Article pubs.acs.org/Macromolecules
Formation of Microgels by Utilizing the Reactivity of Catechols with Radicals Jinqiao Xue,† Zhijun Zhang,† Jingjing Nie,‡ 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: The reactivity of catechols with radicals was applied for the first time to synthesize cross-linked nanostructures, i.e. microgels, without addition of any other cross-linker. Stable microgels with narrow size distribution were successfully obtained via surfactant free emulsion polymerization (SFEP) of acrylamide-type main monomers, namely, acrylamide (AM), N,N-dimethylacrylamide (DMAA), N-vinylpyrrolidone (NVP), N-vinylcaprolactam (VCL), Nisopropylacrylamide (NIPAM), and (dimethylamino)propylmethacrylamide (DMAPM), and vinyl comonomer bearing unprotected catechol in aqueous solution at 70 °C. The formation mechanism of cross-linking network structures was mainly attributed to the reactions between unprotected catechol groups of polymer chains and the radicals of propagating chains during SFEP. With catechol chemistry, microgels with fully water-soluble polymers as scaffolds were achieved without using any surfactant stabilizer.
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chemical sensors, etc.10−25 Reported methods for the fabrication of microgels mainly include emulsion polymerization with added surfactant, surfactant-free emulsion polymerization (SFEP), inverse mini- and microemulsion polymerization, and cross-linking of prepolymer chains, etc.10−25 The use of surfactant makes the resultant microgels suffering from residual surfactant contamination, which significantly disadvantages their applications, especially in biomedical fields. The cross-linking of prepolymer chains requires the prepolymers to be thermosensitive in aqueous solutions and usually leads to the microgels with relatively larger size distribution.26−28 The microgels obtained by SFEP exhibit narrow particle size distribution (PSD) and do not suffer from residual surfactant contamination, which is crucial for their potential applications in biomedical fields. However, only limited monomers are adaptable for the preparation of microgels by using SFEP in aqueous solution. SFEP usually requires the as-formed polymers to be thermosensitive, typically with a lower critical solution temperature (LCST) in aqueous solution. The asformed polymers transform from soluble coil chains into insoluble collapsed globules during polymerization due to their thermosensitive character, and the collapsed globules are crosslinked by cross-linker molecules, leading to the formation of microgels. As a result, monomers like N-isopropylacrylamide (NIPAM), N-vinylcaprolactam (VCL) and N,N-diethylacrylamide (DEAAM) are mainly used as scaffold monomers
INTRODUCTION Catechols have been identified to play an essential role in mussel adhesion and widely used as an important building block for the fabrication of mussel-inspired adhesives and coatings as well as surface modification in the recent decades.1−4 Monomers bearing catechol groups protected or not have also been successfully (co)polymerized, forming a large range of catechol-based polymer materials with special structures and properties.5 Furthermore, it is well-known that catechols are polymerization inhibitors, which could react with radicals, forming aryloxy free radicals.6 The radical (co)polymerization of unprotected catechol bearing vinyl monomers is thus expected to give branched polymers because the catechol group of one polymer chain might react with a radical existing in another chain during radical polymerization, forming an interchain C−O or C−C bond.5,7 However, in all the reported works of radical (co)polymerization involving unprotected catechol bearing vinyl monomers, the possible reactions between catechols and propagating radicals have not yet been systematically discussed and explored although some insoluble materials have been observed.1,8,9 We hypothesized that the reactions between catechols and propagating radicals might be applicable for fabricating cross-linked nanostructures, which is not yet reported. Microgels are three-dimensional cross-linked colloidal particles, which swell in aqueous solution. Microgels possess simultaneously the unique properties of hydrogels and colloidal particles and have found wide potential applications in various fields like controlled release, separation technology, bio- and © XXXX American Chemical Society
