Novel Water-Soluble Diorganyl Tellurides with Thiol Peroxidase and Antioxidant Activity.
Novel water-soluble diaryl tellurides, alkyl aryl tellurides, and dialkyl tellurides carrying sulfopropyl groups were prepared and found to possess potent peroxide decomposing and chain-breaking antioxidative capacity. The dilithium, disodium, dipotassium, and bis-tetramethylammonium salts of bis(4-hydroxyphenyl) telluride (4) were treated with 2.3 equiv of 1,3-propanesultone in aqueous tert-butyl alcohol to give the corresponding salts 5 of bis-O-sulfopropylated diaryl telluride. A variety of diaryl ditellurides were reduced with sodium borohydride in ethanol. Upon addition of propanesultone to the resulting sodium arenetellurolates, the corresponding 3-aryltellurenylpropanesulfonic acid sodium salts 8 were precipitated. Diphenyl diselenide and dibutyl ditelluride reacted similarly to afford the sodium salts of 3-benzeneselenenylpropanesulfonic acid (9) and 4-telluraoctanesulfonic acid (10), respectively. The glutathione peroxidase-like activity of the water-soluble compounds was assessed at pH = 7.4 by using the coupled GSSG reductase assay. Dialkyl telluride 10 turned out to be the most efficient catalyst. Several alkyl aryl tellurides 8 were also more efficient than any of the previously tested organotellurium compounds in this model. Bulky and electron-withdrawing aryl substituents seemed to reduce activity, whereas electron-donating groups enhanced it. Alkyl aryl selenide 9 was void of any catalytic activity. The novel compounds were also assessed by (1)H NMR spectroscopy for their capacity to catalyze the hydrogen peroxide oxidation of N-acetylcysteine in D(2)O under acidic conditions. In the presence of 0.01 mol % of the organotellurium catalyst, the thiol concentration was reduced to 50% within 12 min for the most active catalyst (compound 5b). Although many of the compounds showed high catalytic activity, it was not possible to rationalize their relative efficiency. The capacity of the novel organotellurium compounds to act as a scavengers of 1,1-diphenyl-2-picrylhydrazyl (DPPH) was also investigated. The organotelluriums seem to act primarily as electron donors in their reaction with DPPH. Compounds 8d, 10, and 8b were the most effective scavengers. Bulky or electron-withdrawing aryl substituents caused a reduction in activity, whereas electron-donating ones enhanced it. None of the compounds could match vitamin E in their scavanging capacity.
Kanda
Takahiro
T
Uppsala University, Institute of Chemistry, Department of Organic Chemistry, Box 531, S-751 21 Uppsala, Sweden, Division of Biochemical Toxicology, Institute of Environmental Medicine, Karolinska Institute, Box 210, S-171 77 Stockholm, Sweden, and Arizona Cancer Center, University of Arizona, Tucson, Arizona 85724-5024.
Engman
Lars
L
Cotgreave
Ian A.
IA
Powis
Garth
G