ARTICLE pubs.acs.org/Langmuir
Novel Multiresponsive Microgels: Synthesis and Characterization Studies Vural B€ut€un,* Ahmet Atay, Cansel Tuncer, and Yasemin BasDepartment of Chemistry, Faculty of Arts and Science, Eskisehir Osmangazi University, 26480 Eskisehir, Turkey
bS Supporting Information ABSTRACT: The dispersion polymerization of 2-(N-morpholino)ethyl methacrylate (MEMA) in the presence of ethylene glycol dimethylacrylate (EGDMA) cross-linker and diblock copolymer stabilizer in n-hexane afforded sterically stabilized multiresponsive PMEMA microgels. By changing the reaction parameters, a wide range of particle sizes (120720 nm) was obtained. Both dynamic light scattering and electron microscopy studies confirmed monodisperse spherical morphologies. These microgels had a response to the solution pH, temperature, and ionic strength. As expected, PMEMA microgels acquired cationic character at low pH because of the protonation of all morpholino groups. Although PMEMA microgels are in a swollen state in both acidic media and at low temperatures, they are in a deswollen state in basic media at high temperatures and in the presence of electrolytes above pH 6. In addition to these multiresponsive behaviors, PMEMA microgels have the ability to swell in various organic solvents. They also interact very well with magnetic particles and gain responsiveness to the magnetic field. Multiresponsive behaviors of PMEMA microgels were investigated by using DLS, UVvis spectrophotometry, and zeta potentiometry.
’ INTRODUCTION In recent years, “smart” materials and systems that sense and respond to their environmental stimuli have been the focus of considerable interest in terms of both fundamental and applied perspectives. Polymeric gels are in the group of smart materials, and they respond to external stimuli by changing their size. Microgels are cross-linked spherical polymer particles that range in size between 1 and 1000 nm.13 Microgel particles consist of a polymer chain network in a swelled or collapsed state depending on their external conditions.4,5 They can be sensitive to various external stimuli depending on the monomers used in the synthesis, such as the electrolyte concentration,6 sugar content,7 temperature,2,3,5,8,9 pH.915 Microgels have become fascinating because of their good biocompatibility, excellent (de)swelling properties, globularity, various sizes, and large surface areas.3 Applications of these microgels are used in various fields including drug delivery systems,8,1618 bioseparations,19,20 nanometal reactors,2123 and organicinorganic hybrid materials.24 Methods have been reported for the preparation of microgel particles, namely, emulsion polymerization,11,13,21,25 dispersion polymerization,26 surfactant-free emulsion polymerization,2,14,15 distillationprecipitation polymerization,8,10,27,28 and microemulsion polymerization.29 Surfactants, water-soluble functional polymers, copolymers, and polymer lattices can be used as stabilizers to provide an effective stabilization of colloidal systems and to control the morphology and size of polymer particles.30 Poly(ethylene glycol)methyl ether methacrylate,25,31 sytrene-capped r 2011 American Chemical Society
poly[2-(dimethylamino)ethyl methacrylate],25 poly(ethyleneoxide),32 poly(2-vinyl pyridine-co-butyl methacrylate) (P2VP-co-BMA),33 and Pluronics (a triblock copolymer of propylene oxide and ethylene oxide)26 were commonly used as stabilizers. The first class of microgels is thermoresponsive microgels. They can be prepared from a variety of polymers including poly(N,N0 -diethylacrylamide),2 poly(N-isopropylacrylamide),5 poly[(N-isopropylacrylamide-co-3-(trimethoxysilyl)propyl methacrylate)], 3 poly(N-isopropyl acrylamide/acrylamide), 9 poly (N-isopropylacrylamide-co-tert-butyl acrylate),9 and poly(N-isopropylacrylamide-co-acrylic acid).34 Thermoresponsive microgels exhibit a significant volume phase change at a certain temperature called the volume phase transition temperature (VPTT).5,35 Poly(N-isopropyl acrylamide), PNIPAM, is the most studied thermoresponsive microgel because of the fact that PNIPAM has a “biocompatible” VPTT. Its lower critical solution temperature (LCST) is about 32 °C in neutral aqueous solutions.5 Above the LCST, the particles exist in their nonsolvated latex form, and below the LCST, they become hydrophilic and water-swollen microgels are obtained. This property of PNIPAM is more advantageous for in vivo studies such as threats, controlled drug release, and diagnosis. Du et al. have reported an example of a thermoresponsive microgel based on NIPAM by using a different method than a Received: July 12, 2011 Revised: August 23, 2011 Published: August 26, 2011 12657
