Hydropersulfides (RSSH) are formed endogenously via the reaction of the gaseous biotransmitter hydrogen sulfide (H2S) and disulfides (RSSR) and/or sulfenic acids (RSOH). RSSH have been investigated for their ability to store H2S in vivo and as a line of defense against oxidative stress, from which it is clear that RSSH are much more reactive to two-electron oxidants than thiols. Herein we describe the results of our investigations into the H-atom transfer chemistry of RSSH, contrasting it with the well-known H-atom transfer chemistry of thiols. In fact, RSSH are excellent H-atom donors to alkyl (k similar to 5 X 10(8) alkoxyl (k similar to 1 X 10(9) M-1 s(-1)), peroxyl (k similar to 2 X 10(6) M-1 s(-1)), alkoxyl (k similar to 1 x 10(10) s(-1)) radicals, besting thiols by as little as 1 order and as much as 4 orders of magnitude. The inherently high reactivity of RSSH to H-atom transfer is based largely on thermodynamic factors; the weak RSS H bond dissociation enthalpy (-70 kcal/mol) and the associated high stability of the perthiyl radical make the foregoing reactions exothermic by 15-34 kcal/ mol. Of particular relevance in the context of oxidative stress is the reactivity of RSSH to peroxyl radicals, where favorable thermodynamics are bolstered by a secondary orbital interaction in the transition state of the formal H-atom transfer that drives the inherent reactivity of RSSH to match that of alpha-tocopherol (alpha-TOH), nature's premier radical-trapping antioxidant. Significantly, the reactivity of RSSH eclipses that of alpha-TOH in H-bond-accepting media because of their low H-bond acidity (a/21 0.1). This affords RSSH a unique versatility compared to other highly reactive radical-trapping antioxidants (e.g., phenols, diarylamines, hydroxylamines, sulfenic acids), which tend to have high H-bond acidities. Moreover, the perthiyl radicals that result are highly persistent under autoxidation conditions and undergo very rapid dimerization (k = 5 x 10(9) M-1 s(-1)) in lieu of reacting with O-2 or autoxidizable substrates.