168
T. A. Zubatiuk et al.
possible to assume that each tautomer of protonated nucleotide can exist in several
stable conformations characterized by different energy. Therefore, comprehensive
evaluation of PA requires careful consideration of the population of conformers
of non-protonated anionic DNTs and each tautomer of protonated molecules and
should be calculated using the analysis of the population of the stable conformers.
Taking into account that each tautomer exists in several conformations, the observed PA represents a average value. Therefore, a PA for every protonation site was
calculated using Eq. (5.2):
(5.2)
where E tot is the total energy of protonated (mXMP-H) and non-protonated (mXMP)
nucleotide obtained from DFT calculations, E corr is the thermal correction to enthalpy, and the term of 5/2RT includes ΔnRT for acid–base reaction and translational
energy of proton. M represents the number of conformers of a protonated tautomer
of nucleotide, N is the number of conformers of non-protonated nucleotide, and P
is the population of each conformer calculated using a Boltzmann distribution function (0 ≤ P i ≤ 1).
The PA of nucleobases in DNTs was calculated in the same way, taking into account the population of all tautomers of protonated nucleotide using the following
Eq. (5.3):
(5.3)
where K is the number of tautomers for protonated nucleotide and P n is the population of each tautomer. PA values for all conformers and tautomers were calculated
at 298 K.
The analysis of population of different conformers of monoanionic DNTs
showed that in the gas phase, they exist in form of only one conformer. This is S/
anti conformer for mTMP, mCMP, mAMP and S/syn-conformer for mGMP. The
appearance of the polar environment, simulated with PCM model, leads to larger
conformational space. The greatest population in this space has N/anti conformer
for mTMP, mCMP and mAMP. S/syn-conformer retains a dominant position for
(
)
(
)
(
)
(
)
(
)
(
)
1
1
5 / 2
M
tot
corr
i
i
i
i
N
tot
corr
j
j
j
j
PA
E mXMP H
E
mXMP H P
E mXMP
E
mXMP P
RT
=
=
= -
-
+
-
-
+
+
∑
∑
(
)
(
)
(
)
(
)
(
)
1
1
1
(
) 5 / 2
K
M
n
tot
corr
i
i
i
n
i
N
tot
corr
j
j
j
j
PA
P
E mXMP H
E
mXMP H P
E mXMP
E
mXMP P
RT
=
=
=
= -
-
+
-
-
+
+
∑ ∑
∑
T. A. Zubatiuk et al.
possible to assume that each tautomer of protonated nucleotide can exist in several
stable conformations characterized by different energy. Therefore, comprehensive
evaluation of PA requires careful consideration of the population of conformers
of non-protonated anionic DNTs and each tautomer of protonated molecules and
should be calculated using the analysis of the population of the stable conformers.
Taking into account that each tautomer exists in several conformations, the observed PA represents a average value. Therefore, a PA for every protonation site was
calculated using Eq. (5.2):
(5.2)
where E tot is the total energy of protonated (mXMP-H) and non-protonated (mXMP)
nucleotide obtained from DFT calculations, E corr is the thermal correction to enthalpy, and the term of 5/2RT includes ΔnRT for acid–base reaction and translational
energy of proton. M represents the number of conformers of a protonated tautomer
of nucleotide, N is the number of conformers of non-protonated nucleotide, and P
is the population of each conformer calculated using a Boltzmann distribution function (0 ≤ P i ≤ 1).
The PA of nucleobases in DNTs was calculated in the same way, taking into account the population of all tautomers of protonated nucleotide using the following
Eq. (5.3):
(5.3)
where K is the number of tautomers for protonated nucleotide and P n is the population of each tautomer. PA values for all conformers and tautomers were calculated
at 298 K.
The analysis of population of different conformers of monoanionic DNTs
showed that in the gas phase, they exist in form of only one conformer. This is S/
anti conformer for mTMP, mCMP, mAMP and S/syn-conformer for mGMP. The
appearance of the polar environment, simulated with PCM model, leads to larger
conformational space. The greatest population in this space has N/anti conformer
for mTMP, mCMP and mAMP. S/syn-conformer retains a dominant position for
(
)
(
)
(
)
(
)
(
)
(
)
1
1
5 / 2
M
tot
corr
i
i
i
i
N
tot
corr
j
j
j
j
PA
E mXMP H
E
mXMP H P
E mXMP
E
mXMP P
RT
=
=
= -
-
+
-
-
+
+
∑
∑
(
)
(
)
(
)
(
)
(
)
1
1
1
(
) 5 / 2
K
M
n
tot
corr
i
i
i
n
i
N
tot
corr
j
j
j
j
PA
P
E mXMP H
E
mXMP H P
E mXMP
E
mXMP P
RT
=
=
=
= -
-
+
-
-
+
+
∑ ∑
∑