Highly Responsive Hydrogel Prepared Using Poly(N

Dec 20, 2016 - We then prepared a polymer network in which PR molecules with several dangling PNIPA chains were connected by PNIPA chains using a clic...
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Highly Responsive Hydrogel Prepared Using Poly(N‑isopropylacrylamide)-Grafted Polyrotaxane as a Building Block Designed by Reversible Deactivation Radical Polymerization and Click Chemistry Atsushi Yasumoto,† Hiroaki Gotoh,† Yoshie Gotoh,† Abu Bin Imran,† Mitsuo Hara,† Takahiro Seki,† Yasuhiro Sakai,‡ Kohzo Ito,‡ and Yukikazu Takeoka*,† †

Department of Molecular Design and Engineering, Graduate School of Engineering, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8603, Japan ‡ Department of Advanced Materials Science, Graduate School of Frontier Sciences, The University of Tokyo, 5-1-5 Kashiwanoha, Kashiwa, Chiba 277-8561, Japan S Supporting Information *

ABSTRACT: We prepared building blocks with the ability to form a polymer network, a polyrotaxane (PR) structure that enhances the flexibility of the polymer network, and thermosensitive dangling chains that impart the polymer network with rapid sensitivity. First, thermosensitive poly(N-isopropylacrylamide) (PNIPA) was grafted from α-cyclodextrin, a cyclic molecule of PR, via controlled radical polymerization. The terminal chlorinated alkyl group of the grafted PNIPA was then modified with azide or alkyne. As a result, we obtained two types of PNIPA-grafted PR molecules with different terminations of PNIPA as building blocks. We then prepared a polymer network in which PR molecules with several dangling PNIPA chains were connected by PNIPA chains using a click reaction. Because of the presence of the dangling PNIPA chains, the obtained hydrogel exhibits rapid responses to changes in water temperature; it also exhibits flexibility due to the presence of the PR structure.

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INTRODUCTION Polymer gels can change their volumes and shapes reversibly due to variations in the interaction between the polymer chains and solvents in the polymer gels, which, in turn, are a result of changes in their environment.1 Such stimuli-responsive polymer gels have been studied for practical applications, such as artificial muscles,2 drug delivery systems,3 and sensor materials,4,5 because the release properties of solutes and the mechanical and molecular recognition properties of the polymer gels depend on their volumes and shapes. Practical uses of stimuli-responsive polymer gels have been under investigation for several years, but they have by no means been achieved. Some practical issues related to the properties of stimuli-responsive polymer gels have been disputed, including their mechanical brittleness6−10 and slow response to stimuli.11−13 In past studies of polymer gels, the main approaches used to obtain polymer gels that exhibit the expected physical properties have been the selection of relatively simple, lowmolecular-weight monomers and cross-linkers, the determination of the amounts of these reactants, and the initiation of the polymerization of these reactants.14 The main parameters that decide the nature of the polymer gels are the type and amount of the reactants used. However, in most cases in which © XXXX American Chemical Society

general radical polymerization is used for the polymerization, the resultant polymer gels consist of inhomogeneous polymer networks.15,16 Mechanical brittleness is attributed, in part, to the intrinsic inhomogeneity of the polymer networks that are chemically cross-linked by covalent bonds. In such polymer gels, the stress on the polymer network, caused by the distortion of polymer gels, is concentrated on shorter polymer chains. As a result, the polymer network is mechanically disrupted. Improving the mechanical properties and the stimuli sensitivity of polymer gels prepared by such a conventional method is difficult. If the network structures could be precisely controlled, other physical properties, in addition to the mechanical properties and the stimuli-sensitivity of the polymer gels, could be manipulated to obtain polymer gels with the desired properties. Recently, precise synthesis techniques such as controlled radical polymerization17−19 and click chemistry20,21 have become important for the preparation of polymers with precise structures. Supramolecular polymers can also be easily synthesized by self-assembly reactions.22−29 If we can Received: September 10, 2016 Revised: December 4, 2016

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DOI: 10.1021/acs.macromol.6b01955 Macromolecules XXXX, XXX, XXX−XXX

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Macromolecules Scheme 1. Synthesis N3-PNIPA-iPR and Al-PNIPA-iPR via One-Pot Syntheses from iPR-MI

PEG).37 Because each polymer contains both amine and carboxylic acid end groups, they obtained a homogeneous polymer network through the formation of amide linkages between the different Tetra-PEG compounds. Such a homogeneous network structure results in a polymer gel with wonderful mechanical performance because of the uniform stress achieved through the polymer structure. The homogeneous polymer network, which reflects the molecular structure of the Tetra-PEG hydrogel as a building block, leads to an improvement in the mechanical properties of the polymer gel. As previously explained, we can systematically design polymer network structures with desired functions by devising macromolecular architectures to create the polymer networks. If we use precisely prepared, well-suited macromolecules as the building blocks for constructing the polymer networks, we may gain the ability to control other physical properties of polymer gels in addition to their mechanical properties.11 As previously mentioned, we have already demonstrated a simple method of preparing extremely stretchable polymer gels by introducing PR structures into the polymer networks as a result of the pulley effect.32−35,38,39 In this study, in addition to introducing a PR structure that provides expansibility to polymer gels, we attempted to incorporate dangling polymer chains into the polymer network; such chains enhance the response speed of the polymer gels to environmental changes.11,12 In this work, we first explain the strategy used to construct the desired polymer network that exhibits both flexibility and a rapid response to environmental changes. As the starting chemical used to prepare the building blocks for the desired polymer network (Scheme 1), we used an ionic PR derivative35

