Effect of solvent and counterions upon structure and NMR spin-spin coupling constants in heparin disaccharide.

Density functional theory (DFT) has been used to analyze structure and NMR spin-spin coupling constants in heparin disaccharide. Both B3LYP/6-311++G** and M05-2X/6-311++G** methods have been used for optimization of disaccharide geometry. Solvent effect was treated by use of explicit water molecules. Solvent-caused variations of DFT-computed indirect one-bond proton-carbon coupling constants up to 17 Hz between isolated and solvated states, however, had a limited influence upon magnitudes of proton-proton spin-spin coupling constants. Interatomic distances and bond and torsion angles indicated that the structure of the 2-O-sulfated iduronic acid residue affected the geometry of the N,6-sulfated glucosamine residue. Optimized disaccharide geometry showed that the change of counterion (Ca(2+) instead of Na(+)) influenced geometry of pyranose rings and the glycosidic linkage conformation. DFT-computed three-bond proton-proton spin-spin coupling constants agreed well with published experimental data and indicated that the population of the (1)C(4) chair form of the 2-O-sulfated iduronic acid residue increased in the presence of Ca(2+) ions compared to the presence of Na(+) ions. Analysis also showed that the Fermi contact term was not always dominant and that paramagnetic and diamagnetic contributions considerably influenced magnitudes of proton-proton spin-spin coupling constants.