Phosphate Ester Cleavage in Ribose-5-phosphate Induced by OH Radicals in Deoxygenated Aqueous Solution

Summary

The reaction of OH radicals and H atoms with ribose-5-phosphate (10⁻² M) in deoxygenated aqueous solution at room temperature (dose-rate 2·1 × 10¹⁷ eV/ml · min, dose 5 × 10¹⁸−15 × 10¹⁸ eV/ml) leads to the following dephosphorylation products (G-values): ribo-pentodialdose 1 (0·2), 2-hydroxy-4-oxoglutaraldehyde 2 (0·06), 5-deoxy-erythro-pentos-4-ulose 3 (0·1) and 3-oxoglutaraldehyde 4 (0·06). In addition, some minor phosphate free products (total G = 0·09) are formed. G(inorganic phosphate) = 1·3 and G(H₂O₂) = 0·3. On the addition of 10⁻³ M (Fe(III) ions, G(1) and G(3) increase to 0·6 and 0·4, respectively. In the presence of 10⁻³ M Fe(II), G(1) and G(3) change to 0·4 and 0·8, respectively. The other dephosphorylation products are suppressed by the iron ions. G(1) also increases on the addition of increasing amounts of H₂O₂. Each product can be assigned a precursor radical formed by hydrogen abstraction from C-5, C-4 or C-3 of the ribose-5-phosphate molecule. Products 1 and 2 are formed by oxydative dephosphorylation of an α-phospho radical with preceding H₂O elimination for product 2. Elimination of H₃PO₄ from a β-phospho radical leads to product 3; product 4 is formed by elimination of two molecules of H₂O from its precursor radical and hydrolytic cleavage of an enol phosphate bond. Deuterium-labelling experiments and the effects of the iron ions and of H₂O₂ support the mechanisms proposed. The importance of the dephosphorylation mechanisms for the formation of strand breaks in DNA is discussed with special reference to the effects of the radiosensitizers.