Copper(II) Macrocycles Cleave Single-Stranded and Double-Stranded DNA under Both Aerobic and Anaerobic Conditions

Abstract

The mechanism of copper(II) 1,4,7-triazacyclononane dichloride [Cu([9]aneN3)Cl2]-catalyzed hydrolysis of activated phosphodiesters has been established. We now report that Cu([9]aneN3)Cl2 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]aneN3)Cl2 is efficiently and nonspecifically degraded. Supercoiled plasmid DNA (form I) incubated with Cu([9]aneN3)Cl2 is nicked to relaxed circular DNA (form II) and then more slowly degraded to form III (linear). A related complex, [Cu(i-Pr3[9]aneN3)(OH2)(CF3SO3)]CF3SO3, displays a marked increase in DNA cleavage activity relative to the parent Cu([9]aneN3)Cl2. Interestingly, there appear to be at least two different mechanisms of DNA degradation: an O2-dependent pathway and an O2-independent pathway. This is one of only a few well-defined metal complexes demonstrated to cleave DNA in the absence of O2 or some other oxidant.