Structures of furanosides: Density functional calculations and high-resolution X-ray and neutron diffraction crystal structures

Highly accurate and precise crystal structures of methyl alpha-D-arabinofur anoside, methyl beta-D-ribofuranosidc, methyl alpha-D-lyxofuranoside, and m ethyl alpha-D-xylofuranoside have been determined at 100 K by X-ray crystal lography. The structures of methyl alpha-D-arabinofuranoside and methyl bet a-D-ribofuranoside have also been determined at 15 K by neutron diffraction . Equilibrium (r(e)) geometries of the same compounds were computed by mean s of density functional methods using a variety of exchange-correlation fun ctionals and a sequence of basis sets. The validity of the computed results was assessed by several criteria including agreement between computed and observed bond distances and bond angles, agreement between computed and obs erved ring conformations, and basis set convergence of the computed geometr ical parameters. Particular reference was made to computed internal hydroge n bond parameters, which are especially sensitive to the quality of the the oretical treatment. Because of the intrinsic sensitivity of the conformatio n of the five-membered ring to bond lengths and bond angles, molecular mech anics and small basis set SCF treatments are wholly inadequate. Local densi ty functional theory also fails because of a tendency to strongly underesti mate internal hydrogen bond distances. When the B3LYP exchange-correlation functional is used, bond lengths and bond angles agree with the neutron dif fraction values to within their experimental uncertainty and the ring confo rmation is qualitatively correct, as long as a basis set of at least double -zeta plus polarization quality (such as cc-pVDZ) is used. Further expansio n of the basis set leads to more accurate equilibrium bond lengths: and bon d angles but does not appreciably affect the ring conformation. For methyl alpha-D-arabinofuranoside, methyl beta-D-ribofuranoside, and methyl alpha-D -xylofuranoside, there is very good correspondence between the best compute d and observed ring conformations, even though some intermolecular hydrogen bonds in the crystal give way to internal hydrogen bonds in the predicted gas-phase structures. On the other hand, in the case of methyl alpha-D-lyxo furanoside, an O2H ... O4 internal hydrogen bond between the ring oxygen O4 and the hydroxyl hydrogen of a ring carbon (O2H) in the computed structure leads to a very large change of ring conformation from the northeast corne r of the pseudorotation pathway (P = 28 degrees, crystal) to the southeast corner (P = 130 degrees, computed).