Morphological behavior of fullerene‐steroid hybrid derivatives

Abstract

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.