Content uploaded by Chryssostomos Chatgilialoglu
Author content
All content in this area was uploaded by Chryssostomos Chatgilialoglu on Jul 14, 2016
Content may be subject to copyright.
FULL PAPER
PPS
www.rsc.org/pps
The photochemistry of 8-bromo-2-deoxyadenosine. A direct entry to
cyclopurine lesions
Liliana B. Jimenez,a,bSusana Encinas,aMiguel A. Miranda,*aMaria Luisa Navacchiaband
Chryssostomos Chatgilialoglu*b
aDepartamento de Qu´
ımica/Instituto de Tecnolog´
ıa Qu´
ımica UPV-CSIC, Universidad
Polit´
ecnica de Valencia, Camino de Vera s/n, E-46022, Valencia, Spain.
E-mail: mmiranda@qim.upv.es; Fax: 34 96 3877809; Tel: 34 96 3877804
bISOF, Consiglio Nazionale delle Ricerche, Via P. Gobetti 101, I-40129, Bologna, Italy.
E-mail: chrys@isof.cnr.it; Fax: 39 051 6398349; Tel: 39 051 6398309
Received 19th July 2004, Accepted 28th September 2004
First published as an Advance Article on the web 22nd October 2004
The UV photolysis of 8-bromo-2-deoxyadenosine has been investigated in different solvents and in the presence of
additives like halide anions. Photolytic cleavage of the C–Br bond leads to formation of the C8 radical. In methanol,
subsequent hydrogen abstraction from the solvent is the main radical reaction; however, in water or acetonitrile
intramolecular hydrogen abstraction from the sugar moiety, to give the C5radical, is the major path. This C5radical
undergoes a cyclization reaction on the adenine and gives the aminyl radical. A rate constant of 1.8 ×105s−1has
been measured by laser flash photolysis in CH3CN for this unimolecular process. Product studies from steady-state
photolysis in acetonitrile have shown the conversion of 8-bromo-2-deoxyadenosine to 5,8-cyclo-2-deoxyadenosine
in 65% yield and in a diastereoisomeric ratio (5R):(5
S)=1.7. Evidence supporting that the equilibrium Br•+
Br−Br2
•−plays an important role in this synthetically useful radical cascade is obtained by regulating the relative
concentrations of the two reactive oxidizing species.
Introduction
Cyclopurine lesions, in particular 5,8-cyclo-2-deoxyadenosine
(5,8-cyclodAdo), are observed among the decomposition prod-
ucts of DNA when exposed to ionizing radiations or when
treated chemically by one-electron reductants.1Apart from the
usual glycosidic bond, in these moieties there is an additional
base-sugar linkage between the C8 and C5positions. From a
mechanistic point of view, it has been verified that the C5radical
initially generated by hydrogen abstraction, intramolecularly
attacks the aromatic ring of the base moiety to form cyclopurines
as the final products after oxidation.2
The chemical synthesis of the two diastereoisomeric forms of
5,8-cyclodAdo, i.e. (5R)- and (5S)-isomers, as well as their
incorporation on specific sites of DNA, is of considerable
importance in order to investigate the biological impact of
cyclopurines on the conformation and function of the double
helix. The existing approaches are mainly limited to low yield
multiple-step syntheses. The (5S)-isomer of 5,8-cyclodAdo
was prepared in seven steps starting from N6-benzoyl-dAdo in
an overall yield <10%.3Preparation of the (5R)-isomer was
further achieved by two additional steps, involving inversion of
configuration at the C5position.4Synthetic oligonucleotides
that contain these modified derivatives at selected sites were also
prepared,3,4 and some biochemical and biophysical features of
such lesions have already been obtained.5,6
Some of us recently investigated the reaction of hydrated elec-
trons (eaq
−) with 8-bromo-2-deoxyadenosine (1) by radiolytic
methods.2It was found that 1is prompt to capture electrons and
rapidly loses the bromide ion, to give the corresponding radical
in the C8 position (2), which in turn abstracts intramolecularly
a hydrogen atom exclusively from the C5position to selectively
afford the desired C5radical 3(Scheme 1). This allowed for the
first time the study the fate of the 2-deoxyadenosin-5-yl radical
properly and in particular the cyclization step, which occurs
with a rate constant kc=1.6 ×105s−1. Both species 3and
the cyclized aminyl radical are readily oxidized by Fe(CN)63−,
the rate constants being 4.2 ×109and 8.3 ×108M−1s−1,
respectively, whereas the aminyl radical can also be reduced by
strong reductants.2
In the present paper, we describe a photochemical study of 1
under various conditions.7It will be shown that a synthetically
useful radical cascade process has been developed allowing for
a one-pot conversion of 1to 5,8-cyclodAdo in a very good
yield and in a diastereoisomeric ratio strongly dependent on the
experimental conditions.
