Assessment of the electrostatic binding of ferrocenylmethyl-nitroaniline derivatives to DNA: A combined experimental and theoretical study

The present study investigates the electrostatic binding interactions between ferrocenylmethylnitroaniline derivatives and DNA using a combination of experimental and theoretical approaches. The objective is to elucidate the binding mechanisms and evaluate the potential of these derivatives as DNA -targeting agents. Experimental techniques, including cyclic voltammetry (CV) and UV - Vis spectroscopy (UV - Vis), were employed to assess the binding affinity and conformational changes in DNA upon interaction with the derivatives. Our findings reveal that the ferrocenylmethylnitroaniline derivatives exhibit strong electrostatic interactions with DNA, as confirmed by the negative formal potential shift observed in CV. The binding constants and free binding energies obtained from the docking simulation were found to be consistent with those obtained from CV and UV - Vis spectral analysis. Furthermore, the binding site size was determined from the voltametric data. Complementary theoretical calculations such as geometry optimization, MEP analysis, Mulliken charge distribution, and HOMOLUMO surface were performed by DFT approach (B3LYP/aug-cc-pVTZ/6-311 ++G (d,p)) to gain insights into the structural data, active regions, and chemical reactivity of derivatives. Molecular docking simulation verifies that electrostatic attraction plays a fundamental role in the interaction of Fc2N, Fc3N, and Fc4N with DNA. The molecular dynamics simulations elucidated the stability of DNA-ligand complexes formed with Fc2N, Fc3N, and Fc4N compounds. Analysis of root mean square deviation (RMSD) and radius of gyration (Rg) indicated stable binding and maintained compactness of DNA structures, underscoring the robustness of these interactions for potential therapeutic applications. Top of Form