Novel [60]fullerene-steroid hybrids have been synthesized by Bingel-Hirsch cyclopropanation reaction between C 60 and steroid malonates, leading to conjugates in which a [60]fullerene unit is connected to one or two dehydroepiandrosterone moieties, an important naturally occurring steroid hormone. The obtained derivatives have been fully characterized by a whole set of instrumental techniques in order to determine their chemical structure. Moreover, their electrochemical properties, investigated by cyclic voltammetry, revealed the presence of three reversible reduction waves for both hybrids. Furthermore, Transmission Electron Microscopy studies allowed to [a

We report the synthesis and characterization of a fullerene‐steroid hybrid that contains H 2 @C 60 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 H 2 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‐H 2 @C 60 as anti‐SARS‐Cov‐2 agent.

Over the years, fullerene has been covalently linked to other polar structures, increasing its aqueous solubility, thereby improving its potential use for biological and biomedical applications. Here, we report on the self‐organization characteristics in water of fullerene‐steroid hybrid derivatives with broad structural features. A library of 12 hybrid derivatives was prepared and classified into three groups: (1) mono adducts with only one steroid molecule and one fullerene moiety fused; (2) hybrids bearing wings with one fullerene moiety and two steroid molecules; and (3) a structure with two fullerene moieties linked to one steroid molecule and a mixture of two different monoaducts where C60‐malonate is attached to the A or D ring of steroid moiety. Different spectroscopic techniques characterized all synthesized fullerene derivatives, such as nuclear magnetic resonance (NMR) experiments (1H and 13C), Fourier transform infrared spectroscopy (FTIR), and high‐resolution mass spectrometry (HRMS). The morphology of the derivatives in aqueous solution was determined by transmission electron microscopy (TEM). In general, all the derivatives were organized into spherical nanoscale structures, where the structural characteristics defined the particle size distribution (PSD), showing a broad range of sizes from 6 to over 50 nm, and only a low percentage of larger particles were observed. The presence of dehydroepiandrosterone moieties in fullerene derivatives bearing wings and the increase in lipophilicity conferred by two C60 in the same structure induced more homogeneous and smaller particles, ranging from 6 to 20 nm. A preliminary computational study of the wing aggregates IIb showed that theoretical curve aggregates are more stable than linear ones supporting our TEM and PDS results.

Invited for this month's cover are the collaborating groups of Dr. Margarita Suárez at Universidad de La Habana, Cuba, and Dr. Nazario Martín at Universidad Complutense de Madrid, Spain, together with groups at other institutions worldwide. The Front Cover shows a representation of the H2@C60 hybrid molecule with a dehydroepiandrosterone moiety interacting with the active site of the SARS Cov‐2. Read the full text of the article at 10.1002/cplu.202000770.

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.