Thionitrous acid (HSNO), a potential key intermediate in biological signaling pathways, has been proposed to link NO and H 2 S biochemistries, but its existence and stability in vivo remains controversial. We establish that HSNO is spontaneously formed in high concentration when NO and H 2 S gases are mixed at room temperature in the presence of metallic surfaces. Our measurements reveal that HSNO is formed by the reaction H 2 S + N 2 O 3 → HSNO + HNO 2 , where N 2 O 3 is a product of NO disproportionation. These studies also suggest that further reaction of HSNO with H 2 S may form HNO and HSSH. The length of the SN bond has been derived to high precision, and is found to be unusually long: 1.84 Å the longest SN bond reported to date for an R-SNO compound. The present structural and, particularly, reactivity investigations of this elusive molecule provide a rm foundation to better understand its potential physiological chemistry and propensity to undergo SN bond clevage in vivo.The intriguing similarities between the biological proles of NO and H 2 S, two important gasotransmitters acting notably as blood pressure mediators, have raised questions about the possibility of`cross-talk' between the two species.
1Such an interaction could explain the surprisingly benecial eects of these signaling molecules as it may allow H 2 S to modulate the availability of NO within the body.2 The vast majority of NO in vivo is bound as S-nitrosothiols (RSNO), a family of molecules well known for their crucial role in response to oxygen deprivation 35 as well as for being important biological reservoir for NO. 6,7 RSNOs are typically formed through the reaction of nitrosylating agents with thiols (RSH), 8 Once formed, RSNOs can also act as nitrosylating agents thus highlighting their role as NO shuttles at the cellular level.The simplest RSNO, thionitrous acid (HSNO), has been proposed to be the product of the reaction between NO and H 2 S; 9 other possible species have been implicated in this cross-talk', including nitrosopersulde (SSNO − ) and Nnitrosohydroxylamine-N -sulfonate.10 Unlike larger RSNOs, HSNO is thought to be able to freely diuse through cell membranes 2 suggesting that it has the ability to transnitrosate proteins removed from the sites where NO is synthesized, and therefore could play a key role in cellular redox regulation.11 Understanding the role of small molecules such as NO and HNO in biological signal transduction has resulted in important advances in medicine. 12,13 To shed light on the role of HSNO in vivo, sensors are currently being developed to image this elusive molecule. However, the biochemistry (formation, transport, decomposition) of HSNO remains poorly understood and the structure of the molecule has not been determined to date. HSNO has been spectroscopically characterized by infrared measurements in low temperature argon matrices.14,15 The molecule was produced from photolysis of HNSO, a low-lying stable structural isomer of HSNO (∆H ≥ 10 kcal/mol, 16 see Supplementary Information). ...
