Sulfation of agarose with ammonium sulfamate: A combined experimental and theoretical study

Agarose sulfates are bioactive modified polysaccharides important for application. To obtain the bioactive agarose derivatives and expand the range of their potential use, the modification with some functional groups is needed. Agarose sulfates exhibit the anticoagulant, hypolipidemic, and other-type bioactivity. In this study, different methods for preparation of agarose sulfates using nontoxic ammonium sulfamate are investigated. Several activators and catalysts of the process of sulfation with ammonium sulfamate are examined. It is shown that urea does not significantly activate ammonium sulfamate in the sulfation reaction, while potassium permanganate ensures a sulfur content of up to 13.2 wt% in the synthesized agarose sulfate. When Lewis acids (titanium and aluminum oxides) are used, the sulfur content in agarose sulfates can only reach 7.3 wt%. The catalysts with the Brønsted acid sites used in the synthesis of sulfated agarose can provide sulfur contents of up to 14.6 wt% in it. The incorporation of a sulfate group into the agarose molecule has been confirmed by elemental analysis and Fourier-transform infrared spectroscopy: the absorption bands at 1249 cm‒1 have been observed in the spectra. The X-ray diffraction and atomic force microscopy studies have revealed no ammonium sulfamate inclusions. According to the X-ray diffraction patterns, sulfation of agarose enhances its X-ray amorphism. It has been established from the atomic force microscopy images that the incorporation of a sulfate group into the agarose molecule changes the size of particles on the film surface from 42 to 80 nm. The theoretical examination of initial and sulfated agarose has been carried out within the density functional theory. The molecular geometry, vibration assignments, HOMO‒LUMO, molecular electrostatic potential maps, and electronic properties of the substances have been established by the quantum-chemical calculations in the framework of the density functional theory.