Langmuir 2004, 20, 2123-2133
2123
Functional Group Distributions in Carboxylic Acid Containing Poly(N-isopropylacrylamide) Microgels Todd Hoare and Robert Pelton* Department of Chemical Engineering, McMaster University, 1280 Main Street West, Hamilton, Ontario, Canada L8S 4L7 Received June 27, 2003. In Final Form: October 24, 2003
Control of the functional group distribution is of fundamental importance in the design of functional polymer particles, particularly in biological applications. Surface-functionalized particles are useful for bioconjugation and medical diagnostics, while internally functionalized particles may have applications in drug delivery. We have prepared a series of temperature-sensitive poly(N-isopropylacrylamide) (PNIPAM)based microgels containing carboxylic acid functional groups via copolymerization with methacrylic acid and acrylamide, which was selectively hydrolyzed under optimized conditions to generate the carboxylic acid functionality. The resulting microgels were analyzed using conductometric and potentiometric titration, dynamic light scattering, and electrophoresis. Acrylamide-containing microgels hydrolyzed below the volume phase transition temperature (VPTT) show broad particle size versus temperature profiles, relatively low electrophoretic mobilities at basic pH, and time-dependent base titration profiles, suggesting the presence of internal functional groups whose titration is diffusion-controlled. Methacrylic acid containing microgels show sharper particle size versus temperature profiles, higher electrophoretic mobilities at basic pH, and time-independent base titration profiles, suggesting the presence of a “core-shell” structure with primarily surface functionalization. Similar results were obtained when acrylamide-containing microgels were hydrolyzed at temperatures above the VPTT. Thus, through selection of comonomer and hydrolysis conditions, we have developed strategies to control and characterize the number and distribution of carboxylic acid functional groups in PNIPAM-based microgels.
Introduction
* To whom correspondence should be addressed. Telephone: (905) 525-9140 ext. 27045. Fax: (905) 528-5114. E-mail: peltonrh@ mcmaster.ca.
In recent years, considerable interest has been focused on the development of “smart” aqueous microgels, that is, microgels whose properties change dramatically upon the application of a specific environmental stimulus. While a variety of polymer systems have been explored,1 most attention has focused on microgels based on poly(Nisopropylacrylamide) (herein referred to as PNIPAM). First synthesized in our group,10 PNIPAM-based microgels exhibit an extreme response to changes in temperature. Linear PNIPAM has a lower critical solution temperature (LCST) of 32 °C in aqueous solution,11,12 at which point the polymer reversibly switches from a fully soluble, hydrophilic random coil at lower temperatures to an insoluble globule at higher temperatures. When crosslinked into a colloidal gel, PNIPAM-based microgels exhibit this temperature responsiveness by undergoing a reversible deswelling volume phase transition between 32 and 35 °C (the volume phase transition temperature, or VPTT). This phenomenon provides reversible, temperature-sensitive control over the refractive index, particle size, electrophoretic mobility, and water content of the colloidal gels. Since the initial preparation, the synthesis, volume phase transition behavior, and applications of PNIPAM-based microgels have been studied extensively in the literature, and PNIPAM-based gels have been used as thermoreversible viscosity controllers,13 water adsorbents for protein solution concentration,14 and temperature-sensitive optical filters.15
(1) Pelton, R. H. Adv. Colloid Interface Sci. 2000, 85, 1. (2) Park, T. G.; Hoffman, A. S. J. Polym. Sci., Part A 1992, 30, 505. (3) Kuentz, A.; Riess, H. G.; Meybeck, A.; Tranchant, J. F. World Patent WO 9509874, 1995. (4) Saatweber, D.; Vogt-Birnbrich, B. Prog. Org. Coat. 1996, 28, 33. (5) Yamaguchi, T. European Patent EP 859015 A2, 1998. (6) Bialek, J. M.; Jones, M. G. World Patent WO 2001010235, 2000. (7) Dawson, J. C.; Le, H. V. World Patent WO 9602608, 1996. (8) Kiser, P. F.; Wilson, G.; Needham, D. Nature 1998, 394, 459. (9) Wolfe, M. S. Prog. Org. Coat. 1992, 20, 487.
