Chemistry Reference
In-Depth Information
2
0
-deoxyguanosine (dG) adduct
has the characteristic structure previously
observed for the reaction of carbocyclic ions such as
109
with dG.
13,14
64g
and
64n
.
147-149
These are also the major DNA adducts obtained from
in vivo
or
in vitro
experiments
with the parent amines.
138
Some heterocyclic ions are subject to acid-base reactions that occur within the
readily accessible pH range.
148,150,153
For example,
k
nuc
/
k
s
for trapping of
103h
by
N
3
,Br
, and d
G
is pH dependent, decreasing from pH 3 to 8 and conforming to a
titration curve.
148
These results are consistent with deprotonation of 9-NH to yield a
neutral quinonoid species
Similar C-8 adducts have been isolated from the reactions of
103b
, and
103f-i
110h
that is trapped with less efficiency by nonsolvent
(Scheme 4.31).
148
nucleophiles than
103h
In support of this interpretation, it was
found that the 9-NMe cation
that cannot be deprotonated at 9-N exhibits a pH
invariant
k
nuc
/
k
s
that is very similar in magnitude to
k
nuc
/
k
s
measured for
103i
at low
pH.
148
McClelland and Licence discovered similar pH-dependent trapping of the
cation
103h
obtained from LFP of the corresponding azide, but no evidence for
deprotonation of
103m
.
153
They measured the p
K
a
and the rate constants shown in
Scheme 4.31. They also discovered that
103n
103m
was protonated at low pH to yield the
.
153
Trapping of this species by Br
was demonstrated.
153
The dication
reacts with solvent with a rate constant that is about double that for the nitrenium
ion.
153
This is intermediate in behavior between the benzidine nitrenium ions
dication
111m
64ff
(
k
s
þ
2
and
64ee
k
s
) and simple carbocyclic nitrenium ions such as
64g
and
64n
(
k
s
þ
2
k
s
).
If
k
az
for
10
9
M
1
s
1
, and
k
s
/
k
s
o
for
103h
is diffusion limited at 5.0
103h
is the
same as for
103m
, the kinetic parameters for
103h
shown in Scheme 4.31 can be
estimated.
148
The substitution of 1-CH in
kinetically
destabilizes the cation by a factor of about 35 in keeping with estimates based
on
103m
by 1-N in
103h
.
148
Substitution of 9-CH
2
in
103a
103c
64g
103m
kinetically
stabilizes the cation by a factor of about 3-4.
153
Perhaps, the most surprising result is
and
by 9-NH in
SCHEME 4.31.
Acid-base properties of
103h
and
103m
.
