Chemistry Reference
In-Depth Information
favourable in the LHT conformation. The preference for the DHT atropisomer for
these three 3
Raising the pH from 3 to 7 increased the D type CD signal intensity, indicating
that the DHT form is favoured upon 3
′
-GMP complexes appears to be due to such a hydrogen bonding (SSC).
-phosphate group deprotonation, most likely
due to formation of stronger phosphate/N1H
cis
G hydrogen bonds at neutral pH.
Above pH 7 the D type CD signal starts to decrease, and the intensity is nearly
zero at pH 9. At pH
′
9, where N1H deprotonation occurs,
125
the N1 atom has lost its
proton and no phosphate/N1H hydrogen bond can exist. Our NMR/CD studies with
pipen, Me
2
dab and bip-Pt(3
∼
′
- GMP)
2
complexes support this interpretation.
76,102
5.5.3 Conformers in Cisplatin Adducts with 5
¢
- GMP : Interplay between
SSC and FSC
At neutral pH, the CD signals of
cis
- (NH
3
)
2
Pt(5
′
- GMP)
2
, pn - Pt(5
′
- GMP)
2
and en -
Pt(5
- GMP)
2
are of the L type, indicating that the major conformation is L HT
(Figure 5.10 ).
105
Intramolecular hydrogen bonding between the phosphate group of
one 5
′
′
-GMP and the N1H of the
cis
5
′
-GMP (SSC) is more favourable in the L HT
than in the D HT conformer.
The CD data point to substantial differences in signal intensity among 5
- GMP
adducts of different carrier ligands [
cis
- (NH
3
)
2
, pn, en]. One obvious potential factor
is the bite angle of the carrier ligand(s). The very low CD intensity of the en-Pt(5
′
-
GMP)
2
complex suggests that the low bite angle of the en ligand reduces the
strength of the SSC interaction.
Raising the pH from
′
3 to 7 increased the L type CD signal intensity, indicating
that the LHT form is more favoured upon 5
∼
- phosphate group deprotonation, pos-
sibly because of stronger phosphate/N1H hydrogen bond at neutral pH. As the pH
was raised further, the CD signals decreased in intensity and partially inverted at
pH 10, suggesting a bias toward the DHT form after N1H deprotonation.
105
The
preference for the LHT atropisomer up to pH 9 is likely to stem from the 5
′
′
-
phosphate group of each 5
′
-GMP forming a hydrogen bond with the N1H of the
cis
5
- phosphate protrudes toward the
cis
nucleotide (assuming the nucleotides keep the preferred
anti
conformation). On
the other hand, the bias towards the
′
-GMP (SSC). In the LHT conformation the 5
′
DHT form observed at pH 10 can be explained
as follows. In the DHT conformation the 5
-phosphate is directed towards and can
directly reach the
cis
amine and form an H-bond (FSC). It is worth nothing that the
latter hydrogen bonding interaction is found in relevant X-ray structures. It is there-
fore most likely that the presence of 5
′
- phosphate/NH
cis
amine hydrogen bonding
is responsible for the stabilization of the DHT form at high pH (such hydrogen
bonding is masked at acidic and neutral pH by the dominating SSC interactions).
′
5.5.4 Conformers in Cisplatin Adducts with 1 - Me - 5
′
- GMP : The Role of FSC
The CD signals of pn - Pt(1 - Me - 5
′
- GMP)
2
and en - Pt(1 - Me - 5
′
- GMP)
2
had signs oppo-
site to those of 5
- GMP adducts (Figure 5.10 ).
105
The signs indicate that the major
atropisomer of the 1 - Me - 5
′
′
- GMP adducts is D HT.
