Oxygen-dependent DNA damage amplification involving 5,6-dihydrothymidin-5-yl in a structurally minimal system

5,6-Dihydrothymidin-5-yl (1) was independently generated in a dinucleotide from a phenyl selenide precursor (4). Under free radical chain propagation conditions, the products-resulting from hydrogen atom donation and radical-pair reaction are the major observed products in the absence of O-2. The stereoselectivity of the trapping process is dependent on the structure of the hydrogen-atom donor. No evidence for internucleotidyl hydrogen atom abstraction by 1 was detected. The tandem lesion (17) resulting from hydrogen atom abstraction from the Cl ' position of the adjacent 2 ' -deoxyuridine by the peroxyl radical derived from 1 (3) is observed under aerobic conditions. The structure of this product is confirmed by independent synthesis and its transformation into a second independently synthesized product (24). Internucleotidyl hydrogen atom abstraction is effected selectively by the SS-diastereomer of the peroxyl radical. The formation of dinucleotide 17 provides further support for the novel O-2-dependent DNA damage amplification mechanism involving 1 reported previously (Greenberg, M. M.; et al. J. Am. Chem. Sec. 1997, 119, 1828).