Chemistry Reference
In-Depth Information
5.3 Guanine
cis
Amine Interactions
5.3.1 Steric Interaction between G and
cis
Amine
As already pointed out in Section 5.2.1, in HT conformers having '6-in' conforma-
tion, the relevant steric interactions involve the G H8 and the
cis
amine. Hence the
major HT conformer found for Me
2
dab and bip-PtG
2
adducts has the guanine H8
located on the same side of the coordination plane as the
cis
amine N - H and on the
opposite side from the
cis
amine N-CH
2
X group (' major ' HT conformers in Figure
5.7). In the HH conformer (Section 5.2.2) the guanines tend to have '6-out' confor-
mation and therefore the relevant interactions involve the guanine six-membered
rings and the
cis
amine substituents. In order to have moderately stable HH con-
formers it is required that at least one guanine has the six-membered ring on the
side of the coordination plane where the
cis
amine has a nonbulky substituent (such
as an N-H). Steric clash between the six-membered ring of each guanine and the
cis
amine substituent positioned on the same side of the platinum coordination
plane renders the HH conformer particularly unstable in adducts with tertiary
amines (such as Me
4
dab and Me
4
dach reported in Figure 5.5)
117,118,120
or N - donor
heterocycles (such as phenanthroline and 2,9-dimethylphenanthroline).
121
5.3.2 Guanine O 6 - NH
cis
Amine H - Bond Interactions
At basic pH (
10), the N1H deprotonation eliminates the SSC phosphate/N1H
cis
G interactions that stabilize the LHT conformer for 5
∼
′
-GMP adducts and the D HT
conformer for 3
-GMP adducts (Section 5.2.3). On the other hand, N1H deprotona-
tion greatly increases the capacity of the G O6 to act as a hydrogen bond acceptor.
It was observed that, upon N1H deprotonation at basic pH, the less abundant HT
conformer of the moderately dynamic Me
2
dab - PtG
2
model compounds becomes
more favoured (Table 5.1). (Such an increase in the concentration of the minor HT
conformer at basic pH is not observed for the
R,S,S,R
confi guration of the diamine
and 5
′
-GMP nucleotide for the reason discussed in the next section.)
113
The ' minor '
HTs have the G O6 of each guanine on the same side of the platinum coordination
plane as the N-H of the
cis
amine (Figure 5.7); therefore, their increase in concen-
tration at basic pH is likely to stem from G O6/NH Me
2
dab hydrogen bonding, now
favoured as a result of an increased capacity of the G O6 to act as a hydrogen bond
acceptor.
′
5.3.3 Phosphate/ NH
cis
Amine H - Bond Interaction, FSC
When G has a 5
-phosphate group, conformer distribution could also be infl uenced
by phosphate/NH
cis
amine hydrogen-bond interactions. Such an interaction should
favour the DHT conformer because for this conformer the 5
′
- phosphate protrudes
toward the
cis
amine (assuming the nucleotides have the favoured
anti
conforma-
tion, Figure 5.7). As noted in the previous section, at basic pH the L HT conformer
is unexpectedly disfavoured (Table 5.1) for (
R,S,S,R
) - Me
2
dab - Pt(5
′
′
- GMP)
2
although
