Chemistry Reference
In-Depth Information
and C1
′
hydrogens.
57,88
This preference stems from the accessibility of the C4
′
which,
along with the C5
hydrogens, project into the minor groove and are the most solvent
accessible of the deoxyribose hydrogens in normal B-form DNA.
86
Cr(V) is consid-
ered to preferentially attack the C4
′
hydrogen of deoxyri-
bose because it is easier to remove a hydrogen from a tertiary rather than a
secondary carbon despite the fact that the C5
′
hydrogen and not the C5
′
′
hydrogens are slightly more solvent
accessible.
88
While the tertiary C1
hydrogen is also oriented towards the minor
groove, it is not as readily accessible for oxidation by chromium, as H1
′
abstraction
requires that an oxidant bind to the minor groove and then orient itself directly
towards the H1
′
′
position.
89
In the presence of hydrogen peroxide, (1 mM) abstrac-
tion of the C1
hydrogen has been observed.
90
Reactions with hydrogen peroxide
are considered of little signifi cance in the overall scheme of chromium-induced
genetic damage, since physiological concentrations of hydrogen peroxide are much
lower than 1 mM.
56
However, a model metastable Cr(V) complex with the bis-tris
buffer designated Cr(V)-BT has shown the formation of the deoxyribose oxidation
product 5 - methylene - 2 - furanone (5 - MF) that would indicate a classical C1
′
hydro-
gen abstraction mechanism (Figure 17.9).
57
It is proposed that the correct orienta-
tion for hydrogen abstraction at C1
′
by this Cr(V) complex is generated through
interaction with the phosphate backbone of DNA.
57
This Cr(V) complex also showed
a smaller amount of C4
′
oxidation product.
A different model Cr(V) complex, bis(2 - ethyl - 2 - hydroxybutyrato)oxochromat
e(V) or Cr(V)-ehba (which is proposed to resemble the Cr(V)-ascorbate complexes
formed during ascorbate-induced Cr(VI) reduction; Figure 17.3A), has been shown
to abstract the C4
′
′
hydrogen of deoxyribose. This C4
′
hydrogen abstraction mechanism
B
OR
OR
O
-
O
-
O
P
O
P
+
B
B
O
O
Cr(V)-BT
O
O
O
O
O
2
H
H
H
H
H1'
H
H
H
H
H
O
O
5-methylene-2-furanone
(5-MF)
O
-
O
-
O
P
O
P
OR
OR
+
OR
O
-
O
P
OH
free 3'-phosphate termini
Figure 17.9
Abstraction of the C1
hydrogen by Cr(V)-BT leads to formation of the free base,
the 5-methylene-2-furanone sugar product and frank strand scission
57
′
