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Synthesis and characterization of tannin grafted polycaprolactone
Journal of Colloid and Interface Science 479 (2016) 160–164
Contents lists available at ScienceDirect
Journal of Colloid and Interface Science journal homepage: www.elsevier.com/locate/jcis
Regular Article
Synthesis and characterization of tannin grafted polycaprolactone Ping Song a, Suchen Jiang a, Yajun Ren a, Xue Zhang a, Tiankui Qiao a, Xiaofeng Song a,⇑, Qimin Liu a, Xuesi Chen b a b
School of Chemical Engineering, Changchun University of Technology, Changchun 130012, PR China Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, PR China
g r a p h i c a l a b s t r a c t A novel tannin grafted polycaprolactone is firstly synthesized via ring-opening polymerization reaction. With PCL molecular chain grows, TA-g-PCL is changed from amorphous form to crystalline structure, and it is dissoluble in chloroform.
a r t i c l e
i n f o
Article history: Received 2 April 2016 Revised 24 June 2016 Accepted 26 June 2016 Available online 27 June 2016 Keywords: Tannin Graft Polycaprolactone Thermodynamics Dissolubility
a b s t r a c t Tannin and biodegradable polyester have attracted increasing interest for biomedical applications. To improve their compatibility, a novel tannin grafted polycaprolactone (TA-g-PCL) has been synthesized via ring-opening polymerization reaction. The structure of the product is characterized with FTIR, 1H NMR and GPC. GPC results show that the experimental molecular weight is far less than the theoretical due to complicated stereo structure and large steric hindrance of tannic molecule, but the polydispersity of the product is narrow. At 115.76:1 of molar ratio of CL to tannin, molecular weight of the product reaches the maximum. Thermodynamics properties and dissolubility of TA-g-PCL are closely related to its molecular weight. With PCL molecular chain grows, TA-g-PCL changes from amorphous form to crystalline structure, and its dissolubility in chloroform is also enhanced significantly. Ó 2016 Elsevier Inc. All rights reserved.
1. Introduction
⇑ Corresponding author. E-mail address: [email protected] (X. Song). http://dx.doi.org/10.1016/j.jcis.2016.06.056 0021-9797/Ó 2016 Elsevier Inc. All rights reserved.
Biodegradable polyesters such as poly-lactic acid (PLA), polyglycolic acid (PGA), and poly-caprolactone (PCL) as well as their copolymers have excellent biodegradability and biocompatibility [1,2]. They have been broadly used in biomedical products like
P. Song et al. / Journal of Colloid and Interface Science 479 (2016) 160–164
sutures, bone screws, tissue engineering scaffolds and drug delivery carrier [3–6]. However, the poor bioactivity of biodegradable polyester limits its effect on the recovery of tissues damaged by accident or human disease [7,8]. Then the introduction of bioactive molecules into biodegradable polyester has attracted considerable attention in recent years. For example, an iodine bearing copolymer was synthesized by iodine-functionalized caprolactone monomer reacting with e-caprolactone at 100 °C in toluene with methanol as initiator [9]. The yielded polymer was a promising candidate as temporary reconstruction or drug delivery materials. Poly(meso-lactide-co-g-chitosan) was also reported to reinforce the adsorption of drugs and adhesion of cells as a new biomedical material [10]. Tannin (TA) is a natural polyphenols containing polyphenolic group connected to a polyhydric alcohol core through ester linkages. It has been explored for biomedical application due to diverse biological activities including antioxidant, anticarcinogenic [11– 13] and capability of interaction with proteins [14]. Studies on TA concentrate in ionic pairing, [15] hydrogen bonding, [16–18] and metal coordination [19] so far. For example, Cao reported that poly(triethylene glycol methyl acrylate-co-tocopheryl acrylate) complexed with TA was used as a potential antioxidant prodrug to enable localized neuro-protection [20]. Biodegradable polyesters blended with TA can potentially enhance polymeric biological performances, but little attention has been paid to their blending method. Original TA is hardly dispersed in the polyesters due to their mutual incompatibility. If both were directly blended together, interfacial separation would easily occur in use, resulting in divorce of TA from polyesters. In this work, a tannin grafted polycaprolactone (TA-g-PCL) was synthesized, and its architecture and molecular weight were investigated by FTIR, 1H NMR spectroscopy and gel permeation chromatography (GPC). The influence of molecular weight on the thermodynamics properties and solubility of TA-g-PCL were well determined. 