Received: June 19, 2017
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DOI: 10.1021/acs.macromol.7b01304 Macromolecules XXXX, XXX, XXX−XXX
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Macromolecules Table 1. Experimental Conditions and Related Properties of the Obtained Microgels DMAa
microgel code poly(NIPAM-coDMA) poly(NIPAM-coDMA)-1/10 poly(NIPAM-coDMA)-1/12 poly(NIPAM-coDMA)-1/16 poly(NIPAM-coDMA)-1/20 poly(DMAPMco-DMA) poly(VCL-coDMA) poly(NVP-coDMA) poly(AM-coDMA) poly(DMAA-coDMA)
SLS
DLS
TEM
feeding amount (mmol)
feeding mass fraction (%)
measured mass fraction (%)
unreacted catechol moiety (mass fraction) (%)b
Rgc (nm)
Rhc (nm)
PDIc
RDMFd (nm)
Rg/Rh
Dwatere (nm)
DDMFf (nm)
0.108
16.3
18.5
2.6
84
123
0.049
160
0.68
136 ± 12
276 ± 43
0.086
13.4
14.3
1.9
64
103
0.077
196
0.62
120 ± 10
174 ± 12
0.072
11.5
17.2
1.6
79
144
0.051
167
0.55
150 ± 14
261 ± 25
0.054
8.9
6.9
0.9
77
106
0.053
207
0.73
112 ± 12
191 ± 43
0.043
7.2
6.0
0.6
88
114
0.046
190
0.77
118 ± 14
176 ± 14
0.108
12.2
16.4
0.8
78
75
0.076
90
1.04
75 ± 5
95 ± 35
0.108
14.1
5.7
0.8
118
153
0.068
209
0.77
260 ± 20
440 ± 88
0.108
16.5
38.2
0.7
63
72
0.080
155
0.88
78 ± 7
110 ± 25
0.108
21.6
12.3
4.1
981
0.239
1212
1174 ± 106
1223 ± 182
0.108
17.7
15.7
0.6
240
0.029
290
280 ± 30
441 ± 81
183
0.76
The feeding amounts of acrylamide-type main monomer were fixed as 0.862 mmol. The contents of DMA in the obtained microgels were quantitatively determined from the intensity of corresponding characteristic absorbance λmax in UV−vis spectra of the microgels by referring to the standard absorption curve of DMA. bThe contents of unreacted catechol moiety in the microgels were determined using the method developed by Waite and Benetict. cThe gyration radius Rg, hydrodynamic radius Rh, and corresponding polydispersity index (PDI) of microgels dispersed in water measured by SLS and DLS at 25 °C, respectively. dThe hydrodynamic radii of microgels dispersed in DMF measured by DLS at 25 °C. eThe TEM diameters of microgels dispersed in water. fThe TEM diameters of microgels dispersed in DMF. a
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for the microgels prepared via SFEP.29 Functional comonomers could be then incorporated purposely to tune the structures and properties of the targeted microgels. For fully water-soluble polymers without thermosensitivity, the corresponding monomers could be hardly used as scaffold monomers for fabricating microgels via SFEP because no collapsed precursory particles could be formed during polymerization. It thus remains a challenge task to obtain microgels with fully water-soluble polymers as scaffolds without using surfactant stabilizer for the increasing interests in the application of microgels in biomedical fields. It would be also significant if the range of monomers, which are adaptable for SFEP, could be expanded. By utilizing the fast reaction of ethylene glycol dimethacrylate (EGDMA) and the hydrophobic nature of polyEGDMA, which could form the nucleuses of microgels at the early stage of SFEP, we have previously reported the fabrication of poly(Nvinylpyrrolidinone) (PNVP) microgels via SFEP with Nvinylpyrrolidinone (NVP) as the monomer and EGDMA as the cross-linker at 60 °C.30 However, the obtained PNVP microgels showed rough surfaces due to the fast reaction rates of cross-linker EGDMA. In the present work, we shall report for the first time that the reactivity of catechols with radicals could be directly applied for the fabrication of microgels by using SFEP in aqueous solution. The formation mechanism of cross-linking networks was proposed and discussed in detail. We shall also show that catechol chemistry in aqueous solution could expand the monomer type, which is suitable for the preparation of microgels using SFEP, to fully water-soluble acrylamide-type monomers. With catechol chemistry, the microgels with fully water-soluble polymers as main scaffolds could be achieved by using SFEP in aqueous solution without addition of any other cross-linker and surfactant stabilizer.
