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<p>We combine state-of-the-art computational
crystal structure prediction (CSP) techniques with a wide range of experimental
crystallization methods to understand and explore crystal structure in
pharmaceuticals and minimize the risk of unanticipated late-appearing
polymorphs. Initially, we demonstrate
the power of CSP to rationalize the difficulty in obtaining polymorphs of the
well-known pharmaceutical isoniazid and show that CSP provides the structure of
the recently discovered, but unsolved, Form III of this drug despite there
being only a single known form for almost 70 years. More dramatically, our blind CSP study
predicts a significant risk of polymorphism for the related iproniazid.
Employing a wide variety of experimental techniques, including high-pressure
experiments, we experimentally obtained the first three known non-solvated
crystal forms of iproniazid, all of which were successfully predicted in the
CSP procedure. We demonstrate the power
of CSP methods and free energy calculations to rationalize the observed
elusiveness of the third form of iproniazid, the success of high-pressure
experiments in obtaining it, and the ability of our synergistic
computational-experimental approach to “de-risk” solid form landscapes.</p>
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Half-metallicity in uranium intermetallics: crystal structure prediction of a high-pressure phase of UCo
