Supramolecular Copolymerization of Short Peptides and

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Supramolecular Co-Polymerization of Short Peptides and Polyoxometalates: toward the fabrication of Underwater Adhesives Jing Xu, Xiangyi Li, Xiaodong Li, Bao Li, Lixin Wu, Wen Li, Xiaoming Xie, and Rong Xue Biomacromolecules, Just Accepted Manuscript • DOI: 10.1021/acs.biomac.7b00817 • Publication Date (Web): 07 Sep 2017 Downloaded from http://pubs.acs.org on September 8, 2017

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Supramolecular Co-Polymerization of Short Peptides and Polyoxometalates: toward the fabrication of Underwater Adhesives Jing Xu,a Xiangyi Li,a Xiaodong Li,a Bao Li,a Lixin Wu,a Wen Li,a* Xiaoming Xie,a Rong Xue*b a

State key laboratory of supramolecular structure and materials, Institute of theoretical

chemistry, Jilin University, Qianjin Avenue 2699, Changchun 130012, China. b

National Analytical Research Center of Electrochemistry and Spectroscopy, Changchun

Institute of Applied Chemistry, Chinese Academy of Sciences, 5625 Renmin Street, Changchun 130022, China.

ABSTRACT. Peptide assembly has reached exquisite levels of efficiency in the creation of bioactive materials. However, we have not yet been able to take what we have learned from peptide assembly to develop a general strategy for the fabrication of biomimetic underwater adhesives, which retain significant advantages as medical glue for clinical treatment. Herein we report a simple approach to prepare peptide-based adhesives through the supramolecular polymerization of cationic peptides drove by polyoxometalates (PMs). Mass spectra, Fouriertransform infrared spectra and

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W NMR spectra confirmed the structural integrity of peptides

and PMs during the co-assembly process. Scanning electron microscopy demonstrated that the multivalent interactions between peptides and polyoxometaltes led to the formation of robust 3D

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network structures. The rheological study revealed that the peptide/PM assemblies exhibited mechanically rigid gel-like behavior and self-healing property. Interestingly, the assemblies showed the capacity to adhere various wet solid materials under waterline. The shear strength of the peptide-based adhesives are stronger than that of the commercially available fibrin glue. This finding is exciting and serves to expand our capability of the fabrication of peptide-based materials.

KEYWORDS. short peptides, polyoxometalates, co-assembly, supramolecular polymerization, underwater adhesion.

INTRODUCTION Underwater adhesion is an attractive theme in the fields of materials science, biological and supramolecular chemistry, because of the great promise in hemostasis, repair of living tissues, fixing bones.1-5 In this framework, aquatic organisms are true experts, which evolved unique ability to fix themselves on diverse solid surface through secreting adhesive protein complexes under the waterline.6-9 These proteins usually fold and/or self-assemble into 3D networks to improve the internal cohesion forces as well as the bulk mechanical strength.10-12 Concomitantly, the highly concentrated functional residues (such as polar, hydroxylated or phosphorylated groups) contribute to the enhanced interfacial binding through polyvalent interactions.2,13 The primary structures of the natural adhesive proteins are strongly dependent on the type of aquatic organisms. For example, mussel adhesive proteins carry high content of dihydroxyphenylalanine (DOPA), for its capabilities of high surface affinity and bulk crosslinking.[6,14,15] Sandcastle worms attach to wet surface through delivering adhesive coacervate consisting of oppositely charged protein complexes.16,17 Barnacle’s adhesion does not rely on the fractions of


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hydroxylated or phosphorylated amino acid residues. Their adhesive proteins are consist of completely natural amino acids.9,

