Catalytic oxidation and reduction reactions of hydrophilic carbon clusters with NADH and cytochrome C: features of an electron transport nanozyme

Paul J. Derry; Lizanne G. Nilewski; William K. A. Sikkema; Kimberly Mendoza; Almaz Jalilov; Vladimir Berka; Emily A. McHugh; Ah-Lim Tsai; James M. Tour; Thomas A. Kent

doi:10.1039/C9NR00807A

Catalytic oxidation and reduction reactions of hydrophilic carbon clusters with NADH and cytochrome C: features of an electron transport nanozyme†

Paul J. Derry,

^ab Lizanne G. Nilewski,

^c William K. A. Sikkema,^c Kimberly Mendoza,

^c Almaz Jalilov,

^d Vladimir Berka,^e Emily A. McHugh,^c Ah-Lim Tsai,^e James M. Tour

*^cfg and Thomas A. Kent

*^ach

Author affiliations

* Corresponding authors

^a Texas A&M Health Science Center Institute of Biosciences and Technology, Houston, Texas 77030, USA
E-mail: tkent@tamhsc.edu

^b Neurology and Center for Translational Research in Inflammatory Diseases, Michel E. DeBakey VA Medical Center, Houston, Texas 77030, USA

^c Department of Chemistry, Rice University, 6100 Main Street, Houston, Texas 77005, USA
E-mail: tour@rice.edu

^d Department of Chemistry and Center for Integrative Petroleum Research, King Fahd University of Petroleum and Minerals, Dhahran, Saudi Arabia

^e Hematology, Internal Medicine, University of Texas Houston Medical School, Houston, Texas 77030, USA

^f The NanoCarbon Center, Rice University, 6100 Main Street, Houston, Texas 77005, USA

^g Department of Materials Science and NanoEngineering, Rice University, 6100 Main Street, Houston, Texas 77005, USA

^h Stanley H. Appel Department of Neurology, Houston Methodist Hospital and Institute of Academic Medicine, Houston, Texas 77030, USA

Abstract

Previously, our group reported on the promising efficacy of poly(ethylene glycol)-hydrophilic carbon clusters (PEG-HCCs) to work as broadly active and high capacity antioxidants in brain ischemia and injury models including stroke and traumatic brain injury coupled with hemorrhagic shock. PEG-HCCs are a carbon nanomaterial derived from harsh oxidation of single wall carbon nanotubes and covalently modified with poly(ethylene glycol). They retain no tubular remnants and are composed of a highly oxidized carbon core functionalized with epoxy, peroxyl, quinone, ketone, carboxylate, and hydroxyl groups. HCCs are the redox active carbon core of PEG-HCCs, which have a broad reduction potential range starting at +200 mV and extending to −2 V. Here we describe a new property of these materials: the ability to catalytically transfer electrons between key surrogates and proteins of the mitochondrial electron transport complex in a catalytic fashion consistent with the concept of a nanozyme. The estimated reduction potential of PEG-HCCs is similar to that of ubiquinone and they enabled the catalytic transfer of electrons from low reduction potential species to higher reduction electron transport complex constituents. PEG-HCCs accelerated the reduction of resazurin (a test indicator of mitochondrial viability) and cytochrome c by NADH and ascorbic acid in solution. Kinetic experiments suggested a transient tertiary complex. Electron paramagnetic resonance demonstrated NADH increased the magnitude of PEG-HCCs’ intrinsic radical, which then reduced upon subsequent addition of cytochrome c or resazurin. Deconvolution microscopy identified PEG-HCCs in close proximity to mitochondria after brief incubation with cultured SHSY-5Y human neuroblastoma cells. Compared to methylene blue (MB), considered a prototypical small molecule electron transport shuttle, PEG-HCCs were more protective against toxic effects of hydrogen peroxide in vitro and did not demonstrate impaired cell viability as did MB. PEG-HCCs were protective in vitro when cells were exposed to sodium cyanide, a mitochondrial complex IV poison. Because mitochondria are a major source of free radicals in pathology, we suggest that this newly described nanozyme action helps explain their in vivo efficacy in a range of injury models. These findings may also extend their use to mitochondrial disorders.

This article is part of the themed collection: Celebrating our 2020 Prize and Award winners

Nanoscale

Catalytic oxidation and reduction reactions of hydrophilic carbon clusters with NADH and cytochrome C: features of an electron transport nanozyme†

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Catalytic oxidation and reduction reactions of hydrophilic carbon clusters with NADH and cytochrome C: features of an electron transport nanozyme

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