The behavior of triplet thymine in a model B-DNA strand. Energetics and spin density localization revealed by ab initio molecular dynamics simulations.

Among the natural occurring nucleobases, thymine presents the lowest triplet state, hence it represents a hotspot for energy transfer and photosensitization. In turn, the population of the triplet state may lead to thymine dimerization and hence to the production of toxic DNA lesions and has been the subject of intensive theoretical and experimental investigations. Relying on QM/MM molecular dynamics simulations, we have sought to situate the energy of the lowest triplet state of thymine embedded in a B-DNA environment. The energy gap varies between 305 and 329 kJ.mol−1 when a single thymine is treated at the quantum chemistry level, depending on its position in the model double-stranded 16-bp oligonucleotide. The energy of triplet state decreases up to 300 kJ.mol−1, due to polarization effects, when we consider coupled stacked nucleobases up to the inclusion of four nucleobases. Our value lies in good agreement with the energy inferred experimentally by Miranda and coworkers (270 kJ.mol−1), and our theoretical exploration opens the door to investigations toward other more complex and biological relevant environments, such as thymines embedded in nucleosome core particles. Our investigations also provide a reference for further studies using semiempirical approaches such as density functional based tight binding, allowing to further rationalize sequence effects.