Effect of a Bromo Substituent on the Glutathione Peroxidase Activity of a Pyridoxine-like Diselenide
2015 (English)In: The Journal of Organic Chemistry, Vol. 50, no 15, 7385-7395 p.Article in journal (Refereed) Published
In search for better mimics of the glutathioneperoxidase enzymes, pyridoxine-like diselenides 6 and 11,carrying a 6-bromo substituent, were prepared. Reaction of2,6-dibromo-3-pyridinol 5 with sodium diselenide provided 6via aromatic nucleophilic substitution of the 2-bromosubstituent. LiAlH4 caused reduction of all four ester groupsand returned 11 after acidic workup. The X-ray structure of 6showed that the dipyridyl diselenide moiety was kept in analmost planar, transoid conformation. According to NBOanalysis,this was due to weak intramolecular Se···O (1.1 kcal/mol) and Se···N-interactions (2.5 kcal/mol). That the 6-bromo substituent increased the positive charge on seleniumwas confirmed by NPA-analysis and seen in calculated andobserved 77Se NMR-shifts. Diselenide 6 showed a more than 3-fold higher reactivity than the corresponding des-bromocompound 3a and ebselen when evaluated in the coupled reductase assay. Experiments followed for longer time (2 h) confirmedthat diselenide 6 is a better GPx-catalyst than 11. On the basis of 77Se-NMR experiments, a catalytic mechanism for diselenide 6was proposed involving selenol, selenosulfide and seleninic acid intermediates. At low concentration (10 μM) where it showedonly minimal toxicity, it could scavenge ROS produced by MNC- and PMNC-cells more efficiently than Trolox.
Place, publisher, year, edition, pages
2015. Vol. 50, no 15, 7385-7395 p.
Chemical Sciences Engineering and Technology
Research subject Chemistry with specialization in Organic Chemistry; Engineering Science with specialization in Materials Science
IdentifiersURN: urn:nbn:se:uu:diva-259460DOI: 10.1021/acs.joc.5b00797ISI: 000359393500007OAI: oai:DiVA.org:uu-259460DiVA: diva2:844254
FunderSwedish Research CouncilCarl Tryggers foundation , CTS 13:120 13:346