On the mechanism of action of fullerene derivatives in superoxide dismutation.

We have studied the mechanism of the antioxidant activity of C(60) derivatives at the BP86/TZP level with inclusion of solvent effects (DMSO) by using the COSMO approach. The reaction studied here involves degradation of the biologically relevant superoxide radical (O(2)(-)), which is linked to tissue damage in several human disorders. Several fullerene derivatives have experimentally been shown to be protective in cell culture and animal models of injury, but precisely how these compounds protect biological systems is still unknown. We have investigated the activity of tris-malonyl C(60) (also called C(3)), which efficiently removes the superoxide anion with an activity in the range of several biologically effective, metal-containing superoxide dismutase mimetics. The antioxidant properties of C(3) are attributed to the high affinity of C(60) to accept electrons. Our results show that once the superoxide radical is in contact with the surface of C(3), its unpaired electron is transferred to the fullerene. This process, which converts the damaging O(2)(-) to neutral oxygen O(2), is the rate-determining step of the reaction. Afterwards, another superoxide radical reacts with C(3)(*-) to form hydrogen peroxide and in the process takes up the additional electron that was transferred in the first step. The overall process is clearly exothermic and, in general, involves reaction steps with relatively low activation barriers. The capability of C(3) to degrade a highly reactive oxygen species that is linked to several human diseases is of immediate interest for future applications in the field of biology and medicine.