Indeno(1,2,3-cd)pyrene

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The correct title of this article is Indeno[1,2,3-cd]pyrene. The substitution of any brackets is due to technical restrictions.
Indeno(1,2,3-cd)pyrene
Indeno(1,2,3-cd)pyrene 200.svg
Names
Other names
    • o-Phenylenepyrene
    • 1,10-(o-Phenylene)pyrene
Identifiers
3D model (JSmol)
ChEBI
ChEMBL
ChemSpider
ECHA InfoCard 100.005.359 OOjs UI icon edit-ltr-progressive.svg
EC Number
  • 205-893-2
KEGG
PubChem CID
RTECS number
  • NK9300000
UNII
UN number 3077
  • InChI=1S/C22H12/c1-2-7-17-16(6-1)18-11-10-14-9-8-13-4-3-5-15-12-19(17)22(18)21(14)20(13)15/h1-12H
    Key: SXQBHARYMNFBPS-UHFFFAOYSA-N
  • C1=CC=C2C(=C1)C3=C4C2=CC5=CC=CC6=C5C4=C(C=C6)C=C3
Properties
C22H12
Molar mass 276.338 g·mol−1
AppearanceYellow crystals [1]
Melting point 164 °C (327 °F; 437 K) [1]
Boiling point 536 °C (997 °F; 809 K) [1]
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).

Indeno(1,2,3-cd)pyrene is a polycyclic aromatic hydrocarbon (PAH), one of 16 PAHs generally measured in studies of environmental exposure and air pollution. Many compounds of this class are formed when burning coal, oil, gas, wood, household waste and tobacco, and can bind to or form small particles in the air. The compounds are known to have toxic, mutagenic and/or carcinogenic properties. Over 100 different PAHs have been identified in environmental samples, including indeno(1,2,3-cd)pyrene (IP). [2] In 1962, the National Cancer Institute reported that indeno(1,2,3-cd)pyrene has a slight tumor activity. [3] This was confirmed in 1973 by the IARC in mice testing. [4]

Contents

Production

In nature, IP is formed when burning coal, oil, gas, wood, household waste and tobacco. There are various pathways in which nature can produce PAHs, but the most important mechanism to form such compounds is based on hydrogen abstraction-acetylene addition (HACA). This is accepted as the major reaction route to form PAHs in combustion flames. [5]

When producing IP in the lab, there are two efficient synthetic approaches. The first one is by forming a reactive diazonium intermediate out of 2-(pyren-1-yl)aniline. When this intermediate is formed, it can react with a tethered polycyclic aromatic moiety at room temperature. This is done by an intramolecular aromatic substitution. [6] The reactivity of this reaction is controlled by the substrate concentration and its stoichiometry. tBuONO is used as a reagent (figure 1). [7] The second way to synthesize IP is with a one-pot synthesis. With 4-bromopyrene as starting material and by adding Pd3(dba)2, P(Cy)2 and BDU in DMF, the final product will form (figure 2). [8]

Chemical properties

Reactions with electrophiles

Indeno(1,2,3-cd)pyrene can undergo reaction with bromine or fluorine to 12-bromoindeno(1,2,3-cd)pyrene [9] and 2-fluoroindeno(1,2,3-cd)pyrene [10] respectively.

Nitration

The reaction with indeno(1,2,3-cd)pyrene can be performed using NHO3 in an acetyl nitrate solution. The reaction yielded IP-NO2 which was regioselective, the nitrate group being added mainly to the 12 position which is the same as the Friedel-Crafts acylation and bromination [2]

Physical properties

Indeno(1,2,3-cd)pyrene (IP) is classified as a polycyclic aromatic hydrocarbon (PAH) and appears as a yellow crystal. It contains five benzene rings and one cyclopentane, resulting in a planar molecule. There is no stereochemistry present in IP, but there are resonance structures due to benzene’s conjugated pi electrons. They can move freely within the cycling rings, providing stabilization energy. [11]

