Abstract
To improve the solubility and bioactivity of chitosan, a new class of carboxymethyl chitosan derivatives possessing sulfonium salts was successfully designed and synthesized, including Methyl sulfide carboxymethyl chitosan (MCMCS), Ethyl sulfide carboxymethyl chitosan (ECMCS), Propyl sulfide carboxymethyl chitosan (PCMCS), and Butyl sulfide carboxymethyl chitosan (BCMCS). To determine the structure of the new class of the derivatives, methods of the Fourier transform infrared spectroscopy (FT-IR), 1H nuclear magnetic resonance spectrometer (1H NMR), and 13C nuclear magnetic resonance spectrometer (13C NMR) were used. Moreover, the antioxidant activity of the derivatives for three types of free radicals, i.e., hydroxyl radical, superoxide radical, and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical was evaluated in vitro. In addition, the L929 cells were adopted to test the cytotoxicity of chitosan and its derivatives by CCK-8 assay. The class of the carboxymethyl chitosan derivatives showed a strong scavenging ability against the three free radicals at 1.6 mg/mL, with scavenging rate of over 70% and some up to 100%. At this high rate, the overall cell viability in the toxicity test reached more than 80%, indicating that the synthetic derivative had a little cytotoxicity. The results show that the introduction of carboxymethyl group to chitosan increased the water-solubility of chitosan, and the combination of sulfonate ions with different chain lengths further enhanced the antioxidant activity of chitosan. Therefore, the sulfonium-containing carboxymethyl chitosan derivatives had excellent bioactivity with good application prospects in food, biomedicine, and medical fields.
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Data Availability Statement
The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.
References
Adjimani J P, Asare P. 2015. Antioxidant and free radical scavenging activity of iron chelators. Toxicology Reports, 2: 721–728, https://doi.org/10.1016/j.toxrep.2015.04.005.
Almada M, Leal-Martínez B H, Hassan N, Kogan M J, Burboa M G, Topete A, Valdez M A, Juárez J. 2017. Photothermal conversion efficiency and cytotoxic effect of gold nanorods stabilized with chitosan, alginate and poly(vinyl alcohol). Materials Science and Engineering: C, 77: 583–593, https://doi.org/10.1016/j.msec.2017.03.218.
Ankri S, Mirelman D. 1999. Antimicrobial properties of allicin from garlic. Microbes and Infection, 1(2): 125–129, https://doi.org/10.1016/S1286-4579(99)80003-3.
Burits M, Bucar F. 2000. Antioxidant activity of Nigella sativa essential oil. Phytotherapy Research, 14(5): 323–328, https://doi.org/10.1002/1099-1573(200008)14:5<323::AID-PTR621>3.0.CO;2-Q.
Chen J H, Ho C T. 1997. Antioxidant activities of caffeic acid and its related hydroxycinnamic acid compounds. Journal of Agricultural and Food Chemistry, 45(7): 2 374–2 378, https://doi.org/10.1021/jf970055t.
Chen L Y, Du Y M, Zeng X Q. 2003. Relationships between the molecular structure and moisture-absorption and moisture-retention abilities of carboxymethyl chitosan: II. Effect of degree of deacetylation and carboxymethylation. Carbohydrate Research, 338(7): 333–340, https://doi.org/10.1016/S0008-6215(02)00462-7.
Chen L Y, Tian Z G, Du Y M. 2004a. Synthesis and pH sensitivity of carboxymethyl chitosan-based polyampholyte hydrogels for protein carrier matrices. Biomaterials, 25(17): 3 725–3 732, https://doi.org/10.1016/j.biomaterials.2003.09.100.
Chen S C, Wu Y C, Mi F L, Lin Y H, Yu L C, Sung H W. 2004b. A novel pH-sensitive hydrogel composed of N, O-carboxymethyl chitosan and alginate cross-linked by genipin for protein drug delivery. Journal of Controlled Release, 96(2): 285–300, https://doi.org/10.1016/j.jconrel.2004.02.002.
Chen X G, Park H J. 2003. Chemical characteristics of O-carboxymethyl chitosans related to the preparation conditions. Carbohydrate Polymers, 53(4): 355–359, https://doi.org/10.1016/S0144-8617(03)00051-1.
El Ashry E S H, El-Rafey E, Rezki N, Abou-Elnaga H H, Bakry W M A, Boghdadi Y M. 2014. Evaluation of some functionalized imidazoles and 1, 2, 4-triazoles as antioxidant additives for industrial lubricating oils and correlating the results with the structures of additives using empirical AM1 calculations. Journal of Saudi Chemical Society, 18(5): 443–449, https://doi.org/10.1016/j.jscs.2011.09.010.
