Chemistry Reference
In-Depth Information
platinum coordination plane, the dach ligand has an N-H on each side of the plane.
Nevertheless, a slight difference in the stereochemistry of the two protons (one N-H
has ' quasi axial ' and the other ' quasi equatorial ' character) is suffi cient to induce a
signifi cant change in the relative stabilities of the dach-PtG
2
DHT and L HT con-
formers. At acidic and neutral pH the stability of HT conformers is governed by G
to G dipole-dipole interaction, which is greater for the six-membered ring of each
guanine leaning toward the
cis
G. Such a '6-in' canting of the two guanines can be
hampered by the steric interaction between the H8 of each guanine and the substitu-
ent on the
cis
amine that is on the same side of the platinum coordination plane.
Such a repulsion is greater for a 'quasi equatorial' N-H than for a 'quasi axial' N-H.
Therefore the DHT conformer is stabilized in the (
S,S
) - dach - PtG
2
complex, while
the LHT conformer is stabilized in the (
R,R
) - dach - PtG
2
species (this can be seen
in Figure 5.7 if the larger circles now represent 'quasi equatorial' protons and the
smaller circles 'quasi axial' protons). Indeed the CD spectrum is typical of a D HT
conformer in the former case and of a LHT conformer in the latter case.
128
At basic pH, deprotonation of the guanine N1-H renders the O6 a much better
H-bond acceptor; therefore, the stability of the HT conformers is governed by the
guanine O6/NH of the
cis
amine H-bond interaction. Such a guanine O6/NH
cis
amine interaction is more favourable for a 'quasi axial' than for a 'quasi equatorial'
N-H. As a consequence, at basic pH the CD spectrum of (
S,S
) - dach - PtG
2
has the
signature of a LHT conformer, while the CD spectrum of (
R,R
) - dach - PtG
2
has
the signature of a DHT conformer (this can also be seen in Figure 5.7, assuming the
larger circles to represent 'quasi equatorial' protons and the smaller circles 'quasi
axial ' protons).
128
5.5.6 Quantifying the Atropisomer Distribution in Adducts of Cisplatin or
Analogous A
2
Pt(5
¢
- GMP )
2
Complexes with Achiral Primary Diamines
CD spectroscopy is an empirical method at the current state of theoretical under-
standing of CD spectral transitions in these types of complexes, therefore it cannot
be used for a quantitative estimate of different conformers, for which we have to
rely upon NMR data.
Very recently, by lowering the temperature down to 238 K, it has been possible
to observe different conformers of (
cis
- 1,4 - dach)Pt(5
′
- GMP)
2
(1,4 - dach = 1,4 -
diaminocyclohexane for which the N-Pt-N bite angle is
97 ° ). The percentages of
the HH, LHT and DHT conformers were estimated from intensities of
1
H NMR
signals to be 33, 57 and 16%, respectively. This is the fi rst case in which the abun-
dance of the three possible rotamers has been determined in A
2
Pt(5
≥
′
- GMP)
2
adducts
with primary diamines.
129
5.6 Retro Models Applied to Adducts with Tethered Guanine Bases
The
cis
- (NH
3
)
2
Pt(GpG) and
cis
- (NH
3
)
2
Pt(d(GpG)) complexes, the simplest G-
linked models of the major cisplatin-DNA adduct, have been characterized by a
