A Ruthenium(II) Complex as a Luminescent Probe for DNA Mismatches and Abasic Sites
[Ru(bpy)_2(BNIQ)]^(2+) (BNIQ = Benzo[c][1,7]naphthyridine-1-isoquinoline), which incorporates the sterically expansive BNIQ ligand, is a highly selective luminescent probe for DNA mismatches and abasic sites, possessing a 500-fold higher binding affinity toward these destabilized regions relative to well-matched base pairs. As a result of this higher binding affinity, the complex exhibits an enhanced steady-state emission in the presence of DNA duplexes containing a single base mismatch or abasic site compared to fully well-matched DNA. Luminescence quenching experiments with Cu(phen)_2^(2+) and [Fe(CN)_6]^(3–) implicate binding of the complex to a mismatch from the minor groove via metalloinsertion. The emission response of the complex to different single base mismatches, binding preferentially to the more destabilized mismatches, is also consistent with binding by metalloinsertion. This work shows that high selectivity toward destabilized regions in duplex DNA can be achieved through the rational design of a complex with a sterically expansive aromatic ligand.
© 2017 American Chemical Society. ACS AuthorChoice - This is an open access article published under an ACS AuthorChoice License, which permits copying and redistribution of the article or any adaptations for non-commercial purposes. Received: April 26, 2017; Published: June 28, 2017. We thank the NIH (GM033309) for its financial support. L.M. thanks the Belgian American Educational Foundation for the Cabeaux–Jacobs Fellowship. We are grateful to the Beckman Institute Laser Resource Center (BILRC) at Caltech for facilities. We also thank Scott Virgil of the Caltech Center for Catalysis and Chemical Synthesis for his assistance in the BNIQ ligand synthesis and Shuo Shi for preliminary work on the ligand synthesis. The authors declare no competing financial interest.
Published - acs.inorgchem.7b01037
Supplemental Material - ic7b01037_si_001.pdf