🔗 Disappearing Polymorphs

In materials science, disappearing polymorphs (or perverse polymorphism) describes a phenomenon in which a seemingly stable crystal structure is suddenly unable to be produced, instead transforming into a polymorph, or differing crystal structure with the same chemical composition, during nucleation. Sometimes the resulting transformation is extremely hard or impractical to reverse, because the new polymorph may be more stable. It is hypothesized that contact with a single microscopic seed crystal of the new polymorph can be enough to start a chain reaction causing the transformation of a much larger mass of material. Widespread contamination with such microscopic seed crystals may lead to the impression that the original polymorph has "disappeared."

This is of concern to both the pharmaceutical and computer hardware industry, where disappearing polymorphs can ruin the effectiveness of their products, and make it impossible to manufacture the original product if there is any contamination. There have been cases of laboratories growing crystals of a particular structure and when they try to recreate this, the original crystal structure isn't created but a new crystal structure is. The drug paroxetine was subject to a lawsuit that hinged on such a pair of polymorphs, and multiple life-saving drugs, such as ritonavir, have been recalled due to unexpected polymorphism. Although it may seem like a so-called disappearing polymorph has disappeared for good, it is believed that it is always possible in principle to reconstruct the original polymorph, though doing so may be impractically difficult. Disappearing polymorphs are generally metastable forms, that are replaced by a more stable form.

It is hypothesized that "unintentional seeding" may also be responsible for the phenomenon in which it often becomes easier to crystallize synthetic compounds over time.