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Notes Using Benzophenone-Functionalized Phosphonic Acid To Attach Thin Polymer Films to Titanium Surfaces Nina Griep-Raming,† Matthias Karger,‡ and Henning Menzel*,† Institut fu¨ r Technische Chemie, Abt. TC Makromolekularer Stoffe, Technische Universita¨ t Braunschweig, Hans-Sommer-Strasse 10, 38106 Braunschweig, Germany, and Institut fu¨ r Elektrische Messtechnik und Grundlagen der Elektrotechnik, Technische Universita¨ t Braunschweig, 38106 Braunschweig, Germany Received June 15, 2004. In Final Form: September 24, 2004
Introduction Because of their good mechanical properties, titanium and its alloys are widely used for medical applications such as orthopedic and dental implants.1 Although they are generally considered as biocompatible, many efforts have been made to tailor the surface properties of the metal to further improve the interaction of the implant surface2-8 with the natural environment. Most of these publications reported the use of self-assembled monolayers (SAMs) of unfunctionalized or functionalized silanes2-4 or phosphonates.5-7 Some of these films improve the osseointegration after further functionalizing with bioactive substances such as the cell-adhesive RGD-peptide4,6 or the protein BMP-23 for example. In comparison to silanes, SAMs of phosphonates have the advantage of a higher hydrolytic stability6,8,9 and that no surface conditioning (like acid treatment) is required in order to obtain high coverage.3,10 Recently Schwartz et al.11 developed a simple but effective route to immobilize stable phosphonic acid monolayers onto titanium surfaces. By simply heating the deposited phosphonate on the surface before rinsing, they obtained stable ordered monolayers of alkylphosphonates. * Corresponding author. Tel: ++49-531-391-5361. Fax: ++49531-391-5357. E-mail:
[email protected] (H. Menzel). † Institut fu ¨ r Technische Chemie. ‡ Institut fu ¨ r Elektrische Messtechnik und Grundlagen der Elektrotechnik. (1) Williams, D. F. Titanium in Medicine; Springer-Verlag: Berlin, Heidelberg, 2001. (2) Nanci, A.; Wust, J. D.; Peru, L.; Brunet, P.; Sharma, V.; Zalzal, S.; McKee, M. D. J. Biomed. Mater. Res. 1998, 40, 324-335. (3) Jennissen, H. P.; Zumbrink, T.; Chatzinilolaidou, M.; Stepphuhn, J. Mater.-wiss. U. Werkstofftech. 1999, 30, 838-845. (4) Xiao, S.-J.; Textor, M.; Spencer, N. D. Langmuir 1998, 14, 55075516. (5) Viornery, C.; Chevolot, Y.; Le´onard, D.; Aronsson, B.-O.; Pe´chy, P.; Mathieu, H. J.; Descouts, P.; Gra¨tzel, M. Langmuir 2002, 18, 25822589. (6) Schwartz, J.; Avaltroni, M. J.; Danahy, M. P.; Silverman, B. M.; Hanson, E. L.; Schwarzbauer, J. E.; Midwood, K. S.; Gawalt, E. S. Mater. Sci. Eng. 2003, 23C, 395-400. (7) Gawalt, E. S.; Avaltroni, M. J.; Danahy, M. P.; Silverman, B. M.; Hanson, E. L.; Schwarzbauer, J. E.; Midwood, K. S.; Schwartz, J. Langmuir 2003, 19, 200-204. (8) Helmy, R.; Fadeev, A. Y. Langmuir 2002, 18, 8924-8928. (9) Marcinko, S.; Fadeev, A. Y. Langmuir 2004, 20, 2270-2273. (10) Gawalt, E. S.; Brault-Rios, K.; Dixon, M. S.; Tang, D. C.; Schwartz, J. Langmuir 2001, 17, 6743-6745. (11) Gawalt, E. S.; Avaltroni, M. J.; Koch, N.; Schwartz, J. Langmuir 2001, 17, 5736-5738.
