José Miguel Delgado

The crystal structures of two arylcyclohexylamine derivatives – methoxmetamine·HCl (2-(3-methoxyphenyl)-2-(methylamino)cyclohexan-1-one hydrochloride, MMXE·HCl) and methoxetamine·HCl (2-(ethylamino)-2-(3-methoxyphenyl)cyclohexan-1-one hydrochloride, MXE·HCl) – have been determined using laboratory X-ray powder diffraction data contained in the Powder Diffraction File ^™ . MMXE·HCl and MXE·HCl exhibit anesthetic and sedative effects and have been illicitly used as recreational drugs due to their dissociative hallucinogenic and euphoriant effects. The structure determination of MMXE·HCl and MXE·HCl was carried out with DASH, and the Rietveld refinements were performed with TOPAS Academic in monoclinic unit cells. The parameters obtained for MMXE·HCl were a = 15.0429(5) Å, b = 14.0721(5) Å, c = 6.5716(2) Å, β = 90.9864(14)°, and V = 1,390.91(8) Å ³ , with Z = 4 and space group P 2 ₁ / n. The parameters obtained for MXE·HCl were a = 8.7772(5) Å, b = 9.9528(7) Å, c = 8.5841(6) Å, β = 100.276(3)°, and V = 737.86(8) Å ³ , with Z = 2 and space group P 2 ₁ . The structures were validated by dispersion-corrected DFT calculations. Hirshfeld surface analysis and fingerprint plots calculations are also reported.

The room-temperature X-ray powder diffraction data for bosentan monohydrate, an API used in the treatment of pulmonary arterial hypertension, is presented. Bosentan monohydrate is monoclinic, P 2 ₁ / c (No. 14), with unit cell parameters a = 12.4520(7) Å, b = 15.110(1) Å, c = 15.0849(9) Å, β = 95.119(5)°, V = 2827.0(3) Å ³ , Z = 4. All the diffraction maxima recorded were indexed and are consistent with the P 2 ₁ / c space group. The crystal structure of this material corresponds to the phase associated with Cambridge Structural Database entry NEQHEY, which was determined at 123 K. The successful Rietveld refinement, carried out with TOPAS-Academic, showed the single-phase nature of the material and the good quality of the data. A comprehensive analysis of intra- and intermolecular interactions corroborates that the structure is dominated by extensive hydrogen bonding, accompanied by C▬H⋯π and π⋯π interactions. Hirshfeld surface analysis and fingerprint plots indicate that the most important interactions are H⋯H and O⋯H/H⋯O in bosentan and the water molecule and C⋯H/H⋯C interactions in bosentan.

The previously unindexed laboratory X-ray powder diffraction data of mosapride dihydrogen citrate dihydrate, an API used to stimulate gastrointestinal motility, has been recorded at room temperature. Using these data, the crystal structure of this API has been refined in space group P 2 ₁ / c (No. 14) with a = 18.707(4) Å, b = 9.6187(1) Å, c = 18.2176(4) Å, β = 114.164(1)°, V = 2990.74(8) Å ³ , and Z = 4. The structure of this material corresponds to the phase associated with CSD Refcode LUWPOL determined at 93 K. The Rietveld refinement, carried out with TOPAS-Academic, proved the single nature of the sample and the quality of the data recorded.

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 P 2 ₁ 2 ₁ 2 ₁ , with unit-cell parameters a = 6.3208(3) Å, b = 10.6681(5) Å, c = 28.1754(10) Å, V = 1899.89(14) Å 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, 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.

