no report on self-organization occurring with the combination of two good polymeric solvents. However, biologically based polymers with biodegradability and nontoxicity have been widely studied over several decades in terms of bionanoparticles11-14 because of their potential for (7) Alexandridis, P.; Yang, L. Macromolecules 2000, 33, 3382-3391. (8) Zhang, G.; Jiang, M.; Zhua, L.; Wu, C. Polymer 2001, 42, 151-159. (9) Moffitt, M.; Khougaz, K.; Eisenberg, A. Acc. Chem. Res. 1996, 29, 95102. (10) Dou, H.; Jiang, M.; Peng, H.; Chen, D.; Hong, Y. Angew. Chem., Int. Ed. 2003, 42, 1516-1519. (11) (a) Kaneko, T.; Higashi, M.; Matsusaki, M.; Akagi, T.; Akashi, M. Chem. Mater. 2005, 17, 2484-2486. (b) Itoh, Y.; Matsusaki, M.; Kida, T.; Akashi, M. Chem. Lett. 2004, 33, 1552-1553. (12) Liu, X. M.; Sun, Q. S.; Wang, H. J.; Zhang, L.; Wang, J. Y. Biomaterials 2005, 26, 109-115.
10.1021/la063260o CCC: $37.00 © 2007 American Chemical Society Published on Web 02/20/2007
3486 Langmuir, Vol. 23, No. 7, 2007
Letters
Figure 1. (A) Polymerization scheme of 4HCA and DHCA. (B) Schematic illustration of hyperbranched architecture of P(4HCA-co-DHCA).
loading drugs and agricultural chemicals. We developed novel biopolymer types from phytomonomers,14 4-hydroxycinnamic acid (4HCA), and 3,4-dihydroxycinnamic acid (DHCA) that are widespread in plant cell walls as intermediate metabolites of the biosynthetic pathway of lignin and other biological materials.15,16 The aforementioned chemicals contain cinnamoyl groups as photoreactive centers, which undergo at least two photoreactions such as [2 + 2] cycloaddition and E-Z isomerization. P(4HCAco-DHCA)s form hyperbranched architectures and show phototuned hydrolyses and environmental degradation. If copolymers can form nanoscale particles, then degradable bionanocarriers can be developed. Herein we show the particulation behavior of P(4HCA-coDHCA)s by testing their solubility in detail. We find that both trifluoroacetic acid (TFA) and N,N-dimethylformamide (DMF) are good copolymeric solvents and that the solution mixing of TFA/DMF leads to an inducement of the particulation of copolymers. Experimental Section P(4HCA-co-DHCA) copolymers (Figure 1) were prepared by polycondensing 4HCA and DHCA with different compositions at 200 °C for 6 h in the presence of acetic anhydride as a condensation reagent and sodium acetate as a transesterfication catalyst using a reported method.14-16 4HCA compositions of copolymers in total units were 100, 79, 62, and 55 mol % as confirmed by 1H NMR. The number-average and weight-average molecular weights of the copolymers ranged from Mn ) 1.8 × 104 to 4.4 × 104 and from Mw ) 4.5 × 104 to 9.1 × 104, respectively. Scanning electron microscopy (13) (a) Zhao, C.; Sun, S.; Yang, K.; Nomizu, M.; Nishi, N. J. Appl. Polym. Sci. 2005, 98, 1668-1673. (b) Zhao, C.; Yang, K.; Wen, X.; Li, F.; Zhang, B.; Nomizu, M.; Nishi. N. J. Appl. Polym. Sci. 2005, 98, 1674-1678. (14) Kaneko, T.; Hang, T. T.; Shi, D. J.; Akashi, M. Nat. Mater. 2006, 5, 966-970. (15) Kaneko, T.; Matsusaki, M.; Hang, T. T.; Akashi, M. Macromol. Rapid Commun. 2004, 25, 673-677. (16) Matsusaki, M.; Hang, T. T.; Kaneko, T.; Akashi, M. Biomaterials 2005, 26, 6263-6270.
Figure 2. (A) Solution appearance change of copolymer with 55 mol % 4HCA in the TFA and DMF solution. (B-E) SEM images of a dried mixture of a TFA and DMF solution. TFA/DMF (v/v): (B) 10:1, (C) 1:1, (D) 1:8, and (E) 1:30.
Letters
Langmuir, Vol. 23, No. 7, 2007 3487
Figure 3. (A) 1H NMR spectra of DMF, TFA, and a mixture of DMF/TFA (1:1). (B) Proposed reaction occurring in the mixture of DMF and TFA solvents. (SEM) observations were made with a Hitachi S-4100H SEM instrument after samples were spattered onto gold and dried at room temperature. Fourier transform infrared (Perkin-Elmer Spectrum One) spectra, 1H NMR (JEOL JNM-GSX400, 400 MHz) spectra, and an optical polarized microscope (Olympus BX51) were used to observe the reactions of DMF and TFA.
