Density functional theory (DFT) computation of pristine and metal-doped MC59 (M = Au, Hf, Hg, Ir) fullerenes as nitrosourea drug delivery systems

In recent times, C60 fullerene and its derivatives have drawn increasing attention in nanomedicine due to their bioavailability and low toxicity. Herein, we investigated the interactions of nitrosourea (NU) drug with pristine and metal-doped MC59 (M = Au, Hf, Hg, Ir) at the M06–2X/gen/LanL2DZ/def2-SVP level of theory. The structural, adsorption energy, charge transfer, electronic, QTAIM, and NCI analyses were investigated based on the density functional theory (DFT). In contrast to physisorption of NU drug on the pristine C60 surface, the metal-doped NU@MC59 complexes have stronger interactions and are chemically adsorbed on the metal-doped fullerene surfaces, with NU@HfC59 having the strongest interaction. Similarly, metal-doping altered global hardness and energy gap values such that reactivity and sensitivity increased for NU@HfC59, NU@HgC59, and NU@IrC59. Meanwhile, the reactivity and sensitivity decreased for NU@AuC59. Among all the complexes, NU@HfC59 exhibited the highest electrical conductivity and sensitivity due to its least HOMO-LUMO energy gap value. The QTAIM and NCI analyses indicated that the complexes are formed predominantly via non-covalent interactions. The results suggest that metal doping enhanced the sensitivity and conductivity of pristine C60. With moderate adsorption energy and low recovery time, especially for HfC59 and IrC59 fullerenes, this indicates that the metal-doped fullerenes are promising nitrosourea drug delivery candidates in nanomedicine. [Display omitted] •Potential usage of pristine and M-doped (M = Au, Hf, Hg, Ir) MC59 fullerenes for nitrosourea (NU) drug delivery was explored.•The NU drug was weakly physisorbed on the pristine C60 fullerene surface.•The Au, Hf, Hg, and Ir metal doping improved NU adsorption and subsequent chemisorption.•Charge transfers from the NU drug to the M-doped fullerenes, as evident from the increased dipole moment upon metal doping.•Due to their higher reactivity and sensitivity to NU, Hf and Ir-doped MC59 fullerenes are promising drug delivery candidates.