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Inspired by these natural sources, various artificial

polymers have been prepared to perform the underwater adhesion through introducing the concept of catechol chemistry and/or the ionic cross-linking of polyelectrolytes into the molecular design.1,2,5,20-26 However, the preparation of many those materials usually involves multi-step procedures, time consuming process, harsh conditions and toxic reagents. Recently, the preparation of underwater adhesive has been revolutionized with the advent of co-assembly of natural constitutes and biocompatible polymers.23,24,27 Especially, the wet adhesives obtained from the aqueous co-assembly of tannic acid with poly(ethylene glycol) have been demonstrated as a biodegradable patch for the in vivo detection of gastroesophageal reflux disease.27 These pioneering investigations will open up a wide variety of possibilities for the creation of adhesives through a very flexible choice of biocompatible constitutes. Peptides, acting as a kind of versatile building blocks, hold salient advantages, including biocompatibility, biodegradability, molecular diversity, easy synthesis and tunable bioactivity from a biological aspect.28-34 Peptide assemblies have been extensively investigated to fabricate nanostructures,35-38 catalysis,39,40 sensors,41,42 and bioactive materials.43-46 Although, peptide segments, encoding the polar and charged side chains, are necessary to produce interfacial adhesion,11 they are far from being optimized and explored to produce biomimetic adhesives. From molecular design and synthesis aspect, short peptide molecules are expected to be much easier than natural proteins. In the viewpoint of medical applications, peptides are more compatible and safe than most covalent polymers. Several research groups reported that some polypeptides derived from natural adhesive proteins showed the propensity to self-assembly into


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wet adhesives.11,47,48 Despite these advances, we are still lacking a simple and universial strategy to create short peptide-based underwater adhesives. To address this issue, short peptide segments have to assemble into soft materials with robust 3D network structures to improve their bulk mechanical strength. Recently, ionic self-assembly of cationic peptides and anionic objects has been explored as a promising approach to fabricate functional assemblies in aqueous solution.30,

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In particularly, stable coacervates,53,54

collagen helices55 and membranes56 have been prepared through multivalent electrostatic interactions between cationic peptides and polyanions. Comparing with conventional polyanions, polyoxometaltes (PMs) possess unique properties, such as high ionization propensity in water, well-defined topology, rigid conformation, atomically precise ensembles, single size distribution and bioactivity.57-59 Baroudi and coworkers have demonstrated that rigid PM nanoclusters could improve the mechanical strength of gelatin hydrogel.60 We have reported that the aqueous assembly of cationic peptides and PMs resulted in the formation of stable nanofibers,61,62 and functional gel materials.63 These findings led us to consider that the co-assembly of PM clusters and short peptides might be a rational method to generate biomimetic adhesives. In work described here, several commercially available peptides (Pep1, Pep4, Pep5 and Pep6), carrying basic amino acid residues and carboxyl side groups, were utilized (Figure 1a). It is expected that the protonated basic residues can electrostatically interact with PM clusters (Figure 1b) to form non-covalently crosslinking network structures, and the carboxyl groups of the peptides can bond to diverse solid surface. We illustrate that the supramolecular co-polymerization of short peptides and PM clusters allowed us to generate underwater adhesives. The present work raises a significant potential in the design and development of novel peptide-based functional materials.


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Figure 1. Schematic structures of short peptides (a) and the polyoxometalates (b). EXPERIMENTAL SECTION Materials. Keggin-type polyoxometalates H4SiW12O40 (SiW) was purchased from Aladdin GmbH. K6CoW12O40 (CoW)64 and H5PMo10V2O40 (PMoV)65 were prepared according to reported procedures. Pep1 (Ac-EEMQRRAD-NH2, pI = 4.7) and Pep4 (Ac-EEMQRR-NH2, pI = 6.24) are commercially anti-wrinkle peptides, which were obtained from Acrose Biotech. Pep5 (RRDVY, pI = 8.6) is a commercially immunomodulatory pentapeptide, which was purchased from Macklin. Pep6 (pI = 6.7) is a small naturally occurring dipeptide composed of alphahistidine and beta-alanine, which could be purchased from Macklin. All the commercially available peptides were used without further purification. Synthesis of Pep2 and Pep3. Pep2 (Ac-EEMQREAD-NH2, pI = 4.0) and Pep3 (AcEEMQEEAD-NH2, pI = 3.5) were synthesized by a standard 9-fluorenylmethoxycarbonyl


