Article pubs.acs.org/Macromolecules
Supramolecular Hydrogel Formation Based on Tannic Acid Hailong Fan,† Le Wang,† Xunda Feng,‡ Yazhong Bu,§ Decheng Wu,§ and Zhaoxia Jin*,† †
Department of Chemistry, Renmin University of China, Beijing 100872, P. R. China Department of Chemical and Environmental Engineering, Yale University, New Haven, Connecticut 06511, United States § Beijing National Laboratory for Molecular Sciences, State Key Laboratory of Polymer Physics & Chemistry, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, P. R. China ‡
S Supporting Information *
ABSTRACT: The development of facile and versatile strategies with low-cost for hydrogel construction is of tremendous scientific interest. Herein, we demonstrate that naturally derived, cost-effective tannic acid (TA) can be an efficient gelation binder for the hydrogel formation with a series of commercially available water-soluble polymers. With a five-polyphenol-arm structure, TA molecules are able to grasp polymer chains through either hydrogen or ionic bonds and cross-link them together by coordinate bonds in the presence of Fe(III) ions. These two interactions can be elegantly balanced by tuning the weight ratios of polymer/TA and TA/ Fe3+, which is the key point for the construction of supramolecular hydrogels. The supramolecular hydrogels exhibit multiple functionalities including mechanical tenability, rapid self-healing, pH-stimuli responsiveness, and free radical scavenging abilities. TA as a dynamic and versatile catechol group modifier provides a simple path to the construction of multifunctional hydrogels, which shows obvious advantages such as easy and green processing, low cost, and large-scale preparation.
1. INTRODUCTION Supramolecular materials based on noncovalent interactions present superior performances,1−5 such as stimuli-responsive,6−9 self-healing,10−12 and shape-memory properties,13−15 which are highly desirable for biomedical applications. Controllable cross-linking of polymer chains into 3D networks is a general way to construct supramolecular gels, which requires the polymers to possess moieties capable of self-assembling into dynamic cross-links.16,17 Such moieties commonly employed to assist the self-assembly by H-bonding, ionic, and host−guest interactions are quadruple H-bonding units,18−20 polyelectrolyte blocks,21−24 and cyclodextrin groups.25−27 As one might expect, some desired moieties in general do not exist in most of the water-soluble polymers. A concerted effort is therefore required, for example, through grafting of the useful moieties onto polymer chains. Recently, it has been a hot topic to utilize metal−ligand interactions for cross-linking in hydrogel construction, especially the catechol−Fe3+ coordinate bonds inspired by the self-repair of mussel threads, in which case catechol moieties (e.g., DOPA) have been grafted onto polymer chains to form the dynamic coordinate cross-links with the aid of Fe ions.28−32 However, such strategies of moiety grafting often rely on precise design of chemistry as well as time-consuming synthesis and purification, and sometimes, they are limited by possible use of expensive reagents and the difficulty in scaling up.20,24,29,33,34 In addition, other factors © XXXX American Chemical Society
affecting the supramolecular self-assembly, such as moiety density, bonding strength, temperature, and pH, must be finely balanced during the gelation.12,35,36 Hence, the facile and versatile strategy for synthesis of supramolecular hydrogel with low-cost binders becomes highly attractive. Tannic acid (TA) is a naturally derived polyphenolic compound and possesses diverse bonding abilities. TA is capable of complexing or cross-linking macromolecules at multibinding sites through multiple interactions, including hydrogen and ionic bonding and hydrophobic interactions.37−39 It also can coordinate with metal ions to form TA−metal networks.40,41 Therefore, TA is an ideal gelation binder in hydrogel formation. However, TA-based gels have been only reported as membrane-like gels generated via layerby-layer assembly.42−44 Although TA−macromolecule complexes have been studied for decades, directly cross-linking polymer solution into hydrogel is still a challenge because the strong multiple interactions often lead to coacervation rather than network formation.39,45−47 The only successful case reported is DNA−TA hydrogels based on the H-bonding between these two macromolecules, in which the high molecular weight of the DNA used in the study may contribute Received: September 27, 2016 Revised: December 24, 2016
A
DOI: 10.1021/acs.macromol.6b02106 Macromolecules XXXX, XXX, XXX−XXX
Article
Macromolecules
Figure 1. Chemical structures of (a) tannic acid, (b) PVP, (c) PEG, (d) PSS, and (e) PDDA.
