2026/07/20 by Touhami Lanez, Elhafnaoui Lanez, Yahia Bekkar +3
Chemistry · Engineering · #Ferrocene Chemistry and Applications #Inorganic and Organometallic Chemistry #Railway Systems and Materials Science
paper · doi:10.1016/j.jorganchem.2026.124247
In this study, we report the structural and computational investigation of N′-ferrocenylmethyl-N′-phenylbenzohydrazide (FcHy) and its unexpected transformation product, compound 2, obtained during treatment with POCl₃ in toluene. The reaction was initially designed to promote intramolecular cyclisation; however, the isolated product indicates a competing cleavage–chlorination pathway. Since no reaction intermediates were isolated or computationally characterised, the proposed mechanism is discussed as a plausible but hypothetical pathway. Compound 2 was characterised by ¹H and ¹³C NMR spectroscopy, and its molecular structure was confirmed by single-crystal X-ray diffraction. Hirshfeld surface analysis was used to examine the dominant intermolecular contacts in the crystal packing, while DFT calculations provided insight into frontier molecular orbitals, molecular electrostatic potential, and electron-localisation features. Molecular docking and 100 ns molecular dynamics simulations were performed against selected cancer-related kinase targets to evaluate the predicted binding behaviour of FcHy and compound 2. The docking results indicated target-dependent binding profiles, with FcHy showing stronger predicted affinity toward PI3K and VEGFR2, whereas compound 2 displayed a more favourable predicted score toward Akt1. MD simulations supported the relative stability of the selected complexes, although these results remain predictive and require experimental biological validation. Overall, this work describes an unexpected POCl₃-induced transformation of a ferrocenyl hydrazide and provides structural and computational insight into the resulting chlorinated N–N derivative.