New SYNTHETIC METHOD OF 13H-DIBENZO[A,DE]ANTHRACENE-13-ONE

The polycyclic aromatic ketone, 13H-dibenzo[a,de]anthracene-13-one (5,6-BBz) is useful as a starting material for synthesis of undecacyclic aromatic compounds by means of condensation. To synthesize 5,6-BBz, glycerol condensation of benzo[a]anthraquinone was conducted. The condensation, however, gave two structural isomers besides 5,6-BBz and the isolation was very difficult; separation of the crude products by column chromatography or high-vacuum sublimation was unsuccessful because of their similarity in structure and vapor pressure. Only a little 5,6-BBz was obtained by repeated recrystallization, but the amount was insufficient for condensation. Thus, we developed a new synthetic method which affords 5,6-BBz selectively. 9-(o-Chlorobenzoyl)anthracene was synthesized by the Friedel-Crafts' reaction of anthracene with o-chlorobenzoyl chloride and aluminum chloride anhydride. In order to suppress the production of 9,10-di(o-chlorobenzoyl) anthracene, the reaction was performed at low temperature. The crude products obtained were purified by column chromatography on activated alumina and then recrystallized with benzene, which yielded yellow crystals of 9-(o-chlorobenzoyl)anthracene. The structure of 9-(o-chlorobenzoyl)anthracene was determined by X-ray diffraction analysis for the first time. Cyclo-dehydrohalogenation of 9-(o-chlorobenzoyl) anthracene gave 5,6-BBz selectively, the amount of which was sufficient for synthesizing undecacyclic aromatic hydrocarbons.     

Synthesis of Hexabenzo[a,cd,f,j,lm,o]perylene

Hexabenzo[a,cd,f,j,lm,o]perylene (HBP), an undecacyclic condensed polycyclic aromatic hydrocarbon with two severely crowded fjord regions, was synthesized by Clar's method; the starting material 8H-benzo[fg]-naphthacene-8-one was newly prepared by the glycerol condensation of 5,12-dihydro-naphthacene-5,12-dione. ¹H and ¹³C NMR spectra of HBP were measured and the chemical shifts were completely assigned. Absorption and fluorescence spectra of HBP were also measured and the effects of nonplanarity on its spectroscopic properties was discussed.     

IDENTIFICATION OF THE C30H16 POLYCYCLIC AROMATIC HYDROCARBON BENZO[cd]NAPHTHO[1,2,3-lm]PERYLENE AS A PRODUCT OF THE SUPERCRITICAL PYROLYSIS OF A SYNTHETIC JET FUEL

Using high-pressure liquid chromatography (HPLC) with ultraviolet-visible (UV) diode-array and mass spectrometric detection, we have analyzed the products of a Fischer-Tropsch synthetic jet fuel pyrolyzed, under supercritical conditions, at 710°C and 42 atm. An eight-ring polycyclic aromatic hydrocarbon, benzo[cd]naphtho[1,2,3-lm]perylene, has been unequivocally identified among the product components by its characteristic ultraviolet-visible absorbance spectrum. First, the unknown product component's HPLC elution behavior and UV absorbance characteristics indicated that it was a planar benzologue of dibenzo[cd,lm]perylene, having a high length-to-breadth ratio. Next, the mass spectrum established the isomer family of the unknown compound as C₃₀H₁₆. The UV absorption spectrum was then progressively analyzed with different solvents to achieve the final identification of benzo[cd]naphtho[1,2,3-lm]perylene. Benzo[cd]naphtho[1,2,3-lm]perylene has never before been reported as a product in any combustion or pyrolysis study.     

SYNTHESIS OF 1-BROMO-6H-BENZO[CD]PYREN-6-ONE

1-Bromonaphthanthrone (1-bromo-6H-benzo[cd]pyren-6-one), a useful starting material for the synthesis of undecacyclic aromatic hydrocarbons, was synthesized by means of glycerol condensation of 1-bromopyrene. The structure of the synthetic product was confirmed by NMR measurements and the ¹ H and ¹³ C chemical shifts were completely assigned. Although the synthetic method provided three possible isomers, 1-, 3-, and 5-bromonaphthanthrone, only 1-bromonaphthanthorone was obtained as a final product. An explanation for the regioselectivity was given in terms of the charge distribution obtained by molecular orbital calculations.     

