pH Responsivity and Micelle Formation of Gradient Copolymers of

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pH Responsivity and Micelle Formation of Gradient Copolymers of Methacrylic Acid and Methyl Methacrylate in Aqueous Solution Ying Zhao,† Ying-Wu Luo,*,† Bo-Geng Li,† and Shiping Zhu*,‡ †

The State Key Laboratory of Chemical Engineering, Department of Chemical and Bio-Chemical Engineering, Zhejiang University, Hangzhou 310027, PR China ‡ Department of Chemical Engineering, McMaster University, Hamilton, Ontario, Canada L8S 4L7 ABSTRACT:

A series of gradient copolymers of methacrylic acid (MAA)/methyl methacrylate (MMA) with four end-to-end composition profiles (uniform, linear gradient, triblock with linear gradient midblock, and diblock) but all having an average chain composition of F MMA ≈ 0.5 and an average chain length of 200 were synthesized via model-based, computer-programmed, semibatch atom-transfer radical copolymerization (ATRcoP). These samples allowed us to investigate systematically the effects of the gradient composition profile on the pH responsivity and micelle formation of the copolymers in an aqueous solution. Measurements included light transmittance, TEM, AFM, DLS, 1H NMR, and pH titration. It was found that linear gradient, triblock, and diblock copolymers formed spherical micelles at high pH. The micelles of the linear gradient copolymer contained MMA units in their hydrophilic shells, and those of the triblock and diblock copolymers had all of their MMA units residing in their cores. The composition profile showed a strong effect on the degree of acid dissociation at a given pH. The conformational transition of the copolymer chains was determined by both the pH value and composition profile. Copolymers having sharper gradients required a lower pH to trigger the conformational transition and a narrower pH range to complete the transition.

’ INTRODUCTION The copolymers of acrylic acid and methacrylic acid are widely used as staliblizers for water dispersion systems.1 These amphiphilic weak polyacids are pH-responsive materials that have attracted increasing interest over the past several decades.2
4 Hydrogels, micelles, surfaces, and bioconjugates derived from pH-responsive polymers have a wide range of applications in many areas, such as drug delivery, biotechnology, chromatography, and sensors.5
7 It is well known that the ionization of the carboxylic acid group significantly affects the hydrophilicity and chain conformation of the polymers. Various application properties such as the swelling and deswelling of hydrogels, the hydrophilicity of surfaces, and the stability of nanophases can thus be readily adjusted and fine tuned. A wealth of systematic studies demonstrated that changes in the polymer molecular weight, chemical composition, and chain architecture allow the easy manipulation of the physical and chemical properties of stimuli-responsive materials.8
10 The rational design of the chain microstructure and the well-controlled synthesis of the polymer are essential in this field for the development of novel materials and applications.11,12 r 2011 American Chemical Society

The recent advent of controlled/living radical polymerization (CLRP) offers a great opportunity to synthesize polymers with tailor-made microstructures. Several CLRP mechanisms, mainly nitroxide-mediated polymerization (NMP),13,14 atom-transfer radical polymerization (ATRP),15
17 and reversible addition
fragmentation chain-transfer radical polymerization (RAFT),18,19 have been discovered and intensively investigated. These polymerization mechanisms have been widely employed to synthesize polymers having a preset molecular weight and a narrow molecular weight distribution. There are numerous successful synthesis examples of well-defined random, block, star, and brush copolymers. Gradient copolymers, of which the chemical composition varies from end to end along the chain backbone, can also be synthesized through the CLRP mechanisms. As a novel type of copolymer, the synthesis of various gradient copolymers and their evaluation with respect to specialty material properties have recently received much attention and ever Received: March 31, 2011 Revised: June 11, 2011 Published: August 06, 2011 11306

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Figure 1. Theoretical composition profiles for the targeted tBMA/ MMA gradient copolymers. The copolymers were hydrolyzed to obtain the corresponding MAA/MMA copolymers for this study.

