Charting the salt–cocrystal continuum of acid–base multicomponent crystals with hybrid density functional theory†

It is shown that periodic density functional theory (DFT) with hybrid exchange–correlation functionals can be applied to determine the chemical nature of acid–base multicomponent crystals. For a test set of experimentally assigned crystals, the energies of reference “pure” cocrystal and salt forms are calculated in an efficient numerical atomic orbital (NAO) formalism. It is found that energy differences from hybrid DFT can reliably place most of the considered crystals in their assigned chemical class. It is further discussed how DFT has reached the maturity where it may help with the interpretation of ambiguous experimental characterizations and transform how different states along the salt–cocrystal continuum are classified.