Studies on thermodynamic nature of steroselectivity for ruthenium(II) polypyridyl complex binding to DNA

A pair of ruthenium(II) complex isomers, Δ- and Λ-[Ru(bpy)2(p-mpip)]2+ {bpy = 2,2′-bipyridine, p-mpip = 2-(4-methylphenyl)imidazo[4,5-f]1,10-phenanthroline} have been synthesized and characterized. Thermodyanmics of binding of the two isomers to calf thymus DNA (CT DNA) has been investigated by isothermal titration calorimetry (ITC). It is rare that the Λ isomer binds to DNA more strongly than the Δ isomer, which has been verified by viscosity measurements, and can be explained by their different thermodynamic driving forces of DNA binding for the first time. This suggests that the dominant factor governing the stereoselectivity of DNA binding of metal complex may be the different thermodynamic driving forces between interactions of its different isomer with DNA. This new finding may be very helpful to understand the nature of steroselective DNA binding of small chiral molecules, and be useful to the development of DNA molecular probes and new DNA targeting therapeutic drugs.