Chemistry Reference
In-Depth Information
most of these cases, the nitrenium ion nitrogen becomes attached to the 8-position of
the guanosine,
in Scheme 3.3. This is unusual in that
most aryl nitrenium ions tend to undergo nucleophile attack at an aromatic ring
carbon rather than at the nitrenium ion nitrogen itself,
2
in Scheme 3.2, and
5
and
6
3
7
8
in
Scheme 3.3. There are many other less common modes of attack of nitrenium ions on
guanosine that are not shown in Schemes 3.2 and 3.3. These include attack of the
nitrenium ion nitrogen on the carbonyl oxygen to form hydroxylamine ether or on
the amino group in the 2-position to form a hydrazine.
The mechanism of addition of the nitrenium nitrogen to the 8-position of
guanosine has generated the most debate, since this mode of reaction generally
predominates and constitutes an unusual pathway of nitrenium ion reactivity.
Theoretical calculations have been applied in attempts to account for this strange
mode of nitrenium ion reactivity. Early studies indicated that initial attack of
the nitrenium ion occurs at the nitrogen in the 7-position of guanosine followed
by a 1,2-shift to the 8-position via one of several possible mechanisms.
20-23
More
recently, direct observation of the intermediates involved in this reaction using
transient laser spectroscopy and flash photolysis show that the nitrenium ion attacks
the 8-position directly without passing through any intermediate adducts (Scheme
3.4),
24,25
and later high-level calculations support this conclusion.
26
The application of nitrenium ions as PAL intermediates has been shown to be
viable through the photolysis of substituted aryl azides that are effective nitrenium
ion precursors (see below). The capability to observe these short-lived reactive
intermediates directly is proving to be a mechanistic tool of great value. McClelland
has pioneered this area of aryl nitrene/nitrenium ion chemistry,
27,28
and shown that
aryl nitrenium ions survive in water into the millisecond time domain. Surprisingly,
in aqueous solutions of guanosine and its derivatives, nitrenium ions react with
guanosine at nearly diffusion-controlled rates,
p
-phenylphenyl nitrenium ion reacts
with
d
G in water with a rate constant of 2.0
in Scheme 3.2, and
and
10
9
M
1
s
1
.
25,29
Most intriguing is
the observation that the initial adduct of 2-fluorenylnitrenium ion with
d
G,
9
,is
surprisingly acidic, p
K
a
¼
3.9, and loses a proton from N
1
to form the iminoquinone
10
, (Scheme 3.4). Thus,
10
would be the predominant species at physiological pHs
O
O
NH
N
NH
N
NH
NH
N
d
G
H
N
H
N
NH
2
N
N
NH
2
p
K
a
=3.9
9
h
ν
, -N
2
,
+H
+
d
Rib
d
Rib
10
-H
N
3
O
N
NH
11
H
N
N
NH
2
d
Rib
SCHEME 3.4.
