Synthesis of polyhedral oligomeric silsesquioxane-n-acetylcysteine conjugate with click chemistry and ıts antioxidant response and biocompatibility

İdil Karaca Açarı; Sevgi Balcıoğlu; Burhan Ateş; Süleyman Köytepe; İsmet Yılmaz; Turgay Seçkin

doi:10.17776/csj.688124

Research Article

Synthesis of polyhedral oligomeric silsesquioxane-n-acetylcysteine conjugate with click chemistry and ıts antioxidant response and biocompatibility

Year 2020, Volume: 41 Issue: 2, 386 - 396, 25.06.2020

İdil Karaca Açarı , Sevgi Balcıoğlu , Burhan Ateş , Süleyman Köytepe , İsmet Yılmaz , Turgay Seçkin

https://doi.org/10.17776/csj.688124

Abstract

In this study, polyhedral oligomeric silsesquioxane-N-acetylcysteine (POSS-NAC) conjugate as a potential antioxidant molecule was synthesized from N-acetylcysteine (NAC) and amino-functional POSS structure by click chemistry. The chemical structures and thermal properties of the synthesised POSS-NAC conjugate was characterized by spectroscopic and thermal analysis techniques. The antioxidant capacity of the POSS-NAC conjugate was also determined by the 2,2’-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical scavenging activity and reducing power methods. According to the reducing power method, POSS-NAC structure has lower reducing activity than standard ascorbic acid and trolox (p<0.001). It was found from the ABTS radical scavenging activity results that the synthesized POSS-NAC conjugate had a significantly higher radical scavenging effect than the standards (p <0.001). Biocompatibility properties of the POSS-NAC structure were detected in vitro cell culture system with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test on L-929 mouse fibroblast cells. The synthesized POSS-NAC conjugate exhibits high antioxidant activity and good biocompatibility.

Keywords

Polyhedral oligomeric silsesquioxane (POSS), , N-Acetylcysteine (NAC), , antioxidant activity, , biocompatibility

Supporting Institution

Inonu University‘s scientific research projects unit (BAP)

Project Number

2013/157

Thanks

Inonu University‘s scientific research projects unit (BAP)

