Department Of Chemistry

Sarah (Sally) Price

Professor of Physical Chemistry

Professor Sally Price is a computational chemist who heads the project “Control and Prediction of the Organic Solid State” CPOSS www.cposs.org.uk . The project started in 2003, and provides computed crystal energy landscapes, the set of crystal structures for an organic molecule which are sufficiently thermodynamically stable to be considered as possible polymorphs.1 Our database covers over 170 systems, from carbonic acid, through some pigments, energetic materials, generic pharmaceuticals such as aspirin and paracetamol, to multi-component systems such as hydrates, cocrystals with caffeine or succinic acid, and some diastereomeric salts. Progress is being made on model modern developmental pharmaceuticals.

The CPOSS group develops a program suite DMACRYS2 for modelling organic crystal structures and their second derivative mechanical and spectroscopic properties, based on using anisotropic atom-atom potentials. The distributed multipole electrostatic model can be obtained by analysis of the molecular wavefunction. This electrostatic model is routinely used in conjunction with empirically fitted exp-6 atom-atom models, and conformational energies derived from single molecule ab initio calculations, for modelling conformationally flexible pharmaceutical molecules. Collaboration with Prof Costas Pantelides and Dr Claire Adjiman, (Process Systems Engineering, Imperial College) has produced a suite of codes for generating crystal energy landscapes for quite large, flexible pharmaceuticals. 3 In collaboration with Dr Alston Misquitta (Queen Mary College), we can derive and use state-of-the-art non-empirical anisotropic atom-atom intermolecular potentials for specific small rigid molecules for high accuracy simulations.

Collaboration with experiment is developing our ability to interpret the crystal energy landscapes to design experiments to find novel polymorphs, help solve structures from powder diffraction or other experimental data, and predict and rationalise static or dynamic disorder. Current EPSRC funded large scale on-going collaborations are with Prof Derek Tocher, UCL Chemistry, Prof Alastair Florence, Institute of Pharmacy and Biomedical Sciences, University of Strathclyde and Prof Alan Jones, UCL Chemical Engineering. Other specific projects involve academic and industrial solid form scientists.

Selected References

1. Price, S. L. Computed crystal energy landscapes for understanding and predicting organic crystal structures and polymorphism. Accounts Chem. Res. 2009, 42, 117-126.

2. Price, S. L.; Leslie, M.; Welch, G. W. A.; Habgood, M.; Price, L. S.; Karamertzanis, P. G.; Day, G. M. Modelling Organic Crystal Structures using Distributed Multipole and Polarizability-Based Model Intermolecular Potentials. Phys. Chem. Chem. Phys. 2010, 12, 8478-8490.

3. Kazantsev, A. V.; Karamertzanis, P. G.; Adjiman, C. S.; Pantelides, C. C.; Price, S. L.; Galek, P. T.; Day, G. M.; Cruz-Cabeza, A. J. Successful prediction of a model pharmaceutical in the fifth blind test of crystal structure prediction. Int. J. Pharm. 2011, 418, 168-178.

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