67
3 Formation of DNA Lesions, its Prevention and Repair
3.3.4 By Nitrogen Dioxide (NO 2
•
)
Formation of the guanine radical G(-H)
•
has been observed experimentally [118].
Reaction of G(-H)
•
with NO 2
•
generates 8-NO 2 G as shown by DFT calculations
[67]. Details in terms of structures and energies for a particular scheme of reaction
between G(-H9
•
) and NO 2
•
leading to the formation of 8-NO 2 G obtained by geometry optimization at the BHandHLYP/6-31G(d, p) level in gas phase followed by
single point energy calculations at the MP2/Aug-cc-pVDZ level of theory in aqueous media are shown in Fig. 3.4. The polarizable continuum model (PCM) [123,
124] was used to study solvation in bulk aqueous media. Water molecules facilitate
proton transfer between different sites. In this case, proton transfer takes place from
C8 to N9 in two steps. It should be noted that addition of NO 2
•
to G(-H)
•
where H9
is removed would not be relevant to the actual DNA since in DNA N9 is bonded to
deoxyribose sugar. Reaction of G(-H)
•
with NO 2
•
has also been suggested to yield
NI [78]. This in general occurs due to the addition of NO 2
•
at the C5 position of G(H)
•
followed by subsequent hydration and decarboxylation. Formation of NI from
2′,3′,5′-Tri-O-acetyl-guanosine has been observed in UV/vis spectroscopy, ESIMS, and NMR studies [113]. Further, it has been found that NI does not degrade to
other products and is quite stable in aqueous solutions at both acidic and basic pH.
Formation of guanine radical cation (G
• +
) has been observed experimentally
when the specimen is exposed to high energy radiation [118]. The reaction of G
• +
with NO 2
•
has been shown to yield 8-NO 2 G
+
[63]. Details of a particular scheme
a
b
c
d
e
Fig. 3.3 Reaction of nitrosoperoxycarbonate anion with guanine. a Initial reactant complex, b,
c, d Intermediates and e Product complex (8-oxoG + NO 2
−
+ CO 2 ). Gibbs barrier (positive) and
released (negative) energies (kcal/mol) at each step obtained at the B3LYP/AUG-cc-pVDZ level
in aqueous media are given near the arrows. The last step is barrierless [65]
3 Formation of DNA Lesions, its Prevention and Repair
3.3.4 By Nitrogen Dioxide (NO 2
•
)
Formation of the guanine radical G(-H)
•
has been observed experimentally [118].
Reaction of G(-H)
•
with NO 2
•
generates 8-NO 2 G as shown by DFT calculations
[67]. Details in terms of structures and energies for a particular scheme of reaction
between G(-H9
•
) and NO 2
•
leading to the formation of 8-NO 2 G obtained by geometry optimization at the BHandHLYP/6-31G(d, p) level in gas phase followed by
single point energy calculations at the MP2/Aug-cc-pVDZ level of theory in aqueous media are shown in Fig. 3.4. The polarizable continuum model (PCM) [123,
124] was used to study solvation in bulk aqueous media. Water molecules facilitate
proton transfer between different sites. In this case, proton transfer takes place from
C8 to N9 in two steps. It should be noted that addition of NO 2
•
to G(-H)
•
where H9
is removed would not be relevant to the actual DNA since in DNA N9 is bonded to
deoxyribose sugar. Reaction of G(-H)
•
with NO 2
•
has also been suggested to yield
NI [78]. This in general occurs due to the addition of NO 2
•
at the C5 position of G(H)
•
followed by subsequent hydration and decarboxylation. Formation of NI from
2′,3′,5′-Tri-O-acetyl-guanosine has been observed in UV/vis spectroscopy, ESIMS, and NMR studies [113]. Further, it has been found that NI does not degrade to
other products and is quite stable in aqueous solutions at both acidic and basic pH.
Formation of guanine radical cation (G
• +
) has been observed experimentally
when the specimen is exposed to high energy radiation [118]. The reaction of G
• +
with NO 2
•
has been shown to yield 8-NO 2 G
+
[63]. Details of a particular scheme
a
b
c
d
e
Fig. 3.3 Reaction of nitrosoperoxycarbonate anion with guanine. a Initial reactant complex, b,
c, d Intermediates and e Product complex (8-oxoG + NO 2
−
+ CO 2 ). Gibbs barrier (positive) and
released (negative) energies (kcal/mol) at each step obtained at the B3LYP/AUG-cc-pVDZ level
in aqueous media are given near the arrows. The last step is barrierless [65]