Synthesis optimization, DFT and physicochemical study of chitosan sulfates

Chitosan is an important biologically active amino polysaccharide. Water-soluble sulfated chitosan deriva-tives are widely used as anticoagulant and antiviral drugs. In this study, new methods for sulfamic acid sulfation of chitosan in the presence of urea in 1,4-dioxane and in a deep eutectic solvent representing a mixture of sulfamic acid and urea have been proposed. Mathematical models of sulfation of chitosan in these systems have been built. The obtained sulfated chitosan derivatives have been investigated by Fourier-transform infrared spectroscopy, X-ray diffractometry, atomic force microscopy, gel permeation chromatography, elemental analysis, and the density functional theory. The introduction of the sulfate group into the chitosan molecule was proven by infrared spectroscopy. When using the sulfamic acid/urea mixture, side reactions of carbamation of chitosan have been observed. It has been established from the atomic force microscopy data that the sulfated chitosan film surface consists of spherical particles par-tially agglomerated with each other. According to the gel permeation chromatography data, sulfated chi-tosan obtained in different systems, but under the same conditions (temperature and time), has different molecular weight distributions. The molecular weight distribution curve of the sulfated chitosan obtained in the sulfamic acid-urea-1,4-dioxane system is significantly shifted to the high-molecular region (Mw -36.6 kDa), while the sulfated chitosan obtained in the sulfamic acid/urea deep eutectic solvent (Mw -27.2 kDa). The density functional theory calculation of chitosan sulfates in the B3LYP/6-31G(d, p) basis set have been made. (c) 2021 Elsevier B.V. All rights reserved.