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Yan, Jiajie
Publications (9 of 9) Show all publications
Poon, J.-f., Yan, J., Jorner, K., Ottosson, H., Donau, C., Singh, V. P., . . . Engman, L. (2018). Substituent Effects in Chain-Breaking Aryltellurophenol Antioxidants. Chemistry - A European Journal, 24(14), 3520-3527
Open this publication in new window or tab >>Substituent Effects in Chain-Breaking Aryltellurophenol Antioxidants
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2018 (English)In: Chemistry - A European Journal, ISSN 0947-6539, E-ISSN 1521-3765, Vol. 24, no 14, p. 3520-3527Article in journal (Refereed) Published
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. 

National Category
Organic Chemistry
Research subject
Chemistry with specialization in Organic Chemistry
Identifiers
urn:nbn:se:uu:diva-329202 (URN)10.1002/chem.201704811 (DOI)000426764400024 ()29266496 (PubMedID)
Funder
Stiftelsen Olle Engkvist Byggmästare, 1016/159ÅForsk (Ångpanneföreningen's Foundation for Research and Development), 16-364
Note

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

Available from: 2017-09-10 Created: 2017-09-10 Last updated: 2018-05-22Bibliographically approved
Singh, V. P., Yan, J., Poon, J.-f., Gates, P. J., Butcher, R. J. & Engman, L. (2017). Chain-Breaking Phenolic 2,3-Dihydrobenzo[b]selenophene Antioxidants: Proximity Effects and Regeneration Studies. Chemistry - A European Journal, 23(60), 15080-15088
Open this publication in new window or tab >>Chain-Breaking Phenolic 2,3-Dihydrobenzo[b]selenophene Antioxidants: Proximity Effects and Regeneration Studies
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2017 (English)In: Chemistry - A European Journal, ISSN 0947-6539, E-ISSN 1521-3765, Vol. 23, no 60, p. 15080-15088Article in journal (Refereed) Published
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.

Keywords
chain-breaking antioxidants, phenols, dihydrobenzoselenophenes, lipid peroxidation, co-antioxidants
National Category
Organic Chemistry
Research subject
Chemistry with specialization in Organic Chemistry
Identifiers
urn:nbn:se:uu:diva-329201 (URN)10.1002/chem.201702350 (DOI)000413768900018 ()28857289 (PubMedID)
Available from: 2017-09-10 Created: 2017-09-10 Last updated: 2018-02-23Bibliographically approved
Singh, V. P., Poon, J.-f., Yan, J., Lu, X., Karlsson Ott, M., Butcher, R. J., . . . Engman, L. (2017). Nitro-, Azo-, and Amino Derivatives of Ebselen: Synthesis, Structure, and Cytoprotective Effects. Journal of Organic Chemistry, 82(1), 313-321
Open this publication in new window or tab >>Nitro-, Azo-, and Amino Derivatives of Ebselen: Synthesis, Structure, and Cytoprotective Effects
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2017 (English)In: Journal of Organic Chemistry, ISSN 0022-3263, E-ISSN 1520-6904, Vol. 82, no 1, p. 313-321Article in journal (Refereed) Published
Abstract [en]

Novel azo-bis-ebselen compounds 7 were prepared by reduction of 7-nitro-2-aryl-1,2-benzisoselenazol-3(2H)ones 3 and 6 with sodium benzenetellurolate; NaTeC6H5, and by reaction of 2-bromo-3-nitrobenzamides with Na2Se2. The X-ray structure of 7b showed that the molecule, due to strong intramolecular secondary Se center dot center dot center dot N interactions, is completely planar. Azo-compounds 7 upon further reaction with NaTeC6H5 were reductively cleaved to provide 2 equiv of the corresponding aromatic amine. The weak Se-N bond was not stable enough to survive the reaction conditions, and diselenides 8 were isolated after workup. Whereas azo-bis-ebselens 7 were poor mimics of the glutathione peroxidase (GPx)-enzymes, nitroebselens 3, 6, and 11b and diselenides 8 were 3-6-fold more active than ebselen. Based on Se-77 NMR. spectroscopy, a catalytic cycle for diselenide 8b, involving aminoebselen 14, was proposed. As assessed by chemiluminescence measurements, the good GPx-mimics could reduce production of reactive oxygen species (ROS) in stimulated human mononuclear cells more efficiently than Trolox. No toxic effects of the, compounds were seen in MC3T3-cells at 25 mu M.