EXPERIMENTAL SECTION
Materials. Dopamine-HCl, N-vinylpyrrolidone (NVP) and N,N,N′,N′-tetramethylethylenediamine (TEMED) were purchased from Acros. Sodium borate, N-isopropylacrylamide (NIPAM), N,Ndimethylacrylamide (DMAA), (dimethylamino)propylmethacrylamide (DMAPM), acrylamide (AM), and potassium persulfate (KPS) were purchased from J&K. N-Vinylcaprolactam (VCL), 2,2′-azobis(2methylpropionamidine) dihydrochloride (AIBA), NaNO2, and Na2MoO4·2H2O were purchased from Aldrich. N-Succinimidyl methacrylate was purchased from TCI. All of the chemicals and solvents were used as received without further purification. Synthesis of Dopamine Methacrylamide (DMA). Briefly, 2 mL of triethylamine was dissolved in 5 mL of DMF, and 1.97 g of dopamine-HCl predissolved in 10 mL of DMF was then added. 1.65 g of N-succinimidyl methacrylate was predissolved in 10 mL of DMF and bubbled with N2 for 30 min, followed by dropwise addition of the mixture prepared above. To keep the solution moderately alkaline, the pH was adjusted to 8.0 or above by using triethylamine. The reaction mixture was stirred for 26 h at room temperature with N2 bubbling. The resultant suspension was then vacuum filtrated, and the pH of the obtained yellow brown solution was reduced to 2 with 6 M HCl. The solution was then concentrated approximately to 2 mL and precipitated in 20 mL of deionized water with vigorous stirring three times. The product was recrystallized from deionized water in the refrigerator overnight and dried under vacuum to give gray powder. The chemical structure of DMA was confirmed by 1H NMR and ESI-MS measurements (see Figures S1 and S2). Preparation of Microgels. Microgels were prepared by surfactant-free emulsion copolymerization (SFEP) of acrylamide-type main monomer with comonomer DMA in aqueous solution at 70 °C. Six different monomers were investigated. They were AM, DMAA, NVP, DMAPM, VCL, and NIPAM. Briefly, given amounts of acrylamide-type main monomer were added into 24 mL of deionized water at 70 °C under vigorous stirring. Oxygen was eliminated by bubbling N2 for 30 min. Afterward, the AIBA aqueous solution (12.5 mg/mL, 2 mL) was injected into the solution to initiate the B
DOI: 10.1021/acs.macromol.7b01304 Macromolecules XXXX, XXX, XXX−XXX
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Scheme 1. Schematic Routine of Microgels Fabricated via SFEP at 70 °C in Aqueous Solution without Addition of Any Other Cross-Linker by Using Acrylamide-Type Monomer as the Scaffold Monomer and Dopamine Methacrylamide (DMA) Bearing Unprotected Catechol Group as the Comonomer
Figure 1. TEM image of poly(NIPAM-co-DMA) microgels (A) dispersed in aqueous solution and (B) redispersed in DMF. The scale bar is 500 nm. (C) UV−vis spectra of Poly(NIPAM-co-DMA) microgel aqueous suspensions (0.15 mg/mL) with different pH values. (D) Hydrodynamic diameter of poly(NIPAM-co-DMA) microgels as a function of pH measured by DLS. monomer. 10 μL of concentrated HCl (36%) was first added into 1 mL of DMA aqueous solution with concentration of 10 mM to give the solution A. The nitrite reagent (0.145 M NaNO2 and 0.041 M Na2MoO4), named as the solution B, was prepared by dissolving 0.12 g of NaNO2 and 0.12 g of Na2MoO4·2H2O in 12 mL of deionized water. 0.05 M HCl was added to given amounts of solution A (5, 10, 20, 30, 40, and 50 μL) to a final volume of 0.6 mL in each case, which gave a colorless mixed solution. 0.6 mL of solution B was then added. Finally, 0.8 mL of 0.1 M NaOH was quickly added, and the UV−vis spectrum of the mixed solution was quickly recorded using a Cary 100 UV−vis spectrophotometer (Varian Australia Pty Ltd.). The absorbance at 500 nm was used to construct the standard curve. The contents of unreacted catechol moiety in the microgels were then determined using the similar procedure described above. 500 μL of 0.05 M HCl was added to 100 μL microgel aqueous suspension (7.5 mg/mL for poly(AM-co-DMA) microgels, 12.5 mg/mL for poly(NIPAM-co-DMA) microgels, and 25.0 mg/mL for the others) to give a milky white aqueous suspension. 0.6 mL of solution B was then added. Finally, 0.8 mL of 0.1 M NaOH was quickly added, and the UV−vis spectrum of the mixed solution was quickly recorded. The absorbance at 500 nm was then used to calculate the amount of free catechol moiety in the microgels.