manipulate these reactions, then we can precisely prepare highperformance polymers with complicated structures. Previous studies have indicated that precisely prepared polymers can form extremely fine nanostructured membranes 30 and sophisticated molecular machines,31 which is not possible with conventionally prepared polymers. Polymer networks prepared using these precisely prepared polymers as building blocks form polymer gels with desirable properties because the constructed polymer network reflects the nature of the building blocks. Ito et al. prepared a polymer gel, called a “slide-ring gel”, using a polyrotaxane (PR) composed of α-cyclodextrin (α-CD) and poly(ethylene glycol) (PEG).32 In the slide-ring gel, α-CD molecules in one PR molecule are cross-linked to α-CD molecules in other PR molecules. The main PEG chains are not fixed at the cross-linking points in the polymer network; instead, they can pass through the holes of figure-eight-shaped junctions freely, which is called the “pulley effect”. The stress concentration on parts of the polymer network is minimized through this effect. As a result, the slide-ring gel exhibits a high extensibility and small hysteresis after undergoing repeated extension and contraction. By using a PR molecule modified with many vinyl sites as a cross-linker to prepare the hydrogels, we can obtain extremely stretchable hydrogels from commonly used monomers.33−35 The mechanical properties of the hydrogels are most likely achieved because of the homogeneous network structures as a result of the pulley effect of the mobile cross-points.36 Sakai et al. reported that they prepared a homogeneous polymer network by coupling two types of star-shaped PEG compounds with four arms of equal molecular weight (TetraB

DOI: 10.1021/acs.macromol.6b01955 Macromolecules XXXX, XXX, XXX−XXX

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Macromolecules

and then purified by distillation under reduced pressure (7.5 mmHg, 95 °C). Me6TREN was obtained as a gift from Mitsubishi Chemical Co. and was distilled at 110 °C at 5 mmHg. Preparation of Polyrotaxane Macroinitiator (iPR-MI). iPR (1.00 g) was dissolved in dried DMF (25 mL) under a nitrogen atmosphere for 12 h. After DMAP (0.30 g) was added, CPCl (568 μL) was added dropwise to the solution in an ice bath using a dripping funnel. The mixture was stirred continuously for 30 min in an ice bath and then stirred for 3 h at room temperature. After the reaction, the alkaline state of the solution was confirmed using pH test paper. In this case, a drop of water was added to the test solution on the pH test paper. The resultant solution was diluted with methanol and dialyzed with a Spectra/Por6 dialysis membrane (MWCO 50 000, Spectrum Laboratories, Inc.) using methanol for 2 days and then using water for 4 days. A white powder was obtained by freeze-drying (FDU-1200 (Tokyo Rikakikai Co., Ltd.)) the solution. The induction amount of the initiator was estimated by 1H NMR of the white sample dissolved in DMSO-d6. Figure S1 shows the 1H NMR spectrum of the obtained iPR-MI. The number of the initiator for each α-CD molecule was estimated using eq 1:

(iPR, Advanced Softmaterials Inc.) with an average of 1.6 carboxyl groups modified on each α-CD molecule because the unmodified PR, which consists of α-CDs and PEG, is sparingly soluble in pure water.40 N-Isopropylacrylamide (NIPA), which polymerizes to form the thermosensitive PNIPA polymer in aqueous solutions,41 was used as a primary component within the polymer network because a thermosensitive polymer network is advantageous since its stimuli sensitivity can be investigated experimentally.5,42−46 The introduction of freely mobile dangling chains into a polymer network will contribute to the improvement of the response speed to changes in the volume of the polymer gel.11,12 In this study, dangling chains of PNIPA were systematically introduced into the polymer network to accelerate the stimuli sensitivity of the polymer gel. In the preparation of PNIPA with a narrow molecular weight distribution, the use of a controlled radical polymerization is highly advantageous. Thus, we modified a controlled-radicalpolymerization initiator with hydroxyl groups on the α-CD molecule of iPR to polymerize NIPA. The chlorinated alkyl group was used as the initiator to polymerize NIPA, and it provides precise control of the polymerization reaction; the resultant PNIPA chain has a chlorinated end group that is useful for other chemical reactions. We used the reactive chlorinated end group to connect two PNIPA chains that were attached onto different iPRs via a cross-linking reaction. Azide− alkyne Huisgen cycloaddition, which is the most widely used click chemistry reaction, was selected as the cross-linking reaction.47 The chlorinated end group of the PNIPA grafted onto iPR was modified into two different groups: an azide group and an alkyne group (Scheme 1). As a result, we obtained two different building blocks composed of PNIPA grafted onto iPR with different end groups. Afterward, the two different building blocks were connected through the click reaction. Eventually, a polymer network that contained mobile cross-linkers, subchains connecting the two mobile cross-linkers with a narrow molecular weight distribution, and dangling chains with a narrow molecular weight distribution was constructed using the previously described procedure. In this study, we investigated the rapid response of the resultant polymer network to changes in temperature.

