Anthanthrene

Last updated
Anthanthrene
Skeletal formula Anthanthrene.png
Skeletal formula
Anthanthrene molecule ball.png
Names
IUPAC name
hexacyclo[11.7.1.1.0.0.0]docosa-1,3(8),4,6,9,11,13,15,17(21),18,20(22)-undecaene
Preferred IUPAC name
Naphtho[7,8,1,2,3-nopqr]tetraphene
Other names
Dibenzo[def,mno]chrysene; Anthanthren; Dibenzo[cd,jk]pyrene
Identifiers
3D model (JSmol)
ChEBI
ChemSpider
ECHA InfoCard 100.005.351 OOjs UI icon edit-ltr-progressive.svg
KEGG
PubChem CID
UNII
  • InChI=1S/C22H12/c1-3-13-7-9-18-12-16-6-2-4-14-8-10-17-11-15(5-1)19(13)21(18)22(17)20(14)16/h1-12H Yes check.svgY
    Key: YFIJJNAKSZUOLT-UHFFFAOYSA-N Yes check.svgY
  • InChI=1/C22H12/c1-3-13-7-9-18-12-16-6-2-4-14-8-10-17-11-15(5-1)19(13)21(18)22(17)20(14)16/h1-12H
    Key: YFIJJNAKSZUOLT-UHFFFAOYAI
  • c6c3ccc2cc1cccc5c1c4c2c3c(cc4cc5)cc6
Properties
C22H12
Molar mass 276.33 g/mol
AppearanceGolden yellow solid
Melting point 261 °C (502 °F; 534 K)
Insoluble
−204.2·10−6 cm3/mol
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
X mark.svgN  verify  (what is  Yes check.svgYX mark.svgN ?)

Anthanthrene(dibenzo[def,mno]chrysene) is a polycyclic aromatic hydrocarbon (PAH) primarily formed during the incomplete combustion of organic materials such as fossil fuels, wood, and tobacco. It is a golden-yellow, odorless solid, and is often released as solid particulate matter attached to soot or aerosols. [1] Unlike other PAH molecules, it lacks a "bay region", a structural pocket that increases reactivity of the molecule. Due to its high lipophilicity, anthanthrene has low water-solubility, and tends to accumulate in lipid-rich environments. [2]

Contents

Anthanthrene is mainly used as a research chemical, and is a promising candidate for organic light emitting diodes (OLEDs). [3] However, it has been shown to contribute to free radical formation and induction of DNA strand breaks, even before external metabolic activation [4] [5] , suggesting carcinogenic and mutagenic risks.

Structure and reactivity

The numbered structural formula of anthanthrene with its K region indicated at carbon 4 and 5. Anthanthrene K region.png
The numbered structural formula of anthanthrene with its K region indicated at carbon 4 and 5.

PAHs often include bay, fjord, K, and L regions, all of which play an important role in the reactivity of these compounds. However, anthanthrene does not contain any bay, fjord or L regions, and only contains a reactive K region at carbon 4 and 5 [6] A K region is a region where the carbon-carbon bond has an ordinary double-bond character and can thus take part in addition reactions. [7]

Besides structural conditions, reactivity is also dependent on chemical conditions. For chemical conversion to its (toxic) metabolites, the K region needs to be in contact with a P450 enzyme. L regions can interfere with the conversion of the K region by initiating other types of reactions instead, so, for metabolites to form, the K region should be sufficiently active, and it should not be hindered by an active L region. Since anthanthrene does not have this L region, the K region can theoretically react unimpeded, forming carcinogenic epoxides alongside other metabolic products. [8]

Though there is limited evidence of anthanthrene causing cancer in humans, repeated exposure has been shown to cause skin cancer in mice. [9] Two other studies found anthanthrene to be mutagenic to human cells and able to cause DNA damage. [8] [10] However, there is some debate as to whether anthanthrene is truly carcinogenic. [11] One study found that the compound is biologically inactive, even though it meets the criteria that the researchers set for carcinogenicity in PAHs. [6] The research hypothesizes that the inactivity is caused by two very reactive carbons (11 and 12) that interfere with the epoxide formation in the K region, but suggest more research is needed. Currently, there is no known antidote for anthanthrene exposure, and PAH exposure is typically handled by symptomatic treatment. [12]

