Computational Insights Into Melanin‐Cu 3 /Ni 3 /Fe 3 /Zn 3 Interactions for Sensing and Biomedical Applications

ABSTRACT In this study, the interaction between melanin and transition‐metal nanoclusters (Cu 3 , Ni 3 , Fe 3 , and Zn 3 ) is systematically examined using density functional theory to assess their potential for sensing and biomedical applications. Multiple adsorption configurations are explored to elucidate the strength, nature, and electronic consequences of melanin‐metal binding. The results reveal a pronounced metal‐dependent interaction pattern, with Fe 3 and Cu 3 nanoclusters exhibiting substantially stronger adsorption than Ni 3 and Zn 3 . Notably, the Fe 3 ‐D4 and Cu 3 ‐D4 configurations display the highest adsorption energies of −116.94 and −82.46 kcal mol −1 , respectively, indicative of strong and spontaneous chemisorption. These interactions are primarily governed by coordination between metal atoms and carbonyl oxygen sites of melanin, accompanied by significant charge transfer and electronic redistribution. Conceptual DFT descriptors further confirm that the most strongly bound complexes exhibit enhanced stability, consistent with the maximum hardness and minimum electrophilicity principles. In contrast, Zn 3 clusters show comparatively weak adsorption and minimal electronic response. Overall, this work provides clear theoretical evidence that Fe 3 and Cu 3 nanoclusters are promising candidates for melanin‐based nanocarrier and sensing platforms, offering valuable insight into the rational design of metal‐biomolecule hybrid systems.