Solution Conformation of Heparin Tetrasaccharide. DFT Analysis of Structure and Spin–Spin Coupling Constants
Density functional theory (DFT) has provided detailed information on the molecular structure and spin⁻spin coupling constants of heparin tetrasaccharide (GlcNS,6S-IdoA2S-GlcNS,6S-IdoA2S-OMe) representing the predominant heparin repeating-sequence. The fully optimised molecular structures o...
| Main Authors: | , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2018-11-01
|
| Series: | Molecules |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1420-3049/23/11/3042 |
| _version_ | 1811227166186143744 |
|---|---|
| author | Miloš Hricovíni Michal Hricovíni |
| author_facet | Miloš Hricovíni Michal Hricovíni |
| author_sort | Miloš Hricovíni |
| collection | DOAJ |
| description | Density functional theory (DFT) has provided detailed information on the molecular structure and spin⁻spin coupling constants of heparin tetrasaccharide (GlcNS,6S-IdoA2S-GlcNS,6S-IdoA2S-OMe) representing the predominant heparin repeating-sequence. The fully optimised molecular structures of two tetrasaccharide conformations (differing from each other in the conformational form of the sulphated iduronic acid residue⁻one <sup>1</sup><i>C</i><sub>4</sub> and the other <sup>2</sup><i>S</i><sub>0</sub>) were obtained using the B3LYP/6-311+G(d,p) level of theory and applying explicit water molecules to simulate the presence of a solvent. The theoretical data provided insight into variations of the bond lengths, bond angles and torsion angles, formations of intra- and intermolecular hydrogen bonds and ionic interactions. Optimised molecular structures indicated the formation of a complex hydrogen bond network, including interresidue and intraresidue bonds. The ionic interactions strongly influence the first hydration shell and, together with hydrogen bonds, play an important role in shaping the 3D tetrasaccharide structure. DFT-derived indirect three⁻bond proton⁻proton coupling constants (<sup>3</sup><i>J</i><sub>H-C-C-H</sub>) showed that the best agreement with experiment was obtained with a weighted average of 67:33 (<sup>1</sup><i>C</i><sub>4</sub>:<sup>2</sup><i>S</i><sub>0</sub>) of the IdoA2S forms. Detailed analysis of Fermi-contact contributions to <sup>3</sup><i>J</i><sub>H-C-C-H</sub> showed that important contributions arise from the oxygen lone pairs of neighbouring oxygen atoms. The analysis also showed that the magnitude of diamagnetic spin⁻orbit contributions are sufficiently large to determine the magnitude of some proton⁻proton coupling constants. The data highlight the need to use appropriate quantum-chemical calculations for a detailed understanding of the solution properties of heparin oligosaccharides. |
| first_indexed | 2024-04-12T09:36:49Z |
| format | Article |
| id | doaj.art-77327b7a42b143b0934b0feaebcca145 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-04-12T09:36:49Z |
| publishDate | 2018-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-77327b7a42b143b0934b0feaebcca1452022-12-22T03:38:12ZengMDPI AGMolecules1420-30492018-11-012311304210.3390/molecules23113042molecules23113042Solution Conformation of Heparin Tetrasaccharide. DFT Analysis of Structure and Spin–Spin Coupling ConstantsMiloš Hricovíni0Michal Hricovíni1Institute of Chemistry, Slovak Academy of Sciences, 84538 Bratislava, SlovakiaInstitute of Chemistry, Slovak Academy of Sciences, 84538 Bratislava, SlovakiaDensity functional theory (DFT) has provided detailed information on the molecular structure and spin⁻spin coupling constants of heparin tetrasaccharide (GlcNS,6S-IdoA2S-GlcNS,6S-IdoA2S-OMe) representing the predominant heparin repeating-sequence. The fully optimised molecular structures of two tetrasaccharide conformations (differing from each other in the conformational form of the sulphated iduronic acid residue⁻one <sup>1</sup><i>C</i><sub>4</sub> and the other <sup>2</sup><i>S</i><sub>0</sub>) were obtained using the B3LYP/6-311+G(d,p) level of theory and applying explicit water molecules to simulate the presence of a solvent. The theoretical data provided insight into variations of the bond lengths, bond angles and torsion angles, formations of intra- and intermolecular hydrogen bonds and ionic interactions. Optimised molecular structures indicated the formation of a complex hydrogen bond network, including interresidue and intraresidue bonds. The ionic interactions strongly influence the first hydration shell and, together with hydrogen bonds, play an important role in shaping the 3D tetrasaccharide structure. DFT-derived indirect three⁻bond proton⁻proton coupling constants (<sup>3</sup><i>J</i><sub>H-C-C-H</sub>) showed that the best agreement with experiment was obtained with a weighted average of 67:33 (<sup>1</sup><i>C</i><sub>4</sub>:<sup>2</sup><i>S</i><sub>0</sub>) of the IdoA2S forms. Detailed analysis of Fermi-contact contributions to <sup>3</sup><i>J</i><sub>H-C-C-H</sub> showed that important contributions arise from the oxygen lone pairs of neighbouring oxygen atoms. The analysis also showed that the magnitude of diamagnetic spin⁻orbit contributions are sufficiently large to determine the magnitude of some proton⁻proton coupling constants. The data highlight the need to use appropriate quantum-chemical calculations for a detailed understanding of the solution properties of heparin oligosaccharides.https://www.mdpi.com/1420-3049/23/11/3042heparin tetrasaccharidesolution structureNMRDFTspin-spin coupling constants |
| spellingShingle | Miloš Hricovíni Michal Hricovíni Solution Conformation of Heparin Tetrasaccharide. DFT Analysis of Structure and Spin–Spin Coupling Constants Molecules heparin tetrasaccharide solution structure NMR DFT spin-spin coupling constants |
| title | Solution Conformation of Heparin Tetrasaccharide. DFT Analysis of Structure and Spin–Spin Coupling Constants |
| title_full | Solution Conformation of Heparin Tetrasaccharide. DFT Analysis of Structure and Spin–Spin Coupling Constants |
| title_fullStr | Solution Conformation of Heparin Tetrasaccharide. DFT Analysis of Structure and Spin–Spin Coupling Constants |
| title_full_unstemmed | Solution Conformation of Heparin Tetrasaccharide. DFT Analysis of Structure and Spin–Spin Coupling Constants |
| title_short | Solution Conformation of Heparin Tetrasaccharide. DFT Analysis of Structure and Spin–Spin Coupling Constants |
| title_sort | solution conformation of heparin tetrasaccharide dft analysis of structure and spin spin coupling constants |
| topic | heparin tetrasaccharide solution structure NMR DFT spin-spin coupling constants |
| url | https://www.mdpi.com/1420-3049/23/11/3042 |
| work_keys_str_mv | AT miloshricovini solutionconformationofheparintetrasaccharidedftanalysisofstructureandspinspincouplingconstants AT michalhricovini solutionconformationofheparintetrasaccharidedftanalysisofstructureandspinspincouplingconstants |