polymerization. After certain times (30 min for the synthesis of poly(AM-co-DMA) microgels, 40 min for poly(DMAPM-co-DMA) microgels, and 10 min for the other systems), given amounts of DMA predissolved in 1 mL of ethanol were then injected into the reaction mixture. The reaction was continued at 70 °C for 6 h. The resultant microgels were purified by dialysis against deionized water in a dialysis tube with molecular weight cutoff (MWCO) of 14 000 at room temperature for 3 days. The detailed feeding amounts of main monomer and comonomer DMA are summarized in Table 1. Control Experiments. The radical homopolymerization of sole NIPAM (0.862 mmol) or DMA (0.108 mmol) was carried out at 70 °C by using AIBA as the initiator. The radical copolymerization of NIPAM (0.862 mmol) and DMA (0.108 mmol) was also carried out at 25 °C by using a redox initiator system of KPS and TEMED. The polymerization procedure was similar to those described above. The radical polymerization of NIPAM was first initiated by KPS and TEMED. One hour later, DMA (0.108 mmol in 1 mL of ethanol) was injected into the reaction mixture. The reaction was then continued at 25 °C for 24 h. Determination of Unreacted Catechol Moiety in Microgels. The contents of unreacted catechol moiety in the microgels were determined using the method developed by Waite and Benetict.31 A standard absorbance curve was first constructed by using DMA C
DOI: 10.1021/acs.macromol.7b01304 Macromolecules XXXX, XXX, XXX−XXX
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Macromolecules Characterization. The 1H NMR spectrum was recorded at room temperature by a Bruker (400 MHz) spectrometer using tetramethylsilane as the internal standard and DMSO-d6 as solvent. Electrospray ionization−tandem mass spectroscopy (ESI-MS) measurement was conducted on a Varian 500 mass spectrometer. Ethanol was used as solvent for DMA. The morphologies of microgels were observed by transmission electron microscopy (TEM) on a HT-7700 electron microscope operated at an acceleration voltage of 100 kV. The TEM samples were prepared by dip-coating with Formvar-coated copper grids into the microgel suspensions. The grids were allowed to dry in air at room temperature before observation. Fourier transform infrared (FT-IR) spectra were recorded on a Vector 22 Bruker spectrometer. The freeze-dried microgels were mixed with KBr powders, and the mixtures were then pressed into the pellets for FT-IR measurements. UV−vis spectra were recorded on a Cary 100 instrument (Varian Australia Pty Ltd.). The pH values of the microgel suspensions were measured by using a pH meter (FE20, METTLER TOLEDO). 1 M NaOH and HCl aqueous solutions were used to adjust the pH value of poly(NIPAM-co-DMA) microgel suspensions (0.15 mg/mL) and DMA aqueous solution (0.1 mg/mL). The hydrodynamic radius Rh, particle size distribution, thermosensitive behavior, and scattering light intensity of the obtained microgels were measured by dynamic light scattering (DLS) at scattering angle θ of 90° by using a 90 Plus particle size analyzer (Brookhaven Instruments Corp.) The wavelength of laser light λ was 635 nm. The gyration radius Rg of the obtained microgels was measured by static light scattering (SLS) on an ALV-CGS-3 light scattering electronics and multiple Tau digital correlator with the laser light wavelength of 632.8 nm in Changchun Institute of Applied Chemistry, Chinese Academy of Sciences. The scattering angle ranged from 45° to 145° with a step of 5°. The sample solutions were equilibrated at 25 °C for 15 min before measurements. The SLS data were well interpreted by Guinier-type plots of ln I(q)−1 ∼ q−1, where I is the scattering intensity and q = (4πn/λ) sin(θ/2). ⟨Rg⟩ was determined from the slope of the plots according to the equation
