b State Key Laboratory of Molecular Engineering of Polymers, Fudan University, Shanghai 200433, China
Supramolecular hydrogels have attracted increasing attention due to their promising applications in biotechnology and bioengineering, which originated from their unique characters, such as self-healing property based on their reversibility, rich chemical functionality and well-defined nanostructures [1, 2, 3, 4]. Compared with the conventional hydrogels connected through covalent interactions, supramolecular hydrogels are formed via non-covalent interactions, including hydrogen bond,π-π stacking, electrostatic interaction, metal-ligand interaction, hydrophobic interaction as well as host-guest inclusion complexation etc. [5, 6, 7, 8, 9]. Owing to the inherent reversible properties of the non-covalent interactions, supramolecular hydrogels are featured by stimuliresponse and thixotropy etc. [10, 11, 12].
In recent years, supramolecular hydrogels based on the complexation between cyclodextrins (CD) and guest molecules have gained much attention because of their potential applications in the field of biomedical engineering [13, 14, 15]. As pioneers in this field, Harada and his co-workers obtained macroscopic supramolecular hydrogels using poly(acrylamide) functionalized with host (cyclodextrin) or guest (adamantane, ferrocene, or azobenzene) moieties [16, 17]. These hydrogels exhibited self-healing properties and the strength of such supramolecular materials could be restored completely through host-guest interactions. However, the synthesis process of these host or guest functionalized polymers is always time-consuming and expensive. In particular, a drawback of the conventional polymeric hydrogels (OR gels) is mechanically weak and brittle property .
To enhance the strength of OR gels, clay was utilized and demonstrated to be effective [19, 20]. Generally, clay was introduced into the hybrid hydrogels by intercalating cationic surfactants into clay sheets in order to expand the spaces between clay sheets, followed by adding monomers, which were further polymerized to produce hydrogels . In this method, cationic surfactants play the role of intercalative agents, which are indispensable to improve the compatibility of clay with organic compounds. Moreover, the addition of intercalative agents makes the hydrogels complicated. In the past few years, Prof. Haraguchi had prepared nanocomposite hydrogels (NC gels) with high mechanical properties, which were composed of specific polymers and a water-swellable inorganic clay [18, 20, 21, 22]. However, specific polymers were utilized in this system, which may limit its application.
To incorporate inorganic species to supramolecular hydrogels, Jiang’s group proposed a concept of "supramolecular cross-linker" (SCL) . Based on this strategy, SiO2, quantum dots (QDs) and graphene have been successfully introduced into the hybrid hydrogels, which exhibited diverse stimuli-response to chemical, redox and thermo changes [1, 23, 24, 25]. Herein, hybrid hydrogels incorporated clay nanosheets were constructed by the SCL technique (Scheme 1). An azobenzene derivative with a pyridinium cation (Azo-N+) and glycidyl methacrylate modified β-CD (GMA-CD) was firstly synthesized. The complex of GMA-CD with Azo-N+ was anchored onto the clay surface to form a suprastructure bearing a double bond due to the electrostatic interaction between clay and the pyridinium cation of Azo-N+. Finally, the obtained supra-structure acts as a supramolecular cross-linker in its copolymerization with macro-monomer containing PEG leading to a hybrid supramolecular hydrogel, which exhibited good stability and shear thinning properties.
|Scheme 1.Preparation of a hybrid hydrogel based on the supramolecular cross-linker.|
Materials: β-Cyclodextrin (β-CD) was recrystallized three times from water. p-Toluenesulfonyl chloride (TsCl) was recrystallized twice from petroleum ether/acetone mixture. Synthetic hectorite "Laponite XLG" (Rockwood Ltd.: [Mg5.34Li0.66- Si8O20(OH)4]Na0.66, layer size = 20-30 nm Ф × 1 nm, cation exchange capacity, CEC = 104 mequiv 100 g-1), 4-phenylazophenol (Aldrich), N, N, N' , N'0'-tetramethylethylenediamine (TEMED, Aldrich) and glycidyl methacrylate (GMA, Acros) and other reagents were commercially available and used as received.
