Steroid-fullerene hybrids as promising derivatives with potential application in medicinal chemistry and materials science

In recent years, fullerenes have gained great interest because their structure enables the development of novel applications based on their chemical and physical properties.1 With a focus on their small size and special structure, there have been considerable reports on their ability to scavenge free radicals, visualize biological processes, and neuroprotective activity. Furthermore, their ability to capture radicals makes them good antioxidants, for developing potential drugs to treat neurodegenerative diseases.2 On the other hand, fullerene derivatives have been used as acceptor materials in solar cells for over two decades, following the demonstration of the first proof-of-concept devices at the end of the last century.3 This work aimed to obtain structurally novel compounds, based on generating molecular hybrids, with applications as anti amyloid-β (Aβ) peptide aggregates and as acceptor material in organic solar cells. For this purpose, fullerenes were covalently bonded to malonyl conjugates substituted with fragments such as steroids and seleno-sugars. Different strategies were designed for obtaining malonyl-steroids and seleno-sugars, as well as for their coupling reaction. The covalent attachment of the conjugates to [60]fullerene was performed by Bingel-Hirsch cyclopropanation. In addition, theoretical calculations at the DFT level of theory were used to predict the synthesized hybrids' molecular structures and to estimate their physicochemical properties. Theoretical calculations based on CNDOL Fockian together with configuration interaction of single excitations (CIS), as well as the experimental results obtained such as TEM and cyclic voltammetry demonstrated that one can be considered an appealing candidate with applications for photovoltaic devices. Molecular docking was employed to determine the potential application of these fullerene derivatives to treat neurodegenerative diseases, focusing on the interaction of these molecules with the (Aβ) peptide.