A DFT study on the physical adsorption of cyclophosphamide derivatives on the surface of fullerene C60 nanocage

• DFT study on the sorption of cyclophosphamide analogs on the surface of C60.
• The endergonic interactions of drugs with C60 with ΔGadsorption > 0.
• The hydrophililic nature of C60-drug complexes with μ ≈ 4.0–5.5 Debye.
• The intermediate character for PO, P–O and P–N polar bonds by QTAIM analysis.
• Interactions between orbitals of C60 and the drug molecules in DOS spectra.

The physical sorption of a series of cyclophosphamide drug derivatives with formula where x = 2, X = F (2), Cl (3), Br (4); x = 3, X = F (5), Cl (6), Br (7) and x = 4, X = F (8), Cl (9), Br (10) on the surface of fullerene C60 was studied using density functional theory (DFT) at B3LYP and B3PW91 levels. The most negative binding energies obtained using the B3LYP approach and corrected for geometrical BSSE and dispersion energies (gCP-D3-ΔEbinding) were measured for compounds 8 (among isolated drugs) and 13 (among complexes). The dipole moments of isolated drugs were obtained close to those of their complexes with C60 (∼4.0–5.5 Debye) indicating their hydrophililic nature that is an appropriate property appealing for drug delivery in biological media. The adsorption of all drugs on the surface of fullerene was endergonic with all of the ΔGadsorption > 0. The ΔHadsorption values at B3PW91 level were only negative for complexes 14–16 indicating their exothermic adsorption nature. The HOMO–LUMO band gaps of complexes 11–19 were about 2.7 eV and are comparable with the gap in C60 but are much smaller than the gaps in isolated drugs 2–10 (6.5–8.0 eV) reflecting the increase in electrical conductivities upon complexation. The QTAIM data supported the covalent character of the C–O, C–N and N–H bonds, the intermediate character of PO, P–O and P–N bonds while the electrostatic nature of PO…C(fullerene) interactions. According to the gCP-D3-ΔEbinding binding energies and ΔHadsorption values at B3LYP level, it seems that the complexes 12 and 13 can be the most promising prodrug + carrier delivery systems.

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