Characterization techniques: 1H NMR spectra were recorded on a Bruker DMX500. UV-vis spectra were taken on a Perkin-Elmer Lambda 35 UV-vis spectrophotometer. FT-IR spectra were recorded on a Nexus 470 FT-IR spectrometer on powder-pressed KBr pellets. Thermal gravimetric analysis (TGA) measurements were carried out on a Perkin Elmer Pyris-1 series thermal analysis system under a flowing nitrogen atmosphere at a scan rate of 20 ℃ min-1 from 50 ℃ to 700 ℃. The rheological behavior of the hydrogels was investigated by a Malvern rheometer using a 40 mm parallel-plate geometry, cone-plate geometry or cup-bob at 25 ℃. Oscillating strain was fixed at 0.1% for all dynamic tests. ITC was carried out on MicroCal VP-ITC at 25 ℃.
Synthesis of 1-(4-(4-(phenyldiazenyl) phenoxy )butyl ) pyridinium bromide (Azo-N+): The synthetic route of Azo-N+ was illustrated in Scheme 2.
Synthesis of 1-(4-(4-bromobutoxy)phenyl)-2-phenyldiazene (Azo-Br): To an acetone solution of 4-(phenyldiazenyl)phenol (5 g, 25 mmol) and 1, 4-dibromobutane (6 mL, 50 mmol), K2CO3 (7.65 g,= mmol) were added. The reaction mixture was allowed to reflux for 24 h under an atmosphere of nitrogen. After cooling to room temperature, the mixture was filtered, concentrated, and recrystallized in petroleum ether, followed by purification by silica gel column chromatography.
Synthesis of 1-(4-(4-(phenyldiazenyl)phenoxy)butyl)pyridinium bromide (Azo-N+): A solution of Azo-Br (2 g, 6 mmol) in 30 mL DMF and pyridine (2.5 mL, 30 mmol) was allowed to react at 100 ℃ for 24 h. After being cooled to room temperature, the mixture was concentrated and precipitated from petroleum ether, followed by recrystallization from ethanol. The 1H NMR spectrum of Azo-N+ in DMSO (Fig. S1 in Supporting information) demonstrated the successful synthesis.
Synthesis of glycidyl methacrylate modified β-CD (GMA-CD): GMA-CD was synthesized according to the literature .
Preparation of the hybrid hydrogel: A certain amount of clay was added to an aqueous solution of Azo-N+ (0.08 g) and GMA-CD (0.4 g), followed by stirring for 24 h. Then K2S2O8, N, N, N', N'- tetramethylethylenediamine (TEMED) and poly(ethylene glycol) (PEG) macro-monomer were added. The mixture was allowed to react for 6 h under an atmosphere of nitrogen and the hybrid hydrogel was obtained.3. Results and discussion 3.1. Complexation between GMA-CD and Azo-N+
UV-vis spectroscopy could provide an important insight into the complexation behavior between cyclodextrins and guest molecules [27, 28]. To reveal the complex inclusion of GMA-CD with Azo-N+, UV-vis spectra of Azo-N+ with different molar ratio of GMA-CD to Azo-N+ were recorded in Fig. 1.With the increasing molar ratio of GMA-CD, the absorption peak of Azo-N+ red shifted and the intensity enhanced, indicating Azo-N+ formed complexes with GMA-CD, which could be further supported by 1H NMR study. As shown in Fig. 2, the addition of GMA-CD to the aqueous solution of Azo-N+ caused remarkable changes,i.e. the peaks of proton Ha broadened, signal of protons Hb, Hc and Hd shifted to a lower field, with chemical shift changes of 0.02, 0.03 and 0.08 ppm, respectively. Thus the aromatic group formed complexes with GMA-CD, in accordance with other CD/Azo supramolecular system . In order to measure their binding ability, isothermal titration calorimetry (ITC) was performed. Titration of GMA-CD to Azo-N+ was carried out and the heat of dilution of Azo-N+ solution was measured as a control and subtracted from the corresponding data. Using the continuous titration mode, the association constant of Azo-N+ with GMA-CD was calculated as 1.83 × 103 L mol-1 (Fig. S2 in Supporting information), with enthalpy change (△H) of -6.23 × 103 J mol-1 and entropy change (△S) of -5.95 J K-1 mol-1, indicating this complexation was driven by enthalpy.
