10.1021/acs.joc.5b00797.s001
Vijay P. Singh
Vijay P.
Singh
Jia-fei Poon
Jia-fei
Poon
Ray J. Butcher
Ray J.
Butcher
Xi Lu
Xi
Lu
Gemma Mestres
Gemma
Mestres
Marjam
Karlsson Ott
Marjam
Karlsson
Ott
Lars Engman
Lars
Engman
Effect of a Bromo Substituent
on the Glutathione Peroxidase
Activity of a Pyridoxine-like Diselenide
American Chemical Society
2015
Glutathione Peroxidase Activity
substituent
ROS
kcal
seleninic acid intermediates
glutathione peroxidase enzymes
diselenide 6
MNC
Se
dipyridyl diselenide moiety
bromo
2015-08-07 00:00:00
Dataset
https://acs.figshare.com/articles/dataset/Effect_of_a_Bromo_Substituent_on_the_Glutathione_Peroxidase_Activity_of_a_Pyridoxine_like_Diselenide/2142754
In search for better mimics of the
glutathione peroxidase enzymes,
pyridoxine-like diselenides <b>6</b> and <b>11</b>, carrying
a 6-bromo substituent, were prepared. Reaction of 2,6-dibromo-3-pyridinol <b>5</b> with sodium diselenide provided <b>6</b> via aromatic
nucleophilic substitution of the 2-bromo substituent. LiAlH<sub>4</sub> caused reduction of all four ester groups and returned <b>11</b> after acidic workup. The X-ray structure of <b>6</b> showed
that the dipyridyl diselenide moiety was kept in an almost planar,
transoid conformation. According to NBO-analysis, 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 selenium was confirmed by NPA-analysis and seen in calculated
and observed <sup>77</sup>Se NMR-shifts. Diselenide <b>6</b> showed a more than 3-fold higher reactivity than the corresponding
des-bromo compound <b>3a</b> and ebselen when evaluated in the
coupled reductase assay. Experiments followed for longer time (2 h)
confirmed that diselenide <b>6</b> is a better GPx-catalyst
than <b>11</b>. On the basis of <sup>77</sup>Se-NMR experiments,
a catalytic mechanism for diselenide <b>6</b> was proposed involving
selenol, selenosulfide and seleninic acid intermediates. At low concentration
(10 μM) where it showed only minimal toxicity, it could scavenge
ROS produced by MNC- and PMNC-cells more efficiently than Trolox.