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

Abstract

The chain-breaking antioxidant activities of reduced form of novel type of geroprotectors, mitochondria-targetedquinones (QH2) have quantitatively been measured for the first time. To this end, the chain peroxidation of methyllinoleate (ML) in Triton micelles was used as a kinetic testing model. The studied QH2 were lipophilictriphenylphosphonium cations conjugated by an aliphatic linker to an antioxidant, i.e. a ubiquinol moiety (MitoQH2) orplastoquinol moiety (SkQH2). The antioxidant activity was characterized by the rate constant k1 for the reaction between QH2 and the lipid peroxyl radical (LO2·) originated from ML: QH2 + LO2· → HQ· + LOOH. All the tested QH2 displayed apronounced antioxidant activity. The oxidized forms of the same compounds did not inhibit ML peroxidation. The value of k1 for SkQH2 far exceeded k1 for MitoQH2. For the biologically active geroprotectors SkQ1H2, the k1 value found to be ashigh as 2.2 × 105 M-1s-1, whereas for MitoQH2, it was 0.58 × 105 M-1s-1. The kinetic behavior of QH2 suggested that SkQ1H2 can rather easily diffuse through lipid-water microheterogeneous systems.