Nitric oxide (nitrogen oxide or nitrogen monoxide) is a colorless gas with the formula NO. It is one of the principal oxides of nitrogen. Nitric oxide is a free radical, i.e., it has an unpaired electron, which is sometimes denoted by a dot in its chemical formula (·N=O or ·NO). Nitric oxide is also a heteronuclear diatomic molecule, a historic class that drew researches which spawned early modern theories of chemical bonding.
|Systematic IUPAC name|
3D model (JSmol)
CompTox Dashboard (EPA)
|Molar mass||30.006 g·mol−1|
|Melting point||−164 °C (−263 °F; 109 K)|
|Boiling point||−152 °C (−242 °F; 121 K)|
|0.0098 g / 100 ml (0 °C) |
0.0056 g / 100 ml (20 °C)
Refractive index (nD)
|linear (point group C∞v)|
Std enthalpy of
|via pulmonary capillary bed|
|Safety data sheet||External MSDS|
|R-phrases (outdated)||R8, R23, R34, R44|
|S-phrases (outdated)||(S1), S17, S23, S36/37/39, S45|
|NFPA 704 (fire diamond)|
|Lethal dose or concentration (LD, LC):|
LC50 (median concentration)
|315 ppm (rabbit, 15 min)|
854 ppm (rat, 4 h)
2500 ppm (mouse, 12 min)
LCLo (lowest published)
|320 ppm (mouse)|
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
An important intermediate in chemical industry, nitric oxide forms in combustion systems and can be generated by lightning in thunderstorms. In mammals, including humans, nitric oxide is a signaling molecule in many physiological and pathological processes. It was proclaimed the "Molecule of the Year" in 1992. The 1998 Nobel Prize in Physiology or Medicine was awarded for discovering nitric oxide's role as a cardiovascular signalling molecule.
With di- and triatomic molecules
Upon condensing to a liquid, nitric oxide dimerizes to dinitrogen dioxide, but the association is weak and reversible. The N–N distance in crystalline NO is 218 pm, nearly twice the N–O distance.
- 2 NO → O2 + N2.
- 2 NO + O2 → 2 NO2.
This conversion has been speculated as occurring via the ONOONO intermediate.
- 4 NO + O2 + 2 H2O → 4 HNO2.
- 2 NO + Cl2 → 2 NOCl.
With NO2, also a radical, NO combines to form the intensely blue dinitrogen trioxide:
- NO + NO2 ⇌ ON−NO2.
The addition of a nitric oxide moiety to another molecule is often referred to as nitrosylation. Nitric oxide reacts with acetone and an alkoxide to a diazeniumdiolate or nitrosohydroxylamine and methyl acetate:
This reaction, which was discovered around 1898, remains of interest in nitric oxide prodrug research. Nitric oxide can also react directly with sodium methoxide, forming sodium formate and nitrous oxide.
Nitric oxide reacts with transition metals to give complexes called metal nitrosyls. The most common bonding mode of nitric oxide is the terminal linear type (M−NO). Alternatively, nitric oxide can serve as a one-electron pseudohalide. In such complexes, the M−N−O group is characterized by an angle between 120° and 140°. The NO group can also bridge between metal centers through the nitrogen atom in a variety of geometries.
Production and preparation
- 4 NH3 + 5 O2 → 4 NO + 6 H2O
The uncatalyzed endothermic reaction of oxygen (O2) and nitrogen (N2), which is effected at high temperature (>2000 °C) by lightning has not been developed into a practical commercial synthesis (see Birkeland–Eyde process):
- N2 + O2 → 2 NO
- 8 HNO3 + 3 Cu → 3 Cu(NO3)2 + 4 H2O + 2 NO
- 2 NaNO2 + 2 NaI + 2 H2SO4 → I2 + 2 Na2SO4 + 2 H2O + 2 NO
- 2 NaNO2 + 2 FeSO4 + 3 H2SO4 → Fe2(SO4)3 + 2 NaHSO4 + 2 H2O + 2 NO
- 3 KNO2 + KNO3 + Cr2O3 → 2 K2CrO4 + 4 NO
The iron(II) sulfate route is simple and has been used in undergraduate laboratory experiments. So-called NONOate compounds are also used for nitric oxide generation.
