Benzo(j)fluoranthene: Difference between revisions

{{short description|Chemical compound}}

{{DISPLAYTITLE:Benzo(''j'')fluoranthene}}

{{Use dmy dates|date=July 2018}}

{{correct title|reason=bracket|edit=substitution|Benzo[''j'']fluoranthene}}

| verifiedrevid = 433351366

| Name =Benzo[''j'']fluoranthene

| ImageFile =Benzo(j)fluoranthene.png

| PIN = Benzo[''j'']fluoranthene

| OtherNames =

|Section1={{Chembox Identifiers

| 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

| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}

| SMILES = c5c3c1cccc2c1c(ccc2)c3c4ccccc4c5

| MeSHName =

| PubChem = 9152

| EC_number = 205-910-3

| RTECS = DF6300000

| UNNumber = 3077

| UNII = P63HLW88W8

| ChemSpiderID = 8798

|Section2={{Chembox Properties

| Formula =C₂₀H₁₂

| MolarMass =252.3093

| Appearance =solid

| Density = 1.286 g/cm₃

| MeltingPtC = 165

| MeltingPt_notes =

| BoilingPt =

|Section3={{Chembox Hazards

| FlashPtC = 228.6

'''Benzo[''j'']fluoranthene''' (B''j''F) 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 [[solvent|solvents]]. Impure samples can appear off white. Closely related isomeric compounds include [[benzo(a)fluoranthene|benzo[''a'']fluoranthene]] (B''a''F), [[benzo(b)fluoranthene|benzo[''b'']fluoranthene]] (B''b''F), [[benzo(e)fluoranthene|benzo[''e'']fluoranthene]] (B''e''F), and [[benzo(k)fluoranthene|benzo[''k'']fluoranthene]] (B''k''F). B''j''F is present in [[fossil fuel|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,<ref>Author unknown (23 June 2005) "Benzo[''j'']fluoranthene". TOXNET http://toxnet.nlm.nih.gov/cgi-bin/sis/search2/f?./temp/~ZHcJmU:1 (last consulted on: 19 March 2015)

</ref> as well as an impurity in some [[oil|oils]] such as soybean oil.<ref>Author unknown (date unknown) "Benzo[''j'']fluoranthene" Sigma-Aldrich [https://archive.today/20150410000756/http://www.sigmaaldrich.com/catalog/product/Fluka/BCR049?lang=en&region=NL] (last consulted on: 19 March 2015)</ref>

==Structure and synthesis==

B''j''F consists of two [[naphthalene]]-like structures which are fused by a [[cyclopentane]] structure. This cyclopentane is not included in the [[aromaticity]] of the molecule. B''j''F can be obtained when either 2-(1-chloroethenyl)benzo[c]phenanthrene or 6-(1-chloroethenyl)chrysene is treated by [[pyrolysis|flash vacuum thermolysis]] (FVT) at high temperatures (above 900&nbsp;°C) followed by ring rearrangements (ring contraction/expansion) to selectively yield B''j''F.<ref>M. Sarobe et al. (1 January 1997) "High temperature gas phase syntheses of C₂₀H₁₂ cyclopenta-fused polycyclic aromatic hydrocarbons: benz[''l'']acephenanthrylene and benz[''j'']acephenanthrylene and their selective rearrangement to benzo[''j'']fluoranthene" ''Journal of the Chemical Society'', Perkin Trans. 2</ref> Benzo[''k'']fluoranthene may also be converted via similar processes to B''j''F by FVT at temperatures of at least 1100&nbsp;°C (6% yield) or at least 1200&nbsp;°C (11% yield) with 38% mass recovery.<ref>M. Sarobe et al. (1999) "Flash Vacuum Thermolysis of Acenaphtho[1,2-α]acenaphthylene, Fluoranthene, Benzo[''k'']- and Benzo[''j'']fluoranthene 2 Homolytic Scission of Carbon2Carbon Single Bonds of Internally Fused Cyclopenta Moieties at ''T'' ≥ 1100°C" ''European Journal of Organic Chemistry''</ref>

==Reactivity==

B''j''F can be functionalized by means of [[electrophilic aromatic substitution]]. In the body it is metabolized into [[phenol|phenols]] (3,4,6 or 10 hydroxy), dihydrodiols (4,5 and 9,10) and 4,5-dione<ref>E.H. Weyand et al. (1993) "Detection of the Major DNA Adducts of Benzo[''j'']fluoranthene in Mouse Skin: Nonclassical Dihydrodiol Epoxides" ''Chemical Research in Toxicology'' 6

</ref> (fig. 1).

