“Inverse Polyampholyte” Hydrogels from Double-Cationic Hydrogels

Article pubs.acs.org/Macromolecules

“Inverse Polyampholyte” Hydrogels from Double-Cationic Hydrogels: Synthesis by RAFT Polymerization and Characterization Kyriaki S. Pafiti, Marios Elladiou, and Costas S. Patrickios* Department of Chemistry, University of Cyprus, P.O. Box 20537, 1678 Nicosia, Cyprus ABSTRACT: We present two novel, homologous, pyridinebased monomers, 2-(pyridin-2-yl)ethyl methacrylate (PyEMA) and (pyridin-2-yl)methyl methacrylate (PyMMA), which, despite their structural similarity, the former can be readily thermolyzed to methacrylic acid, while the latter remains intact under the same conditions. This was most dramatically demonstrated in the present work, where PyEMA and PyMMA were randomly terpolymerized with a dimethacrylate cross-linker using reversible addition−fragmentation chain transfer polymerization to yield weakly double-cationic polyelectrolyte hydrogels of three different compositions which, upon thermal treatment, they were readily converted to polyampholyte hydrogels. While the parent double-cationic polyelectrolyte hydrogels exhibited a swelling response only to low-pH conditions, the daughter polyampholyte hydrogels presented swelling responses to both high- and low-pH conditions. Owing to the relative values of the effective pKa’s of the weakly acidic and weakly basic units, with the latter being lower than the former (“inverse polyampholyte” behavior), the swelling profiles of the daughter hydrogels were insensitive to polyampholyte composition.

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INTRODUCTION We recently discovered that 2-(pyridin-2-yl)ethanol is a good protecting group for methacrylic acid (MAA).1 Thus, 2(pyridin-2-yl)ethyl methacrylate (PyEMA) can be readily polymerized, and the resulting polymer can be subsequently converted to polyMAA and 2-vinylpyridine (2VPy, lowmolecular-weight side product) under relatively mild conditions. These conditions include thermolysis at 130 °C for a few hours either in the bulk or in solution, or alkaline hydrolysis at room temperature.1 The latter deprotection conditions are noteworthy, as most carboxylic acid protecting groups2 are removable under acidic conditions (tert-butyl,3−6 hemiacetal ester,7−12 and trimethylsilyl4,7), with the notable exception of activated esters (pentafluorophenyl and N-hydroxysuccinimidyl13−15) which are also hydrolyzable under alkaline conditions. The facile and quantitative thermolysis of polyPyEMA is also supported by differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA), with the former indicating an endothermic cleavage peak at 175 °C (heating rate of 10 °C min−1) and the latter suggesting loss of exactly the appropriate mass percentage (corresponding to 2VPy) at 200 °C (heating rate also at 10 °C min−1).1 We also determined that the ester of (pyridin-2-yl)methanol with polyMAA, i.e., poly[(pyridin-2-yl)methyl methacrylate] (polyPyMMA), is very stable to thermolysis and reasonably stable to alkaline hydrolysis.16 Thus, copolymers of PyMMA and PyEMA could be selectively cleaved, converting the PyEMA units to MAA units but leaving the PyMMA units intact. This would result in synthetic polyampholytes17−23 with MAA negatively ionizable units and PyMMA positively ionizable units. This was exactly the aim in this investigation: to prepare synthetic polyampholyte hydrogels by combining © 2014 American Chemical Society

these two monomers together with a cross-linker, followed by the selective deprotection of the PyEMA units. Although the literature on synthetic polyampholyte hydrogels is very rich,24 the particular ones would have three important distinguishing features. First, the present polyampholyte hydrogels would be obtained through double-cationic polyelectrolyte precursor hydrogels, based on two homologous (pyridin-2-yl)alkyl methacrylates. Second, the primary chain length of the gels at hand would be well-defined, a result of the controlled radical polymerization method planned to be employed for their syntheses. Finally, the particular polyampholyte hydrogels would be extraordinary in terms of the relative pKa values of the two types of monomer repeating units, with the amine monomer repeating units being more acidic than the carboxylic acid monomer repeating units, leading to “inverse polyampholyte” behavior; this would have certain important implications on the hydrogen ion equilibrium properties of the polyampholyte hydrogels, especially their isoelectric point. In the present work, reversible addition−fragmentation chain transfer (RAFT) polymerization25−29 is used to secure the structural homogeneity of the polymer networks. Three networks with different compositions were prepared and characterized both in the original double-cationic polyelectrolyte form (before deprotection) and in the final polyampholyte (after deprotection) form. In addition to the networks, an equimolar linear statistical PyEMA−PyMMA copolymer was also prepared and used to confirm the selective Received: January 11, 2014 Revised: February 10, 2014 Published: February 17, 2014 1819

dx.doi.org/10.1021/ma500084c | Macromolecules 2014, 47, 1819−1827

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Figure 1. Synthetic route followed for the preparation of the PyMMA and the PyEMA monomers.

