192
M. Ilchenko and I. Dubey
Theoretical study of incorporating 6-thioguanine into a guanine tetrad and their
influence on the metal ion–guanine tetrad was performed by Meng et al. [105]. The
initial structure of the G-quartet has been generated from the coordinates of the
human telomeric DNA (PDB code 1KF1) [37]. The calculation method used was
B3LYP, and the basis set was the standard double-zeta with polarization functions
6-31G*. The geometries, energies and charge distributions were discussed. The effects of different cations (K
+
and Na
+
) on the various tetrads were studied as well.
The calculation results demonstrated that upon the increase of SG units number
the quartet becomes more and more unstable. Without hydration correction, the
Na
+
cation was found to bind more tightly with the tetrad than that of potassium,
whereas when hydration effects were considered the stability sequence changed to
K
+
> Na
+
. More favorable binding of potassium ion comparing to Na
+
in solution
is due to higher dehydration energy of the latter, although Na
+
cation has higher
intrinsic propensity to bind tightly to DNA quadruplexes [106].
Effect of external electric field on H-bonding and π-stacking interactions in guanine aggregates were studied by Jissy and Datta [107]. The DFT calculations were
carried out at the M05-2X level of theory with the 6-31 + G(d, p) basis set. The structure and electronic properties of guanine oligomers and π-stacks of guanine quartets
with circulenes were investigated under an external field through first-principles
calculations. The binding energy of the circulenes with G-quartets were fond to increase on application of an electric field along the stacking direction. Besides that,
the stability of G-quartet–circulene π-stacks was shown to depends on the phase of
the dipole moment (in-phase or out-of-phase) induced by an external electric field.
The stability of stacks of bowl-shaped circulenes with G-quartets depended on the
direction of the applied field.
At the end of this paragraph we would like to mention two pioneering papers
published by Leszczynski, Gu and Bansal [108, 109], where the first HF and DFT
calculations on the stability and structure of G-quartets were performed and the
possibility of the formation of the structures with bifurcated hydrogen bonds was
demonstrated.
Thus, guanine quartets were studied in depth by quantum chemical methods.
Their structural diversity based on different possible patterns of hydrogen bonding
was demonstrated and the key role of metal cations in stabilizing guanine assemblies was shown.
6.3.2.3 DFT Studies on the Structure of G-Octets and Their Metal
Complexes
Guanine octets are more complex structural elements of quadruplex systems than
the quartets. G-octet is the system of two stacked G-quartets interacting via the
π- π-stacking mechanism. This molecular assembly is closer to natural G-quadruplexes which usually contain three or four guanine quartets, thus its modelling is
able to provide more realistic structural and thermodynamic data to be extrapolated
to quadruplex DNA. At the same time, G-octet molecular system is twice as large
M. Ilchenko and I. Dubey
Theoretical study of incorporating 6-thioguanine into a guanine tetrad and their
influence on the metal ion–guanine tetrad was performed by Meng et al. [105]. The
initial structure of the G-quartet has been generated from the coordinates of the
human telomeric DNA (PDB code 1KF1) [37]. The calculation method used was
B3LYP, and the basis set was the standard double-zeta with polarization functions
6-31G*. The geometries, energies and charge distributions were discussed. The effects of different cations (K
+
and Na
+
) on the various tetrads were studied as well.
The calculation results demonstrated that upon the increase of SG units number
the quartet becomes more and more unstable. Without hydration correction, the
Na
+
cation was found to bind more tightly with the tetrad than that of potassium,
whereas when hydration effects were considered the stability sequence changed to
K
+
> Na
+
. More favorable binding of potassium ion comparing to Na
+
in solution
is due to higher dehydration energy of the latter, although Na
+
cation has higher
intrinsic propensity to bind tightly to DNA quadruplexes [106].
Effect of external electric field on H-bonding and π-stacking interactions in guanine aggregates were studied by Jissy and Datta [107]. The DFT calculations were
carried out at the M05-2X level of theory with the 6-31 + G(d, p) basis set. The structure and electronic properties of guanine oligomers and π-stacks of guanine quartets
with circulenes were investigated under an external field through first-principles
calculations. The binding energy of the circulenes with G-quartets were fond to increase on application of an electric field along the stacking direction. Besides that,
the stability of G-quartet–circulene π-stacks was shown to depends on the phase of
the dipole moment (in-phase or out-of-phase) induced by an external electric field.
The stability of stacks of bowl-shaped circulenes with G-quartets depended on the
direction of the applied field.
At the end of this paragraph we would like to mention two pioneering papers
published by Leszczynski, Gu and Bansal [108, 109], where the first HF and DFT
calculations on the stability and structure of G-quartets were performed and the
possibility of the formation of the structures with bifurcated hydrogen bonds was
demonstrated.
Thus, guanine quartets were studied in depth by quantum chemical methods.
Their structural diversity based on different possible patterns of hydrogen bonding
was demonstrated and the key role of metal cations in stabilizing guanine assemblies was shown.
6.3.2.3 DFT Studies on the Structure of G-Octets and Their Metal
Complexes
Guanine octets are more complex structural elements of quadruplex systems than
the quartets. G-octet is the system of two stacked G-quartets interacting via the
π- π-stacking mechanism. This molecular assembly is closer to natural G-quadruplexes which usually contain three or four guanine quartets, thus its modelling is
able to provide more realistic structural and thermodynamic data to be extrapolated
to quadruplex DNA. At the same time, G-octet molecular system is twice as large