2. Experiments 2.1. Materials Tannin (molecular weight = 1300, Shentong Science and Technology Co. Ltd.) was dried at 50 °C in vacuum oven over 6 h. ecaprolactone (99%) (Aldrich Chemical) was purified by distillation under reduced pressure. Stannous octoate (SnOct2) (Sigma Chemical) was dissolved in dehydrated toluene prior to use. All other chemicals such as trichloromethane, methanol, diethyl ether were obtained commercially and used as received. 2.2. Synthesis of TA-g-PCL TA-g-PCLs were synthesized via ring-opening polymerization (ROP) of CL monomer with natural tannin as initiators and SnOct2 as catalyst. Scheme 1 shows the synthetic pathway for TA-g-PCLs. The typical polymerization procedures were described as follows: a dried glass reaction tube was degassed and purged with argon three times. Then 0.5 g tannin, CL monomer (2.77 g, 5.63 g and 11.75 g) and the corresponding amount of 0.1 g/ml of SnOct2/toluene solution (0.10 ml, 0.18 ml or 0.40 ml) were added in sequence into the tube. They were designed as TA-g-PCL-1, TA-gPCL-2 and TA-g-PCL-3, respectively. After the tube was sealed, it was immersed into an oil bath at 120 °C for 24 h. The reaction mixture was cooled and dissolved in methylene chloride, and then was precipitated with an excess of methanol/iced ether (1/10 volume ratio). After that, dissolving and precipitating were repeated two times again, the polymerized products were dried under ambient
161
temperature in a vacuum oven for at least 48 h before further characterization. 2.3. Analysis and characteristics FT-IR spectra of the obtained products were recorded with a FTIR spectrometer (Nicolet iS10, Thermo Fisher Scientific). A little of samples was mixed with KBr powder and cold-pressed into a suitable disk before FTIR measurement. The scanning range was 500–4000 cm 1. Proton nuclear magnetic resonance (1H NMR) spectra were measured on a Bruker 400 MHz spectrometer at room temperature with DMSO-d6 as solvent. The internal standard for 1H NMR was tetramethylsilane or trifluoroacetic acid (11.30 ppm) in deuteriotrifluoroacetic acid (CF3COOD). The molecular weight and distribution of the obtained products were also measured by gel permeation chromatography (GPC). GPC was performed using a Waters Styragel HT6E pump, a Waters 410 refractive index detector. Chloroform was used as eluent at a flow rate of 1.0 ml/min at 35 °C. Polystyrenes with narrow molecular weight distributions were used as standards for calibration. Thermodynamics performance of the samples including the melting point (Tm), crystallization temperature (Tc) and enthalpy of melting (DHm) were determined by differential scanning calorimetry (DSC-7, from Perkin Elmer) at a heating rate of 10 °Cmin 1 from 15 to 200 °C under a N2 atmosphere. Dissolubility of the synthesized product was evaluated in chloroform at room temperature, and was recorded by taking photo. 3. Results and discussion 3.1. Synthesis of TA-g-PCL Fig. 1 shows the FTIR spectra of TA, PCL and TA-g-PCL-2. For original TA, the adsorption bond at 1612 cm 1 and 1535 cm 1 corresponds to the stretching vibration of C@C bond in aromatic ring [21], and the bond at 758 cm 1 is out-of-plane bending vibration of CAH in aromatic compounds. These characteristic bonds also appear in the spectrum of TA-g-PCL-2. At the same time, the carbonyl bond at 1756 cm 1 [22], (CH2)n rocking vibration at 732 cm 1, non-planar vibration at 1294 cm 1 as well as plane shear vibration peak at 1471 cm 1, and CAOAC stretching vibrations bond at 1188 cm 1 [23] which are assigned to PCL are also found in TA-g-PCL-2. To further confirm structure of TA-g-PCL, 1H NMR spectra is also carried out. Fig. 2 gives the typical 1H NMR spectra of TA-g-PCL in DMSO-d6. The methine proton (CH, a) of the glucose core is found at 5.75 ppm, and the peaks ranged from 6.78 to 7.11 ppm are identified as the methine proton (CH, b) of polyphenolic unit [24]. In addition, the four peaks at 2.31 ppm (CH2, c); 1.66 ppm (CH2, d and e); 1.39 ppm (CH2, f); 4.07 ppm (CH2, g) are assigned to the characteristic chemical shifts of branched chain of PCL units [23]. Both FT-IR and 1H NMR results indicate that PCL have been grafted onto tannin. Moreover, the peaks at 9.34 ppm and 9.81 ppm are attributed to the phenolic hydroxyl protons in tannin, showing that a part of hydroxyls survive after the ROP reaction. This will keep tannic bioactivity. The molecular weight and polydispersity of synthesized products are also determined by 1H NMR and GPC. The results are collected in Table 1. It can be found that the experimental numberaverage molecular weight (Mn) is far less than the theoretical Mn due to complicated stereo structure and large steric hindrance of tannic molecule. When the molar ratio of CL monomer to tannin increases from 56.9, 115.76 to 241.81, the Mns calculated by 1H NMR are 1930, 4551 and 2570, respectively. The excessive feeding
162
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Scheme 1. Synthetic pathway for TA-g-PCLs.