Figure 2. Chemical structures and names of the main reagents used for the network synthesis. free radical inhibitor DPPH. Finally, the chemical structures of these monomers were confirmed using 1H and 13C NMR spectroscopy. PyMMA. 1H NMR (CDCl3, δ): 1.88 ppm (s, CH2CCH3, 3 H), 5.21 ppm (s, −OCH2−, 2 H), 5.52 ppm (s, olefinic H trans to CO2, 1 H), 6.11 ppm (s, olefinic H cis to CO2, 1 H), 7.08 ppm (1 H), 7.24 ppm (1 H), 7.56 ppm (1 H) and 8.48 ppm (1 H). 13C NMR (CDCl3, δ): 18.00 ppm (s, CH2CCH3, 1 C), 66.60 ppm (s, −OCH2−, 1 C), 121.14 ppm (s, aromatic, 1 C), 122.44 ppm (s, aromatic, 1 C), 125.82 ppm (s, CH2CCH3, 1 C), 135.65 ppm (s, aromatic, 1 C), 136.41 ppm (s, CH2CCH3, 1 C), 149.05 ppm (s, aromatic, 1 C), 155.72 ppm (s, aromatic, 1 C), and 166.55 ppm (s, CO2, 1 C). PyEMA. 1H NMR (CDCl3, δ): 1.80 ppm (s, CH2CCH3, 3 H), 3.09 ppm (t, −OCH2CH2−, 2 H), 4.45 ppm (t, −OCH2CH2−, 2 H), 5.44 ppm (s, olefinic H trans to CO2, 1 H), 5.95 ppm (s, olefinic H cis to CO2, 1 H), 7.09 ppm (1 H), 7.24 ppm (1 H), 7.51 ppm (1 H), and 8.48 ppm (1 H). 13C NMR (CDCl3, δ): 18.24 ppm (s, CH2CCH3, 1 C), 37.43 ppm (s, −OCH2CH2−, 1 C), 63.84 ppm (s, −OCH2CH2−, 1 C), 121.60 ppm (s, aromatic, 1 C), 123.43 ppm (s, aromatic, 1 C), 125.46 ppm (s, CH2CCH3, 1 C), 136.24 ppm (s, CH2CCH3, 1 C), 136.32 ppm (s, aromatic, 1 C), 149.46 ppm (s, aromatic, 1 C), 158.12 ppm (s, aromatic, 1 C) and 167.25 ppm (s, CO2, 1 C). Network Preparation. The synthesis of the randomly cross-linked PyMMA−PyEMA networks (the term “network” rather than “hydrogel” is used here as preparation takes place in an organic solvent) was accomplished by RAFT polymerization in the presence of EGDMA as cross-linker, 2-CPBD as CTA, AIBN as initiator, and 1,4-dioxane as solvent. Figure 2 displays the chemical structures and names of the monomers, the cross-linker, and the CTA used for the network synthesis. The networks were synthesized by the simultaneous terpolymerization of the two comonomers and the cross-linker. Networks with three different compositions, comprising 30, 52, and 70 mol % PyMMA, were prepared, while the molar ratio of the EGDMA cross-linker to the 2-CPDB CTA used was kept constant at 6:1. Finally, the PyEMA units in the original weakly basic polyelectrolyte network were thermolyzed at 130 °C, thus yielding the MAA units, and resulting in the formation of the polyampholyte networks. The details for the preparation of the near-equimolar randomly cross-linked network PyMMA52-co-PyEMA48-co-EGDMA6 are given below. 2-CPBD (38.5 mg, 0.174 mmol), AIBN (17.8 mg, 0.108 mmol), PyMMA (1.6 mL, 1.6 g, 9.0 mmol), PyEMA (1.6 mL, 1.6 g, 8.4 mmol), EGDMA (0.2 mL, 0.210 g, 1.060 mmol), and 2.6 mL of 1,4-dioxane were transferred to a small Schlenk tube (25 mL capacity)

PyEMA thermal deprotection via solution characterization techniques, not applicable to networks.

