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Regenerable Organochalcogen Antioxidants: An Explorative Study
Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.ORCID-id: 0000-0003-0689-3180
2017 (engelsk)Doktoravhandling, med artikler (Annet vitenskapelig)
Abstract [en]

Antioxidants are widely used to protect organic materials from damages caused by autoxidation, an oxidation process that occurs under normal aerobic conditions. In this thesis, novel multifunctional organoselenium and organotellurium antioxidants were designed, synthesized, and evaluated in search for compounds with better radical-trapping capacity, regenerability, and hydroperoxide-decomposing ability.

Selenium was incorporated into ebselenols and hydroxy-2,3-dihydrobenzo[b]selenophenes and tellurium into diaryl disulfides and aryltellurophenols. All newly developed antioxidants were evaluated in a chlorobenzene/water two-phase lipid peroxidation system containing suitable co-antioxidants in the aqueous phase. Ebselenol carrying a hydroxyl group (OH) ortho to selenium showed a two-fold longer inhibition time than the reference α-tocopherol in the presence of aqueous-phase ascorbic acid. 2,3-Dihydrobenzo[b]selenophenes carrying a 5- or 7-OH outperformed α-tocopherol both when it comes to radical-trapping capacity and regenerability. Alkyltellurothiophenols, in situ formed from their corresponding disulfides by tris(2-carboxyethyl)phosphine, were also efficient regenerable radical-trapping antioxidants. The consumption of N-acetylcysteine in the water phase was followed and found to be limiting for the duration of the inhibition. The hydroperoxide-decomposing ability of all organoselenium antioxidants was evaluated. Ebselenols were often better glutathione peroxidase mimics than the parent.

In an effort to find out more about antioxidant mechanisms, aryltellurophenols carrying electron donating and electron withdrawing groups in the phenolic or aryltelluro parts were synthesized and OH bond dissociation enthalpies, BDEO-Hs, were calculated. Compounds carrying electron donating groups in the phenolic or aryltelluro part of the molecule showed the best radical-trapping capacity. Deuterium labelling experiments suggested that hydrogen atom transfer could be the rate-limiting step in the antioxidant mechanism.  

sted, utgiver, år, opplag, sider
Uppsala: Acta Universitatis Upsaliensis, 2017. , 70 s.
Serie
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1651-6214 ; 1556
Emneord [en]
autoxidation, antioxidant, selenium, tellurium, regenerable, multifunctional, radical-trapping, hydroperoxide-decomposing, co-antioxidant
HSV kategori
Forskningsprogram
Kemi med inriktning mot organisk kemi
Identifikatorer
URN: urn:nbn:se:uu:diva-329217ISBN: 978-91-513-0068-9 (tryckt)OAI: oai:DiVA.org:uu-329217DiVA: diva2:1139922
Disputas
2017-10-27, B7:101a, BMC, Husargatan 3, 751 23, Uppsala, 09:30 (engelsk)
Opponent
Veileder
Tilgjengelig fra: 2017-10-05 Laget: 2017-09-10 Sist oppdatert: 2017-10-18
Delarbeid
1. Multifunctional Antioxidants: Regenerable Radical-Trapping and Hydroperoxide-Decomposing Ebselenols
Åpne denne publikasjonen i ny fane eller vindu >>Multifunctional Antioxidants: Regenerable Radical-Trapping and Hydroperoxide-Decomposing Ebselenols
Vise andre…
2016 (engelsk)Inngår i: Angewandte Chemie International Edition, ISSN 1433-7851, E-ISSN 1521-3773, Vol. 55, nr 11, 3729-3733 s.Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

Regenerable, multifunctional ebselenol antioxidants were prepared that could quench peroxyl radicals more efficiently than -tocopherol. These compounds act as better mimics of the glutathione peroxidase enzymes than ebselen. Production of reactive oxygen species (ROS) and reactive nitrogen species (RNS) in human mononuclear cells was considerably decreased upon exposure to the organoselenium compounds. At a concentration of 25m, the ebselenol derivatives showed minimal toxicity in pre-osteoblast MC3T3cells.