(1)
threshold of monomer concentration CNIPAM for sufficient selfcross-linking lies between 5 and 10 g/L. Insufficient self-crosslinking was already observed at CNIPAM of 5 g/L, and no particles were observed at CNIPAM of 1 g/L. Furthermore, ratios of initiator concentration CKPS to CNIPAM less than ∼0.06 are required for the formation of self-cross-linked PNIPAM particles. Insufficient cross-linking regions were observed when molar ratio of KPS to NIPAM is high so that the polymer chains are highly charged and very hydrophilic. No particles were observed for the extreme case with CKPS/CNIPAM of 0.4. The authors supposed that the ratio of CKPS/CNIPAM was so high that the polymer chains were too hydrophilic to associate in water even at 70 °C.33 In our cases, the concentration of NIPAM was 0.862 mmol in 26 mL of water, corresponding to CNIPAM of 3.75 g/L, which was lower than 5 g/L. The concentration of initiator AIBA was CAIBA of 0.962 g/ L. The corresponding ratio of CAIBA to CNIPAM was about 0.256, which was much higher than 0.06. It was worthy to note that the molar masses of KPS and AIBA were 270.3 and 271.2 g/ mol, respectively. Therefore, the reaction conditions used in the present work well lied in the suggested insufficient self-crosslinking regions of PNIPAM. In such conditions, the self-crosslinking of PNIPAM, if there is any, is not sufficient to give PNIPAM microgels. A certain concentration of DMA is required for the formation of poly(NIPAM-co-DMA) microgels. However, when the feeding molar ratio of DMA/NIPAM reached 1/4, the obtained poly(NIPAM-co-DMA)-1/4 microgels exhibited low colloidal stability in aqueous solution and coagulated quickly at room temperature. In the range of DMA/ NIPAM feeding molar ratio from 1/20 to 1/8, corresponding to the feeding molar of DMA from 0.043 to 0.108 mmol with fixed NIPAM of 0.862 mmol, stable poly(NIPAM-co-DMA) microgels were obtained (Table 1 and Figure 2). Without adding DMA, no microgels could be obtained. Furthermore,
RESULTS AND DISCUSSION We first tested the above hypothesis by radical copolymerization of NIPAM with a comonomer bearing unprotected catechol, namely dopamine methacrylamide (DMA, Figures S1 and S2, Supporting Information) via SFEP in aqueous solution, as shown in Scheme 1. The radical polymerization of NIPAM was first initiated in aqueous solution at 70 °C by adding the initiator, 2,2′-azobis(2-methylpropionamidine) dihydrochloride (AIBA). After 10 min, given amounts of DMA predissolved in 1 mL of ethanol was added (Table 1). The reaction was then allowed to proceed at 70 °C for 6 h. Figure 1A shows the representative TEM image of resultant poly(NIPAM-co-DMA) microgels. The obtained poly(NIPAMco-DMA) microgels are spherical in shape with size of 136 ± 12 nm and narrow PSD. FT-IR spectra of the microgels confirmed the occurrence and completion of radical copolymerization (Figure S3). The effect of DMA feeding amounts on the formation of poly(NIPAM-co-DMA) microgels was further investigated. It was found that poly(NIPAM-co-DMA) microgels could not be obtained when the feeding molar ratio of DMA/NIPAM was smaller than 1/20. Previously, Gao and Frisken32,33 reported that PNIPAM microgels could be formed even without any cross-linker, especially at high polymerization temperature, due to the self-cross-linking of PNIPAM. On the basis of the systematical investigation, the authors summarized the reaction conditions necessary for the production of selfcross-linked PNIPAM microgels.33 For SFEP at 70 °C, the
Figure 2. Representative TEM images of (A) poly(NIPAM-co-DMA)1/10, (B) poly(NIPAM-co-DMA)-1/12, (C) poly(NIPAM-co-DMA)1/16, and (D) poly(NIPAM-co-DMA)-1/20 microgels. The scale bar is 500 nm.
