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We demonstrated that three different types of water-soluble fullerenes materials can intercept all of the major physiologically relevant ROS. C₆₀(C(COOH)₂)₂, C₆₀(OH)₂₂, and Gd@C₈₂(OH)₂₂ can protect cells against H₂O₂-induced oxidative damage, stabilize the mitochondrial membrane potential and reduce intracellular ROS production with the following relative potencies: Gd@C₈₂(OH)₂₂≥C₆₀(OH)₂₂>C₆₀(C(COOH)₂)₂. Consistent with their cytoprotective abilities, these derivatives can scavenge the stable 2,2-diphenyl-1-picryhydrazyl radical (DPPH), and the reactive oxygen species (ROS) superoxide radical anion (O₂⁻), singlet oxygen, and hydroxyl radical (HO), and can also efficiently inhibit lipid peroxidation in vitro. The observed differences in free radical-scavenging capabilities support the hypothesis that both chemical properties, such as surface chemistry induced differences in electron affinity, and …