Polysulfide-1-oxides react with peroxyl radicals as quickly as hindered phenolic antioxidants and do so by a surprising concerted homolytic substitution

Abstract

Polysulfides, important industrial additives and curious natural products, are activated toward substitution by peroxyl radicals upon oxidation to polysulfide-1-oxides.

The chemical biology of the persulfide (RSSH)/perthiyl (RSS·) redox couple and possible role in biological redox signaling

“…Consistent with our results, a recent report from the Pratt lab also finds that perthiyl radical species do not react with O 2 [46]. In this study, photochemically induced homolysis of a tetrasulfide, RSSSSR, transiently generates RSS· (monitored by the absorbance at 375 nm), which then rapidly recombines back to the tetrasulfide (k = 6 x 10 9 M −1 s −1 ).…”

Inspired by garlic: insights on the chemistry of sulfenic acids and the radical-trapping antioxidant activity of organosulfur compounds

“…While further computational investigations failed to identify a radical addition pathway for this reaction, a low energy path for a concerted homolytic substitution (SH 2 ) on the oxidized sulfur atom of the trisulfide-1-oxide to form a peroxysulfinate ester and a perthiyl radical could be readily identified ( Figure 7). 40 Gratifyingly, the barrier for this process (∆G ‡ = 15.1 kcal/mol by CBS-QB3) was fully consistent with the observed kinetics. It seems reasonable to suggest that the peroxysulfinate ester formed will rearrange to a sulfonate ester, while the perthiyl radical likely reacts with O2 to liberate SO2 and produce a thiyl radical, 41 for an overall stoichiometry of 1 -also in agreement with experimental observations.…”

“…40 Moreover, kinetic isotope effects determined for the reactions of di(α,α-dideuteriobenzyl)trisulfide-1-oxide with peroxyl radicals (kH/kD = 1-2) 40 were much smaller than those obtained from D r a f t experiments with the corresponding deuterated petivericin analog (kH/kD = 18.4). 23 The lack of requirement for activated H-atoms in the reactivity of trisulfide-1-oxides became unequivocal when a similar rate constant was determined for the reaction of di-tert-butyl trisulfide-1-oxide with peroxyl radicals (kinh = 1.0×10 4 M -1 s -1 ).…”

“…40 In comparison, dibenzyl trisulfide (like dibenzyl disulfide) reacted very slowly with peroxyl radicals. 40 So, as was true for the disulfides and their corresponding thiosulfinates, introduction of a single oxygen atom on the trisulfide to give a trisulfide-1-oxide increases its reactivity with peroxyl radicals dramatically.…”

“…23 The lack of requirement for activated H-atoms in the reactivity of trisulfide-1-oxides became unequivocal when a similar rate constant was determined for the reaction of di-tert-butyl trisulfide-1-oxide with peroxyl radicals (kinh = 1.0×10 4 M -1 s -1 ). 40 Clearly, another mechanism must exist -and if not H-atom transfer to a peroxyl radical, it must be a radical addition and/or substitution. While further computational investigations failed to identify a radical addition pathway for this reaction, a low energy path for a concerted homolytic substitution (SH 2 ) on the oxidized sulfur atom of the trisulfide-1-oxide to form a peroxysulfinate ester and a perthiyl radical could be readily identified ( Figure 7).…”