Quantifying intermolecular interactions in solid state indapamide and other popular diuretic drugs: Insights from Hirshfeld surface study

• The Hirshfeld surface study is used for the quantitative interpretation of several intercontacts in diuretic drugs.
• The first single crystal structure of indapamide.
• The crystal packing in analyzed compounds is governed mainly by N–H⋯O and C–H⋯O and π⋯π stacking interactions.

Hirshfeld surfaces (HS) and two-dimensional fingerprint plots are used to analyze the intermolecular interactions in indapamide and other popular thiazide diuretic derivatives. The crystal structure of indapamide (INDP) at 100 K determined by single-crystal X-ray analysis, is also reported. The title compound crystallizes in the centrosymmetric I2/a space group with one indapamide and half water molecule (lying on the glide plane) in the asymmetric unit. An interplay of N–H⋯O hydrogen bonds connects the indapamide molecules generating chains with the graph-set motifs: C (8) and C23 (16), and together with C–H⋯O and π⋯π stacking interactions create a 3D net. The Hirshfeld surface study facilitates comparison of diverse and numerous intercontacts, such as H⋯H, O⋯H, Cl⋯H, C⋯C (π⋯π), C⋯O (π⋯lone pair), O⋯O (lone pair⋯lone pair), Cl⋯O, Cl⋯Cl, N⋯N, C⋯H (C–H⋯π) with regard to building self-assembled framework of indapamide and related thiazide derivatives retrieved from the Cambridge Structural Database. The HS analysis highlights that H⋯H, O⋯H/H⋯O and C⋯H/H⋯C contacts play an influential role contributing to about 80% of the HS areas in this class of compounds. Nevertheless, in the case of INDP the H⋯H interactions, while in hydrochlorothiazide (HCTZ) O⋯H/H⋯O are dominant amongst all intercontacts towards the HS. Notably, indapamide has the highest proportion of C⋯C contacts.

The article presents the first single crystal structure of indapamide. The Hirshfeld surface analyses show the differences and similarities of intermolecular interactions within the crystalline state for several popular diuretic drugs.Figure optionsDownload as PowerPoint slide