jz0c02647_si_003.mpg (16.67 MB)

Generating Cocrystal Polymorphs with Information Entropy Driven by Molecular Dynamics-Based Enhanced Sampling

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posted on 03.11.2020, 20:15 by Hongxing Song, Leslie Vogt-Maranto, Ren Wiscons, Adam J. Matzger, Mark E. Tuckerman
Predicting structures of organic molecular cocrystals is a challenging task when considering the immense number of possible intermolecular orientations. Use of the Shannon information entropy, constructed from an intermolecular orientational spatial distribution function, to drive a search for crystal structures via enhanced molecular dynamics can be an efficient way to map out a landscape of putative polymorphs. Here, the Shannon entropy is used to generate a set of collective variables for differentiating polymorphs of a 1:1 cocrystal of resorcinol and urea. We show that driven adiabatic free energy dynamics, a particular enhanced-sampling approach, combined with these entropy variables, can transform the stable phase into alternate polymorphs. Density functional theory calculations confirm that a structure obtained from the enhanced molecular dynamics is stable at pressures above 1 GPa. We thus show that enhanced sampling should be considered an integral component of crystal structure searching protocols for systems with multiple independent molecules.