increasing interest.20
22 Model-based computer-programmed semibatch controlled/living radical copolymerization (CLRcoP) was developed to design gradient copolymers with the desired composition profile (i.e., composition gradient).23 The approach was successfully demonstrated in the RAFT copolymerization (RAFTcoP) of styrene and butyl acrylate24,25 and the atomtransfer radical copolymerization (ATRcoP) of methyl methacrylate (MMA) and t-butyl methacrylate (tBMA).26 Both theoretical27
29 and experimental30,31 investigations suggested that the end-to-end composition profile along the chain is an important microstructural parameter for fine-tuning nanomorphologies and thus the physical and functional properties of the copolymer materials. However, the effect of the composition profile on the characteristic properties of pH-responsive polymers has not been studied to the best of our knowledge. In this work, gradient copolymers of methacrylate acid (MAA)/methyl methacrylate (MMA) used in the design of uniform, linear, triblock, and diblock composition profiles were prepared using semibatch ARTcoP. These copolymers were characterized and evaluated by light transmittance measurements, TEM, AFM, DLS, 1NMR analysis, and pH titration, with the objective being to establish the relationship between their gradient chain microstructure and pH-responsive properties in aqueous solutions.

’ EXPERIMENTAL SECTION Synthesis of Gradient MAA/MMA Copolymers. Uniform, linear, triblock, and diblock tBMA/MMA copolymers were first synthesized using the developed model-based computer-programmed semibatch ATRcoP. The details of the technology were reported in our previous paper.26 The obtained tBMA/MMA gradient copolymers were then hydrolyzed in an acidic environment32 to remove the t-butyl groups on the tBMA units for the corresponding MAA/MMA samples. Figure 1 shows the composition profiles of the four gradient copolymer samples. The gradient becomes sharper in the order of uniform, linear, triblock, and diblock. It should be emphasized that the cumulative MMA compositions of all of the samples were the same (i.e., F MMA = 0.5) and the degrees of polymerization were also the same (i.e., with respect to the targeted 200 monomeric units). The difference lies in the gradient profile (i.e., the end-to-end compositional variation of monomeric units along the chain backbone). Preparation of the MAA/MMA Copolymer Test Solution. The obtained gradient MAA/MMA copolymer cannot be dissolved in pure water directly. First, we adopted a well-established method to prepare the copolymer aqueous solution. The copolymer (1 wt %) was

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dissolved in a dioxane/water (95/5 w/w) mixed solvent. Pure water was then added to the solution at a 0.2 wt %/min rate. However, with the linear gradient copolymer, the polymer precipitated out. Therefore, a 0.2 wt % copolymer solution was prepared for the polymer solution properties study using the following protocol. A 0.4 g MAA/MMA copolymer sample was added to a solution of 4 mL of 1 M NaOH and 100 g of water. The mixture was stirred for 2 h under argon until the grains were dissolved. The pH value of the copolymer solution was then reduced by dripping 80 mL of the 0.05 M HCl solution. Finally, the pH value reached 3.3, the copolymer was precipitated out, and a cloudy dispersion was formed. Extra water was added to lower the copolymer content to 0.2 wt %. The test solution was stirred for another 72 h under argon and was ready for light transmittance measurements and potentiometric titration. TEM. Samples were prepared as follows: a 0.2 wt % P(MAA-gradMMA) aqueous solution was mounted onto 400-mesh copper grids, stained with a 2 wt % tungstophosphoric acid aqueous solution, and dried at room temperature. The TEM observation was made by JEOL JEM-1230. AFM. Samples were made by depositing a drop of a 0.2 wt % copolymer aqueous solution on a silica wafer and drying at room temperature. The AFM observation was made in tapping mode on a Nanoscope III (Veeco). DLS. Dynamic light scattering (DLS) measurements were made on a Malvern Zetasizer 3000 HAS at 25 °C. An aqueous solution of 0.2 wt % copolymer was subject to filtration using a membrane of 0.22 μm pore size before the measurements. GPC. The molecular weight (MW) and the molecular weight distribution (MWD) of the copolymers were determined at 30 °C by a GPC (Waters 2487/630C) equipped with three PL columns (Styragel 10 000, 1000, and 500 Å). THF was used as the eluent at a flow rate of 1 mL/min. Narrow polystyrene (PS) standards with MW ranging from 580 to 7.1  106 g/mol were used in the calibration. Potentiometric Titration. Potentiometric titration was conducted at 25 °C using a PHS-2F pH meter equipped with an E-201-C composite electrode. A 200 g solution containing 0.2 wt % MAA/MMA copolymer was subjected to continuous stirring under the protection of argon. A 1 M NaOH solution was used as the titrant. The test stopped when there was no further change in the pH value between two additions of 25 μL of titrant. Light Transmittance Measurement. The light transmittance through 0.2 wt % MAA/MMA copolymer solutions was determined using an Ultrospec3300 pro UV/vis spectrophotometer at λ = 600 nm through a 1.0 cm quartz sample cell. NMR Measurement. 1H NMR spectra were recorded on a Bruker AC-80 spectrometer operated at 400 MHz in 5 mm tubes and used to estimate the copolymer compositions. Four D2O solution samples containing 0.2 wt % MAA/MMA copolymer were also prepared following the same protocol for the study of the conformational transition during the titration process. After visible flocs disappeared at adequately high pH levels, 1 mL solution samples with different pH values were withdrawn for the 1H NMR analysis.

