Stable selenenium cations: unusual reactivity and excellent glutathione peroxidase-like activity

Abstract

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 Br₂ 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···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···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.