Advertisement

Cellulose

, Volume 10, Issue 1, pp 65–74 | Cite as

Regioselectively Modified Cellulose and Chitosan Derivatives for Mono- and Multilayer Surface Coatings of Hemocompatible Biomaterials

  • Hanno BaumannEmail author
  • Chun Liu
  • Volker Faust
Article

Abstract

In this study different synthetic strategies were developed and applied to introduce solely or in combination heparin/heparansulfate-like functional groups such as N-sulfo, O-sulfo, N-acetyl, and N-carboxymethyl groups into chitosan and cellulose with highest possible regioselectivity and completeness and defined distribution along the polymer chain. Completely substituted 6-amino-6-deoxycellulose and related derivatives were prepared from tosylcellulose (DS 2.02; C6 1.0) by nucleophilic substitution with azido groups only in the 6-position at 50 °C with subsequent reduction to amino groups and completely removing tosyl groups in the 2,3-position. 2,6-Di-O-sulfocellulose was prepared using the reactivity difference between C-2, C-6 and C-3 of cellulose. The reactivity difference between amino groups and hydroxyl groups was used to prepare various N-substituted derivatives. Partially 2,6-di-O-sulfated cellulose was obtained from trimethylsilylcellulose by the insertion of sulfurtrioxide into the Si–O ether linkage. Partially 3-O-sulfocellulose was synthesized by protecting C-2 and C-6 with trifluoroacetyl groups. A copper–chitosan complex was used to synthesize 6-O-sulfochitosan with a DS of 1.0 at C-6 and various partially 6-O-desulfonated products are possible. Using the phthalimido group to increase the solubility of chitosan in DMF, the regioselectivity of 3-O-sulfo groups was improved by regioselective 6-O-desulfonation of nearly complete 3,6-O-disulfochitosan. The platelet adhesion properties of immobilized regioselectively modified water-soluble derivatives on membranes have been tested in vitro. Some regioselectively modified chitosan and cellulose derivatives are potential candidates for the surface coatings of biomaterials if the regioselective reactions are somewhat further optimized.

