The Effects of Counter-ion Condensation and Co-ion Depletion Upon the Rates of Chemical Repair of Poly(U) Radicals by Thiols

Summary Bimolecular rate constants for reactions of poly(U) radicals with a series of thiols of varying net charge (Z) were measured by pulse radiolysis with conductivity detection at low ionic strength. At pH 7 and 18°C the values of k2 (M−1 s−1) were: reduced glutathione (Z = −1), < 500 2-mercaptoethanesulphonic acid (Z = −1), 1·5 × 103; 2-mercaptoethanol (Z = 0), 1·8 × 105; cysteine (Z = 0), 2·0 × 105; cysteamine (Z = +1), 4·1 × 107. Values determined at pH4 were: 2-mercaptoethanol, 6·1 × 105; cysteamine 2·2 × 108; N-(2-mercaptoethyl)-1,3-diaminopropane (WR-1065, Z = +2), 4·6 × 108. The variation in rate with structure could not reasonably be attributed to inherent reactivity differences in the thiols and was ascribed to inhomogeneous distributions of the thiols in solution resulting from electrostatic interactions. Thus, cationic thiols are concentrated ∼100-fold near poly(U), relative to neutral thiols, as a consequence of counter-ion condensation, whereas anionic thiols have a ∼100-fold lower concentration near poly(U) than neutral thiols as a result of co-ion depletion. These results show that the ability of a thiol to repair radical sites in a polyanion is dramatically influenced by its net charge as a consequence of the counter-ion condensation and co-ion depletion phenomena.