Hypoxia-selective DNA interstrand cross-link formation by two modified nucleosides.

Two nitroimidazole modified thymidines 1a and 1b have been synthesized and incorporated into DNA oligomers. The 350 nm photolysis of 1a and 1b generated a 5-(2′-deoxyuridinyl)methyl radical that induced DNA interstrand cross-links (ICL). Higher ICL yield was observed under hypoxic conditions than aerobic conditions. The photoproducts of monomers or DNA oligomers were isolated and characterized by NMR and/or mass spectroscopy.