Why don't we find more polymorphs? The organic solid state as a challenge to theory and experiment.

CCMMP Seminars
Prof Sarah (Sally) Price
Dr A. J. Misquitta
November 18th, 2014 at 14:00
GO Jones Room 610

Crystal Structure Prediction (CSP) studies successfully generate the thermodynamically favourable crystal packings of a molecule. However there are often more such structures than polymorphs found in interdisciplinary studies performed within the project "Control and Prediction of the Organic Solid State" and in collaborations with industrial pharmaceutical scientists. Analysis of the types of structures on the crystal energy landscape suggests that there are a variety of reasons for this. Improved modelling of thermodynamics could eliminate many structures as unstable relative to other phases or show that they are manifest within the dynamic or static disorder in the observed phases. However, other low energy unobserved structures raise the question as to whether they could be found as metastable polymorphs, or within other solid phases, given the right experiment and characterisation technique.  Hence, calculating the crystal energy landscape can help rationalise experimental observations, and set limits to the range of possible polymorphs. However, the examples in this lecture illustrate why we will over-predict polymorphism until we have a quantitative understanding of the kinetic factors that determine the outcome of the huge range of possible crystallisation experiments.