Role of Noncovalent Sulfur···Oxygen Interactions in Phenoxyl Radical Stabilization: Synthesis of Super Tocopherol-like Antioxidants

2-Aryltellurophenols substituted in the aryltelluro or phenolic parts of the molecule were prepared by lithiation of the corresponding tetrahydropyran-protected 2-bromophenol, followed by reaction with a suitable diaryl ditelluride then deprotection. In a two-phase system containing N-acetylcysteine as a co-antioxidant in the aqueous phase, all of the compounds quenched lipid peroxyl radicals more efficiently than α-tocopherol, with three to five-fold longer inhibition times. Thus, these compounds offer better and longer-lasting antioxidant protection than recently prepared alkyltellurophenols. Compounds with electron-donating para substituents in the aryltelluro or phenolic part of the molecule showed the best results. The mechanism for quenching peroxyl radicals was considered and discussed with respect to the calculated O-H bond-dissociation energies, deuterium-labelling experiments and studies of thiol consumption in the aqueous phase.

“…Menichetti et al . recently reported that tocopherol analogue 5 , which contains a benzannulated thiophene moiety, was three‐times more reactive than 4 as a radical‐trapping agent.…”

Section: Introductionmentioning

confidence: 99%

Substituent Effects in Chain‐Breaking Aryltellurophenol Antioxidants

Poon

Yan

Jorner

et al. 2018

“…The bimolecular rate constant for this process is high because the O−H bond dissociation energy, BDE O−H , is low (77.1 kcal mol −1 ). The strength of the O−H bond in compounds 8 – 11 was calculated in the gas phase at the M062X/aug‐ccpVDZ level of theory as the energy difference between the optimized geometry of the molecule and the corresponding phenoxyl radical plus hydrogen atom . The geometry of 11 was in good agreement with the X‐ray structure (for example, the calculated bond lengths C1−Se (1.910 Å) and Se−C8 (1.985 Å) and the angle C1‐Se‐C8 (87.03°) were close to the experimental values shown in Figure ).…”

Section: Resultsmentioning

confidence: 74%

“…Compounds 9 (preparedb yd emethylation of 15 a) 10 and 11 were fully characterized by 1 H, 13 C, and 77 Se NMR spectroscopy and the identityo f11 was confirmed by X-ray crystallography.…”

Section: Synthesismentioning

confidence: 95%

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Chain‐Breaking Phenolic 2,3‐Dihydrobenzo[b]selenophene Antioxidants: Proximity Effects and Regeneration Studies

Singh

Yan

Poon

et al. 2017

Phenolic 2,3-dihydrobenzo[b]selenophene antioxidants bearing an OH-group ortho (9), meta (10, 11) and para (8) to the Se were prepared by seleno-Claisen rearrangement/intramolecular hydroselenation. meta-Isomer (11) was studied by X-ray crystallography. The radical-trapping activity and regenerability of compounds 8-11 were evaluated using a two-phase system in which linoleic acid was undergoing peroxidation in the lipid phase while regeneration of the antioxidant by co-antioxidants (N-acetylcysteine, glutathione, dithiothreitol, ascorbic acid, tris(carboxyethyl)phosphine hydrochloride) was ongoing in the aqueous layer. Compound 9 quenched peroxyl radicals more efficiently than α-tocopherol. It also provided the most long-lasting antioxidant protection. With thiol co-antioxidants it could inhibit peroxidation for more than five-fold longer than the natural product. Regeneration was more efficient when the aqueous phase pH was slightly acidic. Since calculated O-H bond dissociation energies for 8-11 were substantially larger than for α-tocopherol, an antioxidant mechanism involving O-atom transfer from peroxyl to selenium was proposed. The resulting phenolic selenoxide/alkoxyl radical would then exchange a hydrogen atom in a solvent cage before antioxidant regeneration at the aqueous lipid interphase.

“…Engman and co‐workers have studied the effect on antioxidant activity of insertion of sulfur, selenium and tellurium alkyl substituents on the aromatic ring of different tocopherols (compounds 4 , Figure ). We have reported the insertion of sulfur in position 4 of chromane rings of δ ‐, γ ‐, β ‐, and α‐Toc , as well as the transformation of the benzene ring of tocopherol in a benzo[ b ]thiophene aromatic system (derivatives 5 a–d and 6 , Figure ). Eventually, in a recent inspiring paper, Engman described the preparation and antioxidant efficiency of symmetrical ditocopheryl tellurides ( δ , δ ‐ Toc ) 2 Te and ( β , β ‐ Toc ) 2 Te (Figure ) pointing out the underestimated potential of the rare examples of compounds assembled linking together two tocopheryl units .…”

Section: Introductionmentioning

confidence: 99%

Ditocopheryl Sulfides and Disulfides: Synthesis and Antioxidant Profile

Viglianisi

Vasa

Tanini

et al. 2019

Self Cite

Symmetrical ditocopheryl disulfides (Toc)2S2 and symmetrical and unsymmetrical ditocopheryl sulfides (Toc)2S were simply prepared under remarkably mild conditions with complete control of the regiochemistry by using δ‐, γ‐, and β‐tocopheryl‐N‐thiophthalimides (Toc‐NSPht) as common starting materials. The roles of sulfur atom(s), H‐bond and aryl ring substitution pattern on the antioxidant profile of these new compounds, which were assembled by linking together two tocopheryl units, are also discussed.