Contamination of Soil by Polycyclic Aromatic Hydrocarbons in Some Urban Areas

The contamination by 16 polycyclic aromatic hydrocarbons (PAHs) in surface soils, sampled at a 0-5 cm depth in the urban areas of Tallinn, Helsinki, Vilnius, Chicago, London is reported. All samples were analyzed using the same protocol. The median concentrations ( w g/kg) were found to be 117, 539, 127, 3,263, 1,728 for pyrene; 62, 236, 43, 1,634, 1,652 for benzo[ a ]pyrene; 86, 304, 92, 2,295, 2,068 for benzo[ a ]pyrene toxic equivalents, calculated using the benzo[ a ]pyrene toxic equivalency factors; 467, 1,471, 392, 8,981, 6,837 for a total of seven probable human carcinogenic PAHs: benzo[ a ]anthracene, chrysene, benzo[ b ]fluoranthene, benzo[ k ]fluoranthene, benzo[ a ]pyrene, dibenz[ ah ]anthracene, indeno[1,2,3- cd ]pyrene; 911, 2,941, 672, 16,183, 13,718 for the total of 16 PAHs, recommended by the U.S. Environmental Protection Agency: naphthalene, acenaphthylene, acenaphthene, fluorene, phenanthrene, anthracene, fluoranthene, pyrene, benzo[ a ]anthracene, chrysene, benzo[ b ]fluoranthene, benzo[ k ]fluoranthene, benzo[ a ]pyrene, dibenz[ ah ]anthracene, benzo[ ghi ]perylene, indeno[1,2,3- cd ]pyrene in Tallinn ( n = 3), Helsinki ( n = 3), Vilnius ( n = 15), Chicago ( n = 4), London ( n = 3), respectively. The size of the population is a statistically significant factor in urban soil contamination by high-molecular-mass PAHs.     

CONDENSATION PRODUCTS OF 7H-BENZO[DE]NAPHTHACENE-7-ONE

Condensation reaction of 7H-benzo[de]naphthacene-7-one (1 Kohno, Y., Kohno, M., Saito, Y. and Inokuchi, H. 1975. Crystal Structure of Tetrabenzo[a,cd,j,lm]perylene. Acta Cryst., B31: 2076–2080.  [Google Scholar]) was conducted in fused salt using zinc dust at 275°C for 2 h. The reaction products were isolated by column chromatography and then purified by recrystallization, yielding crystals of orange-yellow needles as the main product. This compound with an absorption maximum at 450 nm was identified as trinaphtho[2,3-c; 2′,1′,8′-fgh; 2″,1″,8″-uva]-pentaphene by one-dimensional and two-dimensional ¹H NMR spectroscopy, which was one of expected condensation products. We are now trying to isolate the other expected condensation products, benzo[vwx]dinaphtho[2,1-a; 8′,1′,2′-cde]hexaphene and benzo[cd]naphtho[2,3-f]anthra[3,2,1-lm]perylene, from the byproducts.     

DETERMINATION OF DIBENZO[A,L]PYRENE AND OTHER FJORD-REGION PAH ISOMERS WITH MW 302 IN ENVIRONMENTAL SAMPLES

Polycyclic aromatic hydrocarbons (PAHs) occur in the environment as complex mixtures including compounds with mutagenic and carcinogenic activity. The PAH profile routinely determined in environmental samples at present encompasses isomers with molecular weight (MW) not greater than 300. However, PAHs with MW >300 have been demonstrated for several matrices to contribute up to 50% of the total activity when tested for carcinogenicity in experimental animals. Recent studies indicate that among the dibenzopyrenes with MW 302 dibenzo[a,l]pyrene, possessing a fjord region, is by far the most carcinogenic PAH hitherto identified. To further elucidate the environmental relevance of this compound we have applied the isotope dilution GC/MS technique as analytical procedure to determine this compound and the related fjord region PAH naphtho[1,2-a]- and naphtho[1,2-e]pyrene in various matrices. Identification was based on comparison of UV and mass spectra as well as retention times of authentic reference materials. Determination of these PAHs was achieved after clean-up by several chromatographic steps including fractionation on a modified TABA-silica gel column. Quantitative data for matrices such as two cigarette smoke condensates, motor vehicle exhaust condensate (Otto-type engines), and tar-cork are reported. Based on toxic equivalent factors the relative contribution of dibenzo[a,l]pyrene (5.4–42.3%) to the total carcinogenic activity of a PAH profile will be discussed comprising 14 selected isomers (benzo[b]naphtho[2,1-d]thiophene; cyclopenta[cd]pyrene; benz[a]anthracene; chrysene/triphenylene; sum of benzo[b]-, benzo[k]-, and benzo[j]fluoranthene; benzo[a]pyrene; indeno[1,2,3-cd]pyrene; dibenz[a,h]anthracene; benzo[ghi]perylene; anthanthrene; dibenzo[a,l]pyrene determined in these matrices.     

