We report the synthesis and characterization of a fullerene‐steroid hybrid that contains H₂@C₆₀and 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 H₂located 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^proand 3CL^prorespectively, indicating the potential use of the synthesized steroid‐H₂@C₆₀as anti‐SARS‐Cov‐2 agent.

Cyclopropanation reactions between C₆₀ and different malonates decorated with monosaccharides and steroids using the Bingel‐Hirsch methodology have allowed the obtention of a new family of hybrid compounds in good yields. A complete set of instrumental techniques has allowed us to fully characterize the hybrid derivatives and to determine the chemical structure of monocycloadducts. Besides, the proposed structures were investigated by cyclic voltammetry, which evidenced the exclusive reductive pattern of fullerene Bingel‐type monoadducts. Theoretical calculations at the DFT‐D3(BJ)/PBE 6‐311G(d,p) level of the synthesized conjugates predict the most stable conformation and determine the factors that control the hybrid molecules′ geometry. Some parameters such as polarity, lipophilicity, polar surface area, hydrophilicity index, and solvent‐accessible surface area were also estimated, predicting its potential permeability and capability as cell membrane penetrators. Additionally, a molecular docking simulation has been carried out using the main protease of SARS‐CoV‐2 (Mpro) as the receptor, thus paving the way to study the potential application of these hybrids in biomedicine.

In the last 20 years the exploitation of antioxidant activity of selenobased compounds has improved, just due to the use of Ebselen, a selenocompound, as a Glutathione peroxidase (GPx) mimic. However, their clinical use seems to be compromised by the low solubility in water. To deal with this problem, it is possible to take advantage of the new approach including selenosugars in which selenium replaces heterocyclic oxygen. In this frame, to optimize the antioxidant properties of selenosugars, the glycoconjugation with a polyphenolic unit, which is a molecule capable of inhibiting or disabling the action of free radicals, has been considered in this work. The Mitsunobu reaction mechanism links covalently the primary alcoholic function of selenobased glycosyl donors, coming from the commercially available d‐mannose, and phenolic moiety acceptors, to obtain the corresponding glycoconjugates, has been exploited affording the products in efficient yields. A density functional theory (DFT) theoretical study is carried out to help understand the possible influence of the seleno donor on the reactivity. Crucially, a new pathway based on Pummerer‐like rearrangement followed by a glycosylation, gave a selenosugar with selenium in the ring and bearing an acetal‐like functional group at C‐1. All compounds are characterized by nuclear magnetic resonance (NMR) spectroscopy confirming their structures and purity.

The aggregation of β‐amyloid peptide (Aβ) is associated with neurodegenerative diseases such as Alzheimer's disease (AD). Several therapies aimed at reducing the aggregation of this peptide have emerged as potential strategies for the treatment of AD. This paper describes the design and preparation of new hybrid molecules based on steroids, selenosugars, and [60]fullerene as potential inhibitors of Aβ oligomerization. These moieties were selected based on their antioxidant properties and possible areas of interaction with the Aβ. Cyclopropanations between C ₆₀ and malonates bearing different steroid and selenosugar moieties using the Bingel–Hirsch protocol have enabled the synthesis of functionalized molecular hybrids. The obtained derivatives were characterized by physical and spectroscopic techniques. Theoretical calculations for all the selenium compounds were performed using the density functional theory DFT/B3LYP‐D3(BJ)/6‐311G(2d,p) predicting the most stable conformations of the synthesized derivatives. Relevant geometrical parameters were investigated to relate the stereochemical behavior and the spectroscopic data obtained. The affinity of the compounds for Aβ‐peptide was estimated by molecular docking simulation, which predicted an increase in affinity and interactions for Aβ for the hybrids containing the C ₆₀ core. In addition, parameters such as lipophilicity, polar surface area, and dipole moment were calculated to predict their potential interaction with membrane cells.