Experimental and Theoretical Studies on the Selectivity of GGG Triplets toward One-Electron Oxidation in B-Form DNA

Abstract

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.

Oxidation of Guanine in G, GG, and GGG Sequence Contexts by Aromatic Pyrenyl Radical Cations and Carbonate Radical Anions: Relationship between Kinetics and Distribution of Alkali-Labile Lesions

“…In early experiments it was shown that photoexcitation of DNA in its normal B-type double helical form by intense nano-or picosecond 266 nm laser pulses induces a greater damage of guanines positioned on the 5′-side of purine bases, especially adjacent to guanine, than on guanines adjacent to pyrimidines. 7 This selectivity of G oxidation in different sequence context has been also observed employing one-electron oxidants generated by photosensitization of metal complexes, 3,8 anthraquinones, 4,9 naphthalimides, 10 riboflavin (RF), 11,12 4′-pivaloyl derivatives, 13,14 cyanobenzoyl and cyanobenzophenone substituted 2′-deoxyuridine 15,16 and other chemical one-electron oxidants. 17, 18 Saito and co-workers have shown that the enhancement of oxidative guanine damage increases with the number of contiguous guanines according to 5′-G < 5′-GG < 5′-GGG and that this phenomenon is correlated with the calculated gas phase ionization potentials (IP) for guanines in different sequence contexts.…”

“…[41][42][43] The values of ϕ monotonously increase with increasing concentrations of DNA duplexes (see, Figure S2 in Supporting Information); at a duplex concentration ([duplex]) of 100 μM, practically all BPT molecules are bound to DNA and the ϕ values are in the range of 0.8 to 0.9 for a series of six oligonucleotide duplexes (Table S2, Supporting Information). The binding constants, K = (1.4±0.3)× 10 5 M −1 were obtained by fitting the following equation (12) to the experimental data points ( Figure S2). The values of K are not a function of the number of guanines or of their mode of grouping into separated or contiguous guanines.…”

Direct experimental observation of the low ionization potentials of guanine in free oligonucleotides by using photoelectron spectroscopy

“…Thus, the electronic structure of nucleotides and their ionization properties are essential for understanding the mechanism of DNA damage. Extensive experimental and theoretical studies have focused on these topics (11)(12)(13)(14)(15)(16)(17)(18)(19). In particular, LeBreton and coworkers (9,[20][21][22][23][24] have investigated the ionization of nucleic acid bases, sugar residue, and the phosphate in the gas phase by using UV photoelectron spectroscopy (PES) and then combining these studies and molecular orbital calculations to address the electronic structure of the nucleotides.…”

DNA Radiosensitization: The Search for Repair Refractive Lesions Including Double Strand Breaks and Interstrand Crosslinks

“…1), but this was only recently shown experimentally (Zeng & Wang, 2007). New findings show that electron capture and migration along BrdU-substituted DNA might be contra-thermodynamically selective and, thus far more complicated (Yoshioka et al, 1999;Aflatooni et al, 1998). In cells, radiosensitization by BrdU (typically at ~20-30% thymine replacement) gives about 2-3 fold radiotoxicity enhancement and in most cell types parallels similar increase in the DSB yield, and/or the decreased rate of their repair (Sawada & Okada, 1972).…”