|Fig. 1.UV–vis spectra of Azo-N+ aqueous solution with molar ratio of GMA–CD to Azo-N+ varying from 0:1 (black curve) to 1:1 (red curve), 3:1 (blue curve), 5:1 (magenta curve) and 10:1 (dark yellow curve).|
|Fig. 2.Partial 1H NMR spectra of Azo-N+ before (black curve) and after (red curve) GMA–CD was added in D2O.|
Now that the complexation of Azo-N+ with GMA-CD was demonstrated, we turned to investigate the interaction between clay nanoplatelets and Azo-N+. Azo-N+ was mixed with clay (synthetic hectorite "Laponite XLG") in water. After centrifugation, the obtained solid was washed with ethanol, which was a good solvent for Azo-N+, leading to the formation of hybrid platelets (named C-Azo for abbreviation) due to the ion-exchange reaction. As shown in the infrared spectra (Fig. 3), in addition to the bands arising from the clay, C-Azo shows characteristic absorbance of Azo-N+,i.e. the C-H bending band at 1250 cm-1 and C-H stretching bands between 2800 cm-1 and 3000 cm-1. Furthermore, the band at 3700 cm-1, arising from O-H stretching of SiOH and MgOH on clay [30, 31, 32], is resolved better in the spectrum of C-Azo due to the decrease of the intensity of the partially overlapped broad peak at about 3500 cm-1, which is ascribed to the O-H stretching of water molecules . The content of Azo-N+ in the modified clay is estimated to be 15% by thermogravity analysis (Fig. S3 in Supporting information).
|Fig. 3.FTIR spectra of clay (blue line), Azo-N+ (black line), and C-Azo (red line).|
The complexes of Azo-N+ with GMA-CD was added into clay aqueous solution to prepare the "supramolecular cross-linker" (SCL). Then hybrid hydrogel was obtained by addition of poly(ethylene glycol) (PEG) macro-monomer, initiator and catalyst into the aqueous solution of "supramolecular cross-linker" (SCL), followed by in-situ free radical polymerization. To optimize the condition of hydrogel formation, different amount of Azo-N+/ GMA-CD complex (equiv. molar ratio of GMA-CD to Azo-N+) was added into the clay solution with the molar ratio of Azo-N+ to cation exchange capacity (CEC) of clay ranging from 0.25 to 0.50 and 0.75. Then PEG macro-monomer was added, and the mixture was initiated by potassium persulfate (K2S2O8, KPS), catalyzed by N, N, N', N'-tetramethylethylenediamine (TEMED). As shown in Fig. 4, hydrogels were obtained when the molar ratio of Azo-N+ to cation exchange capacity (CEC) of clay was no more than 0.50, while suspension was obtained when this value was 0.75, due to fewer amounts of water-soluble cations reserved on clay surface after cation exchange. As control, only viscous liquid rather than hydrogel was obtained without GMA-CD or clay nanosheets, revealing that the supramolecuar crosslinker formed via the host- guest complexation between GMA-CD and Azo-N+ as well as electrostatic interaction between Azo-N+ and clay played important role in the hydrogel formation.
|Fig. 4.Images of hydrogels formation with molar ratio of Azo-N+ to cation exchange capacity (CEC) of clay varying from 0.25 (a) to 0.50 (b) and 0.75 (c).|
A hydrogel forms when elastic (or storage) modulus G' surpasses viscous (or loss) modulus G'' , which can be characterized effectively by rheology measurement . In order to test the mechanical properties of the hybrid hydrogel, amplitude sweep measurement was carried out. As shown in Fig. 5, the elastic modulus G0 was higher than the viscous modulus G'' even when strain γ reached 1.0 and the elastic modulus G' kept a constant of 287 Pa when strain varied from 0.01 to 0.12, demonstrating that such hybrid hydrogel was stable and was not prone to be destroyed under the experimental condition. As control, viscous liquid prepared without clay nanosheets was used to measure the elastic and viscous moduli as well. Its rheology behavior was totally different,i.e. the elastic and viscous moduli were rather low, with G' lower than G'' , revealing its viscous property. Thus, clay could enhance the strength of hydrogels to a certain degree. Furthermore, steady rheology measurement was carried out. As shown in Fig. 6, viscosity of such hybrid hydrogel was as high as 4200 Pa s and dropped to 120 Pa s as the shear rate reached 10 s-1, indicating that the hydrogel exhibited shear thinning property which could be useful for its potential applications in nanomedicine [34, 35, 36].
