ANTHRAQUINONE PHOTONUCLEASES - MECHANISMS FOR GG-SELECTIVE AND NONSELECTIVE CLEAVAGE OF DOUBLE-STRANDED DNA

Anthraquinone derivatives 2AQA2(HEt(2)) and 2AQC2(HEt(2)) were examine d as light-activated agents that initiate DNA cleavage. The substituen ts control the electronic configuration of the lowest excited state of the anthraquinone. 2AQC2(HEt(2)) has a lowest n pi excited state and can react by electron transfer or hydrogen atom abstraction. 2AQC2(HE t(2)) has a lowest excited state of pi pi or intramolecular charge-tr ansfer character and reacts only by electron transfer. Spectroscopic e vidence indicates that both quinones bind to double-stranded DNA by in tercalation with essentially the same affinity. Picosecond time-resolv ed 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)) foll owed by treatment with hot piperdine leads to equally effective cleava ge of DNA at the 5'-G of GG steps. These findings indicate that electr on transfer from a DNA base to the excited quinone is the dominant pat h for the GG-selective DNA cleavage. At high concentrations, where som e quinone is free in solution, irradiation of 2AQC2(HEt(2)), but not 2 AQA2(HEt(2)), leads to nonselective spontaneous cleavage of DNA. This second path to DNA cleavage is identified as direct hydrogen atom abst raction from the deoxyribose backbone by excited, nonintercalated 2AQC 2(HEt(2)).