FACTORS CONTROLLING, RELATIVE STABILITY OF ANOMERS AND HYDROXYMETHYL CONFORMERS OF GLUCOPYRANOSE

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.