Racemic d,l-[Co(phen)2dpq]3+-DNA interactions: Investigation into the basis for minor-groove binding and recognition

A study on the minor-groove recognition of B-DNA d(GTCGAC)2 by racemic d,l-[Co(phen)2dpq]3+, where phen and dpq stand for 1,10-phenanthroline and dipyrido [3,2-d:2,3-f]quinoxaline, respectively, was carried out with a one-, two-dimensional (1D, 2D) nuclear magnetic resonance (NMR) methodologies and molecular simulations. NMR investigations revealed that the metal complex intercalates into the DNA base stack from minor groove orientation with dpq as intercalator and dpq ligand participated in the nucleobase stack. Molecular docking simulations of these systems were consistent with the experimental results and revealed that the recognition shows obvious enantioselectivity: the l-isomer is favored at the pyrimidine-purine/purine-pyrimidine region, especially CG/GC sequence, while the d-isomer is favored at the pyrimidine-pyrimidine/purine-purine region, especially TC/AG sequence. Surprisingly, we found that the l-isomer would be enriched when racemic complex was employed. So contrary to general viewpoint, the l-isomer of complex recognized this right hand double helical DNA preferentially. Detailed analysis suggests that it is the electrostatic interactions that determine the steric interactions and then determine the whole recognition event.