Limits...
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.


Related in: MedlinePlus

Accumulation of MitoE2 and MitoE10 by isolated rat liver mitochondria (Mito) energised with the respiratory substrate succinate and their release upon dissipation of the mitochondrial membrane potential with the uncoupler carbonyl cyanide p-trifluoromethoxyphenylhydrazone (FCCP).
© Copyright Policy - CC BY
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4596152&req=5

fig5: Accumulation of MitoE2 and MitoE10 by isolated rat liver mitochondria (Mito) energised with the respiratory substrate succinate and their release upon dissipation of the mitochondrial membrane potential with the uncoupler carbonyl cyanide p-trifluoromethoxyphenylhydrazone (FCCP).

Mentions: This aspect was extended by measuring whether MitoE2 and MitoE10 compounds were accumulated by mitochondria in response to the mitochondrial membrane potential, as is expected for a compound linked to a TPP compound. To measure the uptake of the MitoE compounds an ion-selective electrode was used that responds to the concentration of the TPP cation in solution (Fig. 5). When the MitoE compounds were added to a mitochondrial suspension the ion-selective electrode responded to the increase in concentration of the MitoE compound in the extracellular environment. When the mitochondria were energised with the respiratory substrate succinate a large membrane potential across the mitochondrial inner membrane was established. This led to the extensive accumulation of the compounds within mitochondria, thus lowering the extracellular concentration which is detected by the electrode. Addition of the uncoupler FCCP resulted in the dissipation of the membrane potential and consequent release of the compounds back in to the supernatant and this is evident from the electrode response.


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

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

Accumulation of MitoE2 and MitoE10 by isolated rat liver mitochondria (Mito) energised with the respiratory substrate succinate and their release upon dissipation of the mitochondrial membrane potential with the uncoupler carbonyl cyanide p-trifluoromethoxyphenylhydrazone (FCCP).
© Copyright Policy - CC BY
Related In: Results  -  Collection

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

fig5: Accumulation of MitoE2 and MitoE10 by isolated rat liver mitochondria (Mito) energised with the respiratory substrate succinate and their release upon dissipation of the mitochondrial membrane potential with the uncoupler carbonyl cyanide p-trifluoromethoxyphenylhydrazone (FCCP).
Mentions: This aspect was extended by measuring whether MitoE2 and MitoE10 compounds were accumulated by mitochondria in response to the mitochondrial membrane potential, as is expected for a compound linked to a TPP compound. To measure the uptake of the MitoE compounds an ion-selective electrode was used that responds to the concentration of the TPP cation in solution (Fig. 5). When the MitoE compounds were added to a mitochondrial suspension the ion-selective electrode responded to the increase in concentration of the MitoE compound in the extracellular environment. When the mitochondria were energised with the respiratory substrate succinate a large membrane potential across the mitochondrial inner membrane was established. This led to the extensive accumulation of the compounds within mitochondria, thus lowering the extracellular concentration which is detected by the electrode. Addition of the uncoupler FCCP resulted in the dissipation of the membrane potential and consequent release of the compounds back in to the supernatant and this is evident from the electrode response.

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