THE UNIQUE TAUTOMERIC AND RECOGNITION PROPERTIES OF THIO-THYMINES?

The tautomeric and recognition properties of thymine, 2- and 4-thiothymines have been studied by means of accurate ab initio methods combined with molecular dynamics simulations and free energy calculations. In contrast to previous suggestions in the literature, the replacement of carbonyl oxygens by sulphur atoms does not lead to dramatic changes in tautomeric properties of the pyrimidine derivatives neither in vacuum nor in aqueous solution. Moreover, the presence of thiothymines induces only mild changes in DNA structure, stability and fidelity. Despite the fact that mismatching can largely stabilize minor tautomeric forms, thiothymines are found in the canonical thio-form irrespective of the paired base. Our theoretical results, confirmed by new experimental studies, describe the complete tautomeric and recognition characteristics of thiothymines and demonstrate that both 2-thio and 4-thiothymine are excellent molecules to introduce special chemical properties in modified DNA.