J. Phys. Chem. B 2002, 106, 2843-2847
2843
ARTICLES Effects of Solvent Quality during Polymerization on Network Structure of Cross-Linked Methacrylate Copolymers Jeannine E. Elliott† and Christopher N. Bowman*,†,‡ Department of Chemical Engineering, UniVersity of Colorado, Boulder, Colorado 80309-0424, and Department of RestoratiVe Dentistry, UniVersity of Colorado Health Sciences Center, DenVer, Colorado 80045-0508 ReceiVed: July 24, 2001; In Final Form: NoVember 19, 2001
Processing conditions during free radical polymerization strongly affect the polymer network evolution. This work focuses on how the solvent quality during solution polymerization alters the mechanical and structural properties of the resulting polymer hydrogel network in methacrylate copolymerizations. Two copolymer systems were analyzed: 2/98 diethylene glycol dimethacrylate/methoxyethyl methacrylate and 2/98 diethylene glycol dimethacrylate/octyl methacrylate. Copolymerizations were performed in varying amounts of either hexanol or ethylene glycol diacetate. The equilibrium swelling of bulk DEGDMA was also measured to ascertain how the cross-linking agent interacts with the solvent. To compare the solvent quality of the two solvents, the equilibrium swelling of the copolymer samples was measured in each solvent. The results of dynamic mechanical analysis illustrate that changes in solvent concentration and solvent quality affect the extent of primary cyclization during the polymerization. The results further demonstrate how solvent-polymer interactions influence the network structure in copolymerizations where the monovinyl monomer and crosslinking agents may each interact differently with the solvent. Experimental results are compared to theories for how the structural evolution, especially the cross-link density, changes with solvent amount and quality.
Introduction Because of their biocompatibility and hydrophilic nature, loosely cross-linked polymeric materials that swell in the presence of water are used in a wide range of current and developing biomedical areas including contact lenses, wound bandages and dressings, bioadhesives, cell immobilization, tissue engineering, and drug delivery systems.1-7 When developing a biomaterial for a specific application, it is important to understand how the choices of monomer, comonomer composition, monomer functionality, light intensity, solvent concentration, and solvent quality affect the three-dimensional network structure created during the polymerization and the resulting material properties. Identifying how these polymerization reaction conditions affect the degree of cross-linking is critical as it dictates the mechanical strength, drug delivery rate, and swelling ratio of the hydrogel. Free radical polymerization of multifunctional monomers forms nonideal, heterogeneous polymer networks because of intramolecular cyclization, which leads to microgel formation. Because of this complexity, the network structure of free radical polymerization does not follow the traditional Flory-Stockmayer theory and predictions of how polymerization conditions affect the polymer properties are rarely straightforward. Much research has been conducted in this area to provide a better * To whom all correspondence should be addressed. Fax: 303-492-4341.
[email protected]. † University of Colorado. ‡ University of Colorado Health Sciences Center.
mechanistic understanding of the polymerization process and how polymerization factors, such as those given above, affect the network formation. Significant progress has been made, through both experiments and modeling, by many research groups toward this goal.8-23 One polymerization condition that has not been investigated as thoroughly is how solvent quality affects the network evolution. It has previously been observed that the solvent concentration during the polymerization affects the material properties of the polymer by increasing the rate of primary cyclization of multivinyl monomers during the polymerization.22,24-27 A primary cycle differs from a cross-link in that the propagating free radical reacts intramolecularly with its own pendant double bond, which then loses the opportunity to cross-link. The greater the extent of primary cyclization, the less cross-linked the polymer will be and the larger the mesh size. This phenomenon is observed in the increased equilibrium swelling and reduced mechanical strength found with the increase in solvent concentration during the polymerization. The reason that solvent concentration changes the rate of primary cyclization is explained by the local dynamics of the propagating radical. For low solvent concentrations, the double bond concentration surrounding the free radical is relatively high, leading to a faster rate of propagation and less opportunity for the free radical to cycle by reacting with its own pendant double bonds. On the other hand, high solvent concentration leads to lower double bond concentration and lower propagation rates, so that the possibility of cyclization is enhanced. Thus, the effects of solvent concentration on network formation are explainable.26,28
