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

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 P2(1)2(1)2(1), with unit-cell parameters a= 6.3208(3) angstrom, b = 10.6681(5) angstrom, c = 28.1754(10) angstrom, V = 1899.89(14) angstrom(3), Z = 4. The refinement converged to R-p = 0.0442, R-wp = 0.0577, and GoF = 2.440. The crystal structure is a complex 3D arrangement of DAPHCl moieties held together by hydrogen bonds, pi MIDLINE HORIZONTAL ELLIPSIS pi, and C-HMIDLINE HORIZONTAL ELLIPSIS pi interactions. The chloride ions form layers parallel to the ab plane and are connected by dapoxetinium moieties through N-HMIDLINE HORIZONTAL ELLIPSISCl and C-HMIDLINE HORIZONTAL ELLIPSISCl hydrogen bonds. These layers stack along the c-axis, which are connected by C-HMIDLINE HORIZONTAL ELLIPSIS pi interactions. Hirshfeld surface analysis and fingerprint plot calculations have been performed.