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Within the framework of this research it is firmly
established that in thiocytosines protonation (methylaꢀ
tion) occurs at N(1), although hypothetically there are
several more possible atoms. Having such experimental
material in hands, it is interesting to discuss the ability of
the theory to forecast the observed picture.
There are examples when the analysis of the affinity to
the proton or of the full energy of corresponding tautomer
forms allowed the description of a tautomeric equilibrium.20
These quantities changes concordantly, hence for the
investigated structures only corresponding free energies
(ΔG, RB3LYP/6ꢀ31G(d)) were calculated. In Fig. 5 differꢀ
ences in the free energies of forms protonated (methylated)
at different positions are presented for compound 1.
As seen, in a full agreement with experiment, the comꢀ
putations predict a considerable preferability of the N(1)ꢀ
protonated (methylated) form.
Furthermore, within the framework of the same apꢀ
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of uncharged structure 1 (see Fig. 5, b) was conducted. It
turned out that the tautomer A is be far more stable than
the others both in a neutral molecule (see Fig. 5, b), and
for charged structure, which is in a full agreement with
experiment.
Thus, the thermodynamic approach adequately deꢀ
scribes the picture observed experimentally. Moreover,
taking into consideration the efficiency of such an apꢀ
proach also for other protonated pyrimidines,21 this methꢀ
odology apparently has a good predictability.
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The following conclusions were drawn due to the
1
present study. The efficiency of the use of 2D H—15N
HSQC/HMBC NMR experiments for the determination
of the protonation (methylation) position and tautomeric
composition of nitrogenꢀcontaining heterocycles has been
demonstrated.
For the studied compounds it has been established
that the addition of H (Me) occurs at the atom N(1). The
tautomer with the amine form of a substituent at the posiꢀ
tion 4 is the predominated one.
Ab initio calculations of CS (GIAO B3LYP/6ꢀ31G(d)/
/HF/6ꢀ31G) well reproduce the experimental effects. The
analysis of experimental 15N CS is a reliable tool for the
determination of the protonation (methylation) position
and tautomer structure.
The stability of various protonated (methylated) and
tautomer species is governed by a thermodynamic mechaꢀ
nism.
19. A. A. Balandina, A. A. Kalinin, V. A. Mamedov, B. Figadere,
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Received March 17, 2008;
in revised form June 16, 2008