DFT study of the therapeutic potential of borospherene and metalloborospherenes as a new drug-delivery system for the 5-fluorouracil anticancer drug

Abstract

Based on extensive first-principles calculations, the potential of borospherene (B40) and its exohedral metalloborospherene ([email protected]40 and Au4@B40) for delivery of 5-fluorouracil (5-FU) is examined using density functional theory (DFT) and time-dependent density functional theory (TD-DFT). To investigate the maximum capacity for delivering 5-fluorouracil (5-FU) molecules, up to four Au atoms can be anchored on the exterior surface of the B40 simultaneously, each of Au has the ability to interact with one 5-FU molecule, using only one B40 molecule. The 5-FU can be easily separated from B40, [email protected]40 and Au4@B40 at ambient temperature due to the moderate binding energies and charge-transfer. To comparatively analyze the interaction properties of 5-FU anti-cancer drug at B40, [email protected]40 and Au4@B40 nanocages, the electronic properties, charge distributions, frontier orbital, energy gaps and dipole moment have been examined. Moreover, the natural bond orbital analyses (NBO), the projected densities of states (PDOS) properties, non-covalent interactions (NCI), quantum theory of atoms in molecules (QTAIM) and statistical thermodynamic of these systems were used to investigate the interaction process. The time-dependent density functional calculations (TD-B3LYP) were utilized to simulate UV–visible electronic absorption spectra in the gas and aqueous phases. The results reveal that the 5-FU can be simply protonated in the tumor tissues, facilitating the drug to be released from the B40, [email protected]40 and Au4@B40 nanocages. The solvent effects tend to reduce the 5-FU binding energies in all (5-FU)@B40, [email protected][[email protected]40], (5-FU)4@B40 and (5-FU)4@[Au4@B40] complexes. This is the first study to show that borospherene (B40) and metalloborospherene have a high capacity for delivering of multiple 5-FU molecules.