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Published on: March 18, 2015
Comparative Studies on DNA-Binding Mechanisms between Enantiomers of a Polypyridyl Ruthenium(II) Complex
Yanhong Nie1, Zhongming Dai2, Fozia1,3
1Guangdong Technology Research Center for Marine Algal Bioengineering, Guangdong Provincial Key Laboratory for Plant Epigenetics, Shenzhen Engineering Laboratory for Marine Algal Biotechnology, Shenzhen Key Laboratory of Marine Bioresources and Ecology, Shenzhen Key Laboratory of Microbial Genetic Engineering, Longhua Innovation Institute for Biotechnology, College of Life Sciences and Oceanography, Shenzhen University, Shenzhen 518060, P. R. China.
Abstract:
A pair of ruthenium(II) complex enantiomers, Δ- and Λ-[Ru(bpy)2MBIP]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 Δ-[Ru(bpy)2MBIP]2+ intercalated into DNA more deeply than Λ-[Ru(bpy)2MBIP]2+ did and exhibited a better DNA photocleavage ability. Molecular simulation further indicated that Δ-[Ru(bpy)2MBIP]2+ more preferentially intercalated between the base pairs of CT-DNA to the major groove, and Λ-[Ru(bpy)2MBIP]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 metal-complex-based antitumor drugs with higher efficacy and lower toxicity.
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