Photo-Reactivity of Binaphthalene Triphenylphosphonium Salts: DNA Interstrand Cross-Link Formation and Substituent Effects

Five novel 1,1'-binaphthalene analogues 1a - 1e with triphenylphosphonium (TPP+) salts as a leaving group have been synthesized and characterized as photo-activatable DNA alkylating agents. Phototriggered release of the TPP+ group from 1a - 1e generated naphthalenylmethyl-free radicals that were spontaneously transformed to the corresponding cations directly producing DNA interstrand cross-link (ICL) formation via alkylation. The substituents at position 4 not only affect the efficiency of ICL formation but also influence the reaction rate for DNA cross-linking. Groups with small or medium size favor ICL formation, while a bulky substituent (e.g., phenyl group) prevents DNA interstrand cross-linking. DNA alkylation by the naphthalenylmethyl cations photo-generated from 1a - 1e occurs at dG, dC, and dA, while interstrand cross-linking took place with dG/dC base pairs. The TPP+ salts (1a - 1e) are cations with both lipophiic and hydrophilic properties, which have great potential for biological applications.

Automated summary

Five novel 1,1'-binaphthalene analogues with triphenylphosphonium salts as leaving groups were synthesized and used as photo-activatable DNA alkylating agents. The released naphthalenylmethyl-free radicals spontaneously transformed into cations, leading to DNA interstrand cross-link formation via alkylation. The substituents at position 4 affected both the efficiency and reaction rate of interstrand cross-linking. The TPP+ salts showed both lipophilic and hydrophilic properties, making them suitable for biological applications.