159
5 Molecular Structures, Relative Stability, and Proton Affinities of Nucleotides
mGMP replacement of the hydrogen atom by methyl group results in disappearance
of “artificial” O3′–H...O(H)–P hydrogen bond, which cannot be formed in DNA.
The comparison of intramolecular hydrogen bonds in nucleotides for equilibrium and DNA-like conformations (Tables 5.12–5.14) demonstrates conformational
dependence of hydrogen bond characteristics that is typical for weak H-bonds. A
change of conformation sometimes leads to appreciable variation of reference hydrogen bonds. In particular, H-bonds between the oxygen atoms of backbone and
the hydrogen atoms of sugar in DNA-like conformations are not revealed. This confirms our earlier conclusion that the effective (or specific) hydrogen bonds, because
of their weakness, should be viewed as a kind of electrostatic interactions, rather
than the real hydrogen bonds, as they do not affect the structure and conformational
characteristics of nucleotides. Recognition of such interactions can be made on the
basis of the Bader`s analysis of the electron density distribution.
5.6 Structure of Protonated 2′-Deoxorybonucleotides and
Relative Stability of Conformers
Protonation, in some sense, is one of the simplest acid-base chemical reactions that
are observed in both living systems and inorganic species. In case of DNA, the
protonation of nucleobases significantly influences on it structure and function. In
particular, the protonated cytosine makes significant contribution to the stabilization of DNA triplexes [3, 60, 61]. The protonation can also cause mutations in the
DNA via mispairing of complementary bases [62–65]. It was suggested [66] that the
structures of so-called rare tautomers stabilized by transition metals could also appear in complexes between protonated bases and a metal. Protonation is considered
as a catalytic factor for the hydrolytic cleavage of the N-glycosidic bond [67–70],
high reactivity of the C8 atom in purine bases [71–73], and it is closely related to
the conformational dynamics of nucleotides [74]. Being so important, acid-base
equilibrium involving nucleic acid bases has been widely studied by experimental
and theoretical methods both in gas and condensed phases. There are several fundamental questions for these studies to address, namely, comparative proton affinity of
different nucleobases, preferable sites of protonation within each nucleic acid base,
and changes of the molecular structure and conformational characteristics of DNA
constituents induced by a protonation of nucleobases.
More than 10 years ago the structure of protonated DNTs containing a neutral
phosphate group was investigated only by the semiempirical AM1 method [75, 76].
These studies were focused on calculations of values of the PAs of nucleobases,
without analysis of the conformation of protonated molecules. 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
PAs 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
5 Molecular Structures, Relative Stability, and Proton Affinities of Nucleotides
mGMP replacement of the hydrogen atom by methyl group results in disappearance
of “artificial” O3′–H...O(H)–P hydrogen bond, which cannot be formed in DNA.
The comparison of intramolecular hydrogen bonds in nucleotides for equilibrium and DNA-like conformations (Tables 5.12–5.14) demonstrates conformational
dependence of hydrogen bond characteristics that is typical for weak H-bonds. A
change of conformation sometimes leads to appreciable variation of reference hydrogen bonds. In particular, H-bonds between the oxygen atoms of backbone and
the hydrogen atoms of sugar in DNA-like conformations are not revealed. This confirms our earlier conclusion that the effective (or specific) hydrogen bonds, because
of their weakness, should be viewed as a kind of electrostatic interactions, rather
than the real hydrogen bonds, as they do not affect the structure and conformational
characteristics of nucleotides. Recognition of such interactions can be made on the
basis of the Bader`s analysis of the electron density distribution.
5.6 Structure of Protonated 2′-Deoxorybonucleotides and
Relative Stability of Conformers
Protonation, in some sense, is one of the simplest acid-base chemical reactions that
are observed in both living systems and inorganic species. In case of DNA, the
protonation of nucleobases significantly influences on it structure and function. In
particular, the protonated cytosine makes significant contribution to the stabilization of DNA triplexes [3, 60, 61]. The protonation can also cause mutations in the
DNA via mispairing of complementary bases [62–65]. It was suggested [66] that the
structures of so-called rare tautomers stabilized by transition metals could also appear in complexes between protonated bases and a metal. Protonation is considered
as a catalytic factor for the hydrolytic cleavage of the N-glycosidic bond [67–70],
high reactivity of the C8 atom in purine bases [71–73], and it is closely related to
the conformational dynamics of nucleotides [74]. Being so important, acid-base
equilibrium involving nucleic acid bases has been widely studied by experimental
and theoretical methods both in gas and condensed phases. There are several fundamental questions for these studies to address, namely, comparative proton affinity of
different nucleobases, preferable sites of protonation within each nucleic acid base,
and changes of the molecular structure and conformational characteristics of DNA
constituents induced by a protonation of nucleobases.
More than 10 years ago the structure of protonated DNTs containing a neutral
phosphate group was investigated only by the semiempirical AM1 method [75, 76].
These studies were focused on calculations of values of the PAs of nucleobases,
without analysis of the conformation of protonated molecules. 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
PAs 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