Thermosensitive Ionic Microgels with pH Tunable Degradation via in

Apr 9, 2015 - of N-isopropylacrylamide (NIPAm) and 1-vinylimidazole (VIM) at 70 °C with degradable 1,4-phenylene bis(4-bromobutanoate)...
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Thermosensitive Ionic Microgels with pH Tunable Degradation via in Situ Quaternization Cross-Linking Xianjing Zhou,† Jingjing Nie,‡ Qi Wang,† and Binyang Du*,† †

MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science & Engineering, and Department of Chemistry, Zhejiang University, Hangzhou 310027, China

‡

S Supporting Information *

ABSTRACT: Degradable thermosensitive ionic microgels were synthesized via surfactant-free emulsion polymerization (SFEP) of N-isopropylacrylamide (NIPAm) and 1-vinylimidazole (VIM) at 70 °C with degradable 1,4-phenylene bis(4-bromobutanoate) or 1,6-hexanediol bis(2-bromopropionate) as quaternized cross-linkers. VIM could be quaternized by 1,4-phenylene bis(4bromobutanoate) or 1,6-hexanediol bis(2-bromopropionate), leading to the formation of degradable cross-linking network and ionic microgels. Combined techniques of transmission electron microscopy (TEM), dynamic light scattering (DLS), electrophoretic light scattering (ELS), UV−vis spectroscopy, FT-IR spectra, and gel permeation chromatography (GPC) were employed to systematically investigate the sizes, morphologies, and properties of the obtained microgels before and after degradation as well as the degradation mechanism. The obtained microgels were spherical in shape with narrow size distribution and exhibited thermosensitive behavior and controllable degradation. The disintegration of the microgels was confirmed to be resulted from the hydrolysis of ester bonds of the cross-linkers. The degradation rate of the obtained microgels could be regulated by tuning the pH value of microgel suspensions. The PNI-Ph series of microgels fabricated with 1,4-phenylene bis(4bromobutanoate) as the cross-linking agent could gradually degrade even in neutral solution with lifetimes of 44−53 h, depending on the quaternization ratio. The degradation of PNI-Ph series of microgels experienced two reaction processes, that is, the hydrolysis of ester bonds of the cross-linkers and the oxidation of generated hydroquinone to form benzoquinone. It was also demonstrated that different silica nanostructures could be fabricated by using such degradable thermosensitive ionic microgels as the template at various temperatures.

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INTRODUCTION Microgels are polymeric colloidal particles with three-dimensional cross-linked networks that are swollen in good solvents.1−10 Microgels have sizes of 1−1000 nm and possess the properties of hydrogels and colloidal particles.11 Since Pelton and Chibante12 first reported the thermosensitive poly(N-isopropylacrylamide) (PNIPAm) microgels in 1986, microgels have been proved to be a potential candidate for various cutting edge applications such as controlled release systems, nanoreators, separation technology, catalysis, surface coatings, and enzyme immobilization biosensors.6,13−20 Various multifunctional monomers such as N,N′-methylene bisacrylamide (BIS), divinylbenzene (DVB), ethylene glycol dimetha© XXXX American Chemical Society

crylate (EGDMA), diallyl phthalate (DAP), butanediol diacrylate (BDDA), glycerol dimethacrylate (GDMA), pentaerythritol triacrylate (PETA), acrylated α-, β-, and γ-cyclodextrins, and poly(ethylene glycol) diacrylate (PEGDA) were used as cross-linkers for the syntheses of thermosensitive microgels.5,21−24 The variation of the cross-linkers hence gave additional possibility to tune the size, structures, and properties of the resultant thermosensitive microgels. Received: March 5, 2015 Revised: March 31, 2015

A

DOI: 10.1021/acs.macromol.5b00482 Macromolecules XXXX, XXX, XXX−XXX

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Macromolecules Scheme 1. Synthesis of Degradable Thermosensitive Ionic Microgels via Quaternized Cross-Linking Reaction

main monomer to offer the resultant microgels thermosensitive character. 1-Vinylimidazole (VIM) with tertiary amine was chosen as the quaternizable comonomer. During the SFEP procedure of NIPAm and VIM in the presence of degradable halogenated compound, the quaternized cross-linking reaction between the degradable halogenated compound and the comonomer VIM led to the formation of degradable crosslinking network and thermosensitive ionic microgels. A schematic preparation of degradable thermosensitive ionic microgels is shown in Scheme 1. The obtained microgels were spherical in shape with uniform size distribution and degradable in neutral or alkaline solution depending on the type of halogenated compound. The degradation rate could be finetuned by the pH value. Combined techniques of transmission electron microscopy (TEM), dynamic light scattering (DLS), electrophoretic light scattering (ELS), UV−vis spectroscopy, FT-IR spectra, and gel permeation chromatography (GPC) were employed to systematically investigate the sizes, morphologies, and properties of the obtained microgels before and after degradation as well as the degradation mechanism. It was also demonstrated that such degradable thermosensitive ionic microgels could be used as degradable templates for the preparation of silica nanoparticles with various structures.

