Chiral Ruthenium Dipyrodiphenazine Complexes: DNA Binding and Excited State Relaxation
Ruthenium complexes with aromatic ligands have been extensively studied due to their interesting photophysical properties, including photophysics and electron transfer upon interaction with nucleic acids. For example, the broad absorption spectrum makes them suitable as antenna molecules in photochemical reaction systems and their ability to accept or donate electrons in their excited state could have potential in opto-electronical devices. Many of these molecules show high affinity for DNA. The chirality of the metal center and the large number of possible ligand combinations constitutes a toolkit for design of DNA binders, with potential applications in gene diagnostics and cancer therapeutics.
In this thesis the environment-sensitive photophysics and strong DNA affinity, displayed by ruthenium complexes containing the [Ru(phen)2dppz]2+ chromophore (phen=1,10-phenanthroline, dppz=dipyrido[3,2-a:2',3'-c]phen-azine), have been studied with optical spectroscopy techniques. The excited state relaxation of the chromophore is very sensitive to the environment, dramatically manifested by the >104 increase in emission quantum yield upon binding to DNA compared to water solution, denoted as the "light-switch effect". Excited-state relaxation studies performed in water and glycerol show that at least three excited states of metal-to-ligand charge-transfer character are involved in the decay, the populations of which are sensitive to hydrogen bonding with the solvent.
The second part of the thesis reports on thermodynamic and kinetic DNA binding properties of a dimer of the [Ru(phen)2dppz]2+ chromophore. Flow linear dichroism studies show that all three stereoisomers (.DELTA.-.DELTA., .DELTA.-.LAMDA., and .LAMDA.-.LAMDA.) bind to DNA by a threading bis-intercalative binding mode. Threading of bulky chiral subunits results in very slow reaction kinetics and, in contrast to thermodynamic properties, a pronounced enantioselectivity.
The DNA binding and photophysical properties are finally combined in a study of the .DELTA.-.DELTA.D Ru-dppz dimer interacting with cells. The compound is found to be only moderately toxic to living cells at concentrations below 10-4 M, probably due to poor membrane penetration, but excellent as an emissive marker of DNA in fixated cells.