Unique tautomeric and recognition properties of thioketothymines?

TitleUnique tautomeric and recognition properties of thioketothymines?
Publication TypeJournal Article
Year of Publication2009
AuthorsFaustino, Ignacio, Aviñó Anna, Marchán Ivan, F Luque Javier, Eritja Ramon, and Orozco Modesto
JournalJ Am Chem Soc
Date Published2009 Sep 9
KeywordsBase Pairing, Base Sequence, DNA, Gases, Isomerism, Reproducibility of Results, Thermodynamics, Thymine, Water

The tautomeric and recognition properties of thymine, 2- and 4-thioketothymines 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 sulfur 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 thioketothymines induces only mild changes in DNA structure, stability and fidelity. Despite the fact that mismatching can largely stabilize minor tautomeric forms, thioketothymines are found in the canonical thioketo-form irrespective of the paired base. Our theoretical results, confirmed by new experimental studies, describe the complete tautomeric and recognition characteristics of thioketothymines and demonstrate that both 2-thioketo and 4-thioketothymine are excellent molecules to introduce special chemical properties in modified DNA.