Substituent Effects on the Stability and Antioxidant Activity of Spirodiazaselenuranes

Spirodiazaselenuranes are structurally interesting compounds and the stability of these compounds depends highly on the nature of the substituents attached to the nitrogen atoms. Aromatic substituents are known to play important roles in stabilizing the Se-N bonds in spiro compounds. In this study, several spirodiazaselenuranes are synthesized by introducing benzylic and aliphatic substituents to understand their effect on the stability of the Se-N bonds and the antioxidant activity. Replacement of phenyl substituent by benzyl/alkyl groups significantly reduces the stability of the spirodiazaselenuranes and slows down the oxidative cyclization process. The selenium centre in the spiro compounds undergoes further oxidation to produce the corresponding selenurane oxides, which are stable at room temperature. Comparison of the glutathione peroxidase (GPx) mimetic activity of the compounds showed that the diaryl selenides having heterocyclic rings are significantly more active due to the facile oxidation of the selenium centre. However, the activity is reduced significantly for compounds having aliphatic substituents. In addition to GPx activity, the compounds also inhibit peroxynitrite-mediated nitration and oxidation reaction of protein and small molecules, respectively. The experimental observations suggest that the antioxidant activity is increased considerably upon substitution of the aromatic group with the benzylic/aliphatic substituents on the nitrogen atoms.