Quantum Chemical Properties of Fluorouracil/XZn11O12 (X = Zn, Cu, Fe, Ni) Nanocomplexes and Interactions with Human Serum Albumin.

This research focused on structural, electronic, and interaction properties of fluorouracil (5-FU) adsorbed on transition metal (TM)-doped ZnO nanoclusters (XZn11O12, where X = Zn, Cu, Fe, Ni) using density functional theory (DFT) at the B3LYP/LANL2DZ level of calculations in the gas phase. Among the studied nanocomplexes, 5-FU@NiZn11O12 exhibited the highest dipole moment (8.08 D), indicating strong polarization and potential surface reactivity though it has a less negative adsorption energy (-20.97 kcal/mol) compared to 5-FU@FeZn11O12 (-35.51 kcal/mol) and 5-FU@CuZn11O12 (-28.69 kcal/mol). TM doping significantly reduced the highest occupied molecular orbital-lowest unoccupied molecular orbital gap, with 5-FU@NiZn11O12 showing the lowest value (2.44 eV), followed by 5-FU@FeZn11O12 (2.53 eV) and 5-FU@CuZn11O12 (3.18 eV), suggesting enhanced charge transfer and chemical reactivity. The results from molecular electrostatic potential, quantum theory of atoms in molecules, and non-covalent interaction/reduced density gradient analyses were also in favor of Ni-doped ZnO nanocomplex. Based on the DFT results, 5FU@NiZn11O12 was selected to analyze its interactions with human serum albumin (HSA). From molecular docking of 5-FU@NiZn11O12, binding energy (-5.36 kcal/mol) and inhibition constant (117.15 μM) exhibited stronger interactions with HSA, so that it acts as a potential candidate of drug delivery system for anticancer therapy. However, these predictive insights require further experimental validation.