[[File:BjF with numbered carbon atoms.png|thumb|Figure 1. B''j''F with numbered carbon atoms]]

==Mechanism of action==

B''j''F is categorized by the IARC as possibly [[carcinogen]]ic to human beings, like many other PAHs, on the basis of sufficient evidence in animals.<ref>K.Straif et al. (December 2005) "Carcinogenicity of polycyclic aromatic hydrocarbons" THE LANCET Oncology, vol.6, issue 12</ref> For example, B''j''F is active as a tumor initiator on mouse skin and is carcinogenic in both mouse skin and in rat lungs. Recently, B''j''F was also found to induce tumors in newborn mouse lung and liver.<ref>J.E. Rice et al. (1 December 1987) "Identification of Tumorigenic Metabolites of Benzo[''j'']fluoranthene Formed in Vivo in Mouse Skin" ''Cancer Research'' 47, 6166-6170

</ref> The mechanism of actions of B''j''F 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.<ref>K.Straif et al. (December 2005) "Carcinogenicity of polycyclic aromatic hydrocarbons" ''The Lancet Oncology'', vol.6, issue 12</ref>

==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.<ref>Cook, James Wilfred, C. L. Hewett, and I. Hieger. "106. The isolation of a cancer-producing hydrocarbon from coal tar. Parts I, II, and III." ''Journal of the Chemical Society'' (1933): 395-405.</ref> Benzo[''a'']pyrene now has been well characterized in toxicology reports and is a known potent carcinogen.<ref>Denissenko, Mikhail F., et al. "Preferential formation of benzo[''a'']pyrene adducts at lung cancer mutational hotspots in P53." ''Science'' 274.5286 (1996): 430-432.

</ref> 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.<ref>Singer, B., and D. Grunberger. "Metabolic activation of carcinogens and mutagens." ''Molecular Biology of Mutagens and Carcinogens''. Springer US, 1983. 97-141. {{ISBN|978-1-4613-3772-0}}

</ref> 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.<ref>Denissenko, Mikhail F., et al. "Preferential formation of benzo[''a'']pyrene adducts at lung cancer mutational hotspots in P53." ''Science'' 274.5286 (1996): 430-432.

</ref> 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.<ref>Agency for Toxic Substances and Disease Registry (ATSDR). (1995) "Toxicological profile for Polycyclic Aromatic Hydrocarbons (PAHs)" Atlanta, GA: U.S. Department of Health and Human Services, Public Health Service.

</ref>

===Benzo[''j'']fluoranthene===

Specific studies on B''j''F showed that it exhibits mutagenic toxicity in ''S. typhimurium'' TA98 and TA1000 under the presence of microsomal activation.<ref>E.J. Lavoie et al. (December 1980) "Identification of Mutagenic Dihydrodiols as Metabolites of Benzo[''j'']fluoranthene and Benzo[''k'']fluoranthene" ''Cancer Research'' 40, 4528-4532</ref> B''j''F can form DNA-adducts, covalently binding of chemicals to DNA can result in strand breaks and DNA damage, which ultimately leads to mutations.<ref>Agency for Toxic Substances and Disease Registry (ATSDR). (1995) "Toxicological profile for Polycyclic Aromatic Hydrocarbons (PAHs)" Atlanta, GA: U.S. Department of Health and Human Services, Public Health Service.

</ref> In mice studies B''j''F induced tumorigenic activity on the skin, lung adenomas and liver adenomas/hepatomas.<ref>LaVoie, Edmond J., et al. "Tumour initiating activity of dihydrodiols of benzo[''b'']fluoranthene, benzo[''j'']fluoranthene, and benzo[''k'']fluoranthene." ''Carcinogenesis'' 3.1 (1982): 49-52.

</ref><ref>Habs, M., D. Schmähl, and J. Misfeld. "Local carcinogenicity of some environmentally relevant polycyclic aromatic hydrocarbons after lifelong topical application to mouse skin." ''Archiv für Geschwulstforschung'' 50.3 (1979): 266-274.

</ref><ref>Wynder, Ernest L., and Dietrich Hoffmann. "The carcinogenicity of benzofluoranthenes." Cancer 12.6 (1959): 1194-1199.</ref><ref>Weyand, E. H., et al. "Effect of fluorine substitution on benzo[''j'']fluoranthene genotoxicity." ''Chemico-Biological Interactions'' 84.1 (1992): 37-53

</ref> Lung implantation of B''j''F also induced lung epidermoid carcinomas in 3-month-old female rats.<ref>Deutsch-Wenzel, Reintraud P., et al. "Experimental studies in rat lungs on the carcinogenicity and dose-response relationships of eight frequently occurring environmental polycyclic aromatic hydrocarbons." ''Journal of the National Cancer Institute'' 71.3 (1983): 539-544

</ref> Tail vein injection of B''j''F also causes covalently binding to mouse hemoglobin and serum proteins, with binding to serum proteins being 10-fold higher than to hemoglobin.<ref>Agency for Toxic Substances and Disease Registry (ATSDR). (1995) "Toxicological profile for Polycyclic Aromatic Hydrocarbons (PAHs)" Atlanta, GA: U.S. Department of Health and Human Services, Public Health Service.

</ref>

==References==

{{reflist}}

{{PAHs}}

[[Category:Polycyclic aromatic hydrocarbons]]

[[Category:IARC Group 2B carcinogens]]