posted on 2024-01-19, 16:37authored byYulia Pimonova, John E. Carpenter, Michael Gruenwald
Cocrystallizing
a given molecule with another can be useful for
adjusting the physical properties of molecules in the solid state.
However, most combinations of molecules do not readily cocrystallize
but form either one-component crystals or amorphous solids. Computational
methods of crystal structure prediction can, in principle, identify
the thermodynamically stable cocrystal and thus predict if molecules
will cocrystallize or not. However, the pronounced polymorphism and
tendency of many organic molecules to form disordered solids suggest
that kinetic factors can play an important role in cocrystallization.
The question remains: if a binary system of molecules has a thermodynamically
stable cocrystal, will it indeed cocrystallize? To address this question,
we simulate the crystallization of more than 2600 distinct pairs of
chiral model molecules of similar size in 2D and calculate accurate
crystal energy landscapes for all of them. Our analysis shows that
thermodynamic criteria alone are unreliable in the prediction of cocrystallization.
While the vast majority of cocrystals that form in our simulations
are thermodynamically favorable, most coformer systems that have a
thermodynamically stable cocrystal do not cocrystallize. We furthermore
show that cocrystallization rates increase 3-fold when coformers are
used that do not form well-ordered single-component crystals. Our
results suggest that kinetic factors of cocrystallization are decisive
in many cases.