Exposure

When individuals are rarely exposed to isolated anthanthrene, but rather to a complex mixture of several PAHs including anthanthrene. [12] Anthanthrene and other PAHs get released into the atmosphere by the incomplete combustion of organic materials by humans, [2] such as industrial emissions, vehicle exhaust gas, and cigarette smoke, as well as non-human sources such as forest fires and volcanic eruptions. Anthanthrene exposure mostly occurs through inhalation of polluted air, cigarette smoke, or ingestion of food. [1]

Some professions are exposed to higher levels of PAHs, including anthanthrene. Professions with the highest exposure (>10 μg/m3 ) occur in aluminum work, manufacturing of carbon electrodes, handling of molten tar or pitch, chimney sweeping, and timber impregnation. [13] Currently, there are no established specific exposure limits for anthanthrene. However, regulatory agencies often set limits for PAHs as a group. [14]

Environmental effects

Because PAHs such as anthanthrene have very apolar structures, they can be tightly absorbed to organic compounds in soils and sediments, making them less accessible for biodegradation by microorganisms. However, PAHs can disappear from the soil by flushing into groundwater, irreversible sorption to soil organic matter, volatilisation, photooxidation, abiotic losses, uptake by plants, or microbial degradation. [15]

The uptake of PAHs by plants is dependent on the type of plant, environmental conditions, and the solubility of the PAH. Smaller PAHs will be less hydrophobic and more soluble in water, making it easier for root uptake and translocation. [16] PAHs can also enter plants in a gaseous state via foliar uptake. A plant with a high lipid content has a higher tendency to bind PAHs. PAHs can absorb on the leaf wax's lipophilic surface and can enter internal components of the leaf, so plants that have a large leaf surface area have a higher potential for absorption and accumulation of PAHs. PAHs have a negative effect on the plant's growth and development. [17]

Aquatic organisms are sensitive to contamination by PAHs via direct exposure to contaminated water, sediments, and plants. PAHs will mostly reside in their skin tissues, restricting the organism's metabolism causing biotransformation to occur through food chains. [15] PAHs persisting in soils and sediments leads to constant contamination of aquatic organisms and plants bioaccumulation and biomagnification. [15]

Biotransformation

Three different pathways have been identified for the biotransformation of anthanthrene in bacteria: pathway I, II, and III. These pathways lead to different types of metabolites. Though these metabolites are often simply excreted, they still pose a risk of toxicity. [8]

Pathway I

In pathway I, metabolites are produced through an epoxide formation between the carbons in the K-region. This pathway is enzymatically catalyzed by the cytochrome P450 2B subfamily, which is responsible for monooxygenation. The metabolites 4,5-dihydrodiol, 9-phenol-4,5-dihydrodiol and phenol-dihydrodiol are formed by the enzyme epoxide hydrolase. This enzyme detoxifies the genotoxic 4,5-epoxide formed at the K region.

Pathway II

In pathway II, polynuclear quinones are formed. This pathway uses autoxidation as the means of catalysis, and thus the conversion to 1,6-quinone, 3,6-quinone (genotoxic) and 6,12-quinone happens by oxidation through one electron.

Pathway III

Metabolites formed in pathway III are mono- and diphenols. Similar to Pathway I, Pathway III proceeds via enzymatic catalysis, though in this instance the P450 subfamily is 1A. This group of enzymes causes monooxygenation at the ring in anthanthrene with carbons 1, 2 and 3 (the ring on the top right), leading to the formation of mono- and diphenols by further oxidation.

Molecular mechanism of action

Molecules such as benzo[a]pyrene and chrysene, which are chemically similar to anthanthrene, have binding affinity to the blood protein albumin, allowing transport through the body. [18] This hints that anthanthrene could also be transported through the body mediated by albumin, though there is no experimental proof of this. [8] It is suspected that anthanthrene is primarily metabolized in the liver. [19]

Research suggests that anthanthrene 4,5-epoxide and the 3-hydroxyanthanthrene are the metabolites of anthanthrene that are most mutagenic. [8]

