Chain-breaking antioxidant activity of reduced forms of mitochondria-targeted quinones, a novel type of geroprotectors.
The chain-breaking antioxidant activities of reduced form of novel type of geroprotectors, mitochondria-targeted quinones (QH(2)) have quantitatively been measured for the first time. To this end, the chain peroxidation of methyl linoleate (ML) in Triton micelles was used as a kinetic testing model. The studied QH(2) were lipophilic triphenylphosphonium cations conjugated by an aliphatic linker to an antioxidant, i.e. a ubiquinol moiety (MitoQH(2)) or plastoquinol moiety (SkQH(2)). The antioxidant activity was characterized by the rate constant k(1) for the reaction between QH(2) and the lipid peroxyl radical (LO(2) (.)) originated from ML: QH(2) + LO(2) (.) --> HQ(.) + LOOH. All the tested QH(2) displayed a pronounced antioxidant activity. The oxidized forms of the same compounds did not inhibit ML peroxidation. The value of k(1) for SkQH(2) far exceeded k(1) for MitoQH(2). For the biologically active geroprotectors SkQ1H(2), the k(1) value found to be as high as 2.2 x 10(5) M(-) (1)s(-) (1), whereas for MitoQH(2), it was 0.58 x 10(5) M(-) (1)s(-) (1). The kinetic behavior of QH(2) suggested that SkQ1H(2) can rather easily diffuse through lipid-water microheterogeneous systems.
Roginsky
Vitaly A
VA
N. Semenov Institute of Chemical Physics, Russian Academy of Sciences, 119991 Moscow, Russian Federation.
Tashlitsky
Vadim N
VN
Skulachev
Vladimir P
VP
D000975:Antioxidants / Q000737:chemistry* / Q000494:pharmacology; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D015394:Molecular Structure; D009943:Organophosphorus Compounds / Q000737:chemistry* / Q000494:pharmacology*; D010084:Oxidation-Reduction; D013329:Structure-Activity Relationship; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology
D000975:Antioxidants; D009943:Organophosphorus Compounds; D014451:Ubiquinone; C429014:mitoquinone