[Co(phen)2dpq]3+-sheared DNA interactions: Investigation into the basis for major groove recognition and repair

The interactions between the chiral metal complexes Δ- and Λ-[Co(phen)2dpq]3+ (phen and dpq stand for 1,10-phenanthroline and dipyrido [3,2-d:2,3-f]quinoxaline, respectively; we abbreviated Δ to “D” and Λ to “L”) and sheared DNA d(CCGAATGAGG)2 were studied with molecular modeling method. The results reveal that the interactions show obvious enantio-selectivity, groove-selectivity and site-specificity. The intercalation of d-isomer in A4T5/T5A4 region of DNA major groove was the most preferential binding mode. While when l-isomer intercalated into its preferential binding site (A3A4/G6T5 region of major groove), the conformation of sheared base pairs was converted to the parallel form, that is to say that the sheared mismatch was repair in conformational level. Further analyses show: (1) The steric interaction, especially the electrostatic part, is the determinant of the recognition events; (2) The structural incitant factor of repair events is the inevitable collision between the ancillary ligand phen and mismatched G2 base, while the thermodynamic incitant factor is the great decrease of energy brought by the integral π-π stack among normal bases, mismatched bases and dpq ligand.