Crystal structure from laboratory X-ray powder diffraction data, DFT-D calculations, and Hirshfeld surface analysis of (S)-dapoxetine hydrochloride

Abstract

The previously unreported crystal structure of (S)-Dapoxetine hydrochloride (DAPHCl), the only active pharmaceutical ingredient specially developed for the treatment of premature ejaculation in men, has been determined from laboratory X-ray powder diffraction data with DASH and refined by the Rietveld method with TOPAS-Academic. The structure was evaluated and optimized by dispersion-corrected DFT calculations. This compound crystallizes in an orthorhombic cell, space group P212121, with unit-cell parameters a= 6.3208(3) Å, b = 10.6681(5) Å, c = 28.1754(10) Å, V = 1899.89(14) Å3, Z = 4. The refinement converged to Rp = 0.0442, Rwp = 0.0577, and GoF = 2.440. The crystal structure is a complex 3D arrangement of DAPHCl moieties held together by hydrogen bonds, π⋯π, and C–H⋯π interactions. The chloride ions form layers parallel to the ab plane and are connected by dapoxetinium moieties through N–H⋯Cl and C–H⋯Cl hydrogen bonds. These layers stack along the c-axis, which are connected by C–H⋯π interactions. Hirshfeld surface analysis and fingerprint plot calculations have been performed.