Although polymers offer a wide range of materials that could improve the biocompatible performance of the surface and provide a wide range of functionalities for further modification, few publications have been made that report the bonding of a polymer to a titanium surface.12 Textor et al. report the physisorption of a polycationic polymer onto a negatively charged titanium surface.12 Beside such physical adsorption employing electrostatic interactions, covalent attachment of a polymer to a solid substrate is possible. Generally there are different methods to covalently bind a polymer to a surface. The “grafting onto” method requires a polymer with a special functionality to react with appropriate surface sites. So this approach is restricted to tailored polymers. Furthermore the layer thickness and grafting density are limited.13 Another approach is the “grafting from” method. The polymer is directly grown from an initiator monolayer at the surface. In literature there are examples of grafting from using free radical,13 controlled radical,14 anionic,15 cationic,16 or transition metal catalyzed17 polymerization from the surface. In principle this method is applicable to all polymers that are prepared by a chain growth mechanism. However, the initiator monolayer has to be appropriate and requires extensive synthetic efforts. Recently photochemical grafting methods were developed for glass or silicon surfaces. Here a photoreactive silane anchor is immobilized on the surface, which reacts with the C-H bonds of a polymeric overcoat after illumination with UV light, resulting in a surfaceimmobilized polymer.18,19 This method seems to be an almost universal approach to bind all kinds of different polymers to a surface, and it is fast and easy to conduct. To apply such photochemical grafting methods to titanium and its alloys, the use of a phosphonic acid anchor instead of a silane anchor is favorable, because for biomedical applications the hydrolytic stability of the coating is important for long lasting implants. Here we report the synthesis of a benzophenone-functionalized phosphonic acid, its immobilization onto Ti-6Al-4V surfaces, and its testing as a photochemical anchor for different spin-coated polymers. Results and Discussion The photochemical grafting of polymers has been accomplished on glass and silicon surfaces with two different photoactive systems. Prucker et al.18 used a benzophenone derivative as the photoactive compound. Bartlett et al.19 on the other hand employed an azide (12) Tosatti, S.; De Paul, S. M.; Askendal, A.; VandeVondele, S.; Hubbell, J. A.; Tengvall, P.; Textor, M. Biomaterials 2003, 24, 49494958. (13) Prucker, O.; Ru¨he, J. Macromolecules 1998, 31, 592-601. (14) Bo¨ttcher, H.; Hallensleben, M. L.; Nuss, S.; Wurm, H. Polym. Bull. 2000, 44, 223-229. (15) Jordan, R.; Ulman, A.; Kang, J. F.; Rafailovich, M. H.; Sokolov, J. J. Am. Chem. Soc. 1999, 121, 1016-1022. (16) Jordan, R.; Ulman, A. J. Am. Chem. Soc. 1998, 120, 243-247. (17) Witte, P.; Menzel, H. Macromol. Chem. Phys. 2004, 205, 17351743. (18) Prucker, O.; Naumann, C. A.; Ru¨he, J.; Knoll, W.; Frank, C. W. J. Am. Chem. Soc. 1999, 121, 8766-8770. (19) Bartlett, M. A.; Yan, M. Adv. Mater. 2001, 13, 1449-1451.
