Chemistry Reference
In-Depth Information
Scheme 1.2
sequence was found to be approximately an order of magnitude slower than binding
to TAGT sequences, a result which does not agree with the proposed selectivity rule
for labile metal ion complexes.
Vinje
et al.
10
have investigated the monofunctional reaction kinetics of
[PtCl(dien)]
+
(dien = diethylenetriamine), with the oligodeoxyribonucleotides, III,
IV and V, used for Mn
2+
and Zn
2+
titration (see above). The reaction mixtures
were separated by HPLC and the chromatographic profi les showed a clear dif-
ference in the amount of 3
monoplatinated species between the three
duplexes (Figure 1.10). The reaction pathway of platination of seq. III is shown in
Scheme 1.2 .
Reaction rates for Pt(dien) were determined based on 2D [
1
H,
15
N] HSQC/
HMQC NMR spectroscopy using
15
N-labelled Pt(dien). The time courses for reac-
tion rates of each of the three duplexes are shown in Figure 1.11. Comparison of
the three different duplexes containing the central sections GGX (X = A, T, C),
respectively,
10
shows that the selectivity for covalent platination matches that for
adducts with labile metal ions Mn
2+
and Zn
2+
. The reaction rate for platination is
faster for the 5
′
versus 5
′
′
-G than for the 3
′
-G. The reactivity of the 3
′
- G depends on the adja-
cent residue X in the following order: X = A
>
T
>>
C. For GGA the reaction rate
is 1.2 times faster for 5
′
- G than for 3
′
-G, for GGT the rate of 5
′
- G platination is
about eight times faster than that of 3
′
-G, and for GGC there is no signifi cant adduct
formation at the 3
- G (Table 1.2 ).
When the reaction mixture of the platinated species was aged over several
weeks, the relative amounts of 5
′
HPLC fractions changed. This was also
confi rmed by comparison of the NMR spectra of the aged solutions with those
recorded in the initial kinetic experiments. It was suggested that Pt-N7 bond cleav-
age and isomerization had taken place, similar to that observed for platinated single-
′
and 3
′
