Binding of Ru(bpy)_2(eilatin)^(2+)to Matched and Mismatched DNA
The DNA-binding properties of Ru(bpy)_2(eilatin)^(2+) have been investigated to determine if the sterically expansive eilatin ligand confers specificity for destabilized single-base mismatches in DNA. Competitive DNA photocleavage experiments employing a sequence-neutral metallointercalator, Rh(bpy)_2(phi)^(3+)(phi = 9,10-phenanthrenequinonediimine), and a mismatch-specific metalloinsertor, Rh(bpy)_2(chrysi)^(3+) (chrysi = chrysene-5,6-quinonediimine), reveal that the eilatin complex binds to a CC mismatched site with an apparent binding constant of 2.2(2) × 10^6 M^(−1). Nonetheless, the selectivity in binding mismatched DNA is not high: competitive titrations with Rh(bpy)_2(phi)^(3+) show that the complex binds also to well-matched B-form sites. Thus, Ru(bpy)_2(eilatin)^(2+), despite containing the extremely expansive eilatin ligand, displays lower selectivity for the mismatch than does Rh(bpy)_2(chrysi)^(3+), a metalloinsertor containing the smaller, though still bulky, chrysene-5,6-quinonediimine ligand. In summary, the size and shape of the eilatin ligand allow stacking with both well-matched and mismatched DNA.
© 2008 American Chemical Society. Received April 11, 2008. Publication Date (Web): June 25, 2008. We thank the NIH (Grant GM33309) for their financial support. We also thank Drs. Y. Kashman and Y. Tor for helpful correspondence.
Supplemental Material - ic8006537_si_001.pdf
Accepted Version - nihms97865.pdf