Anthraquinone Photonucleases: Mechanisms for GG-Selective and Nonselective Cleavage of Double-Stranded DNA

Abstract

Anthraquinone derivatives 2AQA2(HEt 2 ) and 2AQC2(HEt 2 ) were examined as light-activated agents that initiate DNA cleavage. The substituents control the electronic configuration of the lowest excited state of the anthraquinone. 2AQC2(HEt 2 ) has a lowest nπ* excited state and can react by electron transfer or hydrogen atom abstraction. 2AQC2(HEt 2 ) has a lowest excited state of ππ* or intramolecular charge-transfer character and reacts only by electron transfer. Spectroscopic evidence indicates that both quinones bind to double-stranded DNA by intercalation with essentially the same affinity. Picosecond time-resolved laser spectroscopy shows that single electron transfer from the DNA bases to either bound quinone occurs rapidly and to the same extent. Irradiation of either intercalated 2AQA2(HEt 2 ) or 2AQC2(HEt 2 ) followed by treatment with hot piperdine leads to equally effective cleavage of DNA at the 5‘-G of GG steps. These findings indicate that electron transfer from a DNA base to the excited quinone is the dominant path for the GG-selective DNA cleavage. At high concentrations, where some quinone is free in solution, irradiation of 2AQC2(HEt 2 ), but not 2AQA2(HEt 2 ), leads to nonselective spontaneous cleavage of DNA. This second path to DNA cleavage is identified as direct hydrogen atom abstraction from the deoxyribose backbone by excited, nonintercalated 2AQC2(HEt 2 ).