EXOCYCLIC HYDROXYMETHYL ROTATIONAL CONFORMERS OF BETA-D-GLUCOPYRANOSEAND ALPHA-D-GLUCOPYRANOSE IN THE GAS-PHASE AND AQUEOUS-SOLUTION

The intrinsic exocyclic hydroxymethyl rotational surface for beta-D-gl ucoppranose as well as the beta-alpha anomer energy difference for D-g lucopyranose has been studied using ab initio quantum mechanical metho ds including continuum solvation, Relevant stationary points, includin g rotational transition states, have been characterized by full geomet ry optimization using the 6-31G(d) basis set for the most stable count erclockwise (cc) overall conformation. Effects of dynamic electron cor relation on both the geometric structures and the relative energetics of this system are also explored using Moller-Plesset perturbation the ory (MP2 through MP4-(SDTQ)) and density functional methods (BLYP). A total of six stationary points, including three minima and three trans ition states, were identified along the exocyclic rotational surface. All three minima were found to be very close in energy with a final or der of GG (0.0) < CT (2.84) < TG (3.05) based on the relative free ene rgy, Delta G(298)degrees determined at the MP4(SDTQ)/6-31G(d)//MP2/6-3 1G(d) level of theory. The rotational transition state free energy dif ferences varied from 18.8 to 28.9 kJ mol-l at the same level of theory with the transition state connecting the TG and GG minima being the l owest. The intrinsic gas-phase beta-alpha anomer free energy differenc e for the cc-TG conformer of D-glucopyranose was also determined at va rious levels of theory. On the basis of the convergence of the MP seri es, this energetic quantity has been estimated at 8 +/- 2 kJ mol(-1) f avoring the or-anomer, and is insensitive to exocyclic hydroxymethyl r otation. Two different solvation models were used to explore the effec ts of aqueous solvation on the energetic parameters mentioned above. T he Onsager continuum solvation model and the self-consistent isodensit y polarized continuum model (SCIPCM) showed significant, yet predictab le, effects on the exocyclic hydroxymethyl rotational surface for beta -D-glucopyranose. Shifts in the relative energetics compared to those for the gas phase ranged from -0.8 to + 2.8 kJ mol(-1) for Onsager dip ole model and -1.6 to as much as +4.7 kJ mol(-1) for the SCIPCM model at the MP2 6-31G(d) level, resulting in a qualitative change in the or dering of the relative stability of the three stable minima. The effec ts of the solvation models on the beta-alpha anomer energy difference were also significant, showing a relative decrease in the beta-alpha a nomer energy difference from the intrinsic gas-phase result. However, it is clear that these specific continuum solvation models alone canno t account for the experimentally observed preference of the beta-anome r in aqueous solution.