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) m ethods, including time-dependent (TD) DFT for calculating electronic transi tion energies, employing a model system consisting of different thymine der ivatives and enzymatic cofactors (FADH(-), 8-HDF, and MTHF). It is found th at the crucial electron-transfer steps, as well as the overall reaction, ar e exothermic and that the splitting of the C6-C6' bond in a thymine dimer r adical 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 a re generally in good agreement with the corresponding energies from previou s estimates that have constituted the foundation of the proposed reaction m echanism. On the basis of this comparison, the results support the proposed model. Moreover, the excellent agreement between theoretical excitation en ergies and experimental data shows that TDDFT can be successfully applied t o large organic molecules.