167
5 Molecular Structures, Relative Stability, and Proton Affinities of Nucleotides
lar, PAs of thymine were found to be considerably lower (8.9−9.2 eV) as compared
to guanine, cytosine, and adenine (9.6−9.9 eV). It should also be noted that there is
a good agreement between experimental and theoretical data. Appearance of a sugar fragment in molecules of 2′-deoxyribonucleosides results in an increase of PAs
of all nucleobases [75, 88–99]. Nevertheless, the PA value for 2′-deoxythymidine
(9.8 eV) remains lower than that for other nucleosides (10.1–10.3 eV). The values
of PA for nucleoside follow the trend: PA (dG) > PA (dC) ≥ PA (dA) >> PA (dT) [88].
According to experimental data [75, 76], the presence of a neutral phosphate group
in DNTs does not influence the PAs of the nucleobases. For instance, the value
of PA for TMP is 9.7−9.8 eV and it amount to 10.1−10.3 eV for CMP, GMP, and
AMP. Whereas for nucleotides the analogous trend is as follows: PA (GMP) ≈ PA
(CMP) ≈ PA (AMP) >> PA (TMP) [96]. In general, these data agree well with results
of semiempirical quantum-chemical calculations by the AM1 method [75].
Further increase of the PA of the nucleobases was found in anions of DNTs [77].
As it was expected, appearance of negative charge due to deprotonation of the phosphate group results in an increase of the PA values by 2.7−2.9 eV. However, similar
to results for isolated bases, the base in the TMP anion has the lowest PA. Besides
that, the PA value for CMP also becomes slightly lower than that for AMP and GMP
(ΔPA ≈ 0.3 eV). In the discussed here investigations, P–O group of phosphate is not
considered as a protonation sites. The PA of P–O is always much higher than PA of
any nucleobase atom.
It should be noted some experimental problems in study of protonation of nucleotides. At the first stage the protonation of phosphate (PU) always happens. This is
explained by the significant difference in the values of PA of nucleobases protonation sites and PU. Therefore, the experimental data reflect the process of protonation of neutral forms of deoxyribonucleotides. But it is well known, that in vivo,
nucleotides have a negative charge, which is balanced by the metal cations (Na
+
or
K
+
). Thus, the issue of nucleobases protonation in monoanionic DNTs remains unanswered in experimental investigations.
According to semiempirical AM1 study [75, 76] of PA of protonated DNTs containing a neutral phosphate group it was concluded that appearance of a phosphate
group in DNTs results in a change of preferable protonation sites. In the case of neutral CMP, GMP, and AMP molecules, the highest PA were found for the N3 atom,
while in TMP the oxygen atom of the C4=O carbonyl group remains the most preferable site for protonation. In the case of anionic DNTs containing a deprotonated
phosphate group, it was concluded on the basis of calculations by the AM1 method
that the N7 atom has the highest PA value for GMP [77]. Other anionic nucleotides
have the same preferable sites of protonation as molecules with a neutral phosphate
group. In the case of anionic AMP, the highest stability of tautomer with the proton
located at the N3 atom was also confirmed by calculations using DFT methods [78].
However, contrary to AM1 data, it was found in the DFT study that the N7 atom
of adenine is the most preferable site for protonation of a molecule with a neutral
phosphate group.
Taking into account that fact one concludes that protonation of anionic nucleotides may lead to significant changes in their conformations and energetic. It is
5 Molecular Structures, Relative Stability, and Proton Affinities of Nucleotides
lar, PAs of thymine were found to be considerably lower (8.9−9.2 eV) as compared
to guanine, cytosine, and adenine (9.6−9.9 eV). It should also be noted that there is
a good agreement between experimental and theoretical data. Appearance of a sugar fragment in molecules of 2′-deoxyribonucleosides results in an increase of PAs
of all nucleobases [75, 88–99]. Nevertheless, the PA value for 2′-deoxythymidine
(9.8 eV) remains lower than that for other nucleosides (10.1–10.3 eV). The values
of PA for nucleoside follow the trend: PA (dG) > PA (dC) ≥ PA (dA) >> PA (dT) [88].
According to experimental data [75, 76], the presence of a neutral phosphate group
in DNTs does not influence the PAs of the nucleobases. For instance, the value
of PA for TMP is 9.7−9.8 eV and it amount to 10.1−10.3 eV for CMP, GMP, and
AMP. Whereas for nucleotides the analogous trend is as follows: PA (GMP) ≈ PA
(CMP) ≈ PA (AMP) >> PA (TMP) [96]. In general, these data agree well with results
of semiempirical quantum-chemical calculations by the AM1 method [75].
Further increase of the PA of the nucleobases was found in anions of DNTs [77].
As it was expected, appearance of negative charge due to deprotonation of the phosphate group results in an increase of the PA values by 2.7−2.9 eV. However, similar
to results for isolated bases, the base in the TMP anion has the lowest PA. Besides
that, the PA value for CMP also becomes slightly lower than that for AMP and GMP
(ΔPA ≈ 0.3 eV). In the discussed here investigations, P–O group of phosphate is not
considered as a protonation sites. The PA of P–O is always much higher than PA of
any nucleobase atom.
It should be noted some experimental problems in study of protonation of nucleotides. At the first stage the protonation of phosphate (PU) always happens. This is
explained by the significant difference in the values of PA of nucleobases protonation sites and PU. Therefore, the experimental data reflect the process of protonation of neutral forms of deoxyribonucleotides. But it is well known, that in vivo,
nucleotides have a negative charge, which is balanced by the metal cations (Na
+
or
K
+
). Thus, the issue of nucleobases protonation in monoanionic DNTs remains unanswered in experimental investigations.
According to semiempirical AM1 study [75, 76] of PA of protonated DNTs containing a neutral phosphate group it was concluded that appearance of a phosphate
group in DNTs results in a change of preferable protonation sites. In the case of neutral CMP, GMP, and AMP molecules, the highest PA were found for the N3 atom,
while in TMP the oxygen atom of the C4=O carbonyl group remains the most preferable site for protonation. In the case of anionic DNTs containing a deprotonated
phosphate group, it was concluded on the basis of calculations by the AM1 method
that the N7 atom has the highest PA value for GMP [77]. Other anionic nucleotides
have the same preferable sites of protonation as molecules with a neutral phosphate
group. In the case of anionic AMP, the highest stability of tautomer with the proton
located at the N3 atom was also confirmed by calculations using DFT methods [78].
However, contrary to AM1 data, it was found in the DFT study that the N7 atom
of adenine is the most preferable site for protonation of a molecule with a neutral
phosphate group.
Taking into account that fact one concludes that protonation of anionic nucleotides may lead to significant changes in their conformations and energetic. It is