Structure-specific binding of [Co(phen)2(HPIP)]3+ to a DNA duplex containing sheared G:A mismatch base pairs

The binding of a Co(III) complex to the decanucleotide d(CCGAATGAGG)2 containing two pairs of G:A mismatches was studied by 2D-NMR, UV absorption, and molecular modeling. NMR investigations indicate that racemic [Co(phen)2(HPIP)]Cl3 [HPIP = 2-(2-hydroxyphenyl) imidazo [4,5-f][1,10] phenanthroline] binds the decanucleotide by intercalation: the HPIP ligand selectively inserts between the stacked bases from the minor groove at the terminal regions and from the major groove at the sheared region. Further, molecular modeling revealed that the recognition shows strong enantioselectivity: the Λ-isomer preferentially intercalates into the T6G7:A5A4 region from the DNA major groove, while Δ-isomer favors the terminal C1C2:G10G9 region and intercalates from the minor groove. Detailed energy analysis suggests that the steric interaction, especially the electrostatic effect, is the primary determinants of the recognition event. Melting experiments indicate that binding stabilizes the DNA duplex and increases the melting temperature by 9.5 °C. The intrinsic binding constant of the complex to the mismatched duplex was determined to be 3.5 × 105 M−1.