(10) Pelton, R. H.; Chibante, P. Colloids Surf. 1986, 20, 247. (11) Heskins, M.; Guillet, J. E. J. Macromol. Sci., Chem. A2 1968, 8, 1441. (12) Schild, H. G. Prog. Polym. Sci. 1992, 17, 163. (13) Kawaguchi, H. Prog. Polym. Sci. 2000, 25, 1171. (14) Cussler, E. L.; Stokar, M. R.; Vararbert, J. E. AIChE J. 1984, 30, 578. (15) Weissman, J. M.; Sunkara, H. B.; Tse, A. S.; Asher, A. S. Science 1996, 274, 959.
Microgels are intermediates between branched and macroscopically cross-linked polymers. Dimensionally, microgels can be considered as colloidal particles and typically have average diameters between 50 nm and 5 µm,1 although larger particles have been produced.2 Microgels behave much like hydrophobic colloids on a macroscopic level; they can be flocculated by the addition of salt or polymeric flocculant and can be readily characterized by standard colloid techniques such as electrophoresis and dynamic light scattering. Structurally, however, microgels resemble a three-dimensional, covalently cross-linked network and can swell in good solvents. On this microscopic level, microgels behave much like a conventional hydrogel and can be described in terms of their water content, average cross-link density, and characteristic time constants for swelling and deswelling. This superposition of the favorable properties of gels (i.e., elasticity, solvent retention, and dimensional stability) within the small dimensions of colloidal particles (facilitating faster swelling kinetics and the formation of ordered arrays) has made microgels of great interest in industries as diverse as cosmetics,3 coatings,4 lubricants,5 food,6 oil recovery,7 drug delivery,8 and industrial processing.9
10.1021/la0351562 CCC: $27.50 © 2004 American Chemical Society Published on Web 02/18/2004
2124
Langmuir, Vol. 20, No. 6, 2004
Hoare and Pelton Table 1. Microgel Preparation Recipes
latex NIPAM MAA-NIPAM AM-NIPAM H-AM-NIPAM-30 H-AM-NIPAM-60
NIPAM (mol) 10-2
1.24 × 1.24 × 10-2 1.24 × 10-2 1.24 × 10-2 1.24 × 10-2
MAA (mol) 0 1.12 × 10-3 0 0 0
AM (mol) 0 0 1.12 × 10-3 1.12 × 10-3 1.12 × 10-3
The use of PNIPAM-only microgels in applications, however, is limited by the relatively narrow range of physical and chemical properties which can be achieved in their synthesis. As a result, finding methods of modifying the physical or chemical behavior of the microgel, generally via the free radical copolymerization of a functional monomer, has become an area of considerable research focus. The functionalization of microgels can achieve several objectives. The volume phase transition behavior of the microgel can be controlled via functional group incorporation. Both the absolute value of the volume phase transition temperature and the breadth of the deswelling transition can be influenced through copolymerization of more hydrophilic or more hydrophobic monomers. Functionalization can also provide reactive sites for postmodification of the gel. This topic has gained particular importance of late in the development of temperaturesensitive bioconjugate microgels used in medical diagnostic applications.16,17 In addition, other smart environmental triggers can be incorporated into the gel to provide multivariable control over the particle swelling. These additional triggers may include pH (ionizable comonomers), ionic strength (charged comonomers), or light (photosensitive comonomers). Designing functionalized microgels with specific properties is complicated by the fact that both the total number of functional groups and the nature of the functional group distribution within the microgel play a critical role in controlling its swelling behavior. The distribution of functional groups strongly affects both the local charge density and the average chain length of PNIPAM-only sequences in the microgel, both of which have been found to influence the onset VPTT and the breadth of the volume phase transition.1,18 In addition, the distribution and accessibility of the functional groups are critical in determining the types of applications suitable for a particular microgel. Microgels suited for bioconjugation would contain functional groups at or near the particle surface which are readily accessible for subsequent chemical reactions, while microgels targeted for drug delivery applications would ideally contain internal functional groups whose access is diffusion-controlled. Despite the importance of functional group distribution in predicting the volume phase transition behavior and applicability of microgel