’ RESULTS AND DISCUSSION Synthesis of Gradient MAA/MMA Copolymers. Uniform, linear, triblock, and diblock copolymers of tBMA/MMA with the degree of polymerization close to 200 were first synthesized and then hydrolyzed to obtain the targeted gradient MAA/MMA copolymer samples. The experimental composition profiles were in an excellent agreement with the theoretical designs, as shown in Figure 2. It should be pointed out that the instantaneous composition of the copolymer chains is not experimentally measurable. The cumulative composition is the one that we measured using NMR. Theoretically, the cumulative composition is an 11307

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Langmuir integration of the instantaneous composition, and it is also true that the latter is a derivative of the former. However, in practice, the differentiation of an experimental cumulative composition profile introduces large errors. In this work, the cumulative profiles in Figure 2 should be treated as being equivalent to their corresponding instantaneous counterparts in Figure 1 and vice versa. Figure 3 shows the GPC curve development with monomer conversion. In most cases, GPC curves as a whole moved to the

Figure 2. Cumulative MMA composition in the gradient tBMA/MMA copolymers as a function of the number-average chain length: the points are experimental data, and the lines are theoretical designs of the cumulative composition profiles corresponding to the instantaneous composition profiles in Figure 1.

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higher-molecular-weight region, suggesting that the polymerization proceeded in a living manner. The PDIs of the final polymers were 1.17 for uniform, 1.12 for linear, 1.18 for triblock, and 1.24 for diblock copolymers, suggesting that the polymerization was well controlled. In the cases of triblock and diblock polymers, a shoulder peak appeared in the late stage of polymerization because of irreversible chain termination. We estimated the number of dead chains by kinetic modeling. As shown in Figure 4, the weight fraction of dead chains remained negligible at low monomer conversions. It

Figure 4. Weight fraction of chains versus monomer conversion estimated through kinetic modeling in the semibatch ATRcoP of tBMA and MMA having various composition profiles.

Figure 3. Development of a GPC curve with monomer conversion during the synthesis of tBMA/MMA copolymers. 11308

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Figure 6. pH dependence of the light transmittance through 0.2 wt % gradient MAA/MMA copolymer solutions. Figure 5. 1H NMR spectra of the triblock copolymer samples: (a) tBMA/MMA copolymer (before hydrolysis) in CDCl3 (i) and (b) MAA/MMA copolymer (after hydrolysis) in DMSO-d6 (j). Peak k is attributed to trapped moisture by the hydrophilic MAA segments.

