Polymorphism and Morphology Folklore

Abstract

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.

Mechanical properties and peculiarities of molecular crystals

“…A large proportion (up to one-third) of molecular crystals can be made to twist as they grow. 38,[110][111][112][113] In some families of crystals, such as binary charge transfer complexes, the proportion can be greater than one-half. 114 This group includes many common materials that have been studied for decades or more.…”

In Situ Observation of Slight Twisting in Hen Egg-White Lysozyme Crystals during Crystal Growth and Dissolution by Digital X-ray Topography

“…Several crystal twisting mechanisms have been reported in previous studies. − The size dependence of twisting magnitude in crystals is identified as one of the characteristics of geometric frustration, a primary mechanism of twisting in molecular crystals. − In the geometrical frustration mechanism, a molecular arrangement corresponding to the twisted crystal is physically preferred, even with elastic stress (strain) associated with the inevitable misfit due to steric hindrances at the molecular scale or small crystalline sizes. However, these twisted crystals cannot be realized globally, i.e., in large crystals, because the elastic energy associated with stress increases as twisted crystal size increases.…”

“…Besides lysozyme and thaumatin, growth-induced twisting has been reported in inorganic crystals, , organic crystals, , pharmaceutical crystals, , semiconductor crystals, and polymer spherulites. , As most of these studies were conducted using optical and electron microscopy, − the observed magnitudes of twisting were significantly larger than those in protein crystals observed using digital X-ray topography. Thus, the evaluation of slight twisting via digital X-ray topography in different materials could lead to the discovery of more twisted crystals.…”

Tailor‐Made Auxiliaries for Polar Growth from Melts

“…To introduce a paper in honor of the 2021 Wolf Prize winners who invented tailor-made additives (or auxiliaries) (TMAs) [1][2][3][4] for transformations of growing crystals, we reckoned correctly that there must be a Yiddish story about a tailor that could provide a point of departure. [5] Can wisdom from a tailor of folklore [6] inform our essay about crystal tailors?…”