Peroxyl Radicals - Free-Radical-Induced DNA Damage and Its Repair - page 171

The mechanistic proposal for the chain reaction of O 2 • − with the DTT anion
represented by reactions (84)−(89) (Lal et al. 1997) deviates slightly from the
original proposal (Zhang et al. 1991). The essential aspect, however, remains the
addition of O 2 • − to the thiolate thereby forming a three-electron-bonded inter-
mediate [reaction (84); for other three-bonded intermediates see Chap. 7.4] and
its subsequent decay into an oxidizing species [reaction (85)]. It has been calcu-
lated that the rate constant of the rate-determining step, reaction (84), is 35 dm 3
mol − 1 s − 1 . This reaction is even slower than the H-abstraction reaction of the HO 2 •
radical discussed above.

The reactivity of a wider range of thiols toward O 2 • − has been studied (Winter-
bourn and Metodiewa 1999), and it has been observed that at pH 7.4 only those
thiols show an appreciable reactivity who have a low p K a value, such as penicil-
lamine and cysteine (at pH 7, the rate constant of O 2 • − with N -actylcysteine is
68 dm 3 mol − 1 s − 1 ; Benrahmoune et al. 2000). This can be rationalized by assuming
that a reasonable thiolate steady-state concentration is required for the reaction
to proceed. In the case of GSH the disulfide was again the major product, but the
formation of some glutathionesulfonic acid was also reported (Winterbourn and
Metodiewa 1994). In the biological context, the reactivity of O 2 • − with GSH is of
major importance. Various rate constants are reported in the literature; the most
recent re-evaluation gives now a value of 200 dm 3 mol − 1 s − 1 , indicating that in a

cellular environment this reaction is too slow to compete with the elimination of
O 2 • − by SOD (Jones et al. 2002, 2003).
In the cellular environment, ascorbic acid (AH 2 ) plays a major role. Its p K a
value is at 4.3 [equilibrium (90)], and hence the ascorbate anion (AH − ) predomi-
nates around neutrality.

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