TOPOGRAPHY OF CYCLODEXTRIN INCLUSION COMPLEXES .27. DISORDERED GUEST AND WATER-MOLECULES - 3-CENTER AND FLIP-FLOP O-H...O HYDROGEN-BONDS IN CRYSTALLINE BETA-CYCLODEXTRIN ETHANOL OCTAHYDRATE AT T = 295 K - A NEUTRON AND X-RAY-DIFFRACTION STUDY

A single crystal neutron diffraction study of partially deuterated beta-cyclodextrin ethanol octahydrate was carried out at T = 295 K, composition (C6H7D3O5)7.C2D5OD.8D2O, space group P2(1), cell constants a = 21.125 (2) angstrom, b = 10.212 (1) angstrom, c = 15.215 (2) angstrom and beta = 111.47 (1) degrees; 4138 unique neutron data (lambda = 1.3167 angstrom) with nominal resolution 0.93 A (2-THETA less-than-or-equal-to 90-degrees). All H and D atoms were located and the structure was refined to R = 6.6%. In the beta-CD molecule, 2-fold orientational disorder is found for two of the seven CH2(6)-O(6) groups and for 15 of the 21 hydroxyl groups; one hydroxyl group is 3-fold disordered. Five water molecules are located between the beta-CD macrocycles; two of them have four partially occupied hydrogen atom sites, two have three hydrogen sites, and only one is ordered. One ethanol and three water molecules are enclosed in the beta-CD cavity, the ethanol molecule occupying two and the water molecules occupying four alternative discrete sites. The ethanol hydroxyl orientation and the water orientations are disordered for all these sites. In both positions, the ethanol molecule has a well-defined site for the oxygen atom, which is determined by hydrogen bond formation, while the CH2-CH3 group vibrates extensively. The two hydrogen-bonding networks in the cavity were assigned individually for both ethanol sites. Hydrogen bonding in the cavity is geometrically disadvantageous, and thermal parameters are higher than for the rest of the structure, indicating considerable solvent mobility in this region. One water molecule forms a hydrogen bond with a glycosidic O(4) oxygen atom of the cavity wall. Out of the 68 symmetry independent hydrogen bonds, 22 (= 32%) are of the three-center and two (=3%) of the four-center type (based on a 2.8 angstrom-cutoff criterion for d(D...O)), and 44 are engaged in O-1/2D...1/2D-O flip-flop type disorder. The latter comprise the seven intramolecular, interglucose O(2)...O(3) interactions with a three-center minor component to the corresponding O(4) atoms. There are minor three-center components O(6)-D...O(5) in four glucoses, and O(5) and O(6) of two glucoses accept a three-center chelated hydrogen bond from a hydroxyl group. In two cases, there are weak minor hydrogen bond components between O(2) and O(3) of the same glucose. An X-ray study of a different crystal of the same partially deuterated compound showed a significantly different arrangement of the solvent molecules in the beta-CD cavity. This implies that in biological crystal structures even of this moderate size hydrogen bonding networks can be reliably determined only for individual single crystals and may be different in others.