HSV kategori
Identifikatorer
urn:nbn:se:uu:diva-280006 (URN)10.1002/anie.201510947 (DOI)000371521000034 ()26879742 (PubMedID)
Forskningsfinansiär
Swedish Research CouncilCarl Tryggers foundation , 13:346, 13:120
Tilgjengelig fra: 2016-03-07 Laget: 2016-03-07 Sist oppdatert: 2017-09-10bibliografisk kontrollert
2. Chain-Breaking Phenolic 2,3-Dihydrobenzo[b]selenophene Antioxidants – Proximity Effects and Regeneration Studies
Åpne denne publikasjonen i ny fane eller vindu >>Chain-Breaking Phenolic 2,3-Dihydrobenzo[b]selenophene Antioxidants – Proximity Effects and Regeneration Studies
Vise andre…
(engelsk)Inngår i: Chemistry - A European Journal, ISSN 0947-6539, E-ISSN 1521-3765Artikkel i tidsskrift (Fagfellevurdert) Accepted
Abstract [en]

Phenolic 2,3-dihydrobenzo[b]selenophene anti-oxidants carrying the 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 where 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.

Emneord
chain-breaking antioxidants, phenols, dihydrobenzoselenophenes, lipid peroxidation, co-antioxidants
HSV kategori
Forskningsprogram
Kemi med inriktning mot organisk kemi
Identifikatorer
urn:nbn:se:uu:diva-329201 (URN)10.1002/chem.201702350 (DOI)
Tilgjengelig fra: 2017-09-10 Laget: 2017-09-10 Sist oppdatert: 2017-09-10
3. Regenerable thiophenolic radical-trapping antioxidants
Åpne denne publikasjonen i ny fane eller vindu >>Regenerable thiophenolic radical-trapping antioxidants
Vise andre…
2015 (engelsk)Inngår i: Organic Letters, ISSN 1523-7060, E-ISSN 1523-7052, Vol. 17, nr 24, 6162-6165 s.Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

Diphenyl disulfides carrying alkyltelluro groups in the o-, m-, and p-positions were prepared using ortho-lithiation and lithium halogen exchange reactions. The novel antioxidants showed only minimal inhibitory effect on the azo-initiated peroxidation of linoleic acid in chlorobenzene until reduced to the corresponding thiophenols by tris(2-carboxyethyl)phosphine (TCEP). The best in situ generated thiophenol (from 7c) under these conditions quenched peroxyl radicals more efficiently than α-tocopherol with an almost 3-fold increase in inhibition time.

HSV kategori
Identifikatorer
urn:nbn:se:uu:diva-269896 (URN)10.1021/acs.orglett.5b03169 (DOI)000366878300057 ()
Forskningsfinansiär
Swedish Research Council, 621-2011-4006Carl Tryggers foundation , CTS:120
Tilgjengelig fra: 2015-12-18 Laget: 2015-12-18 Sist oppdatert: 2017-09-10bibliografisk kontrollert
4. Substituent Effects in Chain-Breaking Aryltellurophenol Antioxidants
Åpne denne publikasjonen i ny fane eller vindu >>Substituent Effects in Chain-Breaking Aryltellurophenol Antioxidants
Vise andre…
(engelsk)Manuskript (preprint) (Annet vitenskapelig)
Abstract [en]

2-Aryltellurophenols substituted in the aryltelluro or phenolic part of the molecule were prepared by lithiation of the corresponding O-THP-protected 2-bromophenol, followed by reaction with a suitable diaryl ditelluride and deprotection. In a two-phase system containing N-acetylcysteine as a co-antioxidant in the aqueous phase, all compounds quenched lipid peroxyl radicals more efficiently than α-tocopherol with 3 to 5-fold longer inhibition times. Compounds carrying electron donating para-substituents in the phenolic or aryltelluro part of the molecule showed the best results. The mechanism for quenching of peroxyl radicals was discussed in the light of calculated OH bond dissociation energies, deuterium labeling experiments and studies of thiol-consumption in the aqueous phase. 

HSV kategori
Forskningsprogram
Kemi med inriktning mot organisk kemi
Identifikatorer
urn:nbn:se:uu:diva-329202 (URN)
Merknad

Poon, J. and Yan, J. are equally contributing.

Tilgjengelig fra: 2017-09-10 Laget: 2017-09-10 Sist oppdatert: 2017-09-16

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