Intermolecular interactions and disorder in six isostructural celecoxib solvates

Six isostructural crystalline solvates of the active pharmaceutical ingredient celecoxib {4-[5-(4-methylphenyl)-3-(trifluoromethyl)pyrazol-1-yl]benzenesulfonamide; C₁₇H₁₄F₃N₃O₂S} are described, containing dimethylformamide (DMF, C₃H₇NO, 1), dimethylacetamide (DMA, C₄H₉NO, 2), N-methylpyrrolidin-2-one (NMP, C₅H₉NO, 3), tetramethylurea (TMU, C₅H₁₂N₂O, 4), 1,3-dimethyl-3,4,5,6-tetrahydropyrimidin-2(1H)-one (DMPU, C₆H₁₂N₂O, 5) or dimethyl sulfoxide (DMSO, C₂H₆OS, 6). The host celecoxib structure contains one-dimensional channel voids accommodating the solvent molecules, which accept hydrogen bonds from the NH₂ groups of two celecoxib molecules. The solvent binding sites have local twofold rotation symmetry, which is consistent with the point symmetry of the solvent molecule in 4 and 5, but introduces orientational disorder for the solvent molecules in 1, 2, 3 and 6. Despite the isostructurality of 1-6, the unit-cell volume and solvent-accessible void space show significant variation. In particular, 4 and 5 show an enlarged and skewed unit cell, which can be attributed to a specific interaction between an N-CH₃ group in the solvent molecule and the toluene group of celecoxib. Intermolecular interaction energies calculated using the PIXEL method show that the total interaction energy between the celecoxib and solvent molecules is broadly correlated with the molecular volume of the solvent, except in 6, where the increased polarity of the S=O bond leads to greater overall stabilization compared to the similarly-sized DMF molecule in 1. In the structures showing disorder, the most stable orientations of the solvent molecules make C-H...O contacts to the S=O groups of celecoxib.