198 Topics in Current Chemistry Editorial Board: A. de Meijere KN ...

4 J.P. Glusker
Perturbations to the directionality of interactions may result from steric interactions
between different neighboring groups around a functional group; they
necessitate a statistical analysis of many different crystal structures containing
the interaction of interest. This type of analysis is made possible by the availability
of computer-based crystallographic databases: the Cambridge Crystallographic
Database [4] contains three-dimensional coordinates of crystal structure
analyses of small molecules containing at least one carbon atom, the Protein
Data Bank contains coordinates of protein and nucleic-acid structures [5,6],and
the Inorganic Crystal Structure Database [7] contains three-dimensional coordinates
for atoms in crystals of inorganic compounds.
A variety of methods can now be used to probe intermolecular interactions.
The structural information on intermolecular interactions obtained from X-ray
and neutron diffraction studies can be compared with gas-phase experimental
data from pure rotational or rotation-vibrational spectra [1] and the energies
obtained from ab initio molecular orbital calculations. It is found that each of
these methods generally gives essentially the same result. While most X-ray
diffraction studies are on crystals of small molecules, comparisons with the
lower-resolution results of protein crystallographic studies give information on
interactions in an environment that consists of about 50% water by volume [8].
Several types of directional intermolecular interactions will be considered in
this article.The main categories are the hydrogen bond (and weaker interactions
that could be considered a subset of this), and metal ion coordination (which
can, in certain cases, be directional in terms of ligand disposition). Examples of
each as they occur in small molecules and proteins will be described and
discussed. Essentially one is looking for rules that govern how molecules interact
with each other and how they bind to each other, so that predictions will be
possible.
2
Methods of Analysis
The orientations of binding between different functional groups on molecules
or ions in the solid state can readily be obtained from three-dimensional crystal
structure coordinates. Instead of calculating the distances between bonded
atoms (as is usual), it is necessary to consider the relationships between nonbonded
atoms, invoking the space-group symmetry where necessary, and then
to calculate their interatomic distances and the directions in which they lie with
respect to some chosen axial system in the crystal. Similar data from solutions
lack directionality because of averaging of the orientations of interactions
throughout the entire solution. Therefore, at present, it is necessary to substitute
averaged data in solution by statistical analyses of interactions as they occur in
the solid state. Interactions in one crystal structure might be biased by packing
requirements of all of the functional groups contained in the particular molecule
that has been crystallized. A statistical analysis, however, which will involve
many crystal structure determinations made for a wide variety of reasons and
on a very diverse sampling of molecular types, should average out any perceived
problems with solid-state distortions.