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Langmuir classical microgel preparation method.3 They first synthesized a poly[N-isopropylacrylamide-co-3-(trimethoxysilyl)propyl methacrylate] [P(NIPAM-co-TMSPMA)] linear copolymer via free radical polymerization, and linear chains were then cross-linked through the hydrolysis and condensation of methoxysilyl at a temperature under the LCST of PNIPAM. In another study, a thermoresponsive microgel system was prepared by the copolymerization of NIPAM and tert-butyl acrylate (tBA) in the presence of the N,N0 -methylene-bis(acrylamide) (MBA) crosslinker. The addition of different amounts of tBA to the microgel system caused a gradual decrease in the volume phase transition temperature of P(NIPAM-co-tBA) in the range of 3318 °C. In addition, the tBA content had a stronger effect on the swelling or deswelling ratio of the microgels at a lower temperature than above the volume phase transition temperature of PNIPAM. The addition of hydrophobic groups to the copolymeric system causes a decrease in diameter by increasing the hydrophicity.9 The second class of microgels is pH-responsive microgels. So far, their various examples have been reported in the literature as poly(acrylic acid)/poly(vinyl amine) (PAAc/PVAm) coreshell particles,10 poly[2-(diethylamino)ethyl methacrylate-co-methacrylic acid], [P(DEA-co-MAA)],11 poly[2-vinylpyridine-co-styrene] [P(2VP-co-St)],14 poly(methacrylic acid-g-ethylene glycol) [P(MAA-g-EG)],26 poly(methyl methacrylate-co-methacrylic acid) [P(MMA-co-MAA)],15 poly(2-vinylpyridine) (P2VP),12,13 poly[(2-dimethylamino)ethyl methacrylate] (PDMA),36 poly[2-(diethylamino)ethyl methacrylate] (PDEA),25,37 and poly[2-(diisopropylamino)ethyl methacrylate] (PDPA).21,25 Sterically stabilized pH-responsive P2VP microgels were first published by Armes et al.12 A wide range of particle radii were obtained by varying the amounts of monomethoxy-capped poly(ethylene glycol) monomethacrylate stabilizer and cationic Aliquat 336 surfactant and initiator via emulsion polymerization. DLS studies confirmed that swelling occurred at low pH because of the protonation of vinyl pyridine groups on P2VP. The swelling kinetics of the latex-to-microgel transition for P2VP microgels were also investigated by the pH jump method using the stopped-flow technique.13 Faster swelling was observed in the presence of salt, and a linear correlation occurred between the swelling time and the diameter of the microgels. Similarly, they also reported the pH-responsive microgels based on both poly[2-(diethylamino)ethyl methacrylate] (PDEA) and poly[2-(diisopropylamino)ethyl methacrylate] (PDPA) with a particle diameter ranging from 250 to 700 nm. Stabilization of the PDEA microgels was provided with charge stabilization, surfactant stabilization, and steric stabilization. The microgel characterization and swellingdeswelling kinetics were investigated with various techniques, such as electron microscopy and turbidimetry.25 In another interesting study, polyampholyte microgel poly[methacrylic acid-co-2-(diethylamino)ethylmethacrylate] [P(MAAco-DEA)] was synthesized via emulsion polymerization.38 These microgels were in a deswollen state between pH 4 and 6 but in a swollen state at both basic pH and low pH values (4 > pH > 6). The stabilization in both acidic and basic solutions was provided by using nonionic poly[(ethylene glycol)methylether methacrylate]. The third class of microgels is salt-responsive microgels. The size change of poly[N-isopropylacrylamide-co-2-(dimethylamino) ethyl methacrylate], P(NIPAM-co-DMA), latexes produced by radical-initiated precipitation polymerization has been examined depending on the salt concentration in the dispersion medium. It was observed that the hydrodynamic radii of the related latexes depended on both the type and concentration of electrolyte that
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Figure 1. PDPA-b-PMEMA diblock copolymer.
was compatible with the Hofmeister series. The effect of electrolytes on the hydrodynamic radius, zeta potential, and colloidal stabilization of microgels was also investigated in detail, and a decrease in the hydrodynamic diameter of the latexes with the ionic strength of the dispersion medium was observed as expected.28 A variation in the hydrodynamic diameter of PNIPAM microgels as a function of the ionic strength by using different electrolytes such as NaCl, Na3Cit, and NaSCN was also studied by Saunders et al.39 They concluded that NaCl was more effective in the LCST of PNIPAM when compared with other salts, whereas PNIPAM showed a VPTT at 34 °C in the absence of salt. The systems mentioned above are responsive to only one stimulus such as pH, temperature, or salt concentration. Multiresponsive microgels are responsive to several of these environmental stimuli. Dual-responsive PNIPAM-based microgels, namely, poly(N-isopropylacrylamide-co-acrylic acid) P(NIPAMco-AAc), were synthesized by Liang et al. via surfactant-free emulsion polymerization. In this system, PNIPAM segments of the microgels are the thermosensitive parts and acrylic acid residues of the microgels enable the systems to be responsive to solution pH.40 In another study, the P(NIPAM/vinyl acetic acid) copolymer as a doubly responsive microgel system was prepared via emulsion polymerization, and the (de)swelling behavior of these copolymers was observed as a function of pH and temperature.41 As far as we know, there is no report in the literature on microgels that are responsive to three or more different external stimuli. Herein, we report the synthesis of a series of novel PMEMA microgels that have a response to external stimuli including pH, temperature, salt concentration, and organic solvents. PMEMA microgels can also interact with Fe3O4 magnetic particles very well, and thus PMEMA microgels can be easily removed from aqueous media by applying a magnetic field. Steric stabilization of PMEMA microgels was provided by using poly[2-(diisopropylamino)ethyl methacrylate]-b-poly[2-(N-morpholino)ethyl methacrylate] (PDPA-b-PMEMA) diblock copolymers (Figure 1). We report on the detailed characterization of PMEMA microgels using various characterization techniques to determine swelling/deswelling behaviors, zeta potentials, and LCSTs.