systems, limited attention has been devoted to the subject in the literature. Zhou and Chu18 have performed studies over a broad range of copolymer compositions with a methacrylic acid (MAA)/ N-isopropylacrylamide (NIPAM) copolymer microgel. For MAA/NIPAM ratios within our range of interest ( 6.5. This pH range corresponds reasonably well to the V2 functional group titration region observed in the fast titration curves, which appeared at 4.7 < pH < 8.4. The particle size versus pH profile shows similar behavior at pH < 9. However, in the range 9 < pH < 10, a statistically significant increase in particle size occurs which is not reflected in the mobility profile (i.e., swelling occurs without a significant change in the surface charge density). The pH range over which this particle size increase occurs corresponds approximately to the proposed diffusion-controlled V3 transition region observed at 8.4 < pH < 10 in the fast conductometric titrations. A large difference is also observed in the total number of charges located on the microgel surface in the MAANIPAM and H-AM-NIPAM systems. Table 4 compares the calculated surface charges and functional group contents of the evaluated microgels. From the mobility results and corresponding particle size data, the total number of charges attributable to -COOH groups on the surface of each microgel can be approximated using hardsphere colloid equations. The measured electrophoretic mobility µ is related to the zeta potential ζ through the Henry equation (eq 1).
by the surface area of the microgel and dividing by the elementary charge; the final relationship is shown as eq 3.
Q)
6πRµη(κR + 1) e(f(κR))
(3)
The total number of charges on the surface of each microgel particle (Q) can subsequently be estimated by multiplying
The electrophoretic mobility at pH 4 can be used to estimate the total number of charges attributable to sulfate residues (originating from decomposition of the persulfate initiator) present on the surface of each microgel. Based on this approximation, H-AM-NIPAM-30 is estimated to have 2.5 times more -COOH groups on its surface than H-AM-NIPAM-60. This ratio is within experimental error of the ratio between the numbers of titratable functional groups detected in fast (2.2 or 4.4 min/unit pH) titrations of the two microgels (Table 3), suggesting a direct correlation between the fast titration results and the number of surface or near-surface functional groups. However, according to the longer, equilibrium titrations, H-AM-NIPAM-30 contains 4.3 times more -COOH functional groups than H-AM-NIPAM-60. These ratios suggest that a more surface-specific carboxylic acid functional group distribution is likely in H-AM-NIPAM-60 compared to H-AM-NIPAM-30, in agreement with titration data. The data in Table 4 also indicate that, while H-AMNIPAM-30 contains 70% of the total number of functional groups present in MAA-NIPAM, its calculated total surface charge is only 27% of that observed for MAA-NIPAM. Furthermore, upon changing the pH from 4 to 10, the surface charge density of MAA-NIPAM increases 5-fold while that of H-AM-NIPAM-30 increases only 3-fold. Both of these results are consistent with the clustering of -COOH groups at or near the microgel surface in MAANIPAM. Volume Phase Transition Behavior. The volume phase transition behavior of the functionalized microgels was investigated both by dynamic light scattering and electrophoretic mobility. Figure 9 illustrates the particle size versus temperature behavior, and Figure 10 shows the temperature dependence of the electrophoretic mobility of the microgels, both at pH 4. With either characterization method, both NIPAM and MAA-NIPAM display a discrete transition completed over a narrow 5-7 °C temperature range and initiated near 32 °C for NIPAM and 35 °C for MAA-NIPAM. The very small VPTT shift observed in the MAA-NIPAM system is likely the result of the similar hydrophilicity of NIPAM and protonated MAA; indeed, protonated carboxylic acid containing comonomers are sufficiently hydrophobic to form water-insoluble complexes with PNIPAM at low pH.27 In contrast, both hydrolyzed and unhydrolyzed AM-NIPAM copolymer microgels display highly continuous, statistically identical transitions also initiated near 32 °C but spanning at least a 12 °C range. Figure 11 shows the particle size versus temperature profiles and Figure 12 shows the electrophoretic mobility
(26) Wiersema, P. H.; Loeb, A. L.; Overbeek, J. Th. G. J. Colloid Interface Sci. 1996, 22, 78.
