No abstract

There has been much current interest in the long-range oxidative damage to DNA through the DNA duplex caused by one-electron oxidations. 1 Hole (radical cation) migration through the DNA duplex has been suggested to play a crucial role in mutagenesis and carcinogenesis caused by carcinogenic agents, ionizing radiation, and high-intensity laser irradiation. 1,2 As is well-known, guanine (G) is the most easily oxidized base, 3 and the electron-loss center created in duplex DNA ultimately ends up at G residues via hole migration through the DNA duplex. Several years ago, we demonstrated both experimentally and by ab initio calculations that 5′-G residues of 5′-GG-3′ steps in B-form DNA are the most easily oxidized due to the GG stacks and can act as thermodynamic sinks in hole migration across the DNA π stack. 4 We also demonstrated that the highest occupied molecular orbital (HOMO) of a GG stack is especially high in energy and concentrated on the 5′-G. 4b Thereafter, examples of 5′-G selective oxidations have been reported in many different systems. These include (i) photooxidation using different types of DNA-binding agents such as Rh(III)-metallointercalators, 1a-c,f substituted anthraquinones, 1d,e,5 riboflavin, 6 naphthalimide derivatives, 4 a p-cyano-substituted benzophenone, 7 and pterins; 8 (ii) chemical oxidation by Ru(III)-metallointercalators 1c,9 and Ni(II)ligand/sulfite system; 10 (iii) two-photon photoionization of DNA with a high-intensity laser pulse (266 nm); 11 and (iv) direct irradiation with a powerful 193-nm excimer laser. 12 Notably, the 5′-G selectivity of 5′-GG-3′ steps is irrelevant to the structural

The selectivity of 5‘-TGGGT-3‘ and 5‘-CGGGC-3‘ sequences toward photoinduced one-electron oxidation was examined experimentally and by ab initio molecular orbital (MO) calculations. It was confirmed experimentally that G2 of 5‘-TG1G2G3T-3‘ is more reactive than G1, while for 5‘-CG1G2G3C-3‘ the selectivity is reversed, that is, G1 > G2. The ab initio MO analyses were performed to elucidate the difference of the selectivities between 5‘-TGGGT-3‘ and 5‘-CGGGC-3‘ sequences. For the 5‘-TGGG-3‘ sequence, the spin densities of G1 • and G2 • in neutral radical (5‘-TG1G2G3-3‘)• have a similar pattern, and the shapes of the corresponding radical orbitals are also very similar. It was concluded that the selectivity is due to the stability of the (5‘-TG1G2G3-3‘)• neutral radicals; that is, 5‘-TG1G2 •G3-3‘ is more stable in energy than 5‘-TG1 •G2G3-3‘. For the 5‘-CGGG-3‘ sequence, it was found that the spin density on N1 of G1 • in neutral radical (5‘-CG1G2G3-3‘)• is distinguishably different from the corresponding spin density of G2 •, which has a pattern similar to those of G1 • and G2 • in 5‘-TG1G2G3-3‘. The radical orbital (SOMO) of G1 • is delocalized on guanine base and up to the paired cytosine base, while the radical orbital of G2 • is essentially localized on guanine base. This drastic difference of the electron population in the radical orbitals, caused by the stacking interaction with the 5‘-side G of the opposite strand, can explain why G1 is more reactive than G2 in the 5‘-CG1G2G3-3‘ sequence.