Fig. 1. FTIR spectrum of TA, PCL and TA-g-PCL-2.
amount of CL monomer not only reduces length of PCL molecular chain, but also turns its polydispersity wide. The phenolic hydroxyl groups with high reactive activity are prior to initiate the ROP of
Fig. 2. 1H NMR spectrum of TA-g-PCL-2.
P. Song et al. / Journal of Colloid and Interface Science 479 (2016) 160–164 Table 1 Synthesis and characteristics of TA-g-PCL. Samples
Mna Theoretical
[CL]/[I]b
Mnc1 Experimental
Mnc2 Experimental
Mw/Mnd
TA-g-PCL-1 TA-g-PCL-2 TA-g-PCL-3
8000 15,000 30,000
56.93 115.76 241.81
– 3513 2414
1930 4551 2570
– 1.18 1.32
a
Theoretical Mn based on the monomer-initiator ratio and assuming 100% conversion. b Molar ratio of e-caprolactone monomer to tannin initiator in feed. c1 and c2 Mn calculated from the results of GPC and 1H NMR spectroscopy, respectively. d Polydispersity (Mw/Mn) determined from GPC.
Table 2 DSC data of different TA-g-PCLs.
a
Samples
Tc (°C)
Tm (°C)
DHm (J/g)
Xca (%)
TA-g-PCL-1 TA-g-PCL-2 TA-g-PCL-3
– 25.34 20.42
– 46.77 46.26
– 84.28 74.00
– 60.38 53.01
Xc(%) = (DHm/139.6) 100%.
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CL. As molecular chain grows to some extent, terminal reactive ability declines, and other phenolic hydroxyl groups could also take part in the ROP to form branched chains with different length. 3.2. Thermodynamics properties of TA-g-PCL To better understand the thermodynamics properties of TA-gPCL, DSC results of different products are summarized in Fig. 3 and Table 2. The cold crystallization (Tc) and melting (Tm) could be clearly observed. Degree of crystallinity (Xc) was figured out according to the equation Xc = (DHm/139.6 J/g) 100%, where DHm stands for the melting enthalpy in J/g that is calculated from the fusion peaks in the first heating run of DSC curve, and 139.6 J/g is the specific enthalpy of melting for 100% crystalline PCL [25]. As shown in Fig. 3, neither cold crystallization peak nor melting peak appears in the DSC curve of TA-g-PCL-1, showing its amorphous feature. On the one hand, PCL molecular chain grafted onto tannin is short at low molar ratio of CL monomer to tannin, active movement of molecular chain make chain folding and regular packing unstable; on the other, tannin is amorphous structure [26]. In contrast, there are the corresponding crystallization and melting peak for TA-g-PCL-2 and TA-g-PCL-3, indicating their crystalline features, and Tc and Tm shifts to the higher temperature with molecular weight increasing. TA-g-PCL-2 has a Tc of 25.34 °C with a Xc of 60.38%, while TA-g-PCL-3 has a Tc of 20.42 °C with a Xc of 53.01%. It is well known that the movements of long molecular chain become difficult, and stable structure is easily formed after chain folding and rearranging. Therefore, Tc and Xc of TA-g-PCL-2 is more than those of TA-g-PCL-3. 3.3. Dissolubility of TA-g-PCL
Fig. 3. DSC thermograms of different TA-g-PCLs.
Chloroform is a good solvent of biodegradable polyester, so Fig. 4 presents dissolubility of different products in chloroform. Original TA still floats on the solvent until 48 h, suggesting that it is not dissoluble in the chloroform at all, and so does TA-g-PCL-1 (Fig. 4d). But TA-g-PCL-2 and TA-g-PCL-3 are dissolved into the chloroform as soon as they are put into the solvent (Fig. 4a), and there is not any visible precipitate or flotage in the small bottle after 48 h (Fig. 4d), indicating that our synthesized products is stable. The solution of TA-g-PCL-2 is clearer compared to that of TA-g-PCL-3. It can be explained that the dissolubility of the products depends on tannin segment when the branched chains of PCL are short. PCL segment plays a key role in the dissolution with PCL molecular weight approaching or exceeding tannin.
Fig. 4. Dissolubility of TA, TA-g-PCL-1, TA-g-PCL-2 and TA-g-PCL-3 in chloroform (from left to right), (a) 0 h, (b) 1 h, (c) 6 h and (d) 48 h.
