Pressure is a valuable tool in the assessment of the solid-state forms of organic materials. It has been repeatedly demonstrated that pressure can enable the isolation of new solid-state forms of pharmaceuticals,^1,2 amino acids,³ energetic materials⁴ as well as other types such as metal-organic framework materials.⁵

This project builds on the EPSRC funded ‘Pressure-Induced Nucleation for the Continuous Manufacture of supramolecular assemblies’ where pressure is used to isolate new multi-component materials for use as seeds in ambient pressure crystallisations.^6–8

We have successfully demonstrated that scale-up and quenching of high-pressure phases can be achieved and are now at the stage in our work to assess the viability of this procedure to multi-component systems.⁹

This PhD program will investigate the discovery and recovery of novel solid-state forms of pharmaceutically relevant materials so that their physicochemical properties can be assessed at ambient pressure. The program will be based around crystallisation methodologies and the characterisation of these materials through the use of multiple techniques.

This work is aligned to the recently awarded EPSRC MediForge Hub (CMAC) & CEDAR CDT programs located at the University of Strathclyde. PhD candidates will have access to state-of-the-art equipment for analysis during their PhD studies as well as access to programs for their own personal development

Techniques used

• High-pressure
• X-ray and neutron diffraction (single crystal and powder)
• IR & Raman spectroscopy
• thermal analysis

References

(1) Boldyreva, E. V. Non-Ambient Conditions in the Investigation and Manufacturing of Drug Forms. Curr. Pharm. Des. 2016, No. 32, 4981–5000.

(2) Jones, E. C. L.; Bebiano, S. S.; Ward, M. R.; Bimbo, L. M.; Oswald, I. D. H. Pressure-Induced Superelastic Behaviour of Isonicotinamide. Chem. Commun. 2021, 57 (89), 11827–11830

(3) Novelli, G.; Maynard-Casely, H. E.; McIntyre, G. J.; Warren, M. R.; Parsons, S. Effect of High Pressure on the Crystal Structures of Polymorphs of L-Histidine. Cryst. Growth Des. 2020, 20 (12), 7788–7804. 

(4) Millar, D. I. A.; Oswald, I. D. H.; Francis, D. J.; Marshall, W. G.; Pulham, C. R.; Cumming, A. S. The Crystal Structure of Beta-RDX-an Elusive Form of an Explosive Revealed. Chem. Commun. Camb. Engl. 2009, No. 5, 562–564.

(5) McMonagle, C. J.; Turner, G. F.; Jones, I.; Allan, D. R.; Warren, M. R.; Kamenev, K. V.; Parsons, S.; Wright, P. A.; Moggach, S. A. Pressure and Guest-Mediated Pore Shape Modification in a Small Pore MOF to 1200 Bar. Chem. Commun. 2022, 58 (82), 11507–11510. 

(6) Ward, M. R.; Younis, S.; Cruz-Cabeza, A. J.; Bull, C. L.; Funnell, N. P.; Oswald, I. D. H. Discovery and Recovery of Delta P-Aminobenzoic Acid. CrystEngComm 2019, 21 (13)

(7) Ward, M. R.; Oswald, I. D. H. Hidden Solvates and Transient Forms of Trimesic Acid. Crystals 2020, 10 (12). 

(8) Ward, M. R.; Bull, C. L.; Funnell, N. P.; Warren, M. R.; Oswald, I. D. H. Exploring the Effects of High Pressure on Hydrogen Bonding in Pharmaceutical Cocrystals: A Systematic Study of Pyridine Dicarboxylic Acid Systems Using Synchrotron and Neutron Diffraction. Int. J. Pharm. 2023, 647, 123514. 

(9) Ward, M. R.; Oswald, I. D. H. Antisolvent Addition at Extreme Conditions. CrystEngComm 2019, 21 (30), 4437–4443.