(27) Kokufuta, E.; Wang, B.; Yoshida, R.; Khokhlov, A. R.; Hirata, M. Macromolecules 1998, 31, 6878.
ζ)
(
)
µη 3 2 0rf(κR)
(1)
Here, R is the microgel radius, η is the solution viscosity, κ is the inverse Debye length, 0 is the permittivity of a vacuum, r is the medium dielectric constant, and f(κR) is Henry’s function for a 1:1 electrolyte.26 Using the zeta potential as an approximation of the surface potential Ψ0, the surface charge density (σ) can be estimated using the Grahame equation (eq 2).
σ)
0rζ(κR + 1) R
(2)
2130
Langmuir, Vol. 20, No. 6, 2004
Figure 9. Hydrodynamic diameter versus temperature profiles for functionalized and reference microgels at pH 4.
Figure 10. Electrophoretic mobility profiles as a function of temperature for functionalized and reference microgels at pH 4.
Hoare and Pelton
Figure 12. Electrophoretic mobility profiles as a function of temperature for functionalized and reference microgels at pH 10.
ratio d(60 °C)/d(25 °C) equal to 0.52 at both pH 4 and pH 10. Ionization of MAA-NIPAM results in a ∼25% increase in particle size, a significantly larger pH-induced swelling than that observed in H-AM-NIPAM-30. Furthermore, instead of a broad, continuous transition, MAA-NIPAM exhibited a discrete two-step transition. The first transition (30 °C < T < 40 °C) is similar in shape and breadth to that observed at low pH and accounts for 75% of the total change in diameter, while the second transition (50 °C < T < 55 °C) is very narrow and accounts for the remaining 25% contraction in particle diameter. This twostep profile is mirrored (qualitatively and quantitatively) in the electrophoretic mobility data. Again, the overall deswelling ratio d(60 °C)/d(25 °C) is unaffected by ionization. The occurrence of such a two-step collapse mechanism is consistent with the microgel having a heterogeneous microstructure with two distinct compositional domains. Discussion
Figure 11. Hydrodynamic diameter versus temperature profiles for functionalized and reference microgels at pH 10.
versus temperature profiles, both at pH 10. AM-NIPAM and NIPAM show behavior identical to that observed at pH 4, as expected given the lack of significant pH-sensitive functional groups in both microgel systems. However, the H-AM-NIPAM-30 profile changes significantly. The absolute particle size at 25 °C increases by ∼15%, while the range over which the volume phase transition occurs is further broadened to at least 15 °C in the particle size data and 20-25 °C in the electrophoretic mobility data. Both of these observations are indicative of the generation of more hydrophilic functionalities. Ionization appears to have no significant effect on the total degree of collapse of H-AM-NIPAM-30 across the VPTT, with the deswelling
The results from this study suggest that two clearly different morphologies of carboxylic acid functionalized microgels have been produced. A proposed schematic picture of these two morphologies is shown in Figure 13. For the H-AM-NIPAM-30 microgel (hydrolyzed below the VPTT), functional groups appear to be distributed throughout the microgel bulk. As a result, the functionalized interior model (Figure 13a) appears to represent the experimental results well. Conversely, in the case of the MAA-NIPAM copolymer microgel and H-AM-NIPAM-60 microgel (hydrolyzed above the VPTT), carboxylic acid functionalities appear to be clustered at or near the surface of the particles. We propose a core-shell model (Figure 13b) to represent this morphology in which a MAA-rich shell and NIPAM-rich core microstructure is maintained. Copolymerization kinetics provides support for the proposed morphologies. Although binary reactivity ratios are generally measured under much lower conversions and in the absence of a third reacting monomer (in this case, the MBA cross-linker), they can still be used as a guideline for broadly comparing the relative reactivities of MAA and AM with NIPAM during the microgel preparation. For the acrylamide (r1)/NIPAM (r2) system, reactivity ratio data of r1 ) 0.95, r2 ) 1.04, and r1r2 ) 0.99 ≈ 1 have been reported,28 suggesting very similar monomer reactivity and a nearly random incorporation of AM into copolymers. Conversely, for the methacrylic acid (28) Mumick, P. S.; McCormick, C. L. Polym. Eng. Sci. 1994, 34, 1419.