A hybrid hydrogel based on the "supramolecular cross-linker" (SCL) was constructed. Such "supramolecular cross-linker" (SCL) was formed through the host-guest complexation between GMA- CD and Azo-N+ as well as electrostatic interaction between Azo-N+ and clay. Further addition of PEG macromonomer, initiator (KPS) and catalyst (TEMED) led to the in-situ free radical polymerization and consequently the formation of hybrid hydrogel. Such hybrid hydrogel exhibited good stability as well as shear thinning properties, endowing potential applications in nanomedicine.Acknowledgments
National Natural Science Foundation of China (No. 21204022), Research Fund for the Doctoral Program of Higher Education of China (No. 20120076120005), the Fundamental Research Funds for the Central Universities, and the Large Instruments Open Foundation of East China Normal University (No. 201409251425) are acknowledged for their financial supports.Appendix A. Supplementary data
Supplementary data associated with this article can be found, in the online version, at http://dx.doi.org/10.1016/j.cclet.2016.02.022.
|||M.Y. Guo, M. Jiang, Supramolecular hydrogels with CdS quantum dots incorporated by host-guest interactions, Macromol. Rapid Commun. 31(2010) 1736-1739.|
|||K. Miyamae, M. Nakahata, Y. Takashima, A. Harada, Self-healing, expansioncontraction, and shape-memory properties of a preorganized supramolecular hydrogel through host-guest interactions, Angew. Chem. Int. Ed. 54(2015) 8984-8987.|
|||X.F. Ji, F.H. Huang, A rapidly self-healing supramolecular polymer hydrogel, Sci. China Chem. 58(2015) 436-437.|
|||H. Chen, X. Ma, S.F. Wu, H. Tian, A rapidly self-healing supramolecular polymer hydrogel with photostimulated room-temperature phosphorescence responsiveness, Angew. Chem. Int. Ed. 53(2014) 14149-14152.|
|||X.Y. Dai, Y.Y. Zhang, L.N. Gao, et al., A mechanically strong, highly stable, thermoplastic, and self-healable supramolecular polymer hydrogel, Adv. Mater. 27(2015) 3566-3571.|
|||Y. Chen, X.H. Pang, C.M. Dong, Dual stimuli-responsive supramolecular polypeptide-based hydrogel and reverse micellar hydrogel mediated by host-guest chemistry, Adv. Funct. Mater. 20(2010) 579-586.|
|||X.J. Xu, E.A. Appel, X. Liu, et al., Formation of cucurbit uril-based supramolecular hydrogel beads using droplet-based microfluidics, Biomacromolecules 16(2015) 2743-2749.|
|||S.Z. Zu, B.H. Han, Aqueous dispersion of graphene sheets stabilized by pluronic copolymers:formation of supramolecular hydrogel, J. Phys. Chem. C 113(2009) 13651-13657.|
|||G.C. Yu, X.Z. Yan, C.Y. Han, F. Huang, Characterization of supramolecular gels, Chem. Soc. Rev. 42(2013) 6697-6722.|
|||X.Z. Yan, F. Wang, B. Zheng, F. Huang, Stimuli-responsive supramolecular polymeric materials, Chem. Soc. Rev. 41(2012) 6042-6065.|
|||H. Komatsu, S. Matsumoto, S. Tamaru, et al., Supramolecular hydrogel exhibiting four basic logic gate functions to fine-tune substance release, J. Am. Chem. Soc. 131(2009) 5580-5585.|
|||M. Ikeda, T. Tanida, T. Yoshii, et al., Installing logic-gate responses to a variety of biological substances in supramolecular hydrogel-enzyme hybrids, Nat. Chem. 6(2014) 511-518.|
|||K.M. Huh, Y.W. Cho, H. Chung, et al., Supramolecular hydrogel formation based on inclusion complexation between poly(ethylene glycol)-modified chitosan and acyclodextrin, Macromol. Biosci. 4(2004) 92-99.|
|||J.H. Yu, H.L. Fan, J. Huang, Fabrication and evaluation of reduction-sensitive supramolecular hydrogel based on cyclodextrin/polymer inclusion for injectable drug-carrier application, Soft Matter 7(2011) 7386-7394.|
