Crystal structure from X-ray powder diffraction data, DFT-D calculation, Hirshfeld surface analysis, and energy frameworks of ( RS )-trichlormethiazide

• Published in: Acta crystallographica. Section E, Crystallographic communications Crystallographic communications, 2022-02, Vol.78 (2), p.140-148
• Main Authors: Toro, Robert A., Dugarte-Dugarte, Analio, Streek, Jacco van de, Henao, José Antonio, Delgado, José Miguel, Díaz de Delgado, Graciela
• Format: Article
• Language: English
• Subjects: dft-d calculations; energy frameworks; hirshfeld surface analysis; powder diffraction; structure determination; trichlormethiazide
• ISSN: 2056-9890; 2056-9890
• DOI: 10.1107/S2056989021013633

The structure of racemic ( RS )-trichlormethiazide [systematic name: ( RS )-6-chloro-3-(dichloromethyl)-1,1-dioxo-3,4-dihydro-2 H -1λ 6 ,2,4-benzothiadiazine-7-sulfonamide], C 8 H 8 Cl 3 N 3 O 4 S 2 ( RS -TCMZ), a diuretic drug used in the treatment of oedema and hypertension, was determined from laboratory X-ray powder diffraction data using DASH [David et al. (2006). J. Appl. Cryst. 39 , 910–915.], refined by the Rietveld method with TOPAS-Academic [Coelho (2018). J. Appl. Cryst. 51 , 210–218], and optimized using DFT-D calculations. The extended structure consists of head-to-tail dimers connected by π–π interactions which, in turn, are connected by C—Cl...π interactions. They form chains propagating along [101], further connected by N—H...O hydrogen bonds to produce layers parallel to the ac plane that stack along the b -axis direction, connected by additional N—H...O hydrogen bonds. The Hirshfeld surface analysis indicates a major contribution of H...O and H...Cl interactions (32.2 and 21.7%, respectively). Energy framework calculations confirm the major contribution of electrostatic interactions ( E elec ) to the total energy ( E tot ). A comparison with the structure of S -TCMZ is also presented.