Functional Group Distributions in Microgels
Figure 13. Proposed carboxylic acid distribution profiles for functionalized PNIPAM-based microgels considered in this study: (a) uniform charge model proposed for AM-NIPAM copolymer microgels hydrolyzed below the VPTT (30 °C); (b) -COOH-rich core, NIPAM-rich shell model proposed for MAANIPAM and AM-NIPAM copolymer microgels hydrolyzed above the VPTT (60 °C).
(r1)/NIPAM (r2) system, reactivity ratios of r1 ) 0.01 and r2 ) 10.2 are reported.29 These figures suggest a high affinity for NIPAM homopolymerization, with MAA monomers more likely to react at higher NIPAM conversions. Thus, the formation of more hydrophilic MAA-rich chains late in the polymerization reaction appears to be likely, consistent with the MAA-rich shell/NIPAM-rich core morphology inferred from the swelling and titration data. The effects of ionic strength and temperature observed in the hydrolysis of AM-NIPAM copolymer microgels give support to the H-AM-NIPAM-30 distributed charge model. In a typical linear polymer hydrolysis, high catalyst concentrations increase the driving force for hydrolysis and screen the electrostatic repulsion between the catalytic hydroxide ions and the generated carboxylic acid groups, while high temperatures increase the chemical rate constant of hydrolysis. Thus, if functional groups reside on the microgel surface and thus remain accessible in the collapsed states induced by the increased ionic strength and temperature, we would expect an acceleration of the hydrolysis rate. However, an overall degree of hydrolysis of only 16% is achieved at 60 °C. Furthermore, virtually no increase in overall hydrolysis is achieved upon increasing the acid concentration 10-fold from pH 1 to [HCl] ) 1 M, and the overall degree of hydrolysis only doubles when the hydroxide concentration is increased more than 100-fold from pH 11 to [NaOH] ) 0.5 M. Together, these observations suggest that gel deswelling due to temperature and ionic strength increases has a tremendously negative impact on the rate and maximum degree of hydrolysis achievable in the AM-NIPAM system. This would be expected if a large fraction of AM functionalities were present within the bulk of the particle, which becomes hydrophobic and relatively inaccessible to solvent diffusion in the collapsed state. The hydrolysis kinetics at 40 °C support this interpretation. At low degrees of hydrolysis, the microgel is collapsed and the accompanying mass transfer limitations account for the extremely low hydrolysis rate. However, the carboxylic acid groups produced during the hydrolysis assist in electrostatically stabilizing the microgel as the hydrolysis proceeds, causing the VPTT of the functionalized microgel to increase with the degree of hydrolysis. In this case, the VPTT shift was sufficient to cause the microgel to swell, (29) Xue, W.; Champ, S.; Huglin, M. B. Polymer 2000, 41, 7575.
Langmuir, Vol. 20, No. 6, 2004 2131
at which point hydroxide ions can more easily diffuse into the particle bulk to access internal AM groups and dramatically accelerate the hydrolysis rate. Nonequilibrium titrations were found to be particularly helpful in gaining some fundamental knowledge regarding the functional group distributions within microgel particles. The complete time independence observed in H-AMNIPAM-60 and MAA-NIPAM titrations suggests that diffusion of OH- toward the titratable functional groups is not significantly hindered by the gel structure. This could be achieved if the functional groups exist primarily near the particle surface. In contrast, the large time dependence observed in H-AM-NIPAM-30 suggests that mass transfer resistance significantly hinders the transport of hydroxide ions toward titratable functional groups within the microgel. In this case, the rate of hydroxide ion addition is faster than the rate of diffusion of hydroxide ions toward the titratable functional groups, inducing both a nonequilibrium lag between the forward and backward titration curve (as in Figure 3c) and a change in the expected partitioning of the titrating species between the gel and bulk phases (the intermediate V3 slope). Nonequilibrium titration behavior may arise from factors other than diffusion. The most common example is the complexation or reaction of two functional groups in the titration sample; in such a case, the titration result is instead dependent on the chemical rate constant of this interaction. Examples of such behavior include the formation of a stable ring structure in maleic acid residues30 or the complexation of the amide group in NIPAM with protonated carboxylic acid residues.19 An analysis of the apparent functional group pKa values as the degree of ionization increases can be used to clarify the origin of the nonequilibrium behavior. The potentiometric titration data are treated according to the method of Kawaguchi et al.31 to calculate the degree of ionization Rd as a function of pH using experimental microgel and blank titration curves. Equation 4 is subsequently used to calculate the apparent pKa as a function of the degree of ionization.
