Synthesis of Cyclic Selenenate/Seleninate Esters Stabilized by ortho-Nitro Coordination: Their Glutathione Peroxidase-Like Activities

The syntheses of selenenate/seleninate esters and related derivatives by aromatic nucleophilic substitution (S(N)Ar) reactions of 2-bromo-3-nitrobenzylalcohol (13) and 2-bromo-3-nitrobenzaldehyde (17) with Na(2)Se(2)/nBuSeNa are described. The reaction of 13 with Na(2)Se(2) at room temperature afforded 7-nitro-1,2-benzisoselenole(3H) (15) instead of the desired diaryl diselenide 14. Oxidation of selenenate ester 15 with hydrogen peroxide afforded the corresponding selenium(IV) derivative, 7-nitro-1,2-benzisoselenole(3H) selenium oxide (18). 2-(Butylselanyl)-3-nitrobenzaldehyde (19) was synthesized by treating compound 17 with in situ generated nBuSeNa. The bromination reaction of selenide 19 did not afford the expected arylselenenyl bromide 20, instead, it resulted in the formation of the unexpected 7-nitro-1,2- benzisoselenol(3 H)-3-ol (21) and 3,3'-oxybis(7-nitro-1,2- benzisoselenole(3H)) (22), respectively. The facile formation of heterocycles 21 and 22 is rationalized in terms of the aromatic ring strain in selenenyl bromide 20. The presence of intramolecular secondary Se center dot center dot center dot O interactions in esters 15, 18, 21, 22, and selenenic anhydride 29 has been confirmed by single-crystal X-ray diffraction studies as well as computational studies. The presence of an intramolecular Se center dot center dot center dot O interaction in esters 4b,8, 15, 18, 21, and 22 has been further proved by natural bond orbital (NBO) and atoms in molecules (AIM) calculations. Glutathione peroxidase-like (GPx) antioxidant activities of 15, 18, 21, 22, and related heterocycles such as 7-nitro-1,2-benzisoselenol(2H)3-one selenium oxide (4b), 7-nitro-1,2benzisoselenol(2 H)-3-one (8), and 29 have been determined by the coupled reductase assay