A Versatile Mismatch Recognition Agent: Specific Cleavage of a Plasmid DNA at a Single Base Mispair

[Rh(bpy)_2(chrysi)]^(3+) is a novel, sterically bulky DNA intercalator that has been designed to bind specifically in the destabilized regions near DNA base mismatches and, upon photoactivation, to cleave the DNA backbone. Here the molecule is shown to be both a general and remarkably specific mismatch recognition agent. Specific DNA cleavage is observed at over 80% of mismatch sites in all the possible single base pair sequence contexts around the mispaired bases. Moreover, the complex is highly site-specific; it is shown to recognize and photocleave at a single base mismatch in a 2725 base pair linearized plasmid heteroduplex. Sterically demanding intercalators such as [Rh(bpy)_2(chrysi)]^(3+) may have application both in mutation detection systems and as mismatch-specific chemotherapeutic agents.