75
3 Formation of DNA Lesions, its Prevention and Repair
attached to four different sites including that attached to the sulphur atom were
found to be moderate while the Gibbs barrier energy for abstraction of a hydrogen
atom attached a nitrogen atom was found to be high. Thus glutathione has been
shown to be an excellent scavenger of OH
•
[155]. Glutathione exists in an anionic
form at physioplogical pH where the glycine moiety is deprotonated while the glutamic acid moiety is in the zwitterionic form [159]. A theoretical study was carried
out at the M05-2X/6-311 + G(d, p) level of theory on the OH
•
scavenging ability
of glutathione where its anionic form (GS
−
) was considered [153]. To treat solvent
effect in water, the SMD continuum model was employed [160]. The SET mechanism was found to be endergonic and hence was ruled out. It was concluded that
glutathione acts as an anti-oxidant exclusively by the HAT mechanism. Further, the
most reactive site was found to be that of sulphur where the hydrogen abstraction
reaction occurred in a barrierless manner and with a high rate constant (1.16 × 10
9
M
−1
s
−1
) [153]. It is clear that the barrier energy for hydrogen abstraction from the
SH group of glutathione is small. However, whether it is negligibly small or not is
still not established [153, 155].
Vitamin B 6 (Fig. 3.7f), also named as pyridoxine, is one of the eight water soluble vitamins of class B [161–163]. A high OH
•
quenching ability was reported for
vitamin B 6 and it was also found to be as effective as Vitamin E (Fig. 3.7i) [161].
Pyridoxine was found to be the most reactive among the vitamin B 6 sub-class of
molecules i.e. pyridoxine, pyridoxal, pyridoxamine and pyridoxal-5-phosphate. In
a recent theoretical study performed on this system at the B3LYP/6-31G(d, p) level
of theory, it was found that it can scavenge up to eight OH
•
[163]. Thus vitamin
B 6 would be very beneficial as an OH
•
scavenger. Hydrogen abstraction reactions
between OH
•
and pyridoxine were found to occur preferentially either from the C8
or the C9 site at the first step (Fig. 3.7f) [163]. In subsequent reactions, addition and
cyclization were also considered. Thus vitamin B 6 is also shown to be an efficient
OH
•
scavenger.
Interestingly, recently, high concentration of molecular hydrogen (H 2 ) has been
shown to scavenge OH
•
. Drinking of water that contains higher level of H 2 has been
shown to decrease urinary 8-oxoG significantly by mainly scavenging OH
•
. It is further suggested that the use of H 2 can be beneficial in the prevention of rheumatoid
arthritis that mainly arises due to OH
•
mediated oxidative stress [164].
A density functional theoretical study was performed on the OH
•
scavenging
property of N-acetylcysteine (NAC) which is a precursor of glutathione (Fig. 3.7g)
[165]. Solvent effect in water was treated employing the PCM. N-acetylcysteine
was found to effectively scavenge OH
•
through the HAT mechanism. This reaction
at the sulphur site was found at the BHandHLYP/Aug-cc-pVDZ level of theory in
polar media to take place barrierlessly and with a high rate constant. However, hydogen abstraction from two carbon sites was also found to contribute significantly
to the OH
•
scavenging ability of N-acetylcysteine.
The mechanism of action of vitamin C (ascorbic acid) as an anti-oxidant towards
OH
•
is well known. At physiological pH, it exists in a monoanionic form (AA
−
). A
theoretical study of the reactions between AA
−
and OH
•
was performed employing
density functional theory [166]. Solevnt effect in water was treated employing the
3 Formation of DNA Lesions, its Prevention and Repair
attached to four different sites including that attached to the sulphur atom were
found to be moderate while the Gibbs barrier energy for abstraction of a hydrogen
atom attached a nitrogen atom was found to be high. Thus glutathione has been
shown to be an excellent scavenger of OH
•
[155]. Glutathione exists in an anionic
form at physioplogical pH where the glycine moiety is deprotonated while the glutamic acid moiety is in the zwitterionic form [159]. A theoretical study was carried
out at the M05-2X/6-311 + G(d, p) level of theory on the OH
•
scavenging ability
of glutathione where its anionic form (GS
−
) was considered [153]. To treat solvent
effect in water, the SMD continuum model was employed [160]. The SET mechanism was found to be endergonic and hence was ruled out. It was concluded that
glutathione acts as an anti-oxidant exclusively by the HAT mechanism. Further, the
most reactive site was found to be that of sulphur where the hydrogen abstraction
reaction occurred in a barrierless manner and with a high rate constant (1.16 × 10
9
M
−1
s
−1
) [153]. It is clear that the barrier energy for hydrogen abstraction from the
SH group of glutathione is small. However, whether it is negligibly small or not is
still not established [153, 155].
Vitamin B 6 (Fig. 3.7f), also named as pyridoxine, is one of the eight water soluble vitamins of class B [161–163]. A high OH
•
quenching ability was reported for
vitamin B 6 and it was also found to be as effective as Vitamin E (Fig. 3.7i) [161].
Pyridoxine was found to be the most reactive among the vitamin B 6 sub-class of
molecules i.e. pyridoxine, pyridoxal, pyridoxamine and pyridoxal-5-phosphate. In
a recent theoretical study performed on this system at the B3LYP/6-31G(d, p) level
of theory, it was found that it can scavenge up to eight OH
•
[163]. Thus vitamin
B 6 would be very beneficial as an OH
•
scavenger. Hydrogen abstraction reactions
between OH
•
and pyridoxine were found to occur preferentially either from the C8
or the C9 site at the first step (Fig. 3.7f) [163]. In subsequent reactions, addition and
cyclization were also considered. Thus vitamin B 6 is also shown to be an efficient
OH
•
scavenger.
Interestingly, recently, high concentration of molecular hydrogen (H 2 ) has been
shown to scavenge OH
•
. Drinking of water that contains higher level of H 2 has been
shown to decrease urinary 8-oxoG significantly by mainly scavenging OH
•
. It is further suggested that the use of H 2 can be beneficial in the prevention of rheumatoid
arthritis that mainly arises due to OH
•
mediated oxidative stress [164].
A density functional theoretical study was performed on the OH
•
scavenging
property of N-acetylcysteine (NAC) which is a precursor of glutathione (Fig. 3.7g)
[165]. Solvent effect in water was treated employing the PCM. N-acetylcysteine
was found to effectively scavenge OH
•
through the HAT mechanism. This reaction
at the sulphur site was found at the BHandHLYP/Aug-cc-pVDZ level of theory in
polar media to take place barrierlessly and with a high rate constant. However, hydogen abstraction from two carbon sites was also found to contribute significantly
to the OH
•
scavenging ability of N-acetylcysteine.
The mechanism of action of vitamin C (ascorbic acid) as an anti-oxidant towards
OH
•
is well known. At physiological pH, it exists in a monoanionic form (AA
−
). A
theoretical study of the reactions between AA
−
and OH
•
was performed employing
density functional theory [166]. Solevnt effect in water was treated employing the