Chain-breaking antioxidant activity of reduced forms ofmitochondria-targeted quinones, a novel type of geroprotectors

Abstract

Thechain-breaking antioxidant activities of reduced form of novel type ofgeroprotectors, mitochondria-targeted quinones (QH₂) havequantitatively been measured for the first time. To this end, the chainperoxidation of methyl linoleate (ML) in Triton micelles was used as akinetic testing model. The studied QH₂ were lipophilictriphenylphosphonium cations conjugated by an aliphatic linker to anantioxidant, i.e. a ubiquinol moiety (MitoQH₂) or plastoquinolmoiety (SkQH₂). The antioxidant activity was characterized bythe rate constant k₁ for the reaction between QH₂ andthe lipid peroxyl radical (LO₂^·) originatedfrom ML: QH₂ + LO₂^· → HQ^· + LOOH. Allthe tested QH₂ displayed a pronounced antioxidant activity. Theoxidized forms of the same compounds did not inhibit ML peroxidation. Thevalue of k₁ for SkQH₂ far exceeded k₁ forMitoQH₂. For the biologically active geroprotectors SkQ1H₂,the k₁ value found to be as high as 2.2 × 10⁵ M^-1s^-1,whereas for MitoQH₂, it was 0.58 × 10⁵ M^-1s^-1. The kineticbehavior of QH₂ suggested that SkQ1H₂ can rathereasily diffuse through lipid-water microheterogeneous systems.