10.1021/jp012845i CCC: $22.00 © 2002 American Chemical Society Published on Web 02/26/2002
2844 J. Phys. Chem. B, Vol. 106, No. 11, 2002 In addition to solvent concentration, solvent quality is expected to affect material properties of the cross-linked polymer as well. The various interactions between the divinyl monomer, developing polymer chain, and solvent and how these interactions shape the network structural evolution are extremely complex. Previous research on the influence of the solvent quality on polymerization has shown that the choice of solvent impacts the polymerization in a variety of manners. Solvent quality affects the diffusion of the polymer chains, the viscosity, the intermolecular termination rate, the primary chain length, the gel point conversion, the reactivity ratios, and the extent of primary and secondary cyclization.21,29-31 This paper focuses on how the solvent quality affects the extent of primary cyclization and the resulting mechanical properties, specifically the molecular weight between cross-links, which is a measure of the mesh size of the polymer. Using both experimental studies and theory, the effect of solvent quality on cross-linking was investigated in two systems. The results further show the complexity of solvent-polymer interactions and how they influence network structure, particularly in copolymerizations where the situation is further complicated by the fact that the monovinyl monomer and cross-linking agent may each interact differently with the solvent. For the experimental studies here, two copolymer systems were studied, 2/98 diethylene glycol dimethacrylate/octyl methacrylate (DEGDMA/ OcMA) and 2/98 diethylene glycol dimethacrylate/methoxyethyl methacrylate (DEGDMA/MEMA). MEMA and OcMA were chosen for the study because they each polymerize to nearly 100% conversion under these conditions. Two solvents were utilized, hexanol and ethylene glycol diacetate. They were chosen because hexanol is a better solvent for OcMA and ethylene glycol diacetate is a better solvent for MEMA. Swelling studies were performed to ascertain solvent quality differences. Experimental Section Materials. Mechanical property studies were performed on two copolymer systems: 2 mol % diethylene glycol dimethacrylate (DEGDMA) with 98 mol % methoxy ethyl methacrylate (MEMA) or 98 mol % n-octyl methacrylate (OcMA). The copolymers were polymerized with 0, 20, and 50 volume % of ethylene glycol diacetate and hexanol. DEGDMA was used as received from Sartomer (West Chester, PA). OcMA and MEMA were purchased from Polysciences, Inc. (Warrington, PA). Hexanol and ethylene glycol diacetate were purchased from Aldrich Chemical Co., and both were used as received. Polymers were initiated with 0.1 wt % 2-2′-azobisisobutyronitrile from Aldrich Chemical Co. (Milwaukee, WI) and thermally polymerized for 1-3 h at 80 °C. Methods. To determine the solvent-polymer interactions, bulk samples of 2/98 DEGDMA/OcMA, 2/98 DEGDMA/ MEMA, and DEGDMA were polymerized without solvent and placed in hexanol or ethylene glycol diacetate to swell. Gravimetric measurements were performed until the change in the swollen polymer weight was less then 0.001 g over a 24 h period, at which point the polymers were assumed to be at equilibrium. A dynamic mechanical analyzer (DMA7e, PerkinElmer, Norwalk, CT) was used to perform the dynamic mechanical measurements.32 The samples used for dynamic mechanical analysis (DMA) were polymerized in a Teflon mold with five wells, each 5 mm × 20 mm × 1 mm. The top was covered with a glass slide held on by two rubber bands and then sealed with high-vacuum silicone grease. Experiments were performed on the DMA to measure moduli and loss tangent as a function of temperature by applying a sinusoidal stress of
Elliott and Bowman
Figure 1. Mc for 2/98 DEGDMA/MEMA copolymers with ethylene glycol diacetate as the solvent (0) and hexanol as the solvent (2). Theoretical Mc assuming no cyclization and 100% conversion (- - -).