References

[1] Kuo S.W. and Chang F.C. POSS related polymer nanocomposites. Prog. Polym. Sci., 36(12) (2011) 1649–1696.
[2] Cordes D.B., Lickiss P.D. and Rataboul F. Recent developments in the chemistry of cubic polyhedral oligosilsesquioxanes. Chem. Rev., 110(4) (2010) 2081–2173.
[3] Shea K.J. and Loy D.A. Bridged polysilsesquioxanes. Molecular-engineered hybrid organic−inorganic materials. Chem. Mater., 13(10) ( 2001) 3306–3319.
[4] Ebunoluwa A., Biswajit S. and Paschalis A. Polyhedral Oligomeric Silsesquioxane (POSS)-Containing Polymer Nanocomposites. Nanomaterials, 2(4) (2012) 445-475.
[5] Shockey E.G., Bolf A.G., Jones P.F., Schurab, J.J., Chaffee K.P., Haddad T.S. and Lichtenhan J.D. Functionalized polyhedral oligomeric silsesquioxanes: New graftable POSS hydride, POSS alfa-olefin, POSS epoxy, and POSS chlorosilane macromers and POSS-siloxane triblocks. Appl. Organomet. Chem., 13(34) (1999) 311-327.
[6] Linchtenhan J.D., Otonari Y.A. and Carr M.J. Linear hybrid polymer building blocks: Methacrylate-functionalized polyhedral oligomeric silsesquioxane monomers and polymers. Macromolecules., 28(24) (1995) 8435-8437.
[7] Wu J. and Mather P.T. POSS polymers: Physical properties and biomaterials applications. Polym. Rev., 49(1) (2009) 25-63.
[8] Kanamori K. and Nakanishi K. Controlled pore formation in organotrialkoxy-silane-derived hybrids: from aerogels to hierarchically porous monoliths. Chem. Soc. Rev., 40(2) (2011) 754-770.
[9] Mantz R.A., Johns P.F., Chaffee K.P., Lichtenhan J.D., Gilman J.W., Ismail I.M.K. and Burmeister M.J. Thermolysis of polyhedral oligomeric silsesquioxane (POSS) macromers and POSS-siloxane copolymers. Chem. Mater., 8(6) (1996) 1250-1259.
[10] Leu C.M., Reddy G.M., Wei K.H. and Shu C.F. Synthesis and dielectric properties of polyimide-chain-end ethered polyhedral oligomeric silsesquioxane nanocomposites. Chem. Mater., 15(11) (2003) 2261-2265.
[11] Köytepe S., Demirel M.H., Gültek A., Seçkin T. Metallo-supramolecular materials based on terpyridine functionalized polyhedral silsesquioxane. Polym Int., 63(4) (2014) 778-787.
[12] Li G.Z., Wang H.N. and Pittman C.U. Polyhedral oligomeric silsesquioxane (POSS) polymers and copolymers. J. Inorg. Organomet. Polym., 11 (3) (2001) 123-154.
[13] Li G.Z., Yamamato T., Nozaki K. and Hikosaka M. Crystallization of ladder like polyphenyl silsesquioxane (PPSQ)/isotactic polystyrene (i-PS) blends. Polymer., 42(20) (2009) 8435-8441.
[14] Liang K., Toghian H., Li G. and Pittman C.U. Synthesis, morphology, and viscoelastic properties of cyanate ester/polyhedral oligomeric silsesquioxane nanocomposites. J. Polym. Sci., 43(17) (2005) 3887-3898.
[15] McCusker C., Carrol J.B. and Rotello V.M. Cationic polyhedral oligomeric silsesquioxane (POSS) units as carriers for drug delivery processes. Chem. Commun., 28(8) (2005) 996-998.
[16] Fong H., Dickens S.H. and Flaim G.M. Evaluation of dental restorative composites containing polyhedral oligomeric silsesquioxane methacrylate. Dent. Mats., 21(6) (2005) 520-529.
[17] Zou Q.C., Yan Q.J., Song G.W., Zhang S.L. and Wu L.M. Detection of DNA using cationic polyhedral oligomeric silsesquioxane nanoparticles as the probe by resonance light scattering technique. Biosens. Bioelectron., 22(7) (2007) 1461-1465.
[18] Sarkar S., Buriesci G., Wojcik A., Aresti N., Hamilton G. and Seifalian A.M. Manufacture of small calibre quadruple lamina vascular bypass grafts using a novel automated extrusion-phase-inversion method and nanocomposite polymer. J. Biomech., 42(6) (2009) 722-730.
[19] Ghanbari H., Kidane A.G., Burriesci G., Ramesh B., Darbyshire A. and Seifalian A.M. The anti-calcification potential of a silsesquioxane nanocomposite polymer under in vitro conditions: Potential material for synthetic leaflet heart valve. Acta Biomater., 6(11) (2010) 4249-4260.
[20] Li G., Wang L., Ni H. and Pittman Jr C.U. Polyhedral oligomeric silsesquioxane (POSS) polymers and copolymers: A review. J. Inorg. Organomet. Polym., 11(3) (2002) 123-154.
[21] Kerksick C. and Willoughby D. The antioxidant role of glutathione and N-acetyl-cysteine supplements and exercise ınduced oxidative stress. J. Int. Soc. Sports Nutr., 2(2) (2005) 38-44.
[22] Ater B., Abraham L. and Ercal N. Antioxidant and free radical scavenging properties of N-acetylsysteine amide (NACA) and comparison with N-acetylcysteine (NAC). Free Rad. Res., 42(4) (2008) 372-377.
[23] Kelly G.S. Clinical applications of N-acetylcysteine. Altern. Med. Rev., 3(2) (1998) 114-127.
[24] Flanagan R.J. and Meredith T.J. Use of N-acetylcysteine in clinical toxicology. Am. J. Med., 91(3C) (1991) 131-139.