10.1021/la0485327 CCC: $27.50 © 2004 American Chemical Society Published on Web 11/19/2004
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Scheme 1. Synthesis of Benzophenone-Functionalized Phosphonic Acid
compound. The benzophenone system is somewhat easier with respect to the synthesis and has already been described for screening of polymers for biomedical applications.20,21 Therefore a benzophenone derivative was chosen as the photoactive group. Because of the better hydrolytic stability of phosphonic acid monolayers on titanium in comparison to silanes,8,9 which is important for biomedical applications, this group was used as surface active headgroup of the anchor molecule. The synthetic route of the anchor containing a benzophenone moiety and a phosphonic acid headgroup is depicted in Scheme 1. Anchor Synthesis. The synthesis of the benzophenone phosphonic acid can be accomplished with good yields in a three-step reaction. In the first step diethyl 3-bromopropylphosphonate (1) is synthesized in an Arbuzov reaction with an excess of 1,3-dibromoethane to control the reaction. The next step is a Williamson ether synthesis between the bromopropylphosphonate and hydroxybenzophenone. The resulting diethyl 3-(4-oxybenzophenone)propylphosphonate (2) can be dealkylated under mild conditions using bromotrimethylsilane instead of acid-catalyzed hydrolytic dealkylation.22 Thus the ether goup is not affected during the reaction. Immobilization of the Anchor. The resulting phosphonic acid (3) can be immobilized onto Ti-6Al-4V surfaces23 using a protocol developed by Schwartz et al.7,11 This protocol involves several cycles of depositing a solution of the anchor in dry tetrahydrofuran on the substrate, evaporating the solvent slowy in a gentle nitrogen flow, subsequent heating, and rinsing five times with dry tetrahydrofuran in an ultrasonic bath. The resulting films have a typical film thickness of about 0.8 ( 0.1 nm (measured by ellipsometry23) similar to values measured for the corresponding silane derivative on silicon wafers.18 Atomic force microscopy (AFM) imaging (see Supporting Information) of the monolayers reveals a continuous but granular structure of the film; thus the substrate is completely covered. A granular structure as a result of an island growth mechanism can be expected from the character of the phosphonate binding to the surface, as suggested by Schwartz et al.6 Contact angles changed from about θadv ) 40° and θrec ) 18° directly after polishing and cleaning of the titanium to θadv ) 70° and θrec ) 36° for the monolayer; however, after aging the substrates have contact angles of about θadv ) 75° and θrec ) 42°, which is fairly near to the monolayer contact angle, and so the measurements were not conclusive. Grazing (20) Dahm, M.; Chang, B. J.; Prucker, O.; Pierkes, M.; Alt, T.; Mayer, E.; Ru¨he, J.; Oeler, H. Ann. Thorac. Surg. 2001, 71 (5 Suppl.), 437-440. (21) Ru¨he, J.; Yano, R.; Lee, J. S.; Ko¨berle, P.; Knoll, W.; Offenha¨user, A. J. Biomater. Sci., Polym. Ed. 1999, 10, 859-874. (22) McKenna, C. E.; Higa, M. T.; Cheung, N. H.; McKenna, M.-C. Tetrah. Lett. 1977, 2, 155-158. (23) For further details see Supporting Information.
Figure 1. IR spectra of bulk 3-(4-oxybenzophenone)propylphosphonic acid (upper trace). GIR spectra of titanium bound 3-(4-oxybenzophenone)propylphosphonic acid (lower trace). Table 1. IR Band Assignment of 3-(4-Oxybenzophenone)propylphosphonic Acid24-26 no.
frequency (cm-1)
1 2 3 4 5 6 7 8 9 10 11
1647 1604 1508, 1444, 1421 1286 1253 1207 1179 1149 1056 1024 987, 955
assignment CdO valence CdC stretching CH2/CH3 deformation CsO valence alkyl-aryl ether PdO stretching CsO stretching (alkyl) PsO valence (antisym.) PsO valence (sym.) PsOH stretching
incidence Fourier transform IR spectra are recorded with an untreated titanium surface as reference. The main bands of the anchor molecule are found in the spectra of the monolayer on titanium (see Figure 1 and Table 1). In comparison to the bulk spectra of the phosphonic acid, the asymmetric and the symmetric stretching vibrations of the P-OH at 955 and 987 cm-1 and the PdO stretching vibration at 1207 cm-1 24,25 disappear in the infrared spectra of the monolayers indicating the mainly tridentate bonding of the anchor to the surface as proposed by Mutin et al.27 This is supported by the appearance of a broad band at 1050-1100 cm-1, which can be assigned as the symmetric strechting mode of a PO32- group.24,25 Remarkable is the disappearance of the carbonyl band at 1647 cm-1. It can be speculated that this band is not detected in the GIR spectrum due to an orientation of the carbonyl group parallel to the surface. However a perfect orientation of the anchor monolayer necessary for a complete disappearance of the band is very unlikely. Thus, no conclusive explanation for the disappearance of the band at 1647 cm-1 can be given. Polymer Layers. The maximum film thickness that can be obtained by the photochemical grafting onto method (24) Thomas, L. C. Interpretation of the Infrared Spectra of Organophosphorus Compounds; Heyden: London, 1974. (25) Pellerite, M. J.; Dunbar, T. D.; Boardman, L. D.; Wood, E. J. J. Phys. Chem. B 2003, 107, 11726-11736. (26) Steiner, G.; Sablinskas, V.; Savchuk, O.; Bariseviciute, R.; Ja¨hne, E.; Adler, H. J.; Salzer, R. J. Mol. Struct. 2003, 661-662, 429-435. (27) Guerrero, G.; Mutin, P. H.; Vioux, A. Chem. Mater. 2001, 13, 4367-4373.
