Chemistry Reference
In-Depth Information
have demonstrated that the three G-quartets of d[(G
3
T
4
G
4
)
2
] create two cation
coordination sites (Figure 3.9f).
176
Analysis of NOE interactions between the protons
of the bound
15
NH
4
+
ions and G-imino protons revealed that ammonium ions are
localized between the pairs of adjacent G-quartets within d[(G
3
T
4
G
4
)
2
] (Figure 3.9 f).
Subsequent titration of KCl into a solution of d[(G
3
T
4
G
4
)
2
] folded in the presence
of
15
NH
4
+
ions revealed a mixed mono-K
+
/mono -
15
NH
4
+
form that represents
an intermediate in the conversion of the di-
15
NH
4
+
form into the di-K
+
form.
176
Similarly,
15
NH
4
+
ions were found to replace Na
+
ions inside this G-quadruplex. The
preference for
15
NH
4
+
over Na
+
ions for the two internal coordination sites is con-
siderably smaller than the preference for K
+
over
15
NH
4
+
ions. Interestingly, the two
coordination sites within d[(G
3
T
4
G
4
)
2
] differ to such a degree that
15
NH
4
+
ions bound
to the site that is closer to the lateral-type loop are always replaced fi rst during
titration by KCl. That is, the second binding site is not occupied by a K
+
ion until a
K
+
ion already resides at the fi rst binding site.
176
Recently,
23
Na NMR demonstrated
the presence of mixed cation species (Na
+
/K
+
, Na
+
,Rb
+
and Na
+
/Sr
2+
) of 5
′
- GMP
associates in solution.
249
A noticeable progress in localization of cations has been made by Wu and
coworkers who demonstrated that tightly bound metal ions can be detected directly
by
23
Na,
39
K and
87
Rb NMR in solution.
249,250
The observation of quadrupolar nuclei
with characteristic rapid relaxation that has traditionally
116,117,251
led to prohibitively
broad lines has been made possible with the appearance of NMR spectrometers
with high magnetic fi elds where separation of signals for channel and free cations
is achievable.
23
Na NMR study has confi rmed that three Na
+
cations reside inside
the bimolecular G-quadruplex d[(G
4
T
4
G
4
)
2
].
252
There was no evidence of Na
+
cations
in the thymine loop. Solid-state NMR spectroscopy has also been used to localize
cations within G-quadruplexes.
150,252 - 254
23
Na chemical shifts for G-
Distinct
quadruplexes formed by self-association of 5
-GMP were interpreted based on
ab
initio
calculations on a G-quadruplex model consisting of four stacked G-
quartets and three channel cations. In this model each cation is sandwiched between
two adjacent G-quartets which are separated by 3.4 Å and twisted by 45 °. The
23
Na
chemical shielding calculations with Na
+
ion located within the G-quartet plane
predicted
23
Na chemical shift (d + 6 ppm), which does not agree with the experimen-
tal data (d
′
17 ppm).
249
It is noteworthy, however, that the localization of Na
+
ions
solely between the neighbouring G-quartet planes is not fully supported by the
available crystal structures discussed above and shown in Figures 3.8 and 3.9.
Tl
+
has been shown to nicely substitute for K
+
in the promotion of G-
quadruplex formation.
100,127,128
205
Tl is a spin-½ nucleus with relatively high receptiv-
ity, in contrast to other monovalent cations. Its potential advantage could be a very
large chemical shift range and thus high sensitivity to the chemical environment of
a metal cation. As expected, the resonances of
205
Tl
+
ions associated with G-quartets
were clearly resolved from the resonance of
205
Tl
+
ions in bulk solution. Strobel and
coworkers have reported the NMR spectra for
205
Tl
+
ions in a solution containing
the tetramolecular G-quadruplex d[(T
2
G
4
T
2
)
4
].
127
The
205
Tl NMR spectrum of this
G-quadruplex shows a cluster of three peaks.
127
The observation of three distinct
205
Tl peaks of approximately equal areas is consistent with a tetramer in which three
Tl
+
ions are localized between the layers of the four G-quartets. The ability of Tl
+
−
