67315-17-7Relevant academic research and scientific papers
Photoemission probes of hydrocarbon-DNA interactions: A comparison of DNA influences on the reactivities of (±)-trans-7,8-dihydroxy-anti-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a] pyrene, benzo[a]pyrene 4,5-oxide, and benz[a]anthracene 5,6-oxide
Urano, Shigeyuki,Price, Harry L.,Fetzer, Sharon M.,Briedis, Anita V.,Milliman, Ann,LeBreton, Pierre R.
, p. 3881 - 3893 (2007/10/02)
Time-resolved fluorescence and UV photoelectron measurements have been employed to examine the influence of calf thymus DNA on the reactivities of epoxides derived from benzo[a]pyrene (BP) and benz[a]anthracene (BA). By monitoring the increase in fluorescence intensity, which accompanies reaction at 23°C, overall, pseudo-first-order rate constants have been measured for reactions of the highly carcinogenic bay region epoxide (±)-trans-7,8-dihydroxy-anti-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BPDE) and of two less carcinogenic K region epoxides benzo[a]pyrene 4,5-oxide (BPO) and benz[a]anthracene 5,6-oxide (BAO). Overall rate constants for hydrolysis and rearrangement reactions have been measured for BPDE, BPO, and BAO in buffer alone (1.0 mM sodium cacodylate, pH 7.1). The rate constants increase in the order BPO ((3.8 ± 0.1) × 10-6 s-1) -5 s-1) -4 s-1). These results have been compared with overall rate constants for reactions, carried out in calf thymus DNA, which result in catalyzed hydrolysis and rearrangement, as well as DNA adduct formation. In DNA, the ordering of the rate constants for BPO and BAO changes from that observed in buffer alone. The rate constants increase in the order BAO ((2.8 ± 0.1) × 10-3 s-1) -2 s-1) -1 s-1). This ordering is the same as the ordering of association constants for the reversible binding to DNA of the fluorescent diols trans-7,8-dihydroxy-7,8-dihydro-BP (BP78D), trans-4,5-dihydroxy-4,5-dihydro-BP (BP45D) and cis-5,6-dihydroxy-5,6-dihydro-BA (BAD), which are model compounds of BPDE, BPO, and BAO, respectively. For the model compounds, the association constants for intercalation increase in the order BAD ((3.6 ± 0.9(× 102 M-1) 3 M-1) 4 M-1). This ordering is consistent with the ordering of the association constants of BPDE ((2.5 ± 0.3) × 104 M-1) and of BPO ((6.0 ± 1.0) × 103 M-1). The temperature dependence of the association constants of the model compounds demonstrates that, for the intercalation of the BP diols into DNA, differences in the enthalpy of binding contribute significantly to differences in the free energy of binding. UV photoelectron data and results from ab initio molecular orbital calculations on BPDE, BPO, and BAO indicate that, for these three epoxides, the association constants increase as the ionization potentials decrease and the polarizabilities increase. The percentage of epoxide reaction that yields DNA adducts has been compared under varying conditions. For long reaction times (>1 h) in systems containing native, calf thymus DNA at low salt concentrations, the ordering of adduct yields is BPO (14.9 ± 1.1%) > BPDE (10.1 ± 3.0%) > BAO (3.6 ± 0.4%). For short reaction times (10 min) in systems containing native DNA stabilized with 0.10 mM Mg2+, the ordering of adduct yields is BPDE (7.3 ± 1.9%) > BPO (1.3 ± 0.1%) > BAO (0.1 ± 0.1%). These results suggest that the ability of an epoxide to form adducts with exposed DNA during long reaction times is less indicative of the genotoxic potency of the epoxide than its ability to form adducts with stabilized DNA during short reaction times.
Solvolysis of K-region arene oxides: Substituent effects on reactions of benz[a]anthracene 5,6-oxide
Nashed, Nashaat T.,Balani, Suresh K.,Loncharich, Richard J.,Sayer, Jane M.,Shipley, David Y.,Mohan, Ram S.,Whalen, Dale L.,Jerina, Donald M.
, p. 3910 - 3919 (2007/10/02)
The solvolytic reactivity and products formed from benz[a]anthracene 5,6-oxide (BA-O) on substitution of a methyl group at positions 1 (1-MBA-O), 4 (4-MBA-O), 7 (7-MBA-O), 11 (11-MBA-O), and 12 (12-MBA-O), on 7,12-dimethyl substitution (7,12-DMBA-O), and on 7-bromo substitution in 1:9 dioxane-water and in methanol at 25°C are reported. These substitutions result in > 150-fold differences in their rates of acid-catalyzed solvolysis and cause marked changes in the distribution of solvent adducts and phenols resulting from isomerization. Optically pure BA-O, 7-MBA-O, 12-MBA-O, and 7,12-DMBA-O as well as their optically pure trans dihydrodiols were utilized to determine the point of attack by water in the hydrolysis reactions. In general, the reactions in aqueous dioxane (0.1 M NaClO4) obeyed the rate equation kobsd = kH[H+] + k0, where kH is the second-order rate constant for acid-catalyzed reaction and k0 is the first-order rate constant for spontaneous reaction, to provide biphasic pH-rate profiles. When ionic strength was maintained with 0.5 M KCl, however, more complex pH-rate profiles were observed for some of the arene oxides due to attack of chloride on the neutral epoxide to produce steady-state concentrations of chlorohydrins. Rate enhancement on methyl substitution is largest (kH, ca. 5-fold) when the methyl group is present in the hindered bay region (C1 or C12) or adjacent to the epoxide at C7. The combined effect of two methyl groups (7,12-DMBA-O) is additive (ca. 25-fold). Theoretical calculations (molecular mechanics by PCMODEL-PI and ab initio by GAUSSIAN 86 and 88 programs) of carbocation stability indicate the importance of steric factors in determining relative reactivity and types of products formed from substituted benz[a]anthracene 5,6-oxides.
Resolution and Absolute Configuration of K-Region Trans Dihydrodiols from Polycyclic Aromatic Hydrocarbons
Balani, S. K.,Bladeren, P. J. van,Shirai, N.,Jerina, D. M.
, p. 1773 - 1778 (2007/10/02)
K-region trans dihydrodiols of benzophenanthrene, chrysene, pyrene, and dibenzacridine have been resolved as their diastereomeric diesters with (-)-(menthyloxy)acetic acid, and their absolute configuration have been assigned by the application of circular dichroism and excition chirality methods.For these as well as the K-region trans dihydrodiol derivatives from five other hydrocarbons, a consistent pattern of physical properties has emerged.The R,R diastereomers are less retained on silica gel HPLC columns when eluted with ether-cyclohexane mixtures and show negative values of D in tetrahydrofuran, the degree of magnetic nonequivalence between HA and HB in the -OCHAHBCO2- portion of the diesters (100 MHz, C6D6) is generally much higher for the S,S enantiomers of the dihydrodiols, and the free R,R dihydrodiols have positive values of D in tetrahydrofuran provided their hydroxyl groups do not have a marked preference for the pseudodiaxial conformation.
