Chemistry Reference
In-Depth Information
Zn
2+
.
76,145 - 147
Millimolar concentrations of Mg
2+
, Ca
2+
, Ba
2+
and Sr
2+
induce polymeric
d(GGA)
n
repeat molecules to form quadruplexes.
148
The studies of the melting temperature of gels formed by 8-bromoguanosine
as a function of monovalent cation species showed that the relative ability to stabi-
lize guanosine gels was K
+
Li
+
.
149
The stabilization of G - quartet
assemblies adopted by GMP follows the following order: K
+
Rb
+
NH
4
+
Na
+
>>
>
>
>
NH
4
+
Rb
+
Na
+
>
>
>
>
Cs
+
Li
+
.
150
This general ordering has proven correct for G-quadruplex structures
adopted by DNA oligonucleotides. Therefore, the melting temperature for a
G-quadruplex is higher in the presence of K
+
ions than in the presence of Na
+
ions. The extent to which K
+
increases the stability of a G-quadruplex over Na
+
depends on the nucleotide sequence and can vary from as little as 2 °C to over
30 ° C.
107,124,151 - 155
The origins of these sequence-dependent differences are likely due
to the K
+
and Na
+
forms of some G-quadruplexes being different in structure and/or
in the number of coordinated cations. There is no simple explanation for the differ-
ence in melting temperatures for the Na
+
and K
+
forms for various G-quadruplexes.
High-resolution X-ray and NMR structures have provided valuable insights into the
effects of cation size and charge on G-quadruplex structure and on the location of
ions within G-quadruplexes, all of which contribute to quadruplex stabiliza-
tion.
99,104,127,156 - 161
In addition, solution-state NMR studies have demonstrated that
cations undergo dynamic exchange between coordination sites in the interior of a
G-quadruplex and with bulk solution.
162 - 165
The G-quadruplex formed by some G-rich sequences in the presence of K
+
ions
can be dramatically different in strand orientation and strand number from the G-
quadruplex formed in the presence of Na
+
ions. The size of a cation and its energy
of (de)hydration both contribute to cation selectivity and the stability of a G-
quadruplex. K
+
is too large to be coordinated in the plane of the G-quartet, whereas
a Na
+
can fi t in the centre of the G-quartet plane (see below). The resulting differ-
ences in K
+
and Na
+
coordination geometries and cation-guanine O6 distances
contribute to a difference in the free energy provided by K
+
versus Na
+
coordination
within a G-quadruplex. To a good approximation, hydration energies of monovalent
ions are inversely proportional to their ionic radii.
166
Thus, the free energy required
to dehydrate K
+
for coordination within a G-quadruplex is less than that required
to dehydrate Na
+
. The net difference between the free energy of coordination within
a G-quadruplex and the free energy of hydration ultimately determines cation
selectivity by G-quadruplexes.
6,153,167,168
A
1
H NMR study by Hud and Feigon
et al.
168
on the bimolecular G-quadruplex adopted by d(G
3
T
4
G
3
) has shown that the pre-
ferred coordination of K
+
over Na
+
is actually driven by the greater energetic cost
of Na
+
versus K
+
dehydration. The intrinsic free energy of Na
+
coordination within
d[(G
3
T
4
G
3
)
2
] is actually more favourable than K
+
coordination.
168
Subsequent com-
puter simulations have provided additional support for the argument that cation
dehydration is the dominant free energy that determines Na
+
versus K
+
selectivity
by G - quartets.
169 - 175
Recent quantitative analysis of the relative concentrations of the three dication
forms of d[(G
3
T
4
G
4
)
2
] (i.e. 2
15
NH
4
+
,
15
NH
4
+
/K
+
and 2 K
+
) at equilibrium, which are
in slow exchange on the NMR timescale, showed that differences in standard Gibbs
free energies are 5.7 kcal mol
− 1
between the di -
15
NH
4
+
and the
15
NH
4
+
/K
+
forms, and
4.3 kcal mol
− 1
between the
15
NH
4
+
/K
+
and the di - K
+
forms.
176
In comparison, the
>