frequency of 1 Hz. These measurements were used to determine the molecular weight between cross-links (Mc). Double-bond conversions were measured by monitoring the carbon-carbon double-bond concentration before and after the polymerization using Fourier transform near-infrared (near-IR) spectroscopy (Magna-IR 750, Nicolet, Madison, WI).33 Results and Discussion Using the DMA, the modulus in the rubbery region of the polymeric materials was measured, and the Mc was calculated.34 Two different copolymer systems were investigated to analyze the way in which the network structure changed with the choice of solvent present during polymerization. The results do not yield a straightforward correlation but elucidate some of the important factors when considering solvent quality. The average molecular weight between cross-links is plotted in Figure 1 for 2% DEGDMA copolymerized with MEMA with 0, 20, and 50 volume % hexanol or ethylene glycol diacetate. The conversion of the samples was measured using near-IR spectroscopy, and all samples achieved near 100% conversion of double bonds. The theoretical Mc, assuming no cyclization and 100% conversion, is also shown in Figure 1. All data points are above the theoretical Mc, indicating that cyclization is present at all solvent concentrations and even in the absence of solvent. As all samples are at 100% conversion, the increase in Mc with solvent concentration shows that primary cyclization rates are further enhanced with dilution during the polymerization. With increasing solvent concentration, the polymer has an increased mesh size and diminished mechanical strength. Our previous work and that of other researchers19,26,27 has described similar results of solvent on network properties. In Figure 1, the polymerization in two solvents, ethylene glycol diacetate and hexanol, is compared. For all data points, the polymer formed in hexanol had a higher Mc than otherwise equivalent polymers formed in ethylene glycol diacetate. The solvent quality of hexanol and ethylene glycol diacetate was compared by swelling samples of the bulk copolymer in each solvent. A thermodynamically good solvent will cause increased swelling, as polymer chains are more fully solvated as compared
Cross-Linked Methacrylate Copolymers
Figure 2. Equilibrium swelling mass ratio of DEGDMA, PEG200DMA, and PEG600DMA in hexanol (clear) and ethylene glycol diacetate (crosshatched).
Figure 3. Schematic of propagating chain conformations in good and poor solvent.
to a thermodynamically poor solvent. The swelling mass ratio (swollen mass/dry mass) of 2/98 DEGDMA/MEMA is 2.3 in hexanol and 2.8 in ethylene glycol diacetate. Uniquely, in a copolymerization, the monovinyl monomer and cross-linking divinyl monomer may each interact differently with the solvent. To determine specifically how the cross-linking agent interacts with the solvent, the equilibrium swelling of pure DEGDMA, PEG400DMA, and PEG600DMA polymers was measured in the two solvents (Figure 2). All of these polymers swelled more in ethylene glycol diacetate. Because it is so highly cross-linked, DEGDMA does not swell extensively in either solvent, but the swelling of the longer poly(ethylene glycol) methacrylates aids in confirming that the small observed increase in swelling in ethylene glycol diacetate is likely real. Thus, in the DEGDMA/MEMA copolymer, both the monovinyl and the divinyl molecules swell more in ethylene glycol diacetate than hexanol. Figure 1 shows that the samples made with hexanol, the poor solvent, have a larger mesh size and undergo more primary cyclization. It is proposed that if the solvent-polymer interaction is poor, growing polymer chains will coil more rather than stretch out, and the likelihood of primary cyclization is greater due to increased proximity of the pendant double bonds (Figure 3a). In another case, if the solvent polymer interactions are good, the radical on the growing polymer chain should extend away from the pendant double bond, and the cyclization rate will be diminished (Figure 3b). In the second experiment, a different monovinyl (OcMA) was chosen that had the reverse swelling behavior in the two
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Figure 4. Mc for 2/98 DEGDMA/OcMA copolymers with ethylene glycol diacetate as the solvent (0) and hexanol as the solvent (2). Theoretical Mc assuming no cyclization and 100% conversion (- - -).
