Vitamin E Chemistry. Nitration of Non-α-tocopherols:  Products and Mechanistic Considerations

Abstract

In contrast to the alpha-form permethylated at the aromatic ring, non-alpha-tocopherols possess free aromatic ring positions which enable them to act as potent scavengers of electrophiles in vivo and in vitro. In preparation of enzymatic studies involving peroxynitrite and other nitrating systems, the behavior of non-alpha-tocopherols under nitration conditions was studied. The nitration products of beta-, gamma-, and delta-tocopherol were identified, comprehensively analytically characterized, and their structure was supported by X-ray crystal structure analysis on truncated model compounds. Even under more drastic nitration conditions, no erosion of the stereochemistry at 2-C occurred. The nitrosation of gamma-tocopherol and delta-tocopherol was re-examined, showing the slow oxidation of the initial nitroso products to the corresponding nitro derivatives by air to be superimposed by a fast equilibrium with the tautomeric ortho-quinone monoxime, which only in the case of gamma-tocopherol released hydroxyl amine at elevated temperatures to afford the stable ortho-quinone. Mononitration of delta-tocopherol selectively proceeded at position 5. This selectivity can be explained by the theory of strain-induced bond localization (SIBL) to the quinoid nitration intermediates. Bisnitration was only insignificantly disfavored by the first nitro group, so that under normal nitration conditions offering an excess of nitrating species only the bisnitration product was found.

Two Faces of Vitamin E in the Lung

“…Thus, because a-tocopherol is 10-fold higher in tissues than g-tocopherol, there is 10-fold more total ROS scavenging by a-tocopherol than g-tocopherol. Besides scavenging ROS, g-tocopherol, in contrast to a-tocopherol, also reacts with reactive nitrogen species, such as peroxynitrite-forming 5-nitro-g-tocopherol (21). g-Tocopherol scavenging of reactive nitrogen species may be beneficial for inflammation with increases in reactive nitrogen species, such as neutrophilic inflammation that is induced by ozone in mice (22).…”

Bromination of Tocopherols: Oxidative Halogenations and Rearrangements

“…A similar pairing of the reactivities has also been found for bromination under apolar conditions [24] and for the nitration of tocopherols. [30] In general, reaction rates were strongly dependent on the reac- tion medium (i.e., the ratio between aqueous buffer and ethanol used and the set pH value). The concentration of the buffer and the type of buffer system -which, of course, had to be inert towards bromine and bromine-derived oxidizing species -were of little influence, by contrast.…”

“…An interesting aspect was the dissimilar natures of the involvements of the para-quinoid compounds para-tocopherylquinone (19) and 2-bromo-para-tocopherylquinone (18) in the reaction, despite their quite similar structures. Both were formed as primary intermediates, the former directly from 3, the latter analogously to the reaction behavior in neutral media via the brominated phenol 17 (cf.…”

“…This was, of course, unacceptable, especially with regard to medical studies. In recent work we have focused on interactions of the tocopherols with nitrosating [17] and nitrating [18] species and have provided complete sets of analytical data, including crystal structures of the corresponding truncated model compounds in which the isoprenoid tocopherol side chains were replaced with methyl groups (cf. 1a-4a in Scheme 1).…”

INTERRELATION OF VITAMIN E ISOFORMS AND ATHEROGENESIS MARKERS IN PATIENTS WITH TYPE 2 DIABETES MELLITUS (literature review and own results)

“…Крiм того, γ-токоферол натепер розглядають як потенцiйний агент щодо по-передження процесiв пухлиноутворення [8]. Слiд також зазначити, що γ-токоферол, на вiдмiну вiд α-токоферолу, здатний реагува-ти з активними формами азоту, такими як пероксинiтрит суттєвою складовою у роз-витку ендотелiальної дисфункцiї [31]. З iн-шого боку, в експериментах in vitro та in vivo було показано, що γ-токоферол у фi-зiологiчних концентрацiях демонструє про-тилежнi α-токоферолу прозапальнi та про-атерогеннi властивостi, пов'язанi з посилен-ням трансендотелiальної мiграцiї лiмфоци-тiв, залежної вiд адгезивних молекул [32].…”