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starting points (/α‐CD) =

I1.6/3 I4.8/6

(1)

where I4.8 and I1.6 are the integral values for the C1H peak (6H) in αCD and the proton peak of methyl (3H) in CPCl, respectively. The initial (starting point) number of chloride ions in one iPR-MI molecule increases as the number of methyl ions increases. The total number of the starting points is calculated by multiplying the number of α-CD in one iPR by the number of starting points estimated by eq 1. Graft Polymerization of PNIPA onto iPR by Reversible Deactivation Radical Polymerization. In a typical experiment, iPRMI (2.5 starting points/α-CD, 10.0 mg) and NIPA (389 mg) were dissolved in dried DMSO (2.3 mL) in a 30 mL eggplant flask under a nitrogen atmosphere. Afterward, ethyl 2-chloropropionate (ECP, 2.2 μL: 1.72 × 10−5 mol) and CuCl (3.40 mg) were added to the solution. After the CuCl was crushed with a glass rod, Me6TREN (9.8 μL) was added to the solution, and the reaction was initiated at 20 °C. A small amount of solution was removed from the reaction solution at a predetermined time interval; the reaction solution was then exposed to air to stop the polymerization. The 1H NMR spectrum of the resultant solution in DMSO-d6 was used to determine the monomer-to-polymer conversion rate. The final product from the polymerization was purified by a dialysis treatment. To separate produced polymers from the free initiator and the macroinitiator, two types of dialysis membranes with molecular weight cutoff values of 1000 and 50 000 were used. The resultant solution was first poured into the dialysis membrane with a molecular weight cutoff of 50 000 and then poured into the larger sized dialysis membrane with a molecular weight cutoff of 1000. The sample was then dialyzed with methanol for 1 day, and the external solution was changed to water. After replenishing the external water several times a day for 2 days to remove the unreacted monomers and Cu catalyst, we separated the solutions in the dialysis membranes into an inner solution in the dialysis membrane with a molecular weight cutoff of 50 000 and an outer solution in the dialysis membrane with a molecular weight cutoff of 1000. The outer solution, which included only the smaller-molecular-weight linear PNIPA prepared from ECP, was freeze-dried, and a partial amount of “free PNIPA” was obtained. For the inner solution, PNIPA-iPR was obtained from iPR-MI after another 2 days of dialysis and freeze-drying of the solution. Preparation of Two Types of Building Blocks by One-Pot Synthesis. Preparation of N3-PNIPA-iPR. In a typical experiment (Table S3, run 3), iPR-MI (100 mg, 270 starting points/iPR-MI), ECP (11.8 μL), CuCl (18.5 mg), Me6TREN (50 μL), and NIPA (1.06 g) were dissolved in dried DMSO (5.76 mL: NIPA/DMSO = 1/6 w/w) in an eggplant flask, and the controlled polymerization was started. In another eggplant flask, NaN3 (150 mg) was dissolved in dried DMSO (4.6 mL) under a nitrogen atmosphere in a glovebox. The NaN3/

EXPERIMENTAL SECTION

Materials. Ionic polyrotaxane (iPR: Mn = 1.56 × 105, Mw/Mn = 1.12, inclusion ratio of α-CD = 27%, Mn of PEG as the main chain = 3.50 × 104, 107 α-CD/iPR, carboxylate ratio = 9 mol %) was kindly provided by Advanced Softmaterials Inc. (Kashiwa, Japan). Copper(I) chloride (CuCl, beads, 99.99%, Tokyo Kasei Kogyo, Tokyo, Japan), N,N-dimethyl-4-aminopyridine (DMAP, Tokyo Kasei Kogyo, Tokyo, Japan), 2-chloropropionyl chloride (CPCl, Tokyo Kasei Kogyo, Tokyo, Japan), 1,6-heptadiyne (Tokyo Kasei Kogyo, Tokyo, Japan), potassium chloride (KCl, Kanto Chemical CO., Inc., Tokyo, Japan), ethyl 2-chloropropionate (ECP, 96%, Wako Pure Chemical Industries, Tokyo, Japan), dimethyl sulfoxide (DMSO, anhydrous, 99.9%, Wako Pure Chemical Industries, Tokyo, Japan), dimethyl-d6 sulfoxide (DMSO-d6, ACROS Organics), sodium azide (NaN3, Sigma-Aldrich, St. Louis, MO), calcium hydride, sodium hydroxide (NaOH, Kishida Chemical Co. Ltd. Japan), chloroform (Kishida Chemical Co. Ltd. Japan), methanol (Kishida Chemical Co. Ltd. Japan), and N,Ndimethylformamide (DMF, Kishida Chemical Co. Ltd. Japan) were used as received. The water used in all experiments was purified using a Direct-Q UV water purification system (Millipore Corp.). NIPA (Kohjin) was recrystallized twice from a toluene−hexane mixed solvent and dried under vacuum prior to use. DMF was first dried over calcium hydride C