Gensch K H, Pitman I H, Higuchi T. 1968. Oxidation of thioethers to sulfoxides by iodine. II. catalytic role of some carboxylic acid anions. Journal of the American Chemical Society, 90(8): 2 096–2 104.
Guo Z Y, Liu H Y, Chen X L, Ji X, Li P C. 2006. Hydroxyl radicals scavenging activity of N-substituted chitosan and quaternized chitosan. Bioorganic & Medicinal Chemistry Letters, 16(24): 6 348–6 350, https://doi.org/10.1016/j.bmcl.2006.09.009.
Guo Z Y, Xing R E, Liu S, Yu H H, Wang P B, Li C P, Li P C. 2005. The synthesis and antioxidant activity of the Schiff bases of chitosan and carboxymethyl chitosan. Bioorganic & Medicinal Chemistry Letters, 15(20): 4 600–4 603, https://doi.org/10.1016/j.bmcl.2005.06.095.
Hu Y X, Zhang J, Yu C W, Li Q, Dong F, Wang G, Guo Z Y. 2014. Synthesis, characterization, and antioxidant properties of novel inulin derivatives with amino-pyridine group. International Journal of Biological Macromolecules, 70: 44–49, https://doi.org/10.1016/j.ijbiomac.2014.06.024.
Jayakumar R, Prabaharan M, Nair S V, Tokura S, Tamura H, Selvamurugan N. 2010. Novel carboxymethyl derivatives of chitin and chitosan materials and their biomedical applications. Progress in Materials Science, 55(7): 675–709, https://doi.org/10.1016/j.pmatsci.2010.03.001.
Kim S K, Rajapakse N. 2005. Enzymatic production and biological activities of chitosan oligosaccharides (COS): a review. Carbohydrate Polymers, 62(4): 357–368, https://doi.org/10.1016/j.carbpol.2005.08.012.
Kim Y H, Kim G H, Yoon K S, Shankar S, Rhim J W. 2020. Comparative antibacterial and antifungal activities of sulfur nanoparticles capped with chitosan. Microbial Pathogenesis, 144: 104178, https://doi.org/10.1016/j.micpath.2020.104178.
Li R S, Wan Q H. 2018. A thioether-embedded mixed-mode cyano-bonded chromatographic stationary phase: preparation, characterization and retention mechanism. Chromatographia, 81(12): 1 623–1 630, https://doi.org/10.1007/s10337-018-3630-1.
Lu G Y, Kong L J, Sheng B Y, Wang G, Gong Y D, Zhang X F. 2007. Degradation of covalently cross-linked carboxymethyl chitosan and its potential application for peripheral nerve regeneration. European Polymer Journal, 43(9): 3 807–3 818, https://doi.org/10.1016/j.eurpolymj.2007.06.016
Mensor L L, Menezes F S, Leitão G G, Reis A S, dos Santos T C, Coube C S, Leitão S G. 2001. Screening of Brazilian plant extracts for antioxidant activity by the use of DPPH free radical method. Phytotherapy Research, 15(2): 127–130, https://doi.org/10.1002/ptr.687.
Mi Y Q, Tan W Q, Zhang J J, Wei L J, Chen Y, Li Q, Dong F, Guo Z Y. 2018. Synthesis, characterization, and antifungal property of hydroxypropyltrimethyl ammonium chitosan halogenated acetates. Marine Drugs, 16(9): 315, https://doi.org/10.3390/md16090315.
Mourya V K, Inamdar N N. 2008. Chitosan-modifications and applications: opportunities galore. Reactive and Functional Polymers, 68(6): 1 013–1 051, https://doi.org/10.1016/j.reactfunctpolym.2008.03.002.
Oh N, Nam K H, Goh M, Ku B C, Kim J G, You N H. 2019. Synthesis of colorless and highly refractive poly(phenylene thioether ether) derived from 2, 7-(4, 4′-diphenol) thiothianthrene. Polymer, 165: 191–197, https://doi.org/10.1016/j.polymer.2019.01.033.
Priyadarshi R, Kim H J, Rhim J W. 2021. Effect of sulfur nanoparticles on properties of alginate-based films for active food packaging applications. Food Hydrocolloids, 110: 106155, https://doi.org/10.1016/j.foodhyd.2020.106155.
Rabea E I, Badawy M E T, Stevens C V, Smagghe G, Steurbaut W. 2003. Chitosan as antimicrobial agent: applications and mode of action. Biomacromolecules, 4(6): 1 457–1 465, https://doi.org/10.1021/bm034130m.