Ecological effect

Studies have been conducted to investigate the ecological effects of several PAHs, including indeno(1,2,3-cd)pyrene (IP). The International Agency for Research on Cancer (IARC) published results claiming that the compound is carcinogenic in several experimental animals. [12] Another research group studied phototoxic effects of IP and they found effects only at very high levels in a cell line of the rainbow trout. Since these levels can never be reached in water for indeno(1,2,3-cd)pyrene, even when it is maximally dissolved, it would not have implications for aquatic animals. [13] IP is only minimally water soluble due to its lipophilic, and thus hydrophobic, character. Lipophilicity is generally inversely proportional to ecotoxicity because compounds with low water solubility (hyrdophobic) are less bioavailable to organisms, as they tend to be bound to organic particulates that reside in sediments in aquatic and marine systems. Low solubility therefore not only decreases phototoxicity but also a large part of toxicity in general. [14] Swedish researchers have also conducted research into the PAH levels in sewage treatment plants in Sweden. They induced EROD activity, which is a measure for toxicity, by incubating chicken embryo liver cells with PAH extracts from the sludge. Indeno(1,2,3-cd)pyrene, which was one of the PAHs investigated, contributed together with 5 other selected PAHs only a minor part of the EROD activity. Therefore, though indeno(1,2,3-cd)pyrene may induce some toxicity in chicken embryo liver, its contribution is likely to be minor. [15]

Mechanism

Indeno(1,2,3-cd)pyrene are among the PAHs considered as possible carcinogens to humans. [12] The PAH family consists of similar molecules and therefore they have a similar mechanism of causing cancer in vivo. The molecule is metabolized in the body by the cytochrome P450 system, resulting in metabolites containing nitro, quinone or hydroxyl groups. [16] This is in line with metabolites formed from other PAHs. [17] The nitro and quinone containing compound turned out to be cytotoxic or carcinogenic, while the hydroxyl containing metabolite did not show any toxicity or carcinogenicity. PAHs including indeno(1,2,3-cd)pyrene may be genotoxic. When PAHs are hydrolyzed, very reactive epoxide groups can be created at certain regions in the molecule. These groups can ultimately form an adduct with the base of a nucleotide in the DNA. [18] DNA adducts with PAHs can disrupt the DNA replication or modify the DNA, by removing bases like adenine and guanine from the nucleotides. [19] This can in the end lead to cell death and the production of truncated or misfolded proteins.

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A carcinogen is any agent that promotes the development of cancer. Carcinogens can include synthetic chemicals, naturally occurring substances, physical agents such as ionizing and non-ionizing radiation, and biologic agents such as viruses and bacteria. Most carcinogens act by creating mutations in DNA that disrupt a cell's normal processes for regulating growth, leading to uncontrolled cellular proliferation. This occurs when the cell's DNA repair processes fail to identify DNA damage allowing the defect to be passed down to daughter cells. The damage accumulates over time. This is typically a multi-step process during which the regulatory mechanisms within the cell are gradually dismantled allowing for unchecked cellular division.

Coal tar is a thick dark liquid which is a by-product of the production of coke and coal gas from coal. It is a type of creosote. It has both medical and industrial uses. Medicinally it is a topical medication applied to skin to treat psoriasis and seborrheic dermatitis (dandruff). It may be used in combination with ultraviolet light therapy. Industrially it is a railroad tie preservative and used in the surfacing of roads. Coal tar was listed as a known human carcinogen in the first Report on Carcinogens from the U.S. Federal Government, issued in 1980.

<span class="mw-page-title-main">Mutagen</span> Physical or chemical agent that increases the rate of genetic mutation

In genetics, a mutagen is a physical or chemical agent that permanently changes genetic material, usually DNA, in an organism and thus increases the frequency of mutations above the natural background level. As many mutations can cause cancer in animals, such mutagens can therefore be carcinogens, although not all necessarily are. All mutagens have characteristic mutational signatures with some chemicals becoming mutagenic through cellular processes.

<span class="mw-page-title-main">Polycyclic aromatic hydrocarbon</span> Hydrocarbon composed of multiple aromatic rings

A polycyclic aromatic hydrocarbon (PAH) is a class of organic compounds that is composed of multiple aromatic rings. The simplest representative is naphthalene, having two aromatic rings, and the three-ring compounds anthracene and phenanthrene. PAHs are uncharged, non-polar and planar. Many are colorless. Many of them are found in coal and in oil deposits, and are also produced by the incomplete combustion of organic matter—for example, in engines and incinerators or when biomass burns in forest fires.