POLYCYCLIC AROMATIC HYDROCARBONS IN BALTIC SEA SEDIMENTS

Present concentrations of parent polycyclic aromatic hydrocarbons (PAHs) were studied in bottom sediments of the Baltic Sea. Sediments were collected in 2001 and 2002 from the Gulf of Finland, the Northern Baltic Proper, the Eastern Gotland Basin, the Southern Baltic Proper, and Kattegat. Parent PAHs were quantified by liquid chromatography with fluorescence detection. The sum of 13 PAHs in 1 cm slices in the first 5 cm varied between 64 and 5161 ng/g (dw) depending on the bottom type. The most contaminated area was in the Eastern Gotland Basin, and the most abundant PAH components found in sediments were fluoranthene, benzo[b]fluoranthene, benzo[ghi]perylene, and indeno[1,2,3-cd]pyrene. The studied PAHs were both pyrolytic and petrogenic in origin. In addition, the concentrations of indeno[1,2,3-cd]pyrene and benzo[ghi]perylene indicated a contribution from diesel engines, which may indicate pollution caused by the steadily increased shipping in the Baltic Sea.     

Synthesis of 1- and 2-Chloro-7 H -benz[ de ]anthr-7-one

Chloro-7 H -benz[ de ]anthr-7-ones (chlorobenzanthrones) are useful as starting materials for synthesis of larger polycyclic aromatic compounds by means of condensation. In the synthesis, the position of the chlorine atom is very important because the structure of condensation products strongly depends on it. For this reason, we have synthesized several chlorobenzanthrones. Although 3- and 4-chlorobenzanthrone were prepared by direct chlorination of benzanthrone and by glycerol condensation of 2-chloroanthraquinone, respectively, the synthesis of 1- and 2-chlorobenzanthrone has not yet been successful. In the present study, we attempted to synthesize them by use of the Sandmeyer reaction. First, we nitrated benzanthrone with nitric acid; 1- and 2-nitrobenzanthrone were obtained by nitration in nitrobenzene at 50-60° and in glacial acetic acid at 105-110°, respectively. Then the nitroderivatives were reduced to corresponding aminoderivatives; the reduction was performed with sodium sulfide for 1-nitrobenzanthrone and with hydrogen chloride and tin for 2-nitrobenzanthrone. Finally, chlorination was carried out by use of the Sandmeyer reaction. The products were separated and purified by column-chromatography. The position of chlorination was confirmed by NMR spectroscopy.     

Extraction of Polycyclic Aromatic Hydrocarbons in Barn Owls ( Tyto Alba ) from Northwest Spain by SFE and HPLC-FL Analysis

Supercritical fluid extraction (SFE) and high-performance liquid chromatography-fluorescence detection (HPLC-FL) were used to determine concentration of anthracene, benzo[ a ]anthracene, benzo[ a ]pyrene, benzo[ b ]fluoranthene, benzo[ ghi ]perylene, benzo[ k ]fluoranthene, chrysene, fluoranthene, pyrene, and indeno[1,2,3- cd ]pyrene in six classes of tissue (heart, liver, intestine, muscle, lung, and kidney) of 11 barn owls from Galicia (northwest Spain). We have detected fluoranthene and pyrene in >40.0% of samples, anthracene in 35.4%, and benzo[ a ]anthracene in 12.3%. Mean concentrations were between 0.398 w g/kg dry weight for anthracene and 4.855 w g/kg dry weight for fluoranthene. Lung and intestine tissues were more polluted than the other tissues.     

Aromatic Core Extension in the Series of N‐Cyclic Bay‐Substituted Perylene G‐Quadruplex Ligands: Increased Telomere Damage,Antitumor Activity,and Strong Selectivity for Neoplastic over Healthy Cells

Based on previous work on both perylene and coronene derivatives as G‐quadruplex binders, a novel chimeric compound was designed: N,N′‐bis[2‐(1‐piperidino)‐ethyl]‐1‐(1‐piperidinyl)‐6‐[2‐(1‐piperidino)‐ethyl]‐benzo[ghi]perylene‐3,4:9,10‐tetracarboxylic diimide (EMICORON), having one piperidinyl group bound to the perylene bay area (positions 1, 12 and 6, 7 of the aromatic core), sufficient to guarantee good selectivity, and an extended aromatic core able to increase the stacking interactions with the terminal tetrad of the G‐quadruplex. The obtained “chimera” molecule, EMICORON, rapidly triggers extensive DNA damage of telomeres, associated with the delocalization of telomeric protein protection of telomeres 1 (POT1), and efficiently limits the growth of both telomerase‐positive and ‐negative tumor cells. Notably, the biological effects of EMICORON are more potent than those of the previously described perylene derivative (PPL3C), and more interestingly, EMICORON appears to be detrimental to transformed and tumor cells, while normal fibroblasts expressing telomerase remain unaffected. These results identify a new promising G‐quadruplex ligand, structurally and biologically similar on one side to coronene and on the other side to a bay‐monosubstituted perylene, that warrants further studies.     