Table 1. Cumulative MMA Copolymer Composition F 2 in P(MAA-grad-MMA) samples

F2

uniform

0.495

linear

0.442

triblock

0.525

diblock

0.470

increased significantly after 50% conversion. At the same conversion, the fraction decreased in the order of triblock > linear > uniform. For the triblock copolymer, the fraction of dead chains was about 0.1 at 80% monomer conversion, 0.15 at 90%, and 23% at 99%. Because the dead chains were generated mainly in a late stage of polymerization, their influence on the triblock chain microstructure was minor. This level of dead chains is common with polymer samples prepared by controlled radical polymerization processes. The gradient tBMA/MMA copolymers were hydrolyzed with HCl to yield the corresponding uniform, linear, triblock, and diblock MAA/MMA copolymers. The hydrolysis was monitored by 1H NMR. Figure 5 shows the 1H NMR spectra of the triblock copolymers of tBMA/MMA and MAA/MMA as an example for comparison. The peak at 1.42 ppm (A) in the tBMA/MMA copolymer sample was assigned to the t-butyl group of tBMA units. After hydrolysis, peak A completely disappeared and a new signal appeared at 12.3 ppm that was assigned to the carboxyl group of MAA units (C). The complete hydrolysis of tBMA to MAA units became evident from the total conversion of the signals. Table 1 gives the MMA compositions incorporated into the gradient MAA/MMA copolymers, which are close to the designed value of 0.5. Gradient MAA/MMA copolymers with the designed composition profiles were thus achieved. Light Transmittance. Figure 5 shows the pH dependence of the light transmittance through aqueous solutions of the uniform, linear, triblock, and diblock MAA/MMA copolymers. The transmittance curve of the diblock MAA/MMA copolymer solution followed an “S” trend. There was a sharp increase in light transmittance in the range of pH 4.4 to 6. The transmittance was about 46% at pH 6. It becomes clear

that the amphiphilic diblock MAA/MMA copolymer formed a micelle structure in the aqueous phase corresponding to the high but incomplete transmittance at pH >6. However, at pH 6, suggesting the total dissolution of the copolymer chains. Lowering the pH from 6 to 4 dramatically reduced the transmittance to about 9%, indicating the formation of particles having larger sizes than those in the diblock copolymer case. The triblock and linear MAA/MMA copolymers have intermediate composition gradients between the diblock and uniform copolymers. These copolymers also formed micelle structures at high pH values as indicated by about 80% light transmittance. At pH linear > triblock > diblock that is not as sharp. In studying the micelle morphology, both TEM and AFM were use to observe the micelles formed in the aqueous solution. The results are shown in Figures 7 and 8. Sphere micelles are clearly seen for the diblock, triblock, and linear copolymers with diameters increasing from 14.7 (diblock) to 15.4 (triblock) to 17.6 nm (linear) at pH 8.26. The micelle size distributions for the diblock, triblock, and linear copolymers were symmetric and narrow, as evident in Figure 8. It is very interesting that the linear copolymer could still form spherical micelles and that with the composition profiles along the polymer chain becoming narrow the micelles become larger. The micelle sizes from TEM appeared to be much smaller than those from AFM and DLS. This is because TEM was operated under high vacuum and the micelles were nearly dry. In contrast, AFM and DLS measured the micelles with water-swollen corona. The aggregate chain number per micelle was estimated to be 68 for diblock, 79 for triblock, and 118 for linear by eq 1 1 FN N̅ agg ¼ πD̅ n 3 6 MW grad

ð1Þ

where the density of the copolymer F is 1.23 g/mol, calculated from averaging the densities of PMAA (1.285 g/mL[106]) and PMMA (1.20 g/mL[107]); N is Avogadro’s constant and MWgrad is the copolymer molecular weight. 11309

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Figure 7. TEM images of the micelle structures formed from (a) diblock P(MAA-di-MMA), (b) triblock P(MAA-tri-MMA), and (c) linear P(MAA-liMMA) in 0.2 wt % aqueous solutions at pH 8.6.

