THEORETICAL-STUDIES OF GC-SPECIFIC PHOTOCLEAVAGE OF DNA VIA ELECTRON-TRANSFER - SIGNIFICANT LOWERING OF IONIZATION-POTENTIAL AND 5'-LOCALIZATION OF HOMO OF STACKED GG BASES IN B-FORM DNA

Ab initio molecular orbital calculations of stacked DNA bases were per formed at the 3-21G() and 6-31G* levels to elucidate the origin of th e 5'-GG-3' sequence specificity for the photocleavage of DNA in the pr esence of electron-accepting photosensitizers. Ionization potentials ( IF) were estimated as Koopman's theorem values for 16 sets of two stac ked nucleobases and seven sets of stacked nucleobase pair systems in a B-form geometry. It was found that the GG/CC system is the lowest amo ng the 10 possible stacked nucleobase pairs and that approximately 70% of the HOMO is localized on the 5'-G of 5'-GG-3'. These calculations indicate that the 5'-G of 5'-GG-3' is the most electron donating site in B DNA and suggest that one-electron transfer from DNA to an electro n acceptor occurs most effectively at 5'-GG-3' sites which are fully c onsistent with the experimental data. In order to know the fate of the cation radical, the vertical IPs were estimated for seven stacked nuc leobase pairs. It was found that the GG/CC system possesses the smalle st vertical IP and that the cation radical is localized on the 5'-G of 5'-GG-3'. These results imply that the 5'-G of 5'-GG-3' is a sink in ''hole'' migration through DNA, i.e., an electron-loss center created in a B-form DNA will end up predominantly on the 5'-G of 5'-GG-3', and suggest that not only the base specificity for initial photoionizatio n but also subsequent energetically favored hole migration to the lowe st 5'-GG-3' site are the origin of the 5'-GG-3' specific cleavage. Cal culations of stacked GGs with various geometries including orientation s of A- and Z-form DNA were also examined.