Neither delta- nor lambda-tris(phenanthroline)ruthenium(II) binds to DNA by classical intercalation

Area of Science:

• Coordination Chemistry
• Biophysical Chemistry
• Molecular Biology

Background:

• The interaction of metal complexes with DNA is crucial for understanding their biological activity.
• The binding mode of ruthenium(II) polypyridyl complexes, such as delta- and lambda-[Ru(o-phen)3]2+, to DNA remains debated.
• Clarifying these interactions is essential for developing novel metallodrugs and probes.

Purpose of the Study:

• To characterize the binding interaction of delta- and lambda-[Ru(o-phen)3]2+ isomers with calf thymus DNA.
• To elucidate the binding mode (electrostatic, intercalation, etc.) of these ruthenium complexes.
• To provide quantitative data on binding affinities and the influence of ionic strength.

Main Methods:

• Equilibrium binding studies were performed to determine binding constants.
• Viscosity measurements were conducted to assess changes in DNA structure upon complex binding.
• The effect of varying sodium ion concentration ([Na+]) on binding constants was analyzed using polyelectrolyte theory.

Main Results:

• Both delta- and lambda-[Ru(o-phen)3]2+ isomers exhibit weak binding to DNA, with binding constants of 4.9 x 10^4 M^-1 and 2.8 x 10^4 M^-1, respectively.
• Analysis of delta log K/delta log [Na+] values (1.37 for delta, 1.24 for lambda) indicates significant electrostatic contributions to binding.
• Viscosity experiments revealed that the lambda isomer does not significantly alter DNA viscosity, while the delta isomer decreases it, ruling out classical intercalation.

Conclusions:

• Both delta- and lambda-[Ru(o-phen)3]2+ isomers bind to DNA primarily through electrostatic interactions.
• The observed viscosity changes suggest that neither isomer binds via classical intercalation into the DNA helix.
• These findings contribute to a better understanding of the DNA-metal complex interactions for ruthenium compounds.