Chemistry Reference
In-Depth Information
3.1 Validation Before Direct-Space Structure Solution
Aspects of validation prior to direct-space structure solution are focused on (1)
establishing the correct representation of molecular geometry to be used in the
direct-space structure solution calculation and (2) establishing independent evidence
for the correct number of molecules in the asymmetric unit.
First we consider setting up a suitable structural model for direct-space structure
solution. In general, the identity of the molecule(s) in the structure and the compo-
sition (e.g. in the case of a solvate or cocrystal phase) may be established readily
by applying a range of analytical techniques, including high-resolution solid-state
NMR. Another important issue concerns details of molecular geometry, recognizing
that many molecules can adopt different tautomeric forms. The structure determina-
tion of red fluorescein [
39
] from powder XRD data provided an early example of the
use of solid-state NMR data to inform the process of setting up a suitable structural
model for direct-space structure solution. In this case, high-resolution solid-state
13
C NMR distinguished the correct tautomeric form of the molecule in the crystal
structure. Clearly, in order to achieve successful structure solution in direct-space
calculations, it is generally crucial to use a geometrically correct representation of the
molecule (including correct assignment of the tautomeric form).
Second, we consider the number of molecules in the asymmetric unit. Following
unit cell determination, the number of molecules in the unit cell is generally
deduced straightforwardly from density considerations, but such information does
not necessarily lead to a unique assignment of the number of molecules in the
asymmetric unit, nor a unique assignment of the space group. In such cases, high-
resolution solid-state NMR can often provide valuable independent information on
the number of molecules in the asymmetric unit, based on the fact that, for example,
the high-resolution solid-state
13
C NMR spectrum of an organic material should
contain one peak for each crystallographically distinguishable carbon atom in the
structure (although, in practice, the actual number of
observed
peaks may be less
than this number due to accidental peak overlap). Thus, after assigning each peak in
the solid-state
13
C NMR spectrum to a specific carbon environment within the
molecule, it is generally straightforward to assess whether there are one, two or
more molecules in the asymmetric unit, or only a fraction of the molecule
(indicating that the molecule is located on a special position).
As an example [
86
], in structure determination of the 1:1 cocrystal formed
between benzoic acid (BA) and pentafluorobenzoic acid (PFBA), the high-resolution
solid-state
13
C NMR spectrum (Fig.
4
) was found to contain two peaks for the
carbon atom of the carboxylic acid group of BA and two peaks for the carbon atom
of the carboxylic acid group of PFBA, leading to the conclusion that the asymmetric
unit comprises two molecules of BA and two molecules of PFBA. In this case,
systematic absences in the powder XRD pattern indicated that the structure is
C-centred and has a
c
-glide plane, and density considerations suggested that there
are eight molecules of BA and eight molecules of PFBA in the unit cell. The
solid-state NMR data therefore point towards Cc as the correct space group
