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

A pair of ruthenium(II) complex enantiomers, Delta- and Lambda-[Ru(bpy)(2)MBIP](2+) (bpy = 2,2'-bipyridine, MBIP = 2-(3-bromophenyl)imidazo-[5,6-f]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 Delta- [Ru(bpy)(2)MBIP](2+) intercalated into DNA more deeply than Lambda-[Ru(bpy)(2)MBIP](2+) did and exhibited a better DNA photocleavage ability. Molecular simulation further indicated that Delta-[Ru(bpy)(2)MBIP](2+) more preferentially intercalated between the base pairs of CT-DNA to the major groove, and Lambda-[Ru(bpy)(2)MBIP](2+) 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 metalcomplex-based antitumor drugs with higher efficacy and lower toxicity.

Automated summary

A pair of ruthenium(II) complex enantiomers were designed and synthesized, and their binding behaviors to CT-DNA were studied. Experimental results showed that both enantiomers bound to CT-DNA through van der Waals force or hydrogen bond, with Delta-[Ru(bpy)(2)MBIP](2+) having deeper insertion and better photocleavage ability. Molecular simulation further revealed the difference in binding modes. These findings are important for understanding the mechanism of metal complex-DNA binding and designing antitumor drugs.