Isolation of Unusual N-Thiophenyl Ebselenamines and other Intermediates during the 77Se NMR Mechanistic Study of Azo-Bis-Ebselen: Their Antioxidant Behaviour against Oxidative Stress

Based on the traditional 77Se NMR spectroscopy investigation, a catalytic cycle for the formation of N-thiophenyl ebselenamine 12 involving diselenide 9, selenenyl sulfide 10 and ebselenamine 7a was reported by the reaction of azo-bis-ebselen 8 with PhSH and H2O2. The signals detected in the 77Se NMR spectrum corresponding to 7a, 10 and 12 were directly isolated from the NMR mixture. Mechanistic investigation for the formation of N-thiophenyl ebselenamine 12 was confirmed from an independent reaction of diselenide 9 and PhSSPh in the presence of H2O2. This was further supported by another diselenide 19 containing p-tolyl group with equimolar amount of H2O2 and PhSH in an independent experiment followed by the 77Se NMR spectroscopy, yielding similar observations. These results, which illustrated diselenide has been observed as the main precursor in the formation of all intermediates. The new novel selenium antioxidants quenched lipidperoxyl radicals much more efficiently than α-tocopherol and were regenerable by the aqueous ascorbic acid in a two-phase (chlorobenzene/water) azo-initiated peroxidation system. The notable benefit of the organoselenium biology, the novel ebselenamine analogues and their corresponding selenenyl sulfides were found to mimic the activity of the glutathione peroxidase enzymes better than ebselen in the coupled reductase assay.