Anthanthrene 4,5-epoxide

The epoxide ring at the 4,5-position is highly strained and electrophilic, making it susceptible to nucleophilic attack by DNA bases, particularly the N7 position of guanine, which results in DNA adducts. If not repaired, these adducts can lead to replication errors, base substitutions (e.g., G→T transversions), and strand breaks, contributing to carcinogenesis. [20]

3-hydroxyanthanthrene

3-hydroxyanthanthrene is further biotransformed into multiple quinones, primarily 3,6-quinone. These quinones are electrophilic, making it possible to react with nucleophiles like DNA bases. The primary site of attack is the guanine at the N7 position, but adenine (N3) and cytosine (N3) can also be involved. The attack on the DNA base causes DNA adducts which lead to replication errors, base substitutions (e.g. G→T transversions), and strand breaks, contributing to carcinogenesis. [21]

It is important to note that much of our understanding of anthanthrene's molecular mechanism of action is inferred from studies on similar PAHs.[ citation needed ] Direct experimental evidence specific to anthanthrene is limited, and further research is needed to confirm its toxic effects.[ citation needed ]

Degradation

Through biotransformation, anthanthrene is converted into various metabolites. In rats, these have been found to primarily be 3-hydroxyanthanthrene and anthanthrene 3,6-quinone. [22] Further metabolic processing yields additional metabolites that have been described before, with significantly increased water solubility compared to the original compound. This allows for excretion through 3 routes: bile, feces, and urine. [23]

PAHs, in general, are mostly excreted through bile, and less in feces and urine. For example, studies on benzo[a]pyrene showed that bile "accounts for [excretion of] approximately 60% of an intravenous dose, while urinary excretion represented only about 3%". [23] This pattern is in general true for higher molecular weight PAHs, like anthanthrene and benzo[a]pyrene. [23] Unfortunately, studies specifically focusing on anthanthrene excretion are limited.

Studies on other PAHs have shown altering urinary excretion percentages, with phenanthrene, pyrene, and benzo[a]pyrene having urinary excretion efficiencies of 40.4%, 11.4%, and 6.3%, respectively. Anthanthrene's urinary excretion rate likely falls on the low side, like benzo[a]pyrene, because of its high molecular weight. [24]

Glucuronic acid conjugates of PAH metabolites in the gastrointestinal tract can be broken down by microorganisms. These metabolites are then released and can be reabsorbed in a process called enterohepatic circulation. [23] This could be happening for anthanthrene metabolites as well, allowing for longer exposure times in the body. Half-life data are unavailable for anthanthrene, but other studies on PAHs show relatively rapid excretion. Research on urinary PAH metabolites has shown that 58-79% of urinary OH-PAHs are often excreted within the first 12 hours after exposure. [25] It is expected that smaller PAHs will be excreted faster than larger PAHs, such as anthanthrene.

