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

Abstract

GRAPHICAL ABSTRACTThe 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.