On the Mechanism of Action of Fullerene Derivatives in Superoxide Dismutation

Abstract

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.

Polyhydroxylated fullerene attenuates oxidative stress-induced apoptosis via a fortifying Nrf2-regulated cellular antioxidant defence system

“…Previous studies have shown that the radical-scavenging abilities of C 60 (OH) 24 have been attributed to the molecular properties of fullerenols, including large electron affinity and formation of electron-deficient areas on the C 60 , 13 and these properties of C 60 (OH) 24 may lead to direct ROS scavenging similar to that catalyzed by superoxide dismutase. 15,46 However, in the present study, our results have clearly indicated that C 60 (OH) 24 protects against H 2 O 2 -induced cell death through activation of Nrf2/ARE signaling and induction of phase II antioxidant enzymes such as HO-1, γ-GCS, and NQO-1, thus providing an insight into mechanisms by which C 60 derivatives exert protective effects against cell death induced by oxidative stress.…”

Therapeutic applications of low-toxicity spherical nanocarbon materials

“…The mechanism of O 2 Á À quenching is similar to that of the quenching of superoxide dismutase. [51][52][53] The radical easily binds to the electron-deficient area of the fullerene surface, resulting in electron transfer to the fullerene cage. Then, the binding of a second superoxide radical anion to an adjacent electron-deficient position induces the destruction of O 2 Á À , production of hydrogen peroxide and regeneration of the original fullerene.…”

The isotopic effects of13C-labeled large carbon cage (C70) fullerenes and their formation process

“…For instance, C 70 and their derivatives exhibited higher photodynamic therapy and antioxidation efficiency due to the much more extended conjugated π-system of the cage, which can efficiently absorb electrons. [8][9][10][11][12] Metallofullerenes of larger carbon cages (e.g. Gd@C 82 and Gd@C 82 (OH) x ) also showed promises as radiotracers, magnetic resonance imaging (MRI) contrast reagents and anticancer drug with high-efficacy and low-toxicity.…”