Structural and Optical Properties of New Naphthalene and Perylene Imide Imidazoles

ABSTRACT

New unsymmetrically substituted naphthalene and perylene imide imidazoles, N-(2-ethylhexyl)-naphthalene-3,4-(4,5-dicyano-1,2-benzimidazole)-9,10-dicarboxyimide and N-(1-heptyloctyl)-perilene-3,4-(4,5-dicyano-1,2-benzimid-azole)-9,10-dicarboxyimide, were synthesized via condensation reactions of diaminophthalonitrile and aromatic monoimide monoanhydride derivatives. Their structural analyses have been conducted by using general spectroscopic methods including FT-IR, ¹H- and ¹³C-NMR, mass and elemental analysis. The molecular structure of naphthalene derivative was also determined by single crystal x-ray diffraction. Electronic absorption and emission properties were investigated on comparison. For studied compounds, both DFT and TDDFT calculations were carried out with the 6-311G(d,p) basis set, taking into account solvation effects by means of polarizable continuum model as implemented in the Gaussian 09 package.     

7-苄氨基-9,10-二氢-1,2,4-三氮唑并[4,3-a]喹啉衍生物的合成及环合反应的探讨

以6-氨基-3,4-二氢-2(1H)-喹啉酮为起始原料,经缩合、还原、硫代、环合等反应合成了5个7-苄氨基-9,10-二氢-1,2,4-三氮唑并[4,3-a]喹啉衍生物。产物的结构经核磁共振谱和质谱确证。     

Nitration of Condensed Polycyclic Aromatic Ketones

Nitration of three isomeric dibenzanthrones, 13H-dibenzo[a,de]-anthracene-13-one(3), 7H-benzo[hi]chrysene-7-one(4), and 7H-dibenzo[a,kl]anthracene-7-one(5), with concentrated nitric acid was studied under various conditions. The nitration of (3) at 15 °C in 1,1,2,2-tetrachloroethane gave the 5-nitro derivative. The nitration of (4) in boiling acetic acid produced the 9-nitro derivative. The nitration of (5) at 70 °C in acetic acid gave the 5-nitro derivative. These nitro compounds are very useful in synthesizing undecacyclic aromatic hydrocarbons.     

苯并[1,2,3]噻二唑-7-醛的合成

以2-氯-3,5-二硝基苯甲酸为起始原料,经过取代、酯化、还原重氮化等反应,合成了苯并[1,2,3]噻二唑-7-羧酸乙酯。并采用二异丁基氢化铝将其一步还原制备了苯并[1,2,3]噻二唑-7-醛。     

Relationship Between Inhaled PAH and Urinary Excretion of Phenanthrene,Pyrene and Benzo[a]pyrene Metabolites in Coke Plant Workers

Abstract

By means of personal air samplers the exposure to polycyclic aromatic hydrocarbons (PAH) of four coke employees working at different locations was measured during 4 running days. Simultaneously the 24 hrs urines were collected. A simple, well reproducible method for the determination of 9,10-dihydroxy-9,10-dihydrobenzo[a]pyrene, 1-; 2-; 3-; 4- and 9-hydroxyphenanthrenes, 1,2-; 3,4-; and 9,10-dihydroxydihydrophenanthrenes as well as 1-hydroxypyrene and 1,2-dihydroxy-1,2-dihydropyrene was used. As expected, workers on the battery topside are most exposed and, accordingly, excrete by far the highest amount of PAH metabolites. A good correlation between the PAH inhaled during 8 hrs and the metabolites excreted in the 24 hrs urine is observed. 20% to 30% of the inhaled phenanthrene is excreted as dihydrodiols, but only 0.5% of the inhaled benzo[a]pyrene forms 9,10-dihydrodiol in the urine. The individual invariance of the metabolite profile of the isomeric phenols and dihydrodiols indicates a genetically caused enzyme pattern of oxygenases, which can or cannot be induced by exogenous factors. More investigations are necessary to clarify whether this metabolic profile may be suitable as a marker for carcinogenic risk.     

