24027-84-7Relevant articles and documents
Influence of Na+ on DNA reactions with aromatic epoxides and diol epoxides: Evidence that DNA catalyzes the formation of benzo[a]pyrene and benz[a]anthracene adducts at intercalation sites
Fernando, Harshica,Huang, Chao-Ran,Milliman, Ann,Shu, Luchuan,LeBreton, Pierre R.
, p. 1391 - 1402 (2007/10/03)
Reactions of the benzo[a]pyrene (BP) and benz[a]anthracene (BA) metabolites, (±)-trans-7, 8-dihydroxy-anti-9, 10-epoxy-7, 8, 9, 10- tetrahydro-BP (BPDE), (±)-trans-3, 4-dihydroxy-anti-1, 2-epoxy-1, 2, 3, 4- tetrahydro-BA (BADE), (±)-BP-4, 5-oxide (BPO), and (±)-BA-5, 6-oxide (BAO), were examined under pseudo-first-order conditions at varying Na+ (2.0-100 mM) and native, calf thymus DNA (ctDNA) concentrations. In 0.2 mM ctDNA and 2.0 mM Na+, at a pH of 7.3, most BPDE, BADE, BPO, and BAO (87-95%) undergo DNA catalyzed hydrolysis or rearrangement. For BPDE and BPO, overall, pseudo- first-order rate constants, k, in 2.0 mM Na+ and 0.2 mM ctDNA are 21-72 times larger than values obtained without DNA. For BADE and BAO, the rate constants are less strongly influenced by DNA; k values in 0.2 mM ctDNA are only 9-12 times larger than values obtained without DNA. Kinetic data for BPDE, BPO, BADE, and BAO and DNA intercalation association constants (K(A)) for BP and BA diols which are model compounds indicate that K(A) values for BPDE and BPO in 2.0 mM Na+ are 6.6-59 times larger than those of BADE and BAO. The greater DNA enhancement of rate constants for BPDE and BPO, versus BADE and BAO, correlates with the larger K(A) values of the BP metabolites. DNA adducts, which account for less than 10% of the yields, also form. For BPDE in 0.20 mM ctDNA, k decreases 5.1 times as the Na+ concentration increases from 2.0 to 100 mM. Nevertheless, the DNA adduct level remains constant over the range of Na+ concentrations examined. These results provide evidence that, for BPDE in 0.20 mM DNA and 2.0 mM Na+, ctDNA adduct formation follows a mechanism which is similar to that for DNA catalyzed hydrolysis. The pseudo-first-order rate constant for adduct formation, k(Ad), given approximately by k(Ad) ? (k(cat, Ad)K(A)[DNA])/(1 + K(A)[DNA]), where k(cat, Ad) is a catalytic rate constant. For BADE, BPO, and BAO, the influence of varying DNA and Na+ concentrations on k values is similar to that for BPDE, and provides evidence that the formation of adducts follows the same rate law.
Methanolysis of K-region arene oxides: Comparison between acid-catalyzed and methoxide ion addition reactions
Nashed, Nashaat T.,Bax, Ad,Loncharich, Richard J.,Sayer, Jane M.,Jerina, Donald M.
, p. 1711 - 1722 (2007/10/02)
Reactions of K-region arene oxides of benz[a]anthracene (BA-O) and its 1-(1-MBA-O), 4- (4-MBA-O), 7-(7-MBA-O), 11- (11-MBA-O), 12-methyl- (12-MBA-O), 7,12-dimethyl-(DMBA-O), and 7-bromo- (7-BrBA-O) substituted derivatives, benzo[a]pyrene (BaP-O), benzo[c]phenanthrene (BcP-O), benzo[e]pyrene (BeP-O), benzo[g]chrysene (BgC-O), chrysene (Chr-O), dibenz[a,h]anthracene (DBA-O), phenanthrene (Phe-O), 3-bromophenanthrene (3-BrPhe-O), and pyrene (Pyr-O) with acid and methoxide ion in methanol, are compared. For the acid-catalyzed reaction, products consist of cis- and trans-methanol adducts and phenols. There is no isotope effect on the ratio of phenols to solvent adducts produced from Phe-O or BcP-O when deuterium is substituted for the hydrogen that migrates. This observation is consistent with a mechanism in which product distribution in acid is determined by the relative rates of solvent capture and conformational inversion of a carbocation intermediate. As expected, only trans-methanol adducts, consisting of regioisomeric mixtures for unsymmetrical arene oxides, are formed from the reaction of methoxide ion with K-region arene oxides. The use of methanol permits the identification of products formed at each benzylic position of unsymmetrical arene oxides. Rate data for reactivity at each position could be fitted to the equation log kMeO/kMeOPhe-O = m(log kH/kHPhe-O) + b, where kMeO and kH are the second-order rate constants of the methoxide ion addition and acid-catalyzed reaction, respectively, and kMeOPhe-O and kHPhe-O are the corresponding rate constants for the reference compound phenanthrene oxide. A plot of log kMeO/kMeOPhe-O vs log kH/kHPhe-O for the reaction of 1-MBA-O, 12-MBA-O, DMBA-O, BcP-O, and BgC-O, which have either a methyl substituent in the bay region or a sterically crowded fjord region which affects the planarity of the molecules, defined one line (m = 0.31 ± 0.02, b = 0.67 ± 0.09), whereas a plot of the data for the reaction of the nearly planar arene oxides BA-O, 4-MBA-O, 7-MBA-O, 11-MBA-O, BaP-O, BeP-O, Chr-O, DBA-O, Phe-O, and Pyr-O defined a different line (m = 0.33 ± 0.07, b = -0.05 ± 0.05). The nonzero intercept for the sterically crowded, nonplanar arene oxides indicates a steric acceleration of their rates of methoxide ion addition. The positive slopes of both lines are consistent with an SN2 mechanism with an unsymmetrical transition state in which the epoxide C-O bond breaking is more advanced than the formation of the new C-O bond to methoxide ion, such that a partial positive charge is developed on the aromatic moiety.
