Recognition of base mismatches in DNA by 5,6-chrysenequinone diimine complexes of rhodium(III): A proposed mechanism for preferential binding in destabilized regions of the double helix

5,6-Chrysenequinone diimine (chrysi) complexes of rhodium(III) have been sh own to be versatile and specific recognition agents for mismatched base pai rs in DNA. The design of these compounds was based on the hypothesis that t h esterically expansive chrysi ligand, which should be too wide to readily intercalate into B-DNA, would bind preferentially in the destabilized regio ns of the DNA helix near base mismatches. In this work, this recognition hy pothesis is comprehensively explored. Comparison of the recognition pattern s of the complex [Rh(bpy)(2)(chrysi)](3+) with a nonsterically demanding an alogue, [Rh(bpy)(2)(phi)](3+) (phi = 9,10-phenanthrenequinone diimine), dem onstrates that the chrysi ligand does disfavor binding to B-DNA and generat e mismatch selectivity. Examination of mismatch recognition by [Rh(byp)(2)( chrysi)](3+) in both constant and variable sequence contexts using photocle avage assays indicates that the recognition of base mismatches is influence d by the amount that a mismatch thermodynamically destabilizes the DNA heli x. Thermodynamic binding constants for the rhodium complex at a range of mi smatch sites have been determined by quantitative photocleavage titration a nd yield values which vary from 1 x 10(6) to 20 x 10(6) M-1. These mismatch -specific binding affinities correlate with independent measurements of the rmodynamic destabilization, supporting the hypothesis that helix destabiliz ation is a factor determining the binding affinity of the metal complex for the mismatched site. Although not the only factor involved in the binding of [Rh(bpy)(2)(chrysi)](3+) to mismatch sites, a model is proposed where he lix destabilization acts as the "door" which permits access of the sterical ly demanding intercalator to the base stack.