Nitrosodisulfide [S₂NO]^- (Perthionitrite) is a True Intermediate during the "Cross-Talk"; of Nitrosyl and Sulfide

NO and H₂S are endogenously produced in humans and show multiple actions relevant to animal and plant physiology. Both gases often exert similar and, in part, interdependent biological actions within the same model system resulting in either mutual attenuation or potentiation responses, the so-called NO/H₂S “cross-talk”. New biological mediators might be involved, and attention is being directed to some early-described N-S hybrid species such as thionitrous acid (HSNO) and thionitrites NOS⁻, as well as to nitrosodisulfide S₂NO⁻ (perthionitrite), the sulfur analog of peroxynitrite.

The reactions of H₂S with low-molecular weight and/or protein S-nitrosothiols might afford a new scenario for the modulation of the S-nitrosothiol profile in the cells. It is currently accepted that HSNO can be initially formed via the transnitrosation of S-nitrosothiols RSNO with H₂S. This mechanism shows an intermediate (I_yellow) with a growing UV-vis absorption band centered at 412 nm.¹ I_yellow attained its maximum absorbance in ~1 min, and was moderately stable for ~1 h, revealing a slow decay. This initial UV-vis display does not match with HSNO, given that HSNO absorb at ~330 nm.^1,2 A high subsequent reactivity of HSNO leading to I_yellow has been invoked for explaining this fact, and two species have been proposed for identifying I_yellow, namely polysulfides HS_n⁻ (n = 2-7)¹ or perthionitrite, S₂NO⁻,^2,3 via the transnitrosation process as follows:

HSNO+HS₂⁻⇌S₂NO⁻+HS⁻+H⁺ (1)

In this contribution, we performed QM-MM molecular dynamics free energy profile determinations, combined with a TD-DFT analysis, in order to contribute to a clear identification of S₂NO^– in different solvents, accounting for the UV-Vis signatures and broadening the mechanistic picture of N/S signaling in biochemistry. Our results strongly support the early formation and survival of the S₂NO^– intermediate in the aqueous solutions, arising from the reaction between HSNO and HS₂^–.

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