Synthesis and Glutathione Peroxidase-Like Activities of Isoselenazolines

Abstract

The aromatic nucleophilic substitution (S(N)Ar) reactions of N-(2-bromo-3-nitrobenzyl)aniline (18), N-(2-bromo-3-nitrobenzyl)-4-methylaniline (19) and N-(2-bromo-3-nitrobenzyl)-4-nitroaniline (20) with [nBuSeNa] afford N-[2-(butylselanyl)-3-nitrobenzyl]aniline (21), N-[2-(butylselanyl)-3-nitrobenzyl]-4-methylaniline (22) and N-[2-(butylselanyl)-3-nitrobenzyl]-4-nitroaniline (23), respectively. The bromination of 21 results in the formation of cyclic isoselenazolines 7-nitro-2-phenyl-2,3-dihydrobenzisoselenazole (27) and 2-(4-bromophenyl)-7-nitro-2,3-dihydrobenzisoselenazole (28). The bromination of 22 affords isoselenazolines 2-(4-methylphenyl)-7-nitro-2,3-dihydrobenzisoselenazole (29) and 2-(2-bromo-4-methylphenyl)-7-nitro-2,3-dihydrobenzisoselenazole (30) along with some other products. The bromination of 23 under identical conditions gave 2-(2-bromo-4-nitrophenyl)-7-nitro-2,3-dihydrobenzisoselenazole (31). The oxidation reaction of 21-22 with H(2)O(2) yielded isoselenazoline Se-oxides 7-nitro-2-phenyl-2,3-dihydrobenzisoselenazole 1-oxide (33) and 2-(4-methylphenyl)-7-nitro-2-phenyl-2,3-dihydrobenzisoselenazole 1-oxide (34), respectively. The new isoselenazolines and isoselenazoline Se-oxides, stabilized by intramolecular secondary Se center dot center dot center dot O interactions, have been structurally characterized by single-crystal X-ray diffraction studies and investigated by computational studies. In addition to the synthesis and characterization, the glutathione peroxidase (GPx)-like activities of isoselenazolines and isoselenazoline Se-oxides have been evaluated by coupled reductase assays.