Oxidative Chemical Nucleases

Abstract

This chapter focuses on the nucleic acid chemistry of 1,10-phenanthroline–copper. Its ability to degrade DNA was discovered through a series of serendipitous discoveries that were made during the course of examining the inhibition of Escherichia coli DNA polymerase by 1,10-phenanthroline (OP). The inhibition of this enzyme as well as other DNA polymerases is due to the oxidative scission of DNA by 2:1 1,10-phenanthroline-cuprous complex in the presence of hydrogen peroxide. The inhibition of the polymerase activity could be explained by the generation of 3' phosphorylated termini that are dead-end inhibitors of the enzyme. Chemical nucleases are redox-active coordination complexes that cleave the phosphodiester bond by oxidative attack on the deoxyribose moiety. Despite the heuristic example provided by the crystal structures of the active sites of nucleases, chemists have not been able to develop simple bioorganic systems that hydrolyze phosphodiester bonds facilely. Many coordination complexes that can cleave DNA and RNA by an oxidative mechanism have been identified. In contrast to the inefficiency of hydrolytic nucleases, the “inert” phosphodiester backbone of DNA and RNA is completely degraded on incubation with a fraction of the concentration of 1,10-phenanthroline–copper in the presence of thiol and oxygen.