6-Amino-6-deoxycellulose Chitosan and cellulose chemistry Hemocompatibility Heparin chemistry N-carboxymethylation N-sulfonation Platelet adhesion tests Sulfation and desulfation reaction Systematic protection group strategy Temperature dependent regioselective substitution 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Amiji M.M. 1998. Platelet adhesion and activation on an amphoteric chitosan derivative bearing sulfonate groups. Colloids Surf. B: Biointerfaces 10: 263-271.Google Scholar
  2. Baumann H. 2001. The role of regioselectively sulphated and acetylated polysaccharide coatings of biomaterials for reducing platelet and plasma protein adhesion. Sem. Thromb. Hemost. 27: 445-464.Google Scholar
  3. Baumann H. and Faust V. 2001. Concepts for improved regioselectivity of O-sulfo, N-sulfo, N-acetyl and N-carboxymethylgroups in chitosan derivatives. Carbohydr. Res. 331: 43-57.Google Scholar
  4. Baumann H., Keller R. and Ruzicka E. 1991. Partially cationized cellulose for non-thrombogenic membrane in the presence of heparin and endothelial cell-surface-heparansulfate (ES-HS). J. Membr. Sci. 61: 253-268.Google Scholar
  5. Baumann H., Keller R. and Baumann U. 1999. Development of microvascular artificial platelet inert blood vessels, basic principles and animal experiments. In: Ottenbrite (ed.), Frontiers in Biomedical Polymer Applications. Technomic Publishing, Lancaster, Basel, pp. 159-174.Google Scholar
  6. Baumann H., Richter A., Klemm D. and Faust V. 2000. Concepts for preparation of novel regioselective modified cellulose derivatives sulfated, aminated, carboxylated and acetylated for hemocompatible ultrathin coatings on biomaterials. Macromol. Chem. Phys. 201: 1950-1962.Google Scholar
  7. Casu B., Johnson E.A., Mantovani M., Mulloy B., Oreste P., Pescador R., Prino G., Torri G. and Zopetti G. 1983. Correlation between structure, fat-clearing and anticoagulant properties of heparins and heparan sulphates. Arzneim. Forsch. 33: 135-142.Google Scholar
  8. Focher B., Massoli A., Torri G., Gervasini A. and Morazzoni F. 1986. High molecular weight chitosan 6-O-sulfate. Synthesis, ESR and NMR characterization. Makromol. Chem. 187: 2609-2620.Google Scholar
  9. Gallagher J.T. and Lyon M. 1989. Molecular organization and functions of heparan sulphate. In: Lane D.A. and Lindahl U. (eds), Heparin, Chemical and Biological Properties, Clinical Applications. Edward Arnold, London, Melbourne, Auckland, pp. 135-158.Google Scholar
  10. Haskins J.F. and Weinstein A.H. 1954. Aminocellulose derivatives. J. Org. Chem. 19: 67-69.Google Scholar
  11. Heinze T., Koschella A., Magdaleno-Maiza L. and Ulrich A.S. 2001. Nucleophilic displacement reactions on tosyl cellulose by chiral amines. Polym. Bull. 46: 7-13.Google Scholar
  12. Holme K.R. and Perlin A.S. 1997. Chitosan N-sulfate. A watersoluble polyelectrolyte. Carbohydr. Res. 302: 7-12.Google Scholar
  13. Huppertz B., Keller R. and Baumann H. 1999. Influence of semisynthetic heparin like molecules with regioselective varied sulfate groups covalently immobilized on polymer surfaces on thrombozyte adhesion. In: Chiellini E., Cohn D., Migliaresi C., Ottenbrite R. and Sunamoto J. (eds), Frontiers in Biomedical Polymers 2. Technomic Publishing, Lancaster, Basel, pp. 115-129.Google Scholar
  14. Kern H., Choi S. and Wenz G. 1998. New functional derivatives from 2,3-di-O-alkylcelluloses. Polym. Prepr. Am. Chem. Soc., Div. Polym. Chem. 39: 80-81.Google Scholar
  15. Klemm D., Heinze T., Stein A. and Liebert T. 1995. Polyglucane derivatives with regular substituent distribution. Macromol. Symp. 99: 129-140.Google Scholar
  16. Lee K.Y., Ha W.S. and Park W.H. 1995. Blood compatibility and biodegradability of partially N-acylated chitosan derivatives. Biomaterials 16: 1211-1216.Google Scholar
  17. Liu C. and Baumann H. 2002. Exclusive and complete introduction of amino groups and their N-sulfo and N-carboxymethyl groups into the 6-position of cellulose without the use of protecting groups. Carbohydr. Res. 337: 1297-1307.Google Scholar
  18. McCormick C.L., Dawsey T.R. and Newman J.K. 1990. Competitive formation of cellulose p-toluenesulfonate and chlorodeoxycellulose during homogeneous reaction of p-toluenesulfonyl chloride with cellulose in N,N-dimethylacetamide-lithium chloride. Carbohydr. Res. 208: 183-191.Google Scholar
  19. Muzzarelli R.A.A., Tanfani F., Emanuelli M. and Mariotti S. 1982. N-carboxymethylidene chitosans and N-carboxymethyl chitosan: novel chelating polyampholytes obtained from chitosan. Carbohydr. Res. 107: 199-214.Google Scholar
  20. Nishimura S.-I., Kai H., Shinada K., Yoshida T., Tokura S., Kurita K., Nakashima H., Yamamoto N. and Uryu T. 1998. Regioselective syntheses of sulfated polysaccharides: specific anti HIV-1 activity of novel chitin sulfates. Carbohydr. Res. 306: 427-433.Google Scholar
  21. Rahn K., Diamantoglou M., Klemm D., Berghmans H. and Heinze T. 1996. Homogeneous synthesis of cellulose p-toluenesulfonates in N,N-dimethylacetamide/LiCl solvent system. Angew. Makromol. Chem. 238: 143-163.Google Scholar
  22. Takano R., Ye Z., Ta Z.V., Hayashi K., Kariya Y. and Hara S. 1998. Specific 6-O-desulfation of heparin. Carbohydr. Lett. 3: 71-77.Google Scholar
  23. Teshirogi T., Yamamoto H., Sakamoto M. and Tonami H. 1979. Synthesis of 6-amino-6-deoxycellulose. Sen'i Gakkaishi 35: T525-T529.Google Scholar
  24. Tumova S., Woods A. and Couchman J.R. 2000. Heparan sulfate proteoglycans on the cell surface: versatile coordinators of cellular functions. Int. J. Biochem. Cell Biol. 32: 269-288.Google Scholar
  25. Uchiyama H. and Nagasawa K. 1991. Changes in the structure and biological property of N,O-sulfate transferred, N-resulfated heparin. J. Biol. Chem. 266: 6756-6760.Google Scholar
  26. Usov A.I., Nosova N.I., Firgang S.I. and Golosa O.P. 1973. Introduction of azide groups into a cellulose molecule and conversion of azide derivatives into aminopolysaccharides. Vysokomol. Soedin., Ser. A 15: 1150-1153.Google Scholar

Copyright information

© Kluwer Academic Publishers 2003

Authors and Affiliations

  1. 1.ITMC, Macromolecular Chemistry and Textile Chemistry, Hemocompatible and Biocompatible BiomaterialsUniversity of Technology AachenAachenGermany

Personalised recommendations