Polymorphic Solid Solutions in Molecular Crystals: Tips, Tricks, and Switches

[Image: see text] Crystal polymorphism has been a topic of much interest for the past 20 years or so, especially since its scientific (and legal) importance to the pharmaceutical industry was realized. By contrast, the formation of solid solutions in molecular crystals has been overlooked despite its long-standing prevalence in the analogous field of inorganic crystals. Wilfully forgotten, crystalline molecular solid solutions may be very common in our world since molecular compounds are rarely produced with 100% purity, and impurities able to form solid solutions are difficult to reject via recrystallization. Given the importance of both polymorphism and solid solutions in molecular crystals, we share here some tips, tricks, and observations to aid in their understanding. First, we propose a nomenclature system fit for the description of molecular crystalline solid solutions capable of polymorphism (tips). Second, we highlight the challenges associated with their experimental and computational characterization (tricks). Third, we show that our recently reported observation that polymorph stabilities can change by virtue of solid solution formation is a general phenomenon, reporting it on a second system (switches). Our work focuses on the historically important compound benzamide forming solid solutions with nicotinamide and 3-fluorobenzamide.