ln I(q)−1 = ln I(0)−1 +
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⟨R g⟩2 3
q2
D
DOI: 10.1021/acs.macromol.7b01304 Macromolecules XXXX, XXX, XXX−XXX
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Macromolecules the radical polymerization of sole DMA (0.108 mmol) at 70 °C resulted in very dilute polyDMA nanoparticles, as shown in Figure S4. These results indicated that the radical (co)polymerization of DMA at 70 °C in aqueous solution led to the formation of cross-linked structures. The hydrodynamic radius ⟨Rh⟩ and radius of gyration ⟨Rg⟩ of the obtained poly(NIPAM-co-DMA) microgels in aqueous solution were then measured by dynamic and static light scattering (DLS and SLS) at 25 °C, respectively. The hydrodynamic diameters (2 × ⟨Rh⟩) of the obtained poly(NIPAM-co-DMA) microgels were larger than those measured from TEM images, indicating that the microgels were in swollen state in aqueous solution. The poly(NIPAM-co-DMA) microgels exhibited narrow particle size distribution in aqueous solutions. (Table 1 and Figure S5). The value of ⟨Rg⟩/⟨Rh⟩ ratio could reflect the cross-linking density distribution of the microgels. For monodispersed hard spheres with constant density, ⟨Rg⟩/⟨Rh⟩ is 0.778. ⟨Rg⟩/⟨Rh⟩ of PNIPAM microgels cross-linked with N,N′-methylenebis(acrylamide) (BIS) usually gives the value in the range of 0.55−0.6, suggesting that the PNIPAM microgels exhibit inhomogeneous cross-linking network structures. The Rg/Rh ratios of the obtained microgels at 25 °C were in the range of 0.55−0.77 (Table 1 and Figure S6), suggesting the formation of cross-linked network. Furthermore, the poly(NIPAM-co-DMA) microgels exhibited reversible thermosensitive swelling−deswelling behavior as a function of temperature, as shown in Figure 3, indicating that
Figure 4. Representative TEM images of the obtained microgels redispersed in DMF: (A) poly(NIPAM-co-DMA)-1/10, (B) poly(NIPAM-co-DMA)-1/12, (C) poly(NIPAM-co-DMA)-1/16, and (D) poly(NIPAM-co-DMA)-1/20 microgels. The scale bar is 500 nm.
well as the larger particle size distributions (Table 1). A similar phenomenon was also observed for the polyDMA nanoparticles in DMF (Figure S8). We also performed the radical copolymerization of NIPAM and DMA at 25 °C by using a redox initiator system of KPS and TEMED. In such case, poly(NIPAM-co-DMA) microgels were obtained again but with large size distribution (Figure S9), which suggested that the formation of cross-linking network structures did not depend on the reaction temperature. We supposed three possible mechanisms for the formation of cross-linking network structure during the radical copolymerization of NIPAM and DMA (Scheme 2), which are (i) the covalent coupling of the catechol groups,34 (ii) the formation of hydrogen bonds between the hydroxyl groups of catechol,35,36 and (iii) the catechol group of one polymer chain reacts with a radical of another propagating chain, forming an interchain C− O or C−C bond.5 The covalent coupling of catechols will result in a characteristic absorbance with λmax of 267 nm in the UV− vis spectra of the products, i.e. microgels.34 However, all the obtained poly(NIPAM-co-DMA) microgels only exhibited one characteristic absorbance at λmax of 282 nm, indicating the existence of unoxidized catechol and the absence of covalent coupled catechols, as shown in Figure 1C.7,34,37 We further tested the effect of pH on the UV−vis spectra of poly(NIPAMco-DMA) microgels (Figure 1C). Note that the pH value of asobtained poly(NIPAM-co-DMA) microgel suspensions was 6.3. For pH ranging from 2 to 10, the λmax (282 nm) of absorbance peak of poly(NIPAM-co-DMA) microgels was unaffected. With increasing pH to 11, a slight red-shift of λmax from 282 to 285 nm was observed. Interestingly, for pH of 12 or 13, a characteristic absorbance with λmax of 264 nm was observed, and the color of poly(NIPAM-co-DMA) microgel aqueous suspensions changed from milky white to brown (Figure S10), implying the auto-oxidation of catechol at pH 12.38 Similar phenomena were observed for comonomer DMA aqueous
Figure 3. Hydrodynamic diameter of poly(NIPAM-co-DMA) series of microgels measured by DLS as a function of measuring temperature. Solid symbols: heating process. Open symbols: cooling process.
