Letter pubs.acs.org/Langmuir
Thermoreversible Nanogel Shuttle between Ionic Liquid and Aqueous Phases Takeshi Ueki,*,† Shota Sawamura, Yutaro Nakamura, Yuzo Kitazawa, Hisashi Kokubo, and Masayoshi Watanabe* Department of Chemistry & Biotechnology, Yokohama National University, 79-5 Tokiwadai, Hodogaya-ku, Yokohama 240-8501, Japan S Supporting Information *
ABSTRACT: We describe a nanogel that can reversibly shuttle between a hydrophobic ionic liquid (IL) phase and an aqueous phase in response to temperature changes. A thermosensitive diblock copolymer, consisting of poly(ethylene oxide) (PEO) as the first segment and a random copolymer of N-isopropylacrylamide (NIPAm) and Nacryloyloxysuccinimide (NAS) as the second segment, was prepared as a nanogel precursor using anionic ring-opening polymerization of EO followed by reversible addition− fragmentation chain-transfer (RAFT) polymerization of NIPAm and NAS. After the micellization of the diblock copolymer in an aqueous solution upon heating to temperatures higher than the lower critical solution temperature (LCST) of the second segment, a coupling reaction of the NAS group of the P(NIPAm-r-NAS) core with ethylenediamine gave a nanogel with a well-solvated PEO corona. The nanogel exhibited contrasting thermosensitivities in the aqueous and IL phases. Dynamic light scattering measurements revealed that the nanogel exhibited LCST phase behavior (low-temperature-swollen/high-temperature-shrunken) in the aqueous phase and the opposite upper critical solution temperature (UCST) phase behavior (high-temperature-swollen/low-temperature-shrunken) in hydrophobic ILs. The nanogel favored the aqueous phase at low temperatures and the IL phase at high temperatures because of the solubility changes in the PEO corona. Upon increasing the temperature, the nanogel underwent a swollen-to-shrunken phase change in the aqueous phase, a transfer from the aqueous phase to the IL phase, and a shrunken-to-swollen phase change in the IL phase. These processes were thermally reversible, which made the round-trip shuttling of the nanogel between the aqueous and IL phases possible.
I
Recently, Lodge and co-workers systematically studied the block copolymer self-assembly in ILs. They prepared an amphiphilic diblock copolymer consisting of poly(1,2-butadiene) and poly(ethylene oxide) (PB-b-PEO). The diblock copolymer showed universal micellar structures (spherical, wormlike, and bilayered vesicles) on varying the length of the PEO-shell block while keeping the PB-core block unchanged.13 Interestingly, they also found for the first time that block copolymer micelles can reversibly make a round-trip between water and water-immiscible IL upon temperature changes, irrespective of micellar morphology.14 They used typical hydrophobic ILs, 1-butyl-3-methylimidazolium hexafluorophosphate ([C4mim]PF6) or 1-ethyl-3-methylimidazolium bis(trifluoromethanesulfonyl)imide ([C2mim][NTf2]), as a solvent. They concluded that the reversible micelle transfer between the two phases is based on the relative affinity changes of the corona PEO chains toward water and IL. PEO is known to show LCST in aqueous solutions at relatively high
onic liquids (ILs) are recognized as the third type of solvent, the other two being aqueous and organic solvents. The characteristic properties of typical ILs that are different from those of conventional solvents are their nonvolatility, high thermal stability, and high ionic conductivity.1−3 We have systematically explored the potential use of ILs as solvents for various polymers, focusing on the development of new materials based on ILs and polymers. When ILs and polymers are compatible, it can afford polymer electrolytes for fabricating energy-conversion and energy-storage devices.4 We are also interested in the phase transitions of polymers (gels) in certain ILs in response to external stimuli.4 It has been found for the first time that poly(N-isopropylacrylamide) (PNIPAm), which is well-known and the most widely studied synthetic polymer showing lower critical solution temperature (LCST) phase behavior in aqueous solutions, exhibits the opposite upper critical solution temperature (UCST) phase behavior in certain ILs.5 The unique phase changes of polymers in ILs are now being developed to obtain novel soft materials such as stimuliresponsive block copolymers,6 thermoreversible gels,7−10 and smart gels using the volume phase transitions of chemically cross-linked gels.11,12 © 2013 American Chemical Society
Received: July 20, 2013 Revised: October 28, 2013 Published: October 29, 2013 13661
dx.doi.org/10.1021/la402688e | Langmuir 2013, 29, 13661−13665
Langmuir
Letter
Figure 1. Schematic of a thermodriven load-transfer-release nanogel. The nanogel exhibits low-temperature-swollen/high-temperature-shrunken volume phase transitions in the upper aqueous phase and the opposite phase behavior in the lower hydrophobic (water-immiscible) IL phase because of the dual thermosensitivity of PNIPAm in both phases. A nanogel surrounded by PEO shells can transfer between aqueous and IL phases.