Figure 8. Micelle size distribution from TEM image statistics in a 0.2 wt % aqueous solution at pH 8.6 (over 200 particles counted for each sample). 11310

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Figure 9. AFM images of the diblock, triblock, and linear copolymer micelles corresponding to Figure 7 under the same conditions.

Figure 10. Dependence of the Rh of P(MAA-grad-MMA) micelles on the pH.

The spherical micelles were also evident in the AFM measurement as shown in Figure 9. The micelles appeared to be larger and were somewhat deformed. The diameters for diblock, triblock, and linear copolymer are 46.2, 50.3, and 58.7 nm, respectively, giving the same trend but much larger sizes than those from TEM observations. It was believed that the micelles observed by AFM were swollen with water whereas those observed by TEM were dried. The pH responsivity of the micelles was monitored by DLS. As shown in Figure 10, over the whole studied pH range, the

Z-average hydrodynamic radius increased in the order of diblock, triblock, and linear copolymers, agreeing with the TEM and AFM results. With an increase in the pH, a clear transition of the volume expansion was observed for all three copolymers. The onset pH value and the broadness of the transition increased with the decreased compositional gradient. The transition clearly suggested a conformational change from collapsed at low pH to highly expanded at high pH, as further supported by NMR and titration. 1 H NMR Analysis. 1H NMR spectra were also recorded to provide evidence for the pH-induced morphological changes in the gradient copolymers in the aqueous phase. Figure 11a
d shows the 1H NMR spectra of uniform, linear, triblock, and diblock MAA/MMA copolymers, respectively, in D2O at various pH levels. The 1H NMR spectrum at pH 7.35 in Figure 11a was typical of the uniform MAA/MMA copolymer solution. The characteristic signal at δ = 3.5 ppm, assigned to
OCH3 of the MMA units, was narrow and well resolved. The signals at δ = 0.8 ppm were attributed to
CH3 pendants of both MAA and MMA units, and the signals at δ = 1.7 ppm represented their
CH2
groups. The proton peak of the carboxylic acid was not observed because of its exchange with D2O. The sharp peaks at δ = 3.62 and 1.75 ppm, which did not change with pH, were assigned to a minor fraction of tetrahydrofunan left in the samples. In the 1 H NMR spectrum at pH 6.75, the MMA/MAA unit molar ratio was estimated to be 1:1 by integrating the signals at δ = 3.5 and 11311

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Figure 11. 1H NMR spectra of the D2O solution containing 0.2 wt % polymer at various pH values and 25 °C. (a) Uniform MAA/MMA copolymer, (b) linear MAA/MMA copolymer, (c) triblock MAA/MMA copolymer, and (d) diblock MAA/MMA copolymer. R is the degree of dissociation of MAA units.

0.8 ppm. This ratio is in perfect agreement with the cumulative MMA copolymer composition of F MMA = 0.5. The uniform MAA/MMA copolymer chains appeared to be in good contact with D2O molecules and were well dissolved in the aqueous phase without the formation of micelles. When the pH decreased from 6.75 to 6.11, the peak at δ = 3.5 ppm was significantly broadened and the peaks at δ = 0.8 and 1.7 ppm became weak, suggesting a lower chain mobility and a decreased solubility of the copolymer.33 The copolymer chains assumed a contracted conformation at pH 5.93. It is well known that an amphiphilic diblock copolymer forms micelles in the aqueous phase. Figure 11d shows the 1H NMR spectra of the diblock MAA/MMA copolymer studied in this work. Over a broad range of pH values, the typical signal at δ = 3.5 ppm assigned to
OCH3 of the MMA units was totally missing because of the high hydrophobicity of the MMA block aggregated in the cores of the micelles. The typical signals of the MAA units at δ = 0.9 and 1.7 ppm were observed and became more clear with the increased pH. As evident from the change in the 0.9 ppm signal, there was a clear conformational transition of the PMAA block in the pH range from 5.38 to 6.05, leading to a significant increase in the mobility of MAA units. Numerous studies using different techniques suggested that PMAA chains underwent a conformational transition between a compact coiled state and a highly extended state in the range of pH 4
6.34
37 At low pH, the chains were in a compact coil conformation. Increasing pH ionized carboxylic acid and converted PMAA to a polyelectrolyte. The electrostatic repulsion of the carboxylic anions overcame short-range hydrophobic interactions between methyl groups on the chain backbone. At a high pH when a certain degree of ionization was reached, a chain expansion took

