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Nitrosamides are
In the organism, the decomposition of ''N''-nitroso ureas with a higher degree of substitution can proceed. An alternative possible formation of diazonium and carbenium ions is through the enzymatic reaction of nitrosamines.
Typical accompanying symptoms during the medical cancer treatment via ''N''-nitroso ureas are the impairment of
chemical compound
A chemical compound is a chemical substance composed of many identical molecules (or molecular entities) containing atoms from more than one chemical element held together by chemical bonds. A molecule consisting of atoms of only one element ...
s that contain of the chemical structure
A chemical structure determination includes a chemist's specifying the molecular geometry and, when feasible and necessary, the electronic structure of the target molecule or other solid. Molecular geometry refers to the spatial arrangement of ...
R1C(=X)N(–R2)–N=O, that is, a nitroso
In organic chemistry, nitroso refers to a functional group in which the nitric oxide () group is attached to an organic moiety (chemistry), moiety. As such, various nitroso groups can be categorized as ''C''-nitroso compounds (e.g., nitrosoalkane ...
group bonded to the nitrogen of an amide
In organic chemistry, an amide, also known as an organic amide or a carboxamide, is a compound with the general formula , where R, R', and R″ represent organic groups or hydrogen atoms. The amide group is called a peptide bond when it i ...
or similar functional group
In organic chemistry, a functional group is a substituent or moiety in a molecule that causes the molecule's characteristic chemical reactions. The same functional group will undergo the same or similar chemical reactions regardless of the r ...
.Hans Marquardt, Siegfried G. Schäfer (Hrsg.): ''Lehrbuch der Toxikologie.'' 2. Auflage, Wissenschaftliche Verlagsgesellschaft mbH Stuttgart, 2004, , S. 747. Specific classes include the ''N''-nitrosamides, ''N''-nitrosourea
Urea, also known as carbamide, is an organic compound with chemical formula . This amide has two amino groups (–) joined by a carbonyl functional group (–C(=O)–). It is thus the simplest amide of carbamic acid.
Urea serves an important ...
s, ''N''-nitrosoguanidine
Guanidine is the compound with the formula HNC(NH2)2. It is a colourless solid that dissolves in polar solvents. It is a strong base that is used in the production of plastics and explosives. It is found in urine predominantly in patients experie ...
s, and ''N''-nitrosocarbamate
In organic chemistry, a carbamate is a category of organic compounds with the general formula and structure , which are formally derived from carbamic acid (). The term includes organic compounds (e.g., the ester ethyl carbamate), formall ...
s. Nitrosamides are usually chemically reactive, metabolically unstable, and often carcinogenic
A carcinogen is any substance, radionuclide, or radiation that promotes carcinogenesis (the formation of cancer). This may be due to the ability to damage the genome or to the disruption of cellular metabolic processes. Several radioactive sub ...
; however, in contrast to the ''N''-nitrosamines, ''N''-nitrosamides are not generally contaminants found in food.
Use
Various chloroethylnitrosoureas (such as ''N, N-bis (2-chloroethyl)nitrosourea, BCNU) have obtained a medical use in the field ofmalignant tumors
Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal bl ...
.Hans Marquardt, Siegfried G. Schäfer (Hrsg.): ''Lehrbuch der Toxikologie.'' 2. Auflage, Wissenschaftliche Verlagsgesellschaft mbH Stuttgart, 2004, , S. 752–753. It is hypothesized that the efficacy against cancer cells is based on the alkylability of guanine cytosine centers in the sequences of the genetic material, especially the oncogene
An oncogene is a gene that has the potential to cause cancer. In tumor cells, these genes are often mutated, or expressed at high levels.
s.
Synthesis
''N''-Nitrosamides can be prepared starting from ''N''-monosubstitutedcarboxamide
In organic chemistry, an amide, also known as an organic amide or a carboxamide, is a compound with the general formula , where R, R', and R″ represent organic groups or hydrogen atoms. The amide group is called a peptide bond when it is ...
s and the nitrosyl cation (which results from the nitrous cation in the presence of strong acids from the nitrous acid
Nitrous acid (molecular formula ) is a weak and monoprotic acid known only in solution, in the gas phase and in the form of nitrite () salts. Nitrous acid is used to make diazonium salts from amines. The resulting diazonium salts are reagent ...
), here exemplified for ''N''-methylacetamide (1).Heinz G. O. Becker, Rainer Beckert, Werner Berger, Günter Domschke, Egon Fanghänel, Mechthild Fischer, Frithjof Gentz, Karl Gewald, Reiner Gluch, Wolf D. Habicher, Hans-Joachim Knölker, Roland Mayer, Peter Meth, Klaus Müller, Dietrich Pavel, Hermann Schmidt, Karl Schollberg, Klaus Schwetlick, Erika Seiler, Günter Zeppenfeld: ''Organikum.'' 24. Auflage, Wiley-VCH Verlag GmbH & Co.KGaA, Weinheim 2015, , S. 648. The carboxamide reacts in a nucleophilic attack at the nitrosyl cation. After the elimination of a proton, an ''N''-nitrosamide (2) is formed from the resulting cation:
Toxicity
The genotoxic effect of the ''N''-nitroso compounds can be attributed to the formation of reactive electrophilic species in themetabolism
Metabolism (, from el, μεταβολή ''metabolē'', "change") is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run ...
.Hans Marquardt, Siegfried G. Schäfer (Hrsg.): ''Lehrbuch der Toxikologie.'' 2. Auflage, Wissenschaftliche Verlagsgesellschaft mbH Stuttgart, 2004, , S. 753–758. The spontaneous decomposition
Decomposition or rot is the process by which dead organic substances are broken down into simpler organic or inorganic matter such as carbon dioxide, water, simple sugars and mineral salts. The process is a part of the nutrient cycle and ...
of ''N''-nitroso-ureas in the aqueous medium of the metabolism, here for example of 1-methylnitrosourea (3), produces diazonium
Diazonium compounds or diazonium salts are a group of organic compounds sharing a common functional group where R can be any organic group, such as an alkyl or an aryl, and X is an inorganic or organic anion, such as a halide.
General properti ...
or carbenium ions, respectively. The decomposition occurs into isocyanic acid
Isocyanic acid is a chemical compound with the structural formula HNCO, which is often written as . It is a colourless, volatile and poisonous substance, with a boiling point of 23.5 °C. It is the predominant tautomer of cyanic acid ().
...
and methyldiazohydroxide. The rearrangement to the diazonium ion and the subsequent elimination of nitrogen results in a carbenium ion (4), which can alkylate nucleophilic intersections of the DNA.
In the organism, the decomposition of ''N''-nitroso ureas with a higher degree of substitution can proceed. An alternative possible formation of diazonium and carbenium ions is through the enzymatic reaction of nitrosamines.
Typical accompanying symptoms during the medical cancer treatment via ''N''-nitroso ureas are the impairment of bone marrow
Bone marrow is a semi-solid biological tissue, tissue found within the Spongy bone, spongy (also known as cancellous) portions of bones. In birds and mammals, bone marrow is the primary site of new blood cell production (or haematopoiesis). It i ...
(damage of the stem cell compartment), lymphatic tissue and the gastrointestinal tract.
References
External links
*{{cite web, url=https://en.wiktionary.org/wiki/nitrosamide, title=nitrosamide, website=Wiktionary, accessdate=2017-08-28 Nitroso compounds Amides