Title
Different approaches to agarose sulfation with sulfamic acid
Authors
ALEKSANDR S. KAZACHENKO, OLGA YU. FETISOVA, ANTON A. KARACHAROV, YAROSLAVA D. BEREZHNAYA, NOUREDDINE ISSAOUI, MAKSIM A. LUTOSHKIN, VALENTIN V. SYCHEV, ANNA S. KAZACHENKO, OMAR M. AL-DOSSARY and LEDA G. BOUSIAKOU,

Received December 4, 2023
Published Volume 58 Issue 1-2 January-February
Keywords agarose, sulfation, sulfated agarose, catalysis, deep eutectic solvent, sulfamic acid

Abstract
Sulfated polysaccharides are important promising biologically active substances with anticoagulant properties. Biological activity is affected by the method of preparation, as well as the type of the polysaccharide and its molecular structure. In this work, we have considered various methods for the synthesis of promising anticoagulants – polysaccharide sulfates using the example of obtaining agarose sulfate. We compared various sulfating agents: chlorosulfonic acid, sulfamic acid, with various activators, and a deep eutectic solvent mixture of sulfamic acid with urea (in the melt). It has been shown that when urea is used as an activator of the process of sulfation of agarose with sulfamic acid in 1,4-dioxane, agarose sulfate with a high sulfur content (up to 14.5 wt%) is formed, which is close to the use of chlorosulfonic acid as a sulfating agent (with the production of agarose sulfate with 15.0 wt% sulfur). The use of solid catalysts in the process of sulfation of agarose with sulfamic acid leads to the production of agarose sulfate with a sulfur content of up to 14.1 wt% (for a catalyst based on the oxidized carbonaceous material Sibunit-4®). Sulfation of agarose in a deep eutectic solvent – a mixture of sulfamic acid with urea – leads to the production of agarose sulfate with a sulfur content of up to 13.7 wt%. The resulting agarose sulfates were characterized by FTIR spectroscopy, X-ray diffraction, elemental analysis, atomic force microscopy and DFT.