Structure of Thiouracils and Their Lower-Energy Tautomers

Structure of Thiouracils and Their Lower-Energy Tautomers 

By the analogy with uracil [20], the potential energy surfaces of tautomer-ization of thiouracils reveal twelve tautomeric forms. The four most stable 

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). 

Returning to the orders of stability of the most stable tautomeric forms of uracil and thiouracil displayed by Eqs.(l)-(4), we find that the thio-substitution has two major effects. One is that it may substantially increase the stability of tautomers whereas the other is that it drastically alters their order of stability. This is vividly seen by comparing (1) with (4). We observe then that the 

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