[Ru(bpy)2(L)]Cl2:: Luminescent metal complexes that bind DNA base mismatches

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 proper ties 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 oligonucleoticles 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 x 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 x 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 1 footprinting assay, a binding constant to a CC mismatch of 8 x 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.