The specific three-dimensional packing of a pharmaceutical molecule in the solid state determines key physical properties, notably bioavailability. As such, the pharmaceutical industry makes significant investment in the characterisation of
different solid-state forms of active pharmaceutical ingredients, including different polymorphs, hydrates and solvates, as well as co-crystals and amorphous dispersions.
Solid-state NMR is a rapidly developing analytical tool that has the advantage of applicability to powdered samples lacking long-range periodic order. In particular, the 1H chemical shift has been shown to be very sensitive to key intermolecular interactions, notably, hydrogen bonding and aromatic pi-pi stacking, which direct the packing of organic molecules.
The project will involve the development and application of high-resolution homonuclear and heteronuclear 1H solid-state NMR experiments that identify close proximities (less than 4Å) between pairs of hydrogen atoms or between a hydrogen atom and a carbon or nitrogen atom, so as to identify, for example, specific intermolecular interactions and packing arrangements. Experiments will be performed in the Warwick Centre for Magnetic Resonance, which houses the biggest concentration of solid-state NMR spectrometers in the UK, including hosting the UK 850 MHz solid-state NMR facility. A combined approach linking experiment with simulation will be employed in the framework of the emerging field of NMR crystallography.
For further information concerning the Warwick NMR group, see: http://www.go.warwick.ac.uk/nmr/