Results and Discussion P(4HCA-co-DHCA) copolymers were polymerized by heat transesterification of the corresponding phytomonomers (Figure 1A) without cross-linking and showed a hyperbranching architecture (Figure 1B).14 We previously showed that copolymers had good solubility in aprotic polar solvents such as N-methyl2-pyrrolidinone owing to the hyperbranching architecture, although the corresponding linear polymer P4HCA was insoluble in aprotic polar solvents. We tested the copolymeric solubility further and made a solution with a concentration of 10 mg/mL and found that copolymers with 4HCA compositions of 79, 62, and 55 mol % were soluble in TFA. In addition, the copolymer with a 4HCA composition of 55 mol % showed good solubility in DMF whereas other copolymers with 4HCA compositions of 79 and 62 mol % were insoluble in DMF. We tried copolymer aggregation tests with 4HCA compositions of 79 and 62 mol %. When the TFA solution was poured into DMF, irregular aggregates were formed. Even with very slow pouring and different volume ratios of the two solvents, uneven precipitates with interconnected spherical shapes were made. To compare results, the TFA solution of the copolymer with a 4HCA composition of 55 mol % was poured into DMF, which is a good solvent. The mixture became turbid, and the turbidity unexpectedly remained for 1 week. We made DMF and TFA copolymer solutions with the same concentration of 10 mg/mL. Both copolymer solutions were transparent. However, the two solutions were mixed with different volume ratios under stirring to create the suspension immediately (Figure 2A). Because the suspension may contain something like nanoparticles, SEM observations of the suspension dried in vacuo at room temperature after stirring for 1 h were made. Figure 2B-E shows the formation of
nanoparticles from the copolymer. The nanoparticle size and morphology depended on the volume ratio of the two solutions. When the composition of TFA was in excess, for example, the ratio of TFA and DMF was 10:1, prepared nanoparticles aggregated (Figure 2B). Monodisperse nanoparticles with a uniform shape (Figure 2C) were obtained when the ratio was 1:1. The size of the nanoparticles was about 350 nm. When a small excess of DMF was present, such as when the ratio of TFA and DMF was 1:8, particles were also prepared (Figure 2D). However, when the ratio was adjusted to 1:30, indicating a large amount of DMF, particles were not formed (Figure 2E). The SEM image showed a filmlike formation that is similar to the SEM image of a single DMF or TFA solution. We also confirmed that heating up to 50 °C had little effect on the size of the nanoparticles. However, with heating above 50 °C, the particles could not be formed because TFA quickly evaporated from the solution. On the basis of the above results, we evaluated the selforganization mechanism of the hyperbranched P(4HCA-coDHCA) in these two good solvents. Because DMF-d6 and TFA-d contain small amounts of DMF and TFA, respectively, 1H NMR spectra of DMF-d6, TFA-d and the mixture (Figure 3A) were recorded. Although the TFA proton appeared at 11.5 ppm, remarkably it shifted 1.5 ppm toward the high-magnetic-field region of the spectrum upon mixing with DMF, indicating a change in the electronic environment of TFA protons. We also obtained IR spectra of TFA and DMF/TFA mixtures. TFA showed a broad IR peak around 3500 cm-1 assigned to the stretching of an OH group. However, the intensity of the TFA OH peak decreased upon mixing with DMF, indicating the transformation of TFA carboxyls into other states such as carboxylate ions. We also measured the conductivity of the solvents. DMF and TFA independent solvents showed an electric resistance of 10-5 Ω/cm, which increased greatly to 10-2 Ω/cm upon solvent DMF/TFA mixing. The electric resistance gradually increased upon TFA additions to DMF until the composition became 1:1. The aforementioned result indicates that ions were generated when the solvents were mixed. The tentative reaction of TFA with
3488 Langmuir, Vol. 23, No. 7, 2007
Figure 4. Optical microscope image around the boundary for the TFA/DMF copolymer solution (55 mol % 4HCA). The boundary is formed by TFA solution dropped into DMF solution. Thick lines are composed of the generating particles.
DMF is shown in Figure 3B. NMR shifts and IR peak changes are well explained by the ionization. DMF forms cations and TFA forms anions in this reaction scheme. Oppositely charged ions easily interact but do not form solid materials. One reason may be that the nonionized DMF and TFA solubilized the TFA/ DMF ionic pair to make a homogeneous-solution-like ionic liquid. The ionization that maintains the liquid state may be a driving force for the copolymer self-organization to create nanoparticles
Letters
because the solubility of copolymers is low in other highly polar solvents such as water and dimethylsulfoxide. Interactions with good solvents may influence polymer aggregates very slowly because ion pairs gradually increase. That is the reason that the interaction can lead to the production of spherical nanoparticles with uniform shapes. We also successfully confirmed the copolymer particulation by optical polarized microscopy. We made a gradient composition of TFA and DMF by slowly inserting an independent solution into the gap of two glass plates from opposite edges. The meeting portion of the two solutions was observed. Figure 4 is the crossedpolarizing microscope image around the boundary. One can see that the black line composed of particle aggregates, indicating a 1:1 composition of TFA and DMF, is the most appropriate condition for preparing the nanoparticles. This result is in agreement with the highest efficiency of ionization in the 1:1 composition. Thus we propose the advantage of using good solvent interactions to produce nanoparticles. We estimate that there might be some other systems with good solvent/solvent interactions, which may lead to new methods for bottom-up preparations of nanomaterials. Moreover, the prepared nanoparticles of photoreactive P(4HCA-co-DHCA) copolymers may also show the photomediated arrangement, which is under investigation. Acknowledgment. This research was primarily supported by a Grant-in-Aid for NEDO (03A44014c) and by Handai FRC. LA063260O
