Design, Synthesis, and Characterization of Binaphthalene Precursors as Photoactivated DNA Interstrand Cross-Linkers

Most recently, alkylation via photogenerated carbocations has been identified as a novel mechanism for photoinduced DNA interstrand cross-link (ICL) formation by bifunctional aryl compounds. However, most compounds showed a low efficiency for DNA cross-linking. Here, we have developed a series of new 1,1′-binaphthalene analogues that efficiently form DNA ICLs upon 350 nm irradiation via generated 2-naphthalenylmethyl cations. The DNA cross-linking efficiency depends on the substituents at position 4 of the naphthalene moiety as well as the leaving groups. Compounds with NO2, Ph, H, Br, or OMe substituents led to 2–4 times higher DNA ICL yields than those with a boronate ester group. Compounds with trimethylammonium salt as a leaving group showed slightly better cross-linking efficiency than those with bromo as a leaving group. Some of these compounds showed a better cross-linking efficiency than that of traditional alkylating agents, such as nitrogen mustard analogues or quinone methide precursors. These ...