3 research outputs found
Beyond H<sub>2</sub>S and NO Interplay: Hydrogen Sulfide and Nitroprusside React Directly to Give Nitroxyl (HNO). A New Pharmacological Source of HNO
Hydrogen sulfide (H<sub>2</sub>S) has been increasingly
recognized as an important signaling molecule that regulates both
blood pressure and neuronal activity. Attention has been drawn to
its interactions with another gasotransmitter, nitric oxide (NO).
Here, we provide evidence that the physiological effects observed
upon the application of sodium nitroprusside (SNP) and H<sub>2</sub>S can be ascribed to the generation of nitroxyl (HNO), which is a
direct product of the reaction between SNP and H<sub>2</sub>S, not
a consequence of released NO subsequently reacting with H<sub>2</sub>S. Intracellular HNO formation has been confirmed, and the subsequent
release of calcitonin gene-related peptide from a mouse heart has
been demonstrated. Unlike with other thiols, SNP reacts with H<sub>2</sub>S in the same way as rhodanese, i.e., the cyanide transforms
into a thiocyanate. These findings shed new light on how H<sub>2</sub>S is understood to interact with nitroprusside. Additionally, they
offer a new and convenient pharmacological source of HNO for therapeutic
purposes
Nitrogen Oxide Atom-Transfer Redox Chemistry; Mechanism of NO<sub>(g)</sub> to Nitrite Conversion Utilizing μ‑oxo Heme-Fe<sup>III</sup>–O–Cu<sup>II</sup>(L) Constructs
While
nitric oxide (NO, nitrogen monoxide) is a critically important
signaling agent, its cellular concentrations must be tightly controlled,
generally through its oxidative conversion to nitrite (NO<sub>2</sub><sup>–</sup>) where it is held in reserve to be reconverted
as needed. In part, this reaction is mediated by the binuclear heme
a<sub>3</sub>/Cu<sub>B</sub> active site of cytochrome <i>c</i> oxidase. In this report, the oxidation of NO<sub>(g)</sub> to nitrite
is shown to occur efficiently in new synthetic μ-oxo heme-Fe<sup>III</sup>–O–Cu<sup>II</sup>(L) constructs (L being
a tridentate or tetradentate pyridyl/alkylamino ligand), and spectroscopic
and kinetic investigations provide detailed mechanistic insights.
Two new X-ray structures of μ-oxo complexes have been determined
and compared to literature analogs. All μ-oxo complexes react
with 2 mol equiv NO<sub>(g)</sub> to give 1:1 mixtures of discrete
[(L)Cu<sup>II</sup>(NO<sub>2</sub><sup>–</sup>)]<sup>+</sup> plus ferrous heme-nitrosyl compounds; when the first NO<sub>(g)</sub> equiv reduces the heme center and itself is oxidized to nitrite,
the second equiv of NO<sub>(g)</sub> traps the ferrous heme thus formed.
For one μ-oxo heme-Fe<sup>III</sup>–O–Cu<sup>II</sup>(L) compound, the reaction with NO<sub>(g)</sub> reveals an intermediate
species (“intermediate”), formally a bis-NO adduct,
[(NO)(porphyrinate)Fe<sup>II</sup>–(NO<sub>2</sub><sup>–</sup>)–Cu<sup>II</sup>(L)]<sup>+</sup> (λ<sub>max</sub> =
433 nm), confirmed by cryo-spray ionization mass spectrometry and
EPR spectroscopy, along with the observation that cooling a 1:1 mixture
of [(L)Cu<sup>II</sup>(NO<sub>2</sub><sup>–</sup>)]<sup>+</sup> and heme-Fe<sup>II</sup>(NO) to −125 °C leads to association
and generation of the key 433 nm UV–vis feature. Kinetic-thermodynamic
parameters obtained from low-temperature stopped-flow measurements
are in excellent agreement with DFT calculations carried out which
describe the sequential addition of NO<sub>(g)</sub> to the μ-oxo
complex
Does Perthionitrite (SSNO<sup>–</sup>) Account for Sustained Bioactivity of NO? A (Bio)chemical Characterization
Hydrogen sulfide (H<sub>2</sub>S)
and nitric oxide (NO) are important signaling molecules that regulate
several physiological functions. Understanding the chemistry behind
their interplay is important for explaining these functions. The reaction
of H<sub>2</sub>S with <i>S</i>-nitrosothiols to form the
smallest <i>S</i>-nitrosothiol, thionitrous acid (HSNO),
is one example of physiologically relevant cross-talk between H<sub>2</sub>S and nitrogen species. Perthionitrite (SSNO<sup>–</sup>) has recently been considered as an important biological source
of NO that is far more stable and longer living than HSNO. In order
to experimentally address this issue here, we prepared SSNO<sup>–</sup> by two different approaches, which lead to two distinct species:
SSNO<sup>–</sup> and dithionitric acid [HON(S)S/HSN(O)S]. (H)S<sub>2</sub>NO species and their reactivity were studied by <sup>15</sup>N NMR, IR, electron paramagnetic resonance and high-resolution electrospray
ionization time-of-flight mass spectrometry, as well as by X-ray structure
analysis and cyclic voltammetry. The obtained results pointed toward
the inherent instability of SSNO<sup>–</sup> in water solutions.
SSNO<sup>–</sup> decomposed readily in the presence of light,
water, or acid, with concomitant formation of elemental sulfur and
HNO. Furthermore, SSNO<sup>−</sup> reacted with H<sub>2</sub>S to generate HSNO. Computational studies on (H)SSNO provided additional
explanations for its instability. Thus, on the basis of our data,
it seems to be less probable that SSNO<sup>–</sup> can serve
as a signaling molecule and biological source of NO. SSNO<sup>–</sup> salts could, however, be used as fast generators of HNO in water
solutions