Nitroso

Wire-frame model of nitroso moiety

Nitroso refers to a functional group in organic chemistry which has the general formula RNO. Nitroso compounds are a class of organic compounds containing the nitroso functional group, R−N=O.

Nitrosyls are molecules with the general formula RNO, where R represents an unspecified substituent.

Nitroso and bent Nitrosyl are synonyms; nitroso is used in organic chemistry, while bent nitrosyl is used in inorganic chemistry. Neither Nitroso nor bent Nitrosyl are identical to linear Nitrosil, which possesses sp hybridization. A common example of a nitroso compound is nitrosyl chloride, NOCl (although its structure is better represented ONCl).

Nitrosyl also refers to the discrete molecule nitric oxide, NO. Nitric oxide is a stable radical, having an unpaired electron.

Reduction of nitric oxide gives the hyponitrite anion, NO⁻:

NO + e⁻ → NO⁻

Oxidation of NO yields the nitrosonium cation, NO⁺:

NO → NO⁺ + e⁻

Nitrosyl as a ligand

Linear and bent metal nitrosyls

Main article: Metal nitrosyl

Nitric oxide can serve as a ligand in complexes. The resulting complexes are called metal nitrosyls, and can bond to a metal atom in two distinct modes: as NO⁺ and as NO⁻. NO⁺ coordinates linearly, the M−N−O angle being 180°, whereas NO⁻ forms a bent geometry, with an M−N−O angle of approximately 120°.

Nitroso compounds

Nitroso compounds can be prepared by the reduction of nitro compounds or by the oxidation of hydroxylamines. A good example is (CH₃)₃CNO, known formally as 2-methyl-2-nitrosopropane, or t-BuNO, which is prepared by the following sequence:^[1]

(CH₃)₃CNH₂ → (CH₃)₃CNO₂

(CH₃)₃CNO₂ → (CH₃)₃CNHOH

(CH₃)₃CNHOH → (CH₃)₃CNO

(CH₃)₃CNO is blue and exists in solution in equilibrium with its dimer, which is colorless, m.p. 80–81 °C.

In the Fischer-Hepp rearrangement aromatic 4-nitroso-anilines are prepared from the corresponding nitrosamines. Another named reaction involving a nitroso compound is the Barton reaction.

Nitrosation vs. nitrosylation

Nitrite can enter two kinds of reaction, depending on the physico-chemical environment.

• Nitrosylation is adding a nitrosyl ion NO⁻ to a metal (e.g. iron) or a thiol, leading to nitrosyl iron Fe-NO (e.g., in nitrosylated heme = nitrosylheme) or S-nitrosothiols (RSNOs).
• Nitrosation is adding a nitrosonium ion NO⁺ to an amine -NH₂ leading to a nitrosamine. This occurs at acidic pH, particularly in the stomach, as shown in the figure below. Primary amines R-NH₂ lead to unstable nitrosamines (that turn to alcool), but secondary amines R1-NH-R2 lead to stable nitrosamines, most of which are carcinogens in rodents.

In food

Nitrosyl-heme

In foodstuffs and in the gastro-intestinal tract, nitrosation and nitrosylation do not have the same consequences on consumer health.

• In cured meat: Meat processed by curing contains nitrite and has a pH of 5 approximately, where almost all nitrite is present as NO₂⁻ (99%). Cured meat is also added with sodium ascorbate (or erythorbate or Vitamin C). As demonstrated by S. Mirvish, ascorbate inhibits nitrosation of amines to nitrosamine, because ascorbate reacts with NO₂⁻ to form NO.^[2][3] Ascorbate and pH 5 thus favor nitrosylation of heme iron, forming nitrosyl-heme, a red pigment when included inside myoglobin, and a pink pigment when it has been released by cooking. It participates to the "bacon flavor" of cured meat: nitrosyl-heme is thus considered a benefit for the meat industry and for consumers.^[4]

• In the stomach: secreted HCl makes an acidic environment (pH=2) and ingested nitrite (with food or saliva) leads to nitrosation of amines, that yields nitrosamines (potential carcinogens). Nitrosation is low if amine concentration is low (e.g., low-protein diet, no fermented food) or if Vitamin C concentration is high (e.g., high fruit diet). Then S-nitrosothiols are formed, that are stable at pH 2.

• In the colon: neutral pH does not favour nitrosation. No nitrosamine is formed in stools, even after addition of a secondary amine or nitrite.^[5] Neutral pH favors NO⁻ release from S-nitrosothiols, and nitrosylation of iron. The previously called NOC (N-nitroso compounds) measured by Bingham's team in stools from red meat-fed volunteers^[6] were, according to Bingham and Kuhnle, largely non-N-nitroso ATNC (Apparent Total Nitroso Compounds), e.g., S-nitrosothiols and nitrosyl iron (as nitrosyl heme).^[7]

See also

• Nitrosamine, the functional group with the NO attached to an amine, such as R₂N-NO
• Nitrosobenzene
• Nitric oxide
• Nitroxyl

References

1. ^ A. Calder, A. R. Forrester, and S. P. Hepburn 2-Methyl-2-nitrosopropane and Its Dimer Organic Syntheses, Coll. Vol. 6, p.803; Vol. 52, p.77. Link
2. ^ PMID 5041776
3. ^ PMID 3756808
4. ^ Honikel, K.O., 2008, "The use an control of nitrate and nitrite for the processing of meat products", Meat Science, 78, 68-76. doi 10.1016/j.meatsci.2007.05.030
5. ^ PMID 7285009
6. ^ PMID 8631138
7. ^ PMID 17761300