Redox chemistry of organoselenium compounds: Ab initio and density functional theory calculations on model systems for transition states and intermediates of the redox cycle of selenoenzymes

Abstract

Ab initio [Hartree-Fock (HF)] and density functional theory (B3LYP) ECPcalculations on intermediates and transition states of the reduction of phenylseleninic acid with hydrogen sulfide and of seleninic acid with benzenethiol as models for the species involved in the redox cycle of selenoenzymes are presented. Selenenyl sulfide is found to be the final product of the reduction reaction with sulfides. Further reduction to the selenol requires surmounting a substantial barrier (∼50 kcal mol −1 ). The final step of the redox cycle-oxidation of the selenol by hydrogen peroxide-is strongly exothermic. In case of the unsubstituted derivative H 2 Se three mechanisms for this oxidation are found [concerted and stepwise 1,2-hydrogen and oxygen shift (TS6A, TS6B, resp.) and a four-membered transition state TS6C]. For the oxidation of phenylselenol only TS6A and TS6B are obtained. For nearly all calculated structures the HF wave functions show a triplet instability. In contrast, at the B3LYP level only TS6C has a significant triplet instability. On the basis of QCISD(T)//QCISD results a mechanism involving TS6C seems highly unlikely.

Cyclic Acyl Disulfides and Acyl Selenylsulfides as the Precursors for Persulfides (RSSH), Selenylsulfides (RSeSH), and Hydrogen Sulfide (H2S)

“…It should be noted that the chemistry and properties of RSeSH are largely unknown in literature, except for a few theoretical studies. 8 The prerequisite of studying selenylsulfides is to have a method that can easily generate RSeSH under mild conditions. As such, we expected acyl selenylsulfides, such as benzothiaselenol-3-one 3 , to be the precursors.…”

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

“…In solution-phase, this proton exchange is affected by acid/base chemistry with the surrounding solvent which is absent in the typical gas-phase theoretical model. Attempts to directly transfer the proton from the thiol to the OH group result in four-centered transition states that are unrealistic for an aqueous-phase reaction, but reasonable for the hypothetic gas-phase reaction [26]. In many cases, strained transition states resulting from direct proton exchange processes are accompanied by large activation barriers.…”

“…The activation barrier for AB TS is only 4.6 kcal/mol above B1 P and the overall reaction is exergonic by 7.8 kcal/mol. (The transition state for the gasphase elimination of water from B by direct proton exchange has an activation barrier of 37.3 kcal/mol (DE à + ZPE(B3LYP/ LANL2DZ(d))) [26]) Therefore, the reverse reaction, adding a water to the Se@O bond (A + H 2 O ? B), is disfavored and the equilibrium lies on the A side.…”

“…Given the higher oxidation state of selenium in the seleninyl sulfides, this competition may be significant for step A2, even in the absence of intramolecular interactions. In an alternate pathway (B1 and B2 in Scheme 2) [20,26], the first thiol reacts to form the four-coordinate hypervalent Se(IV) selenurane intermediate B which is related to A by the addition of water across the Se@O bond. 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].…”

Modeling of Mechanisms of Selenium Bioactivity Using Density Functional Theory

“…The importance of providing a path for proton exchange in these steps is shown through a comparison of models of the GPx-like mechanism through direct proton transfer (65,66). In these models, strained, high-energy transition states were obtained by the requirement that the protons be transferred directly to the acceptor atom.…”