Polysaccharide conformation. Part VIII. Test of energy functions by Monte Carlo calculations for monosaccharides

Internal energies have been calculated for the aldopentopyranoses, as the thermodynamic average over all exocyclic bond conformations for each of the sixteen nonsuperimposable, Reeves C1 chair structures. Contributions were included from van der Waals attraction, van der Waals repulsion, polar interactions, and bond torsion. These results for isolated molecules are compared with relative free energies from experimental measurements on aqueous solutions. Within one group of sugars (α-D-xylose, α-L-lyxose, α-D-lyxose, β-L-arabinose, β-D-lyxose, β-D-ribose, and β-D-arabinose)the calculations agree closely with experiment and the neglect of conformational entropy and specific solvation effects would seem to be justified. The agreement would further suggest that the anomeric effect is included in the energy terms that we would have considered and can therefore be attributed mainly to the interactions between bond dipoles, in line with conclusions from recent quantum mechanical calculations. For the two sugars which have the most favourable stereochemistry for solvation by the structured component of liquid water (α-L-arabinose and β-D-xylose) the calculations fail to predict the full extent of conformational stability. We suggest that the discrepancy is to be attributed to a ‘structured hydration’ that is highly co-operative and rather selective for all-equatorial sugar residues. The remaining sugars(α-D-ribose, α-L-ribose, α-D-arabinose,β-L-ribose, β-L-lyxose, α-L-xylose, and β-L-xylose) are those with 1,3-interactions between diaxial oxygen substituents. Agreement is poor, probably because the calculatios are not adapted to treat such high degrees of steric compression and perhaps also because the experimental data are less reliable for these forms. We conclude that our approach has promise for the calculation of conformational energies of carbohydrates in aqueous solution provided that steric compression is not severe and that allowance is made for the co-operative hydration of structures in which several equatorial oxygen functions are adjacent.