Comparative Computational Study of Interaction of C₆₀-Fullerene and Tris-Malonyl-C₆₀-Fullerene Isomers with Lipid Bilayer: Relation to Their Antioxidant Effect

<div><p>Oxidative stress induced by excessive production of reactive oxygen species (ROS) has been implicated in the etiology of many human diseases. It has been reported that fullerenes and some of their derivatives–carboxyfullerenes–exhibits a strong free radical scavenging capacity. The permeation of C₆₀-fullerene and its amphiphilic derivatives–C₃-tris-malonic-C₆₀-fullerene (C₃) and D₃-tris-malonyl-C₆₀-fullerene (D₃)–through a lipid bilayer mimicking the eukaryotic cell membrane was studied using molecular dynamics (MD) simulations. The free energy profiles along the normal to the bilayer composed of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) for C₆₀, C₃ and D₃ were calculated. We found that C₆₀ molecules alone or in clusters spontaneously translocate to the hydrophobic core of the membrane and stay inside the bilayer during the whole period of simulation time. The incorporation of cluster of fullerenes inside the bilayer changes properties of the bilayer and leads to its deformation. In simulations of the tris-malonic fullerenes we discovered that both isomers, C₃ and D₃, adsorb at the surface of the bilayer but only C₃ tends to be buried in the area of the lipid headgroups forming hydrophobic contacts with the lipid tails. We hypothesize that such position has implications for ROS scavenging mechanism in the specific cell compartments.</p>