EVALUATION OF FERROCENYLMETHYLNUCLEOBASES DERIVATIVES INTERACTING WITH DNA: INSIGHTS FROM ELECTROCHEMICAL, SPECTROSCOPIC, DFT CALCULATION, MOLECULAR DOCKING AND MOLECULAR DYNAMIC SIMULATIONS

This study investigates the binding of ferrocenylmethyl nucleobase derivatives to DNA through electrostatic interactions, employing a combination of experimental and theoretical approaches to elucidate binding mechanisms and explore their potential for DNA targeting. UV–Vis spectroscopy and cyclic voltammetry (CV) were used to evaluate binding affinities and structural alterations in DNA. The derivatives exhibited DNA interactions, evidenced by negative formal potential shifts in CV data. Binding constants and free binding energies derived from docking simulations aligned well with UV–Vis and CV analyses. Additionally, voltammetric data provided insights into the binding site size. Molecular docking simulations confirmed the critical role of electrostatic interactions in the binding of FcMeCy, FcMeTh, and (FcMe)2Ad to DNA. Molecular dynamics simulations further revealed the stability of DNA-ligand complexes, with RMSD and radius of gyration (Rg) analyses indicating compact and stable DNA structures, emphasizing the robustness of these interactions for therapeutic applications. Theoretical investigations, including geometry optimization, Mulliken charge distribution, molecular electrostatic potential (MEP) analysis, and HOMO-LUMO surface analysis using density functional theory (B3LYP/aug-cc-pVTZ/6-311++G(d,p)), offered deeper insights into structural properties, reactive sites, and chemical reactivity. These results provide a comprehensive understanding of the interaction mechanisms and potential applications of these derivatives.