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Figure 2. GIR spectra of surface bound polyvinyl-N-methylacetamide.
is influenced by the molecular weight of the polymer and parameters such as monolayer grafting density, spin cast film thickness, illumination intensity, and illumination time. Because the photochemical group used, is the same as examined by Prucker et al., their parameters for illumination time, illumination intensity and spin cast film thickness were adapted.18 A polymer overcoat of 100 nm is deposited onto the monolayers of the photoactive anchor. After illumination for 35 min, covalent bonding between the monolayer and the polymer is achieved. Only the bound polymer remains at the surface after extraction. With this route, polyvinyl-N-methylacetamide, which is known to give good layers, was deposited onto a Ti-6Al4V surface from methanol solution and subsequently tethered photochemically. The ellipsometric measurements showed a 6 nm thick polymer film on the titanium surface after extraction. GIR measurements prove the presence of the polymer by showing the characteristic carbonyl peak of polyvinyl-N-methylacetamide at 1654 cm-1 (Figure 2). In addition the contact angles changed from θadv ) 70° and θrec ) 36° for the anchor monolayer to θadv ) 27° and θrec ) 13° for the polyvinyl-N-methylacetamide layer. In comparison, a photochemical attached monolayer of the same polymer on silicon surfaces gives within the error of measurement almost the same contact angles of θadv ) 21° and θrec ) 7°. In a control experiment, in which the polymer was spin coated onto a clean titanium surface, after illumination and extraction no peaks in GIR and no film thickness by ellipsometry could be detected. The mechanism of the photochemical grafting onto method accounts for a dependence of the layer thickness of the radius of gyration and therefore the molecular weight of the polymer, as has been shown in previous reports.18,28 Therefore two samples of poly(hydroxyethyl methacrylate) (PHEMA) with 200 000 and 60 000 g/mol and polystyrene samples with molecular weights between 130 000 and 2 000 000 g/mol were examined. For PHEMA the polymer with the higher molecular weight gave the higher film thickness, as indicated by the intensities of the infrared signal. By use of the signal at 1604 cm-1 stemming from the CdC stretching vibration of the anchor (28) Bartlett, M. A.; Yan, M. Polym. Mater. Sci. Eng. 2000, 83, 451452.
Figure 3. GIR spectra of surface bound PHEMA. Mw ) 200 000 g/mol (upper trace) and Mw ) 60 000 g/mol (lower trace).
