A series of 9,10’-anthryl analogs with various leaving groups (L=Br, NMe2, N(CH2CH2)2O, OAc, OCH3, OCHCH=CH2, OCH2Ph, Me3N+, and Ph3P+) were synthesized. Their reactivity towards DNA and the reaction mechanism were investigated by determining DNA interstrand cross-link (ICL) efficiency, radical and carbocation formation, and the cross-linking reaction sites. All compounds induced DNA ICL formation upon 350 nm irradiation via a carbocation that was generated from the oxidation of the corresponding free radicals. The ICL efficiency and the reaction rate significantly depended on the effect of the leaving group. Among all compounds tested, high ICL efficiency and fast reaction rate were observed with compounds carrying a Bromo group, trimethylammonium, and triphenyl phosphonium salt as leaving groups. Both cation-trapping and free radical-trapping adducts were detected in the photoactivation process of these compounds, which provided direct evidence for the proposed mechanism. Heat stability study in combination with sequence study suggested that these photo-generated benzyl cations alkylate DNA at dG, dA, and dC sites.

A series of 9,10’-anthryl analogs with various leaving groups (L=Br, NMe~2~, N(CH~2~CH~2~)2O, OAc, OCH~3~, OCHCH=CH~2~, OCH~2~Ph, Me~3~N+, and Ph~3~P+) were synthesized. Their reactivity towards DNA and the reaction mechanism were investigated by determining DNA interstrand cross-link (ICL) efficiency, radical and carbocation formation, and the cross-linking reaction sites. All compounds induced DNA ICL formation upon 350 nm irradiation via a carbocation that was generated from the oxidation of the corresponding free radicals. The ICL efficiency and the reaction rate significantly depended on the effect of the leaving group. Among all compounds tested, high ICL efficiency and fast reaction rate were observed with compounds carrying a Bromo group, trimethylammonium, and triphenyl phosphonium salt as leaving groups. Both cation-trapping and free radical-trapping adducts were detected in the photoactivation process of these compounds, which provided direct evidence for the proposed mechanism. Heat stability study in combination with sequence study suggested that these photo-generated benzyl cations alkylate DNA at dG, dA, and dC sites.

Leaving groups significantly affect the DNA interstrand cross-link formation efficiency by novel anthracene derivatives.

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