Aromatic Derivatives and Tellurium Analogues of Cyclic Seleninate Esters and Spirodioxyselenuranes That Act as Glutathione Peroxidase Mimetics

Several novel organoselenium and tellurium compounds were prepared and evaluated as mimetics
of the selenoenzyme glutathione peroxidase, which protects cells from oxidative stress by reducing
harmful peroxides with the thiol glutathione. The compounds were tested for catalytic activity in
a model system wherein tert-butyl hydroperoxide or hydrogen peroxide were reduced with benzyl
thiol and the rate of the reaction was measured by monitoring the formation of dibenzyl disulfide.
Thus, aromatic derivatives 19, 22, 24, and 25 proved to be inferior catalysts compared to the parent
cyclic seleninate ester 14 and spirodioxyselenurane 16. In the case of 19 and 22, this was the result
of their rapid conversion to the relatively inert selenenyl sulfides 31 and 32, respectively. In general,
hydrogen peroxide was reduced faster than tert-butyl hydroperoxide in the presence of the selenium-based catalysts. The cyclic tellurinate ester 27 and spirodioxytellurane 29 proved to be superior
catalysts to their selenium analogues 14 and 16, respectively, resulting in the fastest reaction rates
by far of all of the compounds we have investigated to date. Oxidation of 29 with hydrogen peroxide
produced the unusual and unexpected peroxide 33, in which two hypervalent octahedral tellurium
moieties are joined by ether and peroxide bridges. The structure of 33 was confirmed by X-ray
crystallography. Although 33 displayed strong catalytic activity when tested independently in the
model system, its relatively slow formation from the oxidation of 29 rules out its intermediacy in
the catalytic cycle of 29.