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Synthesis of triphenylphosphonium vitamin E derivatives as mitochondria-targeted antioxidants.

Jameson VJ, Cochemé HM, Logan A, Hanton LR, Smith RA, Murphy MP - Tetrahedron (2015)

Bottom Line: A series of mitochondria-targeted antioxidants comprising a lipophilic triphenylphosphonium cation attached to the antioxidant chroman moiety of vitamin E by an alkyl linker have been prepared.The synthesis of a series of mitochondria-targeted vitamin E derivatives with a range of alkyl linkers gave compounds of different hydrophobicities.This work will enable the dependence of antioxidant defence on hydrophobicity to be determined in vivo.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemistry, University of Otago, PO Box 56, Dunedin, 9054, New Zealand.

ABSTRACT

A series of mitochondria-targeted antioxidants comprising a lipophilic triphenylphosphonium cation attached to the antioxidant chroman moiety of vitamin E by an alkyl linker have been prepared. The synthesis of a series of mitochondria-targeted vitamin E derivatives with a range of alkyl linkers gave compounds of different hydrophobicities. This work will enable the dependence of antioxidant defence on hydrophobicity to be determined in vivo.

No MeSH data available.


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Prevention of lipid peroxidation in rat brain homogenates by MitoE compounds and Trolox.
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fig4: Prevention of lipid peroxidation in rat brain homogenates by MitoE compounds and Trolox.

Mentions: To determine whether the biochemical properties and antioxidant efficacy of the chromanol moiety of MitoE were affected by changing the length of alkyl chain conjugating it to the TPP cation, the ability of the most (MitoE10) and least (MitoE2) lipophilic members of the MitoEn series to prevent lipid peroxidation was measured and compared. The ability of the compounds to act as chain breaking antioxidants in the rat brain homogenate system of lipid peroxidation23 was assessed. This system was chosen as comparison of the effects of the antioxidants on preventing lipid peroxidation would not be confounded by differential uptake into mitochondria. Rat brain homogenates were allowed to undergo spontaneous lipid peroxidation, which was assessed by the production of thiobarbituric reactive species (TBARS).22 The effect of MitoE2, and MitoE10 on preventing this peroxidation was then assessed (Fig. 4) and showed that both compounds were of comparable efficacy in preventing lipid peroxidation. Therefore it is concluded that conjugation to the TPP cation by differing alkyl chain lengths to the chromanol moiety does not significantly alter their intrinsic antioxidant efficacy. Consequently any changes in antioxidant efficacy seen in mitochondrial or cell studies can be assigned to differences in uptake, adsorption or recycling. The antioxidant efficacy of the MitoE compounds was far greater than that of Trolox, which contains the same antioxidant chromanol moiety as MitoE, connected to a short-chain carboxylic acid rather than a TPP function, making it far more hydrophilic. This suggests that the lipophilic nature of the TPP moiety enhances the interaction of the antioxidant moiety with the phospholipid bilayer.


Synthesis of triphenylphosphonium vitamin E derivatives as mitochondria-targeted antioxidants.

Jameson VJ, Cochemé HM, Logan A, Hanton LR, Smith RA, Murphy MP - Tetrahedron (2015)

Prevention of lipid peroxidation in rat brain homogenates by MitoE compounds and Trolox.
© Copyright Policy - CC BY
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4596152&req=5

fig4: Prevention of lipid peroxidation in rat brain homogenates by MitoE compounds and Trolox.
Mentions: To determine whether the biochemical properties and antioxidant efficacy of the chromanol moiety of MitoE were affected by changing the length of alkyl chain conjugating it to the TPP cation, the ability of the most (MitoE10) and least (MitoE2) lipophilic members of the MitoEn series to prevent lipid peroxidation was measured and compared. The ability of the compounds to act as chain breaking antioxidants in the rat brain homogenate system of lipid peroxidation23 was assessed. This system was chosen as comparison of the effects of the antioxidants on preventing lipid peroxidation would not be confounded by differential uptake into mitochondria. Rat brain homogenates were allowed to undergo spontaneous lipid peroxidation, which was assessed by the production of thiobarbituric reactive species (TBARS).22 The effect of MitoE2, and MitoE10 on preventing this peroxidation was then assessed (Fig. 4) and showed that both compounds were of comparable efficacy in preventing lipid peroxidation. Therefore it is concluded that conjugation to the TPP cation by differing alkyl chain lengths to the chromanol moiety does not significantly alter their intrinsic antioxidant efficacy. Consequently any changes in antioxidant efficacy seen in mitochondrial or cell studies can be assigned to differences in uptake, adsorption or recycling. The antioxidant efficacy of the MitoE compounds was far greater than that of Trolox, which contains the same antioxidant chromanol moiety as MitoE, connected to a short-chain carboxylic acid rather than a TPP function, making it far more hydrophilic. This suggests that the lipophilic nature of the TPP moiety enhances the interaction of the antioxidant moiety with the phospholipid bilayer.

Bottom Line: A series of mitochondria-targeted antioxidants comprising a lipophilic triphenylphosphonium cation attached to the antioxidant chroman moiety of vitamin E by an alkyl linker have been prepared.The synthesis of a series of mitochondria-targeted vitamin E derivatives with a range of alkyl linkers gave compounds of different hydrophobicities.This work will enable the dependence of antioxidant defence on hydrophobicity to be determined in vivo.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemistry, University of Otago, PO Box 56, Dunedin, 9054, New Zealand.

ABSTRACT

A series of mitochondria-targeted antioxidants comprising a lipophilic triphenylphosphonium cation attached to the antioxidant chroman moiety of vitamin E by an alkyl linker have been prepared. The synthesis of a series of mitochondria-targeted vitamin E derivatives with a range of alkyl linkers gave compounds of different hydrophobicities. This work will enable the dependence of antioxidant defence on hydrophobicity to be determined in vivo.

No MeSH data available.


Related in: MedlinePlus