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Macromolecules DMSO solution (2.3 mL) was added to the other reaction solution after the conversion of the monomer to the polymer by the reversible deactivation radical polymerization increased from 30% to 60%. N3PNIPA-iPR was purified and isolated by dialysis, and freeze-dried, as explained in the purification steps of PNIPA-iPR. Preparation of Al-PNIPA-iPR. 1,6-Heptadiyne (212 μL) was added to the previously described reaction solution used to prepare N3PNIPA-iPR after 24 h; NaN3 was added to the solution in a nitrogen atmosphere. Al-PNIPA-iPR was purified and isolated by dialysis and freeze-drying, as explained in the purification steps for PNIPA-iPR. Preparation of Polymer Network from N3-PNIPA-iPR and AlPNIPA-iPR by a Click Reaction. A polymer gel was prepared using the click reaction between N3-PNIPA-iPR and Al-PNIPA-iPR with the same copper catalyst. In our typical experiment, after mixing the same amount of the building blocks in DMSO with CuCl, and Me6TREN, the reaction solution was left at 25 °C for appropriate length of time. The resultant gel was washed with an adequate amount of water. As a result, the hydrogel was obtained. 1 H NMR Spectroscopy. Polymerization conversion rates were estimated by 1H NMR spectroscopy. 1H NMR spectra were collected on a JNM-GSX400 (JEOL) spectrometer; the samples were dissolved in DMSO-d6. The direct analysis of the polymer from the unpurified reaction mixture should provide more representative values of the polydispersity indexes and the conversion values. Thus, the reaction mixtures were diluted with DMSO-d6 to obtain solute concentrations of approximately 1 wt %; the resulting solutions were used for 1H NMR analysis. The monomer-to-polymer conversion rate was calculated using the previously described method. Gel Permeation Chromatography (GPC) for NumberAveraged Molecular Weight (Mn) and Polydispersity Index (PDI: Mw/Mn) Measurements. We hydrolyzed PNIPA-iPR, N3PNIPA-iPR, and Al-PNIPA-iPR using a high-pH aqueous KCl/NaOH solution (pH > 12). After we neutralized the resultant polymers using hydrochloric acid and purified them by dialysis, we isolated the grafted PNIPAs on each building block. The molecular weight and PDI of these isolated graft PNIPAs and free PNIPAs were measured by GPC. GPC measurements were performed using a GL-7140 HPLC (GL Science), KD-804 and KD-805 columns (Shodex), and a GL-7454 refractive index detector (GL Science) maintained at 20 °C. The eluent was a DMF:chloroform 50:50 (v/v) mixed solvent, which included 5 mM of LiCl, at a flow rate of 1.0 mL min−1. For PNIPA analysis, narrow-disperse poly(methyl methacrylate) (PMMA, Mn = 2000, 8000, 20 000, 50 000, 150 000, and 2 480 000; Aldrich) standards were used for calibration. Data analyses of the GPC charts, such as curve fitting, baseline subtraction, and waveform separation, were performed using the Origin 6.0 software (Origin Lab). FT-IR Spectroscopy. Transmission IR spectra were measured using an FT-IR spectrometer (Varian, 640-IR) to check the azidation and alkyne modification of PNIPA-iPR. Data analyses of the IR spectra were performed using the Resolutions Pro software (Varian). Raman Spectrophotometry. Raman spectra were collected to check the azidation and alkynation of PNIPA-iPR. The spectra were collected using a LAZER Raman microscope (Thermo Fisher Scientific Co., DXR Raman microscope). Dynamic Light Scattering Measurements of PNIPA-iPR. To measure the hydrodynamic radius (Dh) of PNIPA-iPR in water, we used a dynamic light scattering (DLS) measurement system (Malvern Instruments, Zetasizer Nano ZS). A PNIPA-iPR aqueous solution with a concentration of 0.01 wt % was prepared and was placed in the DLS instrument equipped with a Peltier temperature control unit. The temperature is raised 1 °C/min to change the temperature from 15 to 50 °C. However, the temperature is fixed using software program in this instrument when the diffusion coefficient of the polymer is measured. Equilibrium Swelling Ratio of Polymer Gels. A cylindrical polymer gel was prepared in a microcapillary tube with a diameter of ca. 270 μm and was subsequently used for measuring the swelling ratio. The polymer gel sample was immersed in water in a glass cell surrounded by an air jacket. The temperature inside the cell was controlled by flowing water through the air jacket from a circulator

(LAUDA, RE104). The sample was then equilibrated in water at a specific temperature for a certain period. The change in the diameter of the cylindrical polymer gel was monitored under an inverse microscope (Olympus, CKX41) equipped with a measuring unit (Flovel, MC-70). The equilibrium swelling ratios, d/d0, where d0 is the diameter of the cylindrical polymer gel at the preparative state and d is the diameter of an equilibrated cylindrical polymer gel under specific conditions, were measured at various temperatures. Shrinking Kinetics of Polymer Gels. The cylindrical polymer gel was kept in water in the glass cell used for measuring the equilibrated swelling ratio. Two circulators fixed at two different target temperatures were connected to the glass cell (Figure S10). By changing the path of the water flow, we could quickly switch the temperature inside the cell from one temperature to another. The PNIPA gel prepared with BIS was used for comparison.