Especially, the obtained thermosensitive microgels could be degradable if the cross-linker used was degradable. The compounds entrapped within the microgels might be released during the degradation of microgels with a controllable manner. Such degradable microgels have received widespread attention because of their potential utilities for controlled release systems, tissue engineering, and other applications. However, a few degradable microgels were reported up to date.25−30 For example, Pich et al.25 used reactive polyvinylalkoxysiloxanes as cross-linkers (Cross-PAOS) to synthesize degradable thermosensitive poly(N-vinylcaprolactam) microgels, of which the cross-linking sites could be degraded under alkaline conditions. They found that the microgels underwent fastest degradation at pH 12, slower at pH 11, and little changed at pH 10. Liu et al.26 fabricated multifunctional thermosensitive microgels with Nisopropylacrylamide (NIPAm), (2-dimethylamino)ethyl methacrylate (DMAEMA), and 3-acrylamidephenylboronic acid (AAPBA) as the monomers and N,N′-bis(arcyloyl)cystamine (BAC) as the reductive degradable cross-linker. Acid-labile poly(hydroxyethyl methacrylate) (PHEMA) microgels with sizes of 150−475 nm were synthesized in the presence of divinyl-functionalized acetal-based cross-linkers via an inverse emulsion polymerization method.27 Aguirre et al.28 reported the synthesis of enzymatically degradable poly(N-vinylcaprolactam) nanogels with dextran methacrylates as the crosslinkers. Landfester et al.29,30 prepared enzymatically cleavable and light-degradable nanogels by free radical inverse miniemulsion copolymerization of acrylamide (AAm) with acrylatefunctionalized dextrans containing photocleavable linkers. Recently, a type of thermosensitive ionic microgel was developed by us via the simultaneous quaternized cross-linking reaction during the surfactant free emulsion copolymerization (SFEP) of N-isopropylacrylamide (NIPAm) as the main monomer, 1-vinylimidazole (or 4-vinylpyridine) as the comonomer, and 1,4-dibromobutane (or 1,6-dibromohexane) as the cross-linker to quaternize the tertiary amine of the comonomer.31 The resultant microgels exhibited thermosensitive behavior and unique feature of poly(ionic liquid) in aqueous solutions.31 In the present work, we reported the thermosensitive ionic microgels with pH tunable degradation. Two dihalogenated compounds with different degradation properties, namely 1,4-phenylene bis(4-bromobutanoate) and 1,6-hexanediol bis(2-bromopropionate), were designed and synthesized. N-Isopropylacrylamide (NIPAm) was used as the

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EXPERIMENTAL SECTION

Materials. Hydroquinone (HQ), 4-bromobutyryl chloride, Nisopropylacrylamide (NIPAm), 1-vinylimidazole (VIM), 2,2′-azobis(2methylpropionamidine) dihydrochloride (AIBA), triethylamine, dichloromethane, hexanes, ethyl acetate, sodium hydroxide, sodium chloride, hydrogen chloride, benzoquinone, and tetraethyl orthosilicate (TEOS) were used as received without further purification. Synthesis of 1,4-Phenylene Bis(4-bromobutanoate). Hydroquinone (0.22 g, 2.0 mmol, 1.0 equiv) and triethylamine (1.04 mL, 0.74 g, 7.4 mmol, 3.7 equiv) were dissolved in 50 mL of dichloromethane and cooled to 0 °C. 4-Bromobutyryl chloride (0.86 mL, 1.37 g, 7.4 mmol, 3.7 equiv) was then added dropwise to the solution under stirring. The reaction mixture was then warmed to room temperature under stirring overnight. The mixture was washed three times with sodium hydroxide (1 M), followed by aqueous solution of sodium chloride (0.1 M). The organic layers were combined and dried over anhydrous sodium sulfate, filtered, and then concentrated. The crude product was purified by flash column chromatography using 3:1 hexanes/ethyl acetate to give 0.70 g (85.9%) of 1,4-phenylene bis(4-bromobutanoate) as a white solid. 1H NMR and ESI-MS measurements confirmed the chemical structure of 1,4-phenylene bis(4-bromobutanoate) (see Figures S1and S2 in the B

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Macromolecules Table 1. Preparation Conditions and Properties of Degradable Thermosensitive Ionic Microgels cross-linking agent (mmol) sample codes PNI-Ph-1/2 PNI-Ph-2/3 PNI-Ph-1 PNI-hexane-1 a

NIPAm (mmol)

VIM (mmol)

1,4-phenylene bis(4-bromobutanoate)

2

0.3

0.075 0.1 0.15

DLS

1,6-hexanediol bis(2-bromopropionate)

Dha (nm)

PDIb

0.15

733.2 707.5 554.3 516.1

0.095 0.099 0.049 0.076

TEM D (nm)

swelling ratio (V25/V60)

± ± ± ±

26 20 8 39

382 421 410 248

24 26 28 15

Measured at 25 °C. bPDI = polydispersity index of the thermosensitive ionic microgels measured by DLS.