’ MATERIALS AND METHODS Materials. 2-(N-Morpholino)ethyl methacrylate (MEMA, Polysciences, Inc.) and ethylene glycol dimethacrylate (EGDMA, Aldrich) monomers were purged through an basic alumina column to remove the inhibitor. As an initiator, an analytical grade of 2,20 -azobis(2-methylpropionitrile) initiator (AIBN, Acros) was used without further purification. n-Hexane (Merck) and tetrahydrofuran (THF, Labscan) were used as media for the dispersion polymerization. Poly[2-(diisopropylamino)ethyl methacrylate]-b-poly[2-(N-morpholino)ethyl methacrylate] 12658
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Langmuir (PDPA-b-PMEMA) diblock copolymers were used as novel steric stabilizers. Two PDPA-b-PMEMA diblock copolymers were synthesized by using group-transfer polymerization as reported in our previous work.42 The comonomer compositions of both block copolymers were kept the same, but their molecular weights were chosen to be different (Table S1 in the Supporting Information).
Synthesis of PMEMA Microgels via Dispersion Polymerization. Polymerization was carried out in a 100 mL three-necked roundbottomed flask equipped with a reflux condenser and sealed with a rubber septum. Both the diblock copolymer stabilizer (0.75 g) and n-hexane (50 mL) were first transferred to the reaction flask. The solution was purged with nitrogen for 15 min to remove any oxygen and stirred at 250 rpm with a magnetic stirrer. Previously degassed MEMA (5 mL) and the EGDMA cross-linker (between 0.6 and 5.0 mol % on the basis of the MEMA monomer) were added to flask. The system temperature was fixed at 60 °C in an oil bath. Finally, the polymerization commenced upon the addition of a degassed solution of the AIBN initiator (typically 3 mL). The amount of AIBN (60 mg) was fixed at between 0.5 and 1.0 mol % relative to the MEMA monomer. The solution turned milky white within 10 min, and stirring was continued for 24 h at 60 °C. Purification of Microgels. Dialysis and/or centrifugation methods were used to remove unreacted monomers and excess stabilizer or surfactants. The microgel dispersions were centrifuged three times in n-hexane (15 00018 000 rpm). After each centrifugation, the supernatant was removed and the sediment was redispersed. To investigate (de)swelling behaviors in aqueous media, the microgel was freeze dried under high vacuum and redispersed in deionized water. Characterization. Dynamic light scattering (DLS) was used to determine the hydrodynamic diameters and the polydispersity indexes (PDI = μ2/Γ2) of all PMEMA microgels. DLS was conducted on an ALV/CGS-3 compact goniometer system (Malvern, U.K.) equipped with a 22 mW HeNe laser operating at λ0 = 632.8 nm, an avalanche photodiode detector with a high quantum efficiency, and an ALV/LSE5003 multiple τ digital correlator electronic system. The temperature was controlled using both a cell and external bath acting through the sample cell. The morphologies of the microgel particles were investigated by scanning electron microscopy (SEM, JSM 5600LV). SEM samples were sputter coated with a gold layer. The temperature-dependent absorption of PMEMA microgel aqueous dispersions was determined at 500 nm by using a UVvis spectrometer (Perkin Elmer Lambda 35). A small temperature probe was immersed in the upper part of the stirred copolymer solution, and the solution temperature was increased slowly from 15 to 45 °C. The temperature was kept at a designed temperature for 2 min before each measurement. According to both DLS and UV measurements, 2 min is enough to reach the (de)swelling equilibrium for PMEMA microgels. A Zetasizer Nano ZS (Malvern Instrument, Ltd., U.K.) was used to measure the zeta potential as a function of pH. The solution pH of PMEMA microgel samples was adjusted with HCl and KOH, and measurements were repeated three times, with the average of these three measurements being given in Table 2.
’ RESULTS AND DISCUSSION PDPA-b-PMEMA Diblock Copolymer Stabilizer. PMEMA is a weak polybase that is molecularly soluble over a wide pH range, either as a weak cationic polyelectrolyte in acidic media or as a noncharged polymer at neutral or basic pH. It exhibits inverse temperature solubility behavior, and its pKa value is 4.9 as reported in our previous studies.43 Depending on the molecular weight, the cloud points of PMEMA homopolymers range from 34 to 54 °C at pH 7. The water solubility of PMEMA also depends on the ionic strength of the medium above pH 6 at room temperature. It can be salted out relatively easily from aqueous
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solution upon the addition of divalent electrolytes such as Na2SO4 and K2CO3.4245 The PDPA homopolymer dissolves as a cationic polyelectrolyte in acidic solution (pH < 6) because of the protonation of its tertiary amine residues. Precipitation from aqueous solution occurs when the solution pH exceeds the pKa of 6.4 for the PDPA homopolymer because the average degree of protonation drops below a critical value and the chains become hydrophobic.44 In contrast, the PMEMA homopolymer remains water soluble at room temperature in mildly alkaline media in the absence of an electrolyte. In addition, although the PDPA homopolymer is soluble, the PMEMA homopolymer is insoluble in n-alkanes. In view of these observations, we realized that the subtle variation in the hydrophilic/hydrophobic and liophilic/ liophobic balance of the poly[2-(diisopropylamino)ethyl methacrylate]-b-poly[2-(N-morpholino)ethyl methacrylate] (PDPAb-PMEMA) diblock copolymer provided a unique opportunity to prepare two distinct micelle structures from the same diblock copolymer in aqueous solution and in n-alkanes: (i) PDPA-core micelles in aqueous solution at neutral pH by the PMEMA block forming a hydrated corona and (ii) PMEMA-core micelles in n-alkanes by the PDPA block forming a solvated corona.42 Because of micelle formation in n-alkanes, we hypothesized that the PDPA-rich PDPA-b-PMEMA diblock copolymers can be used as a steric stabilizer in the synthesis of PMEMA microgels. Thus, the steric stabilization of PMEMA