Acridizinium salts as a novel class of DNA-binding and site-selective DNA-photodamaging chromophores

It was demonstrated that the interaction of the aminoacridizinium salts 2a- 2d with DNA depends on the substitution pattern of the chromophore. Spectro photometric and fluorometric titrations of the acridizinium salts 2a-2d wit h natural and synthetic polynucleotides reveal that the degree of interacti on of the acridizinium salts 2a-2d with the nucleic acid differs significan tly. The binding mode of the dyes with DNA was evaluated by circular dichro ism and linear dichroism spectroscopy and compared with the parent system 2 c. Whereas the 9-aminoacridizinium (2a) mainly intercalates into DNA, the s alts 2b-c show a higher degree of association to the DNA backbone. The inte rcalated aminoacridizinium 2a caused few strand breaks upon UVA exposure, w hereas the salts 2b-2d exhibit relatively efficient DNA-damaging properties . All acridizinium salts showed a sequence-selective strand cleavage for gu anine-rich DNA regions.