Figure 1. Representative TEM images and the corresponding size distributions of the degradable thermosensitive ionic microgels: (A) PNI-Ph-1/2, (B) PNI-Ph-2/3, (C) PNI-Ph-1, and (D) PNI-hexane-1. Supporting Information). 1H NMR (400 MHz, CDCl3): 2.28 ppm (4H, CH2CH2CH2Br), 2.82 ppm (4H, COOCH2CH2), 3.52 ppm (4H, CH2CH2CH2Br), 7.12 ppm (4H, Ar). ESI-MS (m/z): [M − Br + NH4]+: 346.0, [M + Na]+: 431.8, [M + NH4]+: 425.8, [M − 2Br + Na]+: 274.3. Synthesis of 1,6-Hexanediol Bis(2-bromopropionate). 1,6Hexanediol bis(2-bromopropionate) was synthesized previously.32 Fabrication of Degradable Thermosensitive Ionic Microgels. The degradable thermosensitive ionic microgels were prepared by using N-isopropylacrylamide (NIPAm) as the main monomer, 1vinylimidazole (VIM) as the quaternizable comonomer, and 1,4phenylene bis(4-bromobutanoate) or 1,6-hexanediol bis(2-bromopropionate) as degradable cross-linkers via the simultaneous quaternized cross-linking reaction during the surfactant free emulsion copolymerization (SFEP). Briefly, given amounts of NIPAm, VIM, and 1,4phenylene bis(4-bromobutanoate) [or 1,6-hexanediol bis(2-bromopropionate)] were added into three-necked flask with 45 mL of deionized water. The temperature of the solution was increased to 70 °C under vigorous stirring. Oxygen was eliminated by bubbling nitrogen for 20 min. Then AIBA aqueous solution (5 mg/mL, 5 mL) was injected into the solution to initiate the polymerization. The reaction was continued at 70 °C for 6 h. Table 1 summarizes the preparation conditions of the obtained degradable thermosensitive

ionic microgels. Poly(N-isopropylacrylamide-co-1-vinylimidazole)/1,4phenylene bis(4-bromobutanoate) microgels [P(NIPAm-co-VIM)/1,4phenylene bis(4-bromobutanoate)] and poly(N-isopropylacrylamideco-1-vinylimidazole)/1,6-hexanediol bis(2-bromopropionate) microgels [P(NIPAm-co-VIM)/1,6-hexanediol bis(2-bromopropionate)] were coded as PNI-Ph and PNI-hexane, respectively. The numbers 1/2, 2/3, and 1 mean the feeding quaternization ratio of the microgels, which presented the molar ratio of bromo groups in 1,4-phenylene bis(4-bromobutanoate) or 1,6-hexanediol bis(2-bromopropionate) to imidazole moieties of VIM. The yields of microgels were approximately 74.5−80.5%. The linear copolymer of poly(N-isopropylacrylamide-co-1-vinylimidazole) [P(NIPAm-co-VIM)] was synthesized by free radical copolymerization of NIPAm and VIM as reported previously.31 Degradation of the Thermosensitive Ionic Microgels. In order to study the degradation of the obtained thermosensitive ionic microgels in neutral aqueous solution, the variations of the scattering light intensity and polydispersity index (PDI) of the PNI-Ph and PNIhexane-1 microgels were monitored by dynamic light scattering (DLS) at different times after the polymerization was completed. To study the degradation of thermosensitive ionic microgels in aqueous solution with various pH values, the freshly prepared PNI-Ph and PNI-hexane-1 microgels were directly mixed with HCl or NaOH C

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Figure 2. (A) Hydrodynamic diameters of the PNI-Ph series of degradable thermosensitive ionic microgels measured by DLS as a function of measuring temperature with fixed amount of VIM (0.3 mmol) and various amount of 1,4-phenylene bis(4-bromobutanoate), i.e., with various quaternization ratios. The inset of (A) was the evolution of hydrodynamic diameters of PNI-Ph-1 microgels during the heating and cooling cycles. (B) Size distribution of the PNI-Ph series of microgels measured by DLS at 25 °C. chromatography (GPC) with N,N-dimethylformamide (DMF) as eluent and narrow-polydispersed poly(methyl methacrylate) (PMMA) as the calibration standard. The nitrogen adsorption−desorption isotherms were measured by using a Micromeritics Tristar II 3020 system. Before measuring the isotherms, the samples were pretreated at 80 °C overnight in vacuum. The data were calculated by BJH (Barrett−Joyer−Halenda) and BET (Brunauer−Emmett−Teller) methods. The pore size distribution was calculated from the desorption branch of the isotherm.

