Reactivity and adduct formation of a polyaromatic hydrocarbon, 7-bromomethylbenz[a]anthracene, with chromatin histone proteins

The alkylation of histones by the direct-acting carcinogen 7-bromomethylbenz[a]anthracene was demonstrated both in vivo and in vitro. The relative molar reactivity for mouse liver histones in vivo was H3 greater than H1 greater than H2b greater than H4 greater than H2a. The in vitro modification of histone H3 was examined in detail. Amino acid adducts stable to acid hydrolysis were separated after acetylation by reversed-phase high-performance liquid chromatography and characterized using ultraviolet absorbance spectra and synthetic amino acid adduct standards. Three major adducts were observed and tentatively identified as cysteinyl, lysyl and histidinyl adducts of histone H3.     

Degradation of anthracene, pyrene and benzo[a]-anthracene in aqueous solution by chlorine dioxide

Polycyclic aromatic hydrocarbons (PAHs) constitute an important group of micropollutants, which are known to be mutagenic, carcinogenic and/or co-carcinogenic and relatively persistent in the environment. The effects of chlorine dioxide (ClO2) on the degradation of anthracene (ANTH), pyrene (PYR) and benzo[a]anthracene (BaA) in aqueous solution were investigated using high performance liquid chromatography (HPLC). In preliminary experiments, it was observed that ClO2 could remove these three PAHs effectively within a short time. Several factors including reaction time, the concentration of ClO2 and pH of the reaction mixture influencing the degradation ratio of PAHs have been studied by batch experiments. The results showed that the degradation ratio of PAHs was affected by reaction time and the concentration of ClO2 instead of pH. The degradation ratio of ANTH, PYR and BaA could reach their maximum as approximately 99.0%, 67.5% and 89.5%, respectively, under the condition as follows: reaction time 30, 60 and 120 min, the concentration of ClO2 0.1, 0.4 and 0.5 mmol·L-1, and pH 7.2. ANTH was selected as the representative to study the reaction mechanism with ClO2. The oxidation products formed in the reaction of ANTH with ClO2 were tentatively identified by gas chromatography-mass spectrometry (GC-MS), and the results showed that the main product was 9, 10-anthraquinone, which could be biodegraded more easily and quickly than ANTH. Through analyzing the reaction properties of ANTH and ClO2, the possible pathway for the ANTH-ClO2 reaction was proposed based on the theory of single electron transfer (SET).     

Effects of cluster formation on spectra of benzo[a]pyrene and benzo[e]pyrene

Absorption and fluorescence emission spectra of the polycyclic aromatic hydrocarbons benzo[a]pyrene (BaP) and benzo[e]pyrene (BeP) in solution and adsorbed on silica have been obtained and compared to examine the spectroscopic effects of clustering. Molecular mechanics calculations with the UFF potential were done to optimize monomer, dimer and trimer geometries, and energy differences were determined by MP2/6-31G* calculations. Fluorescence emission spectra of adsorbed BeP and BaP display a red shift that progresses with increased loading, and the two differ in their photodegradation kinetics. The experimental and theoretical results are found to be consistent.     

Measurement of benzo[a]pyrene,benzo[k]fluoranthene and benzo[g,h,i]perylene by ultraviolet spectroscopy

Microchimica Acta - The technique for determining benzo[a]pyrene, benzo[k]fhuoranthene, and benzo[g,h,i]perylene respectively inμg amounts by UV absorption measurements is described. The...     

Reinvestigation of the jutz synthesis of benzo [e] pyrene and benzo [a] pyrene derivatives from benzanthrene

Base-catalyzed reactions of benzanthrene with “vinamidinium salts” ($\text{2a-c}$ ) followed by thermal electrocyclic ring closure are regiospecific affording only benzo [e] pyrene derivatives, contrary to previous claims.     

Diindeno-Fused Dibenzo[a,h]anthracene and Dibenzo[c,l]chrysene: Syntheses,Structural Analyses,and Properties

Diindeno-fused dibenzo[a,h]anthracene 6 and diindeno-fused dibenzo[c,l]chrysene 9 contain the key moieties 1,4-quinodipropene (1,4-QDP) and 2,6-naphthoquinodipropene (2,6-NQDP), respectively, and they both have an open-shell singlet ground state. The latter compound exhibits a strong biradical character and interesting properties, including a low ΔE_T−S (2.44 kcal mol⁻¹), a small HOMO–LUMO gap (1.06 eV), a wide photoabsorption range (250–1172 nm), and a large two-photon absorption cross-section (σ=1342±56 GM). This work verifies that 6 has a slightly larger HOMO–LUMO gap and ΔE_T−S than its helical isomer diindeno[2,1-f:1′,2′-j]picene (DIP), but is a much stronger two-photon absorber, verifying the important effect of geometry on the photophysical properties.     