Experimental
Chemicals
8-Bromo-2-deoxyadenosine was provided by Berry & Asso-
ciates. Sodium iodide, phosphate buffer, 1,4-diazabicyclo[2.2.2]
octane (DABCO) and tetrabutylammonium iodide were pur-
chased from Aldrich. Acetonitrile and methanol, both HPLC
grade, were from Scharlau. Water was purified through a
Millipore Milli-RO plus 30 system.
Instrumentation
Reverse-phase HPLC analysis was performed on a Waters
apparatus equipped with a Teknokroma column (Kromasil
N30396, C18, 5 lm packing), a Waters 2996 photodiode
array detector at fixed wavelength of 254 nm and a Waters
600 controller. Chromatographic system used for analytical
experiments consisted of acetonitrile and water as eluents [linear
gradient from 0 to 5% of acetonitrile (30 min), from 5 to 10% of
acetonitrile (40 min) and from 10 to 30% of acetonitrile (60 min)]
ataflowrateof0.7mLmin
−1.
Steady-state photolysis
Solutions (10 mL) containing bromide 1(ca. 1mM)were
irradiated under N2. The irradiation sources were (A) a 125 W
medium-pressure mercury lamp and (B) a Rayonet multilamp
photoreactor (254 nm lamps). Different solvents were used
DOI:10.1039/b410939b
1042
Photochem. Photobiol. Sci.
, 2004, 3, 1042–1046
This journal is
©
The Royal Society of Chemistry and Owner Societies 2004
Downloaded by CNR Bologna on 09 May 2012
Published on 22 October 2004 on http://pubs.rsc.org | doi:10.1039/B410939B
View Online
/ Journal Homepage
/ Table of Contents for this issue
Scheme 1
(as indicated in Tables 1 and 2). The two diastereoisomers
of 5,8-cyclodAdo were purified on reverse-phase silica gel
(Fluka) eluting with 0, 1, 2 and 3% acetonitrile-containing
water. The UV-positive fractions were collected and lyophilized
to obtain the desired products as pure materials that were
spectroscopically characterized.2
Nanosecond laser flash photolysis
Laser flash photolysis experiments were performed by using
a Q-switched Nd:YAG laser (Quantel Brilliant, at 266 nm,
4 mJ pulse−1, 5 ns fwhm) coupled to a mLFP-111 Luzchem
miniaturized equipment. All transient spectra were recorded
employing 10 ×10 mm quartz cells with 4 mL capacity that were
bubbled during 30 min with N2before acquisition. Photolysis of
1was performed in CH3CNandalsoinCH
3CN/MeOH (v/v
1 : 3). In the case of solutions in CH3CN data were also recorded
in the presence of air or O2. The absorbance of the samples
was kept between 0.20 and 0.60 at the laser wavelength. All the
experiments were carried out at room temperature (22 ◦C).
Results and discussion
Bromide 1was UV-irradiated under a variety of experimental
conditions. The crude reaction mixtures were analyzed by
HPLC coupled with UV (diode-array) and MS (ion trap)
detection, using authentic samples as reference compounds for
the identification of the products. Table 1 and Chart 1 summarize
the experimental findings and the reaction products for which
yields are based on the consumption of starting bromide for a
better comparison.