solutions of different pH and immediately measured by DLS and UV− vis spectrophotometer to monitor the variation of scattering light intensity, PDI, UV−vis absorption, and transmittance spectra as a function of time. Fabrication of Silica Nanostructures with PNI-Ph-1 Microgels as Degradable Templates. Silica nanostructures were prepared in aqueous solution by using PNI-Ph-1 microgels as degradable templates. First, 2.0 g of tetraethyl orthosilicate (TEOS) was added into 18 mL of deionized water; the mixture was then heated to 50 °C and stirred for 3 h. Afterward, 50 mL of freshly prepared PNI-Ph-1 microgels was quickly added into the prehydrolyzed TEOS solution. The mixed solution was continuously stirred for 5 days at 50 or 25 °C. After the completion of reaction, the reaction mixture was purified by centrifugations and washed with deionized water for several times at room temperature. Silica nanoparticles with different structures were obtained. Characterization. 1H NMR spectra were recorded at room temperature by a Bruker (400 MHz) spectrometer using tetramethylsilane as the internal standard and CDCl3 as the solvent. Electrospray ionization−tandem mass spectrometry (ESI-MS) analyses were performed on an Esquire 3000 plus mass spectrometer using methanol as solvent for the halogenated compounds. The morphologies of the degradable thermosensitive ionic microgels and silica nanostructures were observed by transmission electron microscopy (TEM) on a HT-7700 electron microscope operated at an acceleration voltage of 100 kV as well as scanning electron microscopy (SEM) on a Hitachi S4800 electron microscope. The TEM samples were prepared by dip-coating with Formvar-coated copper grids into the sample solutions. The solvent was gently absorbed away by a filter paper. The grids were then allowed to dry in air at room temperature before observation. The SEM samples were prepared by dropping a droplet of the sample solution onto the aluminum foil at room temperature, which was then allowed to dry in air at room temperature. The samples of SEM were coated with platinum vapors before observation. The hydrodynamic diameters, size distributions, thermosensitive behaviors, and scattering light intensities of the obtained degradable thermosensitive ionic microgels were investigated by dynamic light scattering (DLS) at scattering angle θ of 90° by using a 90 Plus particle size analyzer (Brookhaven Instruments Corp.). The zeta-potentials ξ of the ionic microgels were also measured by electrophoretic light scattering (ELS) using the same Zeta Plus particle size analyzer. UV−vis spectra were recorded on a Cary 100 instrument (Varian Australia Pty Ltd.). The pH values of sample solutions were measured by a pH meter (FE20, Mettler Toledo). FT-IR spectra were recorded on a Vector 22 Bruker spectrometer. Weight-average molecular weight (Mw) and polydispersity index (PDI) of the linear copolymer and degradation product of microgels were determined by gel permeation

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RESULTS AND DISCUSSION Fabrication of Degradable Thermosensitive Ionic Microgels. As shown in Scheme 1, two kinds of degradable thermosensitive ionic microgels were successfully obtained with degradable 1,4-phenylene bis(4-bromobutanoate) or 1,6hexanediol bis(2-bromopropionate) as cross-linkers. Figure 1 shows the representative TEM images and the corresponding size distributions of resultant degradable thermosensitive ionic microgels. The obtained degradable thermosensitive ionic microgels were spherical in shape with a narrow size distribution. The average diameters of the microgels with sample codes of PNI-Ph-1/2, PNI-Ph-2/3, PNI-Ph-1, and PNIhexane-1 were about 382 ± 24, 421 ± 26, 410 ± 28, and 248 ± 15 nm, respectively, as calculated from the TEM images (cf. Table 1). The size of microgels with 1,6-hexanediol bis(2bromopropionate) as the cross-linker was slightly smaller than those of microgels with 1,4-phenylene bis(4-bromobutanoate) as the cross-linker. As expected, the PNIPAm microgels exhibit thermosensitive characters. Dynamic light scattering (DLS) was used to investigate the hydrodynamic diameters and thermosensitive behavior of the obtained degradable thermosensitive ionic microgels. Figure 2A shows the hydrodynamic diameters of PNI-Ph series of microgels as a function of temperature. The hydrodynamic diameters decreased with increasing the measuring temperatures. At a given temperature, the hydrodynamic diameters decreased with increasing the quaternization ratio when the amount of comonomer VIM was fixed to be 0.3 mmol. For PNI-Ph series of ionic microgels, the quaternization ratio meant the feeding molar ratio of bromo groups of 1,4phenylene bis(4-bromobutanoate) to the imidazole moieties of VIM in the P(NIPAm-co-VIM)/1,4-phenylene bis(4-bromobutanoate) microgels. What is more, with increasing the quaternization ratio the volume phase transition temperature D