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4. Conclusions To solve the problem of compatibility of tannin with biodegradable polyester and open a new way for the application of tannin, a novel tannin grafted polycaprolactone is firstly synthesized via ring-opening polymerization reaction. FTIR and 1H NMR confirm synthesis of the product and the residual hydroxyls which keep tannic bioactivity. GPC results show that the experimental molecular weight is far less than the theoretical, but the polydispersity of the products is narrow. At 115.76:1 of molar ratio of CL to tannin, molecular weight of the product reaches the maximum. Thermodynamics properties and dissolubility of TA-g-PCL count on the molecular weight of grafted PCL. With PCL molecular chain grows, TA-g-PCL is changed from amorphous form to crystalline structure, and it is dissoluble in chloroform. Then tannin grafted PCL can be well blended with biodegradable polyesters to make tissue engineering scaffold materials or drug delivery systems. Acknowledgements This work was by the project of Science and Technology Bureau of Changchun under Grant (2014KG106), the Natural Science Foundation of Jilin Province under Grant (20130102065JC) and the project of Education Department of Jilin under Grant (2014123). References [1] H.Y. Tian, Z.H. Tang, X.L. Zhuang, X.S. Chen, X.B. Jing, Biodegradable synthetic polymers: preparation, functionalization and biomedical application, Prog. Polym. Sci. 37 (2012) 237–280. [2] H.T. Li, T.K. Qiao, P. Song, H.L. Guo, X.F. Song, B.C. Zhang, X.S. Chen, Star-shaped PCL/PLLA blended fiber membrane via electrospinning, J. Biomater. Sci. Polym. Ed. 26 (7) (2015) 420–432. [3] X. Wen, P.A. Tresco, Fabrication and characterization of permeable degradable poly (DL-lactide-co-glycolide) (PLGA) hollow fiber phase inversion membranes for use as nerve tract guidance channels, Biomaterials 27 (2006) 3800–3809. [4] W.S. Koegler, L.G. Griffith, Osteoblast response to PLGA tissue engineering scaffolds with PEO modified surface chemistries and demonstration of patterned cell response, Biomaterials 25 (2004) 2819–2830. [5] Y. Cheng, S. Deng, P. Chen, R. Ruan, Polylactic acid (PLA) synthesis and modifications: a review, Front. Chem. China 4 (2009) 259–264. [6] T.K. Qiao, P. Song, H.L. Guo, X.F. Song, B.C. Zhang, X.S. Chen, Reinforced electrospun PLLA fiber membrane via chemical crosslinking, Eur. Polym. J. 74 (2016) 101–108. [7] L.S. Nair, C.T. Laurencin, Biodegradable polymers as biomaterials, Prog. Polym. Sci. 32 (2007) 762–798. [8] G. Chen, T. Ushida, T. Tateishi, Scaffold design for tissue engineering, Macromol. Biosci. 2 (2002) 67–77.
[9] S.E. Habnouni, V. Darcos, J. Coudane, Synthesis and ring opening polymerization of a new functional lactone, a-iodo-e-caprolactone: a novel route to functionalized aliphatic polyesters, Macromol. Rapid. Commun. 30 (2009) 165–169. [10] Y.C. Huang, C.C. Huang, Y.Y. Huang, K.S. Chen, Surface modification and characterization of chitosan or PLGA membrane with laminin by chemical and oxygen plasma treatment for neural regeneration, J. Biomed. Mater. Res. A 82 (2007) 842–851. [11] K.S. Chen, Y.C. Hsiao, D.Y. Kuo, M.C. Choua, S.C. Chud, Y.S. Hsieh, T.H. Lin, Tannic acid-induced apoptosis and-enhanced sensitivity to arsenic trioxide in human leukemia HL-60 cells, Leuk. Res. 33 (2) (2009) 297–307. [12] H. Sakagami, Y. Jiang, K. Kusama, T. Atsumi, T. Ueha, M. Toguchi, I. Iwakura, K. Satoh, H. Ito, T. Hatano, T. Yoshida, Cytotoxic activity of hydrolyzable tannins against human oral tumor cell lines – a possible mechanism, Phytomedicine 7 (1) (2000) 39–47. [13] K. Tikoo, M.S. Sane, C. Gupta, Tannic acid ameliorates doxorubicin-induced cardiotoxicity and potentiates its anti-cancer activity: potential role of tannins in cancer chemotherapy, Toxicol. Appl. Pharmacol. 