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EXPERIMENTAL SECTION

Materials. The alcohols (pyridin-2-yl)methanol (purity 98%) and 2-(pyridin-2-yl)ethanol (purity 98%), the cross-linker ethylene glycol dimethacrylate (EGDMA, purity 98%), the chain transfer agent (CTA) 2-cyanopropan-2-yl benzodithioate (2-CPBD, purity >97%), basic alumina (purity ≥98%), calcium hydride (CaH2, purity 90− 95%), 2,2-diphenyl-1-picrylhydrazyl hydrate (DPPH, purity 95%), triethylamine (purity ≥99%), and 1,4-dioxane (purity 99%) were purchased from Aldrich, Germany. The monomers PyMMA and PyEMA were synthesized in our laboratory as detailed in a following section. 2,2′-Azobis(isobutyronitrile) (AIBN, purity 95%), deuterated chloroform (CDCl3), dimethyl sulfoxide (DMSO, ≥99.7%), and deuterated DMSO (d6-DMSO) were purchased from Merck, Germany. Tetrahydrofuran (THF, purity 99.8%, both HPLC and reagent grade) was purchased from Scharlau, Spain. Methods. The EGDMA cross-linker was first passed through a basic alumina column to remove inhibitors and acidic impurities, stirred over CaH2 for 72 h to fully dry it and neutralize any remaining protonic impurities, and vacuum distilled. AIBN was purified by recrystallization twice from ethanol. Finally, 1,4-dioxane, the polymerization solvent, was purified by stirring it over CaH2, followed by vacuum distillation just prior to use. Synthesis of the PyMMA and PyEMA Monomers. The synthesis of the pyridine-based monomers PyMMA and PyEMA was accomplished by the esterification reactions of (pyridin-2-yl)methanol and 2-(pyridin-2-yl)ethanol, respectively, with methacryloyl chloride in the presence of triethylamine in freshly distilled, absolute THF, at 0 °C (Figure 1). For the synthesis of the PyMMA monomer, 10 mL of (pyridin-2-yl)methanol (11.3 g, 0.104 mol) was dissolved in 63 mL of THF. Following that, 72 mL of triethylamine (52.3 g, 0.517 mol) was added to the resulting solution. The mixture was cooled down to 0 °C in an ice bath. Subsequently, 12.1 mL of methacryloyl chloride (13.04 g, 0.125 mol) was added dropwise to the solution, which was stirred for 1 h. Afterward, the reaction mixture was filtered to remove the salt of triethylamine hydrochloride which was formed, and it was subsequently passed through a basic alumina column to remove the excess of methacryloyl chloride/methacrylic acid, while the solvent was evaporated off using a rotary evaporator. For further purification, the PyMMA and the PyEMA monomers were distilled over CaH2 under dynamic vacuum at 110 and 130 °C, respectively, in the presence of 1820


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containing a magnetic stirring bar. The resulting solution was, subsequently, degassed by three freeze−vacuum−thaw cycles, was placed under an argon blanket, and was adjusted to 65 °C using an oil bath where it was kept for 24 h to polymerize. Linear Copolymer Preparation. Because of the ease of analysis and for subsequent comparison with the networks, a linear, statistical near-equimolar PyMMA−PyEMA copolymer was also synthesized by RAFT polymerization. To this end, 38.5 mg of 2-CPBD (0.174 mmol), 17.8 mg of AIBN (0.108 mmol), 1.6 mL of PyMMA (1.6 g, 9.0 mmol), 1.6 mL PyEMA (1.6 g, 8.4 mmol), and 2.6 mL 1,4-dioxane were placed in a 25 mL Schlenk tube containing a magnetic stirring bar. The contents of the tube were, subsequently, degassed by three freeze−vacuum−thaw cycles, were placed under an inert argon atmosphere, and were heated in an oil bath at 65 °C for 24 h. Characterization of the Networks and the Linear (Co)polymers. Determination of the Sol Fraction (Extractables). After their synthesis, the three randomly cross-linked copolyelectrolytic networks were characterized in terms of their sol fraction (extractables). In particular, each whole network was placed in a glass jar containing THF and left there for two weeks to equilibrate and also to release its extractables. Subsequently, the THF solution of the extractables was transferred in to a preweighed round-bottomed flask, followed by the removal of the THF solvent using a rotary evaporator and further drying in a vacuum oven at room temperature for 72 h. The remaining dried mass was weighed, and the sol fraction was calculated as the ratio of the dried mass divided by the theoretical mass of the gel which was estimated as the sum of the masses of the comonomers, the cross-linker, and the CTA. Finally, samples from the extractables were analyzed using gel permeation chromatography (GPC) and 1H NMR spectroscopy to determine their molecular weights and compositions, respectively. Measurement of the Degree of Swelling (DS) in THF. After the extraction of the sol fraction, the three networks were also characterized in terms of their degrees of swelling (DSs) in THF. Three to four pieces from each network were placed in small vials and were weighed to determine their THF-swollen mass, followed by their drying in a vacuum oven at room temperature for 72 h. Subsequently, the dried pieces were reweighed to determine their dry mass, and finally, their DSs in THF were calculated as the ratio of the average swollen network mass (determined three times) divided by the dry network mass. Thermolysis of the PyEMA Units. After the washing out of the extractables and the determination of the DSs in THF, the three copolyelectrolytic networks were thermolyzed in order to convert the PyEMA units to MAA units, resulting in the formation of the ampholytic networks. To this end, several pieces of each THF-swollen network were first dried again and then thermolyzed in a vacuum oven at 130 °C for 24 h. After thermolysis, all the pieces were rinsed for 48 h with THF to extract the thermolysis side-products. The linear PyEMA−PyMMA statistical copolymer was also thermolyzed to convert the PyEMA units to MAA units and transform the double-cationic linear polyelectrolyte to a linear polyampholyte. However, the thermolysis, in this case, took place in DMSO (copolymer concentration = 30% w/w) at 130 °C for 24 h. At the end of the reaction, a sample from the solution of the thermolyzed copolymer was analyzed using 1H NMR spectroscopy in d6-DMSO to confirm the completion of thermolysis. Measurement of the DSs in Water. Before and after thermolysis, the three networks were studied with respect to their DSs in water as a function of pH, covering the pH range from ∼1.5 to ∼12.5. In the case of the double-cationic polyelectrolytic networks (i.e., before thermolysis), several dried network pieces were transferred in to glass vials each containing a volume of 5 mL of water where the precalculated volume of a 0.5 M HCl standard solution had been added in order to adjust the PyMMA and the PyEMA units to the desired degrees of ionization (DI), leading to pH values of the supernatant solutions in the range from 1.4 to 8.5. The necessary volume of the HCl solution for each sample was estimated by multiplying the desired DI (same as the degree of protonation in this case) times the total number of moles of the PyMMA plus the PyEMA