Arene imine derivatives of chrysene and of benzo[g]chrysene: 1a,11c-dihydrochryseno[5,6-b]azirine and 1a,13c-dihydrobenzo[11,12]chryseno[5,6-b]azirine

The syntheses of the K-iraines (which are also benzo-bay-region derivatives) of chrysene ( 1 ) and benzo[g]-chrysene ( 2 ) are described. The preparation of 1a,11c-dihydrochryseno[5,6-b]azirine ( 5 ) was accomplished by treatment of 1a,11c-dihydrochryseno[5,6-b]oxirene ( 4 ) with sodium azide, and the mixture of trans-azido-alcohols 6 and 7 , so formed, was either cyclized with triethyl phosphite, or converted into E-6-azido-5-chloro-5,6-dihydrochrysene ( 8 ) followed by lithium aluminium hydride reduction. The synthesis of 1a,13c-dihydrobenzo-[11,12]chryseno[5,6-b]azirine ( 12 ) included the transformation of the corresponding oxide 11 into a mixture of E-9-azido-9,10-dihydrobenzo[g]chrysen-10-ol ( 13 ) and E-10-azido-9,10-dihydrobenzo[g]chrysen-9-ol ( 14 ), and reaction with tri-n-butylphosphine to give a mixture of Staudinger adducts 15 and 16 that underwent thermal decomposition into 12 upon heating in boiling dichloromethane.     

Second-derivative constant-wavelength synchronous scan spectrofluorimetry for determination of benzo[b]fluoranthene, benzo[a]pyrene and indeno[1,2,3-cd]pyrene in drinking water

The use of derivative constant-wavelength synchronous scan fluorimetry is reported for the determination of three polycyclic aromatic hydrocarbon pollutants in drinking water (linearity range 0.4-4 mug 1(-1)). The limits of detection (LD) and quantification (LQ) (mug 1(-1)) are 0.01 and 0.07 for benzo[b]fluoranthene, 0.03 and 0.12 for benzo[a]pyrene and 0.19 and 0.57 for indeno[1,2,3-cd]pyrene in the presence of three other pollutants, benzo[k]fluoranthene, benzo[ghi]perylene and fluoranthene. The precision (RSD /= 85%) were satisfactory.     

Synthesis of bisimines of pyrene and dibenz[a,h]anthracene

The preparation of 3b,4a,7b,8a-tetrahydro-4H,8H-pyreno[4,5-b:9,10-b']bisazirine and of 1a,6b,7a,12b-tetrahydro-1H,7H-dibenz[3,4:7,8]anthra[1,2-b:5,6-b']bisazirine is described. The corresponding diepoxides were reacted with sodium azide in aqueous acetone and the mixtures of trans-azido alcohols, so formed, were cyclized by tri-n-butylphosphine.     

Oxidized metabolites from benzo[a]pyrene, benzo[e]pyrene, and aza-benzo[a]pyrenes. A computational study of their carbocations formed by epoxide ring opening reactions

A DFT study aimed at understanding structure-reactivity relationships and fluorine substitution effects on carbocation stability in benzo[a]pyrene (BaP), benzo[e]pyrene (BeP), and aza-benzo[a]pyrene (aza-BaP) derivatives are reported. The relative energies of the resulting carbocations are examined and compared, taking into account the available biological activity data on these compounds. O-Protonation of the epoxides and diol epoxides leads to carbocation formation by barrierless processes. Charge delocalization modes in the resulting carbocations were deduced via NPA-derived changes in charges, and fluorine substitution effects were analyzed on the basis of charge density at different carbocation positions. Thus, fluorine substitution at sites bearing negative charge generated inductive destabilization of the carbocation, whereas a fluorine atom at a ring position which presented significant positive charge density produced a less pronounced destabilization due to fluorine p-pi back-bonding. Protonation reactions were also studied for the azaBaPs. In selected cases, the covalent adducts generated via bond formation with the exocyclic nitrogen of cytosine were computed and relative energies and geometries of the resulting adducts were examined.     