place, leading to a change in dimension.38 The range of pH 5.38
6.05 corresponds to the large-scale expansion. Figure 11c shows the 1H NMR spectra of the triblock MAA/ MMA copolymer in D2O. The triblock copolymer had a linear gradient midblock between the PMMA and PMAA blocks. It was believed that the midblock gradient could balance the hydrophilic and hydrophobic properties of the copolymer and provide a transient area. In the range of pH 5.50
6.91, the typical signal assigned to
OCH3 of the MMA units was not seen. The triblock chains formed micelles but the midblocks were buried in the cores of the micelles. In the range of pH 5.50
6.18, there was a remarkable conformational transition of the PMAA block because the typical signals attributed to the MAA units at δ = 0.9 ppm became profound with the increased pH. Figure 11b shows the 1H NMR spectra of the linear MAA/ MMA copolymer. The chain expansion occurred between pH 5.64
6.63. At pH 7.04, the MMA composition was estimated to be 39%, which is lower than the cumulative MMA composition of 45%. A fraction of the MMA units were probably buried in the cores of the micelles and became undetectable by 1H NMR, with the rest of the MMA units residing in the shells. This result agreed well with the core
shell microstructure elucidated by the light transmittance measurement. On the basis of the compositional data and the compositional profile along the chains by NMR, we estimated that the compact hydrophobic cores consisted of 13% chain length whereas the remaining 87% chain length formed the micelle coronas. The core/shell composition of the micelles formed from the linear gradient copolymer was very different from that of the diblock copolymer, as illustrated in Scheme 1. The core/shell ratio of the diblock copolymer micelles was half and half with respect to the chain length. Taking the 11312

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Scheme 1. Conformational Transition of (a) Diblock MAA/MMA Copolymer Chains and (b) Linear MAA/MMA Copolymer Chains in Response to an Increase in the Environmental pH

chemical composition into account, we derived that 75% MMA units and 96% MAA units resided in the corona and 25% MMA units and 4% MAA units were located in the core. It was evident that there was a remarkable chain expansion of the copolymers in aqueous solution when the environmental pH was changed. The transition occurred in the pH ranges of 6.11
6.75, 5.64
6.63, 5.50
6.18, and 5.38
6.05 with uniform, linear, triblock, and diblock copolymers, respectively, which is in good agreement with the DLS results. The sharper the compositional gradient, the lower the pH required to trigger the conformational transition and the narrower the pH range for a complete transition. Potentiometric Titration. The apparent constant of acid dissociation, Ka, is a quantitative parameter characteristic of a pH-stimulus polymer. The pH titration was conducted to investigate further the influence of the compositional gradient in the dissociation of H+ from the copolymers. The gradient MAA/MMA copolymers are weak polyacids, and their dissociation equilibrium can be expressed as follows, Ka

PH rsf P
þ Hþ

ð2Þ

where PH and P
represent the
COOH groups on the gradient MAA/MMA copolymer chains and their anionic counterparts, respectively. The degree of dissociation of
COOH groups, R,

can be determined by the measured pH using the following equation39 R¼

½NaOH0 þ ½Hþ 
½OH
 ½pH0

ð3Þ

where [] denotes the molar concentration and subscript 0 indicates the initial molar concentration. The R value equals 1 when the gradient MAA/MMA copolymer dissociates completely (i.e., all
COOH groups are converted to
COO
groups). Then constant Ka is related to the degree of dissociation through the following equation:40 pKa ¼ pH þ log

