Insertion of a Bulky Rhodium Complex into a DNA Cytosine−Cytosine Mismatch: An NMR Solution Study
The bulky octahedral complex Rh(bpy)_2chrysi^(3+) (chrysi = 5,6-chrysenequinonediimine) binds single-base mismatches in a DNA duplex with micromolar binding affinities and high selectivity. Here we present an NMR solution study to characterize the binding mode of this bulky metal complex with its target CC mismatch in the oligonucleotide duplex (5'-CGGACTCCG-3')_2. Both NOESY and COSY studies indicate that Rh(bpy)_2chrysi^(3+) inserts deeply in the DNA at the mismatch site via the minor groove and with ejection of both destabilized cytosines into the opposite major groove. The insertion only minimally distorts the conformation of the oligonucleotide local to the binding site. Both flanking, well-matched base pairs remain tightly hydrogen-bonded to each other, and 2D DQF-COSY experiments indicate that all sugars maintain their original C_2'-endo conformation. Remarkably, ^(31)P NMR reveals that opening of the phosphate angles from a B_I to a B_(II) conformation is sufficient for insertion of the bulky metal complex. These results corroborate those obtained crystallographically and, importantly, provide structural evidence for this specific insertion mode in solution.
© 2007 American Chemical Society. Received May 31, 2007. Publication Date (Web): September 18, 2007. We are grateful to the National Institutes of Health (Grant GM33309) for their financial support. We also thank the Université Denis Diderot, Paris VII, for sabbatical support to C.C. Additionally we thank P. K. Bhattacharya, K. Crowhurst, M. Shahgholi, and S. Ross for helpful discussions.
Accepted Version - nihms122808.pdf
Supplemental Material - ja0739436_si_001.pdf