AB-INITIO MIA AND MOLECULAR MECHANICS STUDIES OF THE DISTORTED SUCROSE LINKAGE OF RAFFINOSE

A conformational energy map for a tetrahydropyran-tetrahydrofuran anal ogue of sucrose was calculated with ab initio quantum mechanics. Geome tries were optimized at the HF/4-21G level, using the MIA approximatio n. The highest energy (with the exception of trichlorogalactosucrose) corresponding to a conformation of an observed crystal structure was f or the sucrose moiety in crystalline raffinose. It was less than 1.5 k cal/mol above the local minimum occupied by sucrose, and calculations with larger HF basis sets converged at an energy difference of 2.9 kca l/mol. On the other hand, MM3(92) energies for the raffinose conformat ion are improbably high, 7 or 8 kcal/mol above the global minimum, whe ther or not the galactose residue is included in the calculation. Intr a- and intermolecular MM3 forces in a miniature model of crystalline r affinose pentahydrate were unable to account for the observed conforma tion. Also, other observed crystalline sucrose conformations correspon d poorly to low-energy regions on MM2, MM3, and other molecular mechan ics surfaces. About 6 kcal/mol of the 8 kcal/mol difference in conform ational energies comes from the torsion angles involving the anomeric center on the furanose ring. This suggests that even MM3, which has be en very successful in modeling other disaccharides, miscalculates the energies of compounds that have overlapping anomeric sequences.