Synthesis, crystal structure, Hirshfeld surface analysis, DFT studies and DNA binding interactions of N-ferrocenylmethyl-N-(3-cyanophenyl)acetamide

Abstract

This work reports the synthesis, structural characterization, and biomolecular interaction of a new ferrocene-based molecule, N-ferrocenylmethyl-N-(3-cyanophenyl)acetamide (FcCN). The compound was secured through multi-step synthesis and structurally determined by SC-XRD to confirm a very robust sandwich-type ferrocene core with negligible distortion from the acetamide side chain. Electron Localization Function (ELF) and Localized Orbital Locator (LOL) analyses confirmed localized bonding in the organic backbone and delocalized electron density in the ferrocenyl group. Hirshfeld surface analysis showed that the crystal packing is stabilized mostly by H⋯H (53.0 %) and C⋯H/H⋯C (22.1 %) interactions, with significant contributions from N∙∙∙H and O∙∙∙H hydrogen bonds. Electrochemical measurements indicated a drastic negative shift in redox potential and reduction in peak current upon DNA binding, typical of the formation of a slowly diffusing FcCN-DNA adduct. DFT calculations corroborated the experimental data, with a HOMO–LUMO gap of 3.523 eV indicative of favourable stability and reactivity. Molecular docking predicted high DNA binding affinity (-6.9 kcal/mol) through groove interaction, and molecular dynamics simulation attested to the stability of the complex. These data highlight the prospects of FcCN as a redox-active, DNA-targeting entity and add to the increasing interest in ferrocene derivatives as therapeutic agents.