Year: 2017
Type: article
Abstract: We present a periodic density functional theory study of the stability of 350 organic cocrystals relative to their pure single-component structures, the largest study of cocrystals yet performed with high-level computational methods. Our calculations demonstrate that cocrystals are on average 8 kJ mol–1 more stable than their constituent single-component structures and are very rarely (<5% of cases) less stable; cocrystallization is almost always a thermodynamically favorable process. We consider the variation in stability between different categories of systems─hydrogen-bonded, halogen-bonded, and weakly bound cocrystals─finding that, contrary to chemical intuition, the presence of hydrogen or halogen bond interactions is not necessarily a good predictor of stability. Finally, we investigate the correlation of the relative stability with simple chemical descriptors: changes in packing efficiency and hydrogen bond strength. We find some broad qualitative agreement with chemical intuition─more densely packed cocrystals with stronger hydrogen bonding tend to be more stable─but the relationship is weak, suggesting that such simple descriptors do not capture the complex balance of interactions driving cocrystallization. Our conclusions suggest that while cocrystallization is often a thermodynamically favorable process, it remains difficult to formulate general rules to guide synthesis, highlighting the continued importance of high-level computation in predicting and rationalizing such systems.
Source: Crystal Growth & Design
Authors: Christopher R. Taylor, Graeme M. Day
Institution: University of Southampton
Language: English
Subfield: Physical and Theoretical Chemistry
Field: Chemistry
Domain: Physical Sciences
Open Access status: hybrid
Estimated APC paid: $4,500
OpenAlex ID: W2774535559