microgels in n-hexane was provided by using novel PDPA-b-PMEMA diblock copolymers. Synthesis of PMEMA Microgels. The efficient synthesis of sterically stabilized PMEMA microgels with controllable particle diameter has been carried out by using dispersion polymerization. An important advantage of dispersion polymerization is that the size of the microgel can be adjusted by changing various parameters such as the mixing speed, type of solvent, concentration, molecular weight of stabilizers, and polymerization temperature.13,32 The mixing speed (250 rpm) and the amount of MEMA monomer (5 mL) were kept constant in all polymerizations. Depending on the recipe, the radii of microgels in latex form in dispersing media were between 60 and 361 nm in a broad interval and the PDI values were between 0.001 and 0.13 as given in Table 1. These low polydispersity index values referring to narrow particle size distributions indicated that PDPA-rich PDPA-b-PMEMA diblock copolymer stabilizers were favorable to PMEMA microgel synthesis via dispersion polymerization. The stabilization of cross-linked PMEMA homopolymer chains is provided by the physical adsorption of diblock copolymer onto spherical cross-linked PMEMA. The insoluble PMEMA chains are adsorbed as an anchor block onto the particle surface, and solvated PDPA blocks act as a steric stabilizer for the particles to ensure colloidal stability. Different particle radii were obtained by changing various reaction parameters, and these effects on the PMEMA microgel sizes were explained briefly. After synthesis, PMEMA latexes were purified via centrifugation in n-hexane and dried under vacuum. Finally, PMEMA latexes were redispersed in water and their stimuli-responsive behaviors in aqueous media were investigated in detail. Recently, we have also successfully synthesized the PMEMA microgel via aqueous dispersion polymerization at elevated temperature and pH >6 in the presence of salt. Armes’ group has used poly(ethylene glycol) methacrylates and aliquots as stabilizers in the synthesis of pH-responsive microgels,12,13 and both can be used in the synthesis of PMEMA microgels. However, additional cationic stabilizer should be used to obtain a 12659
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Table 1. Recipe for PMEMA Microgel (Cross-Linked Latex Form) Synthesis by Dispersion Polymerization in n-Hexane and a Summary of DLS Measurements in n-Hexane (MEMA, 5 mL; AIBN, 60 mg; Stabilizer, 0.75 g)
Table 2. Hydrodynamic Radii and ζ Values of PMEMA Microgels (VA7) as a Function of Solution pH in the Presence and Absence of Additional Diblock Copolymers at Room Temperature in Aqueous Media
sample code
stabilizer code
cosolvent (THF, vol %)
EGDMA (mL)
radius (nm)
PDI (μ2/Γ2)
radius
ζ
radius
ζ
radius
ζ
pH
(nm)a
(mV)a
(nm)b
(mV)b
(nm)c
(mV)c
VA1
VBI
10
0.25
349
0.05
2
195
+33.30
220
+35.80
168
+38.01
VA2
VBI
10
0.10
353
0.06
4
187
+31.80
202
+31.20
150
+35.60
VA3
VBI
5
0.10
361
0.02
6
123
+12.00
169
+29.00
152
+27.50
0.13
8
113
+0.56
160
+12.00
154
+14.00
0.04
10
102
9.75
149
+6.25
160
+5.00
12
98
16.00
132
+2.16
149
+3.08
VA4 VA5
VBI VBI
0.10 0.05
194 156
VA6 VA7
VBII VBII
0.10 0.05
60 85
0.07 0.12
VA8
VBII
0.03
140
0.01
better stabilization. Our research has been ongoing in this area and will be published in the near future. Effect of the Molecular Weight of the Stabilizer. Two PDPA-b-PMEMA stabilizers (0.75 g, VBI and VBII in Table S1) having the same comonomer composition and different molecular weights were evaluated using the information given in Table 1. Entries VA4-VA6 and VA5-VA7 given in Table 1 show the influence of the stabilizer molecular weight on the resulting PMEMA particle size. Despite using the same amount of stabilizer, the use of stabilizer with a higher molecular weight has caused a lower hydrodynamic diameter. As expected, the particle size decreased with increasing stabilizer molecular weight for PMEMA microgel systems. Thus, it was concluded that this it is a way to control the microgel diameter by using the same masses of stabilizers having the same comonomer compositions but different molecular weights. Use of a Cosolvent. Similarly, the use of a cosolvent in a dispersion medium affects the size of the PMEMA microgels. THF is a good solvent for both blocks of the stabilizer. When we compare the dispersion media, the medium containing THF as a cosolvent is better than n-hexane containing no cosolvent (the PMEMA homopolymer is not soluble in n-hexane but soluble in THF). Because of the fact that the microgel is more or less in a swollen state in the presence of the THF cosolvent, there is an increased radius of the resulting microgel particles (compare VA2, VA3, and VA4 in Table 1). Effect of the Degree of Cross-Linking. The particle diameter and swelling behavior of the PMEMA microgels were also studied to understand the effect of the degree of cross-linking. In the information in Table 1, the EGDMA concentration was varied from 0.6 to 5.0 mol % on the basis of the MEMA monomer. The results showed that the hydrodynamic radius decreased with an increase in cross-linker content. Consequently, using more cross-linking agent in dispersion polymerization causes a more compressive polymer network. As an example, microgels in the desolvated latex form containing 2 and 1 mol % cross-linkers had diameters of 60 nm (VA6) and 140 nm (VA8) in n-hexane, respectively (Table 1). Scanning electron micrographs of various PMEMA microgels are given in Figure 2. The images indicate monodisperse PMEMA microgel latex particles. The PMEMA microgels appear to be uniform in shape and size, and no significant aggregation is observed. pH-Induced Swelling Behavior. The effect of solution pH on the hydrodynamic radius of PMEMA microgels was investigated
a
Only PMEMA microgel dispersion. b After the addition of both MePDMA0.59-b-PMEMA0.41 diblock copolymer stabilizer (0.5 g) and Na2SO4 (0.8 M) to a PMEMA microgel dispersion (50 mL, 1 wt %). c After the addition of a MePDMA0.72-b-PDPA0.28 diblock copolymer stabilizer (0.5 g) to a PMEMA microgel dispersion (50 mL, 1 wt%).