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Macromolecules (VPTT) of the PNI-Ph ionic microgels slightly shifted to the lower temperature, and the temperature range of phase transition became broader. The VPTTs of PNI-Ph-1/2, PNIPh-2/3, and PNI-Ph-1 microgels were 48, 42, and 37 °C, respectively. On one hand, the quaternary ammonium salt of the cross-linked structure increased the hydrophilicity; on the other hand, the phenolic ester structure increased the hydrophobicity. For the PNI-Ph microgels, the latter effect was more obvious. As a result, the VPTT of PNI-Ph series of microgels decreased with increasing the quaternization ratio. Moreover, the quaternization ratio of such thermosensitive ionic microgels represented the cross-linking density of the resultant microgel networks. Increasing the quaternization ratio meant the increase of cross-linking density of the microgel networks, which usually led to the decrease of microgel sizes and the broadened phase transition, as shown in Figure 2A.5,6,13,31,33 Furthermore, the thermosensitive behavior of the ionic microgels was reversible, as shown in the inset of Figure 2A. With decreasing temperature from 70 to 25 °C, the hydrodynamic diameters of the PNI-Ph-1 ionic microgels increased again along the similar track of the heating procedure. No hysteresis of hydrodynamic diameter in the heating-andcooling cycle was observed for PNI-Ph-1 ionic microgels. The swelling ratios of the PNI-Ph series of degradable thermosensitive ionic microgels were also calculated and listed in Table 1. Note that the swelling ratio was given as the ratio of the volume V25 of the microgels at 25 °C to the volume at 60 °C, i.e., V25/V60. Obviously, the swelling ratios of PNI-Ph series of microgels decreased with increasing the quaternization ratio. It was reasonable because increase of quaternization ratio led to the increase of cross-linking density of the microgel networks, which usually resulted in the lower swelling ratio. In addition, the microgels with lower quaternization ratio contained unquaternized imidazole units, which were partially protonated and hence also contributed to the higher swelling ratio. The swelling properties of the obtained microgels could be tuned by the quaternization ratio. Figure 2B shows the size distribution of PNI-Ph series of microgels measured by DLS at 25 °C, which clearly indicated that the obtained degradable thermosensitive ionic microgels were with narrow size distribution. Similarly, reversible thermosensitive behavior and narrow size distribution were observed for PNI-hexane-1 microgels, as shown in Figure S3. The hydrodynamic diameter and swelling ratios of PNI-hexane-1 microgels are given in Table 1. Figure 3 shows the zeta-potentials of the PNI-Ph and PNIhexane-1 series of degradable thermosensitive ionic microgels. As expected, the zeta-potentials of the obtained ionic microgels were positive and increased linearly with increasing the quaternization ratio from 1/2 to 1 for the PNI-Ph series of microgels. The quaternary comonomers of the obtained ionic microgels led to the positive zeta-potentials. The linear increase of zeta-potential with feeding quaternization ratio increasing from 1/2 to 1 suggested that the dibromide cross-linking agents almost completely reacted with the tertiary amines of the comonomers during the radical copolymerization.31 Furthermore, the zeta-potentials of PNI-hexane-1 and PNI-Ph-1 were almost the same when the amounts of quaternized cross-linking agents were fixed. Degradation of the Thermosensitive Ionic Microgels. The dibromo compounds used here to form the quaternized cross-linking networks of the thermosensitive ionic microgels contain ester bonds, which are hydrolyzable in certain

Figure 3. Zeta-potentials of the degradable thermosensitive ionic microgels with various quaternization ratios. All the measurements of zeta-potential were performed at 25 °C. The pH of the obtained ionic microgels was measured to be 6.82 ± 0.04.

circumstances. The hydrolysis of ester bonds would result in the disruption of cross-linked structures and the degradation of the thermosensitive ionic microgels. Furthermore, 1,4-phenylene bis(4-bromobutanoate) and 1,6-hexanediol bis(2-bromopropionate) contain phenolic and alcoholic ester groups, respectively. Therefore, the PNI-Ph series of microgels and PNI-hexane-1 microgels might exhibit various degradation properties. Figure 4A shows the percentage of scattering intensity of the PNI-Ph and PNI-hexane-1 microgels in neutral aqueous solution measured by DLS at 25 °C as a function of time. Note that the scattering intensity of microgels at 0 h was taken as the reference state, and the percentage of scattering intensity was given as the percentage of the scattering intensity of microgels at t h to the reference scattering intensity at 0 h, i.e., (It /I0) × 100%. The smaller the percentage of scattering intensity indicated the greater the degree of degradation. For the PNI-Ph series of microgels, the percentage of light intensity decreased significantly with time (Figure 4A). In addition, the color of the solution changed from milky white to brown for PNI-Ph microgels during degradation (Figure S4). These phenomena indicated that the PNI-Ph series of microgels degraded in neutral aqueous solution. The degradation rate of PNI-Ph microgels decreased with increasing the quaternization ratio. Note that the amount of VIM was fixed to be 0.3 mmol. The kinetic of degradation could be well described by the exponential decay equation given as N (t ) = N0e−t / τ

(1)

N(t) is the quantity (here the percentage of light intensity) at time t, N0 = N(0) is the initial quantity, i.e. the quantity at time t = 0, and τ (called the lifetime) is the time at which the quantity is reduced to 1/e of its initial value. The time required for the decaying quantity to fall to one-half of its initial value is called the half-life, t1/2 = τ ln(2). The degradation rate can be characterized by lifetime τ and half-life t1/2 quantitatively. By fitting the data of Figure 4A with eq 1, the τ’s of PNI-Ph-1/2, PNI-Ph-2/3, and PNI-Ph-1 microgels degraded in neutral aqueous solution were 44, 51, and 53 h, respectively. The t1/2’s were 30, 35, and 37 h, respectively. As mentioned above, increasing the quaternization ratio meant the increase of crosslinking density of the microgel networks; the higher crosslinking density led to the slower degradation rate. Figure 4B shows the polydispersity index (PDI) of the PNI-Ph series of E

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Figure 4. (A) Percentage of scattering intensity (%) and (B) the corresponding polydispersity index of the PNI-Ph and PNI-hexane-1 microgels in neutral aqueous solution measured by DLS at 25 °C as a function of time.

