Nucleobases, Nucleosides and Nucleotides - Free-Radical-Induced DNA Damage and Its Repair - page 283

H-abstraction at C (3 ′ ) in 3 ′ -nucleotides gives rise to an α -phosphatoalkyl radi-

cal (the phosphatoalkyl group in -position favors the rate of H-abstraction less

than an OH group; Schuchmann et al. 1995). From a study on the • OH-induced
reactions of trimethylphosphate, it has been concluded that a hydrolysis of the
• CH 2 OP(O)(OCH 3 ) 2 radical must be very slow at pH 7 and is just noticeable at
high pH (von Sonntag et al. 1972). In the presence of O 2 , the alkyl group is fully
degraded (formation of dimethylphosphate in full yield; Schuchmann and von
Sonntag 1984). The rapid formation of acids ( k = 0.3 + 2.3

α

10 4 [OH − ] s −1 ) has
been attributed to the hydrolysis of the anhydride of formic acid and dimethyl-
phosphoric acid (for the hydrolysis of other anhydrides of formic acid see Leitz-
ke et al. 2003). Much closer to the question of the potential reactions of the C (3

×

)
radical is a study on triisopropyl phosphate (Schuchmann et al. 1984c). In the
presence of O 2 ,

′

50% of • OH gives rise to the formation of diisopropylphosphate,
and acetic acid is an important product (Schuchmann et al. 1995). This points
to the formation of the anhydride of acetic acid and diisopropylphosphoric acid
as an intermediate whose precursor must be an oxyl radical. Translated to the
C (3

∼

′ ) − O • formed upon the bimolecular decay of the C (3 ′ ) − OO • radicals of nucleo-

tides, fragmentation of the C (3 ) bond will occur [reaction (283)], and the

anhydride function in will subsequently hydrolyze [reaction (284)]. Of course,
there are further decay routes, but the reaction sequence shown here must cer-
tainly be of a major importance.

′ ) − C (4 ′

Oxidation of -phosphatoalkyl radicals by TNM leads first to an adduct which

subsequently decays thereby releasing NF − (Schuchmann et al. 1995). Nitroaro-
matic sensistizers form also adducts albeit more slowly than TNM. Oxidation of
α

α

-phosphatoalkyl radicals by Fe(CN) 6 3− is only moderately fast.
Phosphate release yields from some 3

-mononucleotides are compiled
in Table 10.28. The data in N 2 O-saturated solutions indicate that phosphate re-
lease from the 3

′ - and 5 ′

-posi-
tion. Correcting for the fact that under O 2 the • OH yield is about halved, there is
a protecting effect for 3

′ -position is about twice as efficient than that from the 5 ′

-AMP 3 -dAMP and 3 -GMP but an enhancement in the

′ ′ ′

case of 3 ′ -CMP and 3 ′ -UMP. For the 5 ′ -nucleotides, there is always an increase