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Decoding Supramolecular Packing Patterns from Computed Anisotropic Deformability Maps of Molecular Crystals
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Date
2023
Abstract
The ability to encode and embed desired mechanical properties into active pharmaceutical ingredient solid forms would significantly advance drug development. In recent years, computational methods, particularly dispersion-corrected density functional theory (DFT), have come of age, opening the possibility of reliably predicting and rationally engineering the mechanical response of molecular crystals. Here, many-body dispersion and Tkatchenko−Scheffler dispersion-corrected DFT were used to calculate the elastic constants of a series of archetypal systems, including paracetamol and aspirin polymorphs and model hydro-gen-bonded urea and π−π-bound benzene crystals, establishing their structure−mechanics relations. Both methods showed semiquantitative and excellent qualitative agreement with experiment. The calculations revealed that the plane of maximal Young’s modulus generally coincides with extended H-bond or π−π networks, showing how programmable supramolecular packing dictates the mechanical behavior. In a pharmaceutical setting, these structure−mechanics relations can steer the molecular design of solid forms with improved physicochemical and compression properties
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Publisher
American Chemical Society
Citation
The Journal of Physical Chemistry C 127 (11), pp. 5533-5543
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Guerin_2023_Decoding.pdf
Adobe PDF, 5.2 MB