a balance for the strong interactions.48 Therefore, delicate control over the interactions between polymers and TA molecules represents a nontrivial challenge, which has significantly hampered the development of high-performance TA-based hydrogels. Here, we report our efforts to effectively circumvent the above-mentioned challenge by leveraging the versatile bonding abilities of TA. The critical feature of TA is its ability to endow polymers with functional groups required for the hydrogel formation and further cross-link the system into network by introducing coordinate interactions with metal ions. Polymers can be simply functionalized with catechol/pyrogallol groups by TA in aqueous solutions through H-bonding or ionic interactions instead of covalent grafting.49−51 Such polymer/ TA complexes with water cannot form hydrogels but often display either homogeneous solutions or coacervation. However, addition of Fe3+ strikingly transforms the homogeneous polymer/TA complex solutions into hydrogels by pHtunable coordinate interactions between TA and Fe3+. This method provides a controllable solution for TA-based hydrogel construction using readily accessible materials and simple procedures. A series of commercially available watersoluble polymers such as polyvinylpyrrolidone (PVP), poly(ethylene glycol) (PEG), poly(sodium 4-styrenesulfonate) (PSS), and poly(dimethyldiallylammonium chloride) (PDDA) are well suited in the fabrication of TA-based hydrogels. We systematically investigate the phase behavior of the polymer/ TA binary complexes in aqueous solutions, i.e., homogeneous solutions versus coacervation, under different composition ratios of TA/polymer and concentrations of the complexes. For the homogeneous polymer/TA solutions, we demonstrate our success in formulating polymer/TA/Fe3+ ternary complexes to form hydrogels. In these hydrogels, TA interacts with polymers by H-bonds or ionic bonds and connects each other by coordinate bonds in the presence of metal ions. The supramolecular hydrogels show the mechanical tenability, rapid self-healing, pH-stimuli responsive, and free radical scavenging abilities. Moreover, a large amount of hydrogels can be prepared easily at the laboratory scale at once since no complicated synthetic procedure is involved.
acid (TA, ACS reagent), and 2,2′-azino-bis(3-ethylbenzthiazoline-6sulfonic acid) (ABTS, ≥98%) were purchased from Sigma-Aldrich Inc. Polyvinylpyrrolidone (PVP, average Mw 58 000) and poly(styrenesulfonic acid) sodium salt (PSS, Mw 70 000) were purchased from Alfa Aesar Inc. Poly(ethylene glycol) (PEG, Mn 20 000), 2,2-diphenyl-1picrylhydrazyl (DPPH, 96%), anhydrous ferric chloride (FeCl3, ≥99.9%), potassium persulfate (K2S2O8), and sodium hydroxide (NaOH) were purchased from Aladdin Co. (Shanghai, China). Ethanol (AR) was purchased from Sinopharm Chemical Reagent Co. Ltd. All these reagents are used as received. All solutions were prepared by using deionized water. Hydrogel Formation. The hydrogels were formed by dissolving polymer, TA, and FeCl3 in deionized water at desired concentrations. The mixture spontaneously cross-linked into hydrogel by adjusting the pH to ca. 6 with NaOH aqueous solution (3 M). We named the hydrogel as POLYMERxTAy(a:b), where x and y are the weight (mg) of polymer and TA in 1 mL of H2O, respectively; a:b is the molar ratio of TA:Fe3+. Hydrogel formation based on PVP, PEG, and PSS: Take PVP400TA40(3:5) as an example: 40 mg of TA was first dissolved in 0.2 g of water, and then PVP(aq) (400 mg of PVP in 0.75 g of water) was added into TA(aq). After stirring, the mixture was a transparent solution with light yellow color. Then 0.05 g of FeCl3(aq) (contain 6.4 mg of FeCl3) was added into the PVP−TA solution under stirring (the final molar ratio of TA:Fe3+ is 3:5). The mixture spontaneously cross-linked into hydrogel by adjusting pH to 6.1 using NaOH (3 M). Hydrogel formation based on PDDA: 30 mg of TA was first dissolved in 0.2 g of water, and then 0.75 g of PDDA(aq) (20 wt %, contains 150 mg of PDDA) was added into TA(aq). After totally dissolved under stirring, 0.05 g of FeCl3(aq) (contains 4.8 mg of FeCl3) was