Benzo(<i>a</i>)pyrene Carcinogenic compound found in smoke and soot

Benzo[a]pyrene (BaP or B[a]P) is a polycyclic aromatic hydrocarbon and the result of incomplete combustion of organic matter at temperatures between 300 °C (572 °F) and 600 °C (1,112 °F). The ubiquitous compound can be found in coal tar, tobacco smoke and many foods, especially grilled meats. The substance with the formula C20H12 is one of the benzopyrenes, formed by a benzene ring fused to pyrene. Its diol epoxide metabolites, more commonly known as BPDE, react with and bind to DNA, resulting in mutations and eventually cancer. It is listed as a Group 1 carcinogen by the IARC. In the 18th century a scrotal cancer of chimney sweepers, the chimney sweeps' carcinoma, was already known to be connected to soot.

<span class="mw-page-title-main">Methylcholanthrene</span> Chemical compound

Methylcholanthrene is a highly carcinogenic polycyclic aromatic hydrocarbon produced by burning organic compounds at very high temperatures. Methylcholanthrene is also known as 3-methylcholanthrene, 20-methylcholanthrene or the IUPAC name 3-methyl-1,2-dyhydrobenzo[j]aceanthrylene. The short notation often used is 3-MC or MCA. This compound forms pale yellow solid crystals when crystallized from benzene and ether. It has a melting point around 180 °C and its boiling point is around 280 °C at a pressure of 80 mmHg. Methylcholanthrene is used in laboratory studies of chemical carcinogenesis. It is an alkylated derivative of benz[a]anthracene and has a similar UV spectrum. The most common isomer is 3-methylcholanthrene, although the methyl group can occur in other places.

<span class="mw-page-title-main">Pyrene</span> Chemical compound

Pyrene is a polycyclic aromatic hydrocarbon (PAH) consisting of four fused benzene rings, resulting in a flat aromatic system. The chemical formula is C16H10. This yellow-green solid is the smallest peri-fused PAH. Pyrene forms during incomplete combustion of organic compounds.

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<span class="mw-page-title-main">Fluoranthene</span> Chemical compound

Fluoranthene is a polycyclic aromatic hydrocarbon (PAH). The molecule can be viewed as the fusion of naphthalene and benzene unit connected by a five-membered ring. Although samples are often pale yellow, the compound is colorless. It is soluble in nonpolar organic solvents. It is a member of the class of PAHs known as non-alternant PAHs because it has rings other than those with six carbon atoms. It is a structural isomer of the alternant PAH pyrene. It is not as thermodynamically stable as pyrene. Its name is derived from its fluorescence under UV light.

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<span class="mw-page-title-main">DNA adduct</span> Segment of DNA bound to a cancer-causing chemical

In molecular genetics, a DNA adduct is a segment of DNA bound to a cancer-causing chemical. This process could lead to the development of cancerous cells, or carcinogenesis. DNA adducts in scientific experiments are used as biomarkers of exposure. They are especially useful in quantifying an organism's exposure to a carcinogen. The presence of such an adduct indicates prior exposure to a potential carcinogen, but it does not necessarily indicate the presence of cancer in the subject animal.

Chlorinated polycyclic aromatic hydrocarbons (Cl-PAHs) are a group of compounds comprising polycyclic aromatic hydrocarbons with two or more aromatic rings and one or more chlorine atoms attached to the ring system. Cl-PAHs can be divided into two groups: chloro-substituted PAHs, which have one or more hydrogen atoms substituted by a chlorine atom, and chloro-added Cl-PAHs, which have two or more chlorine atoms added to the molecule. They are products of incomplete combustion of organic materials. They have many congeners, and the occurrences and toxicities of the congeners differ. Cl-PAHs are hydrophobic compounds and their persistence within ecosystems is due to their low water solubility. They are structurally similar to other halogenated hydrocarbons such as polychlorinated dibenzo-p-dioxins (PCDDs), dibenzofurans (PCDFs), and polychlorinated biphenyls (PCBs). Cl-PAHs in the environment are strongly susceptible to the effects of gas/particle partitioning, seasonal sources, and climatic conditions.