Detection and assay
Nitric oxide concentration can be determined using a chemiluminescent reaction involving ozone. A sample containing nitric oxide is mixed with a large quantity of ozone. The nitric oxide reacts with the ozone to produce oxygen and nitrogen dioxide, accompanied with emission of light (chemiluminescence):
- NO + O3 → NO2 + O2 + hν
which can be measured with a photodetector. The amount of light produced is proportional to the amount of nitric oxide in the sample.
Other methods of testing include electroanalysis (amperometric approach), where ·NO reacts with an electrode to induce a current or voltage change. The detection of NO radicals in biological tissues is particularly difficult due to the short lifetime and concentration of these radicals in tissues. One of the few practical methods is spin trapping of nitric oxide with iron-dithiocarbamate complexes and subsequent detection of the mono-nitrosyl-iron complex with electron paramagnetic resonance (EPR).
Acid rain deposition
- ·NO + HO2•→ •NO2 + •OH
- ·NO2 + •OH → HNO3
- ·NO + O3 → NO2 + O2
This reaction is also utilized to measure concentrations of ·NO in control volumes.
Precursor to NO2
As seen in the Acid deposition section, nitric oxide can transform into nitrogen dioxide (this can happen with the hydroperoxy radical, HO2•, or diatomic oxygen, O2). Symptoms of short-term nitrogen dioxide exposure include nausea, dyspnea and headache. Long-term effects could include impaired immune and respiratory function.
NO is a gaseous signaling molecule. It is a key vertebrate biological messenger, playing a role in a variety of biological processes. It is a known bioproduct in almost all types of organisms, ranging from bacteria to plants, fungi, and animal cells.
Nitric oxide, known as an endothelium-derived relaxing factor (EDRF), is biosynthesized endogenously from L-arginine, oxygen, and NADPH by various nitric oxide synthase (NOS) enzymes. Reduction of inorganic nitrate may also serve to make nitric oxide. One of the main enzymatic targets of nitric oxide is guanylyl cyclase. The binding of nitric oxide to the haem region of the enzyme leads to activation, in the presence of iron. Nitric oxide is highly reactive (having a lifetime of a few seconds), yet diffuses freely across membranes. These attributes make nitric oxide ideal for a transient paracrine (between adjacent cells) and autocrine (within a single cell) signaling molecule. Once nitric oxide is converted to nitrates and nitrites by oxygen and water, cell signaling is deactivated.
The endothelium (inner lining) of blood vessels uses nitric oxide to signal the surrounding smooth muscle to relax, thus resulting in vasodilation and increasing blood flow. Sildenafil (Viagra) is a common example of a drug that uses the nitric oxide pathway. Sildenafil does not produce nitric oxide, but enhances the signals that are the downstream of the nitric oxide pathway by protecting cyclic guanosine monophosphate (cGMP) from degradation by cGMP-specific phosphodiesterase type 5 (PDE5) in the corpus cavernosum, allowing for the signal to be enhanced, and thus vasodilation. Another endogenous gaseous transmitter, hydrogen sulfide (H2S) works with NO to induce vasodilatation and angiogenesis in a cooperative manner.
Occupational safety and health
In the U.S., the Occupational Safety and Health Administration (OSHA) has set the legal limit (permissible exposure limit) for nitric oxide exposure in the workplace as 25 ppm (30 mg/m3) over an 8-hour workday. The National Institute for Occupational Safety and Health (NIOSH) has set a recommended exposure limit (REL) of 25 ppm (30 mg/m3) over an 8-hour workday. At levels of 100 ppm, nitric oxide is immediately dangerous to life and health.
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