Understanding hydrogen sulfide storage: probing conditions for sulfide release from hydrodisulfides

Abstract

Hydrogen sulfide (H2S) is an important biological signaling agent that exerts action on numerous (patho)physiological processes. Once generated, H2S can be oxidized to generate reductant-labile sulfane sulfur pools, which include hydrodisulfides/persulfides. Despite the importance of hydrodisulfides in H2S storage and signaling, little is known about the physical properties or chemical reactivity of these compounds. We report here the synthesis, isolation, and characterization (NMR, IR, Raman, HRMS, X-ray) of a small-molecule hydrodisulfide and highlight its reactivity with reductants, nucleophiles, electrophiles, acids, and bases. Our experimental results establish that hydrodisulfides release H2S upon reduction and that deprotonation results in disproportionation to the parent thiol and S(0), thus providing a mechanism for transsulfuration in the sulfane sulfur pool.

Scheme 1. Synthesis of TrtSSH

Figure 1

(a) X-ray crystal structure of TrtSSH. Thermal ellipsoids are drawn at the 50% probability level. Hydrogen atoms on the phenyl rings are omitted for clarity. Full crystallographic details are available in the Supporting Information. (b) Infrared (black) and Raman (blue) spectra of TrtSH (top) and TrtSSH (bottom). The Raman spectrum of S₈ (red) is shown for comparison.

Figure 2

(a) ¹H NMR spectra of the conversion of 18 mM TrtSSH (blue circle) to TrtSH (red circle) with 1 equiv of [NBu₄⁺][TFA^–] recorded every 60 s. (b) Addition of PPh₃ (yellow circle) in 0.5 equiv. increments at the end of the reaction shows the clean formation of Ph₃PS (green circle).

Figure 3

Reactivity of TrtSSH with acids, electrophiles (E⁺), reductants ([red]), bases, or nucleophiles (nuc).