DERIVATION OF CLASS-II FORCE-FIELDS - VI - CARBOHYDRATE COMPOUNDS ANDANOMERIC EFFECTS

The methodology for deriving class II force fields has been applied to acetal, hemiacetal, and carbohydrate compounds. A set of eighteen mod el compounds containing one or more anomeric centers was selected for generating the quantum mechanical energy surface, fi-om which the forc e field was derived and the functional form assessed. The quality of t he fit was tested by comparing the energy surface predicted by the for ce field with ab initio results. Structural. energetic, and dynamic pr operties (vibrational frequencies) were analyzed. In addition, alpha a nd beta anomeric equilibrium structures and energies of 2-methoxytetra hydropyran, 2-deoxyribose, and glucose were computed at the HF/6-31G and higher ab initio levels. These calculations provide test data from molecules outside the training set used to derive the force field. Th e quantum calculations were used to assess the ability of the class II force field and two quadratic diagonal (class I) force fields, CVFF, and Homans' extension of the AMBER force field, to account for the ano meric effects on the structural and energetic properties of carbohydra te systems. These class I force fields are unable to account for obser ved structural and energetic trends, exhibiting deviations as large as 5 kcal/mol in relative energies. The class II force field, on the oth er hand, is shown to reproduce anomeric structural as well as energeti c differences. An energy component analysis of this force field shows that the anomeric differences are dominated by torsional energies, alt hough coupling terms, especially angle/torsion, also make significant contributions (roughly 1 kacl/mol in glucose). In addition, the force field accurately accounts for both anomeric and exo-anomeric energy di fferences in 2-methoxytetrahydropyran, and anomeric energy differences in 2-deoxyribose and glucose. (C) 1998 John Wiley & Sons, Inc.