Disaccharide conformational maps: adiabaticity in analogues with variable ring shapes

Relaxed MM3 phi, psi potential energy surfaces ( conformational maps) were calculated for analogues of alpha, alpha-trehalose, beta, beta- trehalose, alpha, beta- trehalose, maltose, cellobiose and galabiose based on 2-methyltetrahydropyran. Starting structures included not only C-4(1) (sugar nomenclature) geometries, but also combinations with C-1(4) conformers, and some flexible (boat or skew) forms. These forms were included as part of continuing efforts to eliminate unwarranted assumptions in modelling studies, as well as to account for new experimental findings. Four to nine maps were obtained for each analogue, and from them adiabatic maps were produced. Although the minimum energy regions always resulted from C-4(1)- C-4(1) geometries, moderate to large parts of most maps had lower energies when one or both rings were in the C-1(4) conformation. Only the adiabatic surface for the (diequatorial) analogue of beta, beta-trehalose was covered entirely by C-4(1)-C-4(1) conformers. For the cellobiose and a, b- trehalose analogues, these conformers covered 74 and 67% of the surfaces, respectively. The remainder of the cellobiose analogue surface was covered by conformers having a C-1(4) conformation at the reducing end, and for the alpha, beta-trehalose analogue, by conformers having C-1(4) shapes for the alpha-linked unit. Adiabatic surfaces of the other three analogues were based on all combinations of C-4(1) and C-1(4) conformers. The normal C-4(1)- C-4(1) combination only covered 37-41% of those surfaces, whereas each of the other three conformations accounted for 10-31%. Although the normal conformation accounted for 97.0-99.8% of the total population, adiabaticity in disaccharide maps is not guaranteed unless variable ring shapes ( another manifestation of the multiple minima problem) are considered.