Polymorphism and Morphology Folklore

Polymorphism of molecular crystals was Joel Bernstein's (1941-2019) scientific focus. Polymorphism also has been the subject of lore: (1) McCrone made popular the belief that the longer you study a substance the more polymorphs you are likely to find, and (2) Bernstein made popular so-called disappearing polymorphs, forms that no matter how long you look you can no longer find (in the absence of extraordinary measures). Here, we add the following lore: (3) Molecular crystals with helicoidal morphologies are as common as those that are polymorphic. The aforementioned observations of McCrone, Bernstein, and the present authors do not rise to the level of scientific principles. They are nevertheless guides grounded in laboratory experience. The experiences out of which the third statement emerges is the work of overlooked researchers, as well as a long list of substances with helicoidal morphologies assembled during the past decade in our laboratories. Here, the claim of the ubiquity of twisted crystals is supported with a particular demonstration with polymorphs of active pharmaceutical ingredients, favorites of Bernstein because of their intersection with the law. It was previously shown that crystallites of particular polymorphs of aspirin and acetaminophen (paracetamol) twist as they grow. No such observations have been made for the other two popular over-the-counter pain relief medicines, ibuprofen and naproxen. They are given here. Twisting among all four common pain medicine crystals seems improbable, to us, and supports a fact about molecular crystal morphology that is not widely appreciated but hiding in plain view.