N’-Ferrocenylmethyl-N’-phenylbenzohydrazide as a potential DNA binding compound: a combined experimental and computational study

Abstract

Due to increased lipophilicity, stability, and decreased cytotoxicity in biological systems, ferrocene derivatives are promising building blocks for therapeutic agents. This manuscript reports the binding of N’-ferrocenylmethyl-N’-phenylbenzohydrazide (FhD) with deoxyribonucleic acid (DNA) studied by absorption spectroscopy and cyclic voltammetry. Binding constants and binding free energies for the FhD-DNA complex were measured using these two methods as 5100 M−1, 6109 M−1 and −21.2 kJ/mol, −21.6 kJ/mol, respectively. DFT calculations were also performed and revealed important physical characteristics of the FhD compound. Subsequently, the system was explored by computational molecular docking, confirming a non-covalent mode of binding via minor groove with a binding energy of −25.5 kJ/mol. Furthermore, molecular dynamics of the docked complex of FhD with DNA were carried out for 100 ns followed by MM-GBSA to have a deep understanding of the complex’s dynamic behavior in physiological systems, and to determine the Gibbs free energy which was −14.31 Kcal/mol over a 100 ns window. The results show important antitumor potential of FhD due to its spontaneous non-covalent interaction with DNA and the efficient binding stability of the FhD-DNA complex in a physiological system.