VIM) linear polymer and PNI-Ph-1 microgels after degradation did not have these characteristic absorption bands, indicating that the ester bonds in the microgel networks disappeared after degradation. These results supported that the degradation of the microgels was indeed resulted from the hydrolysis of ester bonds of the cross-linker, 1,4-phenylene bis(4-bromobutanoate). Figure 6 shows the scattering intensity (kcps, left) and the corresponding PDI (right) of the PNI-Ph-1 and PNI-hexane-1 microgels measured by DLS at 25 °C as a function of pH value. Note that the DLS measurements were immediately carried out after the adjustment of pH value, approximately 5 min. The smaller the value of scattering intensity was, the greater was the degree of degradation. For PNI-Ph-1 microgels (Figure 6A), the scattering intensity did not decrease when the aqueous solution was acidic, neutral, or even weakly alkaline until pH value reached up to 11.7. Further increasing the pH value of the aqueous solution from 11.7 to 12.6 led to the strong decrease of the scattering intensity. When the pH value was 12.6, the scattering intensity had dropped below 30 kcps and kept unchanged with further increasing the pH value. It was reasonable because the hydrolysis of ester bonds took place immediately if the alkaline of solution was strong enough. The evolution of PDI value also indicated that the hydrolysis reaction rapidly occurred when the pH value of microgel suspension was larger than 11.7. The ionic strength of the microgel suspension had not impact on the degradation of the microgels. The ionic strength of the microgel suspension came from the addition of HCl or NaOH solution for adjusting the pH value. When the pH value of the microgel suspension decreased from pH 3.2 to pH 1.3, the ionic strength (I) increased about 100 times from 5.9 × 10−4 to 4.5 × 10−2 M. However, no hydrolysis was observed for the microgels at these acidic conditions. Furthermore, the hydrolysis of microgels took place at pH = 11.7, of which the ionic strength I was 5.6 × 10−3 M. However, no hydrolysis was observed for the microgel suspension with similar ionic strength at pH = 2.2, i.e., I = 6.0 × 10−3 M. Similar results were observed for PNI-hexane-1 microgels (Figure 6B). These results indicated that the degradation extent and rate of PNI-Ph-1 and PNI-hexane-1 microgels could be tuned by varying the pH value of the microgel suspensions. GPC results also indicated that the linear copolymers were obtained after degradation of the PNI-Ph-1 and PNI-hexane-1 microgels in alkaline solution (PNI-Ph-1: Mn = 5.2 × 103, PDI = 1.3; PNI-hexane-1: Mn = 8.3 × 103, PDI =

microgels during the degradation in neutral aqueous solution. PDI was the size distribution of microgel particles; the smaller the value of PDI, the more uniform the particle size. Apparently, the PDI of PNI-Ph microgels increased with time because hydrolysis reaction was random and not uniform in microgels. The strong increase of PDI also confirmed the degradation of PNI-Ph series of microgels. However, compared to the PNI-Ph series of microgels, the percentage of scattering intensity and corresponding PDI value of PNI-hexane-1 microgels were almost unchanged within the experimental times of ca. 175 h, which indicated that PNIhexane-1 microgels were stable in neutral aqueous solution. It was reasonable because the phenolic ester in 1,4-phenylene bis(4-bromobutanoate) was easier to hydrolysis than the alcoholic ester in 1,6-hexanediol bis(2-bromopropionate). FT-IR measurements were carried out to confirm the degradation of P(NIPAm-co-VIM)/1,4-phenylene bis(4-bromobutanoate) microgels. Figure 5 shows the FT-IR spectra of

Figure 5. FT-IR spectra of P(NIPAm-co-VIM) linear polymer (a), PNI-Ph-1 microgels before (b) and after (c) degradation, and 1,4phenylene bis(4-bromobutanoate) (d).

P(NIPAm-co-VIM) linear polymer, PNI-Ph-1 microgels before and after degradation, and 1,4-phenylene bis(4-bromobutanoate). The characteristic absorption bands at 1753 and 1018 cm−1 could be ascribed to the CO stretching vibration and C−O−C stretching vibration of ester bond in 1,4-phenylene bis(4-bromobutanoate) and PNI-Ph-1 microgels before degradation, respectively. However, the spectra of P(NIPAm-coF

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Figure 6. Scattering intensity (black) and the corresponding polydispersity index (blue) of the PNI-Ph-1 (A) and PNI-hexane-1 (B) microgels measured by DLS at 25 °C as a function of pH value.

