DFT investigation of Cu and Ni-doped Be12O12 nanocages for adsorption, sensing, and controlled delivery of anticancer drugs cladribine and cytarabine

Designing effective nanocarriers that can detect drugs and regulate their release simultaneously is essential for enhancing the effectiveness and safety of anticancer treatment. Density functional theory (DFT) calculations were used in this work to study adsorption, sensing, and drug release properties of the anticancer drugs cladribine and cytarabine on pristine, Cu, and Ni-doped Be 12 O 12 nanocages at the B3LYP-D3/6-31G(d, p) level of theory. The adsorption energies corrected for BSSE indicate a thermodynamically favorable interaction in all systems, with the Cladribine@Cu-BeO system demonstrating the highest adsorption energy, -44.772 kcal/mol, and the Ni-doped complexes demonstrating relatively low adsorption energies, which are favorable to drug release. Adsorption of drugs causes strong modulation of the electronic structure, including a sharp decrease in the energy gap from 8.290 eV in pure BeO to about 3.024 eV, Fermi-level shifts, and an increase in electrical conductivity to 4.31 × 10 12 S/m in Ni-doped complexes. The results of TD-DFT calculations indicate that the UV-Vis absorption exhibited strong red shifts as the wavelengths exceeded 300 nm following doping and adsorption. Solvation energies calculated using the CPCM model are highly negative (up to -49.871 kcal/mol), indicating solvent-assisted drug release under physiological conditions. The noncovalent interactions in pure systems, as well as powerful donor-acceptor interactions in doped nanocages, are verified by the non-covalent interaction (NCI), quantum theory of atoms in molecules (QTAIM), and natural bond orbital (NBO) analyses. Altogether, Cu-doped BeO turns out to be the most efficient system of stable drug adsorption and detection, whereas Ni-doped BeO shows better electrical conductivity, rapid recovery, and release of drugs in a solvent, which implies its significance in drug delivery applications. In this study, Be 12 O 12 is considered a computational model system, and since beryllium compounds are known human carcinogens, toxicological studies outside the scope of this DFT study would be required for any biomedical application.