Conformational Analysis of Gentiobiose Using Genetic Algorithm Search and GIAO DFT Calculations with ¹³C CPMAS NMR as a Verification Method

GRAPHICAL ABSTRACT

The ALJAR03 software was implemented performing searches in the dihedral angle conformational space of disaccharides. The angles φ, ψ , and ω around glycosidic linkages, as well as the orientations of hydroxymethyl and hydroxyl groups, were considered. The energy maps were calculated using the MM+ force field. The searches were performed using a genetic algorithm (GA) combined with systematic grid search (GS). The application of a genetic algorithm-assisted grid search (GAAGS) approach yielded a significant reduction in the number of structures to be sampled in order to find the best low-energy conformation, as compared with the standard systematic grid search. Thus, time-consuming gauge-independent atomic orbital (GIAO) calculations of shielding constants can be rationalized and limited to some selected conformations. ¹³C CPMAS NMR chemical shifts for solid gentiobiose were measured and compared with the respective (GIAO DFT) shielding constants calculated for the crystallographic structure and for low-energy conformers. The differences in shielding are associated with the conformational effects (different arrangements of exocyclic groups) and hydrogen bonds. The best agreement (R² = 0.99) between the experimental and calculated chemical shifts was for the XRD structure and for the best conformer (R² = 0.98). Their geometries differ in the orientation of OH groups.

Keywords:

• Genetic algorithm
• ¹³C CPMAS NMR
• Solid-state NMR
• DFT GIAO
• Disaccharides
• Gentiobiose