pKa ) pH - log
(
Rd 1 - Rd
)
(4)
The pKa versus Rd profiles obtained for the slow (67 min/ unit pH) titrations of H-AM-NIPAM-30 and MAA-NIPAM are plotted in Figure 14. The carboxylic acid pKa for MAANIPAM exhibits classical polyelectrolyte behavior, increasing continuously with the degree of ionization. In fact, the pKa versus Rd profile for MAA-NIPAM quantitatively mirrors that of linear poly(acrylic acid) (PAA) at similar concentrations.32 The same trends are observed when the excess electrostatic free energy required for the removal of 1 equiv of protons at a specific degree of ionization (∆Gel), calculated using eq 5, is plotted.
pKa ) pK0 +
(
)
1 ∆Gel(Rd) RT ln(10)
(5)
Here, R is the universal gas constant, T is the absolute temperature, and pK0 is the characteristic ionization equilibrium constant of the carboxylic acid groups in the absence of other ionizing groups (estimated as 4.7 in these (30) Oae, S.; Furukawa, N.; Watanabe, T.; Otsuji, T.; Hamada, M. Bull. Chem. Soc. Jpn. 1965, 38, 1247. (31) Kawaguchi, S.; Yekta, A.; Winnik, M. A. J. Colloid Interface Sci. 1995, 176, 362. (32) Crescenzi, V.; Delben, F.; Quadrifoglio, F.; Dolar, D. J. Phys. Chem. 1973, 77, 539.
2132
Langmuir, Vol. 20, No. 6, 2004
Hoare and Pelton
the overall mobility response to a change in pH. This relationship is expressed as eq 6.
()
( )
d|µ| Q d d|σ| d Q ) ) ∝ ∝ d(pH) d(pH) d(pH) A d(pH) 4πR2
(
)
2|Q| dR 1 d|Q| (6) R d(pH) πr2 d(pH)
microgel systems).33 The quantity ∆Gel estimates the sum of additional energy barriers (in excess of the ionization energy of the functional group) which retard the titration of a functional group at a given degree of ionization. Equation 5 is derived assuming that the excess free energy required for functional group titration is related entirely to electrostatic barriers; given the similarity in the behaviors of MAA-NIPAM and PAA, this is likely the case in the MAA-NIPAM system. In contrast, the pKa and ∆Gel curves for H-AM-NIPAM30 lie significantly above those of MAA-NIPAM and PAA, even though (as electrophoretic mobility measurements indicate) the local charge density in H-AM-NIPAM-30 is substantially lower than that in the MAA-NIPAM or PAA systems. This suggests that barriers other than electrostatics retard the titration of the H-AM-NIPAM-30 gel. Furthermore, both the pKa and ∆Gel of H-AM-NIPAM-30 virtually plateau at Rd > 0.4, suggesting that the excess free energy required to ionize functional groups beyond this degree of ionization is not dependent on the total number of ionized groups. Thus, neither the polyelectrolyte effect nor the breakup of complexation reactions between, for example, NIPAM and protonated carboxyl groups can adequately explain the observed behavior. This is consistent with our argument that the time-dependent titration behavior in H-AM-NIPAM arises from diffusional barriers. The apparent correlation observed between the total number of titratable functional groups measured in fast titrations and the calculated microgel surface charge suggests that nonequilibrium titrations can give a quantitative estimate of the surface carboxylic acid content. On that basis, at least 35% of the total number of -COOH groups in H-AM-NIPAM-30 appears to reside within the bulk of the microgel. Although nonequilibrium titrations have typically been viewed only as problematic experimental complications in the characterization of gel systems,31 these data indicate that they can be extremely useful in comparing gels with different morphologies. The observed pH dependence of the electrophoretic mobility and particle size further supports the proposed morphological models. Since the electrophoretic mobility is directly related to the surface charge density (eq 2), the balance between the change in surface charge (Q) and the increase in particle surface area (A ) 4πR2) will determine
