Nitro‑, Azo‑, and Amino Derivatives of Ebselen: Synthesis, Structure, and Cytoprotective Effects

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···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 77Se 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 μM.