Se. Barrows et al., FACTORS CONTROLLING, RELATIVE STABILITY OF ANOMERS AND HYDROXYMETHYL CONFORMERS OF GLUCOPYRANOSE, Journal of computational chemistry, 19(10), 1998, pp. 1111-1129
The relative energies of 11 different conformers of D-glucose, includi
ng different exo-anomeric orientations and at least one of each hydrox
ymethyl conformer (G(-), G(+), and T) for each of the two anomeric for
ms (alpha and beta), were calculated at much more complete levels of q
uantum mechanical (QM) electronic structure theory than previously ava
ilable, and relative free energies in solution were calculated by addi
ng rotational, vibrational, and aqueous solvation effects. The gas-pha
se results are based on very large basis sets (up to 624 contracted ba
sis functions) and the coupled cluster method for electron correlation
. Solvation Model 5.4/AM1 was used to calculate the effects of aqueous
solvation. Factors contributing to the relative energies of these con
formers have been analyzed. Relative energies varied considerably (up
to 4.5 kcal/mol), depending on the theoretical level, and different le
vels of theory disagreed as to which anomer was lower in energy. The h
ighest-level gas-phase calculations predicted the alpha-anomer to be l
ower in free energy by 0.4 kcal/mol (Boltzmann average). Gas-phase ene
rgies from several different classical force fields were compared to Q
M results. The QM structures optimized at the MP2/cc-pVDZ level of the
ory compared well with experiment for three different crystal structur
es. In water, the beta-anomers were better solvated than the alpha-ano
mers by 0.6 kcal/mol (Boltzmann average). Contributions of individual
hydrophilic groups to the solvation free energies were analyzed. (C) 1
998 John Wiley & Sons, Inc.