163432-96-0Relevant articles and documents
Mechanisms of benzyl group transfer in the decay of (E)-arylmethanediazoates and aryldiazomethanes in aqueous solutions
Finneman, Jari I.,Fishbein, James C.
, p. 4228 - 4239 (1995)
Rate constants are reported for the buffer-independent decay of ten (E)-arylmethanediazoates in aqueous media at 25 °C, ionic strength 1 M (NaClO4), 4% 2-propanol, in the region of pH 4-12. The rate constants are proportional to hydrogen ion concentration at high pH and become pH independent in the low-pH region. Varying concentrations of oxyanion, amine, and hydrazine buffers over the range 0.05-0.2 M increased the pseudo-first-order rate constant for decay of the diazoates by less than 10%. The azide - water selectivities, ka/ks, for partitioning of the benzyl groups in the decay of (E)-(3,5-bis(trifluoromethyl)phenyl)methanediazoate and the (3,5-bis(trifluoromethyl)phenyl)diazomethane are determined to be 0.20 and 0.21 M-1, respectively, in phosphate buffered water and 0.27 and 0.26 M-1, respectively, in 20/80 DMSO-water. It is concluded that these two reactants decompose, in these media, via a common free diazonium ion intermediate that is formed in the case of the diazoate upon unassisted N-O bond cleavage of the diazoic acid. A common rate-limiting step is indicated for all the diazoates by the correlation line for the plot of log k1, the pH independent rate constant, against σ that has a slope q = -1.23. Product ratios for trapping of benzyl groups derived from other pairs of arylmethanediazoates and aryldiazomethanes with less electron withdrawing groups are different outside experimental error, indicating the importance of different nitrogen-separated ion pairs in these reactions. The (E)-(p-methoxy)phenyl)methane-16O-diazoate decomposes in 16O/18O water to give alcohol that has an "excess" abundance of 16O compared to solvent. Decomposition of the same compound in 50/50 trifluoroethanol-water with varying concentrations of azide indicates that azide ion appears to trap a limiting amount, ～80%, of the p-methoxybenzyl group. Quantitative analysis of the data indicates that 16% of the p-methoxybenzyl cation is trapped by solvent at the nitrogen-separated ion pair stage, in the absence of azide ion. There is a 9-fold enhancement of selectivity for trifluoroethanol at the ion pair stage that is ascribed to a proton switch initiated by the leaving hydroxide ion in the ion pair. The values of Ka/ks ～ 0.2 M-1 and kT/kH ～ 0.5-0.6 for the trifluoroethanol-water selectivity and kET/kT ～ 1 for the ethanol-trifluoroethanol selectivity are independent of substituent in the decay of arylmethanediazoates (X = H and EWG) in water, water-trifluoroethanol (50/50), and water-trifluoroethanol-ethanol (50/40/10), respectively. It is concluded from this that the productdetermining steps do not involve chemical bonding but rather rotational/translational reorientation of the nucleophiles in the first solvation sphere of the carbocation intermediates. It is concluded that the values of kH/kT = 0.5-0.6 indicate preferential solvation of the cation precursor by trifluoroethanol. It is shown that a preferential interaction for trifluoroethanol of 1 kcal/mol is required to generate the observed selectivities.
Reaction of malondialdehyde-DNA adducts with hydrazines - Development of a facile assay for quantification of malondialdehyde equivalents in DNA
Otteneder, Michael,Plastaras, John P.,Marnett, Lawrence J.
, p. 312 - 318 (2007/10/03)
Malondialdehyde is a ubiquitous product of lipid peroxidation that reacts with DNA to form premutagenic lesions. Principal among them is pyrimido-[1,2-α]purin-10(3H)-one (M1G). M1G has recently been found to be a reactive electrophile in DNA that couples with amines at basic pH or hydroxylamines at neutral pH. We explored the reaction of M1G with hydrazines because of the possibility that the latter could act as bifunctional nucleophiles to strip the malondialdehyde equivalent from DNA. Pentafluorophenylhydrazine reacted rapidly with M1G to form a hydrazone conjugate. This hydrazone was stable at room temperature and did not cyclize to form the corresponding pyrazole. In contrast, phenylhydrazine and benzylhydrazine reacted with M1G to form phenylpyrazole and benzylpyrazole, respectively. Pentafluorobenzylhydrazine reacted rapidly with M1G to form pentafluorobenzylpyrazole and dG in near quantitative yield. This reaction formed the basis for a quantitative assay for the presence of M1G or M1G equivalents in DNA or protein that utilized gas chromatography/negative chemical ionization mass spectrometry. The assay was extended to the oxopropenyl donors, M1A, base propenal, and Nε-3-oxopropenyl-lysine. Analysis of DNA treated with bleomycin demonstrated a linear increase in the level of oxopropenyl groups that plateaued at approximately 1 oxopropenyl group/100 bases at a bleomycin concentration of 200 μM. Parallel analysis of M1G in the samples revealed that this adduct represents a small fraction of the total oxopropenyl units generated in DNA by treatment with bleomycin.