Chart 1
Table 1 Yields (%) of products 4–9(see Chart 1) obtained by UV photolysis of 1a
Entry Solvent
Photolysis
conditions Conversion (%)
Overall yield
(%) 456789
1H
2O 1.5 hb61 93 21 6 17 10 34 5
2 1.5 hc95 100 31 7 34 19 9
3 1.5 hd48 88 14 6 68
4CH
3OH 1.5 h 97 82 5 2 2 62 11
5CH
3CN 0.5 h 100 96 41 24 17 14
6 1 h 100 90 36 23 18 13
7 2 h 100 86 29 26 14 17
aIrradiation of 1(10 mL tube−1, 1 mM) under N2was performed with a multilamp photoreactor at 254 nm; in this system temperature changed from
20 to 50 ◦C during the reaction course. Yields are based on the conversion of bromide 1. Estimated errors are less than 10% of the stated values. bpH
Changed from 7 to 4 during the reaction course. cpH 7; buffer solution with 10 mM KH2PO4/Na2HPO4.dIn the presence of DABCO (10 equiv);
pH changed from 9 to 8 during the reaction course.
Photochem. Photobiol. Sci.
, 2004, 3, 1042–1046 1043
Downloaded by CNR Bologna on 09 May 2012
Published on 22 October 2004 on http://pubs.rsc.org | doi:10.1039/B410939B
View Online
Table 2 Yields (%) of products 4–10 (see Chart 1) obtained by UV photolysis of 1in the presence of an additivea
Entry Solvent/additive
Photolysis
conditionsbConversion (%)
Overall
yield (%) 4567910
1H
2O/NaBr 3 h, A 58 98 34 13 27 13 7 4
23h,
cA 88 100 16 13 34 10 8 19
3H
2O/NaI 1.5 h, B 100 96 35 11 33 3 14 —
4 3 h, A 100 93 12 9 17 3 32 20
5 1.5 h, B +4h, A 100 100 3 9 24 5 36 23
67h,
cA 100 92 — — 33 3 11 45
7CH
3CN/Bu4N+I−2 min, B 33 100 5 4 28 13 50
8 10 min, B 100 100 3 5 6 16 70
9 30 min, B 100 100 1 2 2 18 77
aYields are based on the conversion of bromide 1. Estimated errors are less than 10% of the stated values. bA: Irradiation of 1(10 mL tube−1,1mM)
under N2was performed with a 125 W medium-pressure mercury lamp; in this system temperature was maintained at 20 ◦C during the reaction
course. B: Irradiation of 1(10 mL tube−1, 1 mM) was performed with a multilamp photoreactor at 254 nm; in this system temperature changed from
20 to 50 ◦C during the reaction course. cBuffer solution with 10 mM KH2PO4/Na2HPO4.
Entry 1 in Table 1 shows the reaction in aqueous medium
and at natural pH. After 1.5 h of photolysis 61% of the starting
material was converted to products. The cyclic products (4and
5) were formed in 27% overall yield and in a ratio (5R):(5
S)=
3.5, together with 17% of hydrated 5-carboxyaldehyde (6)and
10% of reduced product (7). However, the reaction unexpectedly
also led to the formation of 8-bromoadenine (8)andadenine(9)
in 34 and 5% yields, respectively, which are formal products of
glycolysis of the corresponding nucleosides. Indeed, during the
reaction the pH changed from 7 to 4. In order to verify this
hypothesis, the reaction was carried out in a buffered solution
at pH 7 (KH2PO4/Na2HPO410 mM). Under these conditions
(entry 2) a higher conversion was observed, with the suppression
of 8-bromoadenine (8) and the increase of the other five products
including adenine (9), whereas the (5R):(5
S) ratio was slightly
increased.
We also considered that amines may act as electron donors
under our photolytic conditions. Entry 3 shows the reaction
in aqueous medium in the presence of 10 equiv. of DABCO
(10 mM). The efficiency of this reaction was relatively low
with complete suppression of cyclic nucleosides and formation
of large amounts of adenine. During the reaction course the
pH changed from 9 to 8. Similar results were obtained by
replacing DABCO by Et3N (data not shown). Entry 4 shows
the reaction in methanol where 97% consumption of starting
bromide was observed after 1.5 h of irradiation. The increase
of 2-deoxyadenosine (7) to the detriment of cyclic products and
hydrat ed 5-carboxyaldehyde is noteworthy. Entry 5 shows the
reaction in acetonitrile where complete consumption of starting
bromide was observed in a shorter time. Under these conditions,
the formation of cyclic products reached a 65% overall yield
with the suppression of hydrated aldehyde 6.Itisalsoworth
mentioning that the ratio (5R):(5
S)=1.7 in CH3CN is halved
compared to water. By increasing the irradiation time the overall
yield decreased (entries 6 and 7) due to the consumption of (5R)-
isomer (4), whereas the other three products are quite stable.
