Anisotropy of Mechanical Properties of Celecoxib Crystal: Nature and Features from the Standpoint of Modeling Uniaxial Deformations

Abstract— The theoretical study of mechanical properties of the celecoxib (4-[5-(4-methylphenyl)-3-(trifluoromethyl)pyrazol-1-yl]benzenesulfonamide) form III crystal structure (space group P-1) has been carried out. For this purpose, increasing uniaxial deformations of the crystal structure along three axes of the crystal cell were simulated. To obtain the equilibrium structure of this crystal and structures under tensile strain, quantum-chemical calculations with periodic boundary conditions were performed by the DFT method at the PBE0/pob-DZVP2 level and by the HF-3c method with the following semiempirical corrections: Grimme dispersion correction (D3) for weak interactions, atom pair-wise geometrical counterpoise correction (gCP) for basis set superposition error, and correction for short-ranged basis set incompleteness effects (SRB). It was found that the analysis of stiffness tensor of only the equilibrium crystal structure did not provide the complete information about crystal mechanical behavior in different spatial directions, although this analysis made it possible to determine flexibility signs of the celecoxib structure in the (001) plane. In this case, the direction of maximal resistance of the structure to uniaxial deformation is not determined by specific intermolecular bonds and/or chains but is oriented almost parallel to the plane of conformationally rigid phenyl and pyrazole rings of the celecoxib molecule. The virtual tensile test has allowed to predict the manifestation of elastic properties of the celecoxib crystal in the (001) plane, up to 15% stretching along the crystallographic axes a and b. At greater strains along the a axis, a “non-healing” cavity is formed, which corresponds to the experimental observation of crystal transition to a brittle state. Analysis of the tensile test results confirmed the reliability of previously proposed brittleness/plasticity/elasticity signs for the prediction of dynamic mechanical properties, using the celecoxib crystal as an example.