An Androsterone-H₂ @C₆₀ hybrid: Synthesis, Properties and Molecular Docking Simulations with SARS-Cov-2

We report the synthesis and characterization of a fullerene-steroid hybrid that contains H₂ @C₆₀ and a dehydroepiandrosterone moiety synthesized by a cyclopropanation reaction with 76 % yield. Theoretical calculations at the DFT-D3(BJ)/PBE 6-311G(d,p) level predict the most stable conformation and that the saturation of a double bond is the main factor causing the upfield shielding of the signal appearing at -3.13 ppm, which corresponds to the H₂ located inside the fullerene cage. Relevant stereoelectronic parameters were also investigated and reinforce the idea that electronic interactions must be considered to develop studies on chemical-biological interactions. A molecular docking simulation predicted that the binding energy values for the protease-hybrid complexes were -9.9 kcal/mol and -13.5 kcal/mol for PL^pro and 3CL^pro respectively, indicating the potential use of the synthesized steroid-H₂ @C₆₀ as anti-SARS-Cov-2 agent.