Highly efficient conversion of superoxide to oxygen using hydrophilic carbon clusters

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 112; no. 8; pp. 2343 - 2348
• Main Authors: Samuel, Errol L. G., Marcano, Daniela C., Berka, Vladimir, Bitner, Brittany R., Wu, Gang, Potter, Austin, Fabian, Roderic H., Pautler, Robia G., Kent, Thomas A., Tsai, Ah-Lim, Tour, James M.
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 24-02-2015; National Acad Sciences
• Subjects: Antioxidants; Carbon - chemistry; Catalysis; Electrodes; Electron Spin Resonance Spectroscopy; Enzymes; Hydrogen Peroxide - metabolism; Hydrogen-Ion Concentration; Hydrophobic and Hydrophilic Interactions; Hydroxyl Radical - chemistry; Nanoparticles; Oxidative stress; Oxygen; Oxygen - chemistry; Physical Sciences; Polyethylene glycol; Polyethylene Glycols - chemistry; Sodium Hydroxide - chemistry; Superoxide Dismutase - metabolism; Superoxides - chemistry; antioxidant; superoxide dismutase mimetic; carbon nanoparticles; superoxide; hydrophilic carbon clusters
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.1417047112

Many diseases are associated with oxidative stress, which occurs when the production of reactive oxygen species (ROS) overwhelms the scavenging ability of an organism. Here, we evaluated the carbon nanoparticle antioxidant properties of poly(ethylene glycolated) hydrophilic carbon clusters (PEG-HCCs) by electron paramagnetic resonance (EPR) spectroscopy, oxygen electrode, and spectrophotometric assays. These carbon nanoparticles have 1 equivalent of stable radical and showed superoxide (O ₂•⁻) dismutase-like properties yet were inert to nitric oxide (NO •) as well as peroxynitrite (ONOO ⁻). Thus, PEG-HCCs can act as selective antioxidants that do not require regeneration by enzymes. Our steady-state kinetic assay using KO ₂ and direct freeze-trap EPR to follow its decay removed the rate-limiting substrate provision, thus enabling determination of the remarkable intrinsic turnover numbers of O ₂•⁻ to O ₂ by PEG-HCCs at >20,000 s ⁻¹. The major products of this catalytic turnover are O ₂ and H ₂O ₂, making the PEG-HCCs a biomimetic superoxide dismutase.
Significance Mechanistic studies of nontoxic hydrophilic carbon cluster nanoparticles show that they are able to accomplish the direct conversion of superoxide to dioxygen and hydrogen peroxide. This is accomplished faster than in most single-active-site enzymes, and it is precisely what dioxygen-deficient tissue needs in the face of injury where reactive oxygen species, particularly superoxide, overwhelm the natural enzymes required to remove superoxide. We confirm here that the hydrophilic carbon clusters are unreactive toward nitric oxide radical, which is a potent vasodilator that also has an important role in neurotransmission and cytoprotection. The mechanistic results help to explain the preclinical efficacy of these carbon nanoparticles in mitigating the deleterious effects of superoxide on traumatized tissue.