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RESULTS AND DISCUSSION

Preparation of PNIPA-Grafted iPR. We first prepared PNIPA-grafted iPR (PNIPA-iPR), which is the precursor to the building-block molecules. The combination of a chloropropionate-functionalized initiator and CuCl/tris [2-(dimethylamino)ethyl]amine (Me6TREN) as the catalytic system was found to be an effective system for the controlled radical polymerization of NIPA.48 Each α-CD molecule of iPR has approximately 14 available hydroxyl groups at which the initiator can be introduced.49 Initially, we synthesized macroinitiators (iPR-MI) with an average of 0.5−2.5 polymerizable initiators per α-CD molecule in the iPR (Table S1) because PNIPA-iPR has a relatively small amount of grafted PNIPAs that must undergo an inherent coil−globule transition response to changes in temperature. On the basis of the results of our exhaustive study, iPR-MI with approximately 2.5 polymerizable initiators for each α-CD in iPR was eventually used in this research. Aqueous−organic mixed solvents such as N,N-dimethylformamide/water are known to be convenient solvents for the controlled radical polymerization of NIPA to obtain PNIPA with a desired molecular weight and a narrow molecular-weight distribution.48,50 However, as will be explained later, the presence of water is disadvantageous for preparing the two types of building blocks. Thus, we used dried DMSO as the reaction solvent.51−53 2-Chloropropionate (ECP) was added as a free initiator in the reaction solution to control the polymerization process for preparing grafted PNIPA from iPR-MI.54,55 Table S2 shows the results of the controlled radical polymerization of NIPA, initiated from iPR-MI and from ECP under reaction conditions that were identical except for the reaction times. The resultant polymer solution was used to determine the monomer conversion by 1H NMR in d-DMSO (Figure S3) using the following expression:54,55 ⎛ I ⎞ conversion (%) = ⎜1 − 5.5 ⎟ × 100 (%) I3.8 ⎠ ⎝

(2)

The conversion of monomers to polymers was calculated by comparing the peak area of the monomer signals at 5.5 ppm (I5.5, 1H, vinyl proton of the NIPA monomer) with that of the polymer signal at 3.8 ppm (I3.8, 1H, lone proton of the Nisopropyl group of both the NIPA monomer and PNIPA), which were corrected to account for the relative contribution of the monomers. The theoretical value of Mn (Mth) was calculated using the expression D

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Figure 1. Synthesis of PNIPA-iPR with the free initiator: (a) Monomer conversion as a function of polymerization time during the controlled radical polymerization of NIPA. (b) Plots of the number-averaged molecular weight, Mn, and polydispersity index (Mw/Mn) versus conversion. The straight line corresponds to the theoretical Mn versus conversion plot. Solid circles: Mn of grafted-PNIPA; open circles: Mn of free PNIPA; solid diamonds: Mw/Mn of grafted-PNIPA; and open diamonds: Mw/Mn of free PNIPA.

M th =

[M] × M n‐NIPA × conversion (%) ÷ 100 [I]

Scheme 2. Schematic of the Molecular Structure of PNIPAiPR

(3)

where Mn‑NIPA is the molecular weight of NIPA monomer (113.16) and [M] and [I] are the concentrations of the monomer (NIPA) and the initiators (the initiators in iPR-MI and ECP), respectively. Prior to determining the average polymer molecular weight (Mn) and the polydispersity index (PDI) of the PNIPA, we separated PNIPA-iPR and PNIPA by dialysis. The grafted PNIPA molecules in PNIPA-iPR were isolated by hydrolysis of the resultant PNIPA-iPR using an alkali buffer solution. The Mn and the PDI of the resultant polymer solution were examined by gel permeation chromatography (GPC). In these experiments, the controlled radical polymerization provides a high conversion rate that approaches approximately 80% in 24 h (Figure 1a). However, the conversion did not increase beyond 80% when the reaction was extended beyond 24 h. Nonetheless, the GPC traces were reasonably symmetrical with no shoulders or tails even in the cases of higher conversion values. Moreover, the Mn of both the grafted and free PNIPAs increased linearly with increasing conversion rate, and the PDI of these PNIPAs remained low throughout the polymerization (Figure 1b), which indicates that the growth centers were not lost during the reaction, as shown in Figure 1. The Mn of these PNIPAs obtained by GPC was comparable to the target molecular weight at each point in time, which also demonstrates the efficiency of the initiator. In the absence of the free initiator, the polymerization of NIPA from iPR-MI could not be precisely controlled through this approach (Figure S4).54,55 These results indicate that we should stop the polymerization within approximately 20 h so that the end groups of the grafted PNIPA do not become inactive states. As previously described, we successfully synthesized thermosensitive PR molecules containing grafted PNIPA with almost equal Mn values and a narrow PDI distribution on the αCD molecules. Scheme 2 shows a schematic molecular structure of PNIPA-iPR with respect to the sizes and structures of PEG, α-CD, and PNIPA (Figure S5). The grafted PNIPA may attain a slightly elongated state rather than a random coil state in the PNIPA-iPR depending on the average distance