units contained in the sample. The latter was estimated from the sample dry mass and the feed composition in the polymerization, divided by the appropriate average PyMMA−PyEMA monomer molecular weight (184.2 g mol−1 in the case of the equimolar network). In addition to the acidified network samples, three more samples were prepared for each different network. Two of these samples were rendered alkaline by the addition of small volumes of a 0.5 M NaOH standard solution, while the third sample remained neutral (without any addition of HCl or NaOH). The swollen sample masses were measured after 3 weeks of equilibration, and the DSs were again calculated as the ratio of the swollen divided by the dry masses. In the case of the ampholytic networks (i.e., after thermolysis), several dried pieces were transferred in to glass vials containing water (5 mL) plus the necessary amount of acid or base solution to adjust to the desired pH value. The 0.5 M HCl standard solution was used to adjust the pH within the range from 1.4 to 8.0, whereas the 0.5 M NaOH standard solution was employed for adjusting the pH to higher values, from 8.0 to 12.3. The number of moles of NaOH or HCl required for each sample was calculated as the product of the desired degree of deprotonation or protonation times the total number of moles of MAA or PyMMA units contained in the sample. The latter was estimated from the network dry mass, and the feed composition in the polymerization. For these calculations, a linear hydrogen ion titration curve was assumed, in which the targeted degree of protonation or deprotonation was varied from 0 to 1 within the pH range from 1.5 to 12.5. The swollen samples were weighed after three weeks of equilibration, and their DSs were again determined as the ratio of the average values of the swollen divided by the dry masses. Determination of the Isoelectric pH (pI) of the Polyampholyte Hydrogels. The pI of the polyampholyte hydrogels was estimated as the pH at the middle point of the swelling minimum plateau formed in the swelling profile (DS vs pH curve) of the networks. Determination of the Effective pKa Values of the Monomer Repeating Units of the Linear Copolymers. The effective pKa values of the PyMMA, the PyEMA, and the MAA units were calculated from the hydrogen ion titration curves of the linear statistical copolymer before and after thermolysis. Aqueous solutions (1% w/w) of the original double-cationic polyelectrolyte and the final polyampholyte were titrated between pH 2 and 10 using a standard 0.5 M NaOH solution under continuous stirring. The pH was measured using a Corning PS30 portable pH meter. The solution was visually observed at all times during titration, and the pH range where any increased turbidity occurred was noted. The effective pKa values were estimated as the pH at 50% ionization. Gel Permeation Chromatography (GPC). The molecular weights (MW) and the molecular weight dispersities, Đ, of the statistical copolymer and the extractables were determined by GPC using a Polymer Laboratories system equipped with a Waters 515 isocratic pump, an ERC-7515A Polymer Laboratories refractive index (RI) detector, and a Polymer Laboratories PL-Mixed “D” column. The eluent was THF, pumped at 1 mL min−1. The MW calibration was performed using linear poly(methyl methacrylate) (PMMA) standards, also supplied by Polymer Laboratories. Before the analysis, all the samples were dissolved in THF and were filtered through 0.45 μm PTFE syringe filters. Proton Nuclear Magnetic Resonance (1H NMR) Spectroscopy. The compositions of the extractables and the linear copolymer were determined by 1H NMR spectroscopy using a 500 MHz Avance Bruker NMR spectrometer equipped with an Ultrashield magnet. Deuterated chloroform (CDCl3) was used as the NMR solvent for all the samples except for the linear polyampholyte copolymer for which d6-DMSO was used. Differential Scanning Calorimetry (DSC). DSC thermograms were obtained for all three polymer networks and the linear copolymer before and after their thermolysis. The DSC analyses were performed using either one of two Thermal Analysis Instruments (TA) differential scanning calorimeters, models Q100 and Q1000. For the measurements on the Q1000 model instrument, sample amounts of 0.5−2.0 mg were prepared in hermetically sealed DSC pans, whereas 1821


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Figure 3. Synthetic procedure followed for the preparation of the linear near-equimolar statistical polyampholyte. The PyMMA units are shown in blue, the PyEMA units are painted red, and the MAA units are displayed in green. for the Q100 model instrument, sample amounts of 5−10 mg were pressed in regular (nonhermetically sealed) pans. The temperature range covered was from 40 to 375 °C. Thermal Gravimetric Analysis (TGA). TGA thermograms were obtained for all three polymer networks and the linear copolymer before and after their thermolysis. The TGA analyses were performed on a Thermal Analysis Instruments (TA) thermogravimetric analyzer model Q500 using ceramic pans. The temperature range from 40 to 600 °C was covered, whereas sample amounts of around 10 mg were loaded.

