TOPOGRAPHY OF CYCLODEXTRIN INCLUSION COMPLEXES .28. NEUTRON-DIFFRACTION STUDY OF THE HYDROGEN-BONDING IN PARTIALLY DEUTERATED GAMMA-CYCLODEXTRIN.15.7D2O AT T = 110-K

A single-crystal neutron diffraction study of partially deuterated gamma-cyclodextrin (gamma-CD) hydrate, (C6D3H7O5)8.15.7D2O, was carried out at T = 110 K. The crystal is monoclinic, space group P2(1), with cell dimensions a = 16.899 (7) angstrom, b = 10.891 (5) angstrom, c = 20.226 (6) angstrom, beta = 105.06 (2) degrees, Z = 2, and V = 3595 (2) angstrom 3. A total of 10688 reflections were collected with lambda = 1.3196 angstrom on an area detector to the nominal resolution of 0.92 angstrom, yielding 4906 unique reflections with an R(merge) = 0.064 on F2. All H and D atoms for the cyclodextrin molecule and most of the D atoms for the water molecules were located, and the structure was refined to an R factor of 0.093 for 4538 observed reflections (F2 greater-than-or-equal-to sigma(F2)). In the crystal structure, the gamma-CD molecules are arranged in a herringbone pattern forming a cage-type packing. A narrow intermolecular interstitial channel, which is filled with water molecules, runs along the crystallographic b axis at a approximately 1/2 and c approximately 0. Compared with the beta-CD hydrate, which crystallizes in a similar packing arrangement, the cavities of the gamma-CD molecules are not as completely closed at the narrow O(6) hydroxyl group end by adjacent molecules and are connected with the interstitial channel. All glucose residues are in the usual 4C1 chair conformation with a relatively strong distortion of glucose residue 1 (theta-2 = 14.5-degrees). Glucose residue 8, which closes the cavity of a symmetry-related gamma-CD molecule at the wider O(2),O(3) end, and even slightly intrudes into it, is somewhat disordered as a whole. The 15.7 water molecules in the asymmetric unit are distributed over 25 positions. A total of 8.8 water molecules are located in the hydrophobic gamma-CD cavity; they are all positionally disordered and distributed over 17 positions with occupation factors in the range 0.31-0.95. The hydrogen-bond network in the cavity is very complicated due to the severe disorder of the water molecules and could not be reliably assigned in any detail. One water molecule acts as a bridge connection and has hydrogen bonds both to water molecules enclosed in the gamma-CD cavity and to water molecules in the intermolecular interstice, and one water molecule donates a hydrogen bond to glycosidic O(4) of the cavity wall. There are 6.9 water molecules located over 8 sites in the intermolecular interstitial channel, 5 of them are fully occupied, the others are partially occupied, with occupation factors in the range 0.13-0.88. The water molecules in the interstice are better ordered than those in the gamma-CD cavity and have a clearer hydrogen-bonding scheme. One water molecule, which is 2-fold disordered, is isolated from all other water molecule sites and forms hydrogen bonds only to hydroxyl groups of gamma-CD molecules; the others have hydrogen bonds to adjacent water molecules and/or to gamma-CD hydroxyl groups or donate hydrogen bonds to ring oxygen atoms O(5). Of 71 symmetry-independent hydrogen bonds in this crystal structure, 25 (= 35%) are of the three-center type, if a 2.8-angstrom cutoff criterion is used. All O(2) and O(3) hydroxyl groups of neighboring glucose units form interresidue, intramolecular hydrogen bonds, which are major components of unsymmetrical three-center hydrogen bonds donating relatively strong intramolecular components to the corresponding glycosidic O(4) atoms. One primary hydroxyl group donates a minor intraglucose hydrogen-bonding component to O(5) of the same residue; O(5) and O(6) of two glucose accept chelated three-center hydrogen bonds, and in two glucose residues, O(2) and O(3) of the same glucose accept three-center hydrogen bonds. All O-D...O hydrogen bonds are interconnected to form an infinite spatial network, with infinite chains, cycles, and finite chains as motifs, reminiscent of alpha-CD and beta-CD hydrates. Homodromic arrangements of hydrogen bonds dominate in the network and indicate the strong influence of the cooperative effect.