Investigation of intermolecular interactions in finasteride drug crystals in view of X-ray and Hirshfeld surface analysis

• Finasteride DMF pseudopolymorph crystal structure.
• Scrutiny of intermolecular interactions in the finasteride crystals, retrieved from CSD.
• 3D Hirshfeld surface.
• 2D fingerprint plots.

The N,N-dimethylformamide (DMF) solvate hemihydrate (1) of finasteride, has been structurally characterized by single-crystal X-ray diffraction at 100 K and compared with previously reported finasteride crystalline forms. In addition, in order to resolve ambiguity concerning H-bond interactions, the crystal structure of finasteride hemihydrate, (2), originally reported by Schultheiss et al. in 2009, has been redetermined with higher precision. The (1) and (2) pseudopolymorphs of finasteride crystallize as orthorhombic in chiral P212121 space group with two very similar host molecules in the asymmetric unit. The conformation of fused 6-membered rings are screw-boat, chair and chair for both molecules, while 5-membered rings assume chair in (1), and half-chair in (2). There is a fairly close resemblance of the molecular geometry for all analyzed compounds, arising due to the rigid host molecule. Inter- and intramolecular host–host, host–guest strong O–H⋯O, N–H⋯O hydrogen bonds and weak C–H⋯O interactions form 3D net conferring stability to the crystal packing. Finasterides can be classified as synthon pseudopolymorphs. Isostructural solvates crystallizing in the orthorhombic space group P212121, with Z  ′ = 2, exhibit R22(8)C22(15)R22(8)C22(15) network, monoclinic solvate (Z  ′ = 1) possess D11(2)D11(2), while both orthorhombic and monoclinic polymorphs have C(4) motifs, respectively. The structural similarities and subtle differences have been interpreted in view of the 3D Hirshfeld surface analysis and associated 2D fingerprint plots, which enabled detailed qualitative and quantitative insight into the intermolecular interactions. The 97–100% of Hirshfeld surface areas are due to H···H, O···H/H⋯O, C···H/H⋯C and N⋯H/H⋯N contacts. Furthermore, the electrostatic potential has been mapped over the Hirshfeld surfaces to decode the electrostatic complementarities, which exist in the crystal packing.

This manuscript presents a new solvatomorph of the aza-steroid drug finasteride and combines experimental (single-crystal X-ray study) and theoretical, both qualitative and quantitative approach (3D Hirshfeld surfaces and 2D fingerprint plots) in view of intermolecular interactions comparison with the previously reported finasteride crystals.Figure optionsDownload as PowerPoint slide