Synergistic <i>in-silico</i> investigation of amide-functionalised aminomethylferrocene: a promising antiproliferative agent, DFT, molecular docking and molecular dynamics simulations profiling

Theoretical insights into the remarkable anticancer efficacy of C31H35FeN3O4 (a 3-aminomethylferrocene derivative) were explored to rationalise its superior activity against breast cancer, particularly compared with cisplatin and other standard estrogen receptor antagonists. DFT calculations were incorporated to optimise geometries that matched experimental crystallographic data, confirming the robustness of the computational model. Vibrational frequency analysis, supported by potential energy distribution, validates the predicted molecular structure, enabling accurate spectral assignments. TD-DFT analysis revealed strong π→π*, n→π*, and metal-to-ligand charge transfer (MLCT) transitions, while natural bond orbital analysis indicated significant intramolecular electron delocalisation, contributing to the molecule’s stability. Fukui function calculations highlighted the electrophilic and nucleophilic reactive sites, aligning with experimental reactivity patterns. A molecular docking study demonstrated high binding affinity of C31H35FeN3O4 for estrogen receptors, with MolDock scores markedly superior to those of the standard drugs fulvestrant and tamoxifen. Comparative molecular dynamics simulations spanning 250 ns confirmed the stability of the C31H35FeN3O4 oestrogen receptor complex, characterised by low RMSD and RMSF values, with consistent involvement of key residues, including Asn532, Lys531 and Leu384. Collectively, these computational findings offer a detailed mechanistic understanding of the enhanced anticancer activity of C31H35FeN3O4, strongly supporting its potential as a new therapeutic agent for estrogen receptor-positive breast cancer.