|||A. Harada, Y. Takashima, M. Nakahata, Supramolecular polymeric materials via cyclodextrin-guest interactions, Acc. Chem. Res. 47(2014) 2128-2140.|
|||M. Nakahata, Y. Takashima, H. Yamaguchi, A. Harada, Redox-responsive selfhealing materials formed from host-guest polymers, Nat. Commun. 2(2011) 487-502.|
|||H. Yamaguchi, Y. Kobayashi, R. Kobayashi, et al., Photoswitchable gel assembly based on molecular recognition, Nat. Commun. 3(2012) 603.|
|||K. Haraguchi, T. Takehisa, Nanocomposite hydrogels:a unique organic-inorganic network structure with extraordinary mechanical, optical, and swelling/deswelling properties, Adv. Mater. 14(2002) 1120-1124.|
|||M. Alexandre, P. Dubois, Polymer-layered silicate nanocomposites:preparation, properties and uses of a new class of materials, Mater. Sci. Eng. 28(2000) 1-63.|
|||K. Haraguchi, Nanocomposite hydrogels, Curr. Opin. Solid State Mater. Sci. 11(2007) 47-54.|
|||K. Haraguchi, H.J. Li, Control of the coil-to-globule transition and ultrahigh mechanical properties of PNIPA in nanocomposite hydrogels, Angew. Chem. Int. Ed. 44(2005) 6500-6504.|
|||K. Haraguchi, Soft nanohybrid materials consisting of polymer-clay networks, Adv. Polym. Sci. 267(2015) 187-248.|
|||J.H. Liu, G.S. Chen, M.Y. Guo, M. Jiang, Dual stimuli-responsive supramolecular hydrogel based on hybrid inclusion complex (HIC), Macromolecules 43(2010) 8086-8093.|
|||J.H. Liu, G.S. Chen, M. Jiang, Supramolecular hybrid hydrogels from noncovalently functionalized graphene with block copolymers, Macromolecules 44(2011) 7682-7691.|
|||P. Du, G.S. Chen, M. Jiang, Electrochemically sensitive supra-crosslink and its corresponding hydrogel, Sci. China Chem. 55(2012) 836-843.|
|||Y.Y. Liu, X.D. Fan, L. Gao, Synthesis and characterization of β-cyclodextrin based functional monomers and its copolymers with N-isopropylacrylamide, Macromol. Biosci. 3(2003) 715-719.|
|||A.M. Sanchez, R.H. de Rossi, Effect of β-cyclodextrin on the thermal cis-trans isomerization of azobenzenes, J. Org. Chem. 61(1996) 3446-3451.|
|||Y. Liu, Y.L. Zhao, H.Y. Zhang, et al., Spectrophotometric study of inclusion complexation of aliphatic alcohols by β-cyclodextrins with azobenzene tether, J. Phys. Chem. B 108(2004) 8836-8843.|
|||X.J. Liao, G.S. Chen, X.X. Liu, et al., Photoresponsive pseudopolyrotaxane hydrogels based on competition of host-guest Interactions, Angew. Chem. Int. Ed. 49(2010) 4409-4413.|
|||N.N. Herrera, J.M. Letoffe, J.P. Reymond, E. Bourgeat-Lami, Silylation of laponite clay particles with monofunctional and trifunctional vinyl alkoxysilanes, J. Mater. Chem. 15(2005) 863-871.|
|||S. Borsacchi, M. Geppi, L. Ricci, G. Ruggeri, C.A. Veracini, Interactions at the surface of organophilic-modified laponites:a multinuclear solid-state NMR study, Langmuir 23(2007) 3953-3960.|
|||X.J. Liao, G.S. Chen, M. Jiang, Pseudopolyrotaxanes on inorganic nanoplatelets and their supramolecular hydrogels, Langmuir 27(2011) 12650-12656.|
|||Y.F. Xi, Z. Ding, H.P. He, R.L. Frost, Infrared spectroscopy of organoclays synthesized with the surfactant octadecyltrimethylammonium bromide, Spectrochim. Acta, A:Mol. Biomol. Spectrosc. 61(2005) 515-525.|
|||J. Araki, K. Ito, Recent advances in the preparation of cyclodextrin-based polyrotaxanes and their applications to soft materials, Soft Matter 3(2007) 1456-1473.|
|||J. Li, Cyclodextrin inclusion polymers forming hydrogels, Adv. Polym. Sci. 222(2009) 175-203.|
|||X.P. Ni, A.L. Cheng, J. Li, Supramolecular hydrogels based on self-assembly between PEO-PPO-PEO triblock copolymers and a-cyclodextrin, J. Biomed. Mater. Res. A 88(2009) 1031-1036.|