[25] Auroma O.I., Halliwell B., Hoey B.M. and Butler J. The antioxidant action of N-acetylcysteine: its reaction with hydrogen peroxide, hydroxyl radical, superoxide and hypochlorous acid. Free Radic. Biol. Med., 6(6) (1989) 593-597.
[26] Kiskan B., Gacal B., Asan M., Gunaydin E.C., Yilmaz I. and Yagci Y. Synthesis and characterization of pyrrole and thiophene functional polystyrenes via ‘‘click chemistry’’. Polym. Bull., 67(4) (2011) 609-621.
[27] Hein C.D., Liu X-M. and Wang D. Click chemistry, a powerful tool for pharmaceutical sciences. Pharm. Res., 25(10) (2008) 2216-2230.
[28] Caselli E., Ramognoli C., Vahabi R., Taracila M.A., Bonomo R. and Prati, F. Click Chemistry in Lead Optimization of Boronic Acids as β-Lactamase Inhibitors. J. Med. Chem., 58(14) (2015) 5445-5458.
[29] Seçkin T., Gültek A. and Köytepe S. Synthesis and Characterization of Novel Hyperbranched Polyimides Based on Silsesquioxane Nanocomposite Networks. Turk. J. Chem., 29(1) (2005) 49-59.
[30] Zhang X. and Zhang Y. Applications of Azide-Based Bioorthogonal Click Chemistry in Glycobiology. Molecules., 18 (6) (2010) 7145-7159.
[31] Re R., Pellegrini N., Proteggente A., Pannala A., Yang M. and Rice-Evans C. Antioxidant activity applying an improved ABTS radical cation decolorization assay. Free Radic. Biol. Med., 26(10) (1999) 1231-1237.
[32] Hwang J.Y. Antioxidative activity of roasted and defatted peanut kernels. Food Res. Int., 34(7) (2001) 639-647.
[33] Wataha JC., Craig RG. and Hanks CT. Precision of and new methods for testing in vitro alloy cytotoxicity. Dent. Mater., 8(1) (1992) 65-70.
[34] Juciute R., Bukelskiene V., Rutkunas V., Trumpaite-Vanagiene R. and Puriene A. In vitro evaluation of cytotoxicity of permanent prosthetic materials. Baltic Dent. Maxillofac. J., 13(3) (2011) 75-80.
[35] Hirohara T., Kai T., Ohshita J. and Kaneko Y. Preparation of protic ionic liquids containing cyclic oligosiloxane frameworks. RSC Adv., 7 (2017) 10575–10582.
[36] Oussadi K., Montembault V. and Fontaine L. Synthesis of poly(oxyethylene phosphate)‐g‐poly(ethylene oxide) via the “grafting onto” approach by “click” chemistry. J. Polym. Sci. A Polym. Chem., 49 (2011) 5124-5128.
[37] Mahou R. and Wandrey C. Versatile Route to Synthesize Heterobifunctional Poly(ethylene glycol) of Variable Functionality for Subsequent Pegylation. Polymers., 4 (2012) 561-589.
[38] Kunz S., Maturi M.M., Schrader I., Backenköhler J., Tschurl M. and Heiz U., Same ligand – Different binding: A way to control the binding of N-acetyl-cysteine (NAC) to Pt clusters. J. Colloid Interface Sci., 426 (2014) 264–269.
[39] Gültek A., Seçkin T. and Adıgüzel H.İ. Design and characterization of amino and chloro functionalized rhombohedral silsesquioxanes. Turk. J. Chem., 29(4) (2005) 391- 399.
[40] Oehninger L., Stefanopoulou M., Alborzinia H., Schur J., Ledewing S., Naikawa K., Munoz-Castro A., Köster R.W., Baumann K., Wölfl S., Sheldrick W.S. and Ott I. Evaluation of arene ruthenium(II) N-heterocycliccarbene complexes as organometallics interacting with thiol and selenol containing biomolecules. Dalton Trans., 42(5) (2013) 1657-1666.
[41] Demirel M.H., Köytepe S., Gültek A. and Seçkin T. Synthesis and stimuli- responsive properties of the phenanthroline based metallo-supra molecular polymers. J. Polym. Res., 21(2) (2014) 345-355.
[42] Navath R.S., Kurtoğlu Y.E., Wang B., Kannan S., Romero R. and Kannan R.M. Dendrimers-drug conjugates for tailored intracellular drug release based on glutathione levels. Bioconjugate Chem., 19(12) (2008) 2446-2455.
[43] Desai K.G.H., Mallery S.R and Schwendeman S.P. Formulation and characterization of injectable poly(DL-Lactide-co-glycolide) ımplants loaded with N-Acetylcysteine, a MMP inhibitor. Pharm. Res., 25(3) (2008) 586-597.
[44] Cheng Y., Yang H.C., Cho J.H., Lee S.H. and Lim B.S. The effect on N- Acetylcysteine addition on the polymerization behavior of PMMA bone cement. Macromol. Res., 20(9) (2012) 928-938.
[45] Ghanbari H., Cousins BG. and Seifalian AM. A nanocage for nanomedicine: polyhedral oligomeric silsesquioxane (POSS). Macromol. Rapid Commun., 32(14) (2011) 1032-1046.
[46] Kim SK., Heo SJ., Koak JY., Lee JH., Lee YM., Chung DJ., Lee JI. and Hong S.D. A biocompatibility study of a reinforced acrylic-based hybrid denture composite resin with polyhedraloligosilsesquioxane. J. Oral. Rehabil., 34(5) (2007) 389-395.
[47] Punshona G., Vara D.S. Sales K.M., Kidane A.G., Salacinski H.J. and Seifalian A.M. “Interactions between endothelial cells and a poly (carbonate-silsesquioxane-bridge-urea)urethane”. Biomaterials., 26(32) (2005) 6271-6279.
[48] Skaria S. and Schricker S.R. Synthesis and characterization of ınorganic-organic hybrid materials derived from polysilsesquioxanes (POSS). J. Macromol. Sci. A: Pure Appl. Chem., 47(5) (2015) 381-391.