Enantiopreferential DNA binding: [{(5,6-dmp)₂ru}₂( μ -bpm)]⁴⁺ induces a B-to-Z conformational change on DNA

Abstract

The dinuclear ruthenium(II) complex [{(5,6-dmp)₂Ru}₂(μ -bpm)]⁴⁺ (5,6-dmp = 5,6-dimethyl-1,10-phenanthroline; bpm = 2,2'-bipyrimidine) was synthesized and the meso (ΔΛ) and rac (ΔΔ, ΛΛ) diastereoisomers separated using cation-exchange chromatography, and characterized using CHN analysis as well as UV-visible and ¹H NMR spectra. The rac form was interacted with calf thymus DNA (CT DNA) and certain selected dodecanucleotides, like poly d(GC)₁₂ and poly d(AT)₁₂ and the hexanucleotide d(GTCGAC)₂. Absorption, emission and circular dichroic spectral techniques, DNA melting studies and viscometry were used to monitor the interactions. Induced biphasic CD signals due to exciton coupling between dinuclear complexes bound on the DNA nanotemplate and the complexes free in solution were observed in the UV region. In contrast, the mononuclear analogue rac-[Ru(5,6-dmp)₂(bipy)]²⁺ did not show any biphasic CD signal upon an interaction with DNA under identical conditions. An increase in the ionic strength of the buffer and a decrease in the length of the DNA lowered the extent of exciton coupling. Also, the complex preferentially bound to GC, rather than the AT sequence, as revealed from the higher intensity of the biphasic CD signal for the former. An equilibrium dialysis experiment unambiquously revealed the preferential binding of ΔΔ-enantiomer to CT DNA, and also its potential, interestingly, to induce a B-to-Z conformational change on DNA. The latter was confirmed by the ³¹P NMR spectra of poly d(GC)₁₂ bound to the dinuclear complex. A DNA binding model involving the partial insertion of one of the 5,6-dmp ligands of the large dinuclear complex (ΔΔ-enantiomer) between the DNA base pairs in the minor groove was suggested using molecular modeling; this model is preferred over one involving simple, electrostatic groove binding. This is supported by viscometry studies, which indicate an enhancement in the relative viscosity of CT DNA upon an interaction with the dinuclear complex.