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(Fmoc) solid-phase method. The Rink amide MBHA resin was used for peptide synthesis, and HBTU was used as activated reagent. Briefly, the synthesis was initiated using 60 µmol of Fmoc-Rink Amide MBHA resin, and the chain extension was accomplished using an in situ neutralization/HBTU activation procedure, where 3-fold excess of amino acid was pre-activated with 2.7 equiv of HBTU and 6 equiv of DIPEA in DMF (1 mL) for 5 min before it was added to the resin. Each coupling step took a minimum of 7 min. The cycle of Fmoc deprotection and coupling with N terminal-protected amino acids was repeated until the designed peptide sequences were obtained. After Fmoc deprotection of the N-terminal residue, the N terminus of peptide was capped with acetic anhydride. The peptide segments were cleaved from the resin manually by treatment with trifluoroacetic acid (TFA), 1,2-ethanedithiol, and thioanisole (95:2.5:2.5) for 3 h under constant agitation in a rotary shaker (37 oC, 200 rpm of constant agitation). The resultant crude peptides were purified by reverse-phase High Performance Liquid Chromatography (HPLC) on C18 column (Vydac, USA) using binary gradient of water to acetonitrile in the presence of 0.1% TFA, and the column eluents were monitored by UV absorbance at 215 nm. Preparation of Peptide/PM Underwater Adhesives. Polyoxometalates (PMs) and short peptides were dissolved in deionized water, respectively. Then the aqueous solutions of short peptides were added to the solutions of PMs with stirring. The pH value of the final solutions were controlled at around 2 using diluted HCl solution or NaOH solution. Underwater adhesives were immediately observed at the bottom of the reaction glass bottle. All the peptides/PMs adhesive were characterized by Elemental analysis (see supporting information), and Thermogravimetric analysis (Figure S1).


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Primary Characterization of Peptide/PM Adhesives. The adhesives were characterized by matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry (MALDI-TOF MS), Fourier transform infrared (FT-IR) spectroscopy,

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W NMR, Elemental analysis (EA), and

Thermogravimetric analysis (TGA). The mass spectra were recorded using an autoflex TOF/TOF (Bruker, Germany) mass spectrometer, equipped with a nitrogen laser (337 nm, 3 ns pulse). The mass spectrometer was operated in the positive ion reflector mode. The turbid solution of the adhesive was used directly for measurement with α-cyano-4-hydroxycinnamic acid (CHCA) matrix. FT-IR spectra were carried out on a Bruker Optics Vertex 80V FT-IR spectrometer equipped with a DTGS detector (32 scans) at a resolution of 4 cm–1 by using KBr pellet. The individual SiW and the Pep1/SiW adhesive were dissolved in deuterated dimethylsulfoxide (DMSO-d6), respectively, and the 183W NMR spectra were carried out on a Bruker AMX 300 spectrometer with 2.0 M Na2WO4 aqueous solution as an external reference. Elemental analysis (C, H, N) was performed on Vario Micro from Elementar Germany. Thermogravimetric analysis (TGA) was performed on Q500 Thermal Analyzer (New Castle TA Instruments) in flowing nitrogen with a heating rate of 10 oC/min in the temperature range from 25 to 900 oC. Scanning Electron Microscopy. Scanning electron microscopy (SEM) images were acquired on a JEOL FESEM 6700F electron microscope with an accelerating voltage of 15 kV. SEM samples were prepared by casting the heated turbid solutions of adhesives on silicon slices, and then lyophilized under vacuum for 1 day. Cross sections of the adhesives were mounted onto glass slices and sputter-coated with gold. Evaluation of Rheological Behavior. The rheological properties of the Pep1/SiW adhesive were characterized at 25 °C using a TA instrument AR2000 controlled-stress rheometer equipped with 20 mm stainless steel parallel plate geometry. A gap distance of 0.5 mm was used for all