Scheme 1. Preparation of the PEO-b-P(NIPAm-r-NAS) Diblock Copolymer as a Nanogel Precursor
P(NIPAm-r-NAS)), the nanogel precursor, was synthesized using anionic ring-opening polymerization of EO from phenothiazine to give the first segment, followed by the reversible addition−fragmentation chain-transfer (RAFT) random copolymerization of NIPAm and N-acryloyloxysuccinimide (NAS) to give the second segment (Scheme 1). The number-average molecular weights (Mn’s) of the PEO and P(NIPAm-r-NAS) blocks were estimated to be 34 and 16.3 kDa, respectively. Polydispersity indexes of the PEO and the diblock copolymers were estimated to be 1.28 and 1.25, respectively. On the basis of 1H NMR analysis, it was found that the NAS content in the second segment was 15 mol %. The characterization results, including the 1H NMR spectrum and GPC trace of the block copolymer, are summarized in the Supporting Information (Table S1 and Figure S1). The diblock copolymer self-assembled into the P(NIPAm-r-NAS)-core/ PEO-shell micelles in an aqueous solution upon heating to temperatures above the LCST of the second segment. Then, an appropriate amount of a bifunctional amine (ethylenediamine, EDA) was added to the solution for intermolecular crosslinking of block copolymers to form amide bonds via NAS active ester groups (Scheme S1 in the Supporting Information). The progress of the cross-linking reaction was visually confirmed after EDA addition when a slightly bluish tinge, characteristic of the micellar solution, appeared and did not return to the initially completely transparent state even after cooling to room temperature. After the core-cross-linking reaction, the sample solution was dialyzed to remove the unreacted amine and block copolymer chains from the solution.
temperatures, which implies that its solubility decreases with increasing temperature. 1H NMR techniques revealed that the PEO homopolymer could also perform a round-trip shuttling between aqueous and hydrophobic IL phases.15 These pioneering works strongly suggest that various types of submicrometer particles modified with PEO can also reversibly transfer between the aqueous and IL phases. Lodge and coworkers further demonstrated that block copolymer micelles and vesicles decorated with PEO exhibit a round-trip at the interface between aqueous and IL phases.16−18 Schubert and co-workers also reported novel polymer shuttle systems based on oxazoline-based block copolymers.19,20 Here, we present the preparation and characterization of a nanogel consisting of a cross-linked thermosensitive PNIPAm core surrounded by a PEO shell, which provides the driving force for phase transfer (Figure 1). At low temperatures, the PNIPAm core is swollen, but the nanogel shrinks with increasing temperature in aqueous solutions; this process can be utilized to capture certain agents. The shrunken nanogel transfers from the upper aqueous phase to the lower IL phase as the temperature increases, owing to the decreasing water solubility of the modified PEO shell. Further increases in temperature result in the swelling of the nanogel in the IL phase, which can be utilized to release the agent captured in the aqueous phase. Such load-transfer-release nanogel systems may potentially be useful as temperature-controllable microreactors. The target nanogel was prepared by the thermosensitive micellization of a diblock copolymer followed by a cross-linking reaction of the micellar core.21 Diblock copolymer (PEO-b13662
dx.doi.org/10.1021/la402688e | Langmuir 2013, 29, 13661−13665
Langmuir
Letter
Figure 2. (a) Hydrodynamic radius (Rh) of the PEO-b-P(NIPAm-r-NAS) diblock copolymer in water as a function of temperature before the crosslinking reaction. The inset shows the normalized scattering intensity of the diblock copolymer in water as a function of temperature. The scattering intensity of the solution at each temperature divided by that at 11.9 °C is shown as the normalized intensity. (b) Rh of the nanogel in water as a function of temperature.
