Rapid computational prediction of crystalline polymorphism

•  The ability of an organic molecular solid to crystallize into different structures is  a phenomenon known as polymorphism.
•  Polymorphism is an issue of major concern in the pharmaceutical industry.  In many drug compounds, some fraction of the crystal structures that can be formed cause the drug to lose its therapeutic function.  If these structures are not known at the time of the drug’s release onto the market, they can turn up unexpectedly in the manufacturing process with potentially serious consequences.
•  We have developed a computational technique capable of rapidly identifying these different crystalline forms. The method supplements molecular dynamics with an algorithm for smoothly evolving the parameters of the crystalline unit cell (right figure), thereby driving the molecules in the unit cell from one crystal structure to another in a calculation that can be performed in just a few hours on a standard desktop computer.  The method also allows the crystal structures to be ranked according in terms of their thermodynamic stability under a chosen set of external conditions (see figure 2).

figure 2