Tautomeric energies

Theoretical and experimental studies on the reaction of 3,4-bis(methoxycarbonyl)-1,2-dithiete with alkenes and alkynes yielding cycloadducts have been carried out. The activation energy of the interconversion of the 1,2-dithiete to 1,2-dithione was estimated by MO calculations. These calculations (MP2/6-31G(d)) show that the dithiete 19f is 5.8 kcal mol-1 more stable than the ethane-1,2-dithione cis-20f, and the tautomerization energy is 28.5 kcal mol-1 from the thiete 19f and this value of the activation energy supports the possibility of the tautomerization between the 1,2-dithiete 19f and ethane-1,2-dithione cis-20f, at least at high temperature <1996IJQ859>. 

All energies are obtained at G2 level with ZPE corrections at MP2/6-31G. AE is the tautomeric energy difference. PA is the proton affinity of the most stable anion. 

One is then led to ask how the tautomer mechanism can be distinguished from the alternatives, i.e., wobble mispairs of mispairs involving minor tautomer forms base paired to syn isomers. The approach is to compare the energies of the various proposed models including interaction energies, deformation energies, and tautomerization energies to determine which model is more plausible. 

Theoretical studies at varying levels of approximation (CNDO/2, NDDO, MIN-DO/2, MINDO/3, MNDO, and STO-3G methods) have been carried out in order to predict the tautomerization energy AH0 (80CPL(69)537, 83JA3568). In all the cases the stability of the hydroxy form is strongly overestimated. 

It follows from Table 3 that the most stable uracil tautomer is the 2-hydroxy-4-oxo Ti with the tautomerization energy of 10.9 kcal/mol. Despite this fact, it is unable to function as a normal nucleobase due to the absence of the N1-H7 bond connected to the sugar-phosphate backbone although it appears in the modified nucleobases including pseudouridine. Among the normal ones, the 2-oxo-4-hydroxy T2 tautomer of uracil is the most stable one lying above Ti by only 0.9 kcal/mol. Its dipole moment exceeds that of Ti by more than 50% and, therefore, polar solvents may favor T2 rather than Ti (see Section 6). For these two reasons and also because it has the N1-H7 link to the sugar-phosphate backbone, it becomes of a major biophysical interest (see also Sections 4 and 6). 

Rodriguez AM, Giannini FA, Suvire FD, Baldoni HA, Furlan R, Zacchino SA, Beke G, Matyus P, Enriz RD, Csizmadia IG. Correlation of antifungal activity of selected alpha-substituted acetophenones with their keto-enol tautomerization energy. J Mol Struct Theochem 2000 504 35-50. 

Evaluation of Tautomeric Energies, Equilibrium Constants, and Thermodynamic Contributions 2952... 

The relative tautomeric energy is the difference between the internal energy of a given tautomer (b) and that with the lowest internal energy (a) ... 

Table 13.3 Calculated 2-hydroxypyridine-pyrid-2(l H)-one (lA-lB) tautomerization energies in aqueous solution.

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