Stable Selenenium Cations: Unusual Reactivity and Excellent Glutathione Peroxidase-Like Activity

The syntheses of the three selenenium cations 17-19 derived from N-[n-butyl-(3-nitrobenzylimino)]phenyl selenide (14) are described. Precursor 14 was synthesized by treating N(2-bromo-3-nitrobenzylimino)benzene (12) with in situ generated nBuSeNa. The selenenium cation 17 with chloride as counteranion was isolated when 14 was treated with sulfuryl chloride (SO2Cl2) in the presence of triethylamine (Et3N). The selenenium cations with bromide (18) and tribromide (19) as counteranions, were synthesized by treating 14 with Br-2 in the presence of Et3N. Reaction of 19 with thiophenol afforded two unexpected products: the cyclic diselenide 20 and the bicyclic selenide 21. Oxidation of 18 with hydrogen peroxide afforded the ebselen derivative, 2-(4-bromophenyl)-7-nitro-1,2-benzisoselenazol(2H)-3-one Se-oxide (22). The presence of nonbonding Se center dot center dot center dot O/Se-N intramolecular interactions in 18 and 19 have been confirmed by single-crystal X-ray studies. Glutathione peroxidase-like antioxidant activities of 17-19 and related compounds have been determined by the coupled reductase assay. It is proved that the high GPx-like activities of cations involve the formation of corresponding intermediate selenoxide in the catalytic cycle. The isolated selenoxide 22 shows the highest GPx-like activity among the series of compounds. The compounds have been further investigated by density functional theory calculations at the B3LYP level of theory using the 6-31+G(d) basis set to identify nonbonding Se center dot center dot center dot O/N interactions. The second perturbation energy was obtained through natural bond orbital (NBO) analysis and NBO charges were calculated to ascertain the positive charge at the selenium atom. Nucleus-independent chemical shifts (NICS) calculations have also been carried out.