It is worth underlining the different photo-stability of the two
diastereoisomers (see below).
In order to obtain information about the reactive intermedi-
ates involved in these synthetically useful reactions, the photo-
reactivity of 1was investigated by using laser flash photolysis
techniques. Photolysis of the bromo derivative 1in CH3CN with
266 nm laser light, under an anaerobic atmosphere, did not result
in the ‘instantaneous’ formation of a transient. However, the
spectrum shown in Fig. 1 developed in ≈20 ls after the pulse. The
time profile for the transient formation with kmax =360 nm (inset)
followed first-order kinetics with a rate constant k=1.8 ×105s−1
at room temperature. In analogy to the reaction of hydrated
electrons with 1, we assigned this transient to the conjugated
aminyl radical, and the observed rate to the cyclization of C5
radical 3(Scheme 1).3,8 Using CH3CN/CH3OH (v/v 1 : 3) as the
Fig. 1 Absorption spectrum obtained from the laser flash photolysis of
an Ar-purged CH3CN solution containing 1 mM of 1, taken 19 ls after
the pulse. Inset: Time dependence of absorption at 360 nm; the solid line
represents the first-order kinetic fit to the data.
solvent, or CH3CN saturated by air, the absorption at 360 nm
decreased substantially indicating that the precursor radical(s)
reacted efficiently with methanol and molecular oxygen.
The results described above demonstrate that the C–Br bond
in bromide 1is efficiently cleaved by UV light producing Br•
and the neutral r-type radical 2(Scheme 2). In methanol as
the solvent, intermolecular hydrogen abstraction by radical 2is
expected to be favored, as it is exothermic of ca. 20 kcal mol−1,
9to afford mainly the reduction product 7(Table 1, entry 4).
No evidence for formation or disappearance of radical 2was
obtained by laser flash photolysis experiments; however, it is
reported that the rate constant for the reaction of phenyl radical
with CH3OH is 4.4 ×106M−1s−1.10 In acetonitrile, hydrogen
abstraction mainly occurs intramolecularly to give radical 3.
This radical is calculated at the B3LYP/6-31G* level to be nearly
planar p-type with a very low interconversion barrier, and its
cyclization should afford the two aminyl radicals 12 and 13 in
chair conformations.2The fate of radicals 12 and 13 mainly
depends on the redox properties of the reaction partner. We
suggest that these radicals are readily oxidized in the reaction
mixture by transient oxidants (see below) followed by a rapid
deprotonation to afford the corresponding compounds 4and
5. In water, the above mentioned products are accompanied
by large amounts of hydrated 5-carboxyaldehyde 6,which
should be due to the oxidation of radical 3with formation of
oxocarbenium 11 followed by reaction with the medium.
Then, the question arises as to which is the oxidant acting
during the course of the reaction. The simplest answer could be
Br•atoms that are directly obtained from the photolysis of 1.
The redox properties of Br•are well known with E◦(Br•/Br−)=
1.92 V.11 Hence, the oxidation of C5radical 3by Br•is
thermodynamically quite favorable. Based on CH3CH(•)OH
radical for which E◦(CH3CHO, H+/CH3CH(•)OH) =−1.25 V,
1044
Photochem. Photobiol. Sci.