National Category
Organic Chemistry Engineering and Technology
Identifiers
urn:nbn:se:uu:diva-312514 (URN)10.1021/acs.joc.6b02418 (DOI)000391781900030 ()27966348 (PubMedID)
Funder
ÅForsk (Ångpanneföreningen's Foundation for Research and Development), 16-364Stiftelsen Olle Engkvist Byggmästare, 2016/159Carl Tryggers foundation , CTS 13:346
Available from: 2017-01-10 Created: 2017-01-10 Last updated: 2017-11-29Bibliographically approved
Yan, J. (2017). Regenerable Organochalcogen Antioxidants: An Explorative Study. (Doctoral dissertation). Uppsala: Acta Universitatis Upsaliensis
Open this publication in new window or tab >>Regenerable Organochalcogen Antioxidants: An Explorative Study
2017 (English)Doctoral thesis, comprehensive summary (Other academic)
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.  

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2017. p. 70
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1651-6214 ; 1556
Keywords
autoxidation, antioxidant, selenium, tellurium, regenerable, multifunctional, radical-trapping, hydroperoxide-decomposing, co-antioxidant
National Category
Organic Chemistry
Research subject
Chemistry with specialization in Organic Chemistry
Identifiers
urn:nbn:se:uu:diva-329217 (URN)978-91-513-0068-9 (ISBN)
Public defence
2017-10-27, B7:101a, BMC, Husargatan 3, 751 23, Uppsala, 09:30 (English)
Opponent
Supervisors
Available from: 2017-10-05 Created: 2017-09-10 Last updated: 2017-10-18
Poon, J.-F., Yan, J., Singh, V. P., Gates, P. J. & Engman, L. (2016). Alkyltelluro Substitution Improves the Radical-Trapping Capacity of Aromatic Amines. Chemistry - A European Journal, 22(36), 12891-12903
Open this publication in new window or tab >>Alkyltelluro Substitution Improves the Radical-Trapping Capacity of Aromatic Amines
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2016 (English)In: Chemistry - A European Journal, ISSN 0947-6539, E-ISSN 1521-3765, Vol. 22, no 36, p. 12891-12903Article in journal (Refereed) Published
Abstract [en]

The synthesis of a variety of aromatic amines carrying an ortho-alkyltelluro group is described. The new antioxidants quenched lipidperoxyl radicals much more efficiently than α-tocopherol and were regenerable by aqueous-phase N-acetylcysteine in a two-phase peroxidation system. The inhibition time for diaryl amine 9 b was four-fold longer than recorded with α-tocopherol. Thiol consumption in the aqueous phase was found to correlate inversely to the inhibition time and the availability of thiol is the limiting factor for the duration of antioxidant protection. The proposed mechanism for quenching of peroxyl radicals involves O-atom transfer from peroxyl to Te followed by H-atom transfer from amine to alkoxyl radical in a solvent cage.

Keywords
antioxidants; amines; chain-breaking activity; organotellurium; regenerable
National Category
Organic Chemistry
Identifiers
urn:nbn:se:uu:diva-302460 (URN)10.1002/chem.201602377 (DOI)000383758200044 ()27484352 (PubMedID)
Funder
Swedish Research Council, 621-2011-4006
Available from: 2016-09-04 Created: 2016-09-04 Last updated: 2017-11-21Bibliographically approved
Kumar, S., Yan, J., Poon, J.-f., Singh, V. P., Lu, X., Ott, M. K., . . . Kumar, S. (2016). Multifunctional Antioxidants: Regenerable Radical-Trapping and Hydroperoxide-Decomposing Ebselenols. Angewandte Chemie International Edition, 55(11), 3729-3733
Open this publication in new window or tab >>Multifunctional Antioxidants: Regenerable Radical-Trapping and Hydroperoxide-Decomposing Ebselenols
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2016 (English)In: Angewandte Chemie International Edition, ISSN 1433-7851, E-ISSN 1521-3773, Vol. 55, no 11, p. 3729-3733Article in journal (Refereed) 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.