solvents. The 2/98 DEGDMA/OcMA has an equilibrium mass swelling ratio of 2.2 in hexanol and 1.2 in ethylene glycol diacetate. The OcMA copolymer swelled considerably better in hexanol. The polymer in hexanol increased to approximately twice its original mass while it swelled negligibly in the ethylene glycol diacetate. Because of these results, it is expected that the growing polymers of the OcMA copolymer will be more collapsed in ethylene glycol diacetate. However, the DEGDMA/ OcMA copolymer is unlike the DEGDMA/MEMA copolymer where both the monovinyl and the cross-linking agent swelled similarly. In this case, the DEGDMA/OcMA polymer, which consists mainly of OcMA, prefers the hexanol while poly(DEGDMA) is more swellable in ethylene glycol diacetate. In Figure 4, Mc is plotted vs percent solvent for the DEGDMA/OcMA copolymers made with 0, 20, and 50% hexanol or ethylene glycol diacetate. All samples were polymerized to 100% conversion as confirmed by IR. The samples polymerized with hexanol had a higher Mc. In fact, the Mc at each solvent concentration is about 40% higher when polymerized in hexanol. This trend is contrary to our hypothesis that hexanol is the better solvent for the OcMA copolymer and the pendant double bonds and propagating radicals should be most extended away from each other in hexanol, diminishing cyclization and decreasing the Mc. It indicates the complexity in these systems and that the interaction of the bulk copolymer with the solvent is not the only contributor to differences in cross-linking density. It is possible that although the copolymer consists primarily of OcMA, the solvent interactions with DEGDMA also have a significant impact. In previous work, a kinetic model has been developed that predicts the network evolution during free radical multifunctional polymerizations.28 The model has been successfully used to predict the effects of solvent concentration on the degree of cross-linking in loosely cross-linked copolymer systems.26,27 The equations in the model are utilized to consider how the effects of solvent quality on the cross-linking agent and monovinyl monomer each contribute to the polymer structure created. The model predicts the extent of primary cyclization by defining an effective local radical concentration for the pendant double bonds. The rate at which pendant double bonds react by cyclization with the local radicals vs cross-linking with radicals
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in the bulk solution is determined by a kinetic expression that includes these appropriate radical concentrations. The local radical concentration is calculated by defining a volume, which includes both the pendant vinyl and the propagating radical on the same kinetic chain that initially formed the pendant. The radius of the volume represents the distance between the pendant double bond and the radical and is calculated from polymer physics.35 The local radical concentration is a function of time and pendant birth time as it depends on how far the radical has propagated away from the pendant double bond. Using the idea of the local radical concentration, the amount of cyclization that occurs for pendants that are created at a specific time, tb, is calculated explicitly by integrating the pendant cyclization rate expression over the pendant’s lifetime. The fraction of pendants born at a particular birth time that cycle, ψ, is then calculated by eq 1. This derivation is shown in detail in previous work.27,28
ψ )1 - exp
(
)
-3 8πNA[DB]roCnl2
(1)
Here, NA is Avogadro’s number, [DB] is the total double-bond concentration, ro is the cross-linking agent size, Cn is the characteristic ratio,36 and l is the length of a carbon-carbon bond. There are two important parameters that specify the polymer system and are important for the discussion of solvent quality effects on the cross-linking agent and monovinyl monomer: ro, the length of the cross-linking molecule, and Cn, the solvent/ polymer characteristic ratio. The molecular length of the crosslinking molecule, ro, is related to how extended or collapsed the DEGDMA molecule is during the polymerization. Specifically, when one double bond has incorporated into the growing polymer, how far does the other pendant double bond extend out into the solution? Thus, ro is determined by the molecular size of DEGDMA, the cross-linking agent, as well as how it interacts with the solution during polymerization. On the other hand, the characteristic ratio, Cn, is related to how the growing polymer chain, which consists primarily of the monovinyl monomer, interacts with the solution. It varies with solvent quality and the degree of solvation of the propagating polymer chains. Unfortunately, the values of ro and Cn are not known for the specific copolymer-solvent interactions present in our experiments. We can, however, analyze how changes in these parameters