, 2004, 3, 1042–1046
Downloaded by CNR Bologna on 09 May 2012
Published on 22 October 2004 on http://pubs.rsc.org | doi:10.1039/B410939B
View Online
Scheme 2
the driving force for reaction of 3with Br•E◦(Br•/Br−)–
E◦(CH3CHO, H+/CH3CH(•)OH) =3.17 V is quite high and
should bring to a fast process. Similar consideration can be made
for aminyl radicals 12 or 13. Since the E◦(N+/N•)≤0.36 V
(N•refers to radical 12 or 13 and N+to the corresponding
cations),2thedrivingforceforthereactionof12 or 13 with Br•
is ≥1.56 V. Under our experimental conditions, lMlevelofBr
−
should be reached very quickly as the reduction product of Br•
and the equilibrium given in reaction (1) should start to play a
role. Rate and equilibrium constants of this reaction as well as
its temperature-dependence are well known. At 20 ◦Cthevalues
are k1=1.1 ×1010 M−1s−1,k−1=2.7 ×104s−1and K1=3.6 ×
105M−1whereas at 50 ◦C the values are k1=1.9 ×1010 M−1s−1,
k−1=9.2 ×104s−1and K1=2.0 ×105M−1.12 The equilibrium
defined by reaction (1) is important because it regulates the
relative concentrations of solvated reactive species. Basically this
means a conversion of the highly oxidizing Br•[E◦(Br•/Br−)=
1.92 V] to a less oxidizing Br2
−•[E◦(Br2
−•/2Br−)=1.66 V].11
Still, Br2
−•could play the role of an effective oxidant.
Br·+Br−k1
k−1
Br·−
2(1)
In order to obtain further information about the reaction
mechanism and, in particular, to test the ability of halide anions
(Br−or I−)totrapBr
•atoms in the reaction mixture, the reaction
in water was carried out in the presence of NaBr or NaI. Table 2
summarizes the experimental findings. Again yields are based on
the consumption of starting bromide for a better comparison.
Entry 1 in Table 2 shows the results of photolysis of de-aerated
aqueous solution containing 1 mM of 1in the presence of 2
equiv NaBr. The results were similar to the outcome in the
absence of NaBr (entry 1 in Table 1), although the suppression
of 8-bromoadenine (8) and the appearance of small amounts of
a new product, 2,5-dideoxycycloadenosine (10), can be noticed.
However, the same reaction carried out in buffer (pH 7) showed
an increase of this new product to the detriment of (5R)-isomer
4(entry 2). Entry 3 in Table 2 shows the reaction in the presence
of 2 equiv of NaI. Under prolonged photolysis the appearance of
10 mainly to the detriment of (5R)-isomer is again noteworthy
(entries 4 and 5). When the same solution was buffered (entry
6) the (5R)- and (5S)-isomers completely disappeared and the
dideoxy derivative 10 was obtained in a 45% yield. The effect of
iodide in the photolysis of 1in CH3CNwasalsotestedusingthe
soluble source Bu4N+I−(entries 7 and 8). Under these conditions
the cyclonucleosides were formed in small quantities indicating
that C5radical is rapidly trapped prior to cyclization to give
5-carboxaldehyde (6), which further decomposes under the UV
irradition to afford the free adenine base in high yield. Thus,
adenine seems to be produced by photoinduced glycolysis of the
aldehyde.
In the presence of 2 mM NaBr, reaction (1) became the
predominating path of bromine atom since the equilibrium is
completely shifted to the right (K1=3.6 ×105M−1). Rate and
equilibrium constants of reaction (2) as well as its temperature-
dependence are also well known.13 At 20 ◦C the values are k2=
8.9 ×109M−1s−1,k−2=6.5 ×104s−1and K2=1.4 ×105M−1,
which are similar to the corresponding data for reaction (1). It is
reasonable to assume similar data for the reaction of Br•atoms
with I−. Therefore, in the presence of 2 mM of halide anions,
Br2
−•or IBr−•should play only the role of effective oxidants.
Moreover, since I2
−•[E◦(I2
−•/2I−)=1.05 V] is weaker oxidant
than Br2
−•[E◦(Br2
−•/2Br−)=1.66 V] it is reasonable to assume
that IBr−•has an intermediate oxidizing ability, i.e.,E◦(IBr−•/I−,
Br−)≈1.36 V.11
I·+I−k2
k−2
I·−
2(2)
The formation of 2,5-dideoxycycloadenosine (10) is not
straightforward. This compound is clearly formed from the
two 5,8-cyclo-2-deoxyadenosines, (5R)-isomer being the more
reactive. It is favored in aqueous solution, in the presence of
halide anions and with increasing irradiation times. Evidence
supporting that higher temperature and phosphate catalysis
facilitate this process has also been obtained. Although a
detailed mechanistic investigation is beyond the scope of this
paper, a reasonable proposal is a reductive elimination or
photo-induced decomposition. Indeed, Br2
−•[E◦(Br2/Br2
•−)=
0.50 V] and I2
−•[E◦(I2/I2
•−)=0.21 V],11 are known to act as
reductants depending on the reaction partner. Current studies
are in progress to address these issues as well as to investigate
the importance of the reactions in DNA damage and repair.
