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

TL;DR

This study uses quantum chemistry to explore how fluorouracil interacts with metal-doped ZnO nanoclusters and human serum albumin, identifying a promising candidate for drug delivery in cancer therapy.

Contribution

The study introduces Ni-doped ZnO nanocomplexes as a novel platform for fluorouracil delivery with enhanced charge transfer and binding to HSA.

Findings

5-FU@NiZn11O12 has the lowest HOMO-LUMO gap (2.44 eV), indicating enhanced chemical reactivity.

5-FU@NiZn11O12 shows favorable binding to HSA with a binding energy of -5.36 kcal/mol.

Ni-doped ZnO nanocomplexes exhibit strong potential for drug delivery in anticancer therapy.

Abstract

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.

Adsorption of fluorouracil (5‐FU) on XZn11O12 (X = Zn, Cu, Fe, Ni) nanoclusters and its interactions with human serum albumin (HSA) have been studied using density functional theory and molecular docking. Reduced HOMO‐LUMO gap of 5‐FU@NiZn11O12 nanocomplex suggests enhanced charge transfer activity. The favorable binding interactions of 5‐FU@NiZn11O12 with HSA exhibit its potential for drug delivery and anticancer therapy. © 2026 WILEY‐VCH GmbH

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