Luminescent ruthenium probe for DNA mismatches

Abstract

Our lab. has focused on the design of metalloinsertors in an effort to prep. new chemotherapeutic agents targeted towards mismatch repair (MMR) - deficient cells. Metalloinsertors bind selectively to DNA mismatches and show preferential selectivity in MMR- deficient cells. We have also been interested in designing luminescent ruthenium complexes that could function as diagnostic probes for DNA mismatches. It is known that the complex [Ru(bpy)_2(dppz)]^(2+) while non- emissive in aq. soln., exhibits a restored luminescence upon binding to duplex DNA. In this work, a new sterically expansive ligand (BNIQ) was synthesized and coordinated to ruthenium to create a new luminescent complex [Ru(bpy)_2(BNIQ)]^(2+). The luminescent properties of this complex in the presence of well- matched and mismatched DNA duplexes were examd. using steady state and emission lifetime measurements. The complex exhibits an enhanced luminescence in the presence of mismatched DNA relative to well- matched DNA, suggesting that this complex may be utilized as a novel probe for DNA mismatches.

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