Abstract
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.
Highlights
Spirodiazaselenuranes have attracted considerable attention because of their interesting structural and stereochemical properties [1,2,3,4,5]
In 2004, Back and co-workers showed for the first time that spirodioxyselenurane 4 and its tellurium analogue 5 exhibit very good antioxidant activity by mimicking the glutathione peroxidase (GPx) enzyme [12], which protects the organism from oxidative damage by catalyzing the reduction of peroxides using thiol as the cofactor [13,14]
The heterocyclic pyridine substituted selenides (16–18) and spirodiazaselenuranes (30–32) were found to be excellent GPx mimics and effective inhibitors for the PN-mediated nitration and oxidation reactions. This strongly indicates that the stability of the Se-N bonds in the spiro compounds and the antioxidant activity of diaryl selenides and spirodiazaselenuranes are greatly influenced by the heterocylic substituents present at the nitrogen atoms
Summary
Spirodiazaselenuranes have attracted considerable attention because of their interesting structural and stereochemical properties [1,2,3,4,5]. Our group reported a stable spirodiazaselenurane and its tellurium analogue obtained by substituting the hydrogen of the amide moiety with a phenyl substituent [21]. Our previous study by substituting the hydrogen atom on the phenyl group with different electron donating and electron withdrawing atoms or groups showed that the electron donating substituents generally enhance the stability of the Se-N bonds and their antioxidant activity [22]. Selenurane oxides with two oxygen atoms at the axial positions are known, such compounds with two nitrogen atoms bonded to selenium are still unknown. In this regard, the stable selenurane oxide reported in this paper is novel. We report on the GPx-like activity and peroxynitrite scavenging activity of new compounds
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