Almost 50 years after the initial report, the crystal structure of Cu₂GeSe₃, a I₂-IV-VI₃ semiconductor, has been revised using modern single-crystal X-ray diffraction data. The structure of this material can be properly described in the monoclinic space group Cc (No. 9) with unit-cell parameters a = 6.7703 (4) Å, b = 11.8624 (5) Å, c = 6.7705 (4) Å, β = 108.512 (6)°, V = 515.62 (5) ų, Z = 4, rather than in the orthorhombic space group Imm2 (No. 44) with unit-cell parameters a = 11.860 (3), b = 3.960 (1), c = 5.485 (2) Å, V = 257.61 ų, Z = 2, as originally proposed [Parthé & Garín (1971). Monatsh. Chem. 102, 1197–1208]. Contrary to what was observed in the orthorhombic structure, the distortions of the tetrahedra in the monoclinic structure are consistent with the distortions expected from considerations derived from the bond valence model. A brief revision of the structures reported for the I₂-IV-VI₃ family of semiconducting compounds (I: Cu, Ag; IV: Si, Ge, Sn; and VI: S, Se, Te) is also presented.

Several benzothiophene-based compounds, including 1-benzothiophene-2-carboxylic acid, exhibit a wide variety of pharmacological activities. They have been extensively used to treat various types of diseases with high therapeutic effectiveness. In this contribution, the crystal structure of a new polymorph of 1-benzothiophene-2-carboxylic acid (BTCA) was determined from laboratory X-ray powder diffraction data with DASH, refined by the Rietveld method with TOPAS-Academic, and optimized using DFT-D calculations. The new form of 1-benzothiophene-2-carboxylic acid crystallizes in space group C 2/ c (No. 15) with a = 14.635(4), b = 5.8543(9), c = 19.347(3) Å, β = 103.95(1)°, V = 1608.8(6) Å ³ , and Z = 8. The structure is a complex 3D arrangement which can be described in terms of hydrogen-bonded dimers of BTCA molecules, joined by the acid–acid homosynthon, which interact through C–H⋯O hydrogen bonds to produce tapes further connected through head-to-tail π⋯π and edge-to-face C–H⋯π interactions. A comparison with a previously reported triclinic polymorph and with the related 1-benzofuran-2-carboxylic acid (BFCA) is also presented.

It is well-known that the stability, solubility, bioavailability and effectiveness of a pharmaceutical product are affected by the composition (solvates, hydrates, etc.) and the possibility of polymorphism of the Active Pharmaceutical Ingredient (API). In the present study, three different phases of thiocolchicoside, an API used as muscle relaxant, were obtained. The 47 maxima of the X-ray powder diffraction pattern of the raw material were indexed in an orthorhombic unit cell, with a=28.018(7) Å, b=12.519(2) Å, c=8.519(1) Å, V=2988.01 Å3 (M20=56.5; F20=137.6(0.0035,42)) The yellow crystals, obtained after recrystallization of the raw material in water at 37⁰C, produced a pattern with 63 maxima. This pattern was indexed in another orthorhombic unit cell: a=25.264(4) Å, b=13.537(3) Å, c=8.553(1) Å, V=2925.12 Å3 (M20=47.3; F20=131.2 (0.0040, 38)). A third phase was obtained upon heating the yellow crystals. The 51 peaks of its powder pattern are consistent with a monoclinic unit cell with a=17.090(5) Å, b=19.485(5) Å, c=8.526(3) Å, β=100.30(2)⁰, V=2793.34 Å3 (M20=36.5; F30=56.3 (0.0067, 79)). All the patterns were indexed with DicVOL06 and analyzed with NBS*AIDS83. TGA/DSC analysis showed that the raw material is anhydrous, the yellow crystals are dihydrated, and the third phase is anhydrous. It must be noted that, to our knowledge, these phases have not been reported before. The only entry for a thiocolchicoside-related phase, present in the Powder Diffraction File, corresponds to an ethanol solvate hydrate (PDF 02-073-3591), which is also present in the Cambridge Structural Database (REFCODE: THCLCS). The structure of the hydrated phase was determined, from the powder diffraction data, with TALP[1]. It is worth noting the complexity of the thiocolchicoside molecule, the large number of torsion angles that need to be defined and its potentiality for forming hydrogen bonds (see figure 1).