1. Could you explain the significance of your article to the non-specialist?

There is an emerging area of science, increasingly referred to as "NMR Crystallography", which can provide detailed information about crystal structures from NMR spectroscopy techniques. This both adds to and complements the well-known powerful methods based on diffraction, especially for powder (microcrystalline) samples, for which total structure determination is difficult. Chemical shifts form one of the most powerful structural probes available to the NMR spectroscopist and in the case in question these give direct information on the conformation of molecules in a crystalline pharmaceutical drug. However, proper understanding of the relationship of shifts to structure can only be obtained by involving computation of shielding, which we have carried out using a powerful new code "CASTEP". 

 

2. What has motivated you to conduct this work? 

Our motivation stems from the opportunities provided by combining CASTEP computations with newly-implemented pulse sequences for solids such as INADEQUATE and HETCOR. The latter give crucial information on atomic connectivity, which is particularly important when there is more than one independent molecule in the crystal structure (as in the present case).

INADEQUATE two-dimensional 13C spectrum (low-frequency region) of oxybuprocaine hydrochloride Mod. II°, showing the linkages between signals for carbons in the same independent molecule.

 

3. Where do you see this work developing in the future? 

We see this work as leading to a more integrated approach to crystallography, combining solid-state NMR and diffraction in an ever-closer way.

 

4. Are there any particular challenges facing future research in this area? 

The challenges are both computational (e.g. how to incorporate effects of temperature - currently calculations are made essentially on static distributions of atoms) and experimental (limitations on sensitivity and resolution are still moderately severe).