Published July 26, 2004 | public
Journal Article

[Ru(bpy)_2(L)]Cl_2: Luminescent Metal Complexes That Bind DNA Base Mismatches

An error occurred while generating the citation.

Abstract

Here we report the synthesis of luminescent ruthenium complexes that bind DNA base pair mismatches. [Ru(bpy)_2(tpqp)]Cl_2 (tpqp = 7,8,13,14-tetrahydro-6-phenylquino[8,7-k][1,8]phenanthroline), [Ru(bpy)_2(pqp)]Cl_2 (pqp = 6-phenylquino[8,7-k][1,8]phenanthroline), and [Ru(bpy)_2(tactp)]Cl_2 [tactp = 4,5,9,18-tetraazachryseno[9,10-b]triphenylene] have been synthesized, and their spectroscopic properties in the absence and presence of DNA have been examined. While [Ru(bpy)_2(pqp)]^(2+) shows no detectable luminescence, [Ru(bpy)_2(tpqp)]^(2+) is luminescent in the absence and presence of DNA with an excited-state lifetime of 10 ns and a quantum yield of 0.002. Although no increase in emission intensity is associated with binding to mismatch-containing DNA, luminescence quenching experiments and measurements of steady-state fluorescence polarization provide evidence for preferential binding to oligonucleotides containing a CC mismatch. Furthermore, by marking the site of binding through singlet oxygen sensitized damage, the complex has been shown to target a CC mismatch site directly with a specific binding affinity, K_b = 4 × 10^6 M^(-1). [Ru(bpy)_2(tactp)]^(2+), an analogue of [Ru(bpy)_2(dppz)]^(2+) containing a bulky intercalating ligand, is luminescent in aqueous solution at micromolar concentrations and exhibits a 12-fold enhancement in luminescence in the presence of DNA. The complex, however, tends to aggregate in aqueous solution; we find a dimerization constant of 9.8 × 10^5 M^(-1). Again, by singlet oxygen sensitization it is apparent that [Ru(bpy)_2(tactp)]^(2+) binds preferentially to a CC mismatch; using a DNase I footprinting assay, a binding constant to a CC mismatch of 8 × 10^5 M^(-1) is found. Hence results with these novel luminescent complexes support the concept of using a structurally demanding ligand to obtain selectivity in targeting single base mismatches in DNA. The challenge is coupling the differential binding we can obtain to differential luminescence.

Additional Information

© 2004 American Chemical Society. Received January 16, 2004. Publication Date (Web): May 26, 2004. We gratefully acknowledge the NIH (GM33309) for financial support of this work. E.R. also thanks the FWF for a postdoctoral fellowship.

Additional details

Created:
August 19, 2023
Modified:
October 17, 2023