We further confirmed the success of core-cross-linking using dynamic light scattering (DLS) measurements and by comparing the phase behaviors before and after the crosslinking process (Figure 2a,b). Note that the absolute Rh values and their behavior against temperature in Figure 2a,b are different. Before the cross-linking reaction, the micellization process with an increase in temperature can be seen from an increase in the Rh values (Figure 2a). In contrast, lowtemperature-swollen and high-temperature-shrunken swelling behavior, typical of PNIPAm hydrogels, is seen after the coupling reaction (Figure 2b). Before cross-linking, the hydrodynamic radius (Rh) was less than 10 nm at low temperatures, which indicated unimolecular (unimer) dissolution. The Rh of the particles increased significantly to 57 nm above 30 °C. This showed that micellization occurred because of the thermosensitivity of the PNIPAm-based second segment. Representative second cumulant (μ2/Γ2) values at 11.9 °C (unimer) and 50.1 °C (micelle) are 0.826 and 0.224, respectively. However, after the cross-linking reaction with EDA, the temperature dependence of Rh showed the opposite tendency. The Rh values of the nanogel over the entire temperature range were higher than those of the unimers before the cross-linking. This indicates that the particles no longer break into individual polymer chains because of intermolecular cross-linking of the block copolymers. It was confirmed that the core-cross-linking reaction proceeded successfully and that the nanogel exhibited a low-temperature-swollen/high-temperature-shrunken volume phase transition in water, as expected. Representative μ2/Γ2 values at 10.9 °C (swollen gel) and 45.0 °C (shrunken gel) are 0.483 and 0.156, respectively. The shrunken gels have a narrower size distribution because the nanogels are obtained from relatively monodisperse micelles. A broader distribution of the swollen gels might imply a distribution of swelling ratios. The reversibility of the swelling and shrinking phenomena of the nanogel was also confirmed. (Figure S4) We next investigated the swelling/shrinking behavior of the nanogel in an IL. Figure 3 shows the thermosensitivity of the nanogel in [C2mim][NTf2]. Because the thermoreversible round-trip micelles with the PEO shell and low-temperatureshrunken/high-temperature-swollen phase behavior of ion gels in [C2mim][NTf2] have already been reported,11,12 we first studied the thermosensitivity of the nanogel in [C2mim][NTf2]. The nanogel showed thermosensitivity in [C2mim]-
Figure 3. Temperature dependence of Rh of the nanogel in [C2mim][NTf2] as a function of temperature.
[NTf2], as expected. However, the temperatures at which large volume changes occur were significantly lower than those for our previous gels prepared by NIPAm polymerization in the presence of a small amount of methylenebis(acrylamide) as a cross-linker.12 During the heating process, the nanogel continues to swell from 5 °C and stops at around 35 °C, which may be due to the differences in the polymer network structures of the nanogel from block copolymer precursor and the previous gels. In fact, the phase-transition temperature of a polymer (gel) decreases because of random copolymerization with solvatophilic monomers. The unreacted NAS monomer with EDA might remain in the polymer network, decreasing the phase-transition temperature. This was supported by the aggregation temperature of the PEO-b-P(NIPAm-r-NAS) diblock copolymer before the coupling reaction, determined by DLS measurements in water (Figure 2a). The aggregation temperature of the PNIPAm-based block copolymer is known to be ∼32 °C, which does not greatly change even when changing the concentration or molecular weight.22 However, the present result indicates that the block copolymer selfassembles into micelles at temperatures starting from 27 °C, which is clearly lower than the common LCST of PNIPAm. Thus, the volume changes with temperature in the IL phase were too small to achieve the load-transfer-release process. To realize a load-transfer-release microreactor using the nanogel system, it is essential to design the suitable order of transition temperatures: LCST in water < phase-transfer temperature < UCST in ILs.18 Therefore, the UCST of PNIPAm should be higher than the LCST in water. The LCST and UCST of the linear polymer correspond to the phase-change temperatures of 13663
dx.doi.org/10.1021/la402688e | Langmuir 2013, 29, 13661−13665
Langmuir
Letter
the PNIPAm network in the aqueous and IL phases, respectively. We have already discussed the relationship between the UCST phase-transition temperature of PNIPAm and the chemical structure of IL.4 The phase-transition temperature of PNIPAm depends on the chemical structure of the anion of IL rather than that of the cation. The UCST phase transition of the linear PNIPAm polymer was found to be higher in 1-ethyl-3-methylimidazolium bis(pentafluoroethanesulfonyl)imide ([C2mim][BETI]) than in [C2mim][NTf2].4 Thus, we used [C2mim][BETI] as a solvent for swelling ratio measurements of the nanogel. To estimate Rh of the nanogel in [C2mim][BETI] from the Stokes−Einstein relation, the refractive index and viscosity of the IL were independently measured as a function of temperature (Figures S2 and S3). Figure 4 shows the temperature dependence of the
Figure 5. Reversible nanogel transfer between upper aqueous and lower IL ([C2mim][BETI]) phases caused by temperature changes. Nanogel transfer could be detected directly by the Tyndall effect. At lower temperatures, the Tyndall effect was observed only in the upper aqueous phase, whereas nanogel transferred upon heating into the lower IL phase. The transfer process was confirmed to be reversible. To observe the Tyndall effect clearly, incident laser (690 nm,
