<i>In silico</i> study on structural, electronic, and adsorption properties of cisplatin/(TiO ₂ ) _n (n = 2–5) nanoclusters and interactions with hen egg white lysozyme

Abstract This study explored the structural, adsorption, and electronic properties of titania nanostructures loaded with cisplatin (cis) using density functional theory (DFT) at the level of B3LYP/LANL2DZ functional in gas phase, and examined the binding potential of the cis-(TiO 2 ) n (n = 2–5) nanoclusters (NCs) with hen egg white lysozyme (HEWL) via molecular docking. Our results revealed that cisplatin adsorption on (TiO 2 ) n NCs yielded adsorption energies of −56.97, −53.84, −48.40, and −39.23 kcal mol −1 for cis-(TiO 2 ) 2 , cis-(TiO 2 ) 3 , cis-(TiO 2 ) 4 , and cis-(TiO 2 ) 5 NCs, abbreviated as NC1, NC2, NC3, and NC4, respectively. Their interatomic interactions were further evaluated using reduced density gradient (RDG) and quantum theory of atoms in molecules (QTAIM) analyses. Among the studied systems, although NC1 exhibited a less negative adsorption energy compared to the other NCs, it indicated strong surface reactivity. Further, NC1 also showed the highest occupied molecular orbital (HOMO)–lowest unoccupied molecular orbital (LUMO) energy gap of 3.66 eV, suggesting greater charge transfer and reactivity. Additionally, dipole moment, global reactivity descriptors, molecular electrostatic potential (MEP) surface, and natural bond orbital (NBO) results of the NCs were more favorable than those of cisplatin. Based on the DFT results, the protonated NC1, i.e. (TiO 2 ) 2 H 2 was selected for further analysis of its interactions with HEWL. The docking scores of cisplatin, (TiO 2 ) 2 H 2 , and cis-(TiO 2 ) 2 H 2 with HEWL were found to be −4.41, −3.82, and −6.74 kcal mol −1 , respectively, indicating strong binding affinity and therapeutic potential of cis-(TiO 2 ) 2 H 2 . More experimental investigations are required to confirm its effectiveness.