Water-soluble polyol-methanofullerenes as mitochondria-targeted antioxidants: Mechanism of action

Bioorg Med Chem Lett. 2018 Apr 1;28(6):1097-1100. doi: 10.1016/j.bmcl.2018.02.009. Epub 2018 Feb 8.

Abstract

The mechanism of an antioxidant action of water-soluble polyol - methanofullerenes C60[C9H10O4(OH)4]6 and C60[C13H18O4(OH)4]6 as the mild uncouplers of an oxidative phosphorylation and respiration is postulated. According to this mechanism, hydroxyl group of methanofullerenols can be protonated under excess of protons in the intermembrane space of hyperpolarized mitochondria. Protonation of fullerene derivatives is confirmed by the decrease in their negative Zeta potential in the pH below 5.4. Heavily protonated methanofullerenols become positively charged and move into the mitochondrial matrix. As a consequence, the proton gradient is dissipated, which causes a decrease in mitochondrial transmembrane potential (ΔΨm) and reduction in ROS production.

Keywords: Antioxidant activity; Hyperpolarized mitochondria; Methanofullerenols; Protonation; Zeta potential.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antioxidants / chemistry
  • Antioxidants / pharmacology*
  • Dose-Response Relationship, Drug
  • Fullerenes / chemistry
  • Fullerenes / pharmacology*
  • Membrane Potential, Mitochondrial / drug effects
  • Mitochondria / drug effects*
  • Molecular Structure
  • Polymers / chemistry
  • Polymers / pharmacology*
  • Solubility
  • Structure-Activity Relationship
  • Water / chemistry

Substances

  • Antioxidants
  • Fullerenes
  • Polymers
  • polyol
  • Water