DNA Interaction Dynamics of Ruthenium(II) Complexes

Doctoral thesis, 2006

DNA-binding of small synthetic ligands is of great importance in a number of different applications, from medicine to molecular biology. This thesis focuses on interactions between DNA and ruthenium(II) complexes, in particular the dimers [µ-bidppz(L)4Ru2]4+ (L=1,10-phenanthroline (P) or L=2,2’-bipyridine (B)). The kinetic preference of these complexes for long stretches of AT base-pairs may be useful in targeting organisms with an AT-rich genome. The complexes also absorb light in a large part of the UV/Vis spectrum to form long-lived charge separated states which could be used in upcoming fields like sunlight harvesting and nanoelectronics. This work shows that the ruthenium dimers bind to mixed sequence DNA by threading intercalation and that the binding is extremely slow, with rates that are very sensitive to the stereochemistry of the complex. Intercalation into poly(dAdT)2 is significantly faster, up to 2500 times for the most discriminative complex ΛΛ-B. Contrary to earlier reports, P binds in syn conformation, as shown by studies on a new binuclear ruthenium complex [µ-dtpf(phen)4Ru2]4+. This complex is locked in syn conformation and behaves like P when bound to poly(dAdT)2. The origin of the large emission quantum yield of ΔΔ-P when bound to poly(dAdT)2 is investigated and is due to the larger flexibility of poly(dAdT)2 compared to mixed sequence DNA. A method often employed to study dissociation of cationic dyes from DNA is using sodium dodecyl sulphate (SDS) micelles as a scavenger for the dissociated dyes. It is here reported that SDS catalyses the dissociation of P and B and that dissociation rate constants obtained using SDS sequestration are largely over-estimated. Furthermore, a more reliable method, utilizing the large thermodynamic preference of these complexes for poly(dAdT)2, is presented. Using poly(dAdT)2 as a scavenger, it is shown that SDS can increase the dissociation rate up to 50 times and that the catalysis is entropy driven. Finally, the DNA binding of a new ruthenium monomer, [Ru(phendione)2dppz]2+, and its ability to quench the emission of [Ru(phen)2dppz]2+ by electron transfer when simultaneously bound to DNA, is investigated.