degradation and hence with milky white color. It was speculated that the yellow color of PNI-Ph-1 microgels appearing during the degradation procedure might probably come from the hydroquinone generated by the hydrolysis of 1,4-phenylene bis(4-bromobutanoate), which was easily oxidized in air to form a yellow benzoquinone. While for the PNIhexane-1 microgels, the hydrolysis of 1,6-hexanediol bis(2bromopropionate) led to 1,6-hexanediol, which was transparent in aqueous solution. In order to test the speculation mentioned above, the PNIPh-1 and PNI-hexane-1 microgels in aqueous solutions with various pH value were measured by UV−vis spectroscopy, as shown in Figure 8. Note that the microgel samples were freshly prepared and tested immediately. The magenta curve of Figure 8A represented the standard UV−vis spectrum of hydroquinone, which indicated that the absorption maximum of hydroquinone was ca. 288 nm. In terms of the reactivity of its O−H groups, hydroquinone resembles other phenols, being weakly acidic. It can lose one or two protons to form the corresponding phenolate anion in alkaline solution, which leads to a red-shift of absorption maximum.34 For the PNI-Ph-1 microgels (Figure 8A), when the alkaline of aqueous solution was strong enough (e.g., pH = 12.9), an absorption peak at 293 nm appeared, which was the characteristic absorption peak of hydroquinone and the corresponding phenolate anion.

2.9) (Figure S5), which further confirmed that the degradation of the PNI-Ph-1 and PNI-hexane-1 microgels resulted from the hydrolysis of ester bonds of the cross-linkers. Interestingly, the color of PNI-Ph-1 microgels changed from milky white gradually to transparent and then to yellow with the increase of alkaline, and the yellow color deepened with further increasing the pH value, as shown in Figure 7. However,

Figure 7. Photo of PNI-Ph-1 microgels with solution pH value from 11.0 to 13.0.

PNI-hexane-1 microgels only showed the color change from milky white to transparent (Figure S6). The colors of PNI-Ph-1 and PNI-hexane-1 microgels were milky white in the neutral and acidic solution. It was reasonable because the PNI-Ph-1 and PNI-hexane-1 microgels were colloidal suspension before

Figure 8. UV−vis absorption spectra of PNI-Ph-1 (A) and PNI-hexane-1 (B) microgels with various pH value. The magenta curve of (A) represented the standard spectrum of hydroquinone (HQ). G

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Figure 9. (A) UV−vis absorption spectra of PNI-Ph-1 microgels in alkaline solution (pH = 12.6) in 30 min. (B) Standard spectra of hydroquinone (HQ), benzoquinone (BQ), and hydroquinone in the air after 15 min (HQ-15 min).

Figure 10. TEM and SEM images of SiO2 nanoparticles prepared with PNI-Ph-1 microgels as the template at 50 °C (A, B) and 25 °C (C, D), respectively.

However, with the decrease of pH value, the absorption peak at 293 nm gradually weakened until it disappeared. The absorption value of the full spectrum decreased with increasing pH value of the alkaline solution because the transmittance of the PNI-Ph-1 microgel suspension increased with the degradation of PNI-Ph-1 microgels. For the PNI-hexane-1 microgels (Figure 8B), the absorption of UV decreased with increasing pH value of the alkaline solution due to the degradation of PNI-hexane-1 microgels, but no absorption peak appeared. To further study the color change of PNI-Ph-1 microgels in alkaline solution after hydrolysis, the change of UV−vis absorption spectra of PNI-Ph-1 microgels with pH = 12.6 was monitored for 30 min, as shown in Figure 9A. The

absorption peak at 293 nm gradually weakened with increasing time, indicating that hydroquinone was gradually oxidized to form benzoquinone. Figure 9B shows the standard spectra of hydroquinone (HQ), benzoquinone (BQ), and hydroquinone in the air after 15 min (HQ-15 min). The trend of UV−vis absorption spectra of hydroquinone oxidized in air (blue curve in Figure 9B) was the same as the PNI-Ph-1 microgels in alkaline solution after hydrolysis. Therefore, the degradation of PNI-Ph-1 microgels experienced two reaction processes, that is, the hydrolysis of ester bonds of the cross-linkers and the oxidation of generated hydroquinone to form benzoquinone. Although the results of Figure 6 show that the hydrolysis process of microgels in strong alkaline solution was instantaneous, the scattering intensity and polydispersed H

DOI: 10.1021/acs.macromol.5b00482 Macromolecules XXXX, XXX, XXX−XXX

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CONCLUSIONS Two dibromo compounds, i.e. 1,4-phenylene bis(4-bromobutanoate) and 1,6-hexanediol bis(2-bromopropionate) which contained phenolic and alcoholic ester groups, respectively, were synthesized and employed to prepare degradable thermosensitive ionic microgels via in situ quaternization cross-linking of quaternizable comonomer during the surfactant free emulsion copolymerization of thermosensitive monomer N-isopropylacrylamide and the comonomer 1-vinylimidazole at 70 °C. The obtained microgels were spherical in shape with narrow size distribution and exhibited thermosensitive behavior as well as controllable degradation. The disintegration of the microgels was confirmed to be resulted from the hydrolysis of ester bonds of the cross-linkers. The degradation rate of the obtained microgels could be regulated by tuning the pH value of microgel suspensions. The PNI-Ph series of microgels fabricated with 1,4-phenylene bis(4-bromobutanoate) as the cross-linking agent could gradually degrade even in neutral solution with lifetimes of 44−53 h, depending on the quaternization ratio. Increasing the quaternization ratio meant the increase of cross-linking density of the microgel networks and hence the decrease of degradation rate. The degradation of PNI-Ph series of microgels experienced two reaction processes, that is, the hydrolysis of ester bonds of the cross-linkers and the oxidation of generated hydroquinone to form benzoquinone. Furthermore, such degradable thermosensitive ionic microgels could be used as templates for the fabrication of different silica nanostructures at various temperatures.