251 (3) (2011) 191–200. [14] J.P. Van Buren, W.B. Robinson, Formation of complexes between protein and tannic acid, J. Agric. Food Chem. 17 (4) (1969) 772–777. [15] T. Shutava, M. Prouty, D. Kommireddy, Y. Lvov, pH responsive decomposable layer-by-layer nanofilms and capsules on the basis of tannic acid, Macromolecules 38 (2005) 2850–2858. [16] I. Erel-Unal, S. Sukhishvili, Hydrogen-bonded multilayers of a neutral polymer and a polyphenol, Macromolecules 41 (2008) 3962–3970. [17] V. Kozlovskaya, E. Kharlampieva, I. Drachuk, D. Cheng, V.V. Tsukruk, Responsive microcapsule reactors based on hydrogen-bonded tannic acid layer-by-layer assemblies, Soft Matter 6 (2010) 3596–3608. [18] E. Costa, M. Coelho, L.M. Ilharco, A. Aguiar-Ricardo, P.T. Hammond, Tannic acid mediated suppression of PNIPAAm microgels thermoresponsive behavior, Macromolecules 44 (2011) 612–621. [19] H. Ejima, J.J. Richardson, K. Liang, J.P. Best, M.P. van Koeverden, G.K. Such, J. Cui, F. Caruso, One-step assembly of coordination complexes for versatile film and particle engineering, Science 341 (2013) 154–157. [20] Y. Cao, W. He, Water-soluble antioxidant derivative poly(triethylene glycol methyl acrylate-co-a-tocopheryl acrylate) as a potential prodrug to enable localized neuroprotection, Acta Biomater. 9 (1) (2013) 4558–4568. [21] J.S. Jensen, M. Egebo, A.S. Meyer, Identification of spectral regions for the quantification of red wine tannins with Fourier transform mid-infrared spectroscopy, J. Agric. Food Chem. 56 (2008) 3493–3499. [22] D. Mecerreyes, R. Stevens, C. Nguyen, J.A. Pomposo, M. Bengoetxea, H. Grande, Synthesis and characterization of polypyrrole-graft-poly(e-caprolactone) copolymers: new electrically conductive nanocomposites, Synth. Met. 126 (2002) 173–178. [23] R.L. Feng, W.X. Zhu, Z.M. Song, L.Y. Zhao, G.X. zhai, Novel star-type methoxypoly (ethylene glycol) (PEG)-poly(e-caprolactone) (PCL) copolymeric nanoparticles for controlled release of curcumin, J. Nanopart. Res. 15 (6) (2013) 1748–1759. [24] H. Mao, X. Liao, W. Zhang, Recyclable plant tannin-chelated Rh (III) complex catalysts for aqueous-organic biphasic hydrogenation of quinoline, J. Chem. Technol. Biotechnol. 87 (8) (2012) 1104–1110. [25] Z. Ning, N. Jiang, Z. Gan, Four-armed PCL-b-PDLA diblock copolymer: 1. Synthesis, crystallization and degradation, Polym. Degrad. Stab. 107 (2014) 120–128. [26] M. Weng, Z. Qiu, Miscibility and crystallization behavior of biodegradable poly (butylene succinate-co-butylene carbonate) and tannic acid blends, Thermochim. Acta 575 (2014) 262–268.
Contents lists available at ScienceDirect
Journal of Colloid and Interface Science journal homepage: www.elsevier.com/locate/jcis
Regular Article
Synthesis and characterization of tannin grafted polycaprolactone Ping Song a, Suchen Jiang a, Yajun Ren a, Xue Zhang a, Tiankui Qiao a, Xiaofeng Song a,⇑, Qimin Liu a, Xuesi Chen b a b
School of Chemical Engineering, Changchun University of Technology, Changchun 130012, PR China Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, PR China
g r a p h i c a l a b s t r a c t A novel tannin grafted polycaprolactone is firstly synthesized via ring-opening polymerization reaction. With PCL molecular chain grows, TA-g-PCL is changed from amorphous form to crystalline structure, and it is dissoluble in chloroform.
a r t i c l e
i n f o
Article history: Received 2 April 2016 Revised 24 June 2016 Accepted 26 June 2016 Available online 27 June 2016 Keywords: Tannin Graft Polycaprolactone Thermodynamics Dissolubility
a b s t r a c t Tannin and biodegradable polyester have attracted increasing interest for biomedical applications. To improve their compatibility, a novel tannin grafted polycaprolactone (TA-g-PCL) has been synthesized via ring-opening polymerization reaction. The structure of the product is characterized with FTIR, 1H NMR and GPC. GPC results show that the experimental molecular weight is far less than the theoretical due to complicated stereo structure and large steric hindrance of tannic molecule, but the polydispersity of the product is narrow. At 115.76:1 of molar ratio of CL to tannin, molecular weight of the product reaches the maximum. Thermodynamics properties and dissolubility of TA-g-PCL are closely related to its molecular weight. With PCL molecular chain grows, TA-g-PCL changes from amorphous form to crystalline structure, and its dissolubility in chloroform is also enhanced significantly. Ó 2016 Elsevier Inc. All rights reserved.
1. Introduction
⇑ Corresponding author. E-mail address: [email protected] (X. Song). http://dx.doi.org/10.1016/j.jcis.2016.06.056 0021-9797/Ó 2016 Elsevier Inc. All rights reserved.