甲磺酸帕珠沙星的合成

以左氧氟沙星中间体(S)-9,10-二氟-3-甲基-7-氧代-2,3-二氢-7-H吡啶[1,2,3-de][1,4]苯并噁嗪-6-羧酸乙酯为起始原料,经与氰乙酸乙酯进行亲核取代反应、水解脱羧、环合、水解、Hoffman降解,与甲磺酸成盐得甲磺酸帕珠沙星,总收率为38%,产品纯度符合药用标准。     

Application of SPME in the Analysis of Polynuclear Aromatic Hydrocarbons in Water by HPLC with DAD Detection

Determination of polynuclear aromatic hydrocarbons is very important in many laboratories of water quality control. The new Council Directive 98/78/EC states that water intended for human consumption shall be monitored on these parameters and meet the parametric values set out in Annex I (less than 0,10 μg/L for the sum of the concentrations of the specified compounds). The usual methodology of such analysis is based on liquid-liquid extraction followed by evaporation/concentration and clean-up steps. The coupling of Solid Phase Microextraction (SPME), a recent sample preparation technique to HPLC and fluorescence or diode-array detection (DAD) is extremely favourable for these compounds, with the aim to reduce the solvent usage and to simplify the procedure. This technique has been applied to the analysis of the following PAHs: fluoranthene, benzo[b]fluoranthene, benzo[k]fluoranthene, benzo[a]pyrene, benzo[ghi]perylene and indeno[1,2,3-cd]pyrene in model aqueous solutions. In this study we describe the optimisation of SPME-HPLC in the analysis of these compounds. The results obtained suggest that this method can be an alternative to the other sample preparation methods already used in this field.     

NEWLY IDENTIFIED PRODUCTS OF BENZENE DROPLET COMBUSTION: POLYCYCLIC AROMATIC HYDROCARBONS OF THREE TO TEN RINGS

Abstract

In order to investigate further the polycyclic aromatic hydrocarbons (PAH) produced by benzene droplet combustion, we have obtained and analyzed a highly-concentrated benzene droplet combustion sample, using high pressure liquid chromatography (HPLC) with diode-array ultraviolet-visible (UV) absorbance spectroscopy. In addition to benzo[k]fluoranthene, we have identified ten large (5- to 10-ring) PAH never before reported as products of benzene pyrolysis or combustion: dibenz[a,c]anthracene, indeno[1,2,3-cd]fluoranthene, anthanthrene, cyclopenta[cd]benzo[ghi]perylene, coronene, dibenzo[a,i]pyrene, cyclopenta[bc]coronene, benzo[a]coronene, naphtho[8,1,2-abc]coronene, and ovalene. In this sample we have also identified three smaller PAH, benz[f]indene, 2-ethynylanthracene, and benzo[c]phenanthrene, never before reported as products of benzene pyrolysis or combustion. In order to document the unequivocal identification of these compounds as benzene droplet combustion products, we present the UV absorbance spectrum of each newly identified benzene product, along with the matching UV spectrum of the respective PAH reference standard. Several of the identifications have required the acquisition of specially synthesized reference standards. Combined with our previous results, the present findings show that 50 individual PAH (and related compounds), of up to 10 rings in size, are produced during benzene droplet combustion.     

Hemoglobin Adducts of Benzo[a]Pyrene in Tobacco Smokers : Characterization of Benzo[a]Pyrene Adducts in Maternal and Fetal Blood Samples

The formation of hemoglobin - carcinogen adducts has been detected in carcinogen treated animals and in human populations. Although polynuclear aromatic hydrocarbons are ubiquitous in the human environment and DNA - aromatic hydrocarbon adducts have been detected in human tissue, the occurrence of hemoglobin - polynuclear aromatic hydrocarbon adducts in humans has not been thoroughly described. In this study we examined the effects of reaction condition on the extent of in vitro reaction of human hemoglobin and (+) [³H]benzo[a]pyrene-7,8-diol-9,10-epoxide (anti)(BPDE), a metabolite thought to be largely responsible for the carcinogenic effect of benzo[a]pyrene. The chromatographic properties of the resulting hemoglobin - BPDE adducts were examined by conventional DEAE-cellulose ion exchange liquid chromatography and by reversed phase high performance liquid chromatography. Several adducts were formed which were chromatographically resolved from hemoglobin and from the individual globins. We applied these techniques to the qualitative and quantitative assessment of benzo(a)pyrene hemoglobin adducts in smokers, correlating both maternal and fetal adducts with smoking status.