Theoretical Investigations on the Conformation of the β-d-Arabinofuranoside Ring.

A method for the conformational analysis of furanose rings that involves the prediction of (3)JH,H that can be compared directly to experimental values is investigated. This method, which differs from the traditional PSEUROT approach for conformational studies of furanose rings, was previously applied to a number of α-d-arabinofuranosides and enabled the direct comparison of (3)JH,H values to those obtained from NMR spectroscopy. In this paper, the use of this approach to study the conformational preferences of oligosaccharides containing β-linked arabinofuranose residues is reported. Density functional theory (DFT) calculations were carried out to derive Karplus relationships that are specifically tailored for these ring systems. In addition, probability distributions obtained from GLYCAM/AMBER molecular dynamics simulations were employed to calculate (3)JH,H values from these Karplus relationships. However, unlike the results obtained with α-arabinofuranosides, the (3)JH,H values computed for β-arabinofuranosides agreed poorly with experimental values. This prompted the exploration of other methodologies including reevaluation and optimization of the initial MD protocol, use of various force field models, and recalculation of the DFT-derived coupling profiles using an optimized basis set. After extensive investigations, we established that the conformer distributions obtained from MD simulations with the GLYCAM force fields and the furanoside-specific CHARMM force field in combination with the DFT Karplus equations, determined using an augmented basis set (B3LYP/aug-cc-pVTZ-J), produced the best agreement compared to experimental (3)JH,H values. Using these protocols, there is relatively good agreement in (3)JH,H for all coupling pathways with the exception of (3)J2,3 and (3)J3,4, which are underestimated.