Effect of metal ions (Li+, Na+, K+, Mg2+ and Ca2+) and water on the conformational changes of glycosidic bonds in heparin oligosaccharides

Abstract

The effects of complexation by Li⁺, Na⁺, K⁺, Mg²⁺, and Ca²⁺ counterions and water on the molecular structure of the Fondaparinux pentameter (D–E–F–G–H) and its dimer units (D–E, E–F, F–G and G–H) are studied using Becke 3LYP hybrid density functional theory and molecular modeling. The ionic charge state, the number of metal ion adducts and the counterion radii are important factors that influence counterion-induced conformational changes in these pentamers and dimers of heparin. The displacement of the Li⁺, Na⁺, K⁺, Mg²⁺ and Ca²⁺ cations from their binding sites in the salts results in appreciable changes in the anion conformations. The interaction energies are very negative and span a broad range from −1900 to −16 000 kJ mol⁻¹, which is the result of multiple coordinate bonds between ions and basic centers in glycosaminoglycan units.