Enantiopreferential DNA Binding of [Ru^II(l,10-phenanthroline)₃]²⁺ Studied with Linear and Circular Dichroism

Abstract

Circular dichroism (CD) spectroscopy and linear dichroism (LD) spectroscopy have been used to probe the binding of [RuII(1,10-phenanthroline)3]2+ to DNA. Changes in CD and normal absorption upon binding and the LD observed in flow-oriented DNA systems are analyzed to yield information about the binding of the ∆ and ∆ enantiomers. Flow LD shows that both isomers bind to DNA but with different geometries. These two types of binding geometries are observed with DNA and [poly(dA-dT)]2 in a wide range of binding ratios (r = 0.005-0.1 metal/DNA phosphate) and ionic strengths, and also with [poly(dG-dC)]2, indicating that the enantiomerically specific geometry is determined by the “texture” (helical pitch and sense) of the double helix, irrespective of base composition. The A enantiomer of [RuII(1,10-phenanthroline)3]2+ shows a pronounced binding affinity for[poly(dA-dT)]2 at low binding ratios; however, other combinations of the two enantiomers with this polynucleotide, [poly(dG-dC)]2, and DNA show binding affinities that vary depending on the binding ratio, ionic strength, and concentration of the opposite enantiomer. The binding of the ∆ enantiomer strongly affects the DNA orientation, indicating a reduced persistence length. In contrast, the ∆ enantiomer does not markedly affect the DNA orientation, despite the similar binding types and electronic perturbations indicated by the spectroscopic data for both enantiomers. An earlier speculation that the ∆ enantiomer should bind with one of its phenanthroline wings partially intercalated between base pairs is inconsistent with an angle of approximately 70° between the 3-fold axis of the complex and the DNA helix axis as concluded from the LD spectra. Both enantiomers are believed to be accommodated in the major groove, but with somewhat different geometries owing to steric interactions. The spectroscopic data are interpreted by using the results from a perturbation theory analysis. Show more