Anisotropy of mechanical properties of celecoxib crystal: nature and features from the point of uniaxial deformations modelling

The theoretical study of mechanical properties of the celecoxib (4-[5-(4-Methylphenyl)-3-(trifluoromethyl)pyrazol-1-yl]benzenesulfonamide) crystal structure of polymorph III (s.g. P-1) was carried out in this work. For this purpose, increasing uniaxial deformation of the crystal structure along three axes of the crystal cell was simulated. To obtain the equilibrium structure of this crystal and structures under tensile deformations, quantum-chemical calculations with periodic boundary conditions by the DFT method at the PBE0/pob-DZVP2 level, and by the 3-corrected Hartree-Fock method with the following semiempirical corrections: Grimme correction of dispersion interactions (D3) for weak interactions, basis set superposition error removal by atom-pair wise geometrical counterpoise correction (gCP), and correction of short-ranged basis set incompleteness effects (SRB). It was found that the analysis of stiffness tensor of the equilibrium form only does not provide the complete information about crystal mechanical behavior in different spatial directions, although this analysis made possible to determine flexibility signs of the celecoxib structure in the (001) plane. In this case, the direction of maximum 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 deformation 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 has confirmed the reliability of previously proposed brittleness/plasticity/elasticity signs for the prediction of dynamic mechanical properties, using the celecoxib crystal as example.