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experiments. Oscillatory frequency sweep data were collected in the range from 0.1 to 100 rad/s, and the strain amplitude was fixed at 1%. The self-healing property of the adhesive was monitored as follows: the network structure of Pep1/SiW was first broken using 200% strain amplitude, then tracking the recovery in G’ over time by continuing to oscillate the adhesive at low (1%) strain amplitude. All the measurements were repeated a minimum of three times. Shear Adhesion Strength. Lap shear adhesion testing was carried out on Instron 5944 materials testing system. The as-prepared peptide/PM adhesives were scraped from the bottom of the glass bottle and used to adhere two rectangle-shaped substrate surfaces (glass, aluminum, polyether-ether-ketone). A piece of peptide/PM adhesive was placed between the two plates under deionized water and compressed for 15 min using 35 kPa of pressure, which promoted the adhesive to uniformly form a lap shear joint of 1.8 × 2 cm2. The adhered plates were fully immersed in water holder and then clamped into the grips of the materials testing system. Both force and displacement were recorded under waterline using a 100 N load cell and a crosshead speed of 10 mm/min. The shear adhesion strength was obtained from the maximum force at joint failure divided by the overlapping contact area. Each sample was tested on the basis of five replicate measurements and averaged. Fibrin glue was used as a positive control to compare with the peptides/PMs adhesives. RESULTS AND DISCUSSION Preparation and Characterization of Pep1/SiW adhesive. The synthetic procedure is extremely easy: Pep1 (404.7 mg Pep1 dissolved in 0.5 mL deionized water) and H4SiW12O40 (SiW, 540 mg SiW dissolved in 1.0 mL of deionized water) aqueous solution were prepared, respectively. Then the solution of Pep1 was added to the solution of SiW with shaking, and the


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final pH value of the mixed solution was controlled at ~2. As shown in Figure 2a, the mixed solution immediately changed from transparent to a highly viscous water-immiscible adhesive (Pep1/SiW).

Figure 2. Digital images of Pep1, SiW and Pep1/SiW in water (a), and the schematic drawing of the self-assembled network structures of Pep1/SiW (b). We first evaluate the integrality of the components by MALDI-TOF MS, 183W NMR and FT-IR spectra. MALDI-TOF-MS spectra (Figure S2) revealed that the Pep1 segment did not decomposed during the co-assembly process. 183W NMR spectra of Pep1/SiW adhesive in dmsod6 presented one peak at -93.86 ppm (Figure 3), which was in line with that of SiW alone in the same solvent. This result indicated that the SiW cluster remained its Keggin-type structure within the adhesive matrix.


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Figure 3. 183W NMR spectra of Pep1/SiW (39657 scans) and SiW alone (5808 scans) in dmsod6. The signal at 0 ppm is the external reference (2.0 M Na2WO4 aqueous solution). The FT-IR spectra (Figure S3) of SiW alone in the low-frequency-region showed typical bands at 981, 926, 883, 779 cm-1, which were assigned to νas (W = Od), νas (Si-Oa), νas (W-Ob-W), νas (W-Oc-W) stretching vibration modes, respectively.66 In the case of lyophilized Pep1/SiW adhesive (Figure S3), the stretching vibration modes of SiW shift to 974, 922, 882, 800 cm-1, respectively. The band shift arose from the non-covalent interactions between Pep1 and SiW.66,67 Comparing with the amide I band (1654 cm-1) of individual Pep1, the Pep1/SiW powder showed a similar band at 1659 cm-1 (Figure S3), demonstrating that Pep1 molecules adapted random-coil conformation.68,69 CD spectra of the Pep1 further confirm the presence of random-coil structure (Figure S4). The new band at 1720 cm-1 was assigned to the stretching mode of C=O and C-O, respectively, due to the presence of partial carboxyl group -COOH.70 This is not surprise since the pH value of the reaction solution is 2, which is lower than the pK1 of glutamic acid or aspartic acid side chains of Pep1. Elemental analysis (EA) revealed that the lyophilized Pep1/SiW possessed C %, 19.11 %; H %, 3.11 %; N %, 8.58 %, implying that the average molar