Biodegradable polyesters such as poly-lactic acid (PLA), polyglycolic acid (PGA), and poly-caprolactone (PCL) as well as their copolymers have excellent biodegradability and biocompatibility [1,2]. They have been broadly used in biomedical products like
P. Song et al. / Journal of Colloid and Interface Science 479 (2016) 160–164
sutures, bone screws, tissue engineering scaffolds and drug delivery carrier [3–6]. However, the poor bioactivity of biodegradable polyester limits its effect on the recovery of tissues damaged by accident or human disease [7,8]. Then the introduction of bioactive molecules into biodegradable polyester has attracted considerable attention in recent years. For example, an iodine bearing copolymer was synthesized by iodine-functionalized caprolactone monomer reacting with e-caprolactone at 100 °C in toluene with methanol as initiator [9]. The yielded polymer was a promising candidate as temporary reconstruction or drug delivery materials. Poly(meso-lactide-co-g-chitosan) was also reported to reinforce the adsorption of drugs and adhesion of cells as a new biomedical material [10]. Tannin (TA) is a natural polyphenols containing polyphenolic group connected to a polyhydric alcohol core through ester linkages. It has been explored for biomedical application due to diverse biological activities including antioxidant, anticarcinogenic [11– 13] and capability of interaction with proteins [14]. Studies on TA concentrate in ionic pairing, [15] hydrogen bonding, [16–18] and metal coordination [19] so far. For example, Cao reported that poly(triethylene glycol methyl acrylate-co-tocopheryl acrylate) complexed with TA was used as a potential antioxidant prodrug to enable localized neuro-protection [20]. Biodegradable polyesters blended with TA can potentially enhance polymeric biological performances, but little attention has been paid to their blending method. Original TA is hardly dispersed in the polyesters due to their mutual incompatibility. If both were directly blended together, interfacial separation would easily occur in use, resulting in divorce of TA from polyesters. In this work, a tannin grafted polycaprolactone (TA-g-PCL) was synthesized, and its architecture and molecular weight were investigated by FTIR, 1H NMR spectroscopy and gel permeation chromatography (GPC). The influence of molecular weight on the thermodynamics properties and solubility of TA-g-PCL were well determined. 2. Experiments 2.1. Materials Tannin (molecular weight = 1300, Shentong Science and Technology Co. Ltd.) was dried at 50 °C in vacuum oven over 6 h. ecaprolactone (99%) (Aldrich Chemical) was purified by distillation under reduced pressure. Stannous octoate (SnOct2) (Sigma Chemical) was dissolved in dehydrated toluene prior to use. All other chemicals such as trichloromethane, methanol, diethyl ether were obtained commercially and used as received. 2.2. Synthesis of TA-g-PCL TA-g-PCLs were synthesized via ring-opening polymerization (ROP) of CL monomer with natural tannin as initiators and SnOct2 as catalyst. Scheme 1 shows the synthetic pathway for TA-g-PCLs. The typical polymerization procedures were described as follows: a dried glass reaction tube was degassed and purged with argon three times. Then 0.5 g tannin, CL monomer (2.77 g, 5.63 g and 11.75 g) and the corresponding amount of 0.1 g/ml of SnOct2/toluene solution (0.10 ml, 0.18 ml or 0.40 ml) were added in sequence into the tube. They were designed as TA-g-PCL-1, TA-gPCL-2 and TA-g-PCL-3, respectively. After the tube was sealed, it was immersed into an oil bath at 120 °C for 24 h. The reaction mixture was cooled and dissolved in methylene chloride, and then was precipitated with an excess of methanol/iced ether (1/10 volume ratio). After that, dissolving and precipitating were repeated two times again, the polymerized products were dried under ambient
161
temperature in a vacuum oven for at least 48 h before further characterization. 2.3. Analysis and characteristics FT-IR spectra of the obtained products were recorded with a FTIR spectrometer (Nicolet iS10, Thermo Fisher Scientific). A little of samples was mixed with KBr powder and cold-pressed into a suitable disk before FTIR measurement. The scanning range was 500–4000 cm 1. Proton nuclear magnetic resonance (1H NMR) spectra were measured on a Bruker 400 MHz spectrometer at room temperature with DMSO-d6 as solvent. The internal standard for 1H NMR was tetramethylsilane or trifluoroacetic acid (11.30 ppm) in deuteriotrifluoroacetic acid (CF3COOD). The molecular weight and distribution of the obtained products were also measured by gel permeation chromatography (GPC). GPC was performed using a Waters Styragel HT6E pump, a Waters 410 refractive index detector. Chloroform was used as eluent at a flow rate of 1.0 ml/min at 35 °C. Polystyrenes with narrow molecular weight distributions were used as standards for calibration. Thermodynamics performance of the samples including the melting point (Tm), crystallization temperature (Tc) and enthalpy of melting (DHm) were determined by differential scanning calorimetry (DSC-7, from Perkin Elmer) at a heating rate of 10 °Cmin 1 from 15 to 200 °C under a N2 atmosphere. Dissolubility of the synthesized product was evaluated in chloroform at room temperature, and was recorded by taking photo. 