This is in marked contrast to regular polyampholytes which present a large pH window (in between the two pKa values) where both types of units are simultaneously oppositely charged. For the present polymer synthesis, controlled RAFT polymerization was used, while random cross-linking rather than end-linking was chosen for the preparation due to its simplicity employing one synthetic step without intermediate product isolations. Linear Copolymer. Before the network synthesis, a linear, near-equimolar PyMMA−PyEMA statistical copolymer with an overall (nominal) DP of 100, PyMMA52-co-PyEMA48 (GPC: number-average MW = Mn = 24 700, Đ = 1.58, 1H NMR spectroscopy: PyMMA = 52 mol %, monomer conversion = 100%), was synthesized also by RAFT polymerization and studied. The moderately low value of Đ of the copolymer suggested a reasonably controlled polymerization. As analyses of solutions of linear polymers are more straightforward than the analyses of the solid-like hydrogels, the investigation of this linear copolymer before and after thermolysis by 1H NMR spectroscopy and hydrogen ion titration provided a convenient means for confirming the completeness and selectivity of thermolysis in the PyMMA−PyEMA comonomer system. The procedures for the synthesis and thermolysis of this copolymer are displayed in Figure 3. Figures 4a and 4b show the 1H NMR spectra of the linear copolymer before and after its thermolysis, respectively. The 1H NMR spectrum of the original copolymer in Figure 4a bears all

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RESULTS AND DISCUSSION Three polyampholyte hydrogels with different ratios of the weakly acidic MAA units and the very weakly basic PyMMA units were prepared. Our research team has great interest in polyampholyte hydrogels prepared using controlled polymerization methods.30−32 In particular, we have employed group transfer polymerization (GTP)33,34 for the preparation of polyampholyte hydrogels based on end-linked ABA triblock polyampholytes of various acid−base compositions; in the same study, we also synthesized hydrogels based on end-linked statistical polyampholytes as well as randomly cross-linked polyampholyte hydrogels.30 Subsequently, we used GTP for the preparation of polyampholyte hydrogels based on interconnected star polyampholytes; in this case, all polyampholyte hydrogels were equimolar in acid−base composition, but the constituent star architecture varied (star block, statistical, heteroarm).31 Finally, we prepared end-linked ABA triblock polyampholyte gels using a controlled radical polymerization method and, in particular, RAFT polymerization.32 In all these cases, the acid unit precursor was a hemiacetal ester hydrophobic (nonionic) monomer, 2-tetrahydropyranyl methacrylate (THPMA), readily convertible after polymerization to MAA units either thermally or under mildly acidic hydrolysis conditions. Furthermore, the basic units employed were based on a tertiary-amine monomer, 2-(dimethylamino)ethyl methacrylate (DMAEMA), whose pKa value is higher than that of the MAA units. In the present investigation, the acidic monomer employed was also MAA, but originating from a novel, labile, basic monomer. The basic monomer was pyridine-based, possessing a very low pKa value, lower than that of DMAEMA and also even lower than that of MAA. Thus, the PyMMA−MAA combination constitutes an extraordinary monomer pair, where the very weakly basic PyMMA units are more acidic than the weakly acidic MAA units. This leads to the formation of a particular type of polyelectrolyte for which we wish to propose the name “inverse polyampholyte” to signify the fact that the extremely low basicity of the basic units results in materials where positive and negative charges cannot coexist at any pH.

Figure 4. 1H NMR spectra of (a) PyMMA52-co-PyEMA48 (before thermolysis) in CDCl3 and (b) PyMMA52-co-MAA48 (after thermolysis) in d6-DMSO. 1822