by using DLS and is given in Figure 3. As an example, the hydrodynamic radius distributions of 1 mol % cross-linked PMEMA microgels (VA7) in aqueous media at pH 2.0, 6.0, and 10.0 were determined to be 196, 129, and 102 nm, respectively (Figure S1 in the Supporting Information). The polydispersity index values of the VA7 PMEMA microgels over a broad pH range were indicated to be monodisperse particle size distributions (PDI < 0.07). At low pH (pH 2.0), as expected, the microgels had a larger diameter. This swelling is due to the protonation of morpholino groups of PMEMA microgels, which caused not only an electrostatic repulsion among cationic morpholino groups but also an iondipole attraction between cationic microgels and water (Figure S1 in the Supporting Information and Figure 3). As expected, the pH of the aqueous solution influences the size of the PMEMA microgel particles more or less depending on the degree of cross-linking (Figure 3). DLS results for all microgel samples also showed monodisperse particle size distributions, especially in the acidic aqueous medium. The stabilizing moiety, PDPA blocks, are water-soluble at acidic pH at room temperature but insoluble in aqueous media at neutral and basic pH. Because of the PDPA blocks that are insoluble above pH 6, the stabilization of the PMEMA microgels was decreased at high pH and thus the PDI values were slightly increased. We have also used UVvis spectroscopy to monitor absorbance values by changing the solution pH of diluted PMEMA microgels. For the solution of this problem, an additional stabilizer usage has been examined. Parallel to DLS measurements, we assumed that the UV absorbance of microgel dispersion could be useful in observing the critical swellingdeswelling pH value of the microgel particles. An increase in the solution pH caused a dramatic decrease on the UV absorbance of the microgels (Figure S2 in the Supporting Information). The critical (de)swelling pH is around pH 5 as expected (around the pKa value of the PMEMA conjugate). As DLS measurements indicated, an increase in the pH causes a deswelling or dehydration of the microgel particle as a result of the deprotonation of MEMA residues. Thus, the smaller particle dispersion, above pH 6, will give less absorption (cf. Figures 3 and Figure S2 in the Supporting Information). Increasing Stabilization with Cationic Diblock Copolymers. Figure 4 shows the pH-induced particle size change by adding two different free polymer chains to the diluted microgel solution. 12660
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Figure 2. SEM images of PMEMA microgels: (a) VA1, (b) VA2, (c) VA4, and (d) VA5.
Figure 3. Variation of the radius of PMEMA microgels with the solution pH (VA1, VA2, and VA3).
Swellingdeswelling behavior was examined by adding selectively quaternized MePDMA0.59-b-PMEMA0.41 (Mn = 46 100 g/mol, Mw/Mn = 1.07) and MePDMA0.72-b-PDPA0.28 (Mn = 19 200 g/mol, Mw/Mn = 1.12) diblock copolymers to the diluted microgel solution. After the synthesis of PDMA-b-PMEMA and PDMA-b-PDPA diblock copolymers by GTP, the selective quaternization of the DMA residues was carried out using methyl iodide (MeI) as reported elsewhere.43 PMEMA homopolymer can be precipitated via a salting out effect from aqueous solution at a relatively low salt concentration (e.g., 0.10.2 M K2CO3 or Na2SO4), with the cationic PDMA blocks forming solvated coronas and the PMEMA blocks forming the micelle cores.4245 When watersoluble MePDMA-b-PMEMA was added to the aqueous microgel solution, the adsorption of these free polymer chains on the surface of the microgel above pH 6 was provided by enabling the dehydration of the PMEMA block by adding Na2SO4
Figure 4. Changing hydrodynamic radius of PMEMA microgels with solution pH: ()) only the PMEMA microgel, VA7; (b) after the addition of MePDMA0.59-b-PMEMA0.41 and Na2SO4 (0.8 M) to the VA7 dispersion; and (2) MePDMA0.72-b-PDPA0.28 addition to the VA7 microgel dispersion.
