Chemistry Reference
In-Depth Information
ions is not true for all nitrenium ions. The
para
-ethoxyphenyl nitrenium ion
64u
has
10
7
M
1
s
1
and
k
d
G
/
k
s
18M
1
.
113
This ion has a lifetime in H
2
O that is
k
d
G
2
, and it does generate C-8 adducts from its reaction with dG,
165
but it is
at least 60-fold less selective toward dG than
similar to
64n
. It has been suggested that the
positive charge in
para
-alkoxyphenyl nitrenium ions is so localized at the
para
-O
that there is insufficient cationic character at N for reaction with dG.
113
This pattern
appears to hold, with some exceptions, for the reaction of heteroaryl nitrenium ions
that have a dominant resonance structure with the charge on an endocyclic N.
147-149
High selectivity for reaction of nitrenium ions with dG requires a combination of
relatively long lifetime in water (
64n
50 ns) and sufficient delocalization of the charge
so that some cationic character remains on N.
The Novak group favored a mechanism in which N-7 of dG attacked the ion,
followed by an intramolecular rearrangement to
133
and deprotonation to form the
C-8 adduct,
, because the rate constant for formation of C-8 adducts depends on
the p
K
a
of N-7 of the purine with a
128
2 and
levels off at the diffusion controlled limit for those nucleosides with p
K
a
b
nuc
of 0.7 for those purines with p
K
a
<
2.
14
McClelland and coworkers identified an intermediate generated during the reaction
of
2
(
-deoxyribose) based on the
evidence presented in Scheme 4.37.
17,167
The intermediate detected during LFP
experiments has an absorption spectrum that extends to 400 nm suggesting a highly
conjugated species, a p
K
a
of 3.9 that is consistent with deprotonation of
64g
with dG as
133g
(Ar
¼
2-fluorenyl, Y
¼
H, R
¼
133
to form
134
, and a rate constant for decomposition of the intermediate that is independent of
Ar for the intermediates derived from
64g
,
64n
,
64p
, and
64q
. The pH dependence of
SCHEME 4.37.
Evidence for mechanism of C-8 adduct formation, and the minor adduct
135
.