As the pH is increased and carboxylic acid groups are ionized, the absolute electrophoretic mobility will increase only when d|Q|/d(pH) > (2|Q|/R)(dR/d(pH). Our results indicate that this is the case over the full ionization range for MAA-NIPAM, since the particle size and absolute electrophoretic mobility of MAA-NIPAM both increase continuously with pH. Such concurrent swelling and surface charge density increases would be facilitated if most of the -COOH groups are present at or near the particle surface. In this case, the inequality is satisfied since d|Q|/d(pH) is high when a larger percentage of functional groups contribute directly to increasing the surface charge upon ionization. A similar trend is observed for H-AM-NIPAM-30 over the pH range 4 < pH < 9. However, despite an observed 25 nm increase in particle size at 9 < pH < 10, the electrophoretic mobility remains constant over the same pH range, requiring that d|Q|/d(pH) ) (2|Q|/R)(dR/d(pH)). From this condition, at 9 < pH < 10, a smaller change in total surface charge (d|Q|/d(pH)) accompanies an equivalent degree of swelling (dR/d(pH)) to that observed in the MAA-NIPAM system. Since functional group ionization is the only mechanism of pH-induced swelling for these microgels, this swelling behavior demands that a significant number of ionizable functional groups must reside in the bulk of the H-AMNIPAM-30 microgel, supporting our internal charge model. The pH-induced swelling ratios also indicate microstructural features. Upon changing the pH from 4 to 10, the hydrodynamic diameter of MAA-NIPAM increases 25% while that of H-AM-NIPAM increases only 15%. This observation can be directly attributed to the distribution of charged functional groups in the gel. If charged groups are distributed throughout the particle, ion-ion repulsion would have a minimal effect on the swelling of the microgel since the local polyanion concentrations would be relatively low (i.e., a similar number of charges are distributed over a much larger volume). Thus, a lower degree of swelling would be expected for such microgels at high pH, as shown experimentally for H-AM-NIPAM-30. This explanation is also consistent with that of Kokufuta, who has emphasized the importance of local ion-ion repulsion in determining the degree of swelling of polyelectrolyte NIPAM-based gel systems.19,27 Cross-linker gradients may also contribute to the observed swelling behavior. Reaction kinetics and light scattering studies suggest that the MBA cross-linker reacts faster than NIPAM and concentrates in the core of the microgel.34 As a result, the relatively lighter crosslinking present in the carboxylic acid-rich “shell” in MAANIPAM should impose a lower elastic resistance to gel swelling than the higher cross-link density in the bulk of the particle where many of the carboxylic acid groups in H-AM-NIPAM-30 are located. Volume phase transition data also support the proposed models in Figure 13. Broad volume phase transitions such as that observed for H-AM-NIPAM-30 have been previ-
(33) Morawetz, H. Macromolecules in Solutions; John Wiley and Sons: New York, 1965.
(34) Varga, I.; Gilanyi, T.; Meszaros, R.; Filipcsei, G.; Zrinyi, M. J. Phys. Chem. B 2001, 105, 9071.
Figure 14. Variations in the apparent dissociation constant (pKa) and (inset) the excess electrostatic free energy (∆Gel) as a function of the degree of ionization for H-AM-NIPAM-30 and MAA-NIPAM microgels compared with the same data for linear poly(acrylic acid).
