Theoretical and computational insight into the supramolecular assemblies of Schiff bases involving hydrogen bonding and C-H…π interactions: Synthesis, X-ray characterization, Hirshfeld surface analysis, anticancer activity and molecular docking analysis

Abstract The present study examines the significance of various non-covalent interactions in the supramolecular assembly of (E)-1-(1-(4-nitrophenyl)ethylidene)-2-phenylhydrazine 1c and (E)-3-bromo-N'-(1-phenylethylidene)benzohydrazide 2d. The synthesized compounds were fully characterized by spectroscopic methods and single crystal X-ray diffraction analysis. The topology of the supramolecular assemblies was controlled by various non-covalent interactions including classical hydrogen bonding, C-H…π and Br…Br interactions which were examined in detail using several theoretical methods and DFT calculations. The optimized geometric parameters of compounds 1c and 2d were calculated using density functional theory (DFT/B3LYP) quantum chemical method with the 6-311++G(d,p) basis set using the crystallographic coordinates. Additionally, fragments contributing to the HOMO and LUMO molecular orbitals were investigated at the same level of theory. The nature and various types of intermolecular interactions in the crystal structures was also investigated by Hirshfeld surface analysis. The synthesized Schiff bases were also studied for their potential as drugs and physicochemical properties. Bioevaluation against four cancer cell lines (NCI-H460, NCI-H460/Bcl-2, MDA-MB-231 and MCF-7) showed that compound 1c was a more potent inducer of toxicity compared to 2d. The putative binding modes of the bioactive Schiff bases were investigated using molecular docking tools and the results revealed that both the inhibitors were stabilized in the active pocket of the enzyme via the formation of various interactions with the key amino acid residues.