Günther Koltzenburg

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.

Reactions of 1,1-dialkoxyalkene radical cations in aqueous solution with OH–, HPO42–, and H2O. Electron spin resonance spectroscopic, pulse conductometric, and product analytical studies

The reactions of H2O, HPO42–, and OH– with eight, 1,1-dialkoxyalkene radical cations have been studied in aqueous solution by e.s.r. spectroscopy and in part by pulse conductometry and product analysis. Hydroxide ion reacts with the radical cations with rate constants ranging from k 2 × 108 for species (5) to 6 × 109 l mol–1 s–1 for (6), producing mainly alkoxycarbonylalkyl radicals. With (1) and with (6), in addition, the formation of 1,1-dialkoxy-2-hydroxyethyl radicals was observed and e.s.r. parameters are given. The HPO42– anion was found to react with four of the radical cations to form phosphato-dianion-substituted radicals, (RO)2(PO42–)C–ĊH2(e.s.r. parameters are given), with k values ranging from 2 × 106 for (1) to 3 × 108 l mol–1 s–1 for (6). Water reacted analogously with rate constants ranging from k 3 × 102 for (1) to 104 s–1 for (27) at 20 °C, the reaction yielding 2,2-dialkoxy-2-hydroxyethyl radicals (e.s.r. parameters are given) and protons. Attack of water occurs virtually only at the dioxygen-substituted carbon as is shown in one example. Product analysis by g.l.c.–m.s. of the higher boiling material from 60Co γ-irradiation of N2O-saturated aqueous solutions of (CH3O)2CH–CH2Cl gave evidence for the formation of dimers and cross-dimers of the radicals ĊH2OCH(OCH3)CH2Cl, CH3OCOĊH2, (CH3O)2CHĊHCl, (CH3O)2ĊHCH2, and (CH3O)2ĊH2OH. Structures and yields of the products agree with the conclusions drawn from e.s.r. spectroscopic and conductometric measurements.

Formation and structure of 1,1-dialkoxyalkene radical cations in aqueous solution. An in situ electron spin resonance and pulse conductivity study

The radical cations (1), (10), (11a and b), and (12)–(15) have been produced in aqueous solution and have been identified by e.s.r. spectroscopy and conductivity investigation. The open chain radical cations exist in Z,E-configurations. They exhibit two sets of aδH couplings. The larger couplings were assigned to the protons in groups with the Z-configuration. In all cases the radical spin is located mainly at the carbon atoms. Under our conditions radical (13) disappeared pseudo-monomolecularly upon reaction with water (k= 7 × 103 s–1) whereas the other radical cations are longer lived and decayed bimolecularly with diffusion controlled rates. The radical cations were generated from open chain or cyclic acetals bearing Br, Cl, or CH3CO2 groups β to the acetal CH group, e.g.(CH3O)2CH–CH2Cl or (CH2O)2CH–CH2Cl. These substrates were subjected to hydrogen abstraction by OH˙ or SO4˙– radicals or triplet acetone in aqueous solution. Hydrogen abstraction from the acetal CH group led to radicals which undergo fast heterolytic dissociation into radical cations and leaving group anions, e.g.(CH3O)2Ċ–CH2Cl →(CH3O)2C–ĊH2+ Cl–.

Elimination of Ammonium Ion from the a-Hydroxyalkyl Radicals of Serine and Threonine in Aqueous Solution and the Difference in the Reaction Mechanism

Abstract The zwitterionic radicals HO-ĊH-CH(COO-)NH3+ (4a) and HO-Ċ(CH3)-CH(COO-)NH3+ (4b) are the main species produced upon OH· radical attack in aqueous solutions at pH 3-7 at the amino acids serine, HO-CH2-CH(COO-)NH3+, or threonine, HO-CH(CH3)-CH(COO-)NH3+, respectively. Both radicals undergo elimination of NH4+ ion to form the radicals O=CH-ĊH-COO- (7) or CH3-CO-ĊH-COO- (9) respectively. The pKa of the serine-derived cationic radical HO-ĊH-CH(COOH)NH3+ (3a) (3a ⇄ 4a + H+), was determined by ESR spectroscopy to 2.2 ± 0.1 at 276 K. From kinetic data the pKa(OH) of radical 4a (4a ⇄ O-ĊH-CH(COO-)NH3+ (5a) + H+) was calculated to 7.0. The elimination of NH3 takes place from the ketyl radical 5a (type-B mechanism), the rate constant was calculated from kinetic data to 2.4 × 106 s-1 at 290 K. The half-lives of radicals 4a and 4b were measured by time-resolved conductivity changes upon pulse radiolysis, 170 ± 10 μs for 4a and 26 ± 2 μs for 4b, at 290 K and pH 5.8 . With the threonine derived radicals elimination of NH3 takes place at the stage of the α-hydroxyalkyl radical 4b (type-A mechanism). In this series the pKa of the product radical CH3-CO-ĊH-COOH (8) (8 ⇄ 9 + H+), was determined by ERS spectroscopy to 2.7 ± 0.1. The reasons for the observed mechanistic differences (type-A versus type-B decay) are discussed. As further examples for a type-B decay some preliminary data on the elimination of HF from the radicals CF3-Ċ(OH)-CF3 and CF3-ĊH-OH have been added.