Thermodynamics of the photoenzymic repair mechanism studied by density functional theory

The thermodynamics of the different steps in the photoenzymic fragmentation of a thymine dimer is investigated using density functional theory (DFT) methods, including time-dependent (TD) DFT for calculating electronic transition energies, employing a model system consisting of different thymine derivatives and enzymatic cofactors (FADH(-), 8-HDF, and MTHF). It is found that the crucial electron-transfer steps, as well as the overall reaction, are exothermic and that the splitting of the C6-C6' bond in a thymine dimer radical anion is slightly exothermic (2.4 kcal mol(-1)) with a 2.3 kcal mol(-1) energy barrier. The reaction energies assigned to the different steps are generally in good agreement with the corresponding energies from previous estimates that have constituted the foundation of the proposed reaction mechanism. On the basis of this comparison, the results support the proposed model. Moreover, the excellent agreement between theoretical excitation energies and experimental data shows that TDDFT can be successfully applied to large organic molecules.