between α-CD molecules. Consequently, we can predict that PNIPA-iPR becomes a polymer brush in aqueous solutions at temperatures lower than the general coil−globule transition temperature of PNIPA. Physical Properties of PNIPA-iPR in Aqueous Solution. Figure 2 shows the hydrodynamic radius (Dh) of PNIPA-iPR in pure water, as measured by the dynamic light scattering method, as a function of the temperature. The value

Figure 2. Hydrodynamic radius (Dh) of PNIPA-iPR, with the grafted PNIPA having a Mn of 3.4 × 103 in pure water, as a function of temperature; the Dh was measured by dynamic light scattering. E

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Figure 3. FT-IR (left) and Raman (right) spectra of PNIPA-iPR (black), N3-PNIPA-iPR (red), and Al-PNIPA-iPR (blue).

of Dh for PNIPA-iPR with the grafted PNIPA with a Mn of 3.4 × 103 decreased gradually as the temperature was increased from 26 to 50 °C. Free linear PNIPA with an Mn of approximately 3.0 × 103 in water forms substantial aggregates at approximately 43 °C,56 whereas the high-molecular-weight PNIPA flocculates substantially at approximately 32 °C. The difference in temperature sensitivity between PNIPA-iPR and the free linear PNIPA despite their equivalent molecular weights indicates that the PNIPAs grafted onto IPR form slightly elongated brushes (Scheme 2), as expected; it also indicates that the grafted PNIPAs interact with each other in the PNIPA-iPR molecule. As a result, the wide range of changes observed in the dissolved state of PNIPA-iPR as a function of temperature is assumed to be a result of the decreasing degree of freedom of the grafted PNIPA.54,55 However, the PNIPAiPR obtained under this experimental conditions described in Scheme 2 was used as a precursor for the building block to prepare the resulting polymer network because PNIPA-iPR exhibits sufficient temperature sensitivity derived from the PNIPA. Preparation of the Two Types of Building Blocks. Here, we describe the synthesis of the two different building blocks using PNIPA-iPR. A one-pot synthesis was used to prepare the building blocks with either azide or alkyne end groups from PNIPA-iPR after the controlled radical polymerization of NIPA from iPR-MI. Sodium azide (NaN3) was added to the reaction solution in which NIPA was polymerized from iPR-MI, and the conversion of NIPA to PNIPA ranged from approximately 40% to 70% (Tables S3 and S4). In this synthesis, dried DMSO was used as the solvent because the ester groups in iPR-MI can be hydrolyzed by sodium azide in the presence of water. Figure 3a shows the FT-IR spectra of PNIPA-iPR (black line) and the resultant polymer (red line) after the addition of NaN3. We confirmed a characteristic asymmetric stretching vibration of N−N for the azide group (Figure S7) at approximately 2112 cm−1 in the spectrum of the resultant polymer (N3-PNIPA-iPR).52 The molecular weight of the isolated PNIPA with the −Cl end group from PNIPA-iPR and that of the PNIPA with the −N3 end group from N3PNIPA-iPR were measured using GPC; the measured values are identical (Tables S2 and S3). N3-PNIPA-iPR was successfully prepared through the aforementioned one-pot synthesis. The reaction mechanism of this one-pot reaction is shown in Scheme 3.57 During the controlled radical polymer-

Scheme 3. Reaction Mechanism of the One-Pot Azidation

ization, known as atom transfer radical polymerization (ATRP), the end group of the polymer is in a state of dynamic equilibrium between a dormant species with alkyl halides (IMn-Cl) and a radical species (I-Mn•). In a typical ATRP process, the dormant species is activated by a transition-metal complex such as a copper complex ([CuL]+) to generate a radical (I-Mn•) via a one-electron-transfer process. Simultaneously, the transition metal is oxidized ([CuLCl]+). If azide ions (N3) are added to the reaction solution during ATRP, the transition metal forms a complex with the azide ion ([CuLN3]+), and the azide ion subsequently recombines with the end portion of the polymer (I-Mn-N3). In the presence of only halogen ions, the polymerization reaction can restart because the dissociation reaction is reversible. By contrast, the polymerization reaction stops when the azide ion binds to the polymerization growth terminal because dissociation of the combined azide ion at this terminal is difficult. We synthesized the alkyne terminal-connected PNIPA-iPR (Al-PNIPA-iPR) by reacting N3-PNIPA-iPR with 1,6-heptadiyne using the Huisgen reaction, one of the most popular click chemistry reactions. The complex composed of CuCl and Me6TREN was used as the catalyst for the ATRP process; this complex can also serve as a catalyst for the Huisgen reaction. We attempted to synthesize Al-PNIPA-iPR from iPR-MI using consecutive ATRP, azidation, and Huisgen reaction processes with the same copper complex as a common catalyst and without refining operations between these reactions. To avoid intramolecular click chemistry, an excess of 1,6-heptadiyne was added to the reaction solution. Figure 3a shows the FT-IR spectrum of the resultant product (the blue line). The N−N asymmetric stretching vibration of the azide group observed at approximately 2112 cm−1 in the FT-IR spectrum for N3PNIPA-iPR disappeared 24 h after the addition of 1,6heptadiyne to the reaction solution. In the corresponding Raman spectra, the characteristic stretching vibration of CC F

