Fluorinated cellobiose and maltose as stand-ins for energy surface calculations

To better understand computational predictions of disaccharide conformations, phi,psi maps were constructed for two analogs in which all hydroxyl groups were replaced with fluorine atoms (F-cellobiose and F-maltose). These molecules do not permit hydrogen bonding but should give better steric representation than analogs in which hydrogen atoms replaced exo-cyclic groups. Hartree Fock and B3LYP density functional quantum mechanics (QM) theory were used. The preferred ring shape for fluorinated glucose depends on the level of QM theory, but over the limited phi,psi space that was. studied, the rings remained in the C-4(1) form. Also, fluorine atoms are remote enough that they do not affect the torsional energies for the glycosidic bonds. F-Cellobiose maps were predictive of the conformations in crystals, but F-maltose maps were less so. The QM F-cellobiose map and an MM4::QM hybrid map for cellobiose itself were similar. However, the hybrid maltose map had many more experimental conformations within its 2-kcal/mol contour than did the QM F-maltose map. The apparent mean strength of an intra-molecular, inter-residue hydrogen bond is about 3 kcal/mol, based on the energy for many of the hydrogen bonded maltose structures on the F-maltose map. The F-maltose map was similar to a new QM map for an analog of maltose in which all hydroxyl groups were replaced with hydrogen atoms. Published by Elsevier Ltd.