Nitroso

Structural formula of nitroso moiety

Nitroso refers to a functional group in organic chemistry which has the NO group attached to an organic moiety. As such, various nitroso groups can be categorized as C-nitroso compounds (e.g., nitrosoalkanes; R−N=O), S-nitroso compounds (nitrosothiols; RS−N=O), N-nitroso compounds (e.g., nitrosamines, R¹N(−R²)−N=O), and O-nitroso compounds (alkyl nitrites; RO−N=O).

Nitrosyls are non-organic compounds containing the NO group, for example directly bound to the metal via the N atom, giving a metal–NO moiety. Alternatively, a nonmetal example is the common reagent nitrosyl chloride (Cl−N=O).

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

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 extreme modes: as NO⁺ and as NO⁻. It is generally assumed that 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°. However, the results of many studies have shown that the ionic descriptions of the NO ligand do not correlate with metal–NO geometry. A more realistic description of electron-counting in metal–nitrosyl chemistry is given by the Enemark–Feltham notation.

Organonitroso 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-nitrosoanilines are prepared from the corresponding nitrosamines. Another named reaction involving a nitroso compound is the Barton reaction.

Organonitroso compounds serve as a ligands for transition metals.^[2]

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 conversion occurs at acidic pH, particularly in the stomach, as shown in the equation for the formation of N-phenylnitrosamine:

  NO−
  2 + H⁺ ⇌ HONO

  HONO + H⁺ ⇌ H₂O + NO⁺

  C₆H₅NH₂ + NO⁺ → C₆H₅N(H)NO + H⁺

Many primary alkyl N-nitroso compounds, such as CH₃N(H)NO, tend to be unstable with respect to hydrolysis to the alcohol. Those derived from secondary amines (e.g., (CH₃)₂NNO derived from dimethylamine) are more robust. It is these N-nitrosamines that 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 NO−
  2 (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 NO−
  2 to form NO.^[3][4] Ascorbate and pH 5 thus favor nitrosylation of heme iron, forming nitrosylheme, 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: nitrosylheme is thus considered a benefit for the meat industry and for consumers.^[5]
• In the stomach: secreted Hydrogen Chloride 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 favor nitrosation. No nitrosamine is formed in stools, even after addition of a secondary amine or nitrite.^[6] 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^[7] 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).^[8]

See also

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

References

1. ↑ Calder, A.; Forrester, A. R.; Hepburn, S. P. "2-Methyl-2-nitrosopropane and Its Dimer". Org. Synth. 52: 77. ; Coll. Vol., 6,, p. 803 
2. ↑ Pilato, R. S.; McGettigan, C.; Geoffroy, G. L.; Rheingold, A. L.; Geib, S. J. (1990). "tert-Butylnitroso complexes. Structural characterization of W(CO)₅(N(O)Bu-tert) and [CpFe(CO)(PPh₃)(N(O)Bu-tert)]⁺". Organometallics. 9: 312–17. doi:10.1021/om00116a004. 
3. ↑ "Ascorbate–nitrite reaction: possible means of blocking the formation of carcinogenic N-nitroso compounds". Science. 177 (4043): 65–8. July 1972. Bibcode:1972Sci...177...65M. doi:10.1126/science.177.4043.65. PMID 5041776. 
4. ↑ "Effects of vitamins C and E on N-nitroso compound formation, carcinogenesis, and cancer". Cancer. 58 (8 Suppl): 1842–50. October 1986. doi:10.1002/1097-0142(19861015)58:8+<1842::aid-cncr2820581410>3.0.co;2-#. PMID 3756808. 
5. ↑ 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. 
6. ↑ "Absence of volatile nitrosamines in human feces". Cancer Res. 41 (10): 3992–4. October 1981. PMID 7285009. 
7. ↑ "Does increased endogenous formation of N-nitroso compounds in the human colon explain the association between red meat and colon cancer?". Carcinogenesis. 17 (3): 515–23. March 1996. doi:10.1093/carcin/17.3.515. PMID 8631138. 
8. ↑ "Diet-induced endogenous formation of nitroso compounds in the GI tract". Free Radic. Biol. Med. 43 (7): 1040–7. October 2007. doi:10.1016/j.freeradbiomed.2007.03.011. PMID 17761300.