Conclusions
Selective generation of C5radical in 2-deoxyadenosine has
been achieved by UV photolysis of C–Br in 8-bromo-2-
deoxyadenosine (1) followed by fast radical translocation. The
reactivity of C5radical has been studied in some details in
different solvents and in the presence of additives like halide
anions. An expedient one-pot procedure has also been developed
Photochem. Photobiol. Sci.
, 2004, 3, 1042–1046 1045
Downloaded by CNR Bologna on 09 May 2012
Published on 22 October 2004 on http://pubs.rsc.org | doi:10.1039/B410939B
View Online
that allows the conversion of 8-bromo-2-deoxyadenosine (1)to
5,8-cyclo-2-deoxyadenosine (5,8-cyclodAdo) in 65% and in a
diastereoisomeric ratio (5R):(5
S)=1.7 by UV photolysis in
acetonitrile. This radical cascade consists of photolytic cleavage
of the C–Br bond to give the C8 radical, a radical translocation
from C8 to C5position, a cyclization of C5radicaltothe
adenine moiety with a rate constant of 1.8 ×105s−1to give an
aminyl radical and its final oxidation. The evidence supports
the suggestion that the equilibrium Br•+Br−Br2
•−plays an
important role by regulating the relative concentrations of the
two reactive oxidizing species has been obtained.
Acknowledgements
We thank Clara Caminal for providing us with a pure sample of
5-carboxyaldehyde-2-deoxyadenosine, which has been used as
reference in this work. Work supported in part by the European
Community’s Marie Curie Research Training Network under
contract MRTN-CT-2003-505086 [CLUSTOXDNA]. We also
thank the financial support given by the Spanish MCYT (BQU
2001-2725 and Ram´
on y Cajal project to S.E.), the Generalitat
Valenciana (Grupos 03/082, CTBPRB/2003/68 and Project
GV04A-349) and the UPV (Project PPI-06-03).
References
1(a) For example, see: M.-L. Dirksen, W. F. Brakely, E. Hol-
witt and M. Dizdaroglu, Effect of DNA conformation on
the hydroxyl radical-induced formation of 5,8-cyclopurine-2-
deoxyribonucleoside residues in DNA, Int. J. Radiat. Biol., 1988,
54, 195–204; (b) M. Dizdaroglu, P. Jaruga and H. Rodriguez,
Identification and quantification of 5,8-cyclo-2-deoxyadenosine in
DNA by liquid chromatography/mass spectrometry, Free Radical
Biol. Med., 2001, 30, 774–784; (c) P. Jaruga, M. Birincioglu, H.
Rodriguez and M. Dizdaroglu, Mass spectrometric assays for the
tandem lesion 5,8-cyclo-2-deoxyguanosine in mammalian DNA,
Biochemistry, 2002, 41, 3703–3711; (d) M. Birincioglu, P. Jaruga, G.
Chowdhury, H. Rodriguez, M. Dizdaroglu and K. S. Gates, DNA
base damage by the antitumor agent 3-amino-1,2,4-benzotriazine
1,4-dioxide (tirapazamine), J. Am. Chem. Soc., 2003, 125, 11607–
11615.
2(a) C. Chatgilialoglu, M. Guerra and Q. C. Mulazzani, Model
studies of DNA C5radicals. Selective generation and reactivity
of 2-deoxyadenosin-5-yl radical, J. Am. Chem. Soc., 2003, 125,
3839–3848; (b) R. Flyunt, R. Bazzanini, C. Chatgilialoglu and
Q. G. Mulazzani, Fate of the 2-deoxyadenosin-5-yl radical under
anaerobic conditions, J. Am. Chem. Soc., 2000, 122, 4225–4226.
3 A. Romieu, D. Gasparutto, D. Molko and J. Cadet, Site-specific
introduction of (5S)-5,8-cyclo-2-deoxyadenosineinto oligodeoxyri-
bonucleotides, J. Org. C h e m ., 1998, 63, 5245–5249.