National Category
Natural Sciences Engineering and Technology
Identifiers
urn:nbn:se:uu:diva-280006 (URN)10.1002/anie.201510947 (DOI)000371521000034 ()26879742 (PubMedID)
Funder
Swedish Research CouncilCarl Tryggers foundation , 13:346, 13:120
Available from: 2016-03-07 Created: 2016-03-07 Last updated: 2017-11-30Bibliographically approved
Poon, J.-f., Yan, J., Singh, V. P., Gates, P. J. & Engman, L. (2016). Regenerable Radical-Trapping Tellurobistocopherol Antioxidants. Journal of Organic Chemistry, 81(24), 12540-12544
Open this publication in new window or tab >>Regenerable Radical-Trapping Tellurobistocopherol Antioxidants
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2016 (English)In: Journal of Organic Chemistry, ISSN 0022-3263, E-ISSN 1520-6904, Vol. 81, no 24, p. 12540-12544Article in journal (Refereed) Published
Abstract [en]

Tellurobistocopherols 911 were prepared by lithiation of the corresponding bromotocopherols, reaction with tellurium tetrachloride and reductive workup. Compounds 911 quenched linoleic-acid-derived peroxyl radicals much more efficiently than α-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 7-fold longer than that recorded with α-tocopherol. Thiol consumption in the aqueous phase was monitored and found to be inversely related to the inhibition time.

National Category
Organic Chemistry
Identifiers
urn:nbn:se:uu:diva-302464 (URN)10.1021/acs.joc.6b02450 (DOI)000390180100051 ()
Note

Authors in list of papers in thesis: Poon, J.; Yan, J.; Gates, P.; Engman, L.

Available from: 2016-09-04 Created: 2016-09-04 Last updated: 2017-11-21Bibliographically approved
Poon, J.-f., Singh, V. P., Yan, J. & Engman, L. (2015). Regenerable Antioxidants - Introduction of Chalcogen Substituents into Tocopherols. Chemistry - A European Journal, 21(6), 2447-2457
Open this publication in new window or tab >>Regenerable Antioxidants - Introduction of Chalcogen Substituents into Tocopherols
2015 (English)In: Chemistry - A European Journal, ISSN 0947-6539, E-ISSN 1521-3765, Vol. 21, no 6, p. 2447-2457Article in journal (Refereed) Published
Abstract [en]

To improve the radical-trapping capacity of the natural antioxidants, alkylthio-, alkylseleno-, and alkyltelluro groups were introduced into all vacant aromatic positions in β-, γ- and δ-tocopherol. Reaction of the tocopherols with electrophilic chalcogen reagents generated by persulfate oxidation of dialkyl dichalcogenides provided convenient but low-yielding access to many sulfur and selenium derivatives, but failed in the case of tellurium. An approach based on lithiation of the appropriate bromo-tocopherol, insertion of chalcogen into the carbon-lithium bond, air-oxidation to a dichalcogenide, and final borohydride reduction/alkylation turned out to be generally applicable to the synthesis of all chalcogen derivatives. Whereas alkylthio- and alkylseleno analogues were generally poorer quenchers of lipid peroxyl radicals than the corresponding parents, all tellurium compounds showed a substantially improved radical-trapping activity. Introduction of alkyltelluro groups into the tocopherol scaffold also caused a dramatic increase in the regenerability of the antioxidant. In a two-phase lipid peroxidation system containing N-acetylcysteine as a water-soluble co-antioxidant the inhibition time was up to six-fold higher than that recorded for the natural antioxidants.

National Category
Chemical Sciences
Identifiers
urn:nbn:se:uu:diva-243231 (URN)10.1002/chem.201405895 (DOI)000348510400023 ()
Note

De två första författarna delar förstaförfattarskapet.

Available from: 2015-02-05 Created: 2015-02-05 Last updated: 2017-12-05Bibliographically approved
Yan, J., Poon, J.-f., Singh, V. P., Gates, P. & Engman, L. (2015). Regenerable thiophenolic radical-trapping antioxidants. Organic Letters, 17(24), 6162-6165
Open this publication in new window or tab >>Regenerable thiophenolic radical-trapping antioxidants
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2015 (English)In: Organic Letters, ISSN 1523-7060, E-ISSN 1523-7052, Vol. 17, no 24, p. 6162-6165Article in journal (Refereed) 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.

National Category
Organic Chemistry
Identifiers
urn:nbn:se:uu:diva-269896 (URN)10.1021/acs.orglett.5b03169 (DOI)000366878300057 ()
Funder
Swedish Research Council, 621-2011-4006Carl Tryggers foundation , CTS:120
Available from: 2015-12-18 Created: 2015-12-18 Last updated: 2017-12-01Bibliographically approved
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