Experimental and theoretical evidence for cyclic selenurane formation during selenomethionine oxidation

Abstract

The oxidation products of selenomethionine (SeMet) have been studied via experimental (77)Se NMR and theoretical (77)Se chemical shifts. Four signals are observed: a diastereomeric pair of selenoxides at 840 ppm and two unidentified resonances at 703 and 716 ppm. Theoretical DeltaG and chemical shifts suggest the 703 and 716 ppm resonances correspond to hypervalent selenium heterocycles, called selenuranes, formed by reaction with the amine or acid group of the amino acid and the selenoxide. To identify which of these selenuranes is formed, the amine and acid groups were individually protected. The N-formyl SeMet formed only the selenoxide pair at 840 ppm. The oxidized SeMet methyl ester produced signals at 703 and 716 ppm which are assigned as the Se-N selenurane.

Model mechanisms of sulfhydryl oxidation by methyl- and benzeneseleninic acid, inhibitors of zinc-finger transcription factors

“…These results are consistent with the assignment of the intermediate as the seleninyl sulfide A by Kice and Lee [20] who noted that selenoxides are known to strongly associate with water, but do not form the hydrate [58]. Whereas our DFT analysis [31] of the oxidation of selenomethionine showed that hydrate formation is highly endothermic (28 kcal/ mol), the DG for interconversion of A and B is much lower (<10 kcal/mol), suggesting that the intermediate may be the selenurane under certain conditions. Scheme 3.…”

“…In terms of the pH-dependence observed by Kice and Lee [20], these observations may suggest that path A1 or the seleninyl sulfide product is favored under basic conditions whereas the selenurane intermediate is preferred under acidic conditions. This conclusion is consistent with the occurrence of a selenurane in equilibrium with the selenoxide of SeMet, observed experimentally by our research group [31].…”

“…Similar 'hydrates' have been proposed for selenoxides, but none have been directly observed, although the related spiro selenuranes are have been synthesized by Back et al [27]. Asymmetric selenuranes have been obtained for constrained selenoxides [28][29][30], and recent experimental and theoretical evidence points to the formation of an Se-N selenurane for the selenoxide of selenomethionine [31]. In addition, a selenurane intermediate analogous to B has been proposed as an intermediate in one of the proposed mechanisms for scavenging of reactive oxygen species by ebselen [32].…”

Synthesis and characterization ofSe-adenosyl-L-selenohomocysteine selenoxide

“…[28-30] The selenium analog of methionine ( 4 , X = Se) is also easily oxidized with biological oxidants such as hydrogen peroxide to give a mixture of selenoxide 7 (X = Se) and hydrate in the neutral pH range. [28,31,32] NMR data is pH dependent, and only single compounds are seen at low pH[28,33] and at high pH. [28,32] These data are consistent with studies of other selenoxides.…”

Modeling of Mechanisms of Selenium Bioactivity Using Density Functional Theory

“…They identified the intermediate as either a seleninyl sulfide (A) or a hypervalent selenurane (B) resulting from reaction of the first equivalent of thiol with seleninic acid (Scheme 4). Selenuranes such as B have been proposed as intermediates in ROS scavenging by several organoselenium compounds (79)(80)(81). The second step consisted of the conversion of the intermediate to the selenenic acid, which is rapidly converted to the selenenyl sulfide.…”