1
R R

ð4Þ

pKa reflects the overall acid dissociation equilibrium. Aqueous solutions containing 0.2 wt % gradient MAA/MMA copolymers were prepared and titrated with a 1 M NaOH solution. Figure 10 plots pKa against R for the uniform, linear, triblock, and diblock MAA/MMA copolymers, respectively. In contrast to the constant pKa for a small molecular carboxylic acid, the pKa values of the four copolymers all varied with the degree of dissociation. The acid dissociation was clearly influenced by the charge density on the copolymer backbones because of an electrostatic effect. The dissociation of
COOH groups is hindered by their neighboring 11313

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Table 2. Change in Free Energy during Acid Dissociation of the Four Types of MAA/MMA Copolymers (25 °C) sample

ΔG (kJ/mol)a

ΔGel (kJ/mol)b

ΔGc (kJ/mol)c

uniform

3.04

2.07

0.97

linear triblock

2.95 4.02

2.58 3.65

0.36 0.37

diblock

4.81

4.58

0.23

ΔG is the change in the total free energy during acid dissociation. b ΔGel is the part resulting from electrostatic interaction. c ΔGc is the part resulting from the conformational transition. a

Figure 12. Plot of pKa vs R for the uniform, linear, triblock, and diblock MAA/MMA copolymers in a 0.2 wt % aqueous solution at 25 °C.


COO
anions that attracted proton cations H+. The attraction forces increased with the increased R, and as a result, the pKa increased. A significant increase in pKa from R = 0 to 1 was seen in every type of copolymer studied. A transitional plateau region for the linear, triblock, and diblock copolymers and a decreasing region for the uniform copolymer in the pKa versus R curves were evident in Figure 12. The transitional regions measured by titration in Figure 12 coincided with those measured by DLS in Figure 10 and by NMR in Figure 11. These intermediate regions resulted from an expansion of the copolymer chains, which was brought about by the electrostatic repulsion between the intramolecular
COO
groups. The pKa values for the linear, triblock, and diblock copolymers remained almost unchanged in the intermediate regions because of the counteraction of the chain expansion by increased ionization. Although further ionization generated more neighboring
COO
groups and made
COOH harder to dissociate because of its attraction, the chain expansion increased their distances and thus balanced the attractive forces. However, in the case of the uniform copolymer, the chain expansion was so dramatic that the local
COO
density actually decreased. The dissociation of H+ became easier with the increased ionization, resulting in the decrease in pKa as seen in Figure 12. Once the copolymer chain was fully extended, the pKa increased again with the degree of dissociation. Extrapolating the titration curves in Figure 12 to R = 0 gave an initial pKa (pK0) of 5.6 for all of the copolymers, in agreement with the data by Ravi and co-workers.39 K0 is an intrinsic constant of the acid dissociation (i.e., the spontaneous dissociation of
COOH groups without a neighboring electrostatic effect), which is independent of the copolymer composition gradient. The intrinsic dissociation constant K0 can be related to the change in the standard free energy associated with the acid dissociation. The apparent dissociation constant Ka of the gradient copolymers reflects the change in free energy due to the electrostatic interaction (ΔGel) and the change in energy due to the conformational expansion (ΔGc). The change in free energy (ΔG) is given by40 Z

1

ΔG ¼ 2:30RT

½pKa
pK0  dR

ð5Þ

0

Using the method of Nagasawa and Holtzer,41 we calculated the respective changes in the free energy for the uniform, linear, triblock, and diblock copolymers as summarized in Table 2.

Figure 13. Plot of R vs pH for the uniform, linear, triblock, and diblock MAA/MMA copolymers in a 0.2 wt % solution at 25 °C.