3. Results and discussion 3.1. Synthesis of TA-g-PCL Fig. 1 shows the FTIR spectra of TA, PCL and TA-g-PCL-2. For original TA, the adsorption bond at 1612 cm 1 and 1535 cm 1 corresponds to the stretching vibration of C@C bond in aromatic ring [21], and the bond at 758 cm 1 is out-of-plane bending vibration of CAH in aromatic compounds. These characteristic bonds also appear in the spectrum of TA-g-PCL-2. At the same time, the carbonyl bond at 1756 cm 1 [22], (CH2)n rocking vibration at 732 cm 1, non-planar vibration at 1294 cm 1 as well as plane shear vibration peak at 1471 cm 1, and CAOAC stretching vibrations bond at 1188 cm 1 [23] which are assigned to PCL are also found in TA-g-PCL-2. To further confirm structure of TA-g-PCL, 1H NMR spectra is also carried out. Fig. 2 gives the typical 1H NMR spectra of TA-g-PCL in DMSO-d6. The methine proton (CH, a) of the glucose core is found at 5.75 ppm, and the peaks ranged from 6.78 to 7.11 ppm are identified as the methine proton (CH, b) of polyphenolic unit [24]. In addition, the four peaks at 2.31 ppm (CH2, c); 1.66 ppm (CH2, d and e); 1.39 ppm (CH2, f); 4.07 ppm (CH2, g) are assigned to the characteristic chemical shifts of branched chain of PCL units [23]. Both FT-IR and 1H NMR results indicate that PCL have been grafted onto tannin. Moreover, the peaks at 9.34 ppm and 9.81 ppm are attributed to the phenolic hydroxyl protons in tannin, showing that a part of hydroxyls survive after the ROP reaction. This will keep tannic bioactivity. The molecular weight and polydispersity of synthesized products are also determined by 1H NMR and GPC. The results are collected in Table 1. It can be found that the experimental numberaverage molecular weight (Mn) is far less than the theoretical Mn due to complicated stereo structure and large steric hindrance of tannic molecule. When the molar ratio of CL monomer to tannin increases from 56.9, 115.76 to 241.81, the Mns calculated by 1H NMR are 1930, 4551 and 2570, respectively. The excessive feeding
162
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Scheme 1. Synthetic pathway for TA-g-PCLs.
Fig. 1. FTIR spectrum of TA, PCL and TA-g-PCL-2.
amount of CL monomer not only reduces length of PCL molecular chain, but also turns its polydispersity wide. The phenolic hydroxyl groups with high reactive activity are prior to initiate the ROP of
Fig. 2. 1H NMR spectrum of TA-g-PCL-2.
P. Song et al. / Journal of Colloid and Interface Science 479 (2016) 160–164 Table 1 Synthesis and characteristics of TA-g-PCL. Samples
Mna Theoretical
[CL]/[I]b
Mnc1 Experimental
Mnc2 Experimental
Mw/Mnd
TA-g-PCL-1 TA-g-PCL-2 TA-g-PCL-3
8000 15,000 30,000
56.93 115.76 241.81
– 3513 2414
1930 4551 2570
– 1.18 1.32
a
Theoretical Mn based on the monomer-initiator ratio and assuming 100% conversion. b Molar ratio of e-caprolactone monomer to tannin initiator in feed. c1 and c2 Mn calculated from the results of GPC and 1H NMR spectroscopy, respectively. d Polydispersity (Mw/Mn) determined from GPC.
Table 2 DSC data of different TA-g-PCLs.
a
Samples
Tc (°C)
Tm (°C)
DHm (J/g)
Xca (%)
TA-g-PCL-1 TA-g-PCL-2 TA-g-PCL-3
– 25.34 20.42
– 46.77 46.26
– 84.28 74.00
– 60.38 53.01
Xc(%) = (DHm/139.6) 100%.
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CL. As molecular chain grows to some extent, terminal reactive ability declines, and other phenolic hydroxyl groups could also take part in the ROP to form branched chains with different length. 3.2. Thermodynamics properties of TA-g-PCL To better understand the thermodynamics properties of TA-gPCL, DSC results of different products are summarized in Fig. 3 and Table 2. The cold crystallization (Tc) and melting (Tm) could be clearly observed. Degree of crystallinity (Xc) was figured out according to the equation Xc = (DHm/139.6 J/g) 100%, where DHm stands for the melting enthalpy in J/g that is calculated from the fusion peaks in the first heating run of DSC curve, and 139.6 J/g is the specific enthalpy of melting for 100% crystalline PCL [25]. As shown in Fig. 3, neither cold crystallization peak nor melting peak appears in the DSC curve of TA-g-PCL-1, showing its amorphous feature. On the one hand, PCL molecular chain grafted onto tannin is short at low molar ratio of CL monomer to tannin, active movement of molecular chain make chain folding and regular packing unstable; on the other, tannin is amorphous structure [26]. In contrast, there are the corresponding crystallization and melting peak for TA-g-PCL-2 and TA-g-PCL-3, indicating their crystalline features, and Tc and Tm shifts to the higher temperature with molecular weight increasing. TA-g-PCL-2 has a Tc of 25.34 °C with a Xc of 60.38%, while TA-g-PCL-3 has a Tc of 20.42 °C with a Xc of 53.01%. It is well known that the movements of long molecular chain become difficult, and stable structure is easily formed after chain folding and rearranging. Therefore, Tc and Xc of TA-g-PCL-2 is more than those of TA-g-PCL-3. 3.3. Dissolubility of TA-g-PCL
Fig. 3. DSC thermograms of different TA-g-PCLs.
