Regenerable Radical-Trapping Tellurobistocopherol Antioxidants

Abstract

General rightsThis document is made available in accordance with publisher policies. Please cite only the published version using the reference above. Abstract: Tellurobistocopherols 9-11 were prepared by lithiation of the corresponding bromotocopherols, reaction with tellurium tetrachloride and reductive work-up.Compounds 9-11 quenched linoleic acid-derived peroxyl radicals much more efficiently than -tocopherol in a chlorobenzene/water two-phase system.N-Acetylcysteine or tris(2-carboxylethyl)phosphine as co-antioxidants in the aqueous phase could regenerate the tellurobistocopherols and increase their inhibition times.Antioxidant 11 inhibited peroxidation for seven-fold longer than recorded with -tocopherol. Thiol-consumption in the aqueous phase was monitored and found to be inversely related to the inhibition time.Oxidative stress is characterized by an imbalance between the production of reactive oxygen species (ROS) and the antioxidant defense systems in favour of the former. 1ROS is known to target lipids in biological systems and this is generally known as lipid peroxidation, an undesired free radical process whereby organic substances, RH, are oxidized to the corresponding hydroperoxides, ROOH (eq 1).Vitamin E, the most important lipid-soluble antioxidant in man, offers protection against lipid peroxidation. Briefly, vitamin E (AH) competes with the propagation event and scavenges peroxyl radicals, ROO·, by hydrogen-atom transfer (HAT) with a rate kinh >> kprop (eq 2). The resulting resonance-stabilized radical A· is unable to propagate the reaction.

Ditocopheryl Sulfides and Disulfides: Synthesis and Antioxidant Profile

“…Very few examples of tocopheryl dimers are known in the literature and just one example relates to chalcogen‐containing derivatives . In this work, the preparation of symmetrical and unsymmetrical ditocopheryl sulfides ( Toc ) S 2 (all possible six combinations from δ‐ , γ‐ , and β‐Toc ) as well as symmetrical ditocopheryl disulfides ( Toc ) 2 S 2 is described.…”

“…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 . Stimulated by this paper and taking into account that all derivatives showed in Figure , independently of the actual antioxidant activity, required for their preparation multistep procedures and, often, harsh reaction conditions, we faced the problem of setting out a simple, regiocontrolled preparation of both ditocopheryl sulfides and disulfides.…”

“…Eventually,i n ar ecent inspiringp aper, [8] Engman described the preparation and antioxidant efficiency of symmetrical ditocopherylt ellurides (d,d-Toc) 2 Te and (b,b-Toc) 2 Te (Figure 1) pointing out the underestimated potentialo ft he rare examples of compounds assembled linkingt ogethertwo tocopheryl units. [8,9] Stimulated by this paper and taking into account that all derivatives showedi nF igure 1, independently of the actual antioxidant activity,r equired for their preparation multistep procedures and, often, harsh reaction conditions,w ef aced the problem of settingo ut as imple, regiocontrolled preparation of both ditocopheryl sulfides and disulfides. The availability of thesec ompounds would allow for ab etter understanding of the role of sulfurr esidues on the antioxidant activity of phenols.I nf act, we have previously reported that ring substitution with sulfur can have astonishingly different outcomeso nt he H-atom transfer ability of phenolic OH groups,d ependingo ns ubtle conformational and geometrice ffects.…”

Small Molecule Catalysts with Therapeutic Potential

“…Originally developed as antioxidants, these agents have turned out to be more of a “loose redox catalytic cannon” in a cellular environment, and hence are able to target certain cells when employed in sub-micromolar concentrations [ 61 , 62 ]. In Group 16, the isosteric replacement along the line of sulphur—selenium—tellurium tends to enhance activity, and numerous tellurium compounds have been considered as potential antioxidants, not only in the context of human health and disease, but also for the preservation of materials and foodstuffs, as the research into radical-chain breaking agents by Engman and colleagues illustrates nicely [ 63 , 64 ]. Concurrently, moving from selenium to tellurium also diminishes any meaningful selectivity for GSH and turns the catalyst somewhat—but not entirely—indiscriminate against protein thiols (PrSH) (see Section 4 ).…”

Heterocoumarins Are Selective Carbonic Anhydrase IX and XII Inhibitors with Cytotoxic Effects against Cancer Cells Lines

“…Diaryl ditelluride 11 was prepared from aryl bromide 10 via lithiation, tellurium insertion, and oxidation in analogy with a literature procedure. 16 The ditelluride acetal derivative 11 was then hydrolyzed with concentrated HCl, and the resulting aldehyde 13 wa scondensed with a Knoevenagel reaction with malonic acid to afford the corresponding cinnamoyl acid derivative 14. Finally, cyclization into tellurocoumarin 15 was obtained by converting compound 14 in situ in the corresponding acyl chloride and subsequently treated with AlCl 3 in dichloromehtyl methyl ether as reported previously in the literature 17 and outlined in Scheme 5.…”