TY - JOUR
T1 - Decoding Supramolecular Packing Patterns from Computed Anisotropic Deformability Maps of Molecular Crystals
AU - Zwane, Reabetswe R.
AU - Klug, Joaquin
AU - Guerin, Sarah
AU - Thompson, Damien
AU - Reilly, Anthony M.
N1 - Publisher Copyright:
© 2023 American Chemical Society. All rights reserved.
PY - 2023/3/23
Y1 - 2023/3/23
N2 - 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 hydrogen-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-πnetworks, 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.
AB - 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 hydrogen-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-πnetworks, 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.
UR - http://www.scopus.com/inward/record.url?scp=85149761093&partnerID=8YFLogxK
U2 - 10.1021/acs.jpcc.2c08212
DO - 10.1021/acs.jpcc.2c08212
M3 - Article
AN - SCOPUS:85149761093
SN - 1932-7447
VL - 127
SP - 5533
EP - 5543
JO - Journal of Physical Chemistry C
JF - Journal of Physical Chemistry C
IS - 11
ER -