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ratio of Pep1 to SiW within the adhesive matrix should be 2 : 1. Thermogravimetric analysis (TGA) also verified the proposed molar ratio. As shown in Figure S1a, a mass loss of 1.4 % from 30 to 180 °C arising from crystal water in the lyophilized Pep1/SiW powder. Assuming that the Pep1 decomposed completely and that the only inorganic residual species at 900 oC were SiO2 and WO3, the total residue species found of 56.0 % (Figure S1a) was in perfect agreement with the calculated value of 55.7 % based on EA result. Microscopic Structures and Rheological Behavior of Pep1/SiW. The intrinsic morphology of the Pep1/SiW adhesive was frozen, lyophilized and then inspected by SEM. It could be observed from Figure 4a that the Pep1/SiW adhesives were composed of macroscopic sheet-like structures. The enlarged SEM image (Figure 4b) showed that the sheet structures were interconnected to form 3D porous networks with a mesh size from several to tens micrometers.


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Figure 4. SEM images of the Pep1/SiW adhesive: a) SEM image at large scale; b) enlarged SEM image of Pep1/SiW from the area in (a) defined by the white rectangle. The viscoelastic property of the Pep1/SiW adhesive was studied by dynamic rheology measurements. As shown in Figure 5a, the storage moduli (G’) was higher than the loss moduli (G’’) in the entire investigated angle frequency range (ω), indicative of gel-like state.21,71 This can also be deduced from the tan δ < 1 (Figure 5a) for all the frequency. The dynamic time sweep experiment (Figure 5b) revealed that the storage modulus (G’) and the loss modulus (G’’) of Pep1/SiW kept no substantial change over time by continuing to oscillate the adhesive sample with low (1 %) strain amplitude and angle frequency (5 rad/s), indicating the good stability of the three-dimensional matrix of the adhesive. We also investigated the self-healing capacity of the Pep1/SiW adhesive. The adhesive was first broken by applying a 200 % strain amplitude sweep to diminish the storage modulus (Figure 5c). The self-healing behavior of the adhesive was subsequently monitored with continuous oscillation at low (1 %) strain amplitude. It was observed that the Pep1/SiW adhesive recovered its’ original modulus value within 4 min (Figure 5d). Additionally, one can observed from Figure 5 that the storage moduli (G’) of Pep1/SiW were quite high (G∞’ ≈ 2 × 106 Pa), implying that our adhesive had high crosslinking density for resisting an applied stress once attaching on the surface of solid substrates.


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Figure 5. Rheological behavior of the Pep1/SiW: (a) frequency sweep analysis at a constant strain of 0.2%; (b) time sweep at 20 oC (frequency = 5 rad/s; strain = 1%); (c) strain sweep at the frequency of 1.0 rad/s; (d) dynamic rheology behavior over time (strain =1 %) after the network structure was broken. Underwater Adhesion. The obtained Pep1/SiW exhibited the ability to bond various dissimilar substrates under waterline (Figure 6). These properties enabled the peptide-based complexes to serve as pressure-sensitive underwater adhesives. To test underwater bonding, the Pep1/SiW adhesive samples were compressed between two same substrates, such as glasses, aluminum or polyether-ether-ketone (PEK), to create a lap shear joint. The adhesive application was performed under deionized water by applying a compressive pressure of 35 kPa and a contact time of 15 min. After that, the adhered plates were pulled apart immediately by a materials testing system equipped with a deionized water holder (Figure 7a). The force vs


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displacement curve (Figure 7b) were obtained when the adhered plates were separated at rate of 10 mm/min (see Movie 1). Maximum force at failure was divided by substrate overlap area to quantify the shear adhesion strength. As show in Figure 7c, the lap shear strength for glass, aluminum and PEK substrates is 27.8 ± 2.5, 24.1 ± 3.1, 29.6 ± 2.9 kPa, respectively. The shear strength of Pep1/SiW on aluminum substrate is higher than that of commercially available fibrin glue (17.7 ± 2.7 kPa) under the same condition. However, it should be noted that the adhesive strength of the present systems remains low comparing to the reported recombinant adhesive proteins.72,73 To evaluate the biocompatibility, the cytotoxicities of individual SiW, Pep1 and Pep1/SiW adhesive against NIH 3T3 cell have been investigated by MTT assays. As shown in Figure S5, no significant influence on the cell viability was observed when the NIH 3T3 cells were incubated for short times (4 or 12 h). At longer incubation times (48 h) the pristine SiW showed obvious toxicity to the cells. However, the Pep1 and Pep1/SiW adhesive showed less cytotoxicity even at long incubation times (48 h).

