Essential Chemistry and Biochemistry Associated with Low Temperature and Freezing - Freeze-drying of Pharmaceuticals and Biopharmaceuticals - page 68

Since the crystal structures of water and PHCs are characterised by
chains, rings and networks of molecules held together (or apart) by more
or less tetrahedrally arranged and more or less linear O-H-O hydrogen
bonds (sp 3 hybridisation of orbitals), X-rays are of limited value. Added
to this limitation is the requirement for a long-range order, necessitating
a certain minimum number of unit cells. Amorphous phases do not
possess such long-range structures, making data processing of diffrac-
tion data less informative, because the substance under test must be
treated as a liquid. Thus, whereas single crystal diffraction data provide
spatial coordinates (of carbon and oxygen atoms), measurements on
liquids only provide statistical probabilities of such coordinates. No
information is provided from which angular coordinates (configuration
of molecules) can be calculated with any degree of confidence.
The situation has been vastly improved since the advent of neutron
scattering because neutrons can ''see'' or be made to ''see'' hydrogen
atoms. It has thus become possible to ''observe'' hydrogen bonds and
the configurational arrangement of O-H groups in space. The method
has also been applied to aqueous solutions, and much valuable infor-
mation about the nature of the so-called hydration shells has become
available. 33 Efforts to gain a better understanding of differences between
PHC crystals and glasses are still continuing, but a comparative neutron
scattering study of glucose in the crystalline, the liquid and the glassy
state has revealed a marked similarity between the intermolecular dis-
tances and configurations of bonds in the crystal and the amorphous
states. 79 Thus, the glass can be regarded, at least structurally, as a
distorted crystal, with distributions of O-O distances and O-H-O
angles. An important difference is that the density and detailed molec-
ular configuration of the glassy state depend on the method of prepa-
ration. Other, but important, marked differences between the two states
show up in their kinetic and transport properties.
At a very fundamental level, PHC-PHC interactions and PHC hy-
dration can be studied by Monte Carlo (MC) and molecular dynamics
(MD) computer simulations. Because of enantiomeric and configura-
tional complexities of molecules with the common formula C(H 2 O) n ,
where commonly 5 o n o 12, such studies require some drastic approx-
imations. Nevertheless, interesting results have been reported, for in-
stance on the respective crystal, fused and glass structures of glucose 80
and on trehalose hydration. 81 At an even more basic level, some marked
differences in PHC -OH group interactions with water have been
reported for PHCs that are isomeric (e.g. glucose, mannose and fruc-
tose) and for the individual -OH groups within the same molecule with
water. 82 At present, non-agreement between results reported by different