Comparative Studies on DNA-Binding Mechanisms between Enantiomers of a Polypyridyl Ruthenium(II) Complex.

A pair of ruthenium(II) complex enantiomers, - and -[Ru(bpy)MBIP] (bpy = 2,2'-bipyridine, MBIP = 2-(3-bromophenyl)imidazo[5,6-]phenanthroline), were designed, synthesized, and characterized. Comparative studies between the enantiomers on their binding behaviors to calf thymus DNA (CT-DNA) were conducted using UV-visible, fluorescence, and circular dichroism spectroscopies, viscosity measurements, isothermal titration calorimetry, a photocleavage experiment, and molecular simulation. The experimental results indicated that both the enantiomers spontaneously bound to CT-DNA through intercalation stabilized by the van der Waals force or the hydrogen bond and driven by enthalpy and that -[Ru(bpy)MBIP] intercalated into DNA more deeply than -[Ru(bpy)MBIP] did and exhibited a better DNA photocleavage ability. Molecular simulation further indicated that -[Ru(bpy)MBIP] more preferentially intercalated between the base pairs of CT-DNA to the major groove, and -[Ru(bpy)MBIP] more favorably intercalated to the minor groove. These research findings should be very helpful to the understanding of the stereoselectivity mechanism of DNA-bindings of metal complexes, and be useful for the design of novel metal-complex-based antitumor drugs with higher efficacy and lower toxicity.