Rinaudo M. 2006. Chitin and chitosan: properties and applications. Progress in Polymer Science, 31(7): 603632, https://doi.org/10.1016/j.progpolymsci.2006.06.001.
Saedi S, Shokri M, Rhim J W. 2020. Antimicrobial activity of sulfur nanoparticles: effect of preparation methods. Arabian Journal of Chemistry, 13(8): 6 580–6 588, https://doi.org/10.1016/j.arabjc.2020.06.014.
Saundane A R, Manjunatha Y. 2016. Synthesis, antimicrobial and antioxidant activities of 2-oxo-6-phenyl-2-yl-4-(2′-phenyl-5′-substituted 1H-indol-3′-yl)-1, 2-dihydro pyridin-3-carbonitriles and their derivatives. Arabian Journal of Chemistry, 9(1): S501–S509, https://doi.org/10.1016/j.arabjc.2011.06.011.
Sun L P, Du Y M, Fan L H, Chen X, Yang J H. 2006. Preparation, characterization and antimicrobial activity of quaternized carboxymethyl chitosan and application as pulp-cap. Polymer, 47(6): 1 796–1 804, https://doi.org/10.1016/j.polymer.2006.01.073.
Tan W Q, Li Q, Dong F, Wei L J, Guo Z Y. 2016. Synthesis, characterization, and antifungal property of chitosan ammonium salts with halogens. International Journal of Biological Macromolecules, 92: 293–298, https://doi.org/10.1016/j.ijbiomac.2016.07.023.
Wang J H, Li D D, Tao W, Lu Y, Yang X Z, Wang J. 2019. Synthesis of an oxidation-sensitive polyphosphoester bearing thioether group for triggered drug release. Biomacromolecules, 20(4): 1 740–1 747, https://doi.org/10.1021/acs.biomac.9b00101.
Xia W S, Liu P, Zhang J L, Chen J. 2011. Biological activities of chitosan and chitooligosaccharides. Food Hydrocolloids, 25(2): 170–179, https://doi.org/10.1016/j.foodhyd.2010.03.003.
Xie W M, Xu P X, Liu Q. 2001. Antioxidant activity of water-soluble chitosan derivatives. Bioorganic & Medicinal Chemistry Letters, 11(13): 1 699–1 701, https://doi.org/10.1016/S0960-894X(01)00285-2.
Xing R E, Liu S, Guo Z Y, Yu H H, Li C P, Ji X, Feng J H, Li P C. 2006. The antioxidant activity of glucosamine hydrochloride in vitro. Bioorganic & Medicinal Chemistry, 14(6): 1 706–1 709, https://doi.org/10.1016/j.bmc.2005.10.018.
Xu T, Xin M H, Li M C, Huang H L, Zhou S Q. 2010. Synthesis, characteristic and antibacterial activity of N, N, N-trimethyl chitosan and its carboxymethyl derivatives. Carbohydrate Polymers, 81(4): 931–936, https://doi.org/10.1016/j.carbpol.2010.04.008.
Zhang J J, Tan W Q, Wang G, Yin X L, Li Q, Dong F, Guo Z Y 2018a. Synthesis, characterization, and the antioxidant activity of N, N, N-trimethyl chitosan salts. International Journal of Biological Macromolecules, 118: 9–14, https://doi.org/10.1016/j.ijbiomac.2018.06.018.
Zhang J J, Tan W Q, Wei L J, Chen Y, Mi Y Q, Sun X Q, Li Q, Dong F, Guo Z Y. 2019. Synthesis of urea-functionalized chitosan derivatives for potential antifungal and antioxidant applications. Carbohydrate Polymers, 215: 108–118, https://doi.org/10.1016/j.carbpol.2019.03.067.
Zhang S, Liu X D, Jin X D, Li H F, Sun J, Gu X Y. 2018b. The novel application of chitosan: Effects of cross-linked chitosan on the fire performance of thermoplastic polyurethane. Carbohydrate Polymers, 189: 313–321, https://doi.org/10.1016/j.carbpol.2018.02.034.
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Supported by the National Key R&D Program of China (No. 2019YFD0900705), the Key Deployment Projects of the Marine Science Research Center of the Chinese Academy of Sciences (No. COMS2020J04), and the Natural Science Foundation of Shandong Province of China (No. ZR2019BD064)
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Sun, X., Zhang, J., Mi, Y. et al. Synthesis, characterization, and antioxidant activity of carboxymethyl chitosan derivatives containing sulfonium salt. J. Ocean. Limnol. 40, 284–295 (2022). https://doi.org/10.1007/s00343-021-0352-2
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DOI: https://doi.org/10.1007/s00343-021-0352-2