Copper(II) macrocycles cleave single-stranded and double-stranded DNA under both aerobic and anaerobic conditions

The mechanism of copper(II) 1,4,7-triazacyclononane dichloride [Cu([9]aneN(3))Cl-2]-catalyzed hydrolysis of activated phosphodiesters has been established. We now report that Cu([9]aneN(3))Cl-2 is also capable of cleaving both single-stranded and double-stranded DNA at near-physiological pH and temperature. Degradation of both single-stranded and double-stranded DNA was revealed by gel electrophoresis and quantitated via fluorimaging of ethidium bromide-stained gels. Single-stranded M13 DNA incubated with Cu([9]aneN(3))Cl-2 is efficiently and nonspecifically degraded. Supercoiled plasmid DNA (form I) incubated with Cu([9]aneN(3))Cl-2 is nicked to relaxed circular DNA (form II) and then more slowly degraded to form III (line ar). A related complex, [Cu(i-Pr-3[9]aneN(3))(OH2)(CF3-SO3)]CF3SO3, displays a marked increase in DNA cleavage activity relative to the parent Cu([9]aneN(3))Cl-2. Interestingly, there appear to be at least two different mechanisms of DNA degradation: an O-2-dependent pathway and an O-2-independent pathway. This is one of only a few well-defined metal complexes demonstrated to cleave DNA in the absence of O-2 or some other oxidant.