(>0.6 M). As can be seen in Figure 4, the addition of both MePDMA-b-PMEMA block copolymer and salt to the medium caused a change in the hydrodynamic radius of the microgel over a wide pH range. At low pH values, salt addition reduced the repulsion among cationic morpholino residues and caused a decrease in the microgel particle diameter. However, when the solution pH was increased to above pH 6, both microgels and PMEMA blocks of the block copolymer were dehydrated as a result of the salting-out effect and the PMEMA block of the block copolymer would either start to adsorb on the PMEMA microgel particles or form a micelle core. DLS studies indicated the adsorption of the PMEMA block of the MePDMA-b-PMEMA diblock copolymer onto the microgel surface and provided better stabilization via a strong interaction between the cationic MePDMA block and the 12661
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solvent above pH 6 (Figure 4). Note that the dehydration of the microgel causes a decrease in diameter as discussed below but the adsorption of the cationic block copolymer resulted in an increase in the microgel diameter. Overall, the addition of both the block copolymer and the salt to the microgel dispersion caused an increase in diameter and a better stabilization above pH 6 in which all MEMA residues are in the neutral form. Similarly, as an additional alternative stabilizer, the MePDMAb-PDPA cationic diblock copolymer having a pH-responsive PDPA block was also examined to obtain a better stabilization of the PMEMA microgel in a basic aqueous solution without the use of any electrolyte. The PDPA homopolymer is soluble with the protonation of tertiary amine groups in an acidic medium (pH 26) and insoluble with deprotonation in a basic medium. In this way, MePDMA-corona and PDPA-core micelles would be obtained in a basic medium. This micelle formation produced in a basic medium helps to increase the stabilization by adsorbing physically onto the PMEMA microgel surface as well. The changes in the microgel radii with solution pH in the presence and absence of these copolymers are shown in Figure 4. Consequently, it has been proven that both copolymers could anchor to the surfaces of PMEMA microgels, and particles coming closer to each other via aggregation was prevented by the cationic characteristics of these additional copolymer stabilizers. These cationic diblock copolymers enhance the stabilization of PMEMA microgels with a permanent cationic charge on the diblock copolymer. Zeta potential measurements also support these DLS
results. The zeta potentials of the microgel particles were all positive at all pH values after the addition of MePDMA-b-PDPA diblock copolymer, especially at pH values above 6. This indicated a better stability of microgels via the addition of these cationic diblock copolymers (Table 2). Temperature-Induced Size Change. Generally, it is believed that the hydrophilichydrophobic pushpull force is responsible for the volume phase transition temperature (VPTT) of PMEMA microgels. Although the hydrophilic forces dominate below the VPTT in aqueous media, the microgel remains in a swollen state but the hydrophobic forces dominate above the VPTT and the microgel shrinks. As reported earlier, the PMEMA homopolymer is soluble in neutral and acidic media at room temperature but less soluble in basic solutions.44 PMEMA microgels would have a thermoresponsive nature in its neutral form (pH > 6) because of the different hydration of PMEMA polymer chains at temperatures below and above the VPTT. DLS is an efficient method of determining the phase-transition behavior of such thermosensitive particles. Thus, the hydrodynamic radii of the PMEMA microgels were measured by dynamic light scattering (DLS) as a function of temperature (Figures S3 and S4 in the Supporting Information). The radii of the microgel particles (VA8) at 14, 32, and 55 °C were measured to be 150 nm (PDI = 0.02), 123 nm (PDI = 0.01), and 104 nm (PDI = 0.01), respectively. For various PMEMA microgels, the hydrodynamic radius decreased dramatically as the temperature reached a certain range, which clearly indicated that the PMEMA microgels were thermoresponsive (Figure S4 in the Supporting Information). A similar study in three different aqueous media (pH 3, 7, and 10) was also performed and investigated the variation of the hydrodynamic radius of the PMEMA microgel particles (Figure 5). In neutral and basic solutions, the size of the microgel decreased gradually until the temperature of the medium reached the LCST (around 35 °C). Above the LCST, the size of the microgel does not change very much with temperature (Figure 5). In an acidic medium, although the temperature of the medium exceeds the LCST because of the protonation of the whole microgel, there was no change in the size of PMEMA microgels because these groups have gained hydrophilic character. Salt-Induced Swelling Behavior. Typically, neutral electrolytes can drastically alter the solution properties of macromolecules, such as the solubility, precipitation temperature, and viscosity. The magnitude of these changes depends on the nature of the ions. The PMEMA homopolymer can be precipitated relatively easily from aqueous solution upon addition of electrolytes such as Na2SO4, K2CO3, and Na3PO4.4245 The effects of electrolyte concentration on the (de)swelling properties of
Figure 5. Changing hydrodynamic radius of PMEMA microgels as a function of solution pH: (acidic) pH 2.0, (neutral) pH 7.0, and (basic) pH 10.0.