<span class="mw-page-title-main">Benzopyrene</span>

A benzopyrene is an organic compound with the formula C20H12. Structurally speaking, the colorless isomers of benzopyrene are pentacyclic hydrocarbons and are fusion products of pyrene and a phenylene group. Two isomeric species of benzopyrene are benzo[a]pyrene and the less common benzo[e]pyrene. They belong to the chemical class of polycyclic aromatic hydrocarbons.

Benzo(<i>j</i>)fluoranthene Chemical compound

Benzo[j]fluoranthene (BjF) is an organic compound with the chemical formula C20H12. Classified as a polycyclic aromatic hydrocarbon (PAH), it is a colourless solid that is poorly soluble in most solvents. Impure samples can appear off white. Closely related isomeric compounds include benzo[a]fluoranthene (BaF), benzo[b]fluoranthene (BbF), benzo[e]fluoranthene (BeF), and benzo[k]fluoranthene (BkF). BjF is present in fossil fuels and is released during incomplete combustion of organic matter. It has been traced in the smoke of cigarettes, exhaust from gasoline engines, emissions from the combustion of various types of coal and emissions from oil heating, as well as an impurity in some oils such as soybean oil.

Dibenz(<i>a</i>,<i>h</i>)anthracene Chemical compound

Dibenz[a,h]anthracene or Benzo[k]tetraphene or 1,2:5,6-Dibenzanthracene is an organic compound with the chemical formula C22H14. It is a polycyclic aromatic hydrocarbon (PAH) made of five fused benzene rings. It is a fused five-ringed PAH which is common as a pollutant of smoke and oils. It is stable and highly genotoxic in bacterial and mammalian cell systems, as it intercalates into DNA and causes mutations.

Dibenz(<i>a</i>,<i>j</i>)anthracene Chemical compound

Dibenz[a,j]anthracene or Benzo[m]tetraphene or 1,2:7,8-Dibenzanthracene is an organic compound with the chemical formula C22H14. It belongs to the class of polycyclic aromatic hydrocarbons (PAHs) and is formed whenever there is incomplete combustion of organic matter. The IARC (International Agency for Research on Cancer) has classified it as possibly carcinogenic to humans, grouped into IARC group 2B.

<span class="mw-page-title-main">Dibenzopyrenes</span> Chemical compound

Dibenzopyrenes are a group of high molecular weight polycyclic aromatic hydrocarbons with the molecular formula C24H14. There are five isomers of dibenzopyrene which differ by the arrangement of aromatic rings: dibenzo[a,e]pyrene, dibenzo[a,h]pyrene, dibenzo[a,i]pyrene, dibenzo[a,l]pyrene, and dibenzo[e,l]pyrene.

Benzo(<i>c</i>)fluorene Chemical compound

Benzo[c]fluorene is a polycyclic aromatic hydrocarbon (PAH) with mutagenic activity. It is a component of coal tar, cigarette smoke and smog and thought to be a major contributor to its carcinogenic properties. The mutagenicity of benzo[c]fluorene is mainly attributed to formation of metabolites that are reactive and capable of forming DNA adducts. According to the KEGG it is a group 3 carcinogen. Other names for benzo[c]fluorene are 7H-benzo[c]fluorene, 3,4-benzofluorene, and NSC 89264.

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(+)-Benzo[a]pyrene-7,8-dihydrodiol-9,10-epoxide is an organic compound with molecular formula C20H14O3. It is a metabolite and derivative of benzo[a]pyrene (found in tobacco smoke) as a result of oxidation to include hydroxyl and epoxide functionalities. (+)-Benzo[a]pyrene-7,8-dihydrodiol-9,10-epoxide binds to the N2 atom of a guanine nucleobase in DNA, distorting the double helix structure by intercalation of the pyrene moiety between base pairs through π-stacking. The carcinogenic properties of tobacco smoking are attributed in part to this compound binding and inactivating the tumor suppression ability of certain genes, leading to genetic mutations and potentially to cancer.

