Nucleobases, Nucleosides and Nucleotides - Free-Radical-Induced DNA Damage and Its Repair - page 201

10.1
General Remarks

In DNA, there are four different nucleobases, the pyrimidines Thy and Cyt, and
the purines Gua and Ade. In RNA, Ura replaces Thy 1 .

In their free-radical chemistry, these nucleobases have many properties in com-
mon. There are, however, also considerable differences which strongly affect the
various reaction pathways. In nucleosides and nucleotides, free-radical attack
mainly occurs at the base moiety. These reactions largely involve addition reac-
tions. Only the sugar moiety and the methyl group in Thy can act as H-donors.
The C (2 )-position is the least likely to be attacked because of the stronger BDEs

of these hydrogens (Miaskiewicz and Osman 1994; Steenken et al. 2001), but this
reaction can become of importance when favored by steric conditions.

′

10.1.1
p K a Values

Ura, Thy and Gua deprotonate at pH < 10 [reaction (1)], but are not protonated
at pH > 3. On the other hand, Cyt and Ade and their nucleosides already become
protonated around pH 4 [e.g., reaction (3)], but, with the exception of Ade itself,
they only deprotonate at very high pH (Table 10.1). The deprotonation of nucleo-
sides at pH > 12 is often due to a deprotonation at the sugar moiety (Velikyan et

1 In this chapter, the three-letter abbreviations (Fasman 1975) are used, and a few examples are
given below. Nucleobases and its derivatives: adenine ( Ade ), guanine ( Gua ), cytosine ( Cyt ), thy-
mine ( Thy ), uracil ( Ura ), 5-bromouracil ( 5BrUra ), 1,3-dimethyluracil ( 1,3Me 2 Ura ), 5,6-dihydro-
uracil ( H 2 Ura ), 5,6-dihydro,5,6-dihydroxythymine, thymine glycol, [ (OH) 2 Thy ], 6-hydroxy-5,6-
dihydrothymine ( 6OHH 2 Thy ). Nucleosides: adenosine ( Ado ), guanosine ( Guo ), Cytidine ( Cyd ),
uridine ( Urd ), 2 ′ -deoxyadenosine ( dAdo ), 2 ′ -deoxyguanosine ( dGuo ), 2 ′ -deoxycytidine ( dCyd ),
thymidine ( Thd ), 2 ′ -deoxy-5-bromouridine ( 5BrdUrd ). Nucleotides: adenosine-3 ′ -phosphate
( Ado-3 ′ -P ), 2 ′ -deoxyadenosine-5 ′ -phosphate ( dAdo-5 ′ -P ).