References

  1. 1 2 "Polycyclic aromatic hydrocarbons". Australian Government: Department of Climate Change, Energy, the Environment and Water. July 29, 2022. Retrieved 14 March 2025.
  2. 1 2 PubChem. "Anthanthrene". pubchem.ncbi.nlm.nih.gov. Retrieved 2025-03-15.
  3. ↑ Shah, Bipin K.; Neckers, Douglas C.; Shi, Jianmin; Forsythe, Eric W.; Morton, David (2005-09-01). "Photophysical Properties of Anthanthrene-Based Tunable Blue Emitters" . The Journal of Physical Chemistry A. 109 (34): 7677–7681. Bibcode:2005JPCA..109.7677S. doi:10.1021/jp052337z. ISSN   1089-5639. PMID   16834141.
  4. ↑ Kodama, M.; Kimura, T.; Nagata, C.; Shudo, K. (December 1978). "Enzymic formation of free radical from anthanthrene and 10-aza-benzo[alpha]pyrene lacking the bay region". Gan. 69 (6): 865–866. ISSN   0016-450X. PMID   750281.
  5. ↑ Platt, Karl L.; Aderhold, Susanne; Kulpe, Kathrin; Fickler, Michael (2008-02-29). "Unexpected DNA damage caused by polycyclic aromatic hydrocarbons under standard laboratory conditions" . Mutation Research/Genetic Toxicology and Environmental Mutagenesis. 650 (2): 96–103. Bibcode:2008MRGTE.650...96P. doi:10.1016/j.mrgentox.2007.09.011. ISSN   1383-5718. PMID   18160334.
  6. 1 2 Pullman, A.; Pullman, B. (1955-01-01), Greenstein, Jeese P.; Haddow, Alexander (eds.), Electronic Structure and Carcinogenic Activity of Aromatic Molecules New Developments , Advances in Cancer Research, vol. 3, Academic Press, pp. 117–169, doi:10.1016/s0065-230x(08)60919-7, ISBN   978-0-12-006603-2, PMID   13248740 , retrieved 2025-03-16{{citation}}: ISBN / Date incompatibility (help)
  7. ↑ Cammack, R. (2006). Oxford Dictionary of Biochemistry and Molecular Biology[K region] (2nd ed.). Oxford University Press. p. 371. ISBN   9780198529170.
  8. 1 2 3 4 5 Platt, Karl L.; Degenhardt, Christian; Grupe, Stefanie; Frank, Heinz; Seidel, Albrecht (2002-03-01). "Microsomal Activation of Dibenzo[def,mno]chrysene (Anthanthrene), a Hexacyclic Aromatic Hydrocarbon without a Bay-Region, to Mutagenic Metabolites" . Chemical Research in Toxicology. 15 (3): 332–342. doi:10.1021/tx010131t. ISSN   0893-228X. PMID   11896680.
  9. ↑ Cavalieri, E.; Mailander, P.; Pelfrene, A. (1977-01-01). "Carcinogenic activity of anthanthrene on mouse skin" . Zeitschrift für Krebsforschung und Klinische Onkologie. 89 (2): 113–118. doi:10.1007/BF00308512. ISSN   1432-1335. PMID   143140.
  10. ↑ Desler, Claus; Johannessen, Christian; Rasmussen, Lene Juel (2009-02-12). "Repair of DNA damage induced by anthanthrene, a polycyclic aromatic hydrocarbon (PAH) without bay or fjord regions" . Chemico-Biological Interactions. 177 (3): 212–217. Bibcode:2009CBI...177..212D. doi:10.1016/j.cbi.2008.10.056. ISSN   0009-2797. PMID   19046955.
  11. ↑ da Silva Junior, Francisco Carlos; Felipe, Maria Beatriz Mesquita Cansanção; Castro, Denis Elvis Farias de; Araújo, Sinara Carla da Silva; Sisenando, Herbert Costa Nóbrega; Batistuzzo de Medeiros, Silvia Regina (2021-06-01). "A look beyond the priority: A systematic review of the genotoxic, mutagenic, and carcinogenic endpoints of non-priority PAHs" . Environmental Pollution. 278 116838. Bibcode:2021EPoll.27816838D. doi:10.1016/j.envpol.2021.116838. ISSN   0269-7491. PMID   33714059.
  12. 1 2 Mumtaz, G., Moiz, J. (1995). Toxicological profile for polycyclic aromatic hrydocarbons. Public Health Service, & Agency for Toxic Substances and Disease Registry.{{cite book}}: CS1 maint: multiple names: authors list (link)
  13. ↑ Brits, M., Schillack, V.R. (2006). "The occupational exposure of polycyclic aromatic hydrocarbons (PAHs)" (PDF). Occupational Health Southern Africa. 12 (4): 23–25.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  14. ↑ "Clean and safe use due to the absence of banned carcinogenic substances - meeting strict EU safety standards". UPM Biochemicals.
