Computational evaluation of Ni@B12N12 and Ti@B12N12 endohedral clusters as carriers for melphalan and sulforaphane anticancer drugs

We present a density functional theory study of the reactivity of M@B12N12 (M = Ni, Ti) clusters in aqueous media and their interaction with melphalan and sulforaphane anticancer drugs. In contrast to previous studies, we obtained a strongly exothermic trapping of metal atoms inside the B12N12 cage. Analysis of the radial distribution function shows that both Ni and Ti atoms distort the cage, but this effect is stronger for titanium. Clear changes in the infrared and ultraviolet/visible spectra provide easy identification of the endohedral complex formation. The distortion of the both geometrical and electronic structures of BN cage leads to a stronger bonding of M@B12N12 to hydrogen, influencing the pH-sensitivity of the endohedral cluster. Nickel weakly changes the binding energy of the carrier to both considered drugs, while the effect of titanium on this energy is very significant. Endohedral doping offers a way for achieving application-appropriate activity and selectivity of the drug delivery system based on the M@B12N12 carrier. © 2025 Elsevier B.V.