Table 3. Summary of DLS Measurements of PMEMA Microgels in Different Organic Solvents at Room Temperature n-hexane
acetone
THF
chloroform
sample code
stabilizer code
radius (nm)
PDI
radius (nm)
PDI
radius (nm)
PDI
radius (nm)
PDI
VA1
VBI
349
0.06
341
0.05
VA1
VBI
349
0.06
VA2
VBI
353
0.06
540
0.08
VA2
VBI
353
0.06
VA3
VBI
361
0.02
430
0.01
VA3
VBI
361
0.02
VA4 VA5
VBI VBI
156 194
0.04 0.13
411 281
0.11 0.06
VA4 VA5
VBI VBI
156 194
0.04 0.13
VA6
VBII
60
0.07
84
0.05
VA6
VBII
60
0.07
VA7
VBII
85
0.12
110
0.08
VA7
VBII
85
0.12
VA8
VBII
140
0.01
155
0.01
VA8
VBII
140
0.01
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Langmuir PMEMA microgels were examined by diluting microgel dispersions with Na2SO4 solutions of different concentration and measuring the change in the particle size (Figure S5 in the Supporting Information). To study the relevance of the ionic strength on particle swellingdeswelling, we fixed the temperature to room temperature. As DLS measurements indicated, the hydrodynamic radius of PMEMA microgels was dramatically decreased with an increase in the ionic strength (Figure S5 in the Supporting Information). The radius of the microgel decreased from 275 to 100 nm by the addition of a tiny amount of Na2SO4 (0.06 M). Similar to other studies reported in the literature,28 our microgel particles have a strong response to ionic strength. In Organic Solvents. PMEMA homopolymers are soluble in many organic solvent such as THF, acetone, and chloroform but are not soluble in n-alkanes.42 Thus, the solvents in which PMEMA is soluble are described as good solvent, and n-alkanes are described as poor solvents for PMEMA microgels. Table 3 shows the hydrodynamic radii and polydispersity index values of
Figure 6. Variation of zeta potentials of PMEMA microgels with pH at room temperature.
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PMEMA microgels in different organic solvents. As seen in Table 3, in general, the radius of the same microgel sample (cross-linked PMEMA latex) is increasing in the order of hexane, acetone, THF, and chloroform. The best solvation occurs with chloroform. It is concluded that, in addition to environmental effects such as pH, temperature, and electrolyte concentration, PMEMA microgels were also sensitive to the nature of organic solvents. Determination of the LCST. The determination of the LCST of the PMEMA microgel aqueous solution is performed by UVvis spectrophotometry. For the determination of LCST values of the PMEMA microgels, the solution was diluted to obtain a concentration of approximately 1 wt %. LCST measurements were evaluated at around neutral pH (between pH 6.8 and 7.7). The absorbance of this dispersion was recorded at 500 nm in the temperature range of 1643 °C. For various PMEMA microgels, the absorbance decreased dramatically as the temperature reached a certain range that clearly indicated that the PMEMA microgels were thermoresponsive (Figure S6 in the Supporting Information). On average, LCST values for PMEMA microgels were determined to be around 34 °C. The microgels are in a swelled or hydrated form below the LCST and absorb more light, but they deswell above the LCST and absorb less light because of their smaller sizes. The size of the microgel does not change very much with temperature above the LCST, and thus the absorbance does not change further at high temperatures (Figure S6 in the Supporting Information). The zeta potential is a very useful and important parameter for obtaining information about the stabilization of nanoparticles or dispersions. Figure 6 shows the zeta potential of PMEMA microgels as a function of pH. It can be seen that all microgels reach their isoelectric point between pH 6 and 8. As expected, the protonation of the MEMA residues led to strongly cationic character at low pH, with zeta potentials of approximately +35 mV. However, the reduction in the zeta potential of the microgels with the addition of KOH is due to the deprotonation of quaternary morpholino groups of the PMEMA microgels.
Figure 7. Interaction of PMEMA microgels (VA2) with magnetic particles: (a) an aqueous PMEMA microgel dispersion (pH 7), (b) hydrophilic acidic Fe3O4 magnetic particles, (c) a solution containing microgel and magnetic particles, and (d) the gathering of microgels and magnetic particles with a magnet. 12663
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Langmuir Interaction with Magnetic Particle. The interactions of microgels with magnetic particles are also interesting for biomedical applications in targeted drug delivery. The typical way to produce magnetic polymer particles includes the process of coating the material by a surfactant and embedding it in the polymer via suspension, emulsion, or precipitation.24,46,47 In this study, we aimed to cover microgel particles with Fe3O4 magnetic nanoparticles by simply mixing both dispersions at neutral pH in which the microgel had a negative zeta potential but the Fe3O4 magnetic particles had a positive zeta potential. If there is an interaction (e.g., iondipole attraction and/or hydrogen bonding) between Fe3O4 magnetic particles and microgels, then the microgel particles would be covered by magnetic nanoparticles under the above conditions and would show a response to the external magnetic field. The interaction between a microgel and Fe3O4 particles should be over lone pair electrons of N atoms of morpholino rings and positively charged Fe3O4 particles (especially Fe ions). Such an interaction might be called a dipoleion interaction. It is well known that magnetic Fe3O4 particles prepared by the coprecipitation method have a large number of hydroxyl groups on its surface in contact with the aqueous phase.47 Thus, more or less, hydrogen bonding might be expected between morpholino N atoms of a microgel and OH groups of magnetic particle as well. As can be seen in Figure 7, after the addition of a few drops of a Fe3O4 magnetic particle dispersion (Figure 7b) to the PMEMA microgel dispersion in the presence of a tiny amount of salt (VA1, Figure 7a), the appearance of the dispersion changed to saddle brown (Figure 7c). When the external magnetic field was applied, it was observed that microgels and magnetic particles were gathered around the magnet, leading to the transparency of the dispersion (Figure 7d). This indicates the adsorption of Fe3O4 nanoparticles on microgel particles. This application can be an appropriate way to repel and eradicate microgels or magnetic iron particles in aqueous media and indicates the potential value of these particles in wastewater treatment and water purification.
