Understanding and engineering non-covalent interactions in crystals, cocrystals, and gels

Molecules can be arranged in numerous ways in crystalline solids, which brings with it the classifications of different solid forms and the nuanced relationships between them. For example, the solid form landscape of a compound can span polymorphs, cocrystals, salts, hydrates, solvates, and inclusion complexes, with the obtained forms being highly dependent on the individual system. This raises fundamental questions: Why are some compounds highly polymorphic while others are not? Why do some compounds tend to form a broad range of cocrystals while others do not mix with cocrystal formers in the solid state? What can the structure of a form tell us about its crystallisation pathway? How can we comprehensively and efficiently screen for solid forms and design new ones?[1] Furthermore, hydrogen bond pairing and supramolecular synthon principles have dominated cocrystal design strategies for decades, but can we exclusively say that hydrogen bonds are the most important interaction in cocrystal systems?

[1] A. V. Hall, A. J. Cruz-Cabeza, and J. W. Steed, Cryst. Growth Des. 2024, 24, (17), 7342-7360.