Chloroform is a good solvent of biodegradable polyester, so Fig. 4 presents dissolubility of different products in chloroform. Original TA still floats on the solvent until 48 h, suggesting that it is not dissoluble in the chloroform at all, and so does TA-g-PCL-1 (Fig. 4d). But TA-g-PCL-2 and TA-g-PCL-3 are dissolved into the chloroform as soon as they are put into the solvent (Fig. 4a), and there is not any visible precipitate or flotage in the small bottle after 48 h (Fig. 4d), indicating that our synthesized products is stable. The solution of TA-g-PCL-2 is clearer compared to that of TA-g-PCL-3. It can be explained that the dissolubility of the products depends on tannin segment when the branched chains of PCL are short. PCL segment plays a key role in the dissolution with PCL molecular weight approaching or exceeding tannin.
Fig. 4. Dissolubility of TA, TA-g-PCL-1, TA-g-PCL-2 and TA-g-PCL-3 in chloroform (from left to right), (a) 0 h, (b) 1 h, (c) 6 h and (d) 48 h.
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4. Conclusions To solve the problem of compatibility of tannin with biodegradable polyester and open a new way for the application of tannin, a novel tannin grafted polycaprolactone is firstly synthesized via ring-opening polymerization reaction. FTIR and 1H NMR confirm synthesis of the product and the residual hydroxyls which keep tannic bioactivity. GPC results show that the experimental molecular weight is far less than the theoretical, but the polydispersity of the products is narrow. At 115.76:1 of molar ratio of CL to tannin, molecular weight of the product reaches the maximum. Thermodynamics properties and dissolubility of TA-g-PCL count on the molecular weight of grafted PCL. With PCL molecular chain grows, TA-g-PCL is changed from amorphous form to crystalline structure, and it is dissoluble in chloroform. Then tannin grafted PCL can be well blended with biodegradable polyesters to make tissue engineering scaffold materials or drug delivery systems. Acknowledgements This work was by the project of Science and Technology Bureau of Changchun under Grant (2014KG106), the Natural Science Foundation of Jilin Province under Grant (20130102065JC) and the project of Education Department of Jilin under Grant (2014123). References [1] H.Y. Tian, Z.H. Tang, X.L. Zhuang, X.S. Chen, X.B. Jing, Biodegradable synthetic polymers: preparation, functionalization and biomedical application, Prog. Polym. Sci. 37 (2012) 237–280. [2] H.T. Li, T.K. Qiao, P. Song, H.L. Guo, X.F. Song, B.C. Zhang, X.S. Chen, Star-shaped PCL/PLLA blended fiber membrane via electrospinning, J. Biomater. Sci. Polym. Ed. 26 (7) (2015) 420–432. [3] X. Wen, P.A. Tresco, Fabrication and characterization of permeable degradable poly (DL-lactide-co-glycolide) (PLGA) hollow fiber phase inversion membranes for use as nerve tract guidance channels, Biomaterials 27 (2006) 3800–3809. [4] W.S. Koegler, L.G. Griffith, Osteoblast response to PLGA tissue engineering scaffolds with PEO modified surface chemistries and demonstration of patterned cell response, Biomaterials 25 (2004) 2819–2830. [5] Y. Cheng, S. Deng, P. Chen, R. Ruan, Polylactic acid (PLA) synthesis and modifications: a review, Front. Chem. China 4 (2009) 259–264. [6] T.K. Qiao, P. Song, H.L. Guo, X.F. Song, B.C. Zhang, X.S. Chen, Reinforced electrospun PLLA fiber membrane via chemical crosslinking, Eur. Polym. J. 74 (2016) 101–108. [7] L.S. Nair, C.T. Laurencin, Biodegradable polymers as biomaterials, Prog. Polym. Sci. 32 (2007) 762–798. [8] G. Chen, T. Ushida, T. Tateishi, Scaffold design for tissue engineering, Macromol. Biosci. 2 (2002) 67–77.
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