Figure 6. Underwater adhesion behavior of Pep1/SiW for attaching various dissimilar substrates.


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Figure 7. Adhesion capacity testing of Pep1/SiW: (a) experimental setup of the underwater bonding of the Pep1/SiW on aluminum (Al) substrates; (b) a typical force vs displacement curve for lap shear joint of Al substrates glued by Pep1/SiW; (c) average shear adhesion strengths of Pep1/SiW bonded different substrates (glass, Al, polyether-ether-ketone (PEK)), and the shear strength of fibrin glue bonded on Al. Considering the protonated arginine residues of Pep1 and the polyanionic character of SiW, we proposed that the multiple electrostatic attractions between SiW and the cationic arginine groups of Pep1 provide main contribution to initiate the supramolecular polymerization of Pep1 in aqueous solution. As shown in Figure 2b, the SiW nanoclusters, acting as multivalent scaffolds, enforced the Pep1 molecules to connect with each other, resulting in the occurrence of supramolecular co-polymerization. With the crosslinking reaction progresses, the network structures of the Pep1/SiW polymers increased gradually and finally water-immiscible adhesive was obtained at macroscopic level. The interconnected networks and the dynamic interactions of the supramolecular polymers in the hydrated state could be responsive for the soft-state and the


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viscoelastic properties observed by rheology. The proposed self-assembly model was supported by the following series of experiments: (1) for comparison purpose, we further designed and synthesized two analogous peptides by replacing one arginine residue of Pep1 with glutamic acid in Pep2 or replacing two arginine residues of Pep1 with glutamic acids in Pep3 (Figure 1a). Poor lap shear strength (1.7 ± 3 kPa) was obtained when mixing SiW with Pep2 in water (Figure S6). In the case of Pep3, no adhesive sample could be observed under same condition (Figure S6a); (2) the spontaneous formation of underwater adhesives was not limited to Pep1 and SiW, since the mixing of Pep1, Pep4, Pep5 or Pep6 with various PM clusters, such as H5PMo10V2O40 (PMoV) and K6CoW12O40 (CoW) also yielded similar adhesives (Figure S7). These facts highlight the critical role of the non-covalent interactions between SiW and the arginine residues of Pep1 in contributing to the formation of cross-linking 3D network structures. We compared the adhesion capacity of different adhesives. As shown in Figure 8, the shear strength of the peptide/PM adhesives is independent on the polyoxometalates (24.1 ± 3.1 kPa for Pep1/SiW, 25.6 ± 2.6 kPa for Pep1/PMoV, 23.3 ± 2.2 kPa for Pep1/CoW), but dependent on the sequence or length of the peptides (24.1 ± 3.1 kPa for Pep1/SiW, 1.7 ± 1.2 kPa for Pep2/SiW, 20.6 ± 3.0 kPa for Pep4/SiW, 16.9 ± 3.5 kPa for Pep5/SiW, 0.8 ± 0.6 kPa for Pep6/SiW).