affect the degree of cyclization. The fraction of pendants that cycle, ψ, increases with decreasing ro and Cn as expected (eq 1). More notably, changes in the value of ro and Cn both weigh equally in their contribution to the fraction of cyclization. It is therefore possible that a decrease in Cn would be overwhelmed by an increase in ro. This situation likely occurs in the DEGDMA/OcMA polymerization in hexanol or ethylene glycol diacetate. OcMA swells better in hexanol than in the ethylene glycol diacetate so the value of Cn should be higher in hexanol. The reverse trend is observed for the cross-linking agent DEGDMA, which swells less in hexanol and would have a lower value of ro. For the DEGDMA/OcMA system, the relative decrease in ro (cross-linking agent solvation) is likely greater than the increase in Cn (growing polymer chain solvation), and the overall extent of cross-linking decreases. Thus, the amount of cross-linking depends heavily on the relative effects of the solvent on both the cross-linking agent and the backbone polymer. Conclusions This work illustrates the importance of solvent quality on cross-linking and polymer network formation. It demonstrates
the complexity of the solvent-polymer interactions, especially when the monovinyl and cross-linking agent are solvated differently by the solvent during solution polymerization. In the DEGDMA/MEMA copolymer, both the backbone, which consists mainly of MEMA, and the bulk DEGDMA polymer swelled more extensively in ethylene glycol diacetate. With the DEGDMA/OcMA copolymer, the monovinyl and cross-linking agent had different swelling preferences. In the first experiment with DEGMA/MEMA, the polymer had a lower Mc in ethylene glycol diacetate, the good solvent. Because the chains are more extended in the good solvent, the cyclization probability will be decreased with a good solvent. Analogously, a poor solvent with collapsed chains should have more cyclization and result in a higher Mc. This same trend was not observed in the DEGDMA/OcMA copolymer experiments. This result is attributed to the fact that the monovinyl and cross-linking agent do not interact with the solvents similarly. An examination of the theory suggests that the extension of the cross-linking agent (ro) in the solvent is as important as how the growing polymer chain interacts with the solvent (Cn) in determining the rate of primary cyclization. This work elucidates several important factors that influence how the choice of solvent affects the network structure and extent of primary cyclization in crosslinked materials. Acknowledgment. The authors acknowledge funding from Industry/University Cooperative Research Center on Fundamentals and Applications of Photopolymerizations, a Graduate Student Fellowship Award from NSF to J.E.E., and the Presidential Faculty Fellow Program at the National Science Foundation. References and Notes (1) Wichterle, O.; Lim, D. Nature 1960, 185, 117. (2) Hydrogels in Medicine and Pharmacy; Peppas, N. A., Ed.; CRC Press: Boca Raton, FL, 1987; Vol. II. (3) Bae, Y. H.; Kim, S. W. AdV. Drug DeliVery ReV. 1993, 11, 109135. (4) Ende, M. T. A.; Peppas, N. A. J. Appl. Polym. Sci. 1996, 59, 673685. (5) Jen, A. C.; Wake, M. C.; Mikos, A. G. Biotechnol. Bioeng. 1996, 50, 357-364. (6) Wheeler, J. C.; Woods, J. A.; Cox, M. J.; Cantrell, R. W.; Watkins, F. H.; Edlich, R. F. J. Long-Term Eff. Med. Implants 1996, 6, 207-217. (7) Kao, F.-J.; Manivannan, G.; Sawan, S. P. J. Biomed. Mater. Res. 1997, 38. (8) Manneville, P.; Seze, L. d. Numerical Methods in the Study of Critical Phenomena; Springer: Berlin, 1981. (9) Boots, H. M. F.; Pandey, R. B. Polym. Bull. 1984, 11, 415-420. (10) Simon, G. P.; Allen, P. E. M.; Bennett, D. J.; Williams, D. R. B.; Williams, E. H. Macromolecules 1989, 22, 3555-3561. (11) Anseth, K. S.; Bowman, C. N. Chem. Eng. Sci. 1994, 49, 22072217. (12) Dusek, K.; Ilavsky, M. J. Polym. Sci. 1975, 53, 57-73. (13) Dusek, K.; Spevacek, K. Polymer 1980, 21, 750-756. (14) Dusek, K. DeVelopments in Polymerization, 3. Network Formation and Cyclization in Polymer Reactions; Applied Science Publishers: Englewood Cliffs, NJ, 1982. (15) Boots, H. M. J.; Kloosterboer, J. G.; Hei, B. M. M. v. d. Br. Polym. J. 1985, 17, 219-223. (16) Tobita, H.; Hamielec, A. E. Macromolecules 1989, 22, 3098-3105. (17) Tobita, H.; Hamielec, A. E. Mackromol. Chem. Macromol. Symp. 1988, 20/21, 501. (18) Landin, D. T.; Macosko, C. W. Macromolecules 1988, 21, 846851. (19) Baker, J. P.; Blanch, H. W.; Prausnitz, J. M. J. Appl. Polym. Sci 1994, 52, 783-788. (20) Anseth, K. S. Photopolymerizations of Multifunctional Monomers: Reaction Mechanisms and Polymer Structural Evolution. Doctorate, University of Colorado at Boulder, 1994. (21) Matsumoto, A. AdV. Polym. Sci. 1995, 123, 41-79. (22) Okay, O.; Kurz, M.; Lutz, K.; Funke, W. Macromolecules 1995, 28, 2728-2737.
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