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 (linear). A related complex, [Cu( i -Pr 3 [9]aneN 3 )(OH 2 )(CF 3 SO 3 )]CF 3 SO 3, 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.