Overcoming the difficulties of predicting conformational polymorph energetics in molecular crystals via correlated wavefunction methods.

ABSTRACT: Molecular crystal structure prediction is increasingly being applied to study the solid form landscapes of larger, more flexible pharmaceutical molecules. Despite many successes in crystal structure prediction, van der Waals-inclusive density functional theory (DFT) methods exhibit serious failures predicting the polymorph stabilities for a number of systems exhibiting conformational polymorphism, where changes in intramolecular conformation lead to different intermolecular crystal packings. Here, the stabilities of the conformational polymorphs of o-acetamidobenzamide, ROY, and oxalyl dihydrazide are examined in detail. DFT functionals that have previously been very successful in crystal structure prediction perform poorly in all three systems, due primarily to the poor intramolecu

SUBMITTER: Greenwell C 

PROVIDER: S-EPMC7059316 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature