Model Reactions for the Degradation of DNA-4′ Radicals in Aqueous Solution. Fast Hydrolysis of α-Alkoxyalkyl Radicals with a Leaving Group in β-Position Followed by Radical Rearrangement and Elimination Reactions

Abstract

α-Alkoxyalkyl radicals with a leaving group L = Cl or OCOCH₃ in β-position are produced by H-abstraction from the corresponding saturated substrates by ^·OH, SO^·₄^- or (CH₃)₃CO^· radicals. From ESR spectroscopic observations it is concluded that in aqueous solution at pH 5 -9 the following fast hydrolysis reactions take place:

The rate constants of these reactions and for the hydrolysis of CH₃O-ĊH-CH₂Cl are k ≥ 10⁶ s^-1, whereas the rate constant for CH3O-ĊH-CH₂OCOCH₃ was determined to be ≈ 2 × 10³ s^-1 at room temperature. The radicals with L = Cl cannot be scavenged by O₂ which fact leads to a value of k ≥ 2 × 10^-7 s^-1. α-Alkoxyalkene radical cations are assumed as intermediates in the hydrolysis reactions. The radicals with L = OCOCH₃ and the radical CH₃O--ĊH-CH₂Cl are observable in acetone solution ESR spectroscopically.

In aqueous solution at pH below 3 proton catalyzed reactions are observed by ESR spectroscopy:

Radicals resulting from H-abstraction at the CH₃O-groups of the substrates or at the 5-positions of the cyclic ethers are also observed. The ESR parameters and the pH-ranges of existence of the above radicals are given. Support of the reported reactions comes from quantitative analysis of stable products such as H⁺, Cl^- or CH₃OH after ⁶⁰Co-γ-irradiation of N₂O saturated aqueous solutions of the substrates.

The behaviour of the radicals is used as a model to describe a modified version of the degradation of DNA-4′ radicals in aqueous solution in the absence of oxygen.