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noteworthy that the linear polyampholyte solution was cloudy within the pH range from 2 to 7 due to the lack of charges (and consequently zero overall charge, too) in this range. Similarly, the linear double-cationic polyelectrolyte solution was cloudy above pH 2.5 due to the deprotonation of its weakly basic monomer repeating units. The deprotection of the PyEMA units in the linear copolymer was also explored using DSC and TGA. Figure 6a presents the DSC traces of the linear statistical copolymer PyMMA 52 -co-PyEMA 48 and the linear homopolymer PyEMA55,1 while Figure 6b shows the corresponding TGA traces. Figure 6 also displays the DSC and TGA traces of networks PyMMA30-co-PyEMA70-co-EGDMA6 and PyMMA52co-PyEMA48-co-EGDMA6. The DSC thermograms in Figure 6a display a clear endothermic peak at approximately 185 °C for all three polymers, corresponding to the cleavage of the PyEMA units. This was also confirmed by the TGA thermograms in Figure 6b where an initial weight loss took place at ∼200 °C, corresponding exactly to the mass percentage of 2-vinylpyridine (2VPy) in the PyEMA units. Further weight loss at ∼400 °C and higher was also observed due to the cleavage of the backbone of the polymers. Network Synthesis. The syntheses of the polymer networks were performed in the same way as for the linear copolymer, but with the extra addition of EGDMA cross-linker. In particular, RAFT polymerization was again the method of synthesis, with 2-CPBD as the CTA, AIBN as the initiator (radical source), and 1,4-dioxane as the polymerization solvent. The loading of the EGDMA cross-linking agent was such that its molar ratio to the 2-CPBD CTA was 6:1, identified as optimal. Comparable cross-linker to CTA active site loadings, ranging from 3 to 5, have been employed in our previous studies on network formation using RAFT polymerization.32,35−39 The polymerizations took place at 65 °C for 24 h. After the polymerizations, the PyEMA units were thermolyzed in a vacuum oven at 130 °C for 24 h, giving MAA units. Note that the thermolysis temperatures of 185 and 200 °C determined using DSC and TGA, respectively, corresponded to almost instantaneous side-group cleavage; cleavage at the lower temperature of 130 °C understandably takes much longer. Figure 7 illustrates the polymerization and the thermolysis procedures employed for the preparation of the polyampholyte networks by the simultaneous terpolymerization of the two comonomers (PyMMA and PyEMA) and the cross-

the signals with the correct intensity according to the copolymer structure. The 1 H NMR spectrum of the thermolyzed copolymer in Figure 4b also confirms the expected structure as the signals from the 2-(pyridine-2-yl)ethyl group completely disappeared (most characteristic being peaks “c” and “d” at 4.4 and 3.2 ppm, respectively), while a new peak “n” appeared at 12.5 ppm, corresponding to the carboxylic acid proton (−COOH) of the MAA unit. The successful formation of the polyampholyte copolymer was also confirmed using hydrogen ion titration. The hydrogen ion titration curves of both the original double-cationic polyelectrolytic copolymer (PyMMA−PyEMA) and the final polyampholytic copolymer (PyMMA−MAA) are plotted in Figure 5, in which the effective pKa values of the various

Figure 5. Hydrogen ion titration curves of the linear double-cationic polyelectrolyte PyMMA52-co-PyEMA48 and the linear polyampholyte PyMMA52-co-MAA48.

protonable groups were determined and indicated with arrows. Unlike the hydrogen ion titration curve of the original copolymer in which the protonable groups exhibited very low pKa values, 2.0 and 2.6, corresponding to the PyMMA and the PyEMA units, respectively, the hydrogen ion titration curve of the polyampholytic copolymer also presented a protonable group with a higher pKa value, of 6.5, corresponding to the newly formed MAA units. For comparison, the pKa values of PyMMA, PyEMA, and MAA, as determined from the hydrogen ion titration of the three respective homopolymers, were found to be 2.2, 3.5, and 6.1, close to those determined in the copolymers, suggesting the absence of significant interactions between the different types of units within the copolymers. It is

Figure 6. (a) DSC and (b) TGA thermograms of the linear PyEMA55 homopolymer, the linear PyMMA52-co-PyEMA48 copolymer, and networks PyMMA30-co-PyEMA70-co-EGDMA6 and PyMMA52-co-PyEMA48-co-EGDMA6. 1823


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Figure 7. Synthetic procedure followed for the preparation of the randomly cross-linked polyampholyte networks. The PyMMA units are shown in blue, the PyEMA units are painted red, the MAA units are displayed in green, and the EGDMA cross-linker units are presented in black.

Table 1. Percentage, Compositions, and Molecular Weights of the Extractables from the Three Polyelectrolyte Networks 1

H NMR results (mol %)

a

GPC results

no.

network structurea

% w/w extractables

PyMMA

PyEMA

PyMMA-co-PyEMA

Mp

Mn

Đ

1

PyMMA30-co-PyEMA70-co-EGDMA6

4.5

40.3

25.7

34.0

2


10.6

27.6

57.5

14.9

3


5.4

40.3

34.0

25.7

4270 133 766 133 5990 129

3600 143 1410 153 5190 139

1.84 1.04 2.12 1.06 1.62 1.04

PyMMA: (pyridin-2-yl)methyl methacrylate; PyEMA: 2-(pyridin-2-yl)ethyl methacrylate.

