Chemistry Reference
In-Depth Information
ligands (for
R,S,S,R
or
S,R,R,S
confi gurations at the N, C, C and N asymmetric
centres) places one N-H and one N-CH
2
X on each side of the platinum coordination
plane. The guanine with the six-membered ring on the side of the coordination plane
as the N-H of the
cis
amine can be canted '6-out' because there is no clash with
an amine substituent and O6 can act as an H-bond acceptor from the N-H. In
contrast, the guanine with the six-membered ring on the side of the N-CH
2
X group
of the
cis
amine will be much less canted and probably canted away from the
cis
amine ('6-in' canting). The former guanine will have a strongly shielded H8 signal,
whereas the second guanine will have an unshielded H8 signal (HH conformers in
Figure 5.7 ).
Removal of the electron-rich O6 atom of guanine, such as in the case of adducts
with benzimidazole (B), not only increases the yield of the HH conformer with
respect to the HT conformers (the dipole-dipole interactions stabilizing the latter
conformers are greatly reduced, if not absent), but also greatly reduces the disper-
sion of the B H2 chemical shifts even in the case of Me
2
dab or bip ligands (B H2
occupies the same position as H8 in G).
119
This behaviour is sketched in Figure
5.8 .
5.2.3 Phosphate N 1 H
cis
G H - Bond Interaction, SSC
Two relevant types of ionizable groups are present in
cis
- A
2
Pt(GMP)
2
adducts. First,
the monoanionic phosphates of the GMP ligands [ROP(OH)O
2
]
−
which have p
K
a
values (5.6 to 6.2)
84 - 86,112
lower than for free 5
- GMP (6.3)
76,79,81 - 83
and become fully
′
7.5.
77 - 80,84
Second, the N1H of each G which deprotonate with
deprotonated by pH
∼
- GMP.
79,80,84
For both the
R,S,S,R
and
S,R,R,S
chiralities of the Me
2
dab and bip - PtG
2
com-
plexes, the percentage of the DHT conformer in the case of 3
9.4
79,83,87,109
versus 9.5 for free 5
p
K
a
values of 8.7 and
∼
′
′
- GMP and the percent-
age of the LHT conformer in the case of 5
′
-GMP were higher near pH 7 than at
lower pH.
76,79 - 81,102,105
We have unravelled the reasons for this difference in the preferred conformer.
104
The phosphate group position is different in 5
′
- GMP versus 3
′
- GMP. For 5
′
- GMP
adducts, the 5
-phosphate group projects toward the
cis
nucleotide in the L HT form,
and away from the
cis
nucleotide in the DHT form (assuming that the nucleotide
maintains the preferred
anti
conformation, Figure 5.9). In contrast, for 3
′
′
- GMP
adducts the 3
-phosphate is close to the
cis
nucleotide in the DHT form and away
from it in the LHT form (this can be seen in a gedanken experiment in which the
phosphates of Figure 5.9 are detached from the 5
′
′
position and attached to the 3
′
position of the ribose). Thus, the relative positions of phosphate groups to the
cis
G
in a HT form with a given chirality are opposite for 3
- GMP adducts.
On these grounds the key factors stabilizing the DHT conformer for 3
′
- GMP versus 5
′
′
- GMP deriva-
tives and the LHT conformer for 5
-GMP adducts near pH 7 appear to be the
phosphate/N1H
cis
G interactions. This represents a third type of internucleotide
interaction. We call such interligand interaction ' second - to - second sphere commu-
nication' (SSC) because the interacting groups are at the periphery of the
cis
nucle-
′
