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

The structure of racemic (RS)-trichlormethiazide [systematic name: (RS)-6-chloro-3-(dichloromethyl)-1,1-dioxo-3,4-dihydro-2H-1 lambda(6),2,4-benzothiadiazine-7-sulfonamide], C8H8Cl3N3O4S2 (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, 910-9151, 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 pi-pi interactions which, in turn, are connected by C- Cl center dot center dot center dot pi interactions. They form chains propagating along [101], further connected by N-H center dot center dot center dot O hydrogen bonds to produce layers parallel to the ac plane that stack along the b-axis direction, connected by additional N-H center dot center dot center dot O hydrogen bonds. The Hirshfeld surface analysis indicates a major contribution of H center dot center dot center dot O and H center dot center dot center dot 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.

Automated summary

The structure of the diuretic drug RS-trichlormethiazide was determined using laboratory X-ray powder diffraction data and different computational methods. The compound forms chains and layers through pi-pi and C-Cl center dot center dot center dot pi interactions, with hydrogen bonds playing a significant role in the overall structure. Hirshfeld surface analysis highlighted the importance of H center dot center dot center dot O and H center dot center dot center dot Cl interactions. The study also compared the structure with that of S-trichlormethiazide.