a-Lactose monohydrate : a redetermination at 150 K

# 2005 International Union of Crystallography Printed in Great Britain – all rights reserved The structure of the monohydrate of -4-( -d-galactopyranosido)-d-glucopyranose, more commonly known as -lactose monohydrate, C12H22O11 H2O, has been previously studied by single-crystal diffraction at ca 296 K [Beevers & Hansen (1971). Acta Cryst. B27, 1323–1325; Fries et al. (1971). Acta Cryst. B27, 994–1005; Noordik et al. (1984). Z. Kristallogr. 168, 59–65]. This redetermination at low temperature [150 (2) K] shows improved precision of geometry. Graph-set analysis of the hydrogen-bonding motifs is presented for the first time.


Comment
-Lactose monohydrate, (I), is the most common form of lactose and may be used as the parent material for at least four different (pseudo)polymorphs of this disaccharide (Garnier et al., 2002;Figura & Epple, 1995). This reducing sugar is built from a moiety of -d-galactose and a moiety of -d-glucose, joined by a 1,4 glycosidic bond between C1 0 of the galactose and C4 of the glucose unit (Fig. 1).
A search of the Cambridge Structural Database (Allen, 2002;Fletcher et al., 1996;Version 5.26, November 2004 update) highlighted previous research on this hydrate with data collections performed at ca 296 K (Beevers & Hansen, 1971;Fries et al., 1971;Noordik et al., 1984). The redetermination of (I) presented here, obtained from low temperature [150 (2) K] single-crystal diffraction data, has resulted in improved precision compared to the previously determined room-temperature structures. Standard uncertainties on C-O and C-C bond lengths are improved to ca 0.003 compared to ca 0.004 at room temperature, with an improvement to ca 0.0017 compared to ca 0.002 for standard uncertainties on C-O-C angles. The unit cell volume measured at 150 K [768.85 (14) Å 3 ] is ca 0.88% smaller than that determined at room temperature [775.7 (5) Å 3 ;Noordik et al., 1984], this latter unit-cell volume itself being smaller than that derived from previous measurements.
The unit cell has previously been reported as 7.937 (2) Å , 21.568 (7) Å , 4.815 (1) Å and = 109.77 (2) (Noordik et al., 1984); the unit cell reported here is related to the Noordik unit cell by a simple transformation and is currently regarded as the conventional unit cell, having the shortest possible vectors in the ac plane (International Tables for X-ray Crystal lography, 1969, Vol. 1).
An examination of the final difference Fourier map reveals a peak of 0.27 e Å À3 at a distance of 1.48 Å from C1, close to the equatorial atom H1. Since the and anomers establish a 40:60 equilibrium in solution over time, the question arises whether there is a small component of -lactose present, even though only the -anomer spontaneously crystallizes below 366.5 K (Walstra & Jenness, 1984). In this present determination, the largest ten difference map features lie in the range 0.22-0.32 e Å À3 , so this dubious peak is, in fact, indistinguishable from the noise. This means that, if present at all, the percentage of the -anomer must be in the low single figures and any significant component can definitely be ruled out.
Graph-set analysis of the hydrogen-bonding patterns (Bernstein et al., 1995;Etter et al., 1990) within the structure shows the complicated nature of the linking together of the lactose and water molecules. There are 15 different ring motifs involving one molecule of hydrated -lactose (Figs. 2 and 3). The motifs use either two or three molecules of (I), hydrogen bonding with zero, one or two water molecules. Fig. 4 shows a stacking formation of the lactose molecules when viewed, as a packing plot, along the crystallographic c axis. The molecules are held rigidly by a chain, C 2 2 (4), of hydrogen bonds between O6-H6AÁ Á ÁO2 iii and O2-H2AÁ Á ÁO6 i [symmetry codes: (i) x À 1, y, z À 1; (iii) x, y, 1 + z] propagating along the crystallographic a axis and are also linked through hydrogen bonding to water molecules.

Experimental
Colourless X-ray quality crystals of (I) were produced using powdered d-(+)--lactose monohydrate (supplied by Fluka Biochemica, Stenheim). A 10% aqueous solution of (I) was prepared as in methods previously studied by Larhrib et al. (2003). This solution was then diluted through addition of acetone, resulting in a 35:65 mixture of 10% lactose solution-acetone. Crystallization occurred upon standing at room temperature over a period of 48 h. A second crystalline sample of (I) was produced by a similar method except that acetone was substituted with a 10% potassium methoxide aqueous solution. Diffraction data from this sample were recorded by the EPSRC National Crystallographic Service, affording very similar unit-cell dimensions.  View of (I) along the crystallographic b axis, showing the remaining hydrogen bonding motifs formed between layers of (I) and water molecules; containing O2- View of (I), showing the atom-labelling scheme. Displacement ellipsoids are drawn at the 50% probability level. Only hydroxyl H atoms involved in hydrogen bonding are labelled. Dashed lines indicate hydrogen bonds. One intramolecular hydrogen bond is present, viz. O9-H9AÁ Á ÁO5.
10 1864 reflections 231 parameters H atoms treated by a mixture of independent and constrained refinement Table 1 Selected geometric parameters (Å , ). (17) Table 2 Hydrogen-bond geometry (Å , ). Non-water H atoms were placed in geometric positions using a riding model [C-H = 0.99 (methylene H) and 1.00 Å (methine H); O-H = 0.84 Å ], and U iso (H) = 1.2U eq (C) and 1.5U eq (O). The data set was truncated at 2 = 52 , as only statistically insignificant data were present above this limit. Water H atoms were located in a difference Fourier map and refined using restraints on the O-H bond length [target value 0.840 (15) Å ] and the 1,3-distance [target value 1.43 (2) Å ] and U iso (H) = 1.5U eq (O). In the absence of significant anomalous dispersion effects, 1526 Friedel pairs were merged during the refinement of (I).

Figure 4
Packing diagram of (I), viewed along the crystallographic c axis, showing the hydrogen bonding linking molecules of (I) and water, above and below a central molecule.  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.