It becomes clear that the electrostatic interaction was the major contributor to the change. The ΔGel value increased in the following order: uniform < linear < triblock < diblock. However, ΔGel decreased in the same order: uniform > linear > triblock > diblock. ΔGel represents the additional work required to release one mole of H+ electrostatically attracted by the neighboring
COO
groups.40 It is affected by the charge density of
COO
on the copolymer chain and in turn by the gradient composition profile. The diblock copolymer has the highest ΔGel because of its high MAA unit density, but the uniform copolymer has the lowest ΔGel because the MAA units are uniformly separated by MMA units along the chains. The linear and triblock copolymers are intermediate between the uniform and diblock copolymers. Both light transmittance and 1H NMR analysis suggested the formation of micelles in the linear, triblock, and diblock copolymer aqueous solutions at high pH values. The chain expansion caused by the electrostatic repulsion is thus limited by the micelle structure, and as a result, ΔGc is much lower than that of the uniform copolymer. pH Responsivity of r. Figure 13 shows the plots of R versus pH for the four copolymers in aqueous solution and compares their respective pH responsivities. The R value of the uniform copolymer was most sensitive to pH stimuli, and it sharply increased from pH 5.7 to 6.8. The R increases in the linear, triblock, and diblock copolymers were milder and in different pH ranges between 6 to 9. The linear gradient had a much higher R value than for the triblock and diblock counterparts. With respect to the pH responsivity, the linear gradient is similar to the uniform copolymer. It becomes clear that the degree of dissociation at a given pH value depended significantly on the compositional profile. 11314

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’ CONCLUSIONS A series of well-defined gradient MAA/MMA copolymer samples having approximately the same average chemical composition and chain length but various end-to-end compositional profiles were designed and synthesized with a model-based computer-programmed semibatch ATRcoP. The effect of the compositional profile on the pH responsivity of the copolymers in aqueous solution was investigated by light transmittance, 1H NMR, TEM, AFM, DLS, and pH titration. The following conclusions were reached: (1) The linear, triblock, and diblock copolymers can form spherical micelle structures in aqueous solution, but the uniform copolymer is totally dissoved at high pH values. The micelle core/shell structure is largely determined by the compositional profile. The copolymer gradient thus provides a useful parameter for tuning the micelle structure. All of the MMA units of the diblock copolymer reside in the micelle core, and the core-to-shell ratio with respect to chain length in the linear gradient copolymer is 13 to 87%. (2) All of the copolymers are in a highly compact chain conformation at low pH and are expanded to various levels at high pH. The remarkable chain expansion occurs in different pH ranges for the different gradient copolymer types. The respective pH ranges for the uniform, linear, triblock, and diblock systems are 6.11
6.75, 5.64
6.63, 5.50
6.18, and 5.38
6.05. The sharper the gradient copolymer, the lower the pH required to trigger the conformational change and the narrower the pH range required to complete the transition. (3) The apparent equilibrium constant of
COOH dissociation is significantly influenced by the chain composition profile. The gradient affects the electrostatic interaction of the
COO
groups and thus the conformation of the chains, which in turn influences the pKa value. The electrostatic energy, ΔGel, increases in the order uniform < linear < triblock < diblock, and the conformational energy, ΔGc, decreases in the same order. The degree of
COOH dissociation R is determined by both the pH and compositional profile. This work demonstrated that the compositional profile could be a new parameter for fine tuning the physicochemical properties of (methyl)acrylic acid copolymers, which are widely used as hydrogels, stabilizers for emulsion or dispersion systems, rheology modifiers, and drug-delivery systems. ’ AUTHOR INFORMATION Corresponding Author

*E-mail: [email protected]; [email protected].

’ ACKNOWLEDGMENT We thank the National Science Foundation of China (NSFC) (award nos. 20774087 and 21075181) for financial support and the Ministry of Education of China for the Program for Changjiang Scholars and Innovative Research Team in University and a Changjiang Scholar Visiting Fellowship. ’ REFERENCES (1) Riess, G.; Labbe, C. Macromol. Rapid Commun. 2004, 25, 401–435. (2) Xu, C.; Wayland, B. B.; Fryd, M.; Winey, K. I.; Composto, R. J. Macromolecules 2006, 39, 6063–6070.

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dx.doi.org/10.1021/la2011875 |Langmuir 2011, 27, 11306–11315