(231c) Virtual Coformer Screening by Cloud-Computing Crystal Structure Predictions

One of the most popular strategies of the optimization of drug properties in the pharmaceutical industry appears to be a solid form changing into a cocrystalline form. A number of virtual screening approaches have been previously developed to allow a selection of the most promising cocrystal formers (coformers) for an experimental follow-up. A significant drawback of majority of those methods is related to the lack of accounting for the crystallinity contribution to cocrystal formation. To address this issue, we propose a virtual coformer screening approach based on a modern cloud-computing crystal structure prediction (CSP) technology at a dispersion-corrected density functional theory (DFT-D) level.¹ The CSP-based methods were validated on challenging cases of indomethacin and paracetamol cocrystallization, for which the previously developed approaches provided poor predictions. The calculations demonstrated a dramatic improvement of the virtual coformer screening performance relative to the other methods. It is demonstrated that the crystallinity contribution to the formation of paracetamol and indomethacin cocrystals is a dominant one and, therefore, should not be ignored in the virtual screening calculations.

1. GX Sun, Y Jin, S Li, Z Yang, B Shi, C Chang, YA Abramov. Phys. Chem. Lett. 2020, 11, 8832−8838.