Journal
CHEMISTRY-A EUROPEAN JOURNAL
Volume 23, Issue 24, Pages 5804-5813Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/chem.201700231
Keywords
DNA; DNA-protein cross-link; endoperoxide; guanine; singlet oxygen
Categories
Funding
- National Science Foundation [CHE1464450, CHE1507813]
- Wayne State University
- Direct For Mathematical & Physical Scien
- Division Of Chemistry [1464450, 1507813] Funding Source: National Science Foundation
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Oxidation of guanine in the presence of lysine can lead to guanine-lysine cross-links. The ratio of the C4, C5 and C8 crosslinks depends on the manner of oxidation. TypeII photosensitizers such as Rose Bengal and methylene blue can generate singlet oxygen, which leads to a different ratio of products than oxidation by typeI photosensitizers or by one electron oxidants. Modeling reactions of singlet oxygen can be quite challenging. Reactions have been explored using CASSCF, NEVPT2, DFT, CCSD(T), and BD(T) calculations with SMD implicit solvation. The spin contamination in open-shell calculations were corrected by Yamaguchi's approximate spin projection method. The addition of singlet oxygen to guanine to form guanine endo- peroxide proceeds step-wise via a zwitterionic peroxyl intermediate. The subsequent barrier for ring closure is smaller than the initial barrier for singlet oxygen addition. Ring opening of the endoperoxide by protonation at C4-O is followed by loss of a proton from C8 and dehydration to produce 8-oxoG(ox). The addition of lysine (modelled by methylamine) or water across the C5=N7 double bond of 8-oxoG(ox) is followed by acyl migration to form the final spiro products. The barrier for methylamine addition is significantly lower than for water addition and should be the dominant reaction channel. These results are in good agreement with the experimental results for the formation of guanine-lysine cross-links by oxidation by typeII photosensitizers.
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