Evaluation of peri-like fluorene and carbazole diselenides as glutathione peroxidase mimics

This thesis reports the synthesis and evaluation of 4, 5-disubstituted fluorene and carbazole diselenides as GPx mimics. Chapter 1 describes the role of glutathione peroxidase as an important mammalian antioxidant and investigations towards developing organoselenium molecules as glutathione peroxidase mimics. Chapter 2 describes the preparation of 4,5-disubstituted fluorene diselenides via a dilithiation reaction, as well as the oxidation of these diselenides using mCPBA to monoxides and seleninic anhydrides. A DTT oxidation assay with these compounds showed that the fluorene diselenides have similar activity to the 1,8-naphthalene diselenides developed by Back. Studies have shown that the selenic anhydrides act as precatalysts in the reaction. Chapter 3 reports the elaboration of carbazoles into diselenides via regioselective 4,5-dilithiation. This transformation is made possible by protecting the carbazole with a TIPS protecting group. Further elaboration of the carbazole scaffold gave compounds that were water-soluble. Additionally, two fluorene diselenides were made water-soluble. A waterbased NMR assay were used to determine the catalytic activity of the water-soluble species

Glutathione peroxidase mimics based on conformationally-restricted, peri-like, 4,5-disubstituted fluorene dichalcogenides

International audienceGlutathione peroxidase (GPx) regulates cellular peroxide levels through glutathione oxidation. GPx-mimics based on 4,5-disubstituted fluorene diselenides, their oxides, and ditellurides show catalytic activities consistent with conformational restriction about the dichalcogen bond