Chemistry Reference
In-Depth Information
5.5.1 CD Signature of Conformers
The presence of enhanced CD signals for some
cis
- A
2
PtG
2
complexes was fi rst
reported in 1980,
122
and attempts were later made to interpret the results on a struc-
tural basis.
123,124
However, a convincing interpretation of the results has depended
on subsequent studies with less dynamic complexes.
77,78,107
The CD spectra of (
S,R,R,S
) - Me
2
dab - PtG
2
complexes all had the same shape,
i.e., positive peaks at
250 and 210 nm.
Because all the 2D NMR studies showed that the dominant atropisomer was L HT
(Figure 5.7), this type of CD signal was designated as L. The CD spectra of enantio-
meric (
R,S,S,R
) - Me
2
dab - PtG
2
complexes had signs opposite to those of the corre-
sponding peaks in the (
S,R,R,S
) - Me
2
dab - PtG
2
CD spectra (negative peaks at
∼
285 and 230 nm and negative peaks at
∼
∼
285
and 230 nm and positive peaks at
250 and 210 nm). Because the 2D NMR studies
showed that the dominant atropisomer for (
R,S,S,R
) - Me
2
dab - PtG
2
complexes had
the DHT conformation (Figure 5.7), the latter type of CD signal was designated as
D. Furthermore, the CD signal intensity roughly correlated with the percentage of
the major HT form.
78
Studies with the related bip complexes indicated that a mixture of 25% D HT,
50% HH, and 25% LHT had essentially no CD intensity.
77
The CD intensity
increased as the favoured HT form became dominant with time. Similarly, in a 'pH
jump' experiment performed on (
S,R
) - pipen - Pt(5
∼
- GMP)
2
(Figure 5.5) in which we
monitored the change of atropisomer distribution by using both NMR and CD
spectroscopy,
79
changes in H8 NMR signal intensities corresponded to changes in
CD intensity. On the basis of the above experiments, we interpret the sign of the
CD signal as a refl ection of the D or L conformation of the major HT form. In par-
ticular, the pattern of a positive Cotton effect around 285 nm and a negative Cotton
effect around 250 nm is characteristic of a
′
LHT conformer; the opposite pattern is
characteristic of a D HT conformer.
76
5.5.2 Conformers in Cisplatin Adducts with 3
¢
- GMP : The Role of SSC
The CD signals of cisplatin adducts of G derivatives with no phosphate groups are
weak. No conformer is favoured because the absence of phosphate groups rules out
both FSC and SSC interactions; moreover the two ammine ligands have no chiral
property that can exert a stereochemical control through FFC interactions so favour-
ing a particular conformation. This analysis applies not only to cisplatin, but also to
analogous A
2
PtG
2
complexes with achiral primary diamines because these also have
weak CD signals.
In contrast, at neutral pH,
cis
- (NH
3
)
2
Pt(3
′
- GMP)
2
, pn - Pt(3
′
- GMP)
2
(pn = 1,3 -
- GMP)
2
all showed the D - type CD signal,
105
indicat-
ing that the major atropisomer is DHT (Figure 5.10). The carrier ligand has a
modulating effect on the CD intensity: weakest for en-Pt, strongest for
cis
- (NH
3
)
2
Pt.
The 3
diaminopropane), and en-Pt(3
′
′
-phosphate group from each 3
′
-GMP can form a hydrogen bond with the N1H
of the
cis
3
- GMP in the DHT conformation (assuming the nucleotides keep the
normally preferred
anti
conformation), whereas such hydrogen bonding is less
′
