DNA Binding of Metal Complexes. A Spectroscopic Study of Trigonal Ru(II)phenanthroline Complexes and Uranyl(VI) Ion with Respect to Specific Interactions with DNA

Doctoral thesis, 1992

The interaction of metal complexes with nucleic acids has attracted attention owing to their potentials as optical probes, probes of chirality, and for use as artificial restriction enzymes. To understand the underlying mechanisms in these contexts we studied the binding to DNA of the enantiomers of two chiral ruthenium(II) metal complexes ([Ru(phen)3]2+ and [Ru(phen)2]2+DPPZ) phen=1,10-phenanthroline, DPPZ=dipyrido[3,2-a:2',3'-c]phenazine, and of the linear uranium(VI) complex, uranyl ([UO2]2+), using linear dichroism, circular dichroism and luminescence, as well as nuclear magnetic resonance spectroscopy. For the first metal complex, [Ru(phen)3]2+, both enantiomers (D and L) were found to bind weakly and non-intercalatively in the minor groove of B-form DNA. Each enantiomer exhibits its own unique binding geometry independent of DNA base sequence. Binding affinities, however, vary slightly with base composition. Upon binding, the D enantiomer considerably decreases the flow orientation of DNA due to shortened persistence length. The complex was shown to be unsuitable for probing DNA handedness, since it induces B conformation in Z form DNA. Both D and L of [Ru(phen)2DPPZ]2+ were found to bind strongly (K*108 M-1), and with very similar binding geometries in which the DPPZ wing intercalates between DNA base pairs. However, it is the D enantiomer that is mainly responsible for the luminescence enhancement observed for the racemate. We explain this difference in terms of a slight variation in binding geometry and packing on DNA, giving better access to quenching solvent water in the L complex. Uranyl was shown to bind very strongly to DNA (K*1010 M-1), and drastically affect its hydrodynamical behaviour. We suggest that uranyl binds in the minor groove, probably by coordination of phosphate oxygens by uranium. The LD data is consistent with an orientation in which the long axis of uranyl lies along the groove. Binding is shown to be a prerequisite for uranyl-mediated photocleavage of DNA.