monolayer as internal reference, the band at 1735 cm-1 due to the carbonyl group of the poly(hydroxyethyl methacrylate) is normalized. For the polymer with the bulk radius of gyration (Rg) (calculated according to Prucker18) of 12.3 nm (Mw ) 200 000 g/mol), this gives a value of 3.56 and for the other polymer (Rg ) 6.7 nm; Mw ) 60 000 g/mol) a value of 1.88; thus the ratio of the two normalized bands is 1.89, which is within in the error of the integration the same as the ratio of the two radii of gyration with a value of 1.83. So a higher peak intensity can be correlated with a higher film thickness for the polymer with higher molecular weight (see Figure 3). For polystyrene the film thickness was measured by ellipsometry and plotted as a function of the molecular weight and the bulk radius of gyration (Rg) calculated according to Prucker (see Figure 4). The increase of the layer thickness with Rg is linear as proposed in the literature.18 However the obtained film thicknesses are significantly lower than the values reported by Prucker et al.18 This arises from the various parameters influencing the maximum film thickness. Although most parameters were adapted from Prucker, differences in the grafting density of the monolayer and the light intensity (because of a different illumination system) can explain the deviating film thicknesses. Conclusions The method of benzophenone-based photochemical grafting was expanded to titanium surfaces. The corresponding anchor, a benzophenone with a phosphonic acid group was synthesized in very good yields in a three-step synthesis. It is easy to store and to handle compared to the corresponding silane. Monolayers of the anchor can be prepared by simple depositing-heating-washing cycles. Polymer molecules in direct contact to the benzophenone residues of these monolayers are covalently bound upon illumination with UV light of about 345 nm. As expected from the binding mechanism, the resulting film thickness is a function of the molecular weight of the
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Figure 4. Dependence of the film thickness on the chain dimensions: (A) film thickness vs molecular weight; (B) film thickness vs radius of gyration.
deposited polymer. Altogether the photochemical grafting approach with a phosphonic acid headgroup is very versatile in two respects. First the photochemical covalent attachment offers a wide variety of bonding possibilities: Literally all kinds of polymers can easily be bound to a surface, but the method is not restricted to this purpose. As outlined by Prucker et al. it is also possible to attach Langmuir-Blodgett layers or biomolecules for example.18 Frank et al. described the photochemical attachment of polymer supported lipid bilayers to a surface.29 The second cause for the versatility of the method is the phosphonic acid as the surface active headgroup, which is not limited to titanium surfaces, but they are known to bind also to a wide variety of surfaces such as tantalum,30 aluminum,31 mica,32 zirconium,33,34 silicon,35 steel, stainless steel, copper, brass,36 etc. (29) Shen, W. W.; Boxer, S. G.; Knoll, W.; Frank, C. W. Biomacromolecules 2001, 2, 70-79. (30) Brovelli, D.; Ha¨hner, G.; Ruiz, L.; Hofer, R.; Kraus, G.; Waldner, A.; Schlo¨sser, J.; Oroszlan, P.; Ehrat, M.; Spencer, N. D. Langmuir 1999, 15, 4324-4327. (31) Maege, I.; Jaehne, E.; Henke, A.; Adler, H.-J. P.; Bram, C.; Jung, C.; Stratmann, M. Macromol. Symp. 1997, 126, 7-24.
Acknowledgment. The authors would like to thank Anita Scherbarth for SEC measurements and Dr. Christof Maul for the support with the IR measurements. This work was supported as a part of the SFB 599 (“Biomedical Engineering”) by the Deutsche Forschungsgemeinschaft (DFG). Supporting Information Available: Synthesis of the components used in the benzophenone-functionalized phosphonic acid, preparation of the polymer layers, and characterization of the surface. This material is available free of charge via the Internet at http://pubs.acs.org. LA0485327 (32) Woodward, J. T.; Ulman, A.; Schwartz, D. K. Langmuir 1996, 12, 3626-3629. (33) Gao, W.; Dickinson, L.; Grozinger, C.; Morin, F. G.; Reven, L. Langmuir 1996, 12, 6429-6435. (34) Hofer, R.; Textor, M.; Spencer, N. D. Langmuir 2001, 17, 40141020. (35) Hanson, E. L.; Schwartz, J.; Nickel, B.; Koch, N.; Danisman, M. F. J. Am. Chem. Soc. 2003, 125, 16074-16080. (36) Van Alsten, J. G. Langmuir 1996, 12, 7605-7614.
