Model Studies of DNA Photorepair:  Reduction Potentials of Thymine and Cytosine Cyclobutane Dimers Measured by Fluorescence Quenching

The interactions of various pyrimidines (1,3-dimethylthymine, DMT, 1,3-bis( N 4, N 4 -dimethylcytosin-1-yl)propane, DMC) and their corresponding cis - syn cyclobutane dimers (DMTD and DMCD) with a series of excited-state electron donors were examined with the goal of understanding the energetics and mechanism of UV repair by DNA photolyase. For each substrate there is a good correlation between the excited state oxidation potential ( E ox * ) and the quenching rate constant ( k q ). The value for k q increases as E ox * becomes more negative, asymptotically approaching a value that is at or below the solvent diffusion limit. These data all showed good fits to the Rehm−Weller equation. Reduction potentials for each of the substrates could be extracted from this analysis: −2.20 V (vs SCE) for DMTD; −2.14 V for DMT; −2.17 V for DMCD; and −2.16 for DMC. These values show that the initial electron transfer step in the photolyase mechanism is exergonic by ca. 10−15 kcal/mol. Thus these data support the reductive electron transfer mechanism for DNA photolyases proposed by Jorns et al. ( J. Biol. Chem. 1987, 262, 486−491).