4 A. Romieu, D. Gasparutto and J. Cadet, Synthesis and char-
acterization of oligonucleotides containing 5,8-cyclopurine 2-
deoxyribonucleosides: (5R)-5,8-cyclo-2-deoxyadenosine, (5S)-5,8-
cyclo-2-deoxyguanosine, and (5R)-5,8-cyclo-2-deoxyguanosine,
Chem. Res. Toxicol., 1999, 12, 412–421.
5(a) I. Kuraoka, C. Bender, A. Romieu, J. Cadet, R. D. Wood
and T. Lindahl, Removal of oxygen free-radical-induced 5,8-purine
cyclodeoxynucleosides from DNA by the nucleotide excision-repair
pathway in human cells, Proc. Natl. Acad. Sci. USA, 2000, 97,
3832–3837; (b) I. Kuraoka, P. Robins, C. Masutani, F. Hanaoka, D.
Gasparutto, J. Cadet, R. D. Wood and T. Lindahl, Oxygen free radical
damage to DNA: translesion synthesis by human DNApolymerase g
and resistance to exonuclease action at cyclopurine deoxynucleoside
residues, J. Biol. Chem., 2001, 276, 49283–49288.
6(a) P. J. Brooks, D. S. Wise, D. A. Berry, J. V. Kosmoski, M. J.
Smerdon, R. L. Somers, H. Mackie, A. Y. Spoonde, E. J. Ackerman,
K. Coleman, R. E. Tarone and J. H. Robbins, The oxidative DNA
lesion 5,8-(S)-cyclo-2-deoxyadenosine is repaired by the nucleotide
excision repair pathway and blocks gene expression in mammalian
cells, J. Biol. Chem., 2000, 275, 22355–22362; (b) K. Randerath,
G. D. Zhou, R. L. Somers, J. H. Robbins and P. J. Brooks, A
32P-postlabeling assay for the oxidative DNA lesion 5,8-cyclo-2-
deoxyadenosine in mammalian tissues. Evidence that four type
II I-compounds are dinucleotides containing the lesion in the 3
nucleotide, J. Biol. Chem., 2001, 276, 36051–36057.
7 It was reported in a note as unpublished results that photolysis at
254 nm of a de-aerated aqueous solution of 2afforded (5S)- and
(5R)-isomers of 1in 2 and 12% yields, respectively (ref. 3).
8 For the ribo analogues, see: C. Chatgilialoglu, M. Duca, C. Ferreri,
M. Guerra, M. Ioele, Q. G. Mulazzani, H. Strittmatter and B. Giese,
Selective generation and reactivityof 5-adenosinyl and 2-adenosinyl
radicals, Chem. Eur. J., 2004, 10, 1249–1255.
9 J. Berkowitz, G. B. Ellison and D. Gutman, Three methods to
measure RH bond energies, J. Phys. Chem., 1994, 98, 2744–2765.
10 X. Fang, R. Mertens and C. von Sonntag, Pulse radiolysis of
aryl bromides in aqueous solutions: Some properties of aryl and
arylperoxyl radicals, J. Chem. Soc., Perkin Trans. 2, 1995, 1033–1036.
11 P. Wardman, Reduction potentials of one-electron couples involving
free radicals in aqueous solution, J. Phys. Chem. Ref. Data, 1989, 18,
1637–1755.
12 Y. Liu, A. S. Pimentel, Y. Antoku, B. J. Giles and J. R.
Barker, Temperature-dependent rate and equilibrium constants for
Br.bul.(aq) +Br-(aq).dblarw. Br2-.bul.(aq), J. Phys. Chem. A, 2002,
106, 11075–11082.
13 Y. Liu, R. L. Sheaffer and J. R. Barker, Effects of temperature and
ionic strength on the rate and equilibrium constants for the reaction
I.bul.aq +I-aq.tautm. I2.bul.-2aq, J. Phys. Chem. A, 2003, 107,
10296–10302.
1046
Photochem. Photobiol. Sci.
, 2004, 3, 1042–1046
Downloaded by CNR Bologna on 09 May 2012
Published on 22 October 2004 on http://pubs.rsc.org | doi:10.1039/B410939B
View Online
