Benzo(j)fluoranthene

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Benzo[j]fluoranthene
Benzo(j)fluoranthene.png
Names
Preferred IUPAC name
Benzo[j]fluoranthene
Identifiers
3D model (JSmol)
ChemSpider
ECHA InfoCard 100.005.374 OOjs UI icon edit-ltr-progressive.svg
EC Number
  • 205-910-3
KEGG
PubChem CID
RTECS number
  • DF6300000
UNII
UN number 3077
  • InChI=1S/C20H12/c1-2-8-15-13(5-1)11-12-17-16-9-3-6-14-7-4-10-18(19(14)16)20(15)17/h1-12H Yes check.svgY
    Key: KHNYNFUTFKJLDD-UHFFFAOYSA-N Yes check.svgY
  • InChI=1/C20H12/c1-2-8-15-13(5-1)11-12-17-16-9-3-6-14-7-4-10-18(19(14)16)20(15)17/h1-12H
    Key: KHNYNFUTFKJLDD-UHFFFAOYAB
  • c5c3c1cccc2c1c(ccc2)c3c4ccccc4c5
Properties
C20H12
Molar mass 252.3093
Appearancesolid
Density 1.286 g/cm3
Melting point 165 °C (329 °F; 438 K)
Hazards
Flash point 228.6 °C (443.5 °F; 501.8 K)
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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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, [1] as well as an impurity in some oils such as soybean oil. [2]

Contents

Structure and synthesis

BjF consists of two naphthalene-like structures which are fused by a cyclopentane structure. This cyclopentane is not included in the aromaticity of the molecule. BjF can be obtained when either 2-(1-chloroethenyl)benzo[c]phenanthrene or 6-(1-chloroethenyl)chrysene is treated by flash vacuum thermolysis (FVT) at high temperatures (above 900 °C) followed by ring rearrangements (ring contraction/expansion) to selectively yield BjF. [3] Benzo[k]fluoranthene may also be converted via similar processes to BjF by FVT at temperatures of at least 1100 °C (6% yield) or at least 1200 °C (11% yield) with 38% mass recovery. [4]

Reactivity

BjF can be functionalized by means of electrophilic aromatic substitution. In the body it is metabolized into phenols (3,4,6 or 10 hydroxy), dihydrodiols (4,5 and 9,10) and 4,5-dione [5] (fig. 1).

Figure 1. BjF with numbered carbon atoms BjF with numbered carbon atoms.png
Figure 1. BjF with numbered carbon atoms

Mechanism of action

BjF is categorized by the IARC as possibly carcinogenic to human beings, like many other PAHs, on the basis of sufficient evidence in animals. [6] For example, BjF is active as a tumor initiator on mouse skin and is carcinogenic in both mouse skin and in rat lungs. Recently, BjF was also found to induce tumors in newborn mouse lung and liver. [7] The mechanism of actions of BjF is similar to other PAHs. The diolepoxide mechanism involves formation of stable and unstable DNA adducts, mainly at G and A, which can lead to mutations in proto-oncogenes (RAS) and tumour-suppressor genes (P53). Many polycyclic aromatic hydrocarbon diolepoxides and their precursor diols and epoxides are tumorigenic in animals. The radical cation mechanism involves generation of unstable adducts at G and A, leading to apurinic sites and mutations in HRAS. Orthoquinone formation could lead to stable and unstable DNA adducts and generation of reactive oxygen species, inducing mutations in P53. [8]

Toxicity

PAHs

One of the earliest connection between PAHs, combustion, and cancer was established by Cook and co-workers with the isolation of the carcinogen benzo[a]pyrene from coal tar extract. [9] Benzo[a]pyrene now has been well characterized in toxicology reports and is a known potent carcinogen. [10] Benzo[a]pyrene requires metabolic activation to become, ultimately, BPDE ((±)-anti-7β,8α-dihydroxy-9α,10α-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene) which binds to the DNA to form a covalent trans adducts at the N2 position of guanine. [11] Hereafter binding to DNA at cancer hotspots, especially in the P53 tumour suppressor gene at codons: 157, 248 and 273 (figure 3), it has the possibility of inducing lung cancer. [12] Structural similarity of PAHs contributes to the similarity in metabolism, biotransformation and toxicology. Benzo[a]pyrene has been extensively reviewed and is used as a model for the toxicology and metabolism of other PAHs. [13]

Benzo[j]fluoranthene

Specific studies on BjF showed that it exhibits mutagenic toxicity in S. typhimurium TA98 and TA1000 under the presence of microsomal activation. [14] BjF can form DNA-adducts, covalently binding of chemicals to DNA can result in strand breaks and DNA damage, which ultimately leads to mutations. [15] In mice studies BjF induced tumorigenic activity on the skin, lung adenomas and liver adenomas/hepatomas. [16] [17] [18] [19] Lung implantation of BjF also induced lung epidermoid carcinomas in 3-month-old female rats. [20] Tail vein injection of BjF also causes covalently binding to mouse hemoglobin and serum proteins, with binding to serum proteins being 10-fold higher than to hemoglobin. [21]

Related Research Articles

<span class="mw-page-title-main">Carcinogen</span> Substance, radionuclide, or radiation directly involved in causing cancer

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">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.

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

Myricetin is a member of the flavonoid class of polyphenolic compounds, with antioxidant properties. Common dietary sources include vegetables, fruits, nuts, berries, tea, and red wine.

<span class="mw-page-title-main">CYP1A1</span> Protein-coding gene in the species Homo sapiens

Cytochrome P450, family 1, subfamily A, polypeptide 1 is a protein that in humans is encoded by the CYP1A1 gene. The protein is a member of the cytochrome P450 superfamily of enzymes.

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

Chlorophyllin refers to any one of a group of closely related water-soluble salts that are semi-synthetic derivatives of chlorophyll, differing in the identity of the cations associated with the anion. Its most common form is a sodium/copper derivative used as a food additive and in alternative medicine. As a food coloring agent, copper complex chlorophyllin is known as natural green 3 and has the E number E141.

<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.

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

Chrysene is a polycyclic aromatic hydrocarbon (PAH) with the molecular formula C
18
H
12
that consists of four fused benzene rings. It is a natural constituent of coal tar, from which it was first isolated and characterized. It is also found in creosote at levels of 0.5–6 mg/kg.

Mycobacterium pyrenivorans is a scotochromogenic, rapidly growing mycobacterium, first isolated from an enrichment culture obtained from soil that was highly contaminated with polycyclic aromatic hydrocarbons (PAHs). The soil sample was collected on the site of a former coking plant at Ubach-Palenberg, Germany. Etymology: pyrenivorans; digesting pyrene.

<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.

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.

(+)-Benzo(<i>a</i>)pyrene-7,8-dihydrodiol-9,10-epoxide Cancer-causing agent derived from tobacco smoke

(+)-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.

Indeno(1,2,3-<i>cd</i>)pyrene Polycyclic aromatic hydrocarbon

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. One of these 16 is Indeno[1,2,3-cd]pyrene (IP). IP is the combination of an indeno molecule and a pyrene molecule with a fluoranthene network. In 1962, the National Cancer Institute reported that indeno[1,2,3-cd]pyrene has a slight tumor activity. This was confirmed in 1973 by the IARC in mice testing.

References

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