title: Tocopheramines and tocotrienamines as antioxidants: ESR spectroscopy, rapid kinetics and DFT calculations.
abstract: Tocopheramines (TNH2) and tocotrienamines (T3NH2) are analogues of tocopherols (TOH) and tocotrienols in which phenolic OH is replaced by NH2. It was shown in previous studies that TNH2 and T3NH2 act as potent antioxidants. In this study we compared the one-electron oxidation of TNH2/T3NH2 by diphenyl picryl hydrazyl (DPPH) and galvinoxyl (GOX) radicals with the one of α-TOH as a reference compound using ESR spectroscopy, stopped flow spectrophotometry and density functional theory (DFT) calculations. ESR spectroscopy revealed the presence of tocopheramine radicals during electrochemical oxidation of α-TNH2. Kinetic measurements demonstrated that in apolar n-hexane TNH2/T3NH2 derivatives reacted two to three orders of magnitude slower than α-TOH with the model radicals. DFT calculations indicated that this correlates well with the higher bond dissociation energy (BDE) for N-H in TNH2 than for O-H in α-TOH in pure H-atom transfer (HAT). In the more polar medium ethanol TNH2/T3NH2 derivatives partially reacted faster than α-TOH depending on the reaction partner. DFT calculations suggest that this is due to reaction mechanisms alternative to HAT. According to thermochemistry data sequential proton loss and electron transfer (SPLET) is more favored for α-TOH in ethanol than for TNH2. Therefore, for TNH2 a contribution of the alternative mechanism of sequential electron transfer-proton transfer (SET-PT) could be a possible explanation. These data show that the antioxidant reactivity strongly depends on the structure, reaction partners and environment. According to these findings TNH2/T3NH2 should be superior as antioxidants over α-TOH in polar head group regions of membranes but not in the apolar core of lipid bilayers.
authors.affiliation: Dept. of Internal Medicine, Laboratory of Clinical and Nutritional Biochemistry, University of Perugia, I-06123 Perugia, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Bamonti
authors.forename: Takashi
authors.initials: T
authors.lastname: Hosoya
authors.forename: Katharina F
authors.initials: KF
authors.lastname: Pirker
authors.forename: Stefan
authors.initials: S
authors.lastname: Böhmdorfer
authors.forename: Francesco
authors.initials: F
authors.lastname: Mazzini
authors.forename: Francesco
authors.initials: F
authors.lastname: Galli
authors.forename: Thomas
authors.initials: T
authors.lastname: Netscher
authors.forename: Thomas
authors.initials: T
authors.lastname: Rosenau
authors.forename: Lars
authors.initials: L
authors.lastname: Gille
mesh_terms: D000975:Antioxidants / Q000737:chemistry*; D004578:Electron Spin Resonance Spectroscopy; D007700:Kinetics; D010084:Oxidation-Reduction; D024505:Tocopherols / Q000737:chemistry*; D024508:Tocotrienols / Q000737:chemistry*
chemical_list: D000975:Antioxidants; D024508:Tocotrienols; D024505:Tocopherols
keywords: DFT calculations; ESR spectroscopy; Radicals; Stopped flow spectrophotometry; Tocopheramines