Unveiling the binding mechanism of nitroxoline on a dendron-functionalised fullerene via DFT: towards an advanced nanocarrier

Nitroxoline (NIT) is an antimicrobial agent whose interaction with nanocarriers plays a crucial role in its stability and delivery efficiency. In this work, density functional theory calculations were employed to investigate the adsorption of NIT on pristine and bis-MPA functionalised C60 (FC60). Geometry optimizations and vibrational frequency analyses confirmed that all isolated species and complexes correspond to true minima on the potential energy surface. Frontier molecular orbital and molecular electrostatic potential analyses reveal that bis-MPA functionalization significantly modifies the electronic structure and surface polarity of C60, enhancing its affinity toward NIT. Natural bond orbital analysis demonstrates that complex formation is accompanied by pronounced donor–acceptor interactions and enhanced charge transfer in the functionalised system, as reflected in increased second-order stabilisation energies. Noncovalent interaction analysis provides a real-space visualisation of the interaction landscape, showing that while adsorption on pristine C60 is dominated by weak dispersive interactions, the NIT@FC60 complex benefits from the coexistence of strong localised attractive interactions and van der Waals forces. Quantitative insight from quantum theory of atoms in molecules analysis confirms these findings, revealing the emergence of strong O―H … O hydrogen bonds with partial covalent character in the functionalised system, alongside enhanced π-π stacking with the fullerene surface. Overall, the combined energetic, orbital, real-space, and topological analyses demonstrate that bis-MPA functionalization transforms C60 into a multifunctional nanocarrier capable of engaging NIT through cooperative charge transfer, hydrogen bonding, and dispersion interactions. These results provide a clear molecular-level rationale for the enhanced stability of the NIT@FC60 complex and offer valuable guidelines for the rational design of functionalised fullerene-based drug delivery systems.