Benzo(j)fluoranthene

Updated on Jan 30, 2024

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Formula C20H12		Appearance solid

Natural occurrence

Benzo[j]fluoranthene 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. More than 20% of the carbon in the universe may be associated with PAHs, including the benzofluoranthenes.

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 (>900 °C) followed by ring rearrangements (ring contraction/expansion) to selectively yield BjF. benzo[k]fluoranthene may also be converted via similar processes to BjF by FVT at temperatures ≥ 1100 °C (6% yield) or ≥ 1200 °C (11% yield) with 38% mass recovery.

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(fig. 1).

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. 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. 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.

Metabolism

Despite the ubiquitous occurrence of benzofluoranthenes in the environment, little is known about their metabolic activation. Only one such study has appeared in which the binding of dibenzo(a,e)fluoranthene to nucleic acids was investigated. Here the potential of BjF-9,10-dihydrodiol" and BkF-8,9-dihydrodiol to contribute to the mutagenicity of BjF and BkF toward S. typhimurium TA 100 has been evaluated.

A high-pressure liquid chromatogram of the metabolites of BjF formed in vitro is shown in figure 2. Six bands of metabolites were collected and tested for mutagenicity toward S. typhimurium TA 100 with activation. The results are summarized in Table 1. Band 3 had the highest mutagenic activity, suggesting that this band contained proximate mutagenic metabolites of benzo(y)fluoranthene (ByF). When tested separately, each of Peaks A and B of Band 3 was mutagenic (Table 1). Dihydrodiols are proximate mutagenic metabolites of BjF. BjF-9,10-dihydrodiol was mutagenic only in the presence of rat liver homogenate, indicating that its mutagenic activities resulted from conversion to dihydrodiol-epoxides, as observed with other hydrocarbons. Other metabolites may also contribute to the mutagenicity of BjF. This includes BjF-9,10-epoxide which is the likely precursor to the observed dihydrodiols, but it was not isolated or synthesized. The structure of BjF-9,10-dihydrodiol is similar to those of dihydrodiols which are proximate forms of other carcinogenic polycyclic aromatic hydrocarbons and can form dihydrodiol- epoxides with one carbon of the epoxide ring in a 3-sided "bay region". The presumed ultimate mutagen derived from B(j)F9,10-dihydrodiol, 9,10-dihydro-9,10-dihydroxy- 11,12-epoxybenzo(j)-fluoranthene would have the epoxide ring in a 4-sided, "pseudo-bay region," in which the additional side is derived from the 5-membered ring. Such a dihydrodiol-epoxide would not be expected to be a potent carcinogen. B(j)F-9,10-dihydrodiol is currently being bioassayed on mouse skin for carcinogenicity. It is the conversion of trans-4,5-dihydro-4,5-dihydroxybenzo[j]fluoranthene to anti-4,5-dihydroxy-5,6a-epoxy-4,5,6,6a- tetrahydrobenzo[j]fluoranthene that is principally associated with DNA adduct formation in mouse skin.

PAHs

One of the earliest connection between PAH’s, combustion, and cancer was established by Cook and co-workers with the isolation of the carcinogen benzo[a]pyrene from coal tar extract. Benzo[a]pyrene now has been well characterized in toxicology reports and is a known potent carcinogen. 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. 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. 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.