62697-17-0Relevant articles and documents
New insights on the mechanisms of the pH-independent reactions of benzo[a]pyrene 7,8-diol 9,10-epoxides
Doan,Bin,Yagi,Jerina,Whalen
, p. 6785 - 6791 (2001)
The rates and products of the reactions of (±)-7β,8α-dihydroxy-9β,10β-epoxy-7,8,9, 10-tetrahydrobenzo[α]pyrene alpyrene (1) and (±)-7β,8α-dihydroxy-9α,10α-epoxy-7,8,9, 10-tetrahydrobenzo[α]pyrene (2) in water and dioxane-water mixtures have been determined over a pH range wider than that of earlier studies. This study provides additional insight on the mechanisms of the pH-independent reactions of 1 and 2. The rate profile for reaction of 1 shows acid-catalyzed hydrolysis at pH 11.5. The rate decrease between pH 10 and pH 11.5 is accompanied by a decrease in the yield of tetrols from 60% (pH 8) to 29% (pH 11.2) and is interpreted to be the result of a partial change in mechanism brought about by attack of hydroxide ion acting as a base to deprotonate a carbocation intermediate and regenerate 1 at pH + and HO-, respectively. The lack of a rate depression at pH 10 and the product studies for the reaction of 2 in dilute sodium azide solutions suggest that the tetrol-forming reactions of the pH-independent reaction of 2 are concerted or near-concerted.
Synthesis and hydrolysis of a cis-chlorohydrin derived from a benzo[a]pyrene 7,8-diol 9,10-epoxide
Doan, Lanxuan,Yagi, Haruhiko,Jerina, Donald M.,Whalen, Dale L.
, p. 8012 - 8017 (2007/10/03)
(±)-7β,8α-Dihydroxy-9β,10β-epoxy-7,8,9, 10-tetrahydrobenzo[a]pyrene (DE-1) undergoes reaction with anhydrous HCl in dioxane to yield predominantly (～94%) a single chlorohydrin. This chlorohydrin was assigned structure 9, in which the chloro goup at C-10 is located cis to the C-9 hydroxyl group, on the basis of its 1H NMR spectrum. This result is in contrast to the reaction of a diastereomeric benzo[a]pyrene 7,8-diol 9,10-epoxide (DE-2) with HCl, which yields only transchlorohydrin 8. The hydrolysis of cis-chlorohydrin 9 in 10:90 dioxane - water solutions yields the same ratio of tetrols (～89% cis/11% trans) as that formed by acid-catalyzed hydrolysis of DE-1. This result again contrasts with the hydrolysis of trans-chlorohydrin 8, which undergoes hydrolysis to give tetrols in a ratio different from that from acid-catalyzed hydrolysis of DE-2. A marked common ion rate depression in the hydrolysis of cis-chlorohydrin 9 is observed, which shows that hydrolysis proceeds via an intermediate carbocation that has a sufficient lifetime to be trapped by external chloride ion. The observation that DE-1 reacts with HCl to give mainly the cis-chlorohydrin is rationalized by quantum chemical calculations that suggest that the cis-chlorohydrin is more stable than the epimeric trans-chlorohydrin.
Nitrogen dioxide as an oxidizing agent of 8-oxo-7,8-dihydro-2′-deoxyguanosine but not of 2′-deoxyguanosine
Shafirovich,Cadet,Gasparutto,Dourandin,Geacintov
, p. 233 - 241 (2007/10/03)
The redox reactions of guanine and its widely studied oxidation product, the 8-oxo-7,8-dihydro derivative, are of significant importance for understanding the mechanisms of oxidative damage in DNA. Employing 2′-deoxyguanosine 5′-monophosphate (dGMP) and 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxo-dG) in neutral aqueous solutions as model systems, we have used nanosecond laser flash photolysis to demonstrate that neutral radicals, dGMP(-H)?, derived by the one-electron oxidation and deprotonation of dGMP, can oxidize nitrite anions (NO2-) to the nitrogen dioxide radical ?NO2. In turn, we show that ?NO2 can give rise to a one-electron oxidation of 8-oxo-G, but not of dGMP. The one-electron oxidation of dGMP was initiated by a radical cation generated by the laser pulse-induced photoionization of a pyrene derivative with enhanced water solubility, 7,8,9,10-tetrahydroxytetrahydrobenzo[α]pyrene (BPT). The dGMP(-H)? neutral radicals formed via deprotonation of the dGMP?+ radical cations and identified by their characteristic transient absorption spectrum (λmax ～ 310 nm) oxidize nitrite anions with a rate constant of(2.6 ± 0.3) × 106 M-1 s-1. The 8-oxo-dG is oxidized by ?NO2 with a rate constant of (5.3 ± 0.5) × 106 M-1 s-1. The 8-oxo-dG(-H)? neutral radicals thus generated are clearly identified by their characteristic transient absorption spectra (λmax ～ 320 nm). The rate constant of 8-oxo-dG oxidation (k12) by the ?NO2 one-electron oxidant (the ?NO2/NO2- redox potential, E° ≈ 1.04 V vs NHE) is lower than k12 for a series of oxidizing aromatic radical cations with known redox potentials. The k12 values for 8-oxo-dG oxidation by different aromatic radical cations derived from the photoionization of their parent compounds depend on the redox potentials of the latter, which were in the range of 0.8-1.6 V versus NHE. The magnitude of k12 gradually decreases from a value of 2.2 × 109 M-1 s-1 (E° = 1.62 V) to 5.8 × 108 M-1 s-1 (E° = 1.13 V) and eventually to 5 × 107 M-1 s-1 (E° = 0.91 V). The implications of these results, including the possibility that the redox cycling of the ?NO2/NO2- species can be involved in the further oxidative damage of 8-oxo-dG in DNA in cellular environments, are discussed.
