61490-66-2Relevant articles and documents
Fluorinated alcohol mediated displacement of the C10 acetoxy group of benzo[a]pyrene-7,8,9,10-tetrahydrotetraol tetraacetates: A new route to diol epoxide-deoxyguanosine adducts
Yagi, Haruhiko,Jerina, Donald M.
, p. 9983 - 9990 (2008/03/28)
(Chemical Equation Presented) We describe a novel trifluoroethanol (TFE) or hexafluoropropan-2-ol (HFP) mediated substitution reaction of the bay-region C10 acetoxy group in four stereoisomeric 7,8,9,10-tetraacetoxy-7,8,9, 10-tetrahydrobenzo[a]pyrenes (tetraol tetraacetates, two pairs of cis and trans isomers at the 9,10 positions) by the exocyclic N2-amino group of O6-allyl-3′,5′-di-O-(tert-butyldimethylsilyl)-2′- deoxyguanosine (3). The tetraacetates are derived from cis and trans hydrolysis of (±)-7β,8α-dihydroxy-9β,10β-epoxy-7,8,9,10- tetrahydrobenzo[a]pyrene (B[a]P DE-1) and of (±)-7β,8α- dihydroxy-9α,10α-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (B[a]P DE-2) at C-10 followed by acetylation. Excellent yields and high regioselectivity were observed. Similar cis/trans product ratios were observed for each set of cis and trans tetraol tetraacetates derived from DE-1 (～75/25) and from DE-2 (～67/33) in HFP. This strongly suggests that the substitution proceeds via an SN1 mechanism involving a carbocation intermediate that is common to the cis and trans tetraacetates. Since it is likely that the cis and trans products from 3 arise from different conformations of the carbocation, its lifetime must be sufficiently long to permit conformational equilibration before its capture by the purine nucleophile. The corresponding reaction of (±)-9α-bromo-7β,8α,10β- triacetoxy-7,8,9,10-tetrahydrobenzo[a]pyrene with 3 in HFP was highly regio- and stereoselective and gave exclusively trans 10β-adducts. This newly developed substitution reaction provides an attractive alternative synthetic strategy for the preparation of polycyclic hydrocarbon adducted oligonucleotide building blocks.
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.
Halide effects in the hydrolysis reactions of (±)-7β,8α-dihydroxy- 9α, 10α-epoxy-7,8,9,10-tetrahydrobenzo-[α]pyrene
Lin, Bin,Doan, Lanxuan,Yagi, Haruhiko,Jerina, Donald M.,Whalen, Dale L.
, p. 630 - 638 (2007/10/03)
Rates of reaction of (±)-7β,8α-dihydroxy-9α,10α-epoxy-7,8,9,10- tetrahydrobenzo[α]pyrene (DE-2) have been determined in 1:9 dioxane-water solutions containing 1.0 M KC1, 0.5 M KBr, and 0.1 M NaI over the pH range 4- 13. These pH-rate profiles are more complicated than those for reaction of DE-2 in 0.2 M NaC1O4 solutions and are interpreted in part by mechanisms in which halide ion attacks the diol epoxide as a nucleophile at intermediate pH, resulting in the formation of a trans-halohydrin. Reaction of DE-2 in these halide solutions at pH - , 0.5 M Br-, and 0.1 M I- on DE-2 are the principal reactions in the pH range ca. 6-9, leading to intermediate trans-halohydrins that hydrolyze to tetrols. At pH ca. 9-11, halohydrin formed from attack of halide ion on DE-2 reverts back to epoxide, leading to a negative break in the pH-rate profile. The main product-forming reaction of DE-2 at pH 11.3 is the spontaneous reaction. At pH > 12, the rate of reaction of DE-2 increases due to a second- order reaction of HO- with DE-2.
