Computational prediction of organic crystal structures and polymorphism

Abstract

The development of a robust manufacturing process for solid organic materials, such as pharmaceuticals, can be complicated when the molecules crystallize in different solid forms, including polymorphs. The diverse challenges to computational chemistry in computing the relative thermodynamic stability of different potential crystal structures for a range of organic molecules are outlined. Once the crystal structures which are thermodynamically feasible have been obtained, then comparison with the experimentally known polymorphs can provide interesting insights into crystallization behaviour. Although the computational prediction of polymorphism requires modelling the kinetic factors that can influence crystallization, the computational prediction of the crystal energy landscape is already a valuable complement to experimental searches for polymorphs.

Keywords:

• organic solid state
• lattice energy
• polymorphism

Acknowledgements

This review has mainly drawn from the multidisciplinary project ‘Control and Prediction of the Organic Solid State’ (www.cposs.org.uk) funded by the Basic Technology program of the Research Councils UK. It is impossible to acknowledge all the scientists, from a range of disciplines, who have helped me develop the methodology and interpretation of computed organic crystal energy landscapes, but Drs Panos G. Karamertzanis, Alston Misquitta, Graeme M. Day, Mr Gareth W.A. Welch and Dr Louise S. Price have been particularly helpful with this review. The low energy crystal structures and properties for most of the studies referenced are stored on the National Grid Service dataportal and are available from the author on request.