Figure 8. Aqueous degrees of swelling and degrees of ionization as a function of the supernatant solution pH for the three weakly basic doublecationic polyelectrolyte hydrogels.

pH Dependence of the DSs of the Double-Cationic Polyelectrolyte Hydrogels. The three double-cationic polyelectrolyte (i.e., before thermolysis) networks were characterized in terms of their aqueous DSs (along with the standard deviation of the mean) as a function of pH. The measured DSs and calculated DIs (from the amounts of HCl and polymer network) of the three polyelectrolyte hydrogels are plotted against pH in Figure 8. In these graphs, the DS vs pH curve almost coincided with the corresponding DI vs pH curve, manifesting the important role of charge in hydrogel swelling. All networks began to swell below pH ∼2 due to the ionization of the PyEMA and the PyMMA monomer repeating units in this acidic pH range. Ionization led to accumulation of counteranions to the positively charged pyridine rings and the build-up of an osmotic pressure. Furthermore, the charges themselves resulted in the establishment of electrostatic repulsions between the positively charged chains. Both the osmotic pressure and the repulsions favored network swelling. In all cases, the DS maximum (pH between 1.8 and 2.1) was followed by a decrease at lower pH values (pH < 1.8). This can be attributed to the increase in ionic strength effected by the relatively high concentration of HCl under these rather extremely acidic conditions. Effective pKa Values. The effective pKa values of the three weakly basic polyelectrolyte hydrogels were determined from

linker (EGDMA), followed by the thermal treatment of the resulting double-cationic polyelectrolyte networks. Properties of the Sol Fraction. The sol fraction (extractables) of the three polyelectrolyte networks was determined and characterized using GPC and 1H NMR spectroscopy analyses. Table 1 presents the percentage (w/ w) of the extractables, their composition, and their MW (peak MW, Mp, and number-average MW, Mn) and Đ values. The percentage of the extractables was very low, indicating successful and efficient network formation, also indicating the adequacy of the EGDMA cross-linker at the chosen EGDMA:CTA molar ratio of 6:1 used for cross-linking. From the 1H NMR spectra, it was observed that the extractables mainly consisted of PyMMA and PyEMA monomers, as well as of PyMMA-co-PyEMA hyperbranched chains which had not been incorporated in the network. The PyMMA30-co-PyEMA70co-EGDMA6 network presented the highest percentage of free hyperbranched chains, followed by PyMMA70-co-PyEMA30-coEGDMA6 and PyMMA52-co-PyEMA48-co-EGDMA6. The GPC traces of the extractables from the three networks presented two peaks, a high-MW and broad one corresponding to the hyperbranched copolymer and a low-MW and narrow one due to the unreacted comonomers (PyMMA and PyEMA). Overall comonomer conversion was estimated to be above 90% (network 2) and above 95% (networks 1 and 3). 1824


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especially those in acidic water which were the highest, to hydrogel composition is due to the similarity between the two homologous comonomers, differing only by one methylene group. pH Dependence of the DSs of the Polyampholyte Hydrogels. After thermolysis, the resulting polyampholyte hydrogels were also studied in terms of their aqueous DSs as a function of the solution pH. Figure 10 shows the aqueous swelling curves (along with the standard deviation of the mean) for the three hydrogels, displaying a characteristic minimum at intermediate pH values, flanked by higher DS values at acidic and basic pHs. The swelling minimum is the signature of polyampholyte hydrogels,24,30−32 originating from the lack of net charge at and around the isoelectric point, pI. Within this pH range, there are no repulsive forces, and the system is dominated by van der Waals and hydrophobic attractive forces, leading to a reduced extension of the polyampholyte chains, and also a trend for coalescence among them. The pH range of the swelling minimum was very broad, from ∼2 to ∼11, and insensitive to hydrogel composition. This was probably due to the relative values of the effective pKa’s of the PyMMA and the MAA monomer repeating units, with that of the basic units being lower than that of the acidic units, leading to uncharged units within the pH range between the two pKa values, and insensitivity of the pI to composition. Using the experimentally determined values of the effective pKa’s of the PyMMA and the MAA monomer repeating units of 2.0 and 6.5, pI calculation40,41 led to values close to 4.2 for all three polyampholyte hydrogels, listed in Table 3 and indicated in the

the plots of DI vs solution pH in Figure 8 as the pH at 50% ionization, and they are listed in Table 2. The effective pKa Table 2. Effective pKa Values of the Pyridinyl Units in the Three Weakly Basic Double-Cationic Polyelectrolyte Hydrogels no.

network structurea

effective pKa

1 2 3

PyMMA30-co-PyEMA70-co-EGDMA6 PyMMA52-co-PyEMA48-co-EGDMA6 PyMMA70-co-PyEMA30-co-EGDMA6

1.9 2.1 2.4

a

PyMMA: (pyridin-2-yl)methyl methacrylate; PyEMA: 2-(pyridin-2yl)ethyl methacrylate; EGDMA: ethylene glycol dimethacrylate.

values were between 1.9 and 2.4, being close to (but lower than) the effective pKa values of the corresponding PyMMA and PyEMA monomer repeating units in the linear statistical copolymer of 2.0 and 2.6, respectively. Composition Dependence of the DSs of the DoubleCationic Polyelectrolyte Hydrogels. The DSs in pure water (pH ∼ 8.5) and in acidic water (pH ∼ 2), both taken from Figure 8, as well as the DSs in THF of the three double-cationic polyelectrolyte hydrogels are plotted in Figure 9 as a function

Table 3. Theoretical and Experimental Isoelectric Points of the Three Polyampholyte Hydrogels

