Ab Initio Insight into the Interaction of Metal-Decorated Fluorinated Carbon Fullerenes with Anti-COVID Drugs

Abstract

We theoretically investigated the adsorption of two common anti-COVID drugs, favipiravir and chloroquine, on fluorinated C₆₀ fullerene, decorated with metal ions Cr³⁺, Fe²⁺, Fe³⁺, Ni²⁺. We focused on the effect of fluoridation on the interaction of fullerene with metal ions and drugs in an aqueous solution. We considered three model systems, C₆₀, C₆₀F₂ and C₆₀F₄₈, and represented pristine, low-fluorinated and high-fluorinated fullerenes, respectively. Adsorption energies, deformation of fullerene and drug molecules, frontier molecular orbitals and vibrational spectra were investigated in detail. We found that different drugs and different ions interacted differently with fluorinated fullerenes. Cr³⁺ and Fe²⁺ ions lead to the defluorination of low-fluorinated fullerenes. Favipiravir also leads to their defluorination with the formation of HF molecules. Therefore, fluorinated fullerenes are not suitable for the delivery of favipiravir and similar drugs molecules. In contrast, we found that fluorine enhances the adsorption of Ni²⁺ and Fe³⁺ ions on fullerene and their activity to chloroquine. Ni²⁺-decorated fluorinated fullerenes were found to be stable and suitable carriers for the loading of chloroquine. Clear shifts of infrared, ultraviolet and visible spectra can provide control over the loading of chloroquine on Ni²⁺-doped fluorinated fullerenes.

Keywords: COVID-19; chloroquine; density functional theory; drug delivery; favipiravir; fullerenes.

Figure 1

Chemical structures of (a) favipiravir and (b) chloroquine molecules.

Figure 2

Optimized geometry of the chloroquine molecule loaded on fluorinated fullerenes (a) C₆₀F₂ and (b) C₆₀F₄₈.

Figure 3

Optimized geometries of pristine, low- and high-fluorinated C₆₀ decorated with metal ions: (a) C₆₀Cr³⁺, (b) C₆₀F₂Cr³⁺, (c) C₆₀F₄₈Cr³⁺, (d) C₆₀Fe²⁺, (e) C₆₀F₂Fe²⁺, (f) C₆₀F₄₈Fe²⁺, (g) C₆₀Fe³⁺, (h) C₆₀F₂Fe³⁺, (i) C₆₀F₄₈Fe³⁺, (j) C₆₀Ni²⁺, (k) C₆₀F₂Ni²⁺, (l) C₆₀F₄₈Ni²⁺.

Figure 4

Optimized geometries of chloroquine drug loaded on Ni²⁺-decorated fluorinated fullerenes (a) C₆₀Ni²⁺, (b) C₆₀F₂Ni²⁺ and (c) C₆₀F₄₈Ni²⁺.

Figure 4

Optimized geometries of chloroquine drug loaded on Ni²⁺-decorated fluorinated fullerenes (a) C₆₀Ni²⁺, (b) C₆₀F₂Ni²⁺ and (c) C₆₀F₄₈Ni²⁺.

Figure 5

Ultraviolet and visible spectra of (a) chloroquine drug (black line), C₆₀F₂Ni²⁺ carrier (blue line) and carrier + loaded drug complex (red dashed line). (b) The same spectra for high-fluorinated C₆₀F₄₈Ni²⁺ carrier loaded with chloroquine. The calculated wavelengths corresponding to the transitions are broadened by Gaussian curves with σ = 10 nm.

Figure 6

Infrared spectra of (a) chloroquine drug (black line), C₆₀F₂Ni²⁺ carrier (blue line) and carrier + loaded drug complex (red dashed line). (b) The same spectra for high-fluorinated C₆₀F₄₈Ni²⁺ carrier loaded with chloroquine. The calculated wavelengths corresponding to the transitions are broadened by Gaussian curves with σ = 10 cm⁻¹.