the obtained microgels maintained the characteristic properties of their polymer scaffolds. As expected, the swelling ratio of poly(NIPAM-co-DMA) series of microgels decreased with increasing the feeding amount of comonomer DMA because DMA is a hydrophobic comonomer. To further verify the formation of cross-linking network structures, the obtained poly(NIPAM-co-DMA) microgels and polyDMA nanoparticles were free-dried and then redispersed in DMF, which is a good solvent for the monomers, comonomer, and their corresponding linear (co)polymers. Figures 1B and 4 show the typical TEM images of poly(NIPAM-co-DMA) series of microgels redispersed in DMF. The corresponding hydrodynamic radii were also measured by DLS at 25 °C and given in Table 1, which are much larger than those in water. Figure S7 shows the corresponding particle size distribution of poly(NIPAM-co-DMA) series of microgels redispersed in DMF. It can be clearly seen that the microgels maintained the spherical shape but swelled in DMF, leading to the larger particle sizes as E
DOI: 10.1021/acs.macromol.7b01304 Macromolecules XXXX, XXX, XXX−XXX
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Scheme 2. Possible Mechanisms for the Formation of Cross-Linking Network Structure during the Radical Copolymerization of DMA and the Acrylamide-Type Main Monomer
Figure 5. Representative TEM images of the (A) poly(DMAA-co-DMA) and (B) poly(NVP-co-DMA) microgels dispersed in aqueous solution. The scale bar is 500 nm. (C) UV−vis spectra of the obtained microgel aqueous suspensions. (D) Hydrodynamic diameters of poly(DMAA-co-DMA) and poly(NVP-co-DMA) microgels dispersed in PBS solution measured by DLS as a function of measuring time.
solution (Figure S11). The characteristic absorbances with λmax of 280, 284, and 264 nm were observed for DMA aqueous solutions at pH values of 6.3, 11, and 12, respectively. Furthermore, the microgels are stable in the pH range of 2− 12. The hydrodynamic diameter of microgels slightly varied in the pH range of 2−11 but exhibited a strong increase when pH value changed from 11 to 12 (Figure 1D), which is further confirmed by the TEM observations (Figure S12). For the route ii, if the cross-linking networks were formed via the formation of hydrogen bonds between the hydroxyl groups of catechol, the breaking of hydrogen bonds might lead to the disintegration of the obtained microgels. Borax could form a cyclic bidentate o-benzenediol subunit with catechol and is
widely used as the protecting reagent for catechols.39 We thus added sodium borate (3.25 mM) into the poly(NIPAM-coDMA)-1/10 microgel aqueous suspensions (0.249 mg/mL) in order to break the possible hydrogen bonds between the hydroxyl groups of catechol. The UV−vis spectrum of the microgel suspensions was monitored for 120 h. The λmax of 282 nm did not change over 120 h observation (Figure S13), which indicated that the chemical structure of poly(NIPAM-coDMA)-1/10 microgels was unaffected by sodium borate. Furthermore, the addition of sodium borate only led to a slight increase of hydrodynamic diameter of poly(NIPAM-coDMA)-10 microgels in 120 h as measured by DLS (Figure F
DOI: 10.1021/acs.macromol.7b01304 Macromolecules XXXX, XXX, XXX−XXX
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Macromolecules
catechol group reacted with the radicals during the SFEP. The stability of poly(DMAA-co-DMA) and poly(NVP-coDMA) microgels in phosphate buffer saline (PBS, pH 7.4) solution was also investigated. The results show that poly(DMAA-co-DMA) and poly(NVP-co-DMA) microgels were stable in phosphate buffer saline (PBS, pH 7.4) solution for a wide range of temperatures (Figure 5D), which might make them potentially applicable in biomedical-related fields. Furthermore, all of the obtained microgels in the present work exhibited outstanding long-term stability in aqueous solution at room temperature for more than one year.