Figure 9. Degrees of swelling in THF and in acidic (pH ∼ 2) and in pure (pH ∼ 8.5) water as a function of the composition of the weakly basic double-cationic polyelectrolyte hydrogels.

no.

network structurea

theoretical pIb

middle of pH range of collapse

1 2 3

PyMMA30-co-MAA70-co-EGDMA6 PyMMA52-co-MAA48-co-EGDMA6 PyMMA70-co-MAA30-co-EGDMA6

4.10 4.25 4.40

6.4 ± 0.5 7.1 ± 0.5 5.8 ± 0.5

a

PyMMA: (pyridin-2-yl)methyl methacrylate; MAA: methacrylic acid; EGDMA: ethylene glycol dimethacrylate. bThe calculations40,41 of the theoretical pI values were based on the effective pKa values of the PyMMA and the MAA units of 2.0 and 6.5, respectively.

of hydrogel composition (percentage of PyEMA units). The highest DSs were presented in acidic water, as expected, due to the full ionization of the PyMMA and the PyEMA monomer repeating units and ranged from 7.0 to 8.8. In contrast, the DSs in pure water and in THF for the three hydrogels acquired much lower values, between 2 and 3. The low DSs in pure water are consistent with the hydrophobicity of the two comonomers and the cross-linker. The insensitivity of the DSs,

graphs of Figure 10. These values should be compared with the pH values at the middle of the swelling minimum, also listed in Table 3. These latter values ranged between 6 and 7 and were, therefore, higher than the theoretical pIs. This can be attributed to the different hydrophobicities of the PyMMA and the MAA units. In particular, the PyMMA units are more hydrophobic than the MAA units. Thus, at high pH, when the PyMMA units

Figure 10. Aqueous degrees of swelling as a function of the supernatant solution pH for the three polyampholyte hydrogels. 1825


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are uncharged, a greater degree of ionization of the MAA units is required before the hydrogel starts to swell again. Effect of Polymer Composition on the DSs of the Polyampholyte Hydrogels. Figure 11 presents the effect of

Article

AUTHOR INFORMATION

Corresponding Author

*E-mail: [email protected] (C.S.P.). Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS The authors thank the European Commission for funding this work within the FP7 project SELFMEM (grant agreement no. NMP3-SL-2009-228652). We are also grateful to the A. G. Leventis Foundation and the Cyprus Research Promotion Foundation and the EU Structural and Cohesion Funds for Cyprus (project NEKYP/0308/02) for the establishment of the NMR infrastructure at the University of Cyprus. The European Regional Development Fund and the Republic of Cyprus are also thanked for cofunding infrastructure project NEA YPODOMH/NEKYP/0311/27 through Cyprus Research Promotion Foundation. Finally, we thank our colleagues at the University of Cyprus, Prof. P. A. Koutentis, and Ms. S. I. Mirallai for providing access to their TGA and DSC instruments.

Figure 11. Aqueous degrees of swelling of the polyampholyte hydrogels at alkaline, acidic, and isoelectric pH as a function of the MAA content.

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polymer composition (percentage of MAA units) on the aqueous DSs of the polyampholyte hydrogels at three characteristic pH values, taken from Figure 10. These characteristic pH values were the pI (pH ∼4.2), basic pH (∼12), and acidic pH (∼1.5). The figure shows that the aqueous DSs of the polyampholyte hydrogels around the pI were low and constant at approximately 2, indicating that the hydrogels were in a less expanded state due to the absence of counterions and repulsive forces. The low- and high-pH aqueous DSs of the three polyampholyte hydrogels were high due to the ionization of the PyMMA and the MAA units, respectively. The low-pH aqueous DS of the PyMMA-rich network was higher than that at high pH due to the excess of basic over acidic units, ionizable at low pH. The near-equimolar hydrogel presented almost the same aqueous DSs at low and high pH.

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CONCLUSIONS Three randomly cross-linked polyampholyte hydrogels of different compositions in the positively ionizable PyMMA and the negatively ionizable MAA units, introduced in its PyEMA-protected form, were prepared using RAFT polymerization. The extractables from the networks were low, indicating successful incorporation of the monomer repeating units. The original polyelectrolyte hydrogels swelled only below pH 2 due to the ionization of both the PyMMA and the PyEMA units within this low pH range, while the polyampholyte hydrogels presented typical polyampholyte swelling behavior with collapse at intermediate pH values, around the isoelectric point, pI, and an increase at both low and high pH values. Increased swelling was attributed to the ionization of the PyMMA and the MAA units at low and high pH values, respectively. The pH range of hydrogel collapse was relatively broad, from ∼2 to ∼11, and insensitive to polymer composition. This was due to the relative values of the effective pKa’s of the PyMMA and the MAA monomer repeating units, with that of the basic unit being lower than that of the acidic unit, leading to uncharged units within the pH range between the two pKa values, and insensitivity of the isoelectric point to composition. 1826


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“Inverse Polyampholyte” Hydrogels from Double-Cationic Hydrogels

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