added into the PDDA−TA solution with stirring (the final molar ratio of TA:Fe3+ is 3:5). The mixture spontaneously cross-linked into PDDA150TA30(3:5) hydrogel by adjusting pH to 6.1 using NaOH (3 M). General Characterizations. The pH of the hydrogels was measured using a Mettler-Toledo LE427 pH puncture electrode. Infrared spectra were measured by using a Fourier transform infrared spectrometer (FTIR, Shimadzu Cor. IRPrestige-21). Raman spectra were measured by using a Raman microscope (Horiba Scientific XploRA PLUS) with 785 nm laser light as excitation source, and the laser power was set at 25 mW. Rheological Test. The mechanical properties of the hydrogels were tested using a rheometer (Thermo Scientific HAAKE) with parallel plate geometry (35 mm diameter rotating top plate). The mechanical properties were measured by performing frequency sweeps in the linear viscoelastic range (LVR) at a strain of 1%, while monitoring the storage modulus (G′) and loss modulus (G″). The amplitude sweep was investigated by straining the gels from 1%−
2. EXPERIMENTAL SECTION Materials. Poly(dimethyldiallylammonium chloride) solution (PDDA, average Mw 400 000−500 000, 20 wt % in H2O), tannic B
DOI: 10.1021/acs.macromol.6b02106 Macromolecules XXXX, XXX, XXX−XXX
Article
Macromolecules
Figure 2. FTIR spectra of TA, polymer, and polymer−TA mixture: (a) PVP/TA system, (b) PEG/TA system, (c) PSS/TA system. In the partially magnified spectra, the peaks (green line) were fitted by Gaussian function (red line).
Figure 3. Phase diagrams of (a) PVP/TA mixture, (b) PEG/TA mixture, (c) PSS/TA mixture, and (d) PDDA/TA mixture. The inset pictures in (a) are the digital photos of PVP/TA coacervate (PVP400TA100) and liquid (PVP400TA40) samples. 1000% strain at a frequency of 1 Hz. The self-healing property was investigated by straining the gels under an alternatively changing amplitude of oscillatory force at 1 Hz. The experiments were performed at 25 °C. DPPH Assay for Antioxidant Activities of Different Systems. A fresh DPPH/ethanol (0.1 mM) solution was used for the measurements. TA, TA/Fe(III), PDDA/TA, and PVP/TA aqueous solution were prepared in which the concentration of TA was kept at 1 mg mL−1. The pH values in TA aqueous solution, PDDA/TA (3.75:1 in weight ratio), and PVP/TA (10:1 in weight ratio) solutions were kept at 6.8, but TA/Fe(III) solutions (molar ratio 3:5) at pH 3 and 6.4 were both tested to identify the effect of pH variation on free radical scavenging activity. 50 μL of solution was added in 3 mL of DPPH solution. Scavenging activity was evaluated by measuring the absorbance change at 517 nm after the tested mixture was kept in
the dark for 20 min. For hydrogel: a different amount of hydrogel samples was added in 3 mL of DPPH solution. Scavenging activity was evaluated by measuring the absorbance change at 517 nm after the tested mixture was kept in the dark for 1 h. DPPH radical scavenging activity was calculated as I = [1 − (Ai − Aj)/Ac] × 100%, where Ac is the absorbance of DPPH solution without test sample, Ai is the absorbance of test sample mixed with DPPH solution, and Aj is the absorbance of the test sample without DPPH solution. Each sample was tested three times. ABTS Assay for Antioxidant Activities of Hydrogels. The ABTS•+ was produced by reacting 7.4 mM ABTS in H2O with 2.6 mM potassium persulfate (K2S2O8), stored in the dark at room temperature for 4 h. Before usage, the ABTS•+ solution was diluted to get an absorbance of 0.70 ± 0.02 at 734 nm in ethanol. The hydrogel (10 C
DOI: 10.1021/acs.macromol.6b02106 Macromolecules XXXX, XXX, XXX−XXX
Article
Macromolecules
Figure 4. (a) Viscosities of polymer aqueous solutions and polymer−TA mixtures under different pH conditions at an angular frequency of 10 rad s−1 and a strain of 1%. (b) Storage G′ and loss G″ moduli of PDDA150TA30 hydrogel with angular frequency sweep. The inset photos in (b) are (i) initial PDDA150TA30 mixture at pH 3.02, (ii) the mixture has changed to hydrogel after adjusting the pH to 6.28, and (iii) the mixture was kept for 2 days. mg) was added into 3 mL of ABTS solution and kept in the dark for 20 min before measuring.
