Collective Variables for Conformational Polymorphism in Molecular Crystals

TL;DR

This paper introduces a new method for identifying collective variables to efficiently simulate and understand conformational polymorphism in molecular crystals, demonstrated on the energetic material CL-20.

Contribution

The paper presents a simple dimensionality reduction approach to find collective variables that facilitate conformational transition simulations in molecular crystals.

Findings

Successfully identified collective variables for CL-20 polymorphs.

Reconstructed free energy surfaces revealing new defect and intermediate forms.

Enabled observation of all polymorph transitions in biased simulations.

Abstract

Controlling polymorphism in molecular crystals is crucial in the pharmaceutical, dye, and pesticide industries. However, its theoretical description is extremely challenging, due to the associated long timescales ($ > 1 \, \mu s$). We present an efficient procedure for identifying collective variables that promote transitions between conformational polymorphs in molecular dynamics simulations. It involves applying a simple dimensionality reduction algorithm to data from short ($\sim ps$) simulations of the isolated conformers that correspond to each polymorph. We demonstrate the utility of our method in the challenging case of the important energetic material, CL-20, which has three anhydrous conformational polymorphs at ambient pressure. Using these collective variables in Metadynamics simulations, we observe transitions between all solid polymorphs in the biased trajectories. We reconstruct the free energy surface and identify previously unknown defect and intermediate forms in the transition from one known polymorph to another. Our method provides insights into complex conformational polymorphic transitions of flexible molecular crystals.