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Figure 8. Average shear strength of peptide/PM adhesives bonded to aluminum substrates: (a) Pep1/SiW, Pep1/PMoV, and Pep1/CoW; (b) Pep1/SiW, Pep2/SiW, Pep4/SiW, Pep5/SiW, and Pep6/SiW. pH and salt effect. It should be noted that the supramolecular copolymerization between peptides and PMs can occur at pH > 2, and transparent solutions were observed once the pH value of the reaction solutions was raised above 2.5. It is clear that the electrostatic attractions between basic amino acid residues (Arg, Lys, and His) of peptides and PMs could be suppressed at pH > 2 due to the possible electrostatic repulsion between the deprotonated Glu (or Asp) residues and PMs, and/or the electrostatic attraction between the deprotonated Glu (or Asp) residues and basic amino acid residues. This suggests that the protonated state of the Glu and Asp residues (carboxyl groups) of the short peptides is key point to ensure the ionic complexation of peptides and polyoxometalates. Surprisingly, the resultant adhesives can tolerate the pH variety within 48 hours. As shown in Figure S8, the morphology of the patterned adhesive coatings remained no change within 48 hours when the pH was raised to physiological conditions (pH = 7). With further increasing the aging time, the patterned coatings gradually dissociated (Figure S8). We also investigated the effect of NaCl concentration on the shear strength of Pep1/SiW. First, the Pep1/SiW adhesives (Figure S9) were prepared from parent Pep1 and SiW solutions at various NaCl concentrations. Then, the adhesive application on aluminum substrate and the shear strength measurements were performed under NaCl aqueous solutions with same salt concentrations to the solutions of the parent adhesives. As shown in Figure 9, the adhesive complex prepared without added NaCl showed the highest shear strength (24.1 ± 3.1 kPa), which decreased gradually with increasing the concentrations of NaCl (22.9 ± 3.4 kPa for 50 mM, 20.2 ± 2.3 kPa for 150 mM, 18.4 ± 2.7 kPa for 300 mM, 15.7 ± 3.5 kPa for


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500 mM). This effect implied a reduction in crosslink density of the network structures of Pep1/SiW by suppressing the electrostatic interactions between SiW and protonated arginine side chains of Pep1.

Figure 9. Average shear strength of Pep1/SiW adhesives prepared at different NaCl concentrations (from 0 mM to 500 mM) bonded to aluminum substrates. CONCLUSIONS Biomimetic underwater adhesives were successfully prepared through simple co-assembly of short peptides and polyoxometalates. The PM polyanionic clusters served as “nano-glue” to noncovalently crosslink peptide segments into continuous network superstructures at macroscopic level, which significantly enhanced the internal cohesion as well as the bulk mechanical strength of the hybrid supramolecular polymers. The high content of polar side chains such as (-COOH) encoded in the peptide sequence contributed to the enhanced surface binding, resulting in the formation of biomimetic adhesives under waterline. The multivalent interactions between peptides and PMs bestow the wet adhesives with quickly self-healing property. This co-assembly strategy allows one to explore a remarkably extended sequence diversity of peptides, and provides a versatile platform for the creation of peptide-based biomimetic adhesives. It is also


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expected that this work may open a door to a variety of novel functions and applications beyond simple adhesion by taking full advantages of the PM clusters or other functional polyanions. ASSOCIATED CONTENT Supporting Information. The Supporting Information is available free of charge on the ACS Publications website Description of the preparation of the peptides/polyoxometalates adhesives, TGA, FT-IR, MALDI-TOF-MS and CD spectra, the photographs of various peptides/PMs adhesives (PDF). AUTHOR INFORMATION Corresponding Author *E-mail: [email protected] Notes The authors declare no competing financial interest. ACKNOWLEDGMENT This work was supported by NSFC (21573091, 21634005), the National Basic Research Program (2013CB834503). The authors thank Dr. Rong Xue (Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, China) for her help in operating the 183W NMR and discussions. REFERENCES (1) Zhao, Q.; Lee, D. W.; Ahn, B. K.; Seo, S.; Kaufman, Y.; Israelachvili, J. N.; Waite, J. H. Nat. Mater. 2016, 15, 407-412. (2) Shao, H.; Stewart, R. J. Adv. Mater. 2010, 22, 729-733.


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TOC image: For Table of Contents Use Only

Title: Supramolecular Co-Polymerization of Short Peptides and Polyoxometalates: toward the fabrication of Underwater Adhesives Authors: Jing Xu,a Xiangyi Li,a Xiaodong Li,a Bao Li,a Lixin Wu,a Wen Li,a* Xiaoming Xie,a Rong Xue*b


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Supramolecular Copolymerization of Short Peptides and

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