Hyaluronic acid (HA) is a hydrophilic natural polysaccharide consisting of alternating monosaccharide units of glucuronic acid and N-acetyl glucosamine. In aqueous solutions the electrostatic repulsion of the carboxylate groups hampers the formation of supermolecular structures that can be partially stabilized by the addition of salt. Increased permittivity of the mixed water:organic solvents causes better compensation of the negative charge of HA chains by dissolved cations which changes their interactions with other molecules. In this study we simulate interactions of two HA chains in water:1,4-dioxane and water:tert-butanol mixed solvents with varying NaCl concentrations using molecular dynamics (MD). Anti-parallel double-helix-like duplexes are formed in NaCl-containing water:1,4-dioxane mixture and remain stable even when NaCl is removed. Parallel duplexes separate after a short time. In water:tert-butanol analogous duplexes are unstable. Stability of HA duplexes is thus determined by the solvent composition and the ability of its components to separate in the solvation shell of HA molecules, as well as by the mutual orientation of the chains.
Keywords: Double helix; Duplex; Hyaluronan; Hydrogen bond; Ionic bond; Mixed solvent.
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