The potential of gold clusters as an innovative carrier for the nitrosoureas anticancer drug: Detailed view of NBO and QTAIM analyses

This study employed density functional theory (DFT) calculations to explore the interactions between nitrosourea (Nu) and small gold clusters, specifically Au4 and Au6. The nature of these interactions was further clarified using the quantum theory of atoms in molecules (QTAIM) and natural bond orbital (NBO) analyses. The results reveal that the Nu drug interacts strongly with the gold clusters. Among the conformers studied, the most stable Au4 complex exhibits a binding energy of −23.31 kcal/mol. In comparison, the most stable Au6 conformer, Nu/Au6 (1), shows binding energies of −9.54 kcal/mol in the gas phase and −9.57 kcal/mol in aqueous solution. Importantly, the electronic structure of the Aun clusters undergoes significant changes upon interaction with the Nu molecule. The decrease in the energy gap of the stable complexes serves as a chemical indicator of Nu adsorption. Furthermore, the dipole moments of the complexes increase by 3 %–36 % in aqueous environments compared to the gas phase. Analysis of the Au–O bond in the Nu complexes indicates that the bond is strongest in the Nu–Au4 (2) complex relative to the others studied. Consequently, Nu/Aun complexes show great potential as carriers for delivering the Nu molecule, owing to their strong adsorption energies and good solubility in polar solvents. These findings could contribute to future advancements in nanomedicine.