Ab initio study of lowest-energy conformers of Lewis x (Lex) trisaccharide

This paper presents the first ab initio conformational study of the Gal-beta-1,4-[Fuc-alpha-1,3]-GlcNAc-beta-OCH3 and Gal-beta-1,4-[Fuc-alpha-1,3]-GlcNAc-beta-OH trisaccharides (Lewis x) in the gas phase. Their lowest-energy conformers were selected first by the MM2*-SUMM conformational search technique. MM2* relative energies do not follow the same order for the two similar compounds. The molecular geometries and energies of the lowest-energy rotamers (7 of the acetal and 11 of the hemiacetal) were further analyzed at the HF/6-31G(d) level of theory. The ab initio method yields the same energetic order for the rotamers of the two molecules with considerably larger energetic differences for the first 7 rotamers: the MM2* method provides 0.3-0.5 kcal/mol, whereas the HF/6-31G(d) method provides 4.5 kcal/mol. In the most stable MM2* structures the hydrogen-bonded chains of galactose (in counterclockwise direction) and fucose (in clockwise direction) are not connected. The Gal(OSH) is a hydrogen bond donor (in clockwise direction) to the O3 glycosidic oxygen of GlcNAc. The Fuc(O2H)-->(O=C)GlcNAc interaction connects the fucose and GlcNAc. In contrast, the most stable HF/6-31G(d) structure has a long chain of seven ordered hydrogen bonds including a Gal(O6H)-->(O3)Fuc interaction (with clockwise hydrogen-bonded chain in galactose and fucose). The torsion angles for Fuc-alpha-1,3-GlcNAc and Gal-beta-1,4-GlcNAc glycosidic bonds agree well in the solid, liquid, and gas phases. For example there is a rather good overlap between the GlcNAc moiety of one of the X-ray structures and the most similar HF/6-31G(d) structure. The stacking of the fucose and galactose moieties is similar. The orientations of the hydroxyl groups are usually different, as they are influenced by intramolecular hydrogen bonding in the gas-phase Hartree-Fock structure versus intermolecular hydrogen bonding in the solid-phase X-ray structure.