index of microgels still showed a slight change over measuring time. Therefore, we monitored the hydrolysis process of PNIPh-1 and PNI-hexane-1 microgels in aqueous solution with various pH values for the first 600 s by UV−vis spectroscopy. Figure S7 shows the “1−Transmittance” of PNI-Ph-1 and PNIhexane-1 microgels in aqueous solutions with various pH values as a function of time. Note that the “1−Transmittance” (i.e., 1− T%) here was relative to transmittance (T%); the higher the 1−T% value, the lower the degree of hydrolysis. The microgel samples were freshly prepared and tested immediately. As shown in Figure S7, the 1−T% value was high and did not significantly decrease when the microgels was in weak alkaline solution (pH = 11.9). However, with increasing the pH value, the 1−T% value decreased clearly, and the inflection point shifted to left (short time direction). Similarly, the exponential decay eq 1 was used to fit the hydrolysis data of Figure S7, and the fitting parameters are shown in Table S1. With increasing the pH value from 11.9 to 12.8, the lifetime τ decreased from 4.9 × 106 and 1.2 × 107 s to 5.5 and 0.1 s for PNI-Ph-1 and PNI-hexane-1 microgels, respectively. These results indicated that the hydrolysis rates of PNI-Ph-1 and PNI-hexane-1 microgels could be well regulated by carefully controlling the pH value of the aqueous solution. Fabrication of SiO2 Nanostructures with PNI-Ph-1 Microgels as Degradable Templates. As mentioned above, the PNI-Ph-1 microgels gradually degraded in neutral solution. Here we demonstrated that such microgels could be used as degradable templates for the fabrication of silica nanostructures. Figure 10 shows the typical TEM and SEM images of the SiO2 nanoparticles prepared with PNI-Ph-1 microgels as a template at 50 and 25 °C, respectively. Interestingly, uniform core−shell nanoparticles with diameter and shell thickness of 314 ± 9 nm and 56 ± 7 nm were obtained at 50 °C, whereas open silica nanostructures with sizes of 420 ± 16 nm and narrow size distribution were obtained at 25 °C. These open silica nanostructures were formed by aggregation of many small silica spheres with sizes of ca. 30 nm. At 50 °C, the PNI-Ph-1 microgels were at collapsed state, and the silica nanoparticles could not penetrate into the collapsed microgels but uniformly covered on the surface of microgels and further merged during the condensation of TEOS, forming the core−shell nanoparticles with silica shells and linear copolymer generated from the degradation of microgels as the cores,35 whereas the silica nanoparticles could penetrate into the swelled PNI-Ph-1 microgels at 25 °C. However, the PNI-Ph-1 microgels gradually disintegrated during the condensation reaction of TEOS at 25 °C, leading to the formation of open silica nanostructures. The FT-IR spectra confirmed the degradation of PNI-Ph-1 microgels, as shown in Figure S8. The characteristic absorption bands at 466, 800, 1095, and 964 cm−1 were attributed to −Si−O−Si− and Si−OH groups of SiO2, indicating the presence of silica in the nanoparticles. The characteristic absorption bands at 1459, 1548, and 1652 cm−1 were attributed to −CO−NH− groups of PNIPAm. The linear copolymers from the degradation of PNIPh-1 microgels were adsorbed onto the open silica structures. Furthermore, the degraded microgels/silica core−shell nanoparticles showed the BET surface area and pore volume were 28.4 m2/g and 0.384 cm3/g, respectively (Figure S9). The open silica nanostructures obtained were 110.1 m2/g and 0.444 cm3/ g, respectively. The pore size distribution of open silica nanostructures showed a strong peak located between 4 and 11 nm while the core−shell nanoparticles did not show any peak.

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ASSOCIATED CONTENT

S Supporting Information *

1 H NMR and ESI-MS of 1,4-phenylene bis(4-bromobutanoate), additional DLS data, photos and GPC curves of degraded microgels, FTIR spectra, and BET results of silica nanostructures. This material is available free of charge via the Internet at http://pubs.acs.org.

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AUTHOR INFORMATION

Corresponding Author

*E-mail: [email protected] (B.D.). Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS The authors thank the National Natural Science Foundation of China (Nos. 21274129 and 21322406), the Fundamental Research Funds for the Central Universities (2014XZZX00321), the third level of 2013 Zhejiang Province 151 Talent Project, and Open Research Fund of State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, for financial support.

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