Chemistry Reference
In-Depth Information
carrier ligands, but also for other metals.
85 - 93,96,110,113,115
The nucleotides in the struc-
tures have very similar relationships, with the purine bases having the same relative
positions and the phosphate groups always hydrogen-bonded to the
cis
ligands in a
similar manner. Only very recently has a LHT complex of 5
- GMP been reported,
118
while no example of a
cis
bisnucleotide HH complex has yet been published.
This contrast between the prevalence of FSC in the solid and its relative unim-
portance in solution supports the premise of our retro model studies that the struc-
tures in the solid state of dynamic nucleotide complexes may be very different from
the solution structures.
Interligand interactions, as they result from our retro model studies, can be
grouped in two distinct categories: nucleotide/nucleotide and amine/nucleotide.
Internucleotide interactions concern:
′
(1) Electrostatic attraction in HT conformers between electron-rich guanine O6 and
electron - defi cient H8 of
cis
Gs, both on the same side of the platinum coordina-
tion plane. This interaction is responsible for these conformers generally having
the six-membered ring of each guanine leaning towards the
cis
G so to bring the
two oppositely charged moieties closer to each other ('6-in' conformation).
(2) Electrostatic repulsion in the HH conformer between electron-rich O6s, both
located on the same side of the platinum coordination plane. This interaction
generally leads to ' 6 - out ' canting of the guanines.
(3) H - bond interaction between nucleotide phosphate and N1H of
cis
G (SSC). In
the case of 5
′
-phosphate this interaction will favour LHT (since in L HT each
anti
5
′
- GMP has the 5
′
-phosphate protruding towards the
cis
G), while in the
case of 3
′
- phosphate will favour DHT (since in DHT each
anti
3
′
- GMP has the
3
′
-phosphate protruding towards the
cis
G ) .
Amine/nucleotide interactions can also be of different types:
(1) Steric interaction between amine and
cis
G. In HT conformers (having prefer-
entially the ' 6 - in ' conformation) the relevant interaction involves the guanine
H8 and the
cis
amine substituents, while in the HH conformer (having prefer-
entially the '6-out' conformation) the relevant interaction involves the six-
membered ring of the guanine and the
cis
amine substituents.
(2) H - bond interaction between guanine O6 and N - H of the
cis
amine (when
present). This interaction becomes signifi cant after deprotonation of guanine
N1H at basic pH.
(3) H - bond interaction between nucleotide 5
-phosphate and N-H of the
cis
amine
when present (FSC). For HT conformers, assuming an
anti
conformation of 5
′
′
-
GMP, only D chirality allows for such an interaction.
5.5 Conformer Distribution in Cisplatin Adducts of G Derivatives
NMR methods do not allow detection of individual conformers in fl uxional
cis
-
A
2
PtG
2
complexes with two ammines or a primary diamine ligand. Because of this
dynamic motion problem, we relied heavily on CD spectroscopy to assess the chiral-
ity of the major HT conformer.