’ CONCLUSIONS In this study, a series of novel monodisperse PMEMA microgels were successfully prepared by using novel tertiary amine methacrylate-based water-soluble diblock copolymers as stabilizers. These microgels exhibited multiresponsive behavior in aqueous media. They respond well to solution pH, temperature, ionic strength, type of dispersing media, and magnetic particles. They swell below the LCST (34 °C), swell more at low pH (6), and deswell more and more with increasing salt concentration (pH >6). This is the first study of novel microgels that reversibly respond to the solution pH, salt concentration, and temperature. They also adsorb Fe3O4 magnetic particles very well and gain responsiveness to magnetic fields. They can be considered to be promising materials for various applications such as biomedical applications, wastewater treatment, and water purification. ’ ASSOCIATED CONTENT
bS
Supporting Information. Proton NMR spectroscopy and GPC results for two PDPA-b-PMEMA diblock copolymer stabilizers. Hydrodynamic radius distribution of PMEMA microgel at room temperature at different pH values. Variation of UV
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absorption for PMEMA microgel dispersions with solution pH. Hydrodynamic radius change in the PMEMA microgel as a function of temperature. Variation of the radius of PMEMA microgels as a function of the electrolyte concentration. Variation of the UV absorption of PMEMA microgel dispersions with temperature. This material is available free of charge via the Internet at http://pubs.acs.org.
’ AUTHOR INFORMATION Corresponding Author
*Tel: +90-222-2393750-2751. Fax: +90-222-2393578. E-mail:
[email protected].
’ ACKNOWLEDGMENT We are grateful for the financial support of Eskisehir Osmangazi University (ESOGU). This work was supported by the Commission of Scientific Research Projects of ESOGU (GR/ 200619007). V.B. expresses his gratitude to the Turkish Academy of Sciences (TUBA) as an associate member for financial support. We thank R. B. Karabacak for some DLS measurements. ’ REFERENCES (1) Snowden, M. J.; Thorne, J. T., J. B.; Vine, G. J. Colloid Polym. Sci. 2011, 289, 625–646. (2) Freitag, R.; Panayitou, M.; Pohner, C.; Vandevyver, C.; Wandrey, C.; Hilbrig, F. React. Funct. Polym. 2007, 67, 807–819. (3) Du, B.; Cao, Z.; Chen, T.; Nie, J.; Xu, J.; Fan, Z. Langmuir 2008, 24, 12771–12778. (4) Saunders, B. R.; Vincent, B. Adv. Colloid Interface Sci. 1999, 80, 1–25. (5) Pelton, R. Adv. Colloid Interface Sci. 2000, 85, 1–33. (6) Park, T. G.; Hoffman, A. S. Macromolecules 1993, 26, 5045–5048. (7) Zenkl, G.; Mayr, T.; Khmant, I. Macromol. Biosci. 2008, 8, 146–152. (8) Yang, Y. J.; Wang, Q.; Xu, H. B.; Yang, X. L. Int. J. Pharm. 2008, 361, 189–193. (9) Liang, B. R.; Zhang, Q. S.; Zha, L. S.; Ma, J. H. J. Appl. Polym. Sci. 2007, 103, 2962–2967. (10) Suh, K. D.; Park, Y. H.; Han, J. H. Macromol. Chem. Phys. 2008, 209, 938–943. (11) Tam, K. C.; Tan, B. H.; Ravi, P.; Tan, L. N. J. Colloid Interface Sci. 2007, 309, 453–463. (12) Dupin, D.; Fujii, S.; Armes, S. P.; Reeve, P.; Baxter, S. M. Langmuir 2006, 22, 3381–3387. (13) Armes, S. P.; Dupin, D.; Rosselgong, J.; Routh, A. F. Langmuir 2007, 23, 4035–4041. (14) Loxley, A.; Vincent, B. Colloid Polym. Sci. 1997, 275, 1108–1114. (15) Saunders, B. R.; Crowther, H. M.; Vincent, B. Macromolecules 1997, 30, 482–487. (16) Vinogradov, S. V. Curr. Pharm. Design 2006, 12, 4703–4712. (17) Lopez, V. C.; Hadgraft, J.; Snowden, M. J. Int. J. Pharmaceut. 2005, 292, 137–147. (18) Lopez, V. C.; Raghavan, S. L.; Snowden, M. J. React. Funct. Polym. 2004, 58, 175–185. (19) Kawaguchi, H.; Fujimoto, K. Bioseparation 1998, 7, 253–258. (20) Mori, T.; Maeda, M. Langmuir 2004, 20, 313–319. (21) Vamvakaki, M.; Palioura, D.; Armes, S. P.; Anastasiadis, S. H. Langmuir 2007, 23, 5761–5768. (22) Akamatsu, K.; Shimada, M.; Tsuruoka, T.; Nawafune, H.; Fujii, S.; Nakamura, Y. Langmuir 2010, 26, 1254–1259. (23) Echeverria, C.; Mijangos, C. Macromol. Rapid Commun. 2010, 31, 54–58. (24) Du, B. Y.; Chen, T. Y.; Cao, Z.; Guo, X. L.; Nie, J. J.; Xu, J. T.; Fan, Z. Q. Polymer 2011, 52, 172–179. 12664
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