concentration, which happens in a higher TA/PEG weight ratio with the increasing of PEG concentration. For PSS/TA, no coacervate was detected under experimental condition even though TA/PSS weight ratio is up to 2 (Figure 3c). For PDDA/TA, coacervation occurs when the TA/PDDA weight ratio is up to ca. 0.7−1 (Figure 3d). The difference of coacervation boundaries of tested polymers is caused by multifactors, such as the type of polymers, molar weight of polymers, the concentration, the interactions between polymer and TA, etc. This result indicates that increasing polymer concentration improves the controllability of the interaction between polymer and TA. In the liquid region of Figure 3, the polymers interacted with large amount of TA, or in other words, these polymers are functionalized with large amount of pyrogallol moieties, which provide precondition for gel construction. The pH is another factor that influenced the polymer/TA interactions. As a polyphenol, the form of phenol group (protonated or ionized form) of TA is depending on the solution pH (pKa ∼ 8.5 for TA), which further influences the interaction between polymer and TA.38,39 At acidic conditions, the phenol groups of TA are mainly protonated, which are excellent hydrogen donors for binding with hydrogen-accepting polymers but have weak interaction with cationic polymers. Whereas, at neutral condition, the phenol groups prefer to be ionized, and as a result, the H-bonds between polymer and TA are reduced while the ionic bonds are enhanced between cationic polymer and TA. Erel-Unal and Sukhishvili have systematically studied the association of TA with neutral or charged polymers in solution.39 In their study, PVP/TA formed an insoluble complex at acid conditions (pH 2), but the solution became clear under pH 7.4 due to the ionization of TA. On the contrary, positively charged polymer Q90/TA was solution at pH 2 but changed to insoluble complex in pH 7.5 condition. pH-influenced H-bond interactions of polymer/TA system were also reported by Kharlampieva et al.42,43 In their studies, the thickness and permeability of polymer/TA membrane can be tuned by pH-triggered disruption of intramolecular hydrogen bonds of TA molecules. In our case, the viscosity of initial polymer solution is not affected by the change of pH value (Figure 4a and Figure S1). Introducing TA dramatically increases the viscosity of polymer solution because of the strong interactions between the phenol groups and polymers. The pH value of initial polymer/TA mixtures (in liquid region of Figure 3) is lower than 4 because of the addition of TA. The mixtures have shown clear changes in their viscosities while they were neutralized to pH 6−7. For H-bond
3. RESULTS AND DISCUSSION Polymer/TA Bicomponent System. The interaction between polymer and TA is influenced by the interaction types (H-bond or ionic bond, depending on the chemical structure of polymers), concentrations of polymer and TA, and pH.38,39,52 Figure 1 presents the chemical structures of TA and polymers in our study. The carbonyl,39 ether,53 and sulfonic acid54 groups of PVP, PEG, and PSS, respectively, interact with TA through an H-bond. Cationic polyelectrolyte PDDA interacts with TA by an ionic bond.38 The formation of Hbonds between PVP, PEG, PSS, and TA was confirmed by FTIR characterizations (Figure 2). For PVP−TA, the prominent peak at 1666 cm−1 belongs to the carbonyl stretching of amide in PVP.55 In the complex, this peak shifts to the lower wavenumber at 1660 cm−1 due to the H-bonds between −CO groups and −OH groups.52 The CO vibration in TA is increased from 1713 to 1725 cm−1 (PVP− TA), indicating that the strengthened vibrational energy of the CO bonding is affected by interacting with the hydrogen donor.56 For PEG−TA, the strength of free −OH (3436 cm−1) of TA decreases with the enhancement of hydrogen-bonded −OH (3201 cm−1). The CO vibration in TA is increased from 1713 to 1730 cm−1 (PEG−TA), which is similar to the PVP−TA complex. These two chemical energy shifts indicate the formation of H-bond between TA and PEG, which corresponds to the previous study.53 For PSS−TA, the peaks at 1042 and 1010 cm−1 belong to the sulfonate groups in PSS.57 In the complex, these peaks shift to the lower wavenumber 1037 and 1008 cm−1 due to the H-bonding between −SO groups and −OH groups.58,59 The second factor is the concentrations of TA and polymers. It is worth noting that the concentration of polymers in previous studies of TA−polymer coacervation was in a low range (