Functional Group Distributions in Microgels
ously described for high MAA-content MAA-NIPAM microgels.18 As the percentage of MAA was increased, the chain length distribution of thermosensitive PNIPAM chains (i.e., consecutive NIPAM units incorporated into the copolymer) was broadened and shifted to lower average chain lengths. Since PNIPAM chains with different lengths undergo transitions at different temperatures at a given polymer concentration, a broadening of the NIPAM chain length distribution translates directly into a broader overall volume phase transition. Given that copolymerization kinetics indicates random copolymerization between AM and NIPAM,28 the average PNIPAM chain length in AM-NIPAM should be much shorter and more broadly distributed compared to that of a MAA-NIPAM copolymer, in which copolymerization kinetics indicates a preference for NIPAM homopolymerization.29 Thus, at identical functional group loadings, the internally functionalized H-AM-NIPAM-30 should exhibit a much broader transition than the core-shell MAA-NIPAM microgel, as shown experimentally. The two-step particle size and electrophoretic mobility versus temperature profiles observed with MAA-NIPAM further endorse the proposed heterogeneous microstructural model. A two-step profile has been observed previously in the literature in particle size versus temperature profiles22 and calorimetric data35 for acrylic acid containing microgels with similar functional group loadings; however, both these observations were made in deionized water instead of the 10-3 M KCl used in this study. Kratz et al.22 attribute such a profile to a decrease in the local dielectric constant in the microgel interior as water is expelled upon microgel collapse, reducing the local effective Bjerrum length and initiating counterion condensation or direct association between the charged carboxylic acid groups and H+ ions in the solution. However, if this were the case, we would also expect to observe a two-step transition for the H-AM-NIPAM-30 system, which contains a similar number of carboxylic acid groups which can act as ion condensation sites. Instead, we propose that our morphological models can be used to explain this observation. The primary transition at 35 °C may represent the collapse of the NIPAM-rich core, around which the lightly crosslinked and highly functionalized chains in the particle shell reorient to minimize ion-ion repulsion. Within the plateau region (45-50 °C), the core has fully collapsed while the MAA-rich shell, whose local VPTT is elevated by the high concentration of hydrophilic charged MAA comonomer, remains hydrated. Finally, between 50 and 55 °C, the ion-ion repulsion and hydrogen bonding interactions keeping the MAA-rich shell hydrated are overcome by isopropyl group hydrophobic interactions, collapsing the shell and inducing complete deswelling. (35) Saunders, B. R.; Vincent, B. J. Chem. Soc., Faraday Trans. 1996, 92, 3385.
Langmuir, Vol. 20, No. 6, 2004 2133
Overall, the consistent correlation observed between the proposed microscopic models and results obtained using the wide variety of macroscopic microgel characterization techniques employed in this study strongly support the validity of the models themselves and the utility of the applied techniques in probing microstructures. Summary The major conclusions drawn from this work are as follows: (1) Hydrolysis of acrylamide/N-isopropylacrylamide copolymer microgels at temperatures below the volume phase transition temperature produces microgels with a significant number of carboxylic acid groups located within the bulk of the microgel. From nonequilibrium conductometric titration, it is estimated that at least 35% of carboxylic acid groups are located in the microgel interior. (2) Methacrylic acid/N-isopropylacrylamide copolymer microgels exhibit a core-shell morphology in which most carboxylic acid groups reside at or near the microgel surface. (3) The functional group distribution in hydrolyzed AM-NIPAM copolymer microgels can be influenced by hydrolysis temperature. Conducting the hydrolysis at temperatures above the volume phase transition temperature appears to produce predominantly surfacefunctionalized microgels. (4) Base-catalyzed hydrolysis of acrylamide functionalities in an acrylamide/N-isopropylacrylamide copolymer microgel promotes a higher rate of hydrolysis and higher selectivity toward acrylamide hydrolysis than acidcatalyzed hydrolysis. The optimized conditions were determined as T ) 30 °C and [NaOH] ) 0.5 M. (5) Nonequilibrium conductometric and potentiometric titrations can give semiquantitative information regarding functional group distributions in PNIPAM-based microgel systems. Based on the above conclusions, we believe that we have developed strategies of both controlling and characterizing the number and approximate distribution of carboxylic acid groups within N-isopropylacrylamide-based microgel systems. This development should improve our knowledge concerning how to select NIPAM-based copolymer systems to best fit a wide variety of applications currently proposed for these temperature-sensitive microgels. Acknowledgment. The authors thank the Natural Sciences and Engineering Research Council of Canada (NSERC) for funding and Dr. Donald Hughes for his assistance with running the NMR spectra. LA0351562
