Isomeric nitro substituted symmetrical benzamides: Crystal Structures, Hirshfeld surface analysis, 3D energy frameworks, DNA binding and cell line studies

Abstract Isomeric nitro substituted symmetrical benzamides, 2-nitro-N-(2-nitrobenzoyl)benzamide – ASP4 and 3-nitro-N-(3-nitrobenzoyl)benzamide – ASP5, were synthesized. Analysis of both crystals approved the structures of synthesized compounds as assigned from spectroscopic data. The intermolecular N–H···O and C–H···O hydrogen bonds linked the molecules, through the bifurcated hydrogen bonds, into three-dimensional architectures, in which they may be effective in the stabilizations of the structures. π–π interactions between the benzene rings of neighboring molecules further consolidated the crystal packings. Crystal structures by Hirshfeld surface (HS) analysis specified the substantial contributions for the crystal packing that are from H ... O/O ... H (46.4%) and H ... H (20.3%) (ASP4) and H ... O/O ... H (36.7%), H ... C/C ... H (19.9%) and H ... H (14.1%) (ASP5) interactions. The N–H···O and C–H···O hydrogen bond energies, by computational analysis, were found to be 71.0 and 50.5 kJ mol−1 (for ASP4) and 37.0, 36.9 and 26.0, 24.1 kJ mol−1 (for ASP5). The evaluations of the electrostatic, dispersion and total energy frameworks indicated that the stabilizations were dominated via the dispersion energy contributions in both compounds. DNA binding studies pointed that ASP4 has comparatively stronger interaction with DNA. Glioblastoma cancer (U87) and human embryonic kidney (HEK-293) cell lines studies of both the compounds revealed their promising anticancer drug candidacy. However, ASP4 showed less toxicity towards normal cells, hence comparatively safer than ASP5.