Prof Sally Price

Research Overview

Modelling intermolecular and intramolecular forces for organic molecules

Intermolecular forces determine the structure and physical properties of molecular solids and liquids. For flexible organic molecules, such as typical pharmaceuticals, the molecule can change conformation in the condensed phases in response to the intermolecular forces. We are exploiting recent advances in the theory of intermolecular forces and both periodic and molecular electronic structure methods to develop various approaches to modelling the structure, energies and properties of the organic solid state. Much of this work uses our own program, DMACRYS, for modelling crystal structures with distributed multipole representations of the ab initio molecular charge density

Understanding and predicting organic crystal structures

We are developing various computational “crystal structure prediction” methods to generate the thermodynamically feasible crystal structures of organic molecules. We work closely with both academic and industrial groups involved in polymorph screening to determine which of the calculated structures correspond to observed polymorphs, which may be seen as disorder within crystal structures, and how we can design experiments to find a “predicted” polymorph. This development of our understanding of organic crystallization, and how we interpret the computed crystal energy landscapes has mainly been done through the Control and Prediction of the Organic Solid State (CPOSS) Project. The CPOSS web-site gives more details of Sally's past and current activities and research group.

Experimentally observed conformations

Summary plot of the crystal structure prediction study of 6-[(5-chloro-2-([(4-chloro-2-fluorophenyl)methyl]oxy)phenyl)methyl]-2-pyridinecarboxylic acid (GSK269984B). Each point represents a crystal structure classified by a central torsion angle and acid conformation. The three lowest energy structures and their conformations are shown: remarkably the conformation in the lowest energy and observed crystal structure is very close to the ab initio minimum energy structure ( element colours), and, apart from the hydrogen bonding proton, that in the DMSO solvate (orange) and the NMP solvate ( blue). Reference 2 discusses why no polymorphs were found.

In 2003, before CPOSS started, her group gave her the Sally Price Group Homepage which is kept for sentimental reasons, and also gives an idea of the applications of realistic intermolecular potentials to studying molecular recognition in biochemical processes.