Hricovíni Miloš, Driguez Pierre-Alexandre, Malkina Olga L
Institute of Chemistry, Slovak Academy of Sciences , 845 38 Bratislava, Slovakia.
J Phys Chem B. 2014 Oct 16;118(41):11931-42. doi: 10.1021/jp508045n. Epub 2014 Oct 6.
NMR and density functional theory (DFT) have afforded detailed information on the molecular geometry and spin-spin coupling constants of a trisaccharide from the heparin repeating-sequence. The fully optimized molecular structures of two trisaccharide conformations (differing from each other in the form of the central iduronic acid residue) were obtained using the B3LYP/6-311+G(d,p) level of theory in the presence of solvent, the latter included as either explicit water molecules or via a continuum solvent model. NMR spin-spin coupling constants were also computed using various basis sets and functionals and then compared with measured experimental values. Optimized structures for both conformers showed differences in geometry at the glycosidic linkages and in the formation of intramolecular hydrogen bonds. Three-bond proton-proton coupling constants ((3)JH-C-C-H), based on fully optimized geometry computed using the B3LYP/6-311+G(d,p)/UFF level of theory and hydrated with 57 water molecules, showed that the best agreement with experiment was obtained with the 6-311+G(d,p) basis set and a weighted average of 55:45 ((1)C4:(2)S0) of the IdoA2S forms. Other basis sets, DGDZVP and TZVP, also gave acceptable data for most coupling constants, with DGDZVP outperforming the TZVP. Detailed analysis of Fermi-contact contributions to (3)JH-C-C-H showed that important contributions arise from oxygen at both glycosidic linkages, as well as from oxygen atoms on the neighboring monosaccharide units. Their contribution to the Fermi term cannot be neglected and must be taken into account for a correct description of coupling constants. The analysis also showed that the magnitude of paramagnetic (PSO) and diamagnetic (DSO) spin-orbit contributions is comparable to the magnitude of the Fermi-contact contribution in some coupling constants in the IdoA2S residue. Calculations of the localized molecular orbital contributions to the DSO terms from separate conformational residues showed that the contribution from adjacent residues is not negligible and can be important for the spin-spin coupling constants between protons located close to the geometrical center of the molecule. These contributions should be taken into account when interpreting DSO terms in spin-spin coupling constants especially in large molecules.
核磁共振（NMR）和密度泛函理论（DFT）已提供了有关肝素重复序列中三糖的分子几何结构和自旋-自旋耦合常数的详细信息。使用B3LYP/6-311+G(d,p)理论水平，在有溶剂存在的情况下获得了两种三糖构象（中心艾杜糖醛酸残基形式不同）的完全优化分子结构，溶剂要么以明确的水分子形式包含，要么通过连续介质溶剂模型包含。还使用各种基组和泛函计算了NMR自旋-自旋耦合常数，然后与测量的实验值进行比较。两种构象体的优化结构在糖苷键处的几何结构以及分子内氢键的形成方面存在差异。基于使用B3LYP/6-311+G(d,p)/UFF理论水平并用水合57个水分子计算得到的完全优化几何结构的三键质子-质子耦合常数((3)JH-C-C-H)表明，使用6-311+G(d,p)基组以及IdoA2S形式的55:45((1)C4:(2)S0)加权平均值时，与实验的最佳一致性得以实现。其他基组DGDZVP和TZVP，对于大多数耦合常数也给出了可接受的数据，其中DGDZVP的表现优于TZVP。对费米接触对(3)JH-C-C-H贡献的详细分析表明，重要贡献来自糖苷键处的氧以及相邻单糖单元上的氧原子。它们对费米项的贡献不可忽略，对于正确描述耦合常数必须予以考虑。分析还表明，在IdoA2S残基的某些耦合常数中，顺磁（PSO）和抗磁（DSO）自旋-轨道贡献的大小与费米接触贡献的大小相当。对来自单独构象残基的DSO项的定域分子轨道贡献的计算表明，相邻残基的贡献不可忽略，对于位于分子几何中心附近的质子之间的自旋-自旋耦合常数可能很重要。在解释自旋-自旋耦合常数中的DSO项时，尤其是在大分子中，应考虑这些贡献。