New synthetic approaches to polycyclic aromatic hydrocarbons and their carcinogenic oxidized metabolites: derivatives of benzo[s]picene, benzo[rst]pentaphene, and dibenzo[b,def]chrysene

A new synthetic approach to polycyclic aromatic compounds is described that entails in the key steps double Suzuki coupling of PAH bisboronic acid derivatives with o-bromoaryl aldehydes to furnish aryl dialdehydes that are converted to larger polycyclic aromatic ring systems by either (a) conversion to diolefins by Wittig reaction followed by photocyclization or (b) reductive cyclization with triflic acid and 1,3-propanediol. This synthetic method provides convenient access to as many as three different polycyclic aromatic ring systems from a single Suzuki coupled intermediate. It was utilized to synthesize substituted derivatives of benzo[s]picene, benzo[rst]pentaphene, dibenzo[b,def]chrysene, and 13,14-dihydro-benz[g]indeno[2,1-a]fluorene, as well as the putative carcinogenic bisdihydrodiol metabolites of benzo[s]picene, benzo[rst]pentaphene, and dibenzo[b,def]chrysene.     

A simple method for the determination of benzo[a]pyrene and benzo[k]fluoranthene in a mixture

Atmospheric particulate matter is routinely analysed for the concentration of the carcinogen benzo[a]pyrene (BaP). Benzo[k]fluoranthene (BkF) has identical spectral characteristics and interferes in the fluorimetric estimation. A simple method for the determination of BaP in the presence of BkF is described. Based on quenching of the fluorescence of BaP by the addition of small amounts of nitromethane, the method can be used for accurate estimation for wide concentration ratios of BaP to BkF ranging from 0.1 to 10.0.     

Supersonic jet fluorescence spectrometry of perylene and benzo[a]pyrene

A supersonic jet instrument for fluorescence spectrometry is described. It consists of a high-temperature free expansion nozzle for continuous sample introduction and a vacuum chamber equipped with a high-speed pumping system. Rotationally cooled spectra obtained with the supersonic jet are compared with gas-phase spectra measured at high temperature for perylene and benzo[a]pyrene molecules. Each component of the unresolved band structure in the high-temperature spectra was found to be composed of a rotational congestion of several vibrational bands. For a 1:1 mixture of perylene and benzo[a]pyrene, selective detection is possible by using supersonic jet spectrometry. The detection limit for perylene is 100 ng. The advantage of this technique over other low-temperature spectrometric methods based on Shpol'skii and matrix isolation effects are discussed.     

Synthesis of 13C4-labelled oxidized metabolites of the carcinogenic polycyclic aromatic hydrocarbon benzo[a]pyrene

Polycyclic aromatic hydrocarbons (PAHs), such as benzo[a]pyrene (BaP), are ubiquitous environmental contaminants that are implicated in causing lung cancer. BaP is a component of tobacco smoke that is transformed enzymatically to active forms that interact with DNA. We reported previously development of a sensitive stable isotope dilution LC/MS method for analysis of BaP metabolites. We now report efficient syntheses of ¹³C₄-BaP and the complete set of its ¹³C₄-labelled oxidized metabolites needed as internal standards They include the metabolites not involved in carcinogenesis (Group A) and the metabolites implicated in initiation of cancer (Group B). The synthetic approach is novel, entailing use of Pd-catalyzed Suzuki, Sonogashira, and Hartwig cross-coupling reactions combined with PtCl₂-catalyzed cyclization of acetylenic compounds. This synthetic method requires fewer steps, employs milder conditions, and product isolation is simpler than conventional methods of PAH synthesis. The syntheses of ¹³C₄-BaP and ¹³C₄-BaP-8-ol each require only four steps, and the ¹³C-atoms are all introduced in a single step. ¹³C₄-BaP-8-ol serves as the synthetic precursor of all the oxidized metabolites of ¹³C-BaP implicated in initiation of cancer. The isotopic purities of the synthetic ¹³C₄-BaP metabolites were estimated to be ≥99.9%.     

Synthesis and NMR characterization of a dioxa-analog of benzo[a]pyrene: The 1-benzopyrano[6,5,4-mna]-xanthene (1,6-dioxabenzo[a]pyrene)

1,6-Dioxabenzo[a]pyrene, the first dioxa-analog of benzo[a]pyrene, was synthesized from 5-methoxy-1-naphthol in an eight-step reaction involving two peri-heterocyclizations.