title: Is the chromanol head group of vitamin E nature's final truth on chain-breaking antioxidants?
abstract: Tocopherol is believed to be the most potent naturally occurring chain-breaking antioxidant. Hence, its refined phenolic head group chromanol may represent an optimum evolutionary solution to the problem of free-radical chain reactions in the lipid bilayer. To test the universal validity of this assumption beyond phenolic head groups, we have synthesized aromatic amine analogues of vitamin E and trolox with otherwise closely matching physicochemical properties: NH-toc and NH-trox. We have found that NH-toc and NH-trox were significantly more potent free radical scavengers, lipid peroxidation inhibitors and cytoprotective agents than their phenolic templates, tocopherol and trolox. In a chemical sense, thus, the chromanol head group does not constitute a global optimum for the design of chain-breaking antioxidants.
authors.affiliation: Institute for Pathobiochemistry, University Medical Center of the Johannes Gutenberg University, Mainz, Germany.
authors.forename: Maike J
authors.initials: MJ
authors.lastname: Ohlow
authors.forename: Matthias
authors.initials: M
authors.lastname: Granold
authors.forename: Mathias
authors.initials: M
authors.lastname: Schreckenberger
authors.forename: Bernd
authors.initials: B
authors.lastname: Moosmann
mesh_terms: D000588:Amines / Q000737:chemistry; D000818:Animals; D000975:Antioxidants / Q000737:chemistry*; D002839:Chromans / Q000737:chemistry*; D016166:Free Radical Scavengers / Q000737:chemistry; D005609:Free Radicals / Q000737:chemistry; D008051:Lipid Bilayers / Q000737:chemistry; D015227:Lipid Peroxidation; D015394:Molecular Structure; D010636:Phenols / Q000737:chemistry; D014810:Vitamin E / Q000031:analogs & derivatives*
chemical_list: D000588:Amines; D000975:Antioxidants; D002839:Chromans; D016166:Free Radical Scavengers; D005609:Free Radicals; D008051:Lipid Bilayers; D010636:Phenols; D014810:Vitamin E; C029141:2,2,5,7,8-pentamethyl-1-hydroxychroman; C010643:6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid