[Ru(Me₄phen)₂dppz]²⁺, a Light Switch for DNA Mismatches
[Ru(Me₄phen)₂dppz]²⁺ serves as a luminescent "light switch" for single base mismatches in DNA. The preferential luminescence enhancement observed with mismatches results from two factors: (i) the complex possesses a 26-fold higher binding affinity toward the mismatch compared to well-matched base pairs, and (ii) the excited state emission lifetime of the ruthenium bound to the DNA mismatch is 160 ns versus 35 ns when bound to a matched site. Results indicate that the complex binds to the mismatch through a metalloinsertion binding mode. Cu(phen)₂²⁺ quenching experiments show that the complex binds to the mismatch from the minor groove, characteristic of metalloinsertion. Additionally, the luminescence intensity of the complex with DNA containing single base mismatches correlates with the thermodynamic destabilization of the mismatch, also consistent with binding through metalloinsertion. This complex represents a potentially new early cancer diagnostic for detecting deficiencies in mismatch repair.
© 2016 American Chemical Society. Received: February 23, 2016. Publication Date (Web): April 12, 2016. We are grateful to the NIH (GM033309) for funding this work. L.M. thanks the Belgian American Educational Foundation for the Cabeaux−Jacobs Fellowship. We also thank Sarah Antilla for assisting in studies of the complex. The authors declare no competing financial interest.
Accepted Version - nihms809161.pdf
Supplemental Material - ja6b02022_si_001.pdf