Hydrogen Bonding and Cooperativity in Isolated and Hydrated Sugars:  Mannose, Galactose, Glucose, and Lactose

Abstract

The conformation of phenyl-substituted monosaccharides (mannose, galactose, and glucose) and their singly hydrated complexes has been investigated in the gas phase by means of a combination of mass selected, conformer specific ultraviolet and infrared double resonance hole burning spectroscopy experiments, and ab initio quantum chemistry calculations. In each case, the water molecule inserts into the carbohydrate at a position where it can replace a weak intramolecular interaction by two stronger intermolecular hydrogen bonds. The insertion can produce significant changes in the conformational preferences of the carbohydrates, and there is a clear preference for structures where cooperative effects enhance the stability of the monosaccharide conformers to which the water molecule chooses to bind. The conclusions drawn from the study of monosaccharide-water complexes are extended to the disaccharide lactose and discussed in the light of the underlying mechanisms that may be involved in the binding of carbohydrate assemblies to proteins and the involvement, or not, of key structural water molecules.

Conformational properties of glucose-based disaccharides investigated using molecular dynamics simulations with local elevation umbrella sampling

“…Note that this statement concerning the presumably weak conformational driving force associated with H-bonding 48 pertains to small molecules in an aqueous environment. It may not be applicable to larger systems (e.g., due to H-bonding cooperativity effects [240][241][242]196,[243][244][245][246][247][248][249][250][251][252] in extended chains or reduced local solvation in folded chains) and to other environments (e.g., crystals, fibers, solutions with non-polar solvents, or vacuum). In addition, this hypothesis does not imply that intramolecular H-bonding has no effect on the physico-chemical properties of a specific sugar, because many of these properties are actually defined by a change of environment relative to the bulk aqueous environment at high dilution.…”

Conformation, dynamics, solvation and relative stabilities of selected β-hexopyranoses in water: a molecular dynamics study with the gromos 45A4 force field

“…337 The stability of a hydrogen-bond network (over individual uncorrelated hydrogen-bonds) is certainly a consequence of cooperativity effects (Section 1). The observed preference for a counterclockwise orientation in the four compounds considered (which may not be generalizable to the corresponding a-anomers as well as to other hexopyranoses 162,255,340,345 ) is probably related to its compatibility with the g À preference of / for b-anomers in the gas-phase (exo-anomeric effect; Section 3.3 and Table 2). …”

“…162,163,338 For Man the available quantum-mechanical results 255,337,342 also suggest a counterclockwise network in the lowest-energy conformer, but along with a H 6 !O 4 hydrogen-bond. The same counterclockwise network was also found in previous quantummechanical calculations on Gal or its O 1 -methylated derivative in vacuum, 104,162,163,255,337,340,[343][344][345][346] although most of these calculations (see, however 104,343 ) as well as IR ion-dip experiments on phenyl-b-D D-galactopyranoside in the gas-phase 162,163,344 suggested the presence of a H 6 !O 5 hydrogen-bond (as in Glc) rather than a H 6 !O 4 hydrogen-bond (present simulation) in the lowest-energy conformer. Finally, for Tal, the only quantum-mechanical study available to our knowledge also supports the presence of a H 6 !O 5 hydrogenbond.…”

“…Finally, a number of studies have also underlined the importance of cooperativity effects in intramolecular hydrogen-bonding for this class of compounds. 110,115,130,154,156,[158][159][160][161][162][163][164] Stereoelectronic effects: Stereoelectronic effects result from the particular electronic properties associated with specific molecular fragments in specific geometries. These effects may also involve a dipolar component 165 and thus be somewhat solvent sensitive, 166,167 but this dependence should be limited compared to that of electrostatic effects.…”

Computational study of glucosepane–water and hydrogen bond formation: an electron topology and orbital analysis

“…DFT studies of intramolecular association between hydroxyl groups in D-glucose indicate that hydrogen bonds are responsible for the counter-clockwise arrangement of hydroxyl groups, although such is not the case in its α-D-glucopyranose derivative (Silla, Cormanich, Rittner, & Freitas, 2014;Çarçabal et al, 2005), which is thought to be stabilised by hyperconjugative effects (Silla et al, 2014). NBO orbital and second-order perturbation theory of glucosepane I did not yield delocalisation between the oxygen of either hydroxyl group with the opposite σ*C-O anti-bond.…”