Identification of Key Intermediates during the NO and H₂S Crosstalk Signaling Pathways

Abstract

The stable isomers and electronic states of [S,S,N,O] species are investigated with a special focus on the most relevant isomers that could be involved in the NO/HS cross-talk pathways in biological media. This work identifies eight stable anions, among which are the already known cis-SSNO and trans-SSNO molecules and a new NO-like anionic species, NSO. Our computations show that the previously determined structure in lab experiment is trans-SSNO, which is not relevant for biological activity in vivo. Instead, NSO is proposed as the most likely key intermediate in vivo during important biological processes. This result alleviates the corresponding controversy in the literature.

NO/H2S “Crosstalk” Reactions. The Role of Thionitrites (SNO–) and Perthionitrites (SSNO–)

“…There are several reports on the experimental and computational structures of the SSNO − anion, and we summarize them in Table 2. 19,23,24,41,54 The isomer stabilities and electronic states of different [S,S,N,O] − species have been recently published through gas-phase calculations, searching on the identification of signaling pathways during the NO/H 2 S crosstalk. 54 A main conclusion was that the NS 2 O − isomer is the most stable species relevant to biochemistry; on the other hand, we found cis-SSNO − to be the most stable aqueous species.…”

Rational Design of a Dual‐Reactivity‐Based Fluorescent Probe for Visualizing Intracellular HSNO

“…However, they require the assistance of a specific thiol or transporter . Recently, thionitrous acid (HSNO), the smallest RSNO, has received particular attention as a possible H 2 S‐derived signaling molecule . Evidence suggest that HSNO is a potential key intermediate in cellular redox regulation linking H 2 S and NO.…”

“…Meanwhile, these studies raise interesting questions regarding the formation of HSNO. It has recently been proposed that HSNO is formed through the reaction H 2 S with RSNOs or NO . Thus the role of H 2 S in modulating intracellular RSNO or NO may be related to HSNO generation.…”

Rational Design of a Dual‐Reactivity‐Based Fluorescent Probe for Visualizing Intracellular HSNO

“…[4,5] Recently,t hionitrous acid (HSNO), the smallest RSNO,h as received particular attention as ap ossible H 2 S-derived signaling molecule. [6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22] Evidence suggest that HSNO is apotential key intermediate in cellular redox regulation linking H 2 Sand NO.Unlike larger RSNOs, HSNO is believed to be able to freely diffuse through membranes to reach its intracellular targets so to facilitate transnitrosation of proteins. [6] Thef acile diffusion ability of HSNO could be conducive to understanding the regulated mechanisms for RSNO formation and the process of signaling propagation.…”

“…Meanwhile,these studies raise interesting questions regarding the formation of HSNO.Ithas recently been proposed that HSNO is formed through the reaction H 2 Swith RSNOs or NO. [6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23] Thus the role of H 2 Si nm odulating intracellular RSNO or NO may be related to HSNO generation. In addition, the formation of HSNO may further produce SSNO À [18][19][20][21][22] and this topic remains controversial.…”