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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