1-methylchrysene

BCR Analytical Approach for the Certification of PAHs in Natural Matrix CRMs Prior to the certification analyses for the CRM, each participating laboratory has to prepare standard solutions of the analytes to be determined from certified reference compounds (purity >99.0 %) to calibrate their instruments for response and response linearity (multiple point calibration), detection limit, and reproducibility. In the case of PAH measurements, reference compounds of certified purity are used as internal standards, which are not present at a detectable concentration in the matrix to be analyzed (e.g. indeno[i,2,3-cd]fluoranthene (CRM 267), 5-methylchrysene (CRM 081R), benzo[f ]chry-sene (CRM 046), picene (CRM 168), and/or phenanthrene-dio). 

Methods for the synthesis of the biologically active dihydrodiol and diol epoxide metabolites of both carcinogenic and noncarcinogenic polycyclic aromatic hydrocarbons are reviewed. Four general synthetic routes to the trans-dihydrodiol precursors of the bay region anti and syn diol epoxide derivatives have been developed. Syntheses of the oxidized metabolites of the following hydrocarbons via these methods are described benzo(a)pyrene, benz(a)anthracene, benzo-(e)pyrene, dibenz(a,h)anthracene, triphenylene, phen-anthrene, anthracene, chrysene, benzo(c)phenanthrene, dibenzo(a,i)pyrene, dibenzo(a,h)pyrene, 7-methyl-benz(a)anthracene, 7,12-dimethylbenz(a)anthracene, 3-methylcholanthrene, 5-methylchrysene, fluoranthene, benzo(b)fluoranthene, benzo(j)fluoranthene, benzo(k)-fluoranthene, and dibenzo(a,e)fluoranthene. 

In contrast, the fluorine atom at the peri-position of 12F-5-methylchrysene influences dihydrodiol formation in the adjacent angular ring. Whereas the ratio of 5-MeC-7,8-diol to 5-MeC-l,2-diol in mouse epidermis was 1 1, 2 hr after topical application of [%] 5-MeC, the ratio of 12F-5-methylchrysene-7,8-diol to 12F-5-methylchrysene-1,2-diol was 68 1. In contrast to 5-MeC, the metabolites formed from 12F-5-methylchrysene in mouse skin resulted almost exclusively from oxidation at the 7,8-bond (57). Thus, metabolic switching to the less tumorigenic 7,8-dihydrodiol appears to be the basis for the lower tumorigenicity of 12F-5-methylchrysene compared to 5-MeC. 

Figure 2. Views of some carcinogenic molecules showing K- and bay- regions. Views are given of BP (I), DMBA (II), 3-methyl-cholanthrene (III), ll-methyl-15,16-dihydrocyclopenta[a]phen-anthracene (VII) and 5-methylchrysene (VIII). These and all subsequent ball-and-stick diagrams were drawn using the computer program VIEW (141).

FIGURE 19.24 HPLC separation of a standard mixture of 16 EU-priority PAHs plus EPA-priority PAHs, benzo[e]pyrene and benzo[fc]chrysene. Na=naphthalene, Ac = acenaphthylene, E=fluorene, Pa=phenan-threne, A = anthracene, El = fluoranthene, P = pyrene, BcE = benzo[c]fluoranthene, CPP = cyclopenta[c,4] pyrene, BaA = benz[a]anthracene, Ch = chrysene, 5-MeCh = 5 methylchrysene, BeP = benzo[e]pyrene, BjE = benzo[/ ]fluoranthene, BbF = benzo[h]fluoranthene, BkE = benzo[l ]fluoranthene, BaP = benzo[a]pyrene, DBahA = dibenz[a,/j]anthracene, DBalP = dibenzo[a,l]pyrene, BghiP = benzo[g,/j,i]perylene, IP = indeno [l,2,3-c4]pyrene, DBaeP = dibenzo[a,e]pyrene, BbCh = benzo[h]chrisene, DBaiP = dibenzo[a,i]pyrene,... 

Melphalan Merphalan Mestranol 2-Methylaziridine Methylazoxy-methanol acetate Methyl chloromethyl ether 5-Methylchrysene 4,4 -Methylenebis (2-chloroaniline (MOCA) 4,4 -Methylenebis (N,N-dimethyl-benzenamine) 4,4 -Methylene dianiline Methyl bromide Methyl chloride Methyl hydrazine Methyl iodide... 

The Suzuki cross-coupling reaction is recognized as a novel, abbreviated method for the synthesis of 2-hydroxychrysene, 2-hydroxy-5-methylchrysene, and 8-hydroxy-5-methyl-chrysene from easily accessible reactants (Eq. (8)) [23]. These phenolic compounds constitute precursors for the synthesis of dihydrodiol and bay-region diol epoxide derivatives of chrysene and 5-methylchrysene, which are implicated as the active forms of carcinogenic polynuclear aromatic hydrocarbons. 

C19H10FNS 2-fluoro-benzo(e)(1)benzothiopyrano(4,3-b)in 52831-45-5 454.15 39.497 2 31365 C19H1603 anti-5-methylchrysene-1,2-diol-3,4-epoxide 81851-68-5 610.15 54.562 2... 

C19H13F 9-fluoro-5-methylchrysene 64977-48-6 389.30 33 358 2 31545 C19H24N20 impiramine-N-oxide 2207-85-4 496.40 43.538 2... 

C19H1602 7,8-dihydro-7,8-dihydroxy-5-methylchrysene 67523-22-2 500 40 43 923 2 31676 C19H3602 methyl trans-9-octadecenoate 1937-62-8 617.00 55.232 2... 

When the determination of a crystal structure is difficult or refinement gives a strangely shaped molecule, it is possible that the molecule is disordered in a site in the crystal. This happens when the available space in the crystal is such as to accommodate two different orientations of the molecule. For example, in the crystal structure of 5-methylchrysene, -one of the two molecules in the asymmetric unit is disordered. It was difficult to solve the crystal structure until the nature of the disorder was realized. In a given site, this disordered molecule may be in one of two possible orientations. In some places in the disordered electron density map, atoms in the two orientations of the disordered molecule are near each other and their positions can be approximated (erroneously) by the use of highly anisotropic temperature parameters. The result is that the anisotropic temperature parameters on refinement do not make any sense until the nature of the disorder is understood. 

There may be more than one molecule in the asymmetric unit. This appears to happen more frequently when the molecules have awkward shapes that do not accommodate well to simple packing principles. An example is provided by the crystal structure of 5-methylchrysene in... 

Koehl W, Amin S, Staretz ME, Ueng YF, Yamazaki H, et al. 1996. Metabolism of 5-methylchrysene and 6-methylchrysene by human hepatic and pulmonary cytochrome P450 enzymes. Cancer Res. 56 316-24... 

Myers SR, Flesher JW. 1991b. Metabolism of chrysene, 5-methylchrysene, 6-methylchrysene and... 

Participants were requested to use as much as possible the CRM calibrants from BCR [26]. The use of at least one internal standard was mandatory the participants, however, were left free to select the internal standard(s) best suited to their methods. They had to verify that the selected compound(s) did not occur in the candidate reference material or did not interfere with compounds present in the material. Two internal standards were made available from BCR, namely indeno[l,2,3-c< fluoranthene (CRM 267) and 5-methylchrysene (CRM 08IR). 

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