A density functional theory investigation of metal ion binding sites in monosaccharides

The density functional theory method is used to study metal ion binding to simple carbohydrates such as cis-inositol and beta-D-glucose. The complexes formed between Be2+, Mg2+, Ca2+, and Li+ and cis-inositol and the complexes formed between Ca2+ and beta-D-glucose are optimized and metal binding sites are identified. There are two metal binding sites in cis-inositol and five in beta-D-glucose. Our calculations demonstrate that smaller ions such as Be2+ prefer to bind in the ax-ax-ax site of cis-inositol, while larger ions such Mg2+ and Li+ favor the ax-eq-ax site of cis-inositol. The preferred metal binding site in Ca2+-cis-inositol is defined by four hydroxyl groups instead of three (one equatorial and three axial OH). Among the five metal binding sites in beta-D-glucose, the one defined by the ring oxygen atom, C1-OH and C6-OH is the most preferred site where Ca2+ binds to three oxygen atoms. This tendency of metal ions to maximize interactions with carbohydrate ligands in the gas phase is in agreement with previous experimental and theoretical studies. The relevance of these metal-carbohydrate interactions in cell surface carbohydrate-binding proteins is also discussed. This study has demonstrated that the density functional theory method is a good method for identifying metal ion binding sites in carbohydrates.