S14). No disintegration of microgels was observed, indicating the existence of chemical cross-linking. We consider the route iii as the main mechanism responsible for the formation of cross-linking networks of the microgels. The contents of DMA in the obtained microgels were quantitatively determined from the intensity of corresponding characteristic absorbance λmax of DMA in UV−vis spectra of the microgels (Table 1 and Figure S15). The measured mass fraction of DMA in the obtained poly(NIPAM-co-DMA) microgels was closed to the corresponding feeding mass fraction. Furthermore, no microgels could be obtained when directly mixing NIPAM and DMA at the same time and then initiating the radical copolymerization. Only adding DMA after the radical polymerization of NIPAM proceeded for certain times could give the microgels. This suggests that the existing propagating radicals of polymer chains in aqueous solution are crucial, which are then captured by the unprotected catechols of later added DMA, leading to the formation of cross-linking networks and hence microgels. The content of unreacted catechol moiety in the microgels determined using the Waite and Benetict’s method31 were far less than the feeding amounts of DMA and measured amounts of DMA in the obtained microgels (Table 1, Figures S16−S18), which further supported that most of unprotected catechol group reacted with the radicals in aqueous solution during the SFEP. This novel methodology is applicable for preparing other thermosensitive microgels with VCL and (dimethylamino)propylmethacrylamide (DMAPM) as the scaffold monomers. More importantly, microgels with fully water-soluble polymers as scaffolds were also achieved when acrylamide (AM), N,Ndimethylacrylamide (DMAA), and N-vinylpyrrolidone (NVP) were copolymerized with DMA via SFEP at 70 °C in aqueous solution. Figures 5A and 5B show the typical TEM images of poly(DMAA-co-DMA) and poly(NVP-co-DMA) microgels. The representative TEM images of the poly(VCL-co-DMA), poly(DMAPM-co-DMA), and poly(AM-co-DMA) microgels are given in Figure S19. It is the first time that spherial microgels with poly(DMAA) and poly(NVP) as scaffolds, narrow PSD, and smooth surfaces were reported. The average diameters of poly(VCL-co-DMA), poly(DMAPM-co-DMA), poly(DMAA-co-DMA), poly(AM-co-DMA), and poly(NVPco-DMA) microgels were about 260 ± 20, 75 ± 5, 280 ± 30, 1174 ± 106, and 78 ± 7 nm, respectively (Table 1). FT-IR spectra of the microgels also confirmed the occurrence and completion of radical copolymerization (cf. Figure S3). Similarly, these five kinds of microgels exhibited one characteristic absorbance at λmax of 280−292 nm (Figure 5C), indicating the existence of unoxidized catechol and the absence of covalent coupled catechols.7,34,37 These five kinds of microgels swelled in aqueous solution and exhibited narrow size distribution as measured by DLS (Table 1 and Figure S20). The Rg/Rh ratios of the obtained microgels at 25 °C were in the range 0.76−1.04 (Table 1 and Figure S21). The Rg/Rh values were close to or even higher than 0.778, suggesting that the obtained microgels might have more homogeneous cross-linked network structures. Again, these five kinds of microgels maintained the spherical shape but swelled in DMF, leading to the larger particle sizes as well as the larger particle size distributions (Table 1, Figures S22 and S23). Similarly, the content of unreacted catechol moiety in these microgels were far less than the feeding amounts of DMA and measured amounts of DMA in the corresponding microgels (Table 1, Figures S16−S18), suggesting that most of unprotected
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CONCLUSIONS Stable microgels were successfully obtained via the radical copolymerization of unprotected catechol bearing comonomer DMA and six acrylamide-type main monomers by using SFEP in aqueous solution at 70 °C without addition of any other cross-linkers. The reactions between unprotected catechol groups of polymer chains and the radicals of propagating chains led to the formation of cross-linking network structures. With catechol chemistry, the microgels with fully water-soluble acrylamide-based polymers as the main scaffolds were achieved without using any surfactant stabilizer. These findings might significantly amplify the scope of main scaffold of microgels and the application of the reactivity of catechols with radicals.
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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.7b01304. 1 H NMR and ESI-MS of DMA, SLS and DLS data, photo pictures, FTIR spectra, UV−vis spectra, and additional TEM images of obtained microgels (PDF)
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AUTHOR INFORMATION
Corresponding Author
*E-mail:
[email protected]. ORCID
Binyang Du: 0000-0002-5693-0325 Notes
The authors declare no competing financial interest.
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ACKNOWLEDGMENTS The authors thank the National Natural Science Foundation of China (Nos. 21674097 and 21322406), the second level of 2016 Zhejiang Province 151 Talent Project, and Open Research Fund of State Key Laboratory of Polymer Physics and Chemistry (201601), Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, for financial support.
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DOI: 10.1021/acs.macromol.7b01304 Macromolecules XXXX, XXX, XXX−XXX
