Site-specific DNA oxidation by a dinuclear copper complex containing a photoisomerizable azobenzene ligand

• DNA cleavage by a Cu complex containing a photoisomerizable azobenzene was studied.
• Both the trans and cis isomers showed moderate DNA cleavage activities.
• The trans isomer induced guanine oxidation at the strand–helix junction of DNA.

A dinuclear copper complex possessing an azobenzene backbone (CuII21) was synthesized and its affinity towards DNA was investigated and found to be dependent on the trans–cis isomeric forms. Upon exposure to UV light at 365 nm the trans form of the complex (CuII2trans-1) underwent photoisomerization into the cis-isomer (CuII2cis-1), which reverted to the original trans-form on exposure to visible light at 420 nm. Both the trans and cis isomers exhibited moderate DNA cleavage activity toward plasmid duplex DNA in the presence of a reducing agent 3-mercaptopropionic acid (MPA) suggesting that the CuI species could activate molecular oxygen to form a reactive oxygen species in situ. Interestingly, the isomeric copper complexes showed different site-specificities in the oxidation of an oligodeoxynucleotide having single-strand–double-helix junctions in the sequence. The trans isomer CuI2trans-1 induced oxidation at the consecutive deoxyguanosine site (GG) near the junction; on the other hand, such site-specificity was not observed in the case of CuI2cis-1.

Photoisomerizable dinuclear copper complexes containing an azobenzene structure (Cu2trans-1 and Cu2cis-1) induce DNA oxidation in the presence of 3-mercaptopropionic acid. The trans isomer induces site-specific oxidation at the consecutive deoxyguanosine site near the single-strand–double-helix junction in DNA.Figure optionsDownload as PowerPoint slide