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References

  1. 1 2 3 "Indeno[1,2,3-cd]pyrene". PubChem.
  2. 1 2 Minabe M, Shibuya N. Nitration of indeno[1,2,3-cd]pyrene and mutagenic activities of related compounds. Chem. Res. Toxicol. 1989 Nov 1; 2(6); 357-358
  3. ↑ National Cancer Institute Monograph. 1st ed. National Cancer institute; 1962
  4. ↑ INDENO(1,2,3-cd)PYRENE. IPCS inchem. 1973; 3; 229
  5. ↑ V. V. Kislov, A. I. Sadovnikov, A. M. Mebel; Formation Mechanism of Polycyclic Aromatic Hydrocarbons beyond the Second Aromatic Ring; The Journal Of Physical Chemistry, 2013, number 117; p. 4794 - 4816.
  6. ↑ T. Chatterjee, D. S. Lee, E. J. Cho; Extended Study of Visible-Light-Induced Photocatalytic [4+2] Benzannulation: Synthesis of Polycyclic (Hetero)Aromatics; The Journal of Organic Chemistry, 2017, number 82; p 4369 - 4378
  7. ↑ Y. Choi, T. Chatterjee, J. Kim, J. S. Kim, E. J. Cho; Synthesis of cyclopenta-fused polycyclic aromatic hydrocarbons utilizing aryl-substituted anilines; Organic & Biomolecular Chemistry, 2016, number 14; p. 6804 - 6810.
  8. ↑ H. A. Wegner, H. Reisch, K. Rauch, A. Demeter, K. A. Zachariasse, A. de Meijere, L. T. Scott; Oligoindenopyrenes: A new Class of Polycyclic Aromatics; American Chemical Society, 10/21/2006; p. 9080 - 9087.
  9. ↑ Minabe M, Cho BP, Harvey RG. Polycyclic fluoranthene hydrocarbons. Part 4. Electrophilic substitution of polycyclic fluoranthene hydrocarbons. J. Am. Chem. Soc. 1989 May 1; 111(11); 3809-3812
  10. ↑ Rice JE, Czech A, Hussain N, LaVoie EJ. Synthesis of fluorinated dervatices of benzo[k]fluoranthene and indeno[1,2,3-cd]pyrene and 8,9-dihydro-8,9-epoxybenzo[k]fluoranthene. J. Org. Chem. 1988 April 1; 53(8); 1775-1779
  11. ↑ E. Dybing, P. E. Schwarze, P. Nafstad, K. Victorin, T. M. Penning; Chapter 7. Polycyclic Aromatic Hydrocarbons In Ambient Air and Cancer.
  12. 1 2 IARC. (1983). Indeno(1,2,3-cd)pyrene. 32, 373
  13. ↑ K Schirmer, A.G.J Chan, B.M Greenberg, D.G Dixon, N.C Bols. (1998). Ability of 16 priority PAHs to be photocytotoxic to a cell line from the rainbow trout gill. Toxicology, 127-1–3, 143-155.
  14. ↑ Line E. Sverdrup, Torben Nielsen, and Paul Henning Krogh. (2002) Soil Ecotoxicity of Polycyclic Aromatic Hydrocarbons in Relation to Soil Sorption, Lipophilicity, and Water Solubility. Environmental Science & Technology. 36 (11), 2429-2435
  15. ↑ Magnus Engwall, Björn Brunström, Carina Näf, Katarina Hjelm.(1999). Levels of dioxin-like compounds in sewage sludge determined with a bioassay based on erod induction in chicken embryo liver cultures. Chemosphere, 38-10, 2327-2343.
  16. ↑ Luo, Y., Li, S., She, Y. et al. (2015). Metabolic Transformation of Indeno[1,2,3-cd]pyrene and Toxicities of Its Metabolites. Bull Environ Contam Toxicol 94, 112–117.
  17. ↑ Luo, Y., Dai, J., Zhong, R., She, Y., Liu, R. and Wei, H. (2011), Production of polycyclic aromatic hydrocarbon metabolites from a peroxynitrite/iron(III) porphyrin biomimetic model and their mutagenicities. Environmental Toxicology and Chemistry, 30: 723-729.
  18. ↑ Baird, W. M.; Hooven, L. A.; Mahadevan, B. (2015). "Carcinogenic polycyclic aromatic hydrocarbon-DNA adducts and mechanism of action". Environmental and Molecular Mutagenesis. 45 (2–3): 106–114.
  19. ↑ Ramesh, A.; Walker, S. A.; Hood, D. B.; Guillén, M. D.; Schneider, K.; Weyand, E. H. (2004). "Bioavailability and risk assessment of orally ingested polycyclic aromatic hydrocarbons". International Journal of Toxicology. 23 (5): 301-333.
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