Cocrystals help breaking the “rules” of isostructurality: solid solutions and polymorphism in the malic/tartaric acid system.

Crystalline solid solutions have the potential to afford tunable materials for pharmaceutical and technological applications. Unfortunately, these poorly understood phases are difficult to obtain and, hence, to study. In fact, commonly accepted empirical rules prescribe that only molecules of similar size and electron distribution are mutually soluble in the solid state. Here, despite the evident structural and electronic differences, the enantiomers of malic acid and tartaric acid are crystallized together in a variable stoichiometric ratio to produce both cocrystals and solid solutions. In some cases, physical mixtures are observed. The composition and polymorphism of the crystalline products are explained by DFT-d molecular substitution calculations for the cocrystallized molecules in different (known) structures. At the same time, from a crystal engineering perspective, the behavior of this complex system is rationalized thanks to the existence of intermediate cocrystal forms that merge the structural features of the pure molecular components.