163
5 Molecular Structures, Relative Stability, and Proton Affinities of Nucleotides
an opposite orientation: syn in mTMP−H7 trans and anti-orientation in mTMP−H8
trans. In both cases, the orientation of the base is stabilized by intramolecular hydrogen bonds, namely, strong O−H...O in the C4′-endo/syn conformer of mTMP−H7
trans and considerably weaker C−H...O bonds in the S/anti conformer of mTMP−
H8 trans. It should be noted that only the last type of the hydrogen bonds is observed
in all other conformers of mTMP forms. Some of such hydrogen bonds are quite
strong because of opposite charge assistance, as was mentioned earlier [78]. Nevertheless, the influence of relatively strong C−H...O interactions on the relative energy of conformers is considerably smaller, as compared to the strong conventional
O−H...O hydrogen bond. It is possible to conclude that the mTMP−H7 tautomer
exists exclusively as the C4′-endo/syn conformer, while the conformational state of
the mTMP−H8 tautomer may be described as S/anti with a minor supplement of N/
anti conformer (Table 5.15).
5.6.2 Protonated mCMP
In the case of mCMP, it is possible to suggest existence of three tautomers with a
protonated ring nitrogen atom, carbonyl and amino group (Fig. 5.14). However, results of calculations demonstrated that the mCMP-H8 tautomer does not correspond
to a minimum on the potential energy surface. A proton transfer from the protonated amino group to the phosphate group was revealed during optimization of its
molecular geometry. Therefore, only tautomers with a protonated ring nitrogen and
carbonyl group should be considered. Taking into account two possible orientations
of the OH bond of a protonated carbonyl group, one can conclude that tautomers of
protonated mCMP have three stable conformers similar to a non-protonated molecule (Table 5.15). Only in the case of the mCMP-H7 trans tautomer, protonation
leads to disappearance of the S/anti conformer because of the transition of the base
from anti to syn orientation accompanied by deformation of the furanose ring.
Results of calculations show that protonation of the mCMP yields significant
stabilization of conformers with orthogonal orientation of cytosine with respect to
the C1′-H bond. This conformer possesses the lowest energy among the mCMP-H3
tautomers, and it has only slightly higher energy for the mCMP-H7 tautomer. For
the last tautomer, the most stable conformer is the C4′-endo/syn with trans orientation of the hydrogen atom of a protonated carbonyl group with respect to the N3
atom of the pyrimidine ring (Table 5.15, Fig. 5.14). It should be noted that the
conformers with the lowest energy in both tautomers are stabilized by the N–H…
O (mCMP -H3) and O-H…O (mCMP-H7) hydrogen bonds. The N-H…O bonds
also are found in the C2′-exo/ort conformers of the mCMP-H7 tautomer. However,
its energy is considerably smaller, as compared to the C4′-endo/syn conformer of
mCMP-H7trans. This allows suggesting that the strength of the N-H…O or O-H…
O hydrogen bonds plays a very important role in stabilization of conformers of
protonated mCMP.
5 Molecular Structures, Relative Stability, and Proton Affinities of Nucleotides
an opposite orientation: syn in mTMP−H7 trans and anti-orientation in mTMP−H8
trans. In both cases, the orientation of the base is stabilized by intramolecular hydrogen bonds, namely, strong O−H...O in the C4′-endo/syn conformer of mTMP−H7
trans and considerably weaker C−H...O bonds in the S/anti conformer of mTMP−
H8 trans. It should be noted that only the last type of the hydrogen bonds is observed
in all other conformers of mTMP forms. Some of such hydrogen bonds are quite
strong because of opposite charge assistance, as was mentioned earlier [78]. Nevertheless, the influence of relatively strong C−H...O interactions on the relative energy of conformers is considerably smaller, as compared to the strong conventional
O−H...O hydrogen bond. It is possible to conclude that the mTMP−H7 tautomer
exists exclusively as the C4′-endo/syn conformer, while the conformational state of
the mTMP−H8 tautomer may be described as S/anti with a minor supplement of N/
anti conformer (Table 5.15).
5.6.2 Protonated mCMP
In the case of mCMP, it is possible to suggest existence of three tautomers with a
protonated ring nitrogen atom, carbonyl and amino group (Fig. 5.14). However, results of calculations demonstrated that the mCMP-H8 tautomer does not correspond
to a minimum on the potential energy surface. A proton transfer from the protonated amino group to the phosphate group was revealed during optimization of its
molecular geometry. Therefore, only tautomers with a protonated ring nitrogen and
carbonyl group should be considered. Taking into account two possible orientations
of the OH bond of a protonated carbonyl group, one can conclude that tautomers of
protonated mCMP have three stable conformers similar to a non-protonated molecule (Table 5.15). Only in the case of the mCMP-H7 trans tautomer, protonation
leads to disappearance of the S/anti conformer because of the transition of the base
from anti to syn orientation accompanied by deformation of the furanose ring.
Results of calculations show that protonation of the mCMP yields significant
stabilization of conformers with orthogonal orientation of cytosine with respect to
the C1′-H bond. This conformer possesses the lowest energy among the mCMP-H3
tautomers, and it has only slightly higher energy for the mCMP-H7 tautomer. For
the last tautomer, the most stable conformer is the C4′-endo/syn with trans orientation of the hydrogen atom of a protonated carbonyl group with respect to the N3
atom of the pyrimidine ring (Table 5.15, Fig. 5.14). It should be noted that the
conformers with the lowest energy in both tautomers are stabilized by the N–H…
O (mCMP -H3) and O-H…O (mCMP-H7) hydrogen bonds. The N-H…O bonds
also are found in the C2′-exo/ort conformers of the mCMP-H7 tautomer. However,
its energy is considerably smaller, as compared to the C4′-endo/syn conformer of
mCMP-H7trans. This allows suggesting that the strength of the N-H…O or O-H…
O hydrogen bonds plays a very important role in stabilization of conformers of
protonated mCMP.