  15. 1 2 3 Kariyawasam, Thiloka; Doran, Gregory S.; Howitt, Julia A.; Prenzler, Paul D. (2022-03-01). "Polycyclic aromatic hydrocarbon contamination in soils and sediments: Sustainable approaches for extraction and remediation" . Chemosphere. 291 (Pt 3): 132981. Bibcode:2022Chmsp.29132981K. doi:10.1016/j.chemosphere.2021.132981. ISSN   0045-6535. PMID   34826448.
  16. ↑ Zhang, Shichao; Yao, Hong; Lu, Yintao; Yu, Xiaohua; Wang, Jing; Sun, Shaobin; Liu, Mingli; Li, Desheng; Li, Yi-Fan; Zhang, Dayi (2017-09-22). "Uptake and translocation of polycyclic aromatic hydrocarbons (PAHs) and heavy metals by maize from soil irrigated with wastewater". Scientific Reports. 7 (1): 12165. Bibcode:2017NatSR...712165Z. doi:10.1038/s41598-017-12437-w. ISSN   2045-2322. PMC   5610240 . PMID   28939846.
  17. ↑ Tarigholizadeh, Sarieh; Sushkova, Svetlana; Rajput, Vishnu D.; Ranjan, Anuj; Arora, Jayati; Dudnikova, Tamara; Barbashev, Andrey; Mandzhieva, Saglara; Minkina, Tatiana; Wong, Ming Hung (2024-01-10). "Transfer and Degradation of PAHs in the Soil–Plant System: A Review" . Journal of Agricultural and Food Chemistry. 72 (1): 46–64. Bibcode:2024JAFC...72...46T. doi:10.1021/acs.jafc.3c05589. ISSN   0021-8561. PMID   38108272.
  18. ↑ "T3DB: Anthanthrene". www.t3db.ca. Retrieved 2025-03-17.
  19. ↑ Humans, IARC Working Group on the Evaluation of Carcinogenic Risks to (2010), "Summary of Data Reported and Evaluation", Some Non-heterocyclic Polycyclic Aromatic Hydrocarbons and Some Related Exposures, International Agency for Research on Cancer, retrieved 2025-03-17
  20. ↑ Hwa Yun, Byeong; Guo, Jingshu; Bellamri, Medjda; Turesky, Robert J. (2020). "DNA adducts: Formation, biological effects, and new biospecimens for mass spectrometric measurements in humans". Mass Spectrometry Reviews. 39 (1–2): 55–82. Bibcode:2020MSRv...39...55H. doi:10.1002/mas.21570. ISSN   1098-2787. PMC   6289887 . PMID   29889312.
  21. ↑ Xiong, Yue; Kaw, Han Yeong; Zhu, Lizhong; and Wang, Wei (11 November 2021). "Genotoxicity of quinone: An insight on DNA adducts and its LC-MS-based detection" . Critical Reviews in Environmental Science and Technology. 52 (23): 4217–4240. doi:10.1080/10643389.2021.2001276. ISSN   1064-3389.
  22. ↑ Degenhardt, Christian; Bors, Wolf; Stettmaier, Kurt; Seidel, Albrecht; Frank, Heinz; and Platt, Karl-L. (22 September 2006). "Metabolic Activation of Anthanthrene: Significance of Stable Radicals Derived from its Key Metabolite 3-Hydroxyanthanthrene" . Polycyclic Aromatic Compounds. 10 (1–4): 85–92. doi:10.1080/10406639608034683. ISSN   1040-6638.
  23. 1 2 3 4 Larsen, J.C. (2013). Polyaromatic Hydrocarbons (PAH). Evaluation of health hazards and estimation of a quality criterion in soil. Copenhagen, Denmark: The Danish Environment Protection Agency. pp. 3–23. ISBN   978-87-93026-78-0.
  24. ↑ Motorykin, Oleksii; Santiago-Delgado, Lisandra; Rohlman, Diana; Schrlau, Jill E.; Harper, Barbara; Harris, Stuart; Harding, Anna; Kile, Molly L.; Massey Simonich, Staci L. (2015-05-01). "Metabolism and excretion rates of parent and hydroxy-PAHs in urine collected after consumption of traditionally smoked salmon for Native American volunteers". Science of the Total Environment. 514: 170–177. Bibcode:2015ScTEn.514..170M. doi:10.1016/j.scitotenv.2015.01.083. ISSN   0048-9697. PMC   4361301 . PMID   25659315.
  25. ↑ Li, Zheng; Romanoff, Lovisa; Bartell, Scott; Pittman, Erin N.; Trinidad, Debra A.; McClean, Michael; Webster, Thomas F.; Sjödin, Andreas (2012-07-16). "Excretion Profiles and Half-Lives of Ten Urinary Polycyclic Aromatic Hydrocarbon Metabolites after Dietary Exposure". Chemical Research in Toxicology. 25 (7): 1452–1461. doi:10.1021/tx300108e. ISSN   0893-228X. PMC   4618384 . PMID   22663094.
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