Methyl α-l-rhamnosyl-(1→2)[α-l-rhamnosyl-(1→3)]-α-l-rhamnoside pentahydrate: synchrotron study

The title hydrate, C19H34O13·5H2O, contains a vicinally disubstituted trisaccharide in which the two terminal rhamnosyl sugar groups are positioned adjacent to each other. The conformation of the trisaccharide is described by the glycosidic torsion angles ϕ2 = 48 (1)°, ψ2 = −29 (1)°, ϕ3 = 44 (1)° and ψ3 = 4 (1)°, whereas the ψ2 torsion angle represents a conformation from the major state in solution, the ψ3 torsion angle conformation may have been caught near a potential energy saddle-point when compared to its solution structure, in which at least two but probably three conformational states are populated. Extensive intermolecular O—H⋯O hydrogen bonding is present in the crystal and a water-containing channel is formed along the b-axis direction.


Lars Eriksson and Göran Widmalm Comment
In carbohydrate structures from humans the number of different monosaccharides is quite limited; typically seven different sugars are present in glycoproteins and glycolipids (Varki et al., 1999). Constituents of polysaccharides in man add a few more monosaccharides to the repertoire. In bacteria, however, more than 100 different monosaccharide components have been found (Lindberg, 1998). One of them, L-rhamnose (6-deoxy-L-mannose) is present as a major constituent of the O-antigen polysaccharides from Shigella flexneri (Kulber-Kielb et al., 2007) and is the sole monosaccharide in the repeating unit of an O-antigen from a Klebsiella pneumoniae strain (Ansaruzzaman et al., 1996).
In the title compound (I) the three sugar components are all L-rhamnose residues having the α-anomeric configuration.
The O-methyl residue (a) is vicinally disubstituted at O2 (residue b) and O3 (residue c) which leads to spatial proximity of also the two latter rhamnosyl groups. The major degrees of freedom in trisaccharide (I) are present at the (1 → 2)-and (1 → 3)-linkages, i.e., between residues b and a as well as between residues c and a, respectively. The torsion angles are given by φ2 = 48°, ψ2 = -29°, φ3 = 44° and ψ3 = 4°. In a recent NMR and molecular dynamics (MD) simulation study of (I) in water solution <φ> ≈ 40°, when the exo-anomeric conformation was populated, but non-exo conformations with φ < 0° were also significantly populated (Eklund et al., 2005). The dynamics of the ψ torsion angles were found to be highly correlated with both ψ2 and ψ3 being either > 0° or < 0°. The conformation of the X-ray structure ( Figure 1) is reminiscent of the conformational states found from the MD simulation and the values of the glycosidic torsion angles are observed to correspond to conformational regions that are highly populated, albeit the ψ torsion angles in the solid state structure deviate somewhat from the pattern observed from the molecular simulations with water as a solvent.
In studies of the conformational dynamics of the title trisaccharide trans-glycosidic heteronuclear carbon-proton Calculation of the three-bond coupling constants based on the torsion angles in the crystal structure of the trisaccharide showed that for the φ torsion angles and the ψ torsion angle at the α-(1 → 2)-linkage the differences to the experimental data were not larger than ca 0.5 Hz, indicating that for these torsions the conformation in the solid state is similar to that populated to a large extent in solution. However, for the ψ torsion angle at the α-(1 → 3)-linkage the corresponding difference was larger, ca 1 Hz, suggesting that in the crystal structure the latter torsion describes a conformation that is less populated in water solution. The crystal structure conformation is still, however, one in a low potential energy region, since conformational exchange occurs for both of the ψ torsion angles between states for which ψ takes either positive or negative values according to the molecular dynamics simulation (Eklund et al., 2005). Extensive water-water hydrogen bonding was observed (Table 1) between the title compound and water molecules leading to a water channel in the b-direction ( Fig. 2 and Fig. 3). The title compound showed hydrogen bonds to water and to other adjacent (symmetry related) trisaccharides, but no intra-molecular hydrogen bonds were found.

Experimental
The synthesis of (I) was described by Eklund et al. (2005) in which all three rhamnosyl residues have the L absolute configuration. The trisaccharide was crystallized at ambient temperature by slow evaporation from a mixture of water and ethanol (1:1). The crystal was mounted in a capillary tube and diffraction data were collected at 100 K on beamline I711 at the Swedish synchrotron radiation facility, MAXLAB, Lund.

Refinement
All hydrogen atoms, except those on the water molecules, were geometrically placed and constrained to ride on the parent atom.

Special details
Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.'s are taken into account individually in the estimation of e.s.d.'s in distances, angles and torsion angles; correlations between e.s.d.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.'s is used for estimating e.s.d.'s involving l.s. planes. Refinement. Refinement of F 2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F 2 , conventional R-factors R are based on F, with F set to zero for negative F 2 . The threshold expression of F 2 > σ(F 2 ) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F 2 are statistically about twice as large as those based on F, and R-factors based on ALL data will be even larger.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å 2 )
x y z U iso */U eq OW1 0.93266 (10