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Macromolecules Scheme 4. Syntheses of Polymer Networks Using N3-PNIPA-iPR and Al-PNIPA-iPR

Table 1. Synthesis of Polymer Networks Using N3-PNIPA-iPR and Al-PNIPA-iPR run

N3-PNIPA-iPR

AI-PNIPA-iPR

1 2 3 4

Mn = 8.7 × 103 Mw/Mn = 1.25

Mn = 8.6 × 103 Mw/Mn = 1.27

[N3-PNIPA-iPR]:[AI-PNIPA-iPR]:[Cu]:[L] (PNIPAiPR/DMSO) (wt %) 1:1:1:1 1:1:1:1 1:1:1:1 1:1:1:1

(10) (10) (10) (10)

reaction time (h)

ratio of network chain (%)

ratio of dangling chain (%)

1 5 24 72

36 39 45 46

64 61 55 54

Figure 4. (a) GPC traces for N3-PNIPA-iPR, Al-PNIPA-iPR, and hydrolyzed polymer gels prepared using different reaction times. (b) Change in the ratio of dangling chains and network chains in polymer gels as a function of reaction time.

(Figure S7) was observed at 2110 cm−1 only in the spectrum of the final product (blue line) obtained from the set of consecutive processes (Figure 3b). The molecular weight of the grafted PNIPA on the resultant Al-PNIPA-iPR was

measured by GPC after the hydrolysis of Al-PNIPA-iPR by an alkali solution (Table S4). As shown in the table, no change was observed between the molecular weight of the graftedPNIPA-N3 and that of the grafted-PNIPA-alkyne. On the basis G

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Macromolecules

Figure 5. (a) Equilibrium swelling ratio of cylindrical polymer gels with different amounts of network chains in water as a function of temperature. (b) Shrinking kinetics of cylindrical polymer gels with different amounts of network chains and a conventionally prepared PNIPA gel after a temperature increase from 20 to 40 °C.

of the aforementioned results, we confirmed that Al-PNIPAiPR was also successfully synthesized from iPR-MI via the onepot synthesis. Consequently, the two different building blocks that can form a polymer network were synthesized via a onepot synthesis using PNIPA-iPR as the initial structure. Preparation of Polymer Network from N3-PNIPA-iPR and Al-PNIPA-iPR by a Click Reaction. A polymer gel was prepared using the click reaction between N3-PNIPA-iPR and Al-PNIPA-iPR with the same copper catalyst (Scheme 4 and Table 1). Because intramolecular cross-linking is prevented in these building blocks during the click chemistry, the reacting polymer chains form a polymer network and the unreacted polymer chains can become dangling chains. The reaction solution turned into a polymer gel within 1 h. Figure 4a shows the change in the molecular weights of the polymer chains within the resultant polymer gel as a function of the reaction time. The polymer chains were isolated by hydrolysis of the polymer gel. We calculated the percentage of the polymer network and the dangling components (Table 1 and Figure 4b) by separating the waveforms of the GPC traces (Figure S8). The percentage of the polymer network component increased with increasing reaction time, whereas the percentage of the dangling component decreased. One hour after the reaction was started, 36% of the grafted PNIPA chains were crosslinked; this percentage increased to 46% in 72 h. In the early stages of the cross-linking reaction, the reaction progressed rapidly; however, the reaction stopped after 24 h. A possible reason for the reaction not proceeding further is that the progressive cross-linking reaction prevents the diffusion of each building block and the further interaction between the different types of end groups of each grafted PNIPA. The resultant polymer gel is very flexible and sticky because of the presence of the PR structure, in addition to the presence of the dangling chains (Supporting Information Movie 1). Thermosensitivity of the Polymer Gel in Water. Dependence of the Swelling Degree of the Polymer Gel on the Water Temperature. The temperature-dependent equilibrated swelling degree of the polymer gel in water was

investigated. A tiny cylindrical polymer gel prepared in a micropipet with a 348 μm inner diameter was used to determine the swelling degree. Using the diameter of the polymer gel at a certain temperature, d, and the original size of the polymer gel, d0, which is the same as the size of the inner diameter of the micropipet, we calculated the swelling degree as d/d0.58,59 Figure 5a shows the temperature dependence of the equilibrated swelling degree of the polymer gel synthesized using an equal number of the two building blocks with different cross-linking reaction ratios. The overall equilibrated swelling degree of the polymer gel with a higher cross-linking reaction ratio is smaller than that of the polymer gel with a lower crosslinking reaction ratio. The decrease in the mesh size of the polymer network as the cross-linking reaction progressed resulted in the observed decrease in the swelling degree of the polymer gel.60,61 Evaluation of the Response Speed for the Polymer Gel in Water. Figure 5b shows the kinetic change in the swelling ratio of the polymer gel obtained using a temperature-controlled bath with a circulator to cause a sudden change in the water temperature from 20 to 40 °C. The vertical axis is the swelling ratio (d/d20 °C), where d is the diameter of a tiny cylindrical polymer gel at a certain temperature in water and d20 °C is the diameter of a tiny cylindrical polymer gel at 20 °C in water. The polymer gel composed of the two building blocks with different cross-linking ratios, which we used to measure the equilibrated swelling ratio shown in Figure 5a, was used to observe the kinetic change. The polymer gel prepared with the same amount of NIPA and methylenebis(acrylamide) (BIS) as the cross-linker was used in the comparison.34 The kinetic change in the swelling ratios of these polymer gels was compared after the sudden temperature increase. The PNIPA gel prepared with BIS via a general radical polymerization method contracted drastically at the beginning in response to the sudden change in temperature. However, the formation of a skin layer in the PNIPA gel caused a rapid decrease in the volume change.62 As a result, the volume of the PNIPA gel changed slowly, and the H

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Macromolecules gel retained its opacity. By contrast, the polymer gel composed of PNIPA-iPR-based building blocks exhibited a rapid deswelling rate and shrank isotropically without deforming the polymer gel surface. The polymer gel reached its equilibrium at a transparent shrunken state between 60 and 90 s after the temperature increase. Because the change in the volume of the polymer gel is highly correlated to the change in the water temperature, we confirmed that the polymer gel exhibits an extremely rapid response to temperature changes. The introduction of a large amount of freely mobile dangling chains into the polymer network by design enhanced the shrinking rate of the polymer gel. The results in Figure 5b indicate that an increase in the proportion of the dangling bonds contributed to an increase in the response rate of the change in the volume with respect to temperature.

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AUTHOR INFORMATION

Corresponding Author

*(Y.T.) E-mail [email protected], Fax +81-52789-4669, Tel +81-52-789-4670. ORCID

Yukikazu Takeoka: 0000-0002-1406-0704 Present Address

A.B.I.: Department of Chemistry, Faculty of Engineering, Bangladesh University of Engineering and Technology, Dhaka1000, Bangladesh. Notes

The authors declare no competing financial interest.

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CONCLUSIONS In this study, we prepared PNIPA-grafted PR building blocks with three features that enable the preparation of flexible and rapidly responsive polymer gels: a PR structure that enables flexibility of the polymer network, thermosensitive polymers with grafted reactive end-groups that form the polymer network, and thermosensitive dangling polymer chains that promote the rapid sensitivity of the polymer network. The polymer network with a PR framework and different amounts of dangling PNIPA chains were successfully prepared via click chemistry using two types of PNIPA-grafted PRs as the building blocks. The PNIPA-grafted PRs were synthesized by a reversible deactivation radical polymerization technique. The temperature response of the polymer gel in response to rapid changes in temperature was dramatically faster than that of reference PNIPA gels prepared with BIS using the typical radical polymerization method. We could not measure the mechanical properties of this polymer gel because the gel has a highly adhesive surface that is possibly a consequence of the presence of the dangling chains. However, we confirmed the softness and high tensibility of the polymer gel by touching the gel. This hydrogel may have applications such as actuators and drag reservoir for drug delivery systems. In future work, we plan to prepare more functionalized polymer gels by incorporating specific changes into the accurate design of the building blocks.

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Movie S1 (AVI)

ACKNOWLEDGMENTS Y.T. and K.I. acknowledge the support of ImPACT for “Realizing an Ultrathin and Flexible Tough Polymer”. We are also grateful to Prof. Morita of Osaka Electro-Communication University for helpful discussions and suggestions. NIsopropylacrylamide was kindly provided by Kohjin (Tokyo, Japan).

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REFERENCES

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ASSOCIATED CONTENT

S Supporting Information *

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.macromol.6b01955. Additional data for the tables showing the synthesis of macroinitiator, PNIPA-iPR, N3-PNIPA-iPR, and AlPNIPA-iPR, NMR spectra of iPR-MI, NIPA, PNIPA, and PNIPA-iPR, the plots of Mn vs conversion, and Mw/ Mn vs conversion for the synthesis of PNIPA-iPR, schematic figures of each molecular parts to prepare polymer networks, FT-IR spectra of PNIPA-iPR, N3PNIPA-iPR, and Al- PNIPA-iPR, theoretical FT-IR and Raman spectra for CH3−CC−H, and CH3−N3, GPC traces of hydrolyzed polymer networks, schematic representation of size change in a polymer gel, schematic representation of an apparatus for a water jump system, and the pictures showing the change in the size of cylindrical polymer gel prepared by NIPA and BIS (PDF) I

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