Disaccharide conformational maps: adiabaticity in analogues with variable ring shapes

Abstract

Relaxed MM3 ϕ, ψ potential energy surfaces (conformational maps) were calculated for analogues of α,α-trehalose, β,β-trehalose, α,β-trehalose, maltose, cellobiose and galabiose based on 2-methyltetrahydropyran. Starting structures included not only 4C1 (sugar nomenclature) geometries, but also combinations with 1C4 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 4C1–4C1 geometries, moderate to large parts of most maps had lower energies when one or both rings were in the 1C4 conformation. Only the adiabatic surface for the (diequatorial) analogue of β,β-trehalose was covered entirely by 4C1–4C1 conformers. For the cellobiose and α,β-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 1C4 conformation at the “reducing” end, and for the α,β-trehalose analogue, by conformers having 1C4